AREA 1 - IIS LA PRINCESA

Transcripción

2014
ANNUAL REPORT OF
SCIENTIFIC ACTIVITY
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2014
Neuropharmacology and neuroprotection.
Neurotransmission in the hippocampus.
Clinical pharmacology and pharmacogenetics.
Diagnostic and therapeutic advances in affective
disorders.
Neurosurgery of epilepsy.
Cerebrovascular diseases.
Prognostic and predictor markers in autoimmune diseases.
Esophagogastrointestinal inflammatory diseases.
Progenitors and cell therapy.
Advanced therapies in oncohematology.
Biological, cellular and molecular monitoring in oncohematology.
New diagnostic and therapeutic advances in cardiovascular diseases.
New therapies in infectious pathologies.
Individualized medicine in solid tumors.
ANNUAL REPORT OF
SCIENTIFIC ACTIVITY
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Intercellular communication in the inflammatory
response.
Cellular and molecular responses to Hypoxia.
Animal models of inflammatory diseases and
intercellular signalling.
Cellular mechanisms and molecular determinants of
allergy-based diseases.
Inflammatory processes in nephrological diseases.
Inflammatory mechanisms in pulmonary diseases.
Inflammatory response in hepatic diseases.
Mechanisms and mediators of endocrine diseases.
Children´s development (obesity and growth).
Metabolic syndrome and vascular risk.
INDEX
FOREWORD IP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Letter from the Scientific Director . . . . . . . . . . . . . . . . . . . . . . . . 6
SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
AREA 1 · Cellular and molecular etiopathogenic mechanisms in
inflammatory and autoimmune diseases . . . . . . . . . . . . . . . . . . . . . .31
2014 ANNUAL REPORT OF
SCIENTIFIC ACTIVITY
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© INSTITUTO DE
INVESTIGACIÓN SANITARIA
Hospital Universitario de La Princesa
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AREA 2 · Neurotransmission, pharmacological neuroprotection and
neurodegenerative and neuropsychiatric diseases . . . . . . . . . . . . . 79
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Editing: Ibáñez&Plaza Asociados S.L.
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AREA 3 · Advanced therapies and individualized medicine . . . . . . . . . . . . . . 101
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AREA 3
Diego de León, 62
28006 Madrid
Phone 91 520 25 08
e-mail: [email protected]
Web: www.iis-princesa.org
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–3–
PRÓLOGO FOREWORD
Prólogo IP
Foreword IP
IIS-Princesa 2014
–5–
Carta del Director Científico
Letter from the Scientific Director
Francisco Sánchez Madrid
Director Científico / Scientific Director
Durante el último
año, nuestro IP ha
demostrado su
espíritu innovador
logrando una plena
integración de los
objetivos asistenciales, docentes y
de investigación
consiguiendo
logros en las
mejoras de la
salud y de la
calidad de vida de
los ciudadanos
–6–
C
omo cada año, me complace presentaros la Memoria Científica de
nuestro Instituto. Durante el último
año, nuestro IP ha demostrado su espíritu innovador logrando una plena integración de los
objetivos asistenciales, docentes y de investigación consiguiendo logros en las mejoras de
la salud y de la calidad de vida de los ciudadanos a los que el hospital atiende.
Los orígenes de nuestro IP se remontan varias décadas. En los 160 años de historia de
nuestro hospital, se ha evidenciado el marcado
carácter innovador y de investigación llevado a
cabo. Como ejemplos destacar, la realización
de la primera transfusión sanguínea de España, la primera cirugía con circulación extracorpórea o el primer trasplante alogénico de médula ósea. Todo ello refleja el alto nivel de investigación existente desde los comienzos del
centro. Hace unos años este trabajo fue reconocido y fuimos acreditados, como Instituto de
Investigación Sanitaria. Este reconocimiento
es un reflejo del trabajo que durante muchos
años se ha venido realizando. Desde entonces
y en estos últimos años de andadura, hemos
consolidado nuestra posición como un centro
investigador e innovador de referencia. Claro
ejemplo es la creación de la Unidad de Terapias
Biológicas (UTB) constituyéndose como la primera Unidad Multidisciplinaria con estas características, siendo reconocida por el Consejo
Interterritorial del Ministerio de Sanidad como
Unidad de Buena Práctica en el Sistema Nacional de Salud (SNS).
Por ello hoy me siento muy orgulloso de
presentarles este resumen de nuestra activi-
I
t is a great pleasure to present again
another year the annual Scientific
Report of our Institute (IP). During
last year, our IP has shown its innovative
spirit, reaching complete integration of the
healthcare, teaching and research goals
and fulfilling achievements in the improvement of the health and quality of life of the
people cared for by the hospital.
The origins of our IP date several
decades back. In the 160 years of history
of our Institute, the great innovative nature
of the research carried out has been
demonstrated. Outstanding examples of
this are, the first blood transfusion carried
out in Spain, the first surgery with extracorporeal circulation or the first bone marrow
allogeneic transplant. Altogether, it reflects
the high level of the research developed
since the beginning of our Centre. A few
years ago this work was acknowledged,
and we were accredited as Institute for
Health Research. This acknowledgment is
the result of the work carried out. From
then on, in the last few years we have consolidated our position as an innovation and
research reference centre. A clear example
is the creation of the Biological Therapies
Unit (BTU), established as the first Multidisciplinary Unit with these characteristics,
which has been acknowledged by the Interterritorial Council of the Spanish Ministry
of Health as Unit for Good Practice in the
National Health System (NHS).
For all this, I feel very proud to present the summary of our activity, the result of
dad, fruto de la completa dedicación no sólo
de los investigadores, sino de todo el personal
que de alguna manera contribuye a seguir
mantenido la vocación investigadora característica de nuestro IP.
La investigación llevada a cabo en nuestro
IP tiene como fin primordial, aplicar los conocimientos adquiridos en beneficio del paciente.
Durante el año 2014, se han aprobado casi
100 ensayos clínicos y estudios observacionales, dando lugar a importantes avances, tanto
en el diagnóstico como en el tratamiento de las
enfermedades.
Una de las claves es sin duda su apuesta
clara y decidida por la innovación en biomedicina tanto básica como clínica. Esta investigación de excelencia está centrada especialmente en la traslación a la práctica clínica. De esta forma asistencia e investigación
caminan en la misma dirección, configurando una fórmula de éxito de la que dan muestra los datos de actividad en ambos campos
que permiten dar respuesta a los problemas
de salud de la población con la máxima eficiencia y calidad.
Un año más hemos querido hacer balance
y análisis de lo acontecido en el pasado ejercicio 2014. Esta memoria recoge, en síntesis, la
actividad desarrollada por el IIS-Princesa y
constata una vez más la gradual progresión y
consolidación de la actividad investigadora y el
esfuerzo por hacer que esta sea trasladable en
la atención sanitaria de nuestros pacientes.
Debe servirnos asimismo, como elemento de
reflexión para orientar las estrategias y directrices por las que nos deberíamos guiar en nuestro inmediato futuro.
Quiero agradecer a todas y cada una de las
personas su completa dedicación que hace
posible cada año presentarles unos resultados
tan excelentes.
the full dedication not only of the researchers, but of all the staff who contributes in many ways to keep the tradition of research characteristic of our Institute.
The research carried out in our IP
has the main goal of applying the acquired knowledge to the benefit of our
patients. During 2014, almost 100 clinical trials and observational studies have
been approved, leading to important
advances for both diagnosis and treatment of diseases.
One of the keys is undoubtedly
our clear and strong commitment to innovation in both clinical and basic biomedicine. This research excellence is
particularly focused on the translation
to clinical practice. Thus, research and
health care follow the same direction,
forming a successful formula demonstrated by the activity data in both
fields, that allows responding to the
health problems of the population with
the highest efficiency and quality
One more year we wanted to appraise and analyze what happened in
the past year 2014. This report includes, in short, the activity of the IISPrincesa and remarks, once again, the
gradual progression and consolidation
of the research activity and the effort to
make this translatable to the health care
for our patients. It should also serve as
an element of reflection to steer the
strategies and guidelines that should
guide us in our immediate future.
I want to thank each and every
one for their full dedication that makes it
possible each year to present such excellent results.
During last year,
our IP has shown
its innovative spirit, reaching complete integration
of the healthcare,
teaching and research goals
and fulfilling
achievements in
the improvement
of the health and
quality of life of
the people
–7–
PRÓLOGO IP / FOREWORD IP
ESTRUCTURA ORGANIZATIVA
ORGANISATIONAL CHART
CONSEJO RECTOR
GOVERNING COUNCIL
El Consejo Rector es el órgano de gobierno al que corresponde la
representación, la dirección y la administración del Instituto.
The Governing Council is the governing body which is responsible for
the representation, management and administration of the Institute.
PRESIDENTE / CHAIRMAN
Ilmo. Sr. D. Javier Maldonado González
Viceconsejero de Asistencia Sanitaria de la Comunidad de Madrid.
Deputy Minister of Health Care, Comunidad de Madrid
VICEPRESIDENTE / VICE-CHAIRMAN
Ecxmo. Sr. Rector Magnífico D. José Mª Sanz Martínez
Rector de la UAM
Chancelor of UAM
MIEMBROS / MEMBERS
Dr. Julio Ancochea Bermúdez
Jefe de Servicio de Neumología, Hospital U. La Princesa
Respiratory Department, Hospital U. La Princesa
Dr. Miguel Ángel Andrés Molinero
General Manager, Hospital U. La Princesa
General Manager, Hospital U. La Princesa
D. Alfonso Garrigós Garnica
Director de Gestión, Hospital U. La Princesa
Management Director, Hospital U. La Princesa
Dª. Margarita González Grande
Directora Gerente, Hospital U. Niño Jesús
General Manager, Hospital U. Niño Jesús
D. José Antonio Gutierrez Fuentes
Fundación Lilly
Lilly Foundation
Dª Paloma Martín Martín
Directora General de Investigación,
Formación e Infraestructuras Sanitarias
Dr. Federico Mayor Menéndez
Centro Biología Molecular Severo Ochoa, Madrid
Severo Ochoa Molecular Biology Centre, Madrid
Dra. Ana Miquel Gómez
Gerente adjunto de Planificación y Calidad de Atención Primaria
Consejería de Sanidad de la Comunidad de Madrid
Deputy Manager of Planning and Care Quality, Atención Primaria
Dra. Rosa Mª Ramos Pérez
Directora Gerente, Hospital U. Santa Cristina
Managing Director Hospital U. Santa Cristina
Dr. Francisco Sánchez Madrid
Director Científico, Instituto Investigación Sanitaria IP
Scientific Director of IP
SECRETARIA / SECRETARY
Dª Rosario Ortiz de Urbina Barba
Directora de la Fundación de Investigación Biomédica (FIB),
Hospital U. de La Princesa
Director of FIB, Hospital U. La Princesa.
COMISIÓN DELEGADA
EXECUTIVE COMITEE
La Comisión Delegada es el órgano de gobierno ejecutivo del
Instituto, y es competente para poner en marcha iniciativas de
investigación y desarrollo de proyectos.
The Executive Committee is the executive organ of government of the
Institute and is competent to implement research initiatives and project development.
Dr. Miguel Ángel Andrés Molinero
Director Gerente, Hospital U. La Princesa
Managing Director, Hospital U. La Princesa
VICEPRESIDENTE / VICE-CHAIRMAN
Dr. Antonio García García
Jefe de Sección de Farmacología Clínica, Hospital U. La Prin-cesa
Clinical Pharmacology Department, Hospital U. La Princesa
–9–
MIEMBROS / MEMBERS
Dr. Javier Aspa Marco
Coordinador Unidad Apoyo a la Dirección Científica,
Hospital U. La Princesa
Scientific Management Support Unit, Hospital U. La Princesa
D. Gustavo Casero Balboa
Subdirector de Gestión / RR.HH, Hospital U. La Princesa
Deputy Management Director / Human Resources,
Hospital U. La Princesa
Dr. Manuel Fresno Escudero
D. Alfonso Garrigós Garnica
Director de Gestión y SS.GG, Hospital U. La Princesa
Management Director, Hospital U. La Princesa
Dr. Luis Madero López
Jefe de Servicio de Hematología, Hospital U. Niño Jesús
Hematology Department, Hospital. U. Niño Jesús
Dra. Ana Miquel Gómez
Gerente adjunto de Planificación y Calidad de Atención Primaria de
la Consejería de Sanidad de la Comunidad de Madrid
Deputy Manager of Planning and Care Quality, Atención Primaria,
Dr. Emilio Úcar Corral
Subdirector Médico, Hospital U. Santa Cristina
Medical Deputy Director, Hospital U. Santa Cristina
SECRETRIA / SECRETARY
Dª. Rosario Ortiz de Urbina Barba
Directora de la Fundación de Investigación Biomédica, Hospital U.
de La Princesa
Director of FIB, Hospital U. La Princesa
DIRECTOR CIENTÍFICO
SCIENTIFIC DIRECTOR
El Director Científico del Instituto de Investigación Sanitaria Hospital
Universitario de La Princesa es el responsable de la Dirección
Científica del mismo. Las principales funciones son velar por la
calidad de la investigación realizada, promover las relaciones entre
– 10 –
los grupos de investigación y dirigir las actividades científicas que
se lleven a cabo.
The Scientific Director of the Health Research Institute Hospital
Universitario de La Princesa is responsible for its scientific management. The main functions are to ensure the quality of research, promote relations between research groups and lead the scientific activities carried out in the Institute.
COMITÉ CIENTÍFICO EXTERNO
EXTERNAL SCIENTIFIC COMMITTEE
Dr. Jaime Bosch Genover
Director Científico del CIBERHED
Scientific Director of CIBEREHD
Dr. Xosé R. Bustelo
Centro de Investigación del Cáncer, Salamanca
Cancer Research Center, Salamanca
Dr. José López Barneo
Director del Instituto de Investigación Biomédica, Sevilla
Director of Biomedical Research Institute, Sevilla
Dr. Carlos López Otín
Departamento de Bioquímica y Biología Molecular,
Universidad de Oviedo
Department of Biochemistry and Molecular Biology, University of Oviedo
Dr. Miguel López-Botet Arbona
Director Científico del IMIN, Barcelona
Scientific Director of IMIN, Barcelona
Dr. Felipe Rodríguez de Castro
Catedrático Facultad de Medicina, Universidad de L. P. de Gran Canaria
Professor of Medical School, University of Las Palmas de Gran Canaria
COMISIÓN DE INVESTIGACIÓN
RESEARCH COMMITTEE
El IIS-Princesa, cuenta con una Comisión de Investigación,
encargada de impulsar y coordinar la actividad científica del
Instituto. Todos los miembros de la Comisión de Investigación
son profesionales con trayectoria científica reconocida,
encontrándose adscritos a algún grupo de investigación del
mismo.
The IIS-Princess has a Research Committee, responsible for promoting and coordinating scientific activity at the Institute. All
members of the Research Committee are professionals of recognized scientific track that belong to a research group of the
Institute.
MIEMBROS / MEMBERS
Dr. Francisco Abad Santos
Servicio de Farmacología Clínica, Hospital U. La Princesa
Dr. Adrián Alegre Amor
Servicio de Hematología, Hospital U. La Princesa
Hematology Department, Hospital U. La Princesa
Servicio de Neumología, Hospital U. de La Princesa
Respiratory Department, Hospital U. La Princesa
Dr. Jesús Argente Oliver
Servicio de Endocrinología, Hospital U. Niño Jesús
Endocrinology Department, Hospital U. Niño Jesús
Dr. Javier Aspa Marco
Unidad Apoyo a la Dirección Científica, Hospital U. La Princesa
Scientific Management Support Unit, Hospital U. La Princesa
Dr. Ramón Colomer Bosch
Servicio de Oncología Médica, Hospital U. La Princesa
Medical Oncolgy Department, Hospital U. La Princesa
Dr. Antonio García García
Dr. Carmelo García Monzón
Servicio de Medicina Interna, Hospital U. Santa Cristina
Internal Medicine Department, Hospital U. Santa Cristina
Dr. Isidoro González Álvaro
Servicio de Reumatología, Hospital U. La Princesa
Rheumatology Department, Hospital U. La Princesa
Dra. Mónica Marazuela Azpiroz
Servicio de Endocrinología, Hospital U. La Princesa
Endocrinology Department, Hospital U. La Princesa
Dr. Federico Mayor Menéndez
Dr. Francisco Javier Pérez Gisbert
Servicio de Digestivo, Hospital U. La Princesa
Gastroenterology Department, Hospital U. La Princesa
Dra. Carmen Suárez Fernández
Servicio de Medicina Interna, Hospital U. de La Princesa
Internal Medicine Department, Hospital U. La Princesa
Dra. María Yañez Mó
Unidad de Investigación, Hospital U. Santa Cristina
Research Unit, Hospital U. Santa Cristina
Dª. Mª Ángeles Vallejo Rodríguez
Servicio de Inmunología, Hospital U. La Princesa
Immunology Department, Hospital U. La Princesa
COMITÉ ÉTICO DE INVESTIGACIÓN CLÍNICA
CLINICAL RESEARCH ETHICS COMMITTEE
El Comité Ético de Investigación Clínica (CEIC) se encarga de evaluar los aspectos éticos, metodológicos y legales de los ensayos
clínicos con medicamentos y de aquellos estudios en los que se
lleve a cabo investigación con seres humanos.
The Clinical Research Ethics Committee (CEIC) is responsible for assessing the ethical, methodological and legal aspects of clinical trials with
medicines and those studies in which research is conducted on humans.
VICEPRESIDENTE/ DEPUTY CHAIRMAN
Fundación de Investigación Biomédica, Hospital U. de La Princesa
FIB, Hospital U. La Princesa.
MIEMBROS / MEMBERS
Dr. Enrique Alday Muñoz
Servicio de Anestesia, Hospital U. La Princesa
Anesthesiology Department, Hospital U. La Princesa
– 11 –
Servicio de Oncología Médica, Hospital U. La Princesa
Medical Oncolgy Department, Hospital U. La Princesa
Dra. Carmen del Arco Galán
Servicio de Urgencias, Hospital U. La Princesa
Emergency Department, Hospital U. La Princesa
Dª Mª José Galán Sánchez Heredero
DUE. Hospital U. La Princesa
Nurse, Hospital U. La Princesa
Dr. Carmelo García-Monzón
Servicio de Medicina Interna, Hospital U. Santa Cristina
Internal Medicine Department, Hospital U. Santa Cristina
Dr. Andrés López Romero
Médico, Gerencia Adjunta Planificación y Calidad, Atención
Primaria
Doctor, Primary Care
Dra. Elena Martín Pérez
Servicio de Cirugía General, Hospital U. La Princesa
General Surgery Department, Hospital U. La Princesa
Dª Concepción Martínez Nieto
Servicio de Farmacia, Hospital U. La Princesa
Pharmacy Department, Hospital U. La Princesa
D. Licinio Medina Moreno
Servicio Económico-Financiero, Hospital U. La Princesa
Economic and Financial Service, Hospital U. La Princesa
Dra. Dolores Ochoa Mazarro
D. Igor Pinedo García
Ldo. Derecho, ASJUSA
Lawyer, ASJUSA
Dª Carolina Pozuelo González
Servicio de Farmacia, Atención Primaria
Pharmacy Department, Primary Care
Dr. Eduardo Sánchez Sánchez
Servicio de Medicina Interna, Hospital U. La Princesa
Internal Medicine Department, Hospital U. La Princesa
Dr. Alberto Sebastián Palomino
Dirección, Hospital U. La Princesa
Managment, Hospital U. La Princeas
Dª Alba Serrano Ruiz
Departamento Ensayos Clínicos, FIB, Hospital U. de La Princesa
Clinical Trials Department, FIB, Hospital U. La Princesa
Dª Tania Tineo Drove
DUE. Hospital U. La Princesa
Nurse, Hospital U. La Princesa
– 12 –
SECRETARÍA TÉCNICA / TECHNICAL SECRETARY
Dra. Mara Ortega Gómez
Biobanco, Hospital U. La Princesa
Biobank, Hospital U. La Princesa
SECRETARÍA ADMINISTRATIVA / ADMINISTRATIVE SECRETARY
Dª Cecilia López García
D. Julio Rodríguez de Castro
FUNDACIÓN INVESTIGACIÓN BIOMÉDICA (FIB)
FOUNDATION FOR BIOMEDICAL RESEARCH (FBR)
La Fundación tiene por finalidad gestionar programas y proyectos de
investigación clínica, y otras actividades conexas en el campo de la
Biomedicina, para contribuir a la promoción y protección de la salud de
la población y al progreso y mejora del Sistema Sanitario de la
Comunidad de Madrid, regulado por el artículo 2 de la Ley 12/2001 de
21 de diciembre de Ordenación Sanitaria de la Comunidad de Madrid.
The Foundation aims to manage programs and clinical research projects and other related activities in the field of biomedicine, to contribute to the promotion and protection of health of the population and the
advancement and improvement of the health system of the Community
of Madrid, ruled by Article 2 of Law 12/2001 of 21 December of Health
Planning of the Community of Madrid.
DIRECTOR / DIRECTOR
RECURSOS HUMANOS Y CONTRATOS / HUMAN RESOURCES
DEPARTMENT
Dª Gema Jiménez Jiménez
GESTIÓN DE PROYECTOS / PROJECTS MANAGEMENT
DEPARTMENT
D. Jesús Santamaría Pérez
D. German Fernández Carracedo
CONTABILIDAD / ACCOUNTING DEPARTMENT
D. Jorge Gómez Juan
GESTIÓN DE ENSAYOS CLÍNICOS / CLINICAL TRIALS
MANAGEMENT DEPARTMENT
Dª Alba Serrano Ruiz
GESTIÓN DE INVESTIGACIÓN / RESEARCH MANAGMENT
DEPARTMENT
D. Jesús Capa Algara
GESTIÓN DE INNOVACION / INNOVATION MANAGMENT
DEPARTMENT
D. Antonio Rodriguez Hita
Dª Ana Aroca Martínez
ORDENANZA / ADMINISTRATIVE ASSITANT
D. José Corrochano de la Cruz
– 13 –
ACTIVIDAD CIENTÍFICA
SCIENTIFIC OUTPUT
SCIENTIFIC OUTPUT
En el ámbito científico, la tarea de evaluar los nuevos conocimientos y los resultados de la investigación tiene una gran importancia,
siendo ésta determinante para sus resultados. No sólo se evalúan
los investigadores y sus ideas, sino también la difusión y el impacto de las mismas, así como el valor de las publicaciones resultantes. La evaluación de los resultados de la actividad científica forma
parte del trabajo de investigación y supone un análisis de la medida en que las actividades han alcanzado objetivos específicos.
Los resultados de la investigación se dan a conocer al resto de
la comunidad de investigadores por medio de las publicaciones
científicas, sobre todo a través de los artículos publicados en revistas científicas, con el propósito de que la comunidad contraste,
verifique o rechace el valor de esa investigación.
Uno de los mecanismos para llevar a cabo esta valoración se
hace a través del Factor de Impacto (IF), que mide la frecuencia con
la que una revista ha sido citada en un año concreto. Es un indicador que permite comparar revistas y evaluar la importancia relativa de una revista dentro de un mismo campo científico.
Uno de los índices utilizados internacionalmente para llevar a
cabo esta evaluación es el “Journal Citation Report (JCR)”. Lo
publica y elabora anualmente la agencia Thomson Reuters y será
este índice el que utilizaremos para llevar a cabo la medición de la
calidad de los artículos publicados.
A continuación se muestra un pequeño resumen de los datos
del año 2014 en el contexto de los últimos cinco años, y de acuerdo a lo expresado anteriormente se exponen los datos de aquellos
artículos que publicados (excluyendo aquellos en estado “Epub
ahead of print”) en revistas incluidas en el JCR cuyo factor de
impacto sea superior a 1.
En el 2014 se publicaron 354 artículos, con un factor de
impacto acumulado (FIA) de 1788,675 y un factor de impacto
medio (FIM) de 5.1.
In the scientific field, the task of assessing new knowledge and
research results is of great importance, which is crucial to the
results. Not only researchers and their ideas, but also the spread
and impact of these, as well as the value of the resulting publications are evaluated. The evaluation of the results of scientific activity is part of the research work and is an analysis of the extent to
which the activities have achieved specific goals.
The results of research are made known to the rest of the
research community through scientific publications, especially
– 14 –
through articles published in scientific journals, in order to allow the
scientific community to contrast, verify or reject the value of that
research.
One of the mechanisms to carry out this evaluation is done
through the Impact Factor (IF), which measures the frequency with
which a journal has been cited in a particular year. It is an indicator that allows to compare journals and to assess the relative
importance of a journal within a particular scientific field.
Table 1. Articles Distribution
2009
No. Artículos
2010
2011
2012
2013
2014
276
278
306
350
378
354
FIA
1481,366
1325,793
1471,244
1799,982
2223,79
1788,675
FIM
5,4
4,8
4,8
5,1
5,9
5,1
No. Q1+Q2
226
238
251
281
296
286
% Q1+Q2
82%
86%
82%
80%
78%
81%
1399,027
1257,096
1374,962
1680,175
2079,778
1665,187
87
74
74
69
94
90
32%
27%
24%
20%
25%
25%
903,949
708,873
723,434
893,118
1304,268
920,308
FIA Q1+Q2
No. D1
% D1
FIA D1
Table 1. Articles and their distribution by quartiles
Intercellular Communication in the Inflammatory Response
One of the indexes used internationally to carry out this evaluation
is the "Journal Citation Report (JCR)". It is produced and published
annually by the agency Thomson Reuters, and this index will be used
to perform the measurement of the quality of the published articles.
A brief summary of the data for 2014 in the context of the last
five years is shown, according to the statement above contains
data of articles published (excluding those in the "Epub ahead of
print") in journals included in the JCR, with an impact factor which
exceeds 1.
In 2014 a total of 354 articles were published, with an accumulated impact factor (AIF) of 1788.675 and a mean impact factor (MIF) of 5.1.
GROUP
DIRECTOR
H INDEX
1
78
2
Esteban Veiga Chacón
15
3
María Yáñez Mó
34
4
Miguel Vicente Manzanares
31
56
Ana Carmen Urzainqui Mayayo
15
14
María de las Nieves Navarro Lobato
8
Cellular and Molecular Responses to Hypoxia
Los artículos y su distribución por cuartiles se muestran en la
Tabla 1.
GROUP
DIRECTOR
H INDEX
9
Julián Aragonés López
23
6
Manuel Ortiz de Landázuri Busca
40
7
Antonio Martínez Ruiz
17
8
María Josefa Calzada García
11
10
Susana Cadenas Álvarez
13
The articles and their distribution by quartiles are shown in Table 1.
Existen otros índices de evaluación como es el índice H de Hirsch,
que es un indicador que permite evaluar la producción científica de
un investigador. Fue propuesto por Jorge Hirsch, de la Universidad
de California, en el año 2005. Nos permite medir simultáneamente la calidad (en función del número de citas recibidas) y la cantidad de la producción científica y es muy útil para detectar a los
investigadores más destacados dentro de un área de conocimiento. Da bastante importancia a la cantidad de publicaciones del
autor, valorando de este modo un esfuerzo científico prolongado a
lo largo de toda una vida académica.
There are other evaluation indexes such as H Hirsch index, which
is an indicator to evaluate the scientific output of a researcher. It
was proposed by Jorge Hirsch, from the University of California, in
2005. It enables us to simultaneously measure the quality (depending on the number of citations received) and the amount of scientific production and is very useful for detecting leading researchers
– 15 –
SCIENTIFIC OUTPUT
within an area of knowledge. It gives enough importance to the
number of publications of the author, thus valuing scientific effort
extended over an entire academic life.
Children’s Development (Obesity and Growth)
GROUP
DIRECTOR
H INDEX
26
Jesús Argente Oliver
32
Animal Models of Inflammatory Diseases and Intercellular Signalling
Metabolic Syndrome and Vascular Risk
GROUP
DIRECTOR
H INDEX
11
Federico Mayor Menéndez
38
GROUP
DIRECTOR
H INDEX
12
Manuel Fresno Escudero
42
5
Carmelo García Monzón
25
13
Petronila Penela Márquez
22
17
Cristina Murga Montesinos
19
18
Miguel Ángel Íñiguez Peña
24
Neuropharmacology and Neuroprotection
GROUP
DIRECTOR
H INDEX
28
Antonio García García
48
Etiopathogenic and Immunological
Mechanisms of Dermatological Diseases
Neurotransmission in the Hippocampus
GROUP
DIRECTOR
H INDEX
20
Carlos Blanco Guerra
25
15
María Dolores Ibáñez Sandín
3
GROUP
DIRECTOR
H INDEX
16
Manuela García López
38
Clinical Pharmacology and Pharmacogenetics
Inflammatory Processes in Nephrological Diseases
GROUP
DIRECTOR
H INDEX
21
José Antonio Sánchez Tomero
19
GROUP
DIRECTOR
H INDEX
32
Francisco Abad Santos
12
Diagnostic and Therapeutic Advances in Affective Disorders
Inflammatory Mechanisms in Pulmonary Diseases
GROUP
DIRECTOR
H INDEX
22
Julio Ancochea Bermúdez
20
GROUP
DIRECTOR
H INDEX
33
José Luis Ayuso Mateos
29
Neurosurgery of Epilepsy
Inflammatory Response in Hepatic Diseases
GROUP
DIRECTOR
H INDEX
24
Pedro Lorenzo Majano Rodríguez
20
23
Ricardo Moreno Otero
41
GROUP
DIRECTOR
H INDEX
34
Rafael García de Sola
8
Cerebrovascular Diseases
– 16 –
Mechanisms and Mediators of Endocrine Diseases
GROUP
DIRECTOR
H INDEX
GROUP
DIRECTOR
H INDEX
35
José Aurelio Vivancos Mora
27
25
Mónica Marazuela Azpiroz
31
Ass. 1
Ignacio Lizasoain Hernández
44
Individualized Medicine in Solid Tumors
Prognostic and Predictor Markers in Autoimmune Diseases
GROUP
DIRECTOR
H INDEX
GROUP
DIRECTOR
H INDEX
36
Isidoro González Álvaro
17
40
Ramón Colomer Bosch
42
37
Esteban Daudén Tello
18
53
Almudena Zapatero Laborda
12
54
Laura Cerezo Padellano
10
50
Carlos Manuel Olivier Gómez
2
Ass. 3
José Cordero Ampuero
10
Esophagogastrointestinal Inflammatory Diseases
GROUP
DIRECTOR
H INDEX
38
Javier Pérez Gisbert
49
Progenitors and Cell Therapy
GROUP
DIRECTOR
H INDEX
39
Luis Madero López
17
Advanced Therapies in Oncohematology
GROUP
DIRECTOR
H INDEX
44
Juan Luis Steegmann Olmedillas
19
GUÍAS CLÍNICAS
CLINICAL GUIDELINES
La investigación realizada en seres humanos tiene como objetivo
primordial la obtención de un conocimiento que va más allá del
beneficio del sujeto, y está encaminada a mejorar y optimizar el
tratamiento a los pacientes. En el año 2014, fueron publicadas un
total de 21 guías referidas a diferentes patologías.
Biological, Cellular and Molecular Monitoring in Oncohematology
GROUP
DIRECTOR
H INDEX
45
Elena Fernández Ruiz
20
46
Cecilia Muñoz Calleja
12
New Diagnostic and Therapeutic Advances in Cardiovascular Diseases
GROUP
DIRECTOR
H INDEX
58
Fernando Alfonso Manterola
41
48
Luis J. Jiménez Borreguero
7
57
Carmen Suárez Fernández
19
49
Blanca Novella Arribas
11
New Therapies in Infectious Pathologies
GROUP
DIRECTOR
H INDEX
50
Ignacio de los Santos Gil
13
51
Javier Aspa Marco
15
52
Teresa Alarcón Cavero
27
Research in humans has the primary objective to obtain a knowledge that goes beyond the benefit of the individual and its aimed
to improve and optimize the treatment of patients. In 2014, a total
of 21 guidelines for different diseases were published.
Gorriz JL, Gutiérrez F, Trullàs JC, Arazo P, Arribas JR, Barril G,
Cervero M, Cofán F, Domingo P, Estrada V, Fulladosa X, Galindo MJ,
Gràcia S, Iribarren JA, Knobel H, López-Aldeguer J, Lozano F,
Martínez-Castelao A, Martínez E, Mazuecos MA, Miralles C,
Montañés R, Negredo E, Palacios R, Pérez-Elías MJ, Portilla J,
Praga M, Quereda C, Rivero A, Santamaría JM, Sanz J, Sanz J, Miró
JM. EXECUTIVE SUMMARY OF THE RECOMMENDATIONS ON THE
EVALUATION AND MANAGEMENT OF RENAL DISEASE IN HUMAN
IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS. Enferm Infecc
Microbiol Clin. 32(9):583-97. PMID: 25303781.
Ars E, Bernis C, Fraga G, Martínez V, Martins J, Ortiz A, RodríguezPérez JC, Sans L, Torra R; on behalf of the Spanish Working Group
on Inherited Kidney Disease. SPANISH GUIDELINES FOR THE
MANAGEMENT OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY
DISEASE. .Sep;29(suppl 4):iv95-iv105. Nephrol Dial Transplant (29)
Supl 4:95-105. PMID: 25165191.
– 17 –
SCIENTIFIC OUTPUT
Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J, Almagro P,
Quintano JA, Riesco JA, Trigueros JA, Piñera P, Simón A,
Rodríguez-Hermosa JL, Marco E, López D, Coll R, Coll-Fernández
R, Lobo MÁ, Díez J, Soriano JB, Ancochea J. SPANISH GUIDELINE
FOR COPD (GESEPOC). UPDATE 2014. Arch Bronconeumol. 50
Suppl 1:1-16. PMID: 24507959.
Maestre J, Masjuan J, Martí-Fábregas J, Martínez-Sánchez P,
Martínez-Vila E, Molina C, Nombela F, Ribó M, Rodríguez-Yañez M,
Rubio F, Serena J, Simal P, Vivancos J. GUIDELINES FOR THE PREVENTIVE TREATMENT OF ISCHAEMIC STROKE AND TIA (II).
RECOMMENDATIONS ACCORDING TO AETIOLOGICAL SUB-TYPE.
Neurologia. 29(3):168-183. 2014. PMID: 21937151.
Haro JM, Ayuso-Mateos JL, Bitter I, Demotes-Mainard J, Leboyer
M, Lewis SW, Linszen D, Maj M, McDaid D, Meyer-Lindenberg A,
Robbins TW, Schumann G, Thornicroft G, Van Der Feltz-Cornelis C,
Van Os J, Wahlbeck K, Wittchen HU, Wykes T, Arango C,
Bickenbach J, Brunn M, Cammarata P, Chevreul K, Evans-Lacko S,
Finocchiaro C, Fiorillo A, Forsman AK, Hazo JB, Knappe S, Kuepper
R, Luciano M, Miret M, Obradors-Tarragó C, Pagano G, Papp S,
Walker-Tilley T. ROAMER: ROADMAP FOR MENTAL HEALTH RESEARCH IN EUROPE. Int J Methods Psychiatr Res. 23(1):1-14. PMID:
24375532.
Alonso de Leciñana M, Egido JA, Casado I, Ribó M, Dávalos A,
Masjuan J, Caniego JL, Martínez Vila E, Díez Tejedor E; por el
Comitéad hoc del grupo de Estudio de Enfermedades
Cerebrovasculares de la SEN:, Fuentes Secretaría B, Alvarez-Sabin
J, Arenillas J, Calleja S, Castellanos M, Castillo J, Díaz-Otero F,
López-Fernández JC, Freijo M, Gállego J, García-Pastor A, GilNúñez A, Gilo F, Irimia P, Lago A, Maestre J, Martí-Fábregas J,
Martínez-Sánchez P, Molina C, Morales A, Nombela F, Purroy F,
Rodríguez-Yañez M, Roquer J, Rubio F, Segura T, Serena J, Simal P,
Tejada J, Vivancos J. GUIDELINES FOR THE TREATMENT OF ACUTE
ISCHAEMIC STROKE. Neurologia. 29(2):102-122. 2014. PMID:
22152803.
Vivancos J, Gilo F, Frutos R, Maestre J, García-Pastor A, Quintana
F, Roda JM, Ximénez-Carrillo A, Díez Tejedor E, Fuentes B, Alonso
de Leciñana M, Alvarez-Sabin J, Arenillas J, Calleja S, Casado I,
Castellanos M, Castillo J, Dávalos A, Díaz-Otero F, Egido JA,
Fernández JC, Freijo M, Gállego J, Gil-Núñez A, Irimia P, Lago A,
Masjuan J, Martí-Fábregas J, Martínez-Sánchez P, Martínez-Vila E,
Molina C, Morales A, Nombela F, Purroy F, Ribó M, Rodríguez-Yañez
M, Roquer J, Rubio F, Segura T, Serena J, Simal P, Tejada J; por el
Comitéad hoc del Grupo de Estudio de Enfermedades
Cerebrovasculares de la Sociedad Española de Neurología (SEN).
CLINICAL MANAGEMENT GUIDELINES FOR SUBARACHNOID HAEMORRHAGE. DIAGNOSIS AND TREATMENT. Neurologia. 2012 Oct
6. 29(6):353-70. PMID: 23044408.
Alonso de Leciñana M, Díaz-Guzmán J, Egido JA, García Pastor A,
Martínez-Sánchez P, Vivancos J, Díez-Tejedor E; en nombre del
Comité ad hoc del Foro de Ictus de la Asociación Madrileña de
Neurologia. REFLECTIONS ON ENDOVASCULAR TREATMENT FOR
ISCHAEMIC STROKE. A STROKE CARE PLAN FOR THE REGION OF
MADRID. Neurología.
pii: S0213-4853(14)00086-3. PMID:
24864007.
Fuentes B, Gállego J, Gil-Nuñez A, Morales A, Purroy F, Roquer J,
Segura T, Tejada J, Lago A, Díez-Tejedor E; por el Comité ad hoc del
grupo de Estudio de Enfermedades Cerebrovasculares de la SEN:,
Alonso de Leciñana M, Alvarez-Sabin J, Arenillas J, Calleja S,
Casado I, Castellanos M, Castillo J, Dávalos A, Díaz-Otero F, Egido
JA, López-Fernández JC, Freijo M, García Pastor A, Gilo F, Irimia P,
– 18 –
Del Toro Santos FJ, Castañeda S, Cantero Santamaría JI, Grupo de
Trabajo Observar. INFORME SOBRE LA FALTA DE ADHERENCIA AL
TRATAMIENTO CON FAME SINTÉTICOS EN ARTRITIS REUMATOIDE. Editado por Bate Scientia Salus. ISSN: 2174-8101.
Martín-Martínez MA, González-Juanatey C, Castañeda S, Llorca J,
Ferraz-Amaro I, Fernández-Gutiérrez B, Díaz-González F, GonzálezGay MA. RECOMMENDATIONS FOR THE MANAGEMENT OF CARDIOVASCULAR RISK IN PATIENTS WITH RHEUMATOID ARTHRITIS:
SCIENTIFIC EVIDENCE AND EXPERT OPINION. Semin Arthritis
Rheum (44) 1:1-8. PMID: 24560170.
Rosario García de Vicuña. Coordinadora científica de la Estrategia
y miembro del grupo de Redacción. ESTRATEGIA EN ENFERMEDADES REUMÁTICAS Y MUSCULOESQUELÉTICAS DEL SISTEMA
NACIONAL DE SALUD. Madrid: Ministerio de Sanidad, Servicios
Sociales e Igualdad; 2013
Javier Pérez Gisbert. PROYECTO AHEAD2014. RECOMENDACIONES SOBRE EL USO DE FACTORES PREDICTIVOS EN LA PRÁCTICA
CLÍNICA EN PACIENTES CON EEII. GETECCU
Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos
G, Hamm C, Head SJ, Jüni P, Kappetein AP, Kastrati A, Knuuti J,
Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P,
Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M,
Wijns W, Witkowski A; ESC Committee for Practice Guidelines,
Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H,
Dean V, Deaton C, Erol Ç, Fagard R, Ferrari R, Hasdai D, Hoes AW,
Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A,
Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo
JL, Tendera M, Torbicki A, Wijns W, Windecker S; EACTS Clinical
Guidelines Committee, Sousa Uva M, Achenbach S, Pepper J,
Anyanwu A, Badimon L, Bauersachs J, Baumbach A, Beygui F,
Bonaros N, De Carlo M, Deaton C, Dobrev D, Dunning J, Eeckhout
E, Gielen S, Hasdai D, Kirchhof P, Luckraz H, Mahrholdt H,
Montalescot G, Paparella D, Rastan AJ, Sanmartin M, Sergeant P,
Silber S, Tamargo J, ten Berg J8, Thiele H, van Geuns RJ, Wagner
HO, Wassmann S, Wendler O, Zamorano JL. 2014 ESC/EACTS GUIDELINES ON MYOCARDIAL REVASCULARIZATION: THE TASK
FORCE ON MYOCARDIAL REVASCULARIZATION OF THE EUROPEAN SOCIETY OF CARDIOLOGY (ESC) AND THE EUROPEAN ASSOCIATION FOR CARDIO-THORACIC SURGERY (EACTS). DEVELOPED
WITH THE SPECIAL CONTRIBUTION OF THE EUROPEAN ASSOCIATION OF PERCUTANEOUS CARDIOVASCULAR INTERVENTIONS
(EAPCI). Eur J Cardiothorac Surg. 46(4):517-92. PMID:25173601.
Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V,
Filippatos G, Hamm C, Head SJ, Jüni P, Kappetein AP, Kastrati A,
Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ,
Schauerte P, Uva MS, Stefanini GG, Taggart DP, Torracca L,
Valgimigli M, Wijns W, Witkowski A. 2014 ESC/EACTS GUIDELINES
ON MYOCARDIAL REVASCULARIZATION. Kardiol Pol. 72(12):1253379. PMID :25524605.
Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V,
Filippatos G, Hamm C, Head SJ, Jüni P, Kappetein AP, Kastrati A,
Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ,
Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L,
Valgimigli M, Wijns W, Witkowski A; Authors/Task Force members.
2014 ESC/EACTS GUIDELINES ON MYOCARDIAL REVASCULARIZATION: THE TASK FORCE ON MYOCARDIAL REVASCULARIZATION OF THE EUROPEAN SOCIETY OF CARDIOLOGY (ESC) AND
THE EUROPEAN ASSOCIATION FOR CARDIO-THORACIC SURGERY
(EACTS)DEVELOPED WITH THE SPECIAL CONTRIBUTION OF THE
EUROPEAN ASSOCIATION OF PERCUTANEOUS CARDIOVASCULAR
INTERVENTIONS (EAPCI). Eur Heart J. 35(37):2541-619. PMID:
25173339.
Authors/Task Force members, Elliott PM, Anastasakis A, Borger
MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A,
Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J,
Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten
FH, Tillmanns C, Watkins H; Authors/Task Force members. 2014
ESC GUIDELINES ON DIAGNOSIS AND MANAGEMENT OF HYPERTROPHIC CARDIOMYOPATHY: THE TASK FORCE FOR THE DIAGNOSIS AND MANAGEMENT OF HYPERTROPHIC CARDIOMYOPATHY OF THE EUROPEAN SOCIETY OF CARDIOLOGY (ESC). Eur
Heart J. 35(39):2733-79. PMID :25173338
Expert Panel of GeSIDA and the National Aids Plan, Berenguer J,
Polo R, Lozano F, López Aldeguer J, Antela A, Arribas JR, Asensi V,
Blanco JR, Clotet B, Domingo P, Galindo MJ, Gatell JM, GonzálezGarcía J, Iribarren JA, Locutura J, López JC, Mallolas J, Martínez E,
Miralles C, Miró JM, Moreno S, Palacios R, Pérez Elías MJ, Pineda
JA, Podzamczer D, Portilla J, Pulido F, Ribera E, Riera M, Rubio R,
Santos J, Sanz J, Tuset M, Vidal F, Rivero A. EXECUTIVE SUMMARY
OF THE GESIDA/NATIONAL AIDS PLAN CONSENSUS DOCUMENT
ON ANTIRETROVIRAL THERAPY IN ADULTS INFECTED BY THE
HUMAN IMMUNODEFICIENCY VIRUS UPDATED JANUARY 2014.
Enferm Infecc Microbiol Clin (32) 5:447-458. PMID: 24986715
Juan Berenguer, Jorge Carmena, Mª Angeles Castro, Juan
González, Josep Mª Guardiola, Pablo Labarga, Montse Laguno,
Juan Macías, Andrés Marco, Luz Martin-Carbonero, Josep
Mallolas, Pilar Miralles, José Moltó, Mª Luisa Montes, Javier
Murillas, Enrique Ortega, Juan A Pineda, Carmen Quereda, Antonio
Ribero, Antoni Rimola, Ignacio de los Santos, Mª Jesús Téllez,
Cristina Tural, Eva van den Eynde Coordinadores: Manuel Crespo,
Miguel A Von Wichmann. GUÍA GESIDA DE TRATAMIENTO DE LAS
HEPATITIS VIRALES EN PACIENTES INFECTADOS POR VIH.
http://www.gesida-seimc.org/contenidos/guiasclinicas/borrador/2014/gesida-guiasclinicas-2014-BR-hepatitisviralesvih.pdf.
GESIDA.
Panel de expertos de GESIDA, SEN y SEQC: Gorriz JL, Gutiérrez F,
Trullàs JC, Arazo P, Arribas JR, Barril G, Cervero M, Cofán F,
Domingo P, Estrada V, Fulladosa X, Galindo MJ, Gràcia S, Iribarren
JA, Knobel H, López-Aldeguer J, Lozano F, Martínez-Castelao A,
Martínez E, Mazuecos MA, Miralles C, Montañés R, Negredo E,
Palacios R, Pérez-Elías MJ, Portilla J, Praga M, Quereda C, Rivero
A, Santamaría JM, Sanz J, Sanz J, Miró JM. DOCUMENTO DE CONSENSO SOBRE LA EVALUACIÓN Y MANEJO DE LA AFECTACIÓN
RENAL EN PACIENTES CON INFECCIÓN POR EL VIH JULIO 2014.
GESIDA.
Panel de expertos de GeSIDA y Plan Nacional sobre el SIDA:
Berenguer J, Polo R, Lozano F, López Aldeguer J, Antela A, Arribas
JR, Asensi V, Blanco JR, Clotet B, Domingo P, Galindo MJ, Gatell
– 19 –
SCIENTIFIC OUTPUT
JM, González-García J, Iribarren JA, Locutura J, López JC, Mallolas
J, Martínez E, Miralles C, Miró JM, Moreno S, Palacios R, Pérez
Elías MJ, Pineda JA, Podzamczer D, Portilla J, Pulido F, Ribera E,
Riera M, Rubio R, Santos J, Sanz J, Tuset M, Vidal F, Rivero A.
DOCUMENTO DE CONSENSO DE GESIDA/PLAN NACIONAL SOBRE
EL SIDA RESPECTO AL TRATAMIENTO ANTIRRETROVIRAL EN
ADULTOS INFECTADOS POR EL VIRUS DE LA INMUNODEFICIENCIA
HUMANA ACTUALIZACIÓN ENERO 2014. GESIDA.
Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J, Almagro P,
Quintano JA, Riesco JA, Trigueros JA, Piñera P, Simón A,
Rodríguez-Hermosa JL, Marco E, López D, Coll R, Coll-Fernández
R, Lobo MÁ, Díez J, Soriano JB, Ancochea J. SPANISH GUIDELINE
FOR COPD (GESEPOC). UPDATE 2014. Arch Bronconeumol. 50
Suppl 1:1-16. 2014. PMID: 24507959.
PATENTES
PATENTS
Nuestro IIS-Princesa apuesta por la transferencia de tecnología y
conocimiento, siendo la Unidad de Innovación fundamental para
llevar a cabo esta tarea. Prueba de ello son las patentes que durante el último año han sido solicitadas y concedidas, de las cuales se
muestra un listado a continuación.
Our IIS-Princesa is committed to the transfer of technology and
knowledge, and the Innovation Unit is fundamental to perform this
task. Proof of this are the patents that have been applied for and
granted over the last year. A list of them is shown below.
PATENTES SOLICITADAS
PATENT APPLICATIONS
TITLE: MÉTODO PRONÓSTICO DE ENFERMEDADES AUTOINMUNES
MEDIANTE EL GENOTIPADO DE VARIANTES GENÉTICAS DEL
PÉPTIDO INTESTINAL VASOACTIVO
NUMBER: P201430364
OWNER/S: FIB, Universidad Complutense de Madrid
INVENTORS: González Álvaro, Isidoro; Ortiz García, Ana María;
– 20 –
Lamana Domínguez, Amalia; Pérez Gomariz, Rosa; Martínez Mora,
María del Carmen; Leceta Martínez, Javier; Juarranz Moratilla,
Yasmina.
DATE OF APPLICATION: 17/03/2014
TITLE: ANTIBODY DRUG CONJUGATES
NUMBER: PCT/EP2014/061392
OWNER/S: PHARMA MAR SA.
INVENTORS: Cuevas Marchante, Carmen; Domínguez Correa, Juan
Manuel; Francech Solloso, Andrés; Garranzo García-Ibarrola,
María; Muñoz Alonso, María José; Sánchez Madríd, Francisco;
Zapata Hernández, Juan Manuel; García Arroyo, Alicia; Ursa
Pecharromán, María Ángeles.
TITLE: COMPUESTOS DERIVADOS DE ACRILATO DE 3-ALQUILOAMINO-1H-INDOLILO Y SU USO EN EL TRATAMIENTO DE ENFERMEDADES NEURODEGENERATIVAS
NUMBER: P201400810
OWNER/S: FIB
INVENTORS: León R., Egea J., Buendia I., Navarro E., Michalsca P.,
Gameiro I., López MG.
TITLE: PROCEDIMIENTO PARA LA INHIBICIÓN DE LA PRODUCCIÓN
DE ESPECIES REACTIVAS DE OXÍGENO POR LA MITOCONDRIA, Y
DE LA ADAPTACIÓN A HIPOXIA
NUMBER: P201400968
OWNER/S: FIB HUP, UAM
INVENTORS: Martínez Ruiz A, Hernansanz-Agustín P
PATENTES CONCEDIDAS
GRANTED PATENTS
TITLE: APLICACIÓN TERAPEÚTICA DE AGENTES INHIBIDORES DE
CD44 FRENTE A LA LEUCEMIA LINFOBLÁSTICA AGUDA (ALL)
HUMANA
NUMBER: P201231274
OWNER/S: CSIC, UAM
INVENTORS: Toribio García, María Luisa, García Peydro, Marina,
Sánchez Madrid, Francisco
DATE OF APPLICATION:06/08/2012
GRANT DATE: 06/04/2014
TITLE: COMPOSICIÓN FARMACÉUTICA PARA EL TRATAMIENTO DE
LAS ENFERMEDADES CEREBROVASCULARES
NUMBER: P201101263
OWNER/S: Universidad Complutense de Madrid
INVENTORS: Lizasoain I, Moro MA, Hurtado O, Pradillo J
GRANT DATE: 04/04/2014
TESIS DOCTORALES DEFENDIDAS
DEFENDED DOCTORAL THESES
La gran dedicación de formación del IP se ve reflejada en el gran
número de tesis doctorales que son dirigidas por miembros del IP.
En el seno del IP, durante el año 2014 han sido defendidas 8 tesis
nacionales y 2 internacionales. A continuación se proporciona un
detalle de las mismas.
The great dedication of IP to training is reflected in the large number of doctoral theses supervised by IP members. Within the IP,
during the year 2014 a total of 8 national and 2 international theses have been defended. Details are shown below.
Efecto del estrés prenatal sobre la respuesta metabólica y el
recambio celular en el eje hipocampo-hipotálamo-hipofisiario.
Respuesta a una dieta rica en sacarosa
Doctoral candidate: Eva Baquedano Caballero
Director/s: Laura María Frago Fernández, Jesús Argente Oliver
Caracterización del papel de la ácido graso translocasa CD36
en la enfermedad hepática grasa no alcohólica y en la hepatitis crónica por virus C
Doctoral candidate: Miguel Fernández Bermejo
Director/s: Carmelo García Monzón, Ignacio de los Santos Gil
CALHM1 un nuevo canal de calcio implicado en la Enfermedad
de Alzheimer
Doctoral candidate: Ana José Moreno Ortega
Director/s: María Francisca Cano Abad, Manuela García López
Phase IV, prospective, randomized and comparative study between sequential and concomitant therapy for Helicobacter
pylori eradication in routine clinical practice
Doctoral candidate: Adrian McNicholl
Director/s: Javier Pérez Gisbert
Estudio de los fagos de Helicobacter pylori por métodos fenotípicos y genotípicos
Doctoral candidate: Esteban Aznar Cano
Director/s: Manuel López-Brea Calvo, Teresa Alarcón Cavero
TESIS NACIONALES
SPANISH THESES
Alteraciones en la hematopoyesis y el metabolismo de la L-arginina durante la infección aguda experimental por trypanosoma cruzi
Doctoral candidate: Sofía Carbajosa González
Director/s: Nuria Gironés Pujol
Regulación de la Expresión génica por la prostaglandina F2a en linfocitos T y cardiomiocitos: activacion de la vía de señalización de
calcio/calcineurina/NFAT
Doctoral candidate: Elena Hernández Subirá
Director/s: Miguel Ángel Íñiguez Peña
Efecto de la sobrenutrición neonatal en la respuesta aguda a la leptina em los periodos prepuberal y peripuberal
Doctoral candidate: David Castro González
Director/s: Jesús Argente Oliver, Julie Ann Chowen King
TESIS EUROPEAS
EUROPEAN THESES
GRK2 as a new onco-modulator of breast tumoural transformation through the regulation of the p53/MDM2 axis
Doctoral candidate: Laura Nogués Vera
Director/s: Federico Mayor Menéndez, Petronila Penela
Márquez
Measuring disease activiy in early rheumatoid arthritis: an
emerging challenge/ cómo medir la actividad de la enfermedad en artritis reumatoide precoz: un nuevo reto
Doctoral candidate: Isabel Castrejón Fernández
Director/s: Isidoro González Álvaro, Loreto Carmona Ortells,
Rosario García de Vicuña
– 21 –
SCIENTIFIC OUTPUT
COMUNICACIÓN Y DIFUSIÓN
COMMUNICATION AND DIFUSSION
La difusión no sólo de los resultados, sino también de todas las
ideas y actividades llevadas a cabo, constituye un importante pilar
en nuestro Instituto.
En el momento actual en el que las nuevas tecnologías facilitan dicha difusión nuestra página Web es un gran escaparate que
nos permite la difusión de cualquier actividad llevada a cabo en
nuestro Instituto. A través de ella se difunden los eventos científicos, cursos y congresos, ofertas de empleo y noticias destacables
que tienen lugar en nuestro entorno.
Durante el pasado año, recibió 31.566 visitantes, lo que supone un incremento del 8% respecto al año 2013.
An important mainstay of our Institute is dissemination, not only of
the results, but also of all the ideas and activities carried out.
COUNTRY
2012
2011
IMPROV.
25875
24295
+7%
UK
748
321
+133%
COLOMBIA
357
364
-2%
US
277
221
+25%
BRAZIL
222
25
+788%
SPAIN
– 22 –
Nowadays, when new technologies facilitate such dissemination, our website is a showcase that allows us to spread any activity carried out in our Institute. Scientific events, courses and conferences, job offers and remarkable news that take place in our
environment are disseminated through this website.
During the last year, it received 31 566 visitors, representing an
increase of 8% over 2013.
Además, desde el año 2011 periódicamente se publica un boletín
informativo “Factor de Impacto”, donde no sólo se difunden los avances científicos conseguidos, sino que se dan a conocer las diferentes
líneas de trabajo de cada grupo que conforma nuestro Instituto.
In addition, since 2011 a newsletter "Factor de Impacto” is
published periodically, where not only the scientific advances
achieved are presented, but the different lines of work of each
group that makes up the Institute are also shown.
PLATAFORMAS CIENTÍFICAS
SCIENTIFIC PLATFORMS
PLATAFORMAS DE APOYO
PLATFORM SUPPORT
APOYO METODOLÓGICO
METHODOLOGICAL UNIT
UNIDAD APOYO DIRECCIÓN CIENTÍFICA
SCIENTIFIC MANAGEMENT SUPPORT UNIT
Tiene como fin proporcionar a los equipos de investigación del IP
el apoyo preciso para la elaboración y ejecución de los proyectos
de investigación, con el fin de incrementar la excelencia de la actividad científica del IIS-Princesa.
La Unidad de Apoyo a la Dirección Científica del IIS-Princesa
tiene como principal objetivo la organización, planificación y
coordinación de todas aquellas estructuras de apoyo al ámbito científico y los investigadores del Instituto, bajo la supervisión del Director Científico del Instituto.
The Scientific Management Support Unit of IIS-Princess has
as main objective the organization, planning and coordination
of all structures of support for the scientific environment and
the researchers of the Institute, under the supervision of the
Scientific Director of the Institute.
COORDINADOR / COORDINATOR
Dr. Javier Aspa
ANIMALARIO
ANIMAL FACILITY
El Gabinete Veterinario de la Universidad Autónoma de Madrid
ofrece los servicios a nuestro Instituto. Es un Servicio, cuyo fin
es mantener, producir y controlar los animales de experimentación destinados a la Investigación.
The Veterinary Office of the Universidad Autónoma de Madrid
offers its services to our Institute. It is a service whose purpose is to maintain, produce and control animals for experimental research.
DIRECTOR / DIRECTOR
D. David Muñoz Valverde
It aims to provide to IP research teams support for the development
and implementation of research projects in order to increase the
excellence of the scientific activity of IIS-Princesa.
Dr. Francisco Rodríguez Salvanés
PERSONAL TÉCNICO / TECHNICAL STAFF
Dª. Lorena Vega Piris
BIOBANCO
BIOBANK
La Unidad de Apoyo a la Dirección Científica del IIS-Princesa tiene
como principal objetivo la organización, planificación y coordinación de todas aquellas estructuras de apoyo al ámbito científico y
los investigadores del Instituto, bajo la supervisión del Director
Científico del Instituto.
The Scientific Management Support Unit of IIS-Princess has as
main objective the organization, planning and coordination of all
structures of support for the scientific environment and the
researchers of the Institute, under the supervision of the Scientific
Director of the Institute.
RESPONSABLE CIENTÍFICA / SCIENTIFIC COORDINATOR
Dra. Mara Ortega Gómez
COMITÉ COLABORADOR / SENIOR COMMITTEE
(Oncología Médica/Medical Oncology)
– 23 –
(Reumatología/Rhematology)
Dr. José A. Jiménez Heffernan
(Anatomía Patológica/Pathology)
Dr. Carlos Manuel Olivier Gómez
(Urología/Urology)
PERSONAL TÉCNICO / TECHNICAL STAFF
D. Sergio Luquero Bueno
CITOMETRÍA
FLOW CYTOMETRY UNIT
La Unidad de Citometría de Flujo está ubicada en el Servicio de
Inmunología y de Biología Molecular del Hospital Universitario de La
Princesa y recientemente se ha incorporado a la Red de Laboratorios de
Organismos Públicos de Investigación (REDLAB) de la Comunidad de
Madrid.
La Unidad provee de instrumentación y asistencia técnica a los
investigadores para poder realizar tanto análisis de inmunofenotipo como
la realización de separaciones celulares (cell sorting) en base a parámetros de fluorescencia.
The Flow Cytometry Unit is located in the Department of Immunology and
Molecular Biology, University Hospital of La Princesa and has recently
joined the Network of Laboratories of Public Research Organizations
(REDLAB) of the Community of Madrid.
The unit provides instrumentation and technical assistance to the
researchers to perform both immunophenotype analysis and cell sorting
based on fluorescence parameters.
COORDINADORA / COORDINATOR
Dra. Cecilia Muñoz Calleja
tometría, extracción automatizada de ácidos nucleicos, determinación de
integridad de RNA, PCR y RT-PCR convencional, PCR y RT-PCR en tiempo real, software de búsqueda e integración de datos experimentales y,
recientemente, secuenciación masiva.
The Genomics Unit is responsible for the development and implementation of technologies for molecular biology and genomics, equipment
maintenance, and provision of technical advice on various technologies
to research groups. It uses different technologies as spectrophotometry,
automated extraction of nucleic acids, RNA integrity determination, conventional PCR and RT-PCR, real time PCR and RT-PCR, software for
search and integration of experimental data and, recently, massive
sequencing.
DIRECTOR TÉCNICO / TECHNICAL DIRECTOR
Dr. Fernando Carrasco Ramiro
MICROSCOPÍA ELECTRÓNICA
ELECTRONIC MICROSCOPE SERVICE
El servicio de Microscopía Electrónica de la UAM ofrece asistencia técnica y apoyo científico a los grupos de investigación interesados en emplear técnicas de microscopía electrónica para el análisis ultraestructural de
muestras biológicas y la inmunodetección de antígenos. Se dispone de
un microscopio electrónico de transmisión y el material necesario para la
preparación de muestras.
The Electron Microscopy Service of UAM provides technical assistance
and scientific support to research groups interested in using electron
microscopy techniques for ultrastructural analysis of biological samples
and immunodetection of antigens. It has a transmission electron microscope and the material needed for sample preparation.
Dra. María Teresa Rejas Marco
GENÓMICA
GENOMIC UNIT
PROTEÓMICA
PROTEOMIC UNIT
La Unidad de Genómica es responsable del desarrollo e implementación
de tecnologías de biología molecular y genómica, mantenimiento de
equipos, y provisión de asesoría técnica sobre distintas tecnologías a los
grupos de investigación. Utiliza diferentes tecnologías como espectrofo-
El servicio de Proteómica tiene entre sus objetivos ofrecer apoyo y asesoramiento científico-técnico a los grupos de investigación en la identificación y caracterización de proteínas mediante técnicas de espectrometría de masas (EM).
– 24 –
Proteomics service's objectives are to provide the research groups with
support and scientific and technical advice in the identification and characterization of proteins by mass spectrometry (MS) techniques.
UNIDADES
UNITS
Dª. Ana Isabel Marina Ramirez
UNIDAD DE INNOVACIÓN
INNOVATION UNIT
SALA BLANCA
CLEAN ROOM
La Unidad de Innovación del Hospital de La Princesa nacIó con la
creación del Instituto de Investigación, y es la encargada, con los
recursos existentes, de analizar las nuevas tendencias tecnológicas
y de su implementación en el Instituto. Lo más destacable de su
puesta en marcha fue la creación de la Unidad de Terapias
Biológicas cuyo objetivo principal es contribuir al mejor uso de las
terapias biológicas atendiendo a criterios de eficiencia, seguridad y
coste-efectividad.
La Unidad de Innovación del Instituto de Investigación Sanitaria
Hospital Universitario de La Princesa se consolidó con su incorporación a la Plataforma de Innovación en Tecnologías Médicas y
Sanitarias (ITEMAS) accediendo a la financiación de la convocatoria 2013 de concesión de subvenciones de la Acción Estratégica
en Salud, del Instituto de Salud Carlos III.
La Sala Blanca situada en el Hospital Niño Jesús, es una instalación especializada para trabajar en niveles mínimos o ausentes de contaminación
que cumple los requerimientos de Buenas Prácticas de Fabricación (del
inglés Good Manufacture Practice, GMP). La Sala Blanca tiene la
Certificación de Cumplimiento de Normas de Correcta Fabricación desde
Abril 2010, tanto para Terapia Celular como Terapia Génica.
The clean room located in the Niño Jesús Hospital, is a facility specialized to work with minimal or absent levels of contamination that meets
the requirements of Good Manufacturing Practices (GMP). The Clean
Room has Certification of Compliance with GMP since April 2010, both
for Cell Therapy and Gene Therapy.
Dra. María Antonia Varela-Portas San Juan
VIDEOMICROSCOPÍA CONFOCAL
CONFOCAL MICROSCOPY SERVICE
El Servicio de Videomicroscopía del Instituto ofrece la infraestructura y el
asesoramiento científico-técnico necesario para la realización de estudios de microscopía de fluorescencia, confocal y de onda evanescente,
con especial énfasis en la observación de fenómenos dinámicos en célula viva.
The Institute Videomicroscopy Service provides the infrastructure and
scientific expertise needed for studies of fluorescence, confocal and
evanescent wave microsopy, with special emphasis on the observation
of dynamic processes in living cell.
Dr. Miguel Vicente Manzanares
The Innovation Unit of the Hospital de La Princesa was born with
the foundation of the Research Institute, and is responsible, with
the existing resources, to analyze new technological trends and
their implementation at the Institute. The highlight of its launch was
the creation of the Biological Therapies Unit whose main objective
is to contribute to better use of biological therapies based on criteria of efficiency, safety and cost-effectiveness.
The Innovation Unit of the Health Research Institute Hospital
Universitario de La Princesa was consolidated when it joined the
Platform for Innovation in Medical and Health Technologies (ITEMAS,
getting access to the funding of the 2013 call for grants from the
Strategic Action in Health, from Institute of Health Carlos III.
Dra. Carmen Suárez Fernández
(Sº Medicina Interna, Internal Medicine Department)
COMITÉ DE INNOVACIÓN / INNOVATION COMMITTEE
(Sº Neumología, Respiratory Department)
Dr. Francisco Javier Aspa Marco
((Sº Medicina Interna- Urgencias, Internal Medicine-Emergency
Unit)
– 25 –
Dª Marian Centellas
(Dirección de Enfermería, Nursing Management)
Dr. Jesús Jiménez Borreguero
(Sº Cardiología, Cardiology Department)
Dr. Alberto Morell Baladrón
(Sº Farmacia Hospitalaria, Pharmacy Department)
Dr. Ramón Moreno Balsalobre
(Sº Cirugía Torácica, Thoracic Surgery Department)
D. Francisco Redondo Montserrat
(DUE, Nurse)
Dr. Luis Sánchez-Urdazpal González
(Sº Cirugía General y Aparato Digestivo, General Surgery
Department)
Dr. Alberto Sebastián Palomino
(Dirección de Continuidad Asistencial)
Dra. Gema Vega González
(Sº Medicina Intensiva, Intensive Care Department)
Dr. José Aurelio Vivancos Mora
(Sº Neurología, Neurology Department)
EQUIPO MULTIDISCIPLINAR / MULTIDISCIPLINAR TEAM
(Sº Reumatología, Rheumatology Department)
Dr. Esteban Daudén Tello
(Sº Dermatología, Dermatology Department)
Dr. Javier Pérez Gisbert
(Sº Digestivo, Gastroenterology Department)
Dra. Virginia Meca Lallana
(Sº Neurología, Neurology Department)
UNIDAD DE TERAPIAS BIOLÓGICAS
BIOLOGICAL THERAPY UNIT
The Clinical Trials Unit was created with the primary objective of
promoting clinical research as well as providing support to
researchers. Clinical trials or observational studies promoted
and/or led by researchers are considered independent clinical
research
Las terapias biológicas son el resultado del gran avance paralelo en
el conocimiento de la patogenia de enfermedades inflamatorias y
autoinmunes crónicas y la biotecnología. Su desarrollo constituye
uno de los cambios más relevantes ocurridos en las últimas décadas. Esta Unidad coordina tratamientos eficaces (con un elevado
coste) asegurando la sostenibilidad de los mismos. Su idea principal
es contribuir al mejor uso de las terapias biológicas atendiendo a criterios de rigor científico, seguridad, eficiencia y coste-efectividad.
Biological therapies are the result of the large parallel progress in
understanding the pathogenesis of chronic inflammatory and
autoimmune diseases and in biotechnology. Its development is one
of the most significant changes in recent decades. This Unit coordinates effective treatments (with high cost) ensuring their sustainability. The main idea is to contribute to the better use of biological
therapies based on criteria of scientific thoroughness, safety, efficiency and cost-effectiveness.
Dr. José Mª Álvaro Gracia
(Sº Reumatología, Rheumatology Department)
– 26 –
UNIDAD DE ENSAYOS CLÍNICOS
CLINICAL TRIALS UNIT
La Unidad de Ensayos Clínicos nace con el objetivo principal de
promover la investigación clínica además de dar apoyo a los investigadores. Se considera investigación clínica independiente aquellos ensayos clínicos o estudios observacionales que son promovidos y/o liderados por los propios investigadores.
COMISIONES
COMMITTEES
COMISIÓN DE CALIDAD
QUALITY COMMITTEE
Para alcanzar unos resultados objetivos de excelencia y obtener
una mejora continua, la Comisión de Calidad, no sólo elabora, sino
que supervisa de manera continua la implementación de los procedimientos de calidad establecidos en nuestro Instituto.
To achieve objective results of excellence and get a continuous
improvement, the Quality Commission not only elaborates, but also
continuously monitors the implementation of quality procedures
established in our Institute.
niveles (formación de Grado, Posgrado, Sanitaria Especializada y
Continuada).
Dra. Rosa Gómez de Merodio (Responsable)
Dra. Pilar González
Don Jesús Capa (Secretario)
One of the priorities set by the IIS-Princesa is the promotion and
development of training programs for professionals who are part of
the Centre, with a focus on training for translational research to
improve the competitiveness of institutions and the qualifications of
the personnel that integrates them.
In this sense, all entities that are part of the Health Research Institute
Hospital Universitario de La Princesa have an established training and
teaching track, and have a wide training offer at all levels (training of
undergraduate, graduate, and Continuing Specialized Health).
COMISIÓN DE FORMACIÓN
EDUCATION COMMITTEE
Una de las prioridades establecidas por el IIS-Princesa es el
fomento y desarrollo de programas de formación dirigidos a los
profesionales que forman parte del Centro, con especial interés en
la formación para la investigación traslacional, que mejore la competitividad de las instituciones, así como la cualificación del personal que las integra.
En este sentido, todas las entidades que forman parte del
Instituto de Investigación Sanitaria Hospital Universitario de La
Princesa tienen una trayectoria formativa y docente consolidada,
las cuales presentan una amplia oferta formativa a todos los
Dr Jesús Sanz Sanz (Responsable)
Un representante del Hospital Infantil Universitario Niño Jesús
Un representante del Hospital Universitario Santa Cristina
Un representante de Formación de Pregrado del Hospital Universitario
de La Princesa
Un representante de Formación Posgrado del Hospital Universitario de
La Princesa
Un representante de Formación Continuada del Hospital Universitario
de La Princesa
– 27 –
ÁREAS DE INVESTIGACIÓN
RESEARCH AREAS
ÁREAS DE INVESTIGACIÓN
RESEARCH AREAS
A continuación se muestra un resumen de las tres áreas de investigación en las que está estructurado el Instituto y las líneas que
forman parte de ellas. La actividad científica de cada área muestra
el número de publicaciones, y su factor de impacto medio y acumulado de los 3 últimos años.
Se muestra un resumen de las líneas de investigación actualizadas del año 2014.
A summary of the three research areas in which the Institute is
structured and the lines that are part of them is shown. The
scientific output of each area shows the number of publications and their mean and accumulated impact factor for the
last 3 years.
A summary of current research lines (2014) is shown
below.
AREA 1
MECANISMOS ETIOPATOGÉNICOS CELULARES Y MOLECULARES
EN ENFERMEADES INFLAMATORIAS Y AUTOINMUNES
CELLULAR AND MOLECULAR ETIOPATHOGENIC MECHANISMS IN
INFLAMMATORY AND AUTOIMMUNE DISEASES
LINE
NAME
DIRECTOR
1.1
Intercellular Communication in the Inflammatory Response
1.2
Animal Models of Inflammatory Diseases
and Intercellular Signalling
Julián Aragonés
López
1.3
Animal models of inflammatory diseases
and intercellular signalling
Federico Mayor
Menéndez
1.4
Etiopathogenic and Immunological Mechanisms of Dermatological Diseases
Amaro García
Diez
1.5
Cellular Mechanisms and Molecular Determinants of Allergy-Based Diseases
Carlos Blanco
Guerra
1.6
Inflammatory Processes in Nephrological
Diseases
José Antonio
Sánchez Tomero
1.7
Inflammatory Mechanisms in Pulmonary
Diseases
Julio Ancochea
Bermúdez
1.8
Inflammatory Response in Hepatic Diseases
Pedro L. Majano
Rodríguez
1.9
Mechanisms and Mediators of Endocrine
Diseases
Mónica Marzuela
Azpiroz
1.10
Children´s Development (Obesity and
Growth)
Jesús Argente
Oliver
1.11
Metabolic Syndrome and Vascular Risk
Raffaelle Carraro
AREA 2
NEUTROTRANSMISIÓN, NEUROPORTECCIÓN FARMACOLÓGICA
Y NEURODEGENERATIVA Y ENFERMEDADES
NEUROPSIQUIÁTRICAS
NEUROTRANSMISSION, PHARMACOLOGICAL NEUROPROTECTION AND NEURODEGENERATIVE AND NEUROPSYCHIATRIC
DISEASES
– 28 –
LINE
2.1
2.2
NAME
DIRECTOR
Neuropharmacology and Neuroprotection
Neurotransmission in the Hippocampus
2.3
Clinical Pharmacology and Pharmacogenetics
2.4
Diagnostic and Therapeutic Advances in Affective Disorders
LINE
NAME
DIRECTOR
3.1
Prognostic and Predictor Markers
in Autoimmune Diseases
3.2
Esophagogastrointestinal Inflammatory Diseases
3.3
Progenitors and Cell Therapy
Luis Madero López
3.4
Advanced Therapies in Oncohematology
Juan Luis Steegmann
Olmedillas
3.5
Biological, Cellular and Molecular
Monitoring in Oncohematology
3.6
New Diagnostic and Therapeutic
Advances in Cardiovascular
Diseases
Fernando Alfonso
Manterola
3.7
New Therapies in Infectious Pathologies
3.8
Individualized Medicine in Solid Tumors
2.5
Neurosurgery of Epilepsy
2.6
Cerebrovascular Diseases
José Aurelio Vivancos
Mora
AREA 3
TERAPIAS AVANZADAS Y MEDICINA INDIVIDUALIZADA
ADVANCED THERAPIES AND INDIVIDUALIZED MEDICINE
Isidoro González Álvarez
– 29 –
AREA 1
CELLULAR AND MOLECULAR ETIOPATHOGENIC
MECHANISMS IN INFLAMMATORY AND
AUTOIMMUNE DISEASES
Line 1.1
Intercellular communication in the inflammatory response.
Line 1.2
Cellular and molecular responses to hypoxia.
Line 1.3
Animal models of inflammatory diseases and intercellular signalling.
Line 1.5
Cellular mechanisms and molecular determinants of allergy-based diseases.
Line 1.6
Inflammatory processes in nephrological diseases.
Line 1.7
Inflammatory mechanisms in pulmonary diseases.
Line 1.8
Inflammatory response in hepatic diseases.
Line 1.9
Mechanisms and mediators of endocrine diseases.
Line 1.10
Children´s development (obesity and growth).
Line 1.11
Metabolic syndrome and vascular risk.
– 31 –
AREA 1
CELLULAR AND MOLECULAR
ETIOPATHOGENIC MECHANISMS IN
INFLAMMATORY AND
AUTOIMMUNE DISEASES
– 32 –
AREA 1
CELLULAR AND MOLECULAR ETIOPATHOGENIC
MECHANISMS IN INFLAMMATORY AND
AUTOIMMUNE DISEASES
GROUP 1
HEAD OF LABORATORY
Francisco Sánchez-Madrid.
Scientific Director, Inmmunology.
GROUP MEMBERS
• Francesc Baixauli Celda
• Olga Barreiro del Río
• Noelia Blas Rus
• Eugenio Bustos Moran
• Danay Cibrián Vera
• Hortensia de la Fuente Flores
• Lola Fernández Messina
• Manuel Gómez Gutiérrez
• Cristina Gutiérrez Vázquez
• María José López Campos
• Noa Beatriz Martín Cófreces
• Gloria Martínez del Hoyo Cañizares
• María Mittelbrunn Herrero
• Olga Moreno Gonzalo
• María de las Nieves Navarro Lobato
• Marta Esther Ramírez Huesca
• Vera Rocha Perugini
• María Laura Saiz Álvarez
• Mª Ángeles Ursa Pecharromán
• María Ángeles Vallejo Rodríguez
• Alicia Vara Vega
• Carolina Villarroya Beltri
RESEARCH INTEREST
Lymphocytes exert their functions by communicating with other cells. They form specific immune
synapses with antigen-presenting cells (APCs) and
also secrete soluble mediators. During synapsis,
exosomes—nanovesicles produced by multivesicular bodies (MVBs)—act as “shuttles” that transfer
specific mediators, including microRNAs (miRNA),
to the target cell. Formation of the immune synapse
is triggered by T cell receptor (TCR) stimulation. Its
downstream signaling pathways engage actin and
tubulin-based cytoskeletal networks that control the
spatial and molecular architecture of the IS. One of
these elements is the centrosome or MTOC (microtubule-organizing center). The MTOC governs
directed secretion toward the APC by juxtaposing
the Golgi and endosomal compartments at the T:
APC contact zone. MVBs form part of this assembly
for intracellular transport and sorting. Our group
aims to define the connection between TCR activation and the reorganization of the tubulin cytoskeleton and organelle transport, the delivery of specific
mediators to the APC and other target cells, and the
functional consequences of this mode of cell-cell
communication in the regulation of the immune
inflammatory response.
The group pursues three main lines of investigation.
1) Regulation of immune synapse formation and
function. We are exploring protein multiplexing at
the MTOC, specifically the role of MTOC folding
complexes, and the post-translational modifications
of Ser/Thr kinases and the tubulin deacetylase
HDAC6. We address the molecular mechanisms
that control mitochondria transport during leukocyte-endothelial adhesion and extravasation and
maturation of the IS. We are also analyzing the role
of mitochondrial components in the biogenesis and
secretion of exosomes and their impact on
macrophage and dendritic cell function. 2) Fine tun-
– 33 –
AREA 3 AREA 2 AREA 1
Line 1.1
Intercellular
Communication in the
Inflammatory Response
Cellular and molecular etiopathogenic mechanisms
in inflammatory and autoimmune diseases
ing of T cell biology by miRNAs and exosomes. The
production of exosomes by different T cell subsets is
being examined with the aim of identifying and characterizing specific miRNAs delivered to target cells.
We also investigate the molecular mechanisms
underlying the specific sorting of proteins and
miRNAs to exosomes. This information may allow
engineering of immune cells to produce exosomes
able to specifically modulate the immune response.
3) Immunoregulatory molecules and miRNAs in
inflammatory diseases. We are analyzing the role of
different immunoregulatory molecules such as
CD69, galectins, aminoacid transporters and
HDAC6 in animal models of atherosclerosis and psoriasis in humans in order to identify the molecular
basis of these inflammatory diseases.
• Sánchez Madrid, Francisco. Red cardiovascular.
ISCIII. RD12/0042/0056. 2012-2015.
• Sánchez Madrid, Francisco. Mecanismos reguladores y función polarizada de receptores de
adhesión y quimiotracción y de los componentes
del citoesqueleto que coordina la migración leucocitaria y la sinapsis inmunológica. BFU.058435.
2009-.
• Sánchez Madrid, Francisco. Papel en la fusión de
membrana inducida por vih-1 de los microdominios
adherentes, los complejos de polaridad linfocitaria,
y su conexión con componentes reguladores del
citoesqueleto. FIPSE. 2007-.
Granted 2014:
• Sánchez Madrid, Francisco. Moléculas inmunoreguladoras en inflamación: función de los exosomas
en la comunicación célula-célula. SAF2014-55579R .MINECO. 2015-2017.
MAJOR GRANTS
• Sanchez Madrid, Francisco. Immunoregulatory
molecules as biomarkers predicting response to
biological therapies and disease severity in
immune-mediated inflamatory disorders. BIOMID
PROJECT. PIE13/00041. Proyecto coordinado.
ISCIII. 2014-2016.
• Navarro Lobato, María de las Nieves. Estudio de las
cascadas de señalización de la citoquina proinflamatoria interleuquina 23 implicadas en enfermedades
inflamatorias y autoinmunes. SAF2013-43833-R.
MINECO. 2014-2017.
• Sánchez Madrid, Francisco. Mechanisms of MTOC
guidance and genetic transfer at the immune
synapse: novel modes of immunomodulation.
ERCEA-AdG-2011-294340_GENTRIS. EUROPEAN
RESEARCH Council. 2012-2017
• Sánchez Madrid, Francisco. Nuevos mecanismos
de inmunomodulación: moléculas reguladoras,
polaridad celular y transferencia de información
genética en la comunicación intercelular. MINECO.
SAF2011-25834. 2012-.
• Sánchez Madrid, Francisco. Redes moleculares y
celulares
en
enfermedades
inflamatorias.
MINECO.S2010/BMD-2332. 2012-2015.
– 34 –
PUBLICATIONS (18)
Martín-Cófreces NB, Baixauli F, Sánchez-Madrid F.
Immune synapse: conductor of orchestrated
organelle movement. Trends Cell Biol. 24(1):61-72.
2014. PMID: 24119664. IF: 12,314. DOI:
10.1016/j.tcb.2013.09.005.
http://dx.doi.org/10.1016/j.tcb.2013.09.005
Cortés JR, Sánchez-Díaz R, Bovolenta ER, Barreiro
O, Lasarte S, Matesanz-Marín A, Toribio ML,
Sánchez-Madrid F, Martín P. Maintenance of
immune tolerance by Foxp3+ regulatory T cells
requires CD69 expression. J Autoimmun. 55:51-62.
2014. PMID: 24934597. IF: 7,018. DOI:
10.1016/j.jaut.2014.05.007.
http://dx.doi.org/ 10.1016/j.jaut.2014.05.007
Morlino G, Barreiro O, Baixauli F, Robles-Valero J,
González-Granado JM, Villa-Bellosta R, Cuenca J,
Sánchez-Sorzano CO, Veiga E, Martín-Cófreces NB,
Sánchez-Madrid F. Miro-1 links mitochondria and
microtubule Dynein motors to control lymphocyte
migration and polarity. Mol Cell Biol. 34(8):1412-26.
AREA 1
DOI:
González-Granado JM, Silvestre-Roig C, RochaPerugini V, Trigueros-Motos L, Cibrián D, Morlino G,
Blanco-Berrocal M, Osorio FG, Freije JM, LópezOtín C, Sánchez-Madrid F, Andrés V. Nuclear envelope lamin-A couples actin dynamics with immunological synapse architecture and T cell activation. Sci
Signal. 7(322):ra37. 2014. PMID: 24757177. IF:
6,337. DOI: 10.1126/scisignal.2004872.
http://dx.doi.org/10.1126/scisignal.2004872
Rocha-Perugini V, Gordon-Alonso M, SánchezMadrid F. PIP2: choreographer of actin-adaptor proteins in the HIV-1 dance. Trends Microbiol.
22(7):379-88. 2014. PMID: 24768560. IF: 9,808.
DOI: 10.1016/j.tim.2014.03.009.
http://dx.doi.org/10.1016/j.tim.2014.03.009
Acín-Pérez R, Carrascoso I, Baixauli F, Roche-Molina
M, Latorre-Pellicer A, Fernández-Silva P, Mittelbrunn
M, Sanchez-Madrid F, Pérez-Martos A, Lowell CA,
Manfredi G, Enríquez JA. ROS-triggered phosphorylation of complex II by Fgr kinase regulates cellular
adaptation to fuel use. Cell Metab. 19(6):1020-33.
2014. PMID: 24856931. IF: 16,747. DOI:
10.1016/j.cmet.2014.04.015.
http://dx.doi.org/10.1016/j.cmet.2014.04.015
Navarro MN, Cantrell DA. Serine-threonine kinases in
TCR signaling. Nat Immunol. 15(9):808-14. 2014.
PMID: 25137455. IF: 24,973. DOI: 10.1038/ni.2941.
http://dx.doi.org/10.1038/ni.2941
Villarroya-Beltri C, Baixauli F, Gutiérrez-Vázquez C,
Sánchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin Cancer Biol. 28:313. 2014. PMID: 24769058. IF: 9,143. DOI:
10.1016/j.semcancer.2014.04.009.
http://dx.doi.org/10.1016/j.semcancer.2014.04.009
Herrera-García AM, Domínguez-Luis MJ, ArceFranco M, Armas-González E, Álvarez de La Rosa D,
Machado JD, Pec MK, Feria M, Barreiro O,
Sánchez-Madrid F, Díaz-González F. Prevention of
neutrophil extravasation by α2-adrenoceptor-mediated endothelial stabilization. J Immunol.
193(6):3023-35. 2014. PMID: 25114107. IF: 5,362.
DOI: 10.4049/jimmunol.1400255.
http://dx.doi.org/10.4049/jimmunol.1400255
Rocha-Perugini V, González-Granado JM, Tejera E,
López-Martín S, Yañez-Mó M, Sánchez-Madrid F.
Tetraspanins CD9 and CD151 at the immune synapse
support T-cell integrin signaling. Eur J Immunol.
44(7):1967-1975. 2014. PMID: 24723389. IF: 4,518.
DOI: 10.1002/eji.201344235.
http://dx.doi.org/10.1002/eji.201344235
Navarro MN, Feijoo-Carnero C, Arandilla AG, Trost
M, Cantrell DA. Protein kinase D2 is a digital amplifier of T cell receptor- stimulated diacylglycerol signaling in naïve CD8+ T cells. Sci Signal. 7(348):ra99.
2014. PMID: 25336615. IF: 6,337. DOI:
10.1126/scisignal.2005477.
http://dx.doi.org/10.1126/scisignal.2005477
de la Fuente H, Cruz-Adalia A, Martinez Del Hoyo G,
Cibrián-Vera D, Bonay P, Pérez-Hernández D,
Vázquez J, Navarro P, Gutierrez-Gallego R, RamirezHuesca M, Martín P, Sánchez-Madrid F. The leukocyte
activation receptor CD69 controls T cell differentiation
through its interaction with galectin-1. Mol Cell Biol.
34(13):2479-87. 2014. PMID: 24752896. IF: 5,036.
DOI: 10.1128/MCB.00348-14.
http://dx.doi.org/10.1128/MCB.00348-14
Navarro MN, Goebel J, Hukelmann JL, Cantrell DA.
Quantitative phosphoproteomics of cytotoxic T cells
to reveal protein kinase d 2 regulated networks. Mol
Cell Proteomics. 13(12):3544-57. 2014. PMID:
25266776. IF: 7,254. DOI: 10.1074/mcp.M113.
037242.
http://dx.doi.org/10.1074/mcp.M113.037242
Rajas O, Ortega-Gómez M, Galván Román JM,
Curbelo J, Fernández Jiménez G, Vega Piris L,
Rodríguez Salvanes F, Arnalich B, Luquero Bueno S,
Díaz López A, de la Fuente H, Suárez C, Ancochea J,
Aspa J. The incidence of cardiovascular events after
hospitalization due to CAP and their association with
– 35 –
2014. PMID: 24492963. IF: 5,036.
10.1128/MCB.01177-13.
http://dx.doi.org/10.1128/ MCB.01177-13
different inflammatory markers. BMC Pulm Med.
14(1):197. 2014. PMID: 25495677. IF: 2,489. DOI:
10.1186/1471-2466-14-197.
http://dx.doi.org/10.1186/1471-2466-14-197
Cruz-Adalia A, Ramirez-Santiago G, Calabia-Linares
C, Torres-Torresano M, Feo L, Galán-Díez M,
Fernández-Ruiz E, Pereiro E, Guttmann P, Chiappi M,
Schneider G, Carrascosa JL, Chichón FJ, Martínez Del
Hoyo G, Sánchez-Madrid F, Veiga E. T cells kill bacteria captured by transinfection from dendritic cells and
confer protection in mice. Cell Host Microbe.
15(5):611-22. 2014. PMID: 24832455. IF: 12,194.
DOI: 10.1016/j.chom.2014.04.006.
http://dx.doi.org/10.1016/j.chom.2014.04.006
Esser C, Bachmann A, Kuhn D, Schuldt K, Förster B,
Thiel M, May J, Koch-Nolte F, Yáñez-Mó M, SánchezMadrid F, Schinkel AH, Jalkanen S, Craig AG,
Bruchhaus I, Horstmann RD. Evidence of promiscuous endothelial binding by Plasmodium falciparuminfected erythrocytes. Cell Microbiol. 16(5):701-708.
2014. PMID: 24444337. IF: 4,816. DOI:
10.1111/cmi.12270.
http://dx.doi.org/10.1111/cmi.12270
GROUP 2
HEAD OF LABORATORY
Esteban Veiga Chacón
GROUP MEMBERS
• Aranzazu Cruz Adalia
• Guillermo Ramírez Santiago
• Mónica Torres Torresano
RESEARCH INTEREST
Strippoli R, Loureiro J, Moreno V, Benedicto I, Lozano
ML, Barreiro O, Pellinen T, Minguet S, Foronda M,
Osteso MT, Calvo E, Vázquez J, Cabrera ML, Del Pozo
MA. Caveolin-1 deficiency induces a MEK-ERK1/2Snail-1-dependent epithelial-mesenchymal transition
and fibrosis during peritoneal dialysis. EMBO
Molecular Medicine 7(1):102-123. 2014. PMID:
25550395. IF: 8,245. DOI: 10.15252/emmm.
201404127. 1.
http://dx.doi.org/ 0.15252/emmm.201404127
We are interested in the study of the interactions occurring between pathogenic bacteria and cells of the
immune system. Recently, we discover a novel way for
bacterial capture by T cells i.e. Bacterial transinfection.
Some pathogenic bacteria (Listeria monocytogenes,
Salmonella enterica and Shigella flexneri) are able to
invade T lymphocytes in vivo and modify their behaviour. We were able to dissect the way of bacterial
uptake by T cells; transinfection from previously infected dendritic cells (DCs). The transinfection process
requires direct contact between the two cells and it is
highly enhanced by antigen presentation. This novel
mechanism of T cells for bacteria capture is thousandsfold more effective than direct infections and it is driven
by T cells. Note that some viruses e.g. HIV, use a similar transinfection mechanism to gain CD4+ T cells from
infected DCs. Strikingly, trans infected T cells killed the
captured bacteria within the first hours after infection
and did it more efficiently than professional phagocytes
like DCs.
Moreno V, Gonzalo P, Gómez-Escudero J, Pollán A,
Acín-Pérez R, Breckenridge M, Yáñez-Mó M, Barreiro
O, Orsenigo F, Kadomatsu K, Chen CS, Enríquez JA,
Dejana E, Sánchez-Madrid F, Arroyo AG. An EMMPRIN-γ-catenin-Nm23 complex drives ATP production
and actomyosin contractility at endothelial junctions. J
Cell Sci. 127(Pt 17):3768-81. 2014. PMID: 24994937.
IF: 5,325. DOI: 10.1242/jcs.149518.
http://dx.doi.org/10.1242/jcs.149518
These results, breaking a dogma of immunology, show
that T cells, paradigm of cells of adaptive immunity can
perform functions that were supposed to be exclusive of
components of the innate immunity; T lymphocytes can
capture and kill bacteria in a manner reminiscent of innate
immunity. Moreover, transinfected (ti) T cells secrete large
amounts of proinflammatory cytokines (IL-6, interferon-γ
and, TNF-α), which are known to play important roles in
bacterial clearance and protect efficiently in vivo from
– 36 –
AREA 1
MAJOR GRANTS
• Veiga Chacón, Esteban. Sinapsis inmunológica y
control bacteriano del sistema inmune. Bfu201129450. MICINN. 2012-2014.
Granted 2014
• Veiga Chacón, Esteban. Aplicaciones terapéuticas
de linfocitos transinfectados; nuevos agentes en la
inmunoterapia contra el cáncer. BFU2014-59585-R.
2014-2016.
• Veiga Chacón, Esteban. Red de excelencia para la
explotación de bacterias con fines terapéuticos.
SAF2014-56716-REDT. MINECO.
PUBLICATIONS (3)
Cruz-Adalia A, Ramirez-Santiago G, Calabia-Linares C,
Torres-Torresano M, Feo L, Galán-Díez M, FernándezRuiz E, Pereiro E, Guttmann P, Chiappi M, Schneider G,
Carrascosa JL, Chichón FJ, Martínez Del Hoyo G,
Sánchez-Madrid F, Veiga E. T cells kill bacteria captured by transinfection from dendritic cells and confer
protection in mice. Cell Host Microbe. 15(5):611-22.
2014. PMID: 24832455. IF: 12,194. DOI:
10.1016/j.chom. 2014.04.006.
de la Fuente H, Cruz-Adalia A, Martinez Del Hoyo G,
Cibrián-Vera D, Bonay P, Pérez-Hernández D, Vázquez
J, Navarro P, Gutierrez-Gallego R, Ramirez-Huesca M,
Martín P, Sánchez-Madrid F. The leukocyte activation
receptor CD69 controls T cell differentiation through its
interaction with galectin-1. Mol Cell Biol. 34(13):247987. 2014. PMID: 24752896. IF: 5,036. DOI:
10.1128/MCB.00348-14.
Morlino G, Barreiro O, Baixauli F, Robles-Valero J,
González-Granado JM, Villa-Bellosta R, Cuenca J,
Sánchez-Sorzano CO, Veiga E, Martín-Cófreces NB,
Sánchez-Madrid F. Miro-1 links mitochondria and
microtubule Dynein motors to control lymphocyte
migration and polarity. Mol Cell Biol. 34(8):1412-26.
2014. PMID: 24492963. IF: 5,036. DOI:
10.1128/MCB.01177-13.
GROUP 3
HEAD OF LABORATORY
María Yáñez Mó
GROUP MEMBERS
• Zoraida Andreu Martínez
• Soraya López Martín
• Henar Suárez Montero
RESEARCH INTEREST
For the last years we have focused our research on
two main aspects: 1- intracellular connections of
– 37 –
Listeria monocytogenes challenge.
With this background we are developing 4 major lines of
research. •1 We are investigating whether tiT cells are
bona fine antigen presenting cells (we have data showing
that tiT cells are excellent cross-presenting cells), and the
molecular mechanisms driving the novel roles of tiT cells.
•2 We are studying the possible use of tiT cells in cancer
immunotherapy due to their excellent cross-priming abilities and their hyper-inflammatory nature. We have data
confirming that tiT cells are new very promising troops
joining the fight against cancer. •3 We are expanding our
knowledge in transinfection as a mechanism to
capture/destroy/present bacterial antigens to B cells. •4
We will test whether tiLymphocytes could protect from
bacterial infections as an, alternative to antibiotics, which
is an issue of major relevance, as antimicrobial resistance
has become an increasingly serious threat to global public health according to the world health organization
tetraspanins, in close collaboration with the proteomics group of J Vázquez. We have also maintained
several collaborations to extrapolate the role of
tetraspanin adhesion platforms to the process of
embryonic implantation with the IVI (Valencia). Our
data on the characterization of the intracellular interactome of tetraspanin-enriched microdomains, revealed
a role of these specialized adhesion platforms in the
recruitment of adhesion receptors and, surprisingly,
RNA binding proteins to exosomes. So that 45% of
the proteome of these extracellular vesicles was connected to tetraspanin-enriched microdomains and
deletion of a single tetraspanin was able to selectively
reduce the incorporation of associated molecules to
exosomes.
Our future work intends to profit from all the tools
against tetraspanin molecules and their associated
partners (metalloproteinases and adhesion receptors)
that we have in the lab to study their functional role in
the biogenesis and function of EVs. This information will
be critical for the optimization of those therapies based
on EVs, since it will reveal novel therapeutical targets to
block their secretion, diminish their metastatic or angiogenic capacities, or augment their stability and
immunoregulatory potential.
MAJOR GRANTS
• Yañez Mó, María. Immunoregulatory molecules as
biomarkers predicting response to biological therapies and disease severity in immune-mediated
inflamatory
disorders.
BIOMID
PROJECT.
PIE13/00041. Proyecto coordinado. ISCIII. 20142016.
• Yañez Mó, María. Papel de las tetraspaninas en la
regulación de proteasas de membrana y GTPasas
de bajo peso molecular durante la extravasación leucocitaria y en la biogénesis de exosomas. ISCIII.
PI11/01645. 2012-2014.
Granted 2014
• Yañez Mó, María. Exosomas: la comunicación intercelular como arma terapéutica. Fundación Ramón
Areces. 2015-2017
– 38 –
• Yañez Mó, María. Papel de los microdominios
ricos en tetraspaninas y proteasas asociadas en
la biogénesis y función de los exosomas.
MINECO: BFU2014-55478-R. 2015-2017
PUBLICATIONS
(4)
Ramos-Ibeas P, Calle A, Pericuesta E, LagunaBarraza R, Moros-Mora R, Lopera-Vásquez R,
Maillo V, Yáñez-Mó M, Gutiérrez- Adán A, Rizos D,
Ramírez MÁ. An efficient system to establish biopsy-derived trophoblastic cell lines from bovine
embryos. Biol Reprod. 91(1)15:1-10. 2014. PMID:
24855108. IF: 3,451. DOI: 10.1095/biolreprod.114.118430.
http://dx.doi.org/10.1095/biolreprod.114.118430
Moreno V, Gonzalo P, Gómez-Escudero J, Pollán A,
Acín-Pérez R, Breckenridge M, Yáñez-Mó M,
Barreiro O, Orsenigo F, Kadomatsu K, Chen CS,
Enríquez JA, Dejana E, Sánchez-Madrid F, Arroyo
AG. An EMMPRIN-γ-catenin-Nm23 complex drives
ATP production and actomyosin contractility at
endothelial junctions. J Cell Sci. 127(Pt 17):376881. 2014. PMID: 24994937. IF: 5,325. DOI:
10.1242/jcs.149518.
http://dx.doi.org/10.1242/jcs.149518
Esser C, Bachmann A, Kuhn D, Schuldt K, Förster
B, Thiel M, May J, Koch-Nolte F, Yáñez-Mó M,
Sánchez-Madrid F, Schinkel AH, Jalkanen S, Craig
AG, Bruchhaus I, Horstmann RD. Evidence of
promiscuous endothelial binding by Plasmodium
falciparuminfected erythrocytes. Cell Microbiol.
16(5):701-708. 2014. PMID: 24444337. IF: 4,816.
DOI: 10.1111/cmi.12270.
http://dx.doi.org/10.1111/cmi.12270
Rocha-Perugini V, González-Granado JM, Tejera E,
López-Martín S, Yañez-Mó M, Sánchez-Madrid F.
Tetraspanins CD9 and CD151 at the immune
synapse support T-cell integrin signaling. Eur J
Immunol.
44(7):1967-1975.
2014.
PMID:
24723389. IF: 4,518. DOI: 10.1002/eji.201344235.
http://dx.doi.org/10.1002/eji.201344235
AREA 1
HEAD OF LABORATORY
Miguel Vicente Manzanares
GROUP MEMBERS
• Rocío Aguilar Cuenca
• Cristina Delgado Arévalo
• Lidia Feo Lucas
• Alba Juanes García
• Álvaro Ortega Carrión
We have just applied for renewal of the SAF grant aiming at studying the mechanical signals that drive highspeed amoeboid motility in cancer cells and leukocytes. In the next years, we will elucidate the role of
mechanics in several key processes, e.g. tumor
immune evasion, using advanced techniques such as
the inclusion of microchips inside cells.
MAJOR GRANTS
The Mechanotransduction group has continued evaluating the role of phosphorylation of the force-generating molecule non-muscle myosin II in cell adhesion and
migration. Novel sites have been unveiled and their role
in cell mechanics assessed using high-end microscopy
and other quantitative techniques. Our data has
revealed the existence of an alternative switch in
myosin II that controls the activation of the molecule
and its role in dynamic actin assembly, thus constituting a novel “druggable” site with potential therapeutic
application in metastasis.
• Vicente Manzanares, Miguel. La miosina no muscular de clase ii coordina la señalización adhesiva y de
citocinas con la respuesta celular a las propiedades
mecánicas del microentorno inflamatorio. SAF201124953. MICINN. 2012-2014
• Vicente Manzanares, Miguel. La miosina II integra las
señales mecánicas del microentorno celular y controla
la migración y diferenciación de las células madre.
CIVP16A1831. Fundación Ramón Areces. 2012-2015
• Vicente Manzanares, Miguel. Análisis multiparamétrico de la morfología y migración celular para la asistencia al diagnóstico de enfermedades inflamatorias
y cáncer. WIMASIS. 2012-2014.
• Vicente Manzanares, Miguel. Myosin ii orchestrates
chemical and mechanical signals in inflammation.
Marie Curie- Career Integration Grant (CIG293719).
European Union. 2011-2015
Using the Ramón Areces funding, the group has begun
investigating the role of myosin II in stem cell differentiation. Preliminary data suggest that differential targeting of the signaling cascades that end in myosin II may
skew hMSC differentiation in response to extracellular
mechanical cues, which will have repercussion in the
regenerative schemes aimed at novel organ generation
based in these cells.
Granted 2014:
• Vicente Manzanares, Miguel. Regulación mecánica
de la inducción de tolerancia en células mieloides: un
nuevo mecanismo de evasión inmune tumoral.
Fundación BBVA. 2015-2016.
• Vicente Manzanares, Miguel. Determinantes
Mecánicos de la migración celular y la inmunidad.
SAF2014-54705-R. MINECO. 2015-2017.
RESEARCH INTEREST
Finally, the group has developed a novel approach in
the Institute aimed to quantify forces in migrating cells.
This technique, traction force microscopy, is being
used to evaluate the effect of myosin II mutations that
cause monogenic disease (May-Hegglin syndrome) in
wound healing and adhesion. This is a novel and powerful technique that will help set the group at the forefront of Mechanotransduction field.
PUBLICATIONS (3)
Aguilar-Cuenca, R. Juanes-García, A. VicenteManzanares, M. Myosin II in mechanotransduction: master and commander of cell migration, morphogenesis, and
cancer. Cell Mol Life Sci. 71(3):479-92. 2014. PMID:
– 39 –
GROUP 4
23934154. IF: 5,856. DOI: 10.1007/s00018- 013-14395. http://dx.doi.org/10.1007/s00018-013-1439-5
Aguilar-Cuenca R, Vicente-Manzanares M. Unleashing
mesenchymal chemotaxis. Dev Cell. 31(6):669-70.
2014. PMID: 25535912. IF: 10,366. DOI:
10.1016/j.devcel.2014.12.005.
http://dx.doi.org/10.1016/j.devcel.2014.12.005
Cruz-Adalia A, Ramirez-Santiago G, Calabia-Linares C,
Torres-Torresano M, Feo L, Galán-Díez M, FernándezRuiz E, Pereiro E, Guttmann P, Chiappi M, Schneider G,
Carrascosa JL, Chichón FJ, Martínez Del Hoyo G,
Sánchez-Madrid F, Veiga E. T cells kill bacteria captured by transinfection from dendritic cells and confer
protection in mice. Cell Host Microbe. 15(5):611-22.
2014. PMID: 24832455. IF: 12,194. DOI:
10.1016/j.chom.2014.04.006.
BOOKS
Feo, L. Ortega-Carrión, A. Vicente-Manzanares, M.
CELL MIGRATION. Encyclopedia of Cell Biology, edited by Ralph A. Bradshaw and Philip Stahl. Elsevier.
GROUP 56
HEAD OF LABORATORY
Ana Carmen Urzainqui Mayayo
GROUP MEMBERS
• Rafael González Tajuelo
• Javier Silván Montoya
RESEARCH INTEREST
P-Selectin Glycoprotein Ligand-1 (PSGL-1) is a leucocyte receptor that interacts with P-, E- and L– 40 –
Selectins and is responsible for the initial steps of
leukocyte extravasation to the sites of inflammation.
Our lab has described that PSGL-1 acts as an
immunoregulatory receptor that participates in the
generation of regulatory T cells (Treg) and contributes
to the maintenance of peripheral tolerance in mice.
We have recently described that PSGL-1 KO mice
develop a progressive autoimmune disease similar to
systemic sclerosis (SSc). In addition, we have
observed that P-Selectin deficient mice develop an
autoimmune syndrome that, unlike PSGL-1 KO, generates anti-dsDNA antibodies, do not have skin fibrosis but develop hypodermis inflammation with lipoatrophy, have lung and kidney affectation, and with
aging develop deposits of immunecomplexes in skin
and kidney, characteristics that could match with
systemic lupus erithematosus (SLE). Interestingly, we
have observed that both P-Selectin and PSGL-1 KO
aged mice have the muscular layer of the pulmonary
small vessels thickened, suggesting that they could
develop pulmonary arterial hypertension (PAH), the
most severe form of connective tissue-related
autoimmune disease.
Main research lines: 1) Study of the autoimmune
syndrome developed by P-Selectin KO mice. We are
analyzing the autoimmune syndrome developed in
the P-Selectin KO mice and studying its progression
with aging. We will address the differences between
PSGL-1 and P-Seletin immune system in blood,
skin, lung and kidney to understand the different
alterations found in these KO mice. We will also
address whether the Bone Marrow (BM) precursors
of WT mice can cure or reduce the symptoms of
PSGL-1 KO and P-Selectin KO mice and whether
the BM precursors obtained from PSGL-1 KO and
P-Selectin KO mice can induce the autoimmune
syndrome to the WT mice. 2) Study of PSGL-1 and
P-Selectin implication in the development of PAH.
We will explore the molecular mechanisms responsible for PAH development, such as alterations in
mitochondrial metabolism or in the levels of different
molecules that are altered in PAH patiens such as
thrombospondin-1, angiotensin II and endothelin-1,
and their receptors 3) Implication of PSGL-1 and its
ligands ADAM8, P-Selectin, E-Selectin and LSelectin in human SSc, SLE, mixed connective tis-
AREA 1
sue disease and PAH. We will study the serum levels
of these molecules to find differences that account
for the disease pathogenesis, and to evaluate the
possibility of being used as targets for diagnosis
and/or prognosis. We will also study the immune
system alterations and the PSGL-1 and P-Selectin
implication.
PSGL-1 al desarrollo de enfermedades autoinmunes en
humanos. ISCIII. PI11/01418. 2012-2014.
Granted 2014:
• Urzainqui Mayayo, Ana Carmen. Interacción PSGL-1/pSelectina: homeostasis del sistema inmune, vascular y
reproductor en ratones. Relevancia en el desarrollo de
HAP y enfermedades autoinmunes en humanos.
PI14/01698. ISCIII. 2015-2017.
MAJOR GRANTS
PUBLICATIONS (1)
Pérez-Frias A, González-Tajuelo R, Núñez-Andrade N,
Tejedor R, García- Blanco MJ, Vicente-Rabaneda E,
Castañeda S, Gamallo- Amat C, Fraga J, GarcíaGarcía C, Muñoz-Calleja C, García-Diez A, Urzainqui A.
Development of an autoimmune syndrome affecting
the skin and internal organs in P-Selectin Glycoprotein
Ligand-1 deficient mice. Arthritis and Rheumatology.
66(11):3178-89. 2014. PMID: 25132671. IF: 7,871.
DOI: 10.1002/art.38808.
http://dx.doi.org/10.1002/art.38808
– 41 –
• Urzainqui Mayayo, Ana Carmen. Immunoregulatory
molecules as biomarkers predicting response to biological therapies and disease severity in immune-mediated
inflamatory
disorders.
BIOMID
PROJECT.
PIE13/00041. Proyecto coordinado. ISCIII. 2014-2016.
• Urzainqui Mayayo, Ana Carmen. Estudio del papel de
PSGL-1 en el control del desarrollo de enfermedades
autoinmunes. FUNDACIÓN RAMÓN ARECES. 20122015.
• Urzainqui Mayayo, Ana Carmen. Caracterización de
una enfermedad espontanea autoinmune desarrollada
en ratones deficientes en PSGl-1.contribucion del
Line 1.2
Cellular and molecular
responses to Hypoxia
GROUP 9
HEAD OF LABORATORY
Julián Aragonés López
GROUP MEMBERS
• Ainara Elorza Peregrina
• Florinda Meléndez Rodríguez
• Inés Soro Arnaíz
• María del Mar Torres Capelli
• Qilong Oscar Yang Li
RESEARCH INTEREST
An insufficient oxygen supply (hypoxia) is a hallmark of
numerous life-threatening pathologies with unmet
medical needs such as solid tumor growth, chronic
obstructive pulmonary disease (COPD), ischemic diseases and obesity. Cells are equipped with oxygensensing systems to mount a programmed response
when oxygen becomes limited. Hypoxia-inducible factors (HIF1, HIF2 and HIF3) are central regulators of this
cellular response to oxygen fluctuations. Our current
research interest is focused on the role of the HIF oxygen sensing pathways in cancer, pulmonary disease
and obesity. In particular, we are mainly interested in
cellular metabolic reprogramming, which is one the
central biological function executed by the HIF factors.
1) HIF factors and renal cell carcinoma: the HIF factors
are induced in hypoxic areas in the inner core of the
solid tumors but in clear cell renal cell carcinoma
(ccRCC) - which loss Vhl (the main repressor of HIFs in
normoxia) - show constitutive HIF expression irrespec-
– 42 –
tively of the oxygen levels of the tumor. In these tumors
HIF1 shows its cell autonomous anti-proliferative
capability whereas HIF2 acts as an oncoprotein.
Therefore, ccRCC are being studied extensively to
understand the role of HIF in cancer biology. Our studies have shown that the HIF2a isoform acts as an
mTORC1 activator through the amino acid carrier
SLC7A5, which is essential to sustain ccRCC tumor
growth. We have recently found a novel link between
glucose and lipid metabolism and HIF factors, which
impact remarkably in ccRCC progression.
Independently of these projects in ccRCC tumor
metabolism, we have recently initiated a project identifying unanticipated molecular links between HIF pathways and cancer immunology. 2) HIF factors and airway dysfunction in pulmonary disease: Pulmonary diseases such as chronic obstructive pulmonary disease
(COPD) and sleep-apnea hypoapnea syndrome
(SAHS) are the most common respiratory diseases
causing illness and death, and are being projected to
be the third leading cause of death worldwide by
2020. They are characterized by an insufficient level of
oxygen in the blood (hypoxemia), continuous in the
COPD and intermittent in the SAHS and they are associated to pulmonary oxidative damage, an exaggerated inflammatory response in the lung and systemically. Surprisingly, despite of the fact that lung tissue bronchial epithelium - is a first barrier encountered by
oxygen, the role of the HIF oxygen-sensing responses
in lung pathophysiology remains largely unknown.
Based on (i) our recent studies about the HIF pathways as activators of proliferative markers in bronchial
epithelium including mTORC1, we are currently studying together in collaboration with other researchers
including pneumologists in Hospital de la Princesa IISIP (Dr. Julio Ancochea) the role of HIF oxygen sensing
pathways in (i) lung protection and repair (ii) ventilation
and (iii) their potential to identify novel biomarkers for
diagnosis and prognosis of fatal respiratory diseases.
In particular we are preparing a manuscript about the
central role of the HIF2 pathway in the lung biology
during hypoxic conditions in adults mice as well as
perinatally. 3) HIF factor in white adipose tissue and
obesity: Obesity and associated maladies have
become the leading medical disorders of the 21st century. This is particularly relevant in the aging popula-
AREA 1
MAJOR GRANTS
• Aragonés López, Julián. Papel de los factores de
respuesta a oxigeno HIF en patología pulmonar y biomarcadores diagnostico/pronostico no invasivos en
enfermedad
respiratoria.
SAF2013-46058-R.
Ministerio de Economía y Competitividad. 2014-2016.
• Aragonés López, Julián. Inflamación e hipoxia:
mecanismos en desarrollo y progresión en EPOC y
SAHS. P2010 / BMD-2542. CAM. 2012-2015.
• Aragonés López, Julián. Gaining sage on the epoetins' saga: assessing long term risks and advancing
towards better epoetin driven treatment modalities.
282551. European Comission. 2011-2014.
MAJOR GRANTS
• Ortiz de Landazuri Busca, Manuel. RECAVA.
RD12/0042/0065. ISCIII. 2013-2016.
• Ortiz de Landazuri Busca, Manuel. Inflamación e
hipoxia: mecanismos de desarrollo y progresión en
EPOC Y SAHS. MINECO. S2010/BMD-2542. 20122014.
• Ortiz de Landazuri Busca, Manuel. Metastatic tumours
facilitated by hypoxic tumour microenvironments. (7º
Programa Marco). FP7-HEALTH-2007. CEE. 20072014.
PUBLICATIONS (1)
IPettersen EO, Ebbesen P, Gieling 2014 2,383 3 review
RG, Williams KJ, Dubois L, Lambin P, Ward C, Meehan J,
Kunkler IH, Langdon SP, Ree AH, Flatmark K, Lyng H,
Calzada MJ, Peso LD, Landázuri MO, Görlach A, Flamm
H, Kieninger J, Urban G, Weltin A, Singleton DC, Haider
S, Buffa FM, Harris AL, Scozzafava A, Supuran CT,
Moser I, Jobst G, Busk M, Toustrup K, Overgaard J,
Alsner J, Pouyssegur J, Chiche J, Mazure N, Marchiq I,
Parks S, Ahmed A, Ashcroft M, Pastorekova S, Cao Y,
Rouschop KM, Wouters BG, Koritzinsky M, Mujcic H,
Cojocari D. Targeting tumour hypoxia to prevent cancer
metastasis. From biology, biosensing and technology to
drug development: the METOXIA consortium. J Enzyme
Inhib Med Chem. 2014 Oct 27:1-33. 2014. PMID:
25347767. IF: 2,383.
GROUP 6
HEAD OF LABORATORY
Manuel Ortiz de Landázuri Busca
GROUP 7
HEAD OF LABORATORY
Antonio Martínez Ruiz
GROUP MEMBERS
• Bárbara Acosta Iborra
• Eduardo Balsa Martínez
• Esther Fuertes Yebra
• Ángel Ordóñez Navadijo
GROUP MEMBERS
• Pablo Hernansanz Agustín
• Alicia Izquierdo Álvarez
– 43 –
tion, who are more prone to obesity. We have characterized the molecular changes occurring in humans
and mice during progressive visceral white adipose tissue (WAT) enlargement. We have found a specific
metabolic rewiring during murine WAT expansion
through HIF1α. Since genetic approaches to study the
biology of visceral WAT are still limited, we have established in vivo techniques to explore the role of white
adipose autonomous metabolism in WAT expansion.
By delivering lentiviral short-hairpin sequences locally
in one epididymal WAT depot, using the contralateral
as a control, we have investigated the role of several
metabolic pathways in white adipocyte enlargement.
• Elena Ramos Serrano
• Nuria Sánchez López
RESEARCH INTEREST
The research of the group is centred on two main
lines:
1. Hypoxia signalling by reactive oxygen and nitrogen species
Novel thiol redox proteomics techniques (see below)
have allowed us to identify several proteins that are
differentially oxidised in the acute response of
endothelial cells subjected to hypoxia. We have also
seen that there is an acute increase in protein Snitrosylation and nitration, pointing to an increase of
reactive nitrogen species (RNS). We have developed new methods to precisely measure superoxide production in hypoxia. This has allowed measuring this production at precise time points of acute
hypoxia, and showed that different cell types produce a superoxide burst in acute hypoxia, which
can be a signal for cell adaptation through acute
responses as well as through activation of the HIF
pathway.
We are currently investigating the mechanisms that
lead to this acute production of superoxide. We have
discovered that hypoxia activates the Na+/Ca2+
exchange between mitochondria and the cytoplasm,
and that inhibition or silencing of the mitochondrial
Na+/Ca2+ exchanger (NCLX) inhibits the superoxide
burst and the activation of the HIF pathway in cells
and brain tissue. Searching further for mechanisms
linking acute hypoxia with NCLX activation, we have
found that mitochondrial complex I is involved in
NCLX activation and superoxide production, in line
with the role of acute oxygen sensor that has been
ascribed to this complex. Additional preliminary
results show that NCLX inhibition may also inhibit
ROS production in reperfusion. We have recently
patented the use of NCLX inhibitors as a novel tool
for inhibiting ROS production and the HIF pathway,
which could be useful in the treatment of diseases in
which those two factors are present.
– 44 –
Pathways for the future in this line:
- Study of mechanisms of ROS production and signalling in acute hypoxia, and the role of mitochondria as oxygen sensors.
- Mechanisms of NO production and identification
of S-nitrosylated proteins in acute hypoxia.
- Mechanisms of ROS production in reperfusion,
and role of OXPHOS complexes and NCLX.
- Application of NCLX inhibition to the treatment of
diseases: neurodegenerative diseases (Alzheimer
and Parkinson – both are ongoing in animal models,
in collaboration with the group of Manuela García
López); ischemia/reperfusion injury (ictus, myocardial infarction).
2. Oxidative post-translational modifications and
redox proteomics
We have studied the functional role of S-nitrosylation in several proteins, through collaborations. We
have contributed to generate new hypothesis in the
field of NO signalling and reviewed the role of this
modification in the immune system and neuronal
plasticity. We have developed methods for detecting cysteine oxidative post-translational modifications (thiol redox proteomics), by fluorescent
labelling and 2DE, which we have applied to the
study of hypoxia signalling (see above), acute pancreatitis, and neurogenesis (manuscript in preparation). In collaboration with the group of Jesús
Vázquez (currently at CNIC), we have developed a
thiol redox proteomics method based in highthroughput LC-MS/MS. We are currently developing
the application of this method for clinical samples,
starting with the study of the thiol redox proteome
of heart valves, comparing samples from the two
main diseases that lead to valve replacement and
normofunctional valves from heart donors.
MAJOR GRANTS
• Martínez Ruiz, Antonio. Implicaciones de la hipoxia y las especies reactivas de oxígeno en las
enfermedades neurodegenerativas. Fundación
Domingo Martínez. 2014-2015.
AREA 1
• Martínez Ruiz, Antonio. Modificaciones postraduccionales oxidativas en fisiopatología molecular. ISCIII. PI12/00875. 2013-2015.
• Martínez Ruiz, Antonio. EU-ROS. BM1203. COST.
2012-2016.
• Martínez Ruiz, Antonio. Gasotransmitters: from
basic science to therapeutic applications (ENOG:
European network on gasotransmitters). BM1005.
COST. 2011-2015.
• Martínez Ruiz, Antonio. Chemistry of non-enzymatic protein modification - modulation of protein
structure and function. CM1001. COST. 20102014
• Martínez Ruiz, Antonio. Papel funcional del estrés
oxidativo y nitrosativo en grandes sistemas
biológicos. CSD.070020. 2008-.
GROUP 8
HEAD OF LABORATORY
María Josefa Calzada García
GROUP MEMBERS
• Juan Bustamante Munguira
• David Labrousse Arias
(2)
Hernansanz-Agustín P, Izquierdo-Álvarez A,
Sánchez-Gómez FJ, Ramos E, Villa-Piña T, Lamas
S, Bogdanova A, Martínez-Ruiz A. Acute hypoxia
produces a superoxide burst in cells. Free Radic
Biol Med. 71:146-156. 2014. PMID: 24637263. IF:
5,71. DOI: 10.1016/j.freeradbiomed.2014.03.011.
http://dx.doi.org/10.1016/j.freeradbiomed.2014.03.011
Moreno ML, Escobar J, Izquierdo-Álvarez A, Gil A,
Pérez S, Pereda J, Zapico I, Vento M, Sabater L,
Marina A, Martínez-Ruiz A, Sastre J. Disulfide
stress: a novel type of oxidative stress in acute pancreatitis. Free Radic Biol Med. 70:265-277. 2014.
PMID: 24456905. IF: 5,71. DOI: 10.1016/j.freeradbiomed.2014.01.009.
http://dx.doi.org/10.1016/j.freeradbiomed.2014.01.009
BOOKS
Antonio Martínez-Ruiz, Brian McDonagh, José Antonio
Bárcena. PROTEÓMICA REDOX: ANÁLISIS DE MODIFI-
RESEARCH INTEREST
Hypoxia plays critical roles in the pathobiology of
many diseases, these including cancer and chronic
lung disease, which are responsible for 60% of
deaths in the world. Understanding how cells sense
and respond to changes in oxygen availability and
the physiologic or pathologic consequences in the
context of chronic diseases will have a positive
impact in the diagnosis and treatment of these
pathologies. Our group is currently investigating the
role of hypoxia in the regulation of the matricellular
protein thrombospondin-1 (TSP-1) in the context of
pulmonary hypertension and renal carcinoma.
Pulmonary arterial hypertension (PAH) is a rapidly
progressive pulmonary vascular disease with a multifactorial etiopathogenesis that results in rightsided heart failure and ultimately death. Oxidative
stress is a key event in the pathogenesis of PAH yet
the mechanisms involved remain incompletely
known. Our previous results reported that the
matricellular protein thrombospondin-1 (TSP-1) is
upregulated in lungs from individuals with PAH
while mice lacking TSP-1 are protected from
hypoxia-mediated PAH. In addition, TSP1-mediated activation of its receptor CD47 is increased in
– 45 –
PUBLICATIONS
CACIONES POSTRADUCCIONALES OXIDATIVAS.
MANUAL DE PROTEÓMICA. ISBN: 978-84-697-1281-8
experimental and human PAH, and promotes disease by limiting Cav-1 inhibition of dysregulated
eNOS. Our recent studies give more insight into the
mechanisms by which TSP-1 is regulated in hypoxic lungs and how this contributes to PAH. Proof-ofprinciple study in animals models, and human samples from PAH patients, demonstrates that HIF2α is
necessary for hypoxia-mediated upregulation of
pulmonary TSP-1. In addition, in vitro and ex vivo
studies reveal that TSP-1 contributes to vascular
remodeling by inducing cell migration and regulates
hypoxic pulmonary arterial contractility, both of
them hallmarks in PAH. These results point to TSP1 as a causal molecule in experimental and clinical
PAH and therefore represents a candidate therapeutic target. We are currently investigating an
unsuspected role for TSP-1 to regulate potassium
channels and how this contributes to the accumulation of intracellular calcium that occurs during cell
depolarization before vessel contraction. Our future
goals intend to explore the role of TSP-1 in the
inflammatory process during PAH. Additionally, as
TSP-1 has been found to be increased in several
pulmonary diseases associated with excessive
fibrosis, our findings likely have implications
beyond PAH, and therefore we would like to
explore the role of TSP-1 in other pulmonary diseases. We are currently collaborating with international groups at the University of Pittsburgh in a
project directly connected to our interest in
Pulmonary diseases (NIH-RO1 2011-2015 and
Renewal (2016-2021) under evaluation).
MAJOR GRANTS
• Calzada García, María Josefa. Estudio de nuevas
dianas terapéuticas en la hipertensión pulmonar.
Contribución del nexo tsp1/cd47 en las
propiedades estructurales y funcionales de la arteria pulmonar en modelos de ratón. ISCIII.
PI13/01866. 2014-2016.
• Calzada García, María Josefa. TSP1-CD47 in promotion of PAH-associated vasoconstriction and
– 46 –
vascular overgrowth. FOA: PA10-067. NIH. 20112015.
PUBLICATIONS (1)
Bustamante J, Arévalo A, Tamayo E, Sarria C,
Aguilar-Blanco EM, Heredia M, Almansa R, Rico L,
Iglesias V, Bermejo-Martin JF. Cytokine profiles
linked to fatal outcome in infective prosthetic valve
endocarditis. APMIS. 122(6):526-9. 2014. PMID:
24106887. IF: 1,922. DOI: 10.1111/apm.12189.
http://dx.doi.org/10.1111/apm.12189
GROUP 10
HEAD OF LABORATORY
Susana Cadenas Álvarez
GROUP MEMBERS
• Andrea Anedda
• Elia López Bernardo
RESEARCH INTEREST
Our group studies the function of mitochondria within cells and their implication in the development of
pathological conditions. Uncoupling proteins (UCPs)
have been involved in the control of mitochondrial
reactive oxygen species (ROS) production and the
protection against oxidative stress. Since oxidative
stress underlies a wide variety of pathophysiological
processes, UCPs are potentially important drug targets. The elucidation of the molecular pathways that
control their expression and activity is essential to
develop strategies for modulating their function. An
efficient response to oxidative damage is crucial for
AREA 1
Our group pursues three main lines of research. 1)
The regulation of the expression and function of UCP3
in response to oxidative stress. We have found that
the treatment with hydrogen peroxide (H2O2) induces
UCP3 expression in cells from mouse heart and
skeletal muscle. This effect is mediated by the transcription factor Nrf2. Moreover, we have shown that
UCP3 up-regulation is accompanied by an increase in
the proton conductance of the inner mitochondrial
membrane, which results in a decreased production
of mitochondrial ROS and, consequently, in an
increased cell survival. We are currently investigating
the effects of the lipid peroxidation product 4hydroxy-2-nonenal on UCP3 expression and their
functional consequences. 2) The protective role of
UCP3 against IR injury and its involvement in ischemic
preconditioning (IPC). We have detected Nrf2 nuclear
accumulation and increased UCP3 protein in intact
mouse heart subjected to IR, a condition known to
increase ROS generation. We are currently studying
the potential protective role of UCP3 against IR injury
and its involvement in IPC in the isolated perfused
mouse heart. 3) The implication of Nrf2 in IPC. There
is experimental evidence showing that Nrf2 activation
protects against IR injury. By using Nrf2 activators and
Nrf2 knockout mice, we will study the role of this factor in IPC and the molecular mechanisms involved. In
addition, we have already established collaboration
with cardiac surgeons to study the molecular and cellular alterations taking place in the ischemic human
heart.
MAJOR GRANTS
• Cadenas Álvarez, Susana. Papel cardioprotector del
desacoplamiento mitocondrial en condiciones de
isquemia. ISCIII. PI12/00933. 2012-2015.
• Cadenas Álvarez, Susana. La mitocondria y su implicación
en
patología
humana.
MINECO.
S2010/BMD-2402. 2012-2015.
– 47 –
cell survival, and Nrf2 (nuclear factor erythroid 2related factor 2) is an essential transcription factor
that regulates the expression of several antioxidant
genes via binding to the antioxidant response element (ARE) and plays a pivotal role in cellular defence
against oxidative stress. Among several pathologies
related to oxidative stress, we are particularly interested in cardiac ischemia-reperfusion (IR) injury.
Reperfusion of ischemic myocardium results in an
excessive production of ROS that may cause tissue
damage.
Line 1.3
Animal models of
inflammatory diseases
and intercellular signalling
GROUP 11
HEAD OF LABORATORY
Federico Mayor Menéndez
GROUP MEMBERS
• Sofía Cabezudo Violero
• Julia Palacios García
• Paula Ramos Barbeito
• Catalina Ribas Núñez
• Susana Rojo Berciano
• Guzmán Sánchez Fernández
• Almudena Inés Santos Bajo
RESEARCH INTEREST
Our laboratory is investigating key nodes in signalling networks involved in prevalent age-related pathologies such
as metabolic/cardiovascular diseases and cancer. The
GRK2 kinase is one of those key signalling hubs. The
canonical role of GRK2 is to regulate, together with
arrestins, signaling mediated by multiple G protein-coupled receptors (GPCR), a family of hundreds of membrane
proteins of key physiological and pharmacological importance. In addition, we and other groups have unveiled that
GRK2 can also impact cell signalling networks by directly
interacting and/or phosphorylating non-GPCR components of transduction cascades (such as HDAC6, IRS1,
PI3K, EPAC, Mdm2, Smads or p38 Mapk). Our group has
reported that some of such integrated interactions underlie the participation of GRK2 in the control of cell migration,
angiogenesis or insulin resistance (IR).
Importantly, GRK2 levels/activity are altered in human
pathologies such as cancer, inflammation and cardio-
– 48 –
vascular/ metabolic diseases related to IR. We seek to
understand the mechanisms leading to altered GRK2
expression in these clinical situations, how concurrent
changes in GRK2 levels (involving different cell types
and tissues) integrate at the cellular and organism level,
and how they can foster disease progression, by using
cellular and animal models (including hemizygous, conditional and tissue-specific GRK2-deficient animals), as
well as samples from patients or animal models of disease. This is critical to assess the feasibility of GRK2 as
a useful diagnostic biomarker and/or therapeutic target.
The group pursues three main lines of investigation:
1) Investigate how changes in GRK2 expression in different cell types within a given tumor (tumoral,
macrophages and endothelial cells) might act synergistically to promote different aspects of tumor progression (proliferation, survival, angiogenesis, metastatic
invasion) by modulating either GPCRs or HDAC6-governed networks, among others.
2) Analyze the GRK2 hub as a central integrator of signaling cascades relevant to IR-related pathologies and
co-morbidities in different tissues and cell types (adipose, liver, pancreas, heart, macrophages/immune
cells), by simultaneously modulating both the insulin
cascade and key GPCRs controlling metabolic homeostasis, nutrient sensing or insulin secretion/sensitivity,
as well as other GRK2-interacting signaling proteins
related to IR conditions (such as EPAC, eNOS or p38
Mapk).
3) Explore the functional implications of the Gαq interactome. We have unveiled novel interactions of Gαq
with PB1-domain containing proteins such as PKCζ,
and we are investigating the functional impact of this
new Gαq interactome in cell death, autophagy and
oxidative stress processes and in the development of
cardiovascular diseases.
MAJOR GRANTS
• Mayor Menéndez, Federico. Novel molecular mechanisms linking GRK2 as a new therapeutic target in diabetes. EFSD/Novo Nordisk Partnerhsip for Diabetes
Research in Europe. 2014-2016.
AREA 1
Granted 2014:
• Mayor Menéndez, Federico. Oncogenic receptor network of excellence and training. ONCORNET. European
Union. 2015-2018.
• Ribas Núñez, Catalina. Nuevos complejos funcionales
derivados de la interacción de g αq con proteínas que
contienen dominios pb1 y su posible repercusión en
patologías cardiovasculares. PI14/00201. ISCIII. 20152017.
PUBLICATIONS (7)
Sánchez-Fernández G, Cabezudo S, García-Hoz C,
Benincá C, Aragay AM, Mayor F Jr, Ribas C. Gaq signalling: The new and the old. Cell Signal. 26(5):833-848.
2014. PMID: 24440667. IF: 4,471. DOI: 10.1016/j.cellsig.2014.01.010.
http://dx.doi.org/10.1016/j.cellsig.2014.01.010
Penela P, Nogués L, Mayor F Jr. Role of G protein-coupled receptor kinases in cell migration. Curr Opin Cell
Biol. 27: 10-17. 2014. PMID: 24680425. IF: 8,736. DOI:
10.1016/j.ceb.2013.10.005.
http://dx.doi.org/10.1016/j.ceb.2013.10.005
Fernández-Arenas E, Calleja E, Martínez-Martín N, Gharbi
SI, Navajas R, García-Medel N, Penela P, Alcamí A,
Mayor F Jr, Albar JP, Alarcón B. ß-arrestin-1 mediates the
TCR-triggered re-routing of distal receptors to the
immunological synapse by a PKC- mediated mechanism.
EMBO J. 33(6):559-577. 2014. PMID: 24502978. IF:
10,748. DOI: 10.1002/embj.201386022.
http://dx.doi.org/10.1002/embj.201386022
Willemen HL, Campos PM, Lucas E, Morreale A, GilRedondo R, Agut J, González FV, Ramos P, Heijnen C,
Mayor Jr F, Kavelaars A, Murga C. A novel p38 MAPK
docking groove-targeted compound is a potent inhibitor
of inflammatory hyperalgesia. Biochem J. 459(3):427-39.
2014.
PMID:
24517375.
IF:
4,779.
DOI:
10.1042/BJ20130172.
http://dx.doi.org/10.1042/BJ20130172
Lucas E, Jurado-Pueyo M, Fortuño MA,
Fernández-Veledo S, Vila-Bedmar R, JiménezBorreguero LJ, Lazcano JJ, Gao E, GómezAmbrosi J, Frühbeck G, Koch WJ, Díez J, Mayor F
Jr, Murga C Biochim Biophys Acta. Downregulation
of G protein-coupled receptor kinase 2 levels
enhances cardiac insulin sensitivity and switches
on cardioprotective gene expression patterns.
Biochim Biophys Acta. 1842(12 Pt A):2448-56.
2014. PMID: 25239306. IF: 5,089. DOI:
10.1016/j.bbadis.2014.09.004.
http://dx.doi.org/10.1016/j.bbadis.2014.09.004
Avendaño MS, Lucas E, Jurado-Pueyo M, MartínezRevelles S, Vila-Bedmar R, Mayor F Jr, Salaices M,
Briones AM, Murga C. Increased Nitric Oxide
Bioavailability in Adult GRK2 Hemizygous Mice Protects
Against
Angiotensin
II-Induced
Hypertension.
Hypertension. 63(2):369-75. 2014. PMID: 24191280. IF:
7,632. DOI: 10.1161/HYPERTENSIONAHA.113.01991.
http://dx.doi.org/10.1161/HYPER TENSIONAHA.113.01991
Garcia-Guerra L, Vila-Bedmar R, Carrasco-Rando M,
Cruces-Sande M, Martín M, Ruiz-Gómez A, Ruiz-Gómez
M, Lorenzo M, Fernández-Veledo S, Mayor F Jr, Murga
C, Nieto-Vázquez I. Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase 2. J Mol Cell
Biol. 6(4):299-311. 2014. PMID: 24927997. IF: 8,432.
DOI: 10.1093/jmcb/mju025.
http://dx.doi.org/10.1093/jmcb/mju025
– 49 –
• Mayor
Menéndez,
Federico.
RECAVA.
RD12/0042/0012. ISCIII. 2013-2016.
• Mayor Menéndez, Federico. Redes moleculares y celulares en enfermedades inflamatorias. S-2010/BMD-2332
- Programa de Actividades I+D en BIOMEDICINA. CAM.
2012-2015.
• Mayor Menéndez, Federico. La quinasa GRK2 (G
Protein-Coupled Receptor kinase 2) como un nodo central en las redes de señalización celular. Papel en fisiopatología. SAF2011-23800. MICINN. 2012-2014.
• Ribas Núñez, Catalina. Nuevas vías de señalización iniciadas por interacción entre proteínas GALFAQ y PKCZ
tras activación por GPCRS: su regulación e implicación
en enfermedades cardiovasculares. PI11/00126. ISCIII.
2012-2014.
GROUP 12
HEAD OF LABORATORY
Manuel Fresno Escudero
GROUP MEMBERS
• Ruth Álvarez Díaz
• Alicia Arranz De Miguel
• Beatriz Barrocal López
• Isabel M. Chico-Calero
• Carlos Chillón Marinas
• Natalia Cuesta Rubio
• Mª de los Ángeles de Chorro y de Villa-Ceballos
• Javier Galán Martínez
• Nuria Gironés Pujol
• Alberto Jiménez Buiza
• Marta Jiménez Martínez
• Alba Jiménez Segovia
• María Gema Marín Alberca
• María del Carmen Maza Moreno
• Inés Claire Osma García
• Cristina Poveda Cuevas
• Carmen Punzón Gálvez
• Carmen Mª Sánchez-Valdepeñas Villegas
• Konstantinos Stamatakis Andriani
RESEARCH INTEREST
Our group is analyzing the involvement of Toll-like receptors (TLR)/NFAT/Cyclooxygenase (Cox)-2/prostaglandins
(PGs) in the immune system and inflammatory pathologies as Obesity, Cancer and Sepsis. PGs trigger activation and migration of T lymphocytes, controlling the duration of their interaction with antigen presenting cells.
Macrophage migration is induced by PGs due to activation of p110γ-PI3K by PG receptors. PGF2α negatively
regulates adipocyte differentiation through the transcription factor NFAT. Moreover, NFATc4 deficiency induces
obesity in mice indicating a key role in obesity and fatty
acid metabolism. Cox2 Inhibitors reduce colorectal cancer but have cardiovascular risks. As an alternative therapeutic approach, we have analyzed genes regulated by
– 50 –
Cox2 and select those that could provide a protooncogenic advantage to form tumours and/or metastasize.
Among those, we identified, mPGES1, PMEPA1 and
DUSP10 as Cox2 induced molecules in ovarian or colon
cancer. mPGES1 is involved in increased growth and
induced through a PGF2α/Egr-1 mechanism. DUSP10
controls stress response to serum deprivation and confluence arrest, whereas PMEP1A induces Epithelial
Mesenchymal Transition. DUSP10 inhibits p38 mitogen
activated protein kinase (MAPK) activation, whereas
PMEPA1 inhibit phosphorylation of SMAD1,5,8 by TGFβ.
Different genetic lineages have been defined in
Trypanosoma cruzi, the causative agent of Chagas disease. However, understanding of their comparative biology and pathogenesis is fragmentary. We have identified
different T dependent immune responses both in patients
and mouse model that differ depending of the infecting
strain. Besides, we are studying how the parasite enters,
infects and escapes destruction by myeloid cells, defining
Slamf1 (CD150) as a new T. cruzi receptor. In contrast,
we found that Slamf8 (CD353) is a cell surface receptor
that is expressed upon activation of macrophages by
IFN-γ and plays a negative role in the infection through
repression of the NADPH oxidase.
In the near future, we will continue the studies on the role
of Cox-2/PGF2α and different NFAT family members on
the differentiation of adipocytes and how this translates
into obesity and insulin resistance. Also, apart from finishing the DusP10 and PMEPA1 roles on ovarian and colon
cancer, we will analyze the role of other Cox-2/NFAT
dependent genes we have already identified on colon
cancer and also in Intestinal inflammation. Finally in T.
cruzi we will continue the work on the impact of T. cruzi
genetic variability on the clinical outcome and
immunopathology of Chagas’ disease as well as drug
susceptibility. All intended for improved understanding
and prevention of Chagas’ disease.
MAJOR GRANTS
• Fresno Escudero, Manuel. Immunoregulatory molecules as biomarkers predicting response to biological
AREA 1
•
•
•
•
•
PUBLICATIONS
(6)
Poveda C, Fresno M, Gironès N, Martins-Filho OA,
Ramírez JD, Santi-Rocca J, Marin-Neto JA, Morillo
CA, Rosas F, Guhl F. Cytokine Profiling in Chagas
Disease: Towards Understanding the Association
with Infecting Trypanosoma cruzi Discrete Typing
Units (A BENEFIT TRIAL Sub-Study). PLoS One.
9(3):e91154. 2014. PMID: 24608170. IF: 3,534.
DOI: 10.1371/journal.pone.0091154. eCollection
2014.
http://dx.doi.org/10.1371/journal.pone.0091154.
eCollection 2014
Perez-Molina JA, Poveda C, Martinez-Perez A, Guhl
F, Monge-Maillo B, Fresno M, López-Velez R,
Ramírez JD, Girones N. Distribution of Trypanosoma
cruzi discrete typing units in Bolivian migrants in
Spain. Infect Genet Evol. 21 440-442. 2014. PMID:
24389118.
IF:
3,264.
DOI:
10.1016/j.meegid.2013.12.018.
http://dx.doi.org/10.1016/j.meegid.2013.12.018
Cubillos-Zapata C, Hernández-Jiménez E, Toledano
V, Esteban-Burgos L, Fernández-Ruíz I, Gómez-Piña
V, Del Fresno C, Siliceo M, Prieto-Chinchiña P, Pérez
de Diego R, Boscá L, Fresno M, Arnalich F, LópezCollazo E. NF?B2/p100 Is a Key Factor for
Endotoxin Tolerance in Human Monocytes: A
Demonstration Using Primary Human Monocytes
from Patients with Sepsis. J Immunol. 193(8):4195202. 2014. PMID: 25225662. IF: 5,362. DOI:
10.4049/jimmunol.1400721.
De Winne K, Büscher P, Luquetti AO, Tavares SB,
Oliveira RA, Solari A, Zulantay I, Apt W, Diosque P,
Monje Rumi M, Gironès N, Fresno M, Lopez-Velez R,
Perez-Molina JA, Monge-Maillo B, Garcia L,
Deborggraeve S. The Trypanosoma cruzi satellite
DNA OligoC-TesT and Trypanosoma cruzi kinetoplast DNA OligoC-TesT for diagnosis of Chagas disease: a multi-cohort comparative evaluation study.
PLoS Negl Trop Dis. 8(1):e2633. 2014. PMID:
24392177.
IF:
4,489.
DOI:
10.1371/journal.pntd.0002633. eCollection 2014.
http://dx.doi.org/10.1371/journal.pntd.0002633.
eCollection 2014
Rodriguez HO, Guerrero NA, Fortes A, Santi-Rocca
J, Gironès N, Fresno M. Trypanosoma cruzi strains
cause different miocarditis patterns in infected mice.
Acta Trop. 139:57-66. 2014. PMID: 25017312. IF:
2,519. DOI: 10.1016/j.actatropica.2014.07.005.
http://dx.doi.org/10.1016/j.actatropica.2014.
07.005
– 51 –
•
therapies and disease severity in immune-mediated
inflamatory
disorders.
BIOMID
PROJECT.
Fresno Escudero, Manuel. Prostanoides y receptores
tipo TOLI como mediadores clave y potenciales
dianas terapéuticas en enfermedades crónicas:
cáncer y obesidad. SAF2013-42850. MINECO.
2014-2016.
Fresno Escudero, Manuel. Mediatori dell’infiammazione e angiogenesi: nuovi target per lo sviluppo di farmaci e per terapie personalizzate - mia.
Programa de acción en "desarrollo de estudio de la
educación superior presentada por la universidad de
siena en colaboración con centros de investigación y
empresas". Universidad de Siena, Italia - UE. 20132014.
Fresno Escudero, Manuel. Host-microbe interactions
in health and disease. Interface with the immune system. HOMIN - 317057 - FP7-PEOPLE-2012-ITN. UE
- Marie Curie Actions - Initial Training Networks (ITN).
2013-2017.
Fresno Escudero, Manuel. Identificación de biomarcadores para el seguimiento de pacientes
infectados con distintos linajes de Trypanosoma
cruzi y sometidos a tratamiento. UAM-BANCO DE
SANTANDER Cooperación con América Latina.
2013-2014.
Fresno Escudero, Manuel. Red de investigación
colaborativa en enfermedades tropicales (RICET).
RD12/0018/0004. ISCIII. 2013-2016.
Fresno Escudero, Manuel. Redes moleculares y celulares en enfermedades inflamatorias. S-2010/BMD2332 - Programa de Actividades I+D en BIOMEDICINA. CAM. 2012-2015.
Gironès N, Carbajosa S, Guerrero NA, Poveda C,
Chillón-Marinas C, Fresno M. Global metabolomic
profiling of acute myocarditis caused by
Trypanosoma cruzi infection. PLoS Negl Trop Dis.
8(11):e3337. 2014. PMID: 25412247. IF: 4,489.
DOI: 10.1371/journal.pntd.0003337.
http://journals.plos.org/plosntds/article?id=10.137
1/journal.pntd.0003337
RESEARCH INTEREST
nation or acetylation of manifold regulatory and
effector proteins. These nodes work as molecular
switches that cooperate with oncogenic-signaling
routes or act in normal signaling compensatory
pathways in order to trigger transformation or to
cope with intrinsic tumor-derived vulnerabilities. Our
studies indicate that the serine/threonine kinase
GRK2 is emerging as a relevant modulator of oncogenic signaling modules by its ability to impinge the
ubiquitination and acetylation of manifold proteins in
transformed cells. GRK2 stimulates the activity of
the E3 ligase Mdm2 and the deacetylase HDAC6,
which are key players in cellular transformation by
means of the inhibition of tumor suppressors (p53)
and modulation of molecules involved in cell-cycle
control, angiogenesis, stress responses or metastatic progression. Indeed, concurrent up-regulation of
GRK2, Mdm2 and HDAC6 emerges as a functional
module characteristic of luminal breast cancer cells
that contributes to cellular proliferation and survival.
GRK2 also attenuates the functionality of the kinase
ATM, a central sensor of DNA damage and metabolic stress, which is also engaged in the regulation
of Mdm2 and p53. In addition, our data show that
endothelial GRK2 downregulation is a relevant event
in the angiogenic switch triggered by tumor cells by
favoring a permissive microenvironment for tumor
growth and metastasis.
Breast cancer is one of the most common and heterogeneous cancers, with ductal carcinomas representing 80% of breast tumors. Based on distinctive
molecular profiling, ductal carcinomas are classified
in order of worse prognosis as estrogen-positive
luminal A and luminal B, ERBB2-positive or basallike (ER-, PR-, ERBB2-negative) tumors. Besides
oncogenic drivers underpinning breast ductal carcinomas (PI3K, Ras, mutations in p53), alteration of
relevant signaling nodes can critically modulate cancer progression-related cellular networks to
strength key tumoral hallmarks as aberrant proliferation, angiogenesis or invasion and metastasis.
Some of these molecular nodes integrate multiple
upstream inputs and elicit diverse downstream outputs through the modulation of posttranslational
modifications, including phosphorylation, ubiquiti-
Our main goals are to define the functional intertwinement of Mdm2/p53/ATM/HDAC6 in transformed epithelial cells and in the response of
endothelial cells, to characterize the regulation of
this signaling module by GRK2 under different
tumor-environmental stresses and their consequences on breast tumor progression. Different
integrated responses that contribute to tumor
malignancy such as cellular invasiveness or cellular
senescence are analyzed. We are addressing how
the regulation of Mdm2/ATM/HDAC6 by GRK2
impacts on the metabolic and mitochondrial homeostasis of breast cells when genome integrity is
compromised by nutrient overload, genotoxic
agents or oxidative stress. We are also characterizing the angiogenic response promoted by this signaling module and the molecular mechanisms
GROUP 13
HEAD OF LABORATORY
Petronila Penela Márquez
GROUP MEMBERS
• Adolfo Molejón García
• Laura Nogués Vera
• Clara Reglero Gómez
• Verónica Rivas Guerrero
– 52 –
AREA 1
MAJOR GRANTS
• Penela Márquez, Petronila. Repercusiones de la regulación de MDM2 y p53 por la quinasa GRK2 en cáncer
de mama: estabilidad genómica y quimioresistencia.
ISCIII. PI11/00859. 2012-2014.
• Penela Márquez, Petronila. Estudio de las implicaciones funcionales de la serina-treonina quinasa de
GRK2 en la telangectasia hemorrágica hereditaria.
Fundación Ramón Areces. 2012-2015.
Granted 2014
• Penela Márquez, Petronila. Interrelación de GRK2 con
MDM2 y ATM en inestabilidad genómica por estrés
metabólico y en la invasividad celular y angiogenesis:
oportunidades terapéuticas en tumores de mama.
PI14/00435. ISCIII. 2015-2017.
PUBLICATIONS (2)
Penela P, Nogués L, Mayor F Jr. Role of G proteincoupled receptor kinases in cell migration. Curr
Opin Cell Biol. 27: 10-17. 2014. PMID: 24680425.
IF: 8,736. DOI: 10.1016/j.ceb.2013.10.005.
http://dx.doi.org/10.1016/j.ceb.2013.10.005
Fernández-Arenas E, Calleja E, Martínez-Martín N,
Gharbi SI, Navajas R, García-Medel N, Penela P,
Alcamí A, Mayor F Jr, Albar JP, Alarcón B. ßarrestin-1 mediates the TCR-triggered re-routing of
distal receptors to the immunological synapse by a
PKC- mediated mechanism. EMBO J. 33(6):559577. 2014. PMID: 24502978. IF: 10,748. DOI:
10.1002/embj.201386022.
http://dx.doi.org/10.1002/embj.201386022
GROUP 17
HEAD OF LABORATORY
Cristina Murga Montesinos
GROUP MEMBERS
• Marta Cruces Sande
• Elisa Lucas Fernández
• Rocío Vila Bedmar
RESEARCH INTEREST
Obesity and insulin resistance (IR) are major health
problems that have reached epidemic proportions
worldwide. The inflammatory components of these diseases are being recently unveiled as key factors in both
the aetiology and the development of these diseases.
Cell signalling pathways that serve as nodal points
interconnecting pathological insults and metabolic signals to inflammatory routes are thus a main focus of
research for the mechanistic basis of these pathologies
to be fully understood. In this line, the signalling hub of
the G protein-coupled receptor kinase 2 (GRK2)
emerges as a clear point of control in the metabolic,
stress and inflammatory network of routes controlling
the initiation and progress of these diseases. Given the
lack of selective and potent inhibitors for this kinase,
our group has focused on proof of concept studies in
genetically-modified animal models.
In this context, our group pursues four main lines of
investigation.
1. Preliminary evidence suggests that specific GRK2
effects in macrophages and other inflammatory cells
may contribute to the control of insulin sensitivity, adiposity and obesity in human samples and animal models of these diseases. We will study the influence of
changes in GRK2 expression levels specifically in
macrophages infiltrating white adipose tissue and other
insulin-sensitive organs during fat mass accretion in the
development of obesity-associated weight gain, adiposity and IR.
– 53 –
involved in the concurrent and opposite changes of
GRK2 in the epithelial (up-regulation) and vascular
endothelial (down-modulation) components of
breast tumors, responsible for the intra-tumor vascular remodeling.
2. We will work on the validation of GRK2 as a novel
therapeutic target in the development of obesity and/or
IR using a tamoxifen-inducible mice model that allows
for the deletion of this protein once the pathology has
been established. We will study whether GRK2 deletion
not only prevents (as already published) but can also
revert weight gain and IR, and characterize the main
tissues and cellular functions by which GRK2 could
exert these effects as well as the molecular mechanisms involved.
3. We will analyze the importance of the GRK2 signaling node and changes in its levels or activity in
the development of hepatic steatosis in the form of
non alcoholic steatohepatitis (NASH) and its further
development into more complex pathologies such
as non alcoholic fatty liver disease (NAFLD) that
involve liver inflammation, dysfunction and fibrosis.
We will use mice models of these diseases (including high fat diet feeding and hepatic damage models) in order to test the influence and importance of
the GRK2 node in the genesis or progression of
these pathologies paying particular attention to the
inflammatory component (infiltrates, M1/M2 polarization, secretome,…).
MAJOR GRANTS
Murga Montesinos, Cristina. Joint collaborative effort
in the identification of novel therapeutic targets for
the treatment of diabetes and obesity. UAM. 20132014.
Lucas E, Jurado-Pueyo M, Fortuño MA, FernándezVeledo S, Vila-Bedmar R, Jiménez-Borreguero LJ,
Lazcano JJ, Gao E, Gómez-Ambrosi J, Frühbeck G,
Koch WJ, Díez J, Mayor F Jr, Murga C. Downregulation
of G protein-coupled receptor kinase 2 levels enhances
cardiac insulin sensitivity and switches on cardioprotective gene expression patterns. Biochim Biophys
Acta. 1842(12 Pt A):2448-56. 2014. PMID: 25239306.
IF: 5,089. DOI: 10.1016/j.bbadis.2014.09.004.
Avendaño MS, Lucas E, Jurado-Pueyo M, MartínezRevelles S, Vila-Bedmar R, Mayor F Jr, Salaices M,
Briones AM, Murga C. Increased Nitric Oxide
Bioavailability in Adult GRK2 Hemizygous Mice
Protects Against Angiotensin II-Induced Hypertension.
Hypertension. 63(2):369-75. 2014. PMID: 24191280.
IF:
7,632.
DOI:
10.1161/HYPERTENSIONAHA.113.01991.
http://dx.doi.org/10.1161/HYPER TENSIONAHA.113.01991
Garcia-Guerra L, Vila-Bedmar R, Carrasco-Rando M,
Cruces-Sande M, Martín M, Ruiz-Gómez A, RuizGómez M, Lorenzo M, Fernández-Veledo S, Mayor F
Jr, Murga C, Nieto-Vázquez I. Skeletal muscle myogenesis is regulated by G protein-coupled receptor kinase
2. J Mol Cell Biol. 6(4):299-311. 2014. PMID:
24927997. IF: 8,432. DOI: 10.1093/jmcb/mju025.
http://dx.doi.org/10.1093/jmcb/mju025
GROUP 18
PUBLICATIONS (4)
Willemen HL, Campos PM, Lucas E, Morreale A, GilRedondo R, Agut J, González FV, Ramos P, Heijnen C,
Mayor Jr F, Kavelaars A, Murga C. A novel p38 MAPK
docking groove-targeted compound is a potent
inhibitor of inflammatory hyperalgesia. Biochem J.
459(3):427-39. 2014. PMID: 24517375. IF: 4,779. DOI:
10.1042/BJ20130172.
http://dx.doi.org/10.1042/BJ20130172
– 54 –
HEAD OF LABORATORY
Miguel Ángel Iñiguez Peña
GROUP MEMBERS
• Paloma Guillem Llobat
• Elena Hernández Subirá
• Raquel Nieto Pintado
• Ana Renshaw Calderón
AREA 1
Lipid mediators such as prostanoids or oxidized compounds derived from cholesterol, play an essential role in
the modulation of the inflammatory process associated
with multiple diseases as arthritis, atherosclerosis and
cancer. Prostanoid family include prostaglandins (PGs)
and thromboxanes (TXs), synthesized from arachidonic
acid by the action of cyclooxygenases (COX-1 and COX2) and various PG synthases. On the other hand, LXRs
(Liver X receptors) and their ligands, including oxidized
cholesterol compounds, play a central regulatory role in
lipid uptake, metabolism and efflux through their properties as transcriptional regulators of gene expression. In
addition to their function in lipid metabolism, LXRs have
also been found to modulate immune and inflammatory
responses through the regulation of the expression of
essential genes in the activation of immune cells.
The main objectives of our research include the study of
the molecular mechanisms by which prostanoids and
LXR ligands exert their actions on the immune response
and their involvement in pathologies with inflammatory
processes, using cellular and animal models. These
studies include the analysis of the effects of prostanoids
and LXR ligands, and their interrelationship, through their
actions on cell signaling, and transcriptional activation of
gene expression in various cell types including T lympho-
cytes and macrophages. We are currently investigating
the differential effect of prostanoids as PGF2α or
cyclopentenones on macrophage and T cell activation,
either as positive or negative regulators of the function of
these cells. Our investigations are also aimed to determine the influence of LXR ligands in the modulation of T
cell and macrophage function, with special attention to
their key role as regulators of gene expression in these
cells and to their influence in different parameters of cell
activation.
Advances in the knowledge of the molecular and cellular
basis of the actions of prostanoids and LXR ligands in
inflammation and in the immune response, is especially
relevant, given the growing interest on the influence of
inflammatory processes in multiple pathologies and on
the possibilities for therapeutic intervention by modulating the actions of these agents.
MAJOR GRANTS
• Íñiguez Peña, Miguel Ángel. Acciones de prostanoides
y ligandos del receptor LXR en procesos inflamatorios
y sus implicaciones en la fisiopatología cardiovascular.
SAF2011-23971. MICINN. 2012-2014.
– 55 –
RESEARCH INTEREST
Line 1.5
Cellular mechanisms and
molecular determinants of
allergy-based diseases
GROUP 20
HEAD OF LABORATORY
Carlos Blanco Guerra
GROUP MEMBERS
• María Teresa Belver González
• Álvaro Daschner
• Consolación de Frutos Moreno
• M. Paloma Las Heras Almazán
• María Victoria Múgica García
• Tania María Ramos García
• Ana Valls Sánchez
• Francisco Félix Vega de la Osada
RESEARCH INTEREST
Allergic diseases are increasing worldwide, related
to a complex interaction between genetic and environmental factors, and reaching prevalence rates
higher than 30%. Among them, respiratory allergy,
including bronchial asthma and rhinoconjunctivitis,
is a research priority target for most heath organizations. Nowadays, allergen specific immunotherapy is the only way to modify the natural course of
allergic respiratory diseases. Meanwhile, food allergy is a rising problem, due to both the potential
severity of reactions and to its great impact on
patient quality of life. In this context, it is noteworthy that cross-reactions between certain food- and
inhalant-allergens lead to a complex group of clinical syndromes, complicating the management of
allergic patients. Among cross-reacting pan-aller-
– 56 –
gens, profilins are one of the most relevant in the
Mediterranean area.
Our group has three main research lines:
- Immunotherapy for respiratory allergy: a 2 year
study prolongation of the phase IV study GT-20,
checking immunological changes induced by
grass-pollen immunotherapy on respiratory allergy.
Moreover, a new placebo controlled clinical trial has
been recently started, intended to confirm data
from the previous study, its results will be available
by 2017.
- Food allergy: we continue to work with Centre for
Plant Biotechnology and Genomics (UPM-INIA,
Dra. Díaz-Perales), studying the role of N-glycosylation in kiwi allergy, and its possible relation with
Alternaria respiratory allergy. At the same time, we
have started collaborating in a research project,
focused on nut allergy, which is one of the most
prevalent and severe food allergies.
- Finally, we have recently focused on sensitization
to the pollen-food pan-allergen profilin, which is
associated with bronchial asthma, fruit allergy and
poor immunotherapy response. On one side,
mechanisms responsible for food allergy in profilinsensitized patients will be studied in the context of
another research project (2014-2016) led by Dr.
Barber (from the C.E.U. University). On the other
side, a study focused on T-cell response repertoire
to profilin is currently ongoing (2014-2016), in collaboration with ALK-Denmark.
MAJOR GRANTS
• Daschner, Alvaro. PROYECTO ALERGIA. Diater.
2010-2015.
PUBLICATIONS
(5)
Suárez-Fueyo A, Ramos T, Galán A, Jimeno L,
Wurtzen PA, Marin A, de Frutos C, Blanco C,
Carrera AC, Barber D, Varona R. Grass tablet sub-
AREA 1
Vega F, Ramos T, Las Heras P, Blanco C. Kounis
syndrome associated with brain injury after
Hymenoptera sting: new presentation of an established entity. Int J Cardiol. 176(1):e29-e31. 2014.
PMID: 25061014. IF: 6,175. DOI:
http://dx.doi.org/10.1016/j.ijcard.2014.07.051
González-Fernández J, Rodero M, Daschner A,
Cuéllar C. New insights into the allergenicity of
tropomyosin: a bioinformatics approach. Mol Biol
Rep. 41(10):6509-6517. 2014. PMID: 24985979.
IF: 1,958. DOI: 10.1007/s11033-014-3534-6.
http://dx.doi.org/10.1007/s11033-014-3534-6
Daschner A, Fernández-Fígares V, Rodero M, Valls
A, de Frutos C, Ubeira FM, Cuéllar C. Specific
IgG4: possible role in the pathogenesis and a new
marker in the diagnosis of Anisakis associated
allergic disease. Scan J Immunol. 79(2):120-6.
2014. PMID: 24219647. IF: 1,882. DOI:
10.1111/sji.12129.
http://dx.doi.org/10.1111/sji.12129
Pedrosa M, Prieto-García A, Sala-Cunill A; Spanish
Group for the Study of Bradykinin-Mediated
Angioedema (SGBA) and the Spanish Committee of
Cutaneous Allergy (CCA). Collaborators: Caballero
T, Baeza M, Cabañas R, Campos A, Cimbollek S,
Gómez-Traseira C, Quevedo T, Guilarte M, JuradoPalomo J, Lobera T, López-Serrano M, Marcos C,
Piñero-Saavedra M, Prior N, Sáenz de San Pedro
B, Ferrer M, Barceló J, Daschner A, Echechipía M,
Garcés M, Iriarte P, Jáuregui I, Lázaro M, Quiñones
M, Veleiro B, Villareal O. Management of angioedema without urticaria in the emergency department.
Ann Med 46(8):607-618. 2014. PMID: 25580506.
IF: 4,733. DOI: 10.3109/07853890.2014.949300.
http://informahealthcare.com/doi/abs/10.3109/07
853890.2014.949300
BOOKS
Däschner A. Alimentos fermentados: ¿Pueden igualmente conseguir los efectos postulados de los probióticos?. Medicina Evolucionista II. Aportaciones pluridisciplinares. MedEvo. ISBN: 978-84-617-0375-3
GROUP 15
HEAD OF LABORATORY
María Dolores Ibáñez Sandín
GROUP MEMBERS
• Carmelo Escudero Díez
• Pablo Rodríguez del Rio
• Silvia Sánchez García
RESEARCH INTEREST
The main research programs ongoing are: oral
immunotherapy with several foods, the study of epidemiologic and component resolved diagnosis of nut allergy,
the study on the description of egg allergy immunophenotypes, the study of allergy to penicillins in children
below 14 years old and the study on the different diagnostic procedures of exercise-induced asthma in children
Food allergy
Food immunotherapy:
Our objectives in this field include:
• Design of protocols of oral immunotherapy for egg
and wheat allergy that improve time consumption,
efficacy and safety.
• Determine the efficacy of the aforementioned food
immunotherapy protocols in the long term from the
clinical and immunological points of view.
• Develop a food immunotherapy National Guideline
along with other centres and specialists in the
– 57 –
lingual immunotherapy downregulates the TH2
cytokine response followed by regulatory T-cell
generation. J Allergy Clin Immunol. 133(1):130138.e2. 2014. PMID: 24290282. IF: 11,248. DOI:
10.1016/j.jaci.2013.09.043.
http://dx.doi.org/10.1016/j.jaci.2013.09.043
field, under the framework of the SEAIC and the
SEICAP.
• Finish the project “OmaBase”: Registry of cases of
Omalizumab use in the treatment of food allergy.
Multicentre Registry of cases of patients allergic to
food (milk, eggs and/or vegetables), treated with omalizumab alone or associated to immunotherapy”. This
Project is developing and is now in its final phase, registering the cases of patients allergic to food treated
with Omalizumab under any indication, and following
the evolution of their food allergy, regardless of the
concomitant use of food immunotherapy.
• Fish oral immunotherapy: This multicentre project,
approved by the ethical committee of the HNJ and
the AEMPS, and supported by the SEICAP, is currently starting.
Food allergy epidemiology and food allergens:
• AFRUSEN registry: “Registry of new cases of nut
allergy in a paediatric population: clinical characteristics and sensitization. Multicentre Study“. The main
objectives are to describe the clinical features and
sensitization patterns (molecular diagnosis) of new
onset diagnosis of allergy to the most frequently consumed nuts in Spain and stratify it according to the
different regions.
• OVALE clinical trial: “Description through a microarray assay of immunophenotypes in the antigen
recognition in egg proteins allergy in a paediatric
population. This multicentre project, aims to follow a
cohort of newly diagnosed egg allergic patients and
describe the different clinical and immunological profiles according to their evolution.
Asthma:
It is our goal to develop a position statement based on
expert consensus in the diagnosis of Exercise-Induced
asthma in children.
Drug allergy:
• APENIN survey: “Study of penicillin allergy in childhood”. This study aims to evaluate the efficiency of
the penicillin allergy diagnostic tools among a paediatric population in a real life setting in different spanish allergy departments. In a second stage, a diagnostic procedure algorithm is planned to be delivered
for children below 14 years old.
– 58 –
MAJOR GRANTS
• Ibáñez Sandín, María Dolores. Descripción de
inmunofenotipos en el reconocimiento inmunológico
mediante un ensayo microarray en la alergia a proteínas de huevo en población infantil. OVALE.
PI11/02074. ISCIII. 2012-2014.
• Ibáñez Sandín, María Dolores. Immunoterapia oral
con huevo en alergia mediada por IgE en población
infantil con alergia a huevo persistente: estudio y
seguimiento mediante test de activación de basófilos, liberación de leucotrienos por basófilos y producción in vitro de citoquinas. ALK- Abelló. 20122014.
PUBLICATIONS
(5)
Benedé S, Pérez-Rangel I, Lozano-Ojalvo D, Molina
E, Ibañez MD, López-Fandiño R, López-Expósito I.
Anaphylaxis Induced by a Drug Containing
Lysozyme and Papain: Influence of Papain on the
IgE Response. Int Arch Allergy Immunol. 165(2):8390. 2014. PMID: 25359082. IF: 2,433. DOI:
10.1159/000366101.
http://dx.doi.org/10.1159/000366101
Ruiz-García M, Díez CE, García SS, del Río PR,
Ibáñez MD. Diagnosis and natural history of food
protein-induced enterocolitis syndrome in children
from a tertiary hospital in central Spain. J Investig
Allergol Clin Immunol. 24(5):354-6. 2014. PMID:
25345307. IF: 2,642
Gámez C, Zafra M, Boquete M, Sanz V, Mazzeo C,
Ibáñez MD, Sánchez-García S, Sastre J, del Pozo
V. New shrimp IgE-binding proteins involved in
mite-seafood cross-reactivity. Mol Nutr Food Res.
58(9):1915-25. 2014. PMID: 24978201. IF: 4,909.
DOI: 10.1002/mnfr.201400122.
http://dx.doi.org/10.1002/mnfr.201400122
Rodríguez del Río P, Díaz-Perales A, SanchezGarcía S, Escudero C, do Santos P, Catarino M,
Ibañez MD. Oral immunotherapy in children with
AREA 1
Pfaar O, Demoly P, Gerth van Wijk R, Bonini S,
Bousquet J, Canonica GW, Durham SR, Jacobsen
L, Malling HJ, Mösges R, Papadopoulos NG, Rak
S, Rodriguez del Rio P, Valovirta E, Wahn U,
Calderon MA; European Academy of Allergy and
Clinical Immunology. Recommendations for the
standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper (Ibañez MD).
Allergy. 69(7):854-67. 2014. PMID: 24761804. IF:
5,995. DOI: 10.1111/all.12383.
http://dx.doi.org/10.1111/all.12383
IgE-mediated wheat allergy: outcome and molecular changes. J Investig Allergol Clin Immunol.
24(4):240-8. 2014. PMID: 25219106. IF: 2,642
– 59 –
Line 1.6
Inflammatory processes in
nephrological diseases
GROUP 21
HEAD OF LABORATORY
José Antonio Sánchez Tomero
GROUP MEMBERS
• Abelardo Isaac Aguilera Peralta
• Vicente Álvarez Chiva
• Guillermina Barril Cuadrado
• Carmen Bernis Carro
• Antonio Carlos Fernández Perpén
• Martín Giorgi González
• Isabel Herráez Jiménez
• Almudena Nuñez Sánchez
• Pablo Ruano Suárez
• Laura Salanova Villanueva
• Carmen Sánchez González
RESEARCH INTEREST
Peritoneal Dialysis (PD): Our main line of work is
focused on the study of the mechanisms involved in
the damage induced by DP on the peritoneal membrane. Also, we studied the influence of several drugs
(Paricalcitol, Tamoxifen, Roxiglitazona) in preventing
and repairing damage to the peritoneal membrane. In
the next years we will try to clarify what are the mechanisms responsible for the hyalinizing vascular disease,
the role of alternatively activated macrophages in the
progression of peritoneal damage and analyze the morphological and immunohistochemical findings in peritoneal biopsies from patients treated with conventional
or biocompatible liquids. An ongoing project is to
design a microchip for early diagnosis of mesothelial to
mesenchymal transition in peritoneal membrane noninvasively using the peritoneal effluent. Preliminary data
– 60 –
have shown that peritoneal dialysis, in animals subjected to a cerebral ischemic damage, is able to decrease
the cerebral damage induced by high glutamate levels.
In collaboration with the Neurology Service we are conducting a clinical trial in patients to determine whether
peritoneal dialysis can protect from ischemic brain
damage in the acute phase of ischemic stroke.
Nutrition in Renal disease: We have studied the importance of exercise in proper nutrition and survival of
patients with advanced chronic kidney disease and the
effect of physical training. We have studied the introduction of new scores for nutritional assessment of
renal patients and we intend to study the balance of
myocytokines and its relation to muscle strength and
functionality.
Alterations of Bone and Mineral Metabolism in CKD:
FGF23 is a molecule involved in the metabolism of
phosphorus but can be important as a marker of cardiovascular pathology and survival in renal disease. We
have designed a clinical trial, which already has funding, to analyze the behavior of FGF23 and PTH fragments in patients with chronic kidney disease on peritoneal dialysis program treated with cinacalcet.
MAJOR GRANTS
• Sánchez Tomero, José Antonio. Importancia del ejercicio físico en la nutrición y supervivencia de los
pacientes con enfermedad renal crónica avanzada.
Baxter SA. 2014-2015.
• Sánchez Tomero, José Antonio. Reparación de tejidos mediante la repoblación por progenitores de
médula ósea. Amgen SA y PALEX SA. 2014-2016.
• Sánchez Tomero, José Antonio. Proyecto para la
coordinación y criterios de derivación entre primaria
y especializada en nefrología en el Hospital de La
Princesa. Laboratorios Rovi. 2014-2014.
• Carmen Bernis Carro. European multicenter and
open-label. Controlled randomized trial to evaluate
the efficacy of sequential treatment with tacrolimusrituximab versus steroids plus cyclophosphamide in
patients with primary membranous nephropathy.
STARMEN01-2013. 2014-2016.
AREA 1
PUBLICATIONS (12)
Ruperto M, Sánchez-Muniz FJ, Barril G. A clinical
approach to the nutritional care process in proteinenergy wasting hemodialysis patients. Nutr Hosp.
29(4):735-750. 2014. PMID: 24679014. IF: 1,25. DOI:
10.3305/nh.2014.29.4.7222.
http://dx.doi.org/10.3305/nh.2014.29.4.7222
M. Luisa González-Casaus, Emilio González-Parra,
Carmen
Sánchez-González,
Marta
Albalate,
Concepción de La Piedra-Gordo, Elvira Fernández,
Vicente Torregrosa, Mariano Rodríguez, Víctor Lorenzo.
A lower proportion of circulating active parathyroid hormone in peritoneal dialysis does not allow the pth intermethod adjustment proposed for haemodialysis.
Nefrologia. 34(3):330-340. 2014. PMID: 24798561. IF:
1,442. DOI: 10.3265/Nefrologia.pre2014.Feb.12384.
http://dx.doi.org/10.3265/Nefrologia.pre2014.Feb.123
84
Carolina Gracia-Iguacel, Emilio González-Parra,
Guillermina Barril-Cuadrado, Rosa Sánchez, Jesús
Egido, Alberto Ortiz-Arduán, Juan J. Carrero. Defining
protein-energy wasting syndrome in chronic kidney
disease: prevalence and clinical implications.
Nefrologia. 34(4):507-519. 2014. PMID: 25036065. IF:
1,442. DOI: 10.3265/Nefrologia.pre2014.Apr.12522.
http://dx.doi.org/10.3265/Nefrologia.pre2014.Apr.12522
Panel of experts from the AIDS Working Group (GESIDA) of the Spanish Society of Infectious Diseases and
Clinical Microbiology (SEIMC), the Spanish Society of
Nephrology (S.E.N.), and the Spanish Society of
Clinical Chemistry and Molecular Pathology (SEQC),
Górriz JL, Gutiérrez F, Trullas JC, Arazo P, Arribas JR,
Barril G, Cervero M, Cofan F, Domingo P, Estrada V,
Fulladosa X, Galindo MJ, Gracia S, Iribarren JA, Knobel
H, Lopez-Aldeguer J, Lozano F, Martínez-Castelao A,
Martinez E, Mazuecos MA, Miralles C, Montañes R,
Negredo E, Palacios R, Pérez-Elías MJ, Portilla J,
Praga M, Quereda C, Rivero A, Santamaria JM, Sanz J,
Sanz J, Miró JM. Executive summary of the consensus
document on the management of renal disease in HIVinfected patients. Nefrologia. 34(6):768-788. 2014.
PMID:
25415577.
IF:
1,442.
DOI:
10.3265/Nefrologia.pre2014.Sep.12745.
http://dx.doi.org/10.3265/Nefrologia.pre2014.Sep.127
45
Gorriz JL, Gutiérrez F, Trullàs JC, Arazo P, Arribas JR,
Barril G, Cervero M, Cofán F, Domingo P, Estrada V,
Fulladosa X, Galindo MJ, Gràcia S, Iribarren JA, Knobel
H, López-Aldeguer J, Lozano F, Martínez-Castelao A,
Martínez E, Mazuecos MA, Miralles C, Montañés R,
Praga M, Quereda C, Rivero A, Santamaría JM, Sanz J,
Sanz J, Miró JM. Executive summary of the recommendations on the evaluation and management of
renal disease in human immunodeficiency virus-infected patients. Enferm Infecc Microbiol Clin. 32(9):583-97.
2014. PMID: 25303781. IF: 1,881. DOI:
10.1016/j.eimc.2014.09.002.
http://dx.doi.org/10.1016/j.eimc.2014.09.002
– 61 –
• Sánchez Tomero, José Antonio. Desarrollo de un
programa para el abordaje integral del tratamiento de
la enfermedad renal crónica avanzada. United
Surgical Partners Madrid, SL. Hospital Quirón San
Camilo. 2013-2015.
• Sánchez Tomero, José Antonio. Protective effect of
icodextrin on mesothelial-to-mesenchymal transition
of mesothelial cells induced by peritoneal dialysis fluids. PI 468. Baxter SA. 2013-2014.
• Sánchez Tomero, José Antonio. Estudio de los marcadores de riesgo cardiovascular en la enfermedad
renal y proyección pronóstica. Nipro Europe SA.
2013-2015.
• Barril Cuadrado, Guillermina. Balance de miocitoquinas en hemodiálisis. Variaciones según el esquema de hemodiálisis. SOMANE.2013. Fundación
Médica de Nefrología. 2013-2015.
• Bernis Carro, Carmen. Programa cifra: “utilización de
modelos animales y celulares para caracterizar el fracaso renal agudo y multiorgánico". MINECO.
S2010/BMD-2378. 2012-.
• Aguilera Peralta, Abelardo Isaac. La cavidad abdominal como fuente de factores de riesgo cardiovascular y de ateroesclerosis durante la diálisis peritoneal:
alternativas terapéuticas. ISCIII. PI12/01175. 20122015.
• Sánchez Tomero, José Antonio. ABBOTT. 2009-
Castillo I, Martinez-Ara J, Olea T, Bartolomé J, Madero
R, Hernández E, Bernis, C, Aguilar A, Quiroga JA,
Carreño V, Selgas R. High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies. Kidney Int.
86(3):619-624. 2014. PMID: 24646855. IF: 8,52. DOI:
10.1038/ki.2014.68.
http://dx.doi.org/10.1038/ki.2014.68
Barril G, Quiroga JA, Arenas MD, Espinosa M, GarcíaFernández N, Cigarrán S, Herrero JA, del Peso G, Caro
P, García-Agudo R, Amézquita Y, Blanco A, MartínezRubio P, Alcázar JM, González-Parra E, Martín-Gómez
A, Castillo I, Bartolomé J, Carreño V. Impact of isolated
hepatitis C virus (HCV) core-specific antibody detection
and viral RNA amplification among HCV-seronegative
dialysis patients at risk for infection. J Clin Microbiol.
52(8):3053-3056. 2014. PMID: 24850345. IF: 4,232.
DOI: 10.1128/JCM.01339-14.
http://dx.doi.org/10.1128/JCM.01339-14
Arroyo D, Betriu A, Martinez-Alonso M, Vidal T,
Valdivielso JM, Fernández E; investigators from the
NEFRONA study (Sánchez-Tomero JA). Observational
multicenter study to evaluate the prevalence and
prognosis of subclinical atheromatosis in a Spanish
chronic kidney disease cohort: baseline data from the
NEFRONA study. BMC Nephrol. 15:168. 2014. PMID:
25326683. IF: 1,52. DOI: 10.1186/1471-2369-15168.
http://dx.doi.org/10.1186/1471-2369-15-168
– 62 –
Gutiérrez E, Moreno JA, Praga M; Grupo de Estudio de
Enfermedades Glomerulares de la Sociedad Española
de Nefrología (GLOSEN, Bernis C). Persistent microhaematuria with negative or low proteinuria. Nefrologia.
34(1):110-114. 2014. PMID: 24463867. IF: 1,442. DOI:
10.3265/Nefrologia.pre2013.Jul.12096.
http://dx.doi.org/ 10.3265/Nefrologia.pre2013.Jul.12096
Betriu A, Martinez-Alonso M, Arcidiacono MV,
Cannata-Andia J, Pascual J, Valdivielso JM, Fernández
E; Investigators from the NEFRONA Study (SánchezTomero JA). Prevalence of subclinical atheromatosis
and associated risk factors in chronic kidney disease:
the NEFRONA study. Nephrol Dial Transplant.
29(7):1415-1422. 2014. PMID: 24586070. IF: 3,488.
DOI: 10.1093/ndt/gfu038.
http://dx.doi.org/10.1093/ndt/gfu038
Gutiérrez F, Fulladosa X, Barril G, Domingo P. Renal
Tubular Transporter-Mediated Interactions of HIV
Drugs: Implications for Patient Management. AIDS Rev.
16(4):199-212. 2014. PMID: 25350530. IF: 4,023
Ars E, Bernis C, Fraga G, Martínez V, Martins J, Ortiz A,
Rodríguez-Pérez JC, Sans L, Torra R; on behalf of the
Spanish Working Group on Inherited Kidney Disease.
Spanish guidelines for the management of autosomal
dominant polycystic kidney disease. Nephrol Dial
Transplant. 29(sup 4):95-105. 2014. PMID: 25165191.
IF: 3,488. DOI: 10.1093/ndt/gfu186.
http://dx.doi.org/10.1093/ndt/gfu186
AREA 1
GROUP 22
HEAD OF LABORATORY
Julio Ancochea Bermúdez
GROUP MEMBERS
• Carolina Cisneros Serrano
• Rosa María Girón Moreno
• Ana Martínez Meca
• Silvia Sánchez Cuéllar
• Enrique Domingo Zamora García
RESEARCH INTEREST
Inflammation and reparative process in lung diseases.
Chronic obstructive pulmonary disease (COPD). ApneaHypopnea Syndrome. Idiopathic pulmonary fibrosis (IPF).
Inmunopathogeny. Molecular diagnosis. Cellular diagnosis. New therapeutic approaches. New care models.
Pulmonary diseases are an important social and
healthcare topic, related to its high prevalence and
associated morbimortality. In recent years, our group
has worked on different topics related to lung diseases,
as it is reflected in our publications carried out in collaboration with other research groups.
General objectives: 1. Promote research in lung diseases. 2. Promote care quality in the therapeutic
approach to patients with chronic lung diseases. 3.
Promote research transfer in lung diseases. 4. Create
new lines of investigation in coordination with other
research groups.
Research interests: The Pulmonary Department of La
Princesa Hospital is part of the R+D Biomedicine
Programme. HUP ConSEPOC-CM: Inflammation and
hypoxia: mechanisms of development and progression
of COPD and SAHS (S2010/BMD-2542). Julio
Ancochea is the leader of the group (EPOC- HLPR)
which includes other members of La Princesa Institute
(IP). The role of this group in this project has focused on
the selection, characterization, monitoring and sampling of peripheral venous blood, induced sputum and
exhaled condensate of patients with COPD and SAHS.
Several active clinical trials will be developed during
next years on different respiratory diseases (COPD,
asthma, idiopathic pulmonary fibrosis, bronchiectasis
and cystic fibrosis).
Plan of actions for 2016-2020
• Further develop, maintain and strengthen the respiratory group on chronic respiratory conditions at the La
Princesa research Institute (IP). To help with this
objective we have recruited a new senior investigator
to our working group (J.B. Soriano) through the
Cátedra UAM- Linde Healthcare.
• Complete the European proposal of study MBREATH (COPD Monitoring and Biomarkers) submitted to the European Union Horizon 2020.
• Submitted Tack-SHS Horizon 2020 proposal.
Tackling secondhand tobacco smoke and e-cigarette emissions: exposure assessment, novel interventions, impact on lung diseases and economic
burden in diverse European populations. The
TackSHS Project. Research and Innovation actions.
Topic: Global Alliance for Chronic Diseases.
Prevention and treatment of lung diseases.
Reference: HCO-06-2015
• Submit to Horizon 2020 the IMPACTOR proposal.
Intelligent health platform for the self-Management
and Predictive-monitoring of Asthma, Chronic
obstrucTive pulmOnary disease (COPD) and Related
co-morbidities.
MAJOR GRANTS
• Girón Moreno, Rosa María. Epidemiologia y caracterización clínico-microbiológica de las exacerbaciones
– 63 –
Line 1.7
Inflammatory mechanisms
in pulmonary diseases
•
•
•
•
•
•
•
•
agudas de los pacientes con bronquiectasias no
debidas a fibrosis quística. SEPAR. 2014-2016.
Ancochea Bermúdez, Julio. Design and local implementation of clinical audits in different types of old
(DELICATO). PI13/01993. ISCIII. 2014-2016.
Ancochea Bermúdez, Julio. Síndrome combinado de
fibrosis pulmonar y enfisema (SCFPE): caracterización y despistaje de hipertensión pulmonar. Beca
de investigación futuro. SEPAR. 2014-2015.
Carolina Cisneros Serrano. Eficacia de una estrategia
simple para promover el cumplimiento terapéutico.
SEPAR. 2013-2015.
Ancochea Bermúdez, Julio. Inflamación e hipoxia:
mecanismos de desarrollo y progresión en EPOC y
SAHS. MINECO.S2010/BMD-2542. 2012-.
Girón Moreno, Rosa María. Estudio DAYCA. SEPAR.
2012-2014.
Ancochea Bermúdez, Julio. Programa de telemonitorización a domicilio de pacientes epoc avanzada.
APSU. 2011-2014.
Ancochea Bermúdez, Julio. Estudio fenotipo de riesgo
cardiovascular en la enfermedad pulmonar obstructiva
crónica (CHAIN). SEPAR y Astra Zeneca. 2011-2016.
Ancochea Bermúdez, Julio. Programa de I+D biomedicina. CONSEPOC-CM. Inflamación e hipoxia:
mecanismos de desarrollo y progresión en EPOC y
SAHS. CAM. 2011-2014.
PUBLICATIONS (17)
Garcia-Gutierrez S, Quintana JM, Bilbao A,
Unzurrunzaga A, Esteban C, Baré M, Girón Moreno
RM, Pulido E, Rivas P. Validity of criteria for hospital
admission in exacerbations of COPD. Int J Clin Pract.
68(7):820-9. 2014. PMID: 25077290. IF: 2,538
Segrelles Calvo G, Gómez-Suárez C, Soriano JB,
Zamora E, Gónzalez-Gamarra A, González-Béjar M,
Jordán A, Tadeo E, Sebastián A, Fernández G,
Ancochea J. A home telehealth program for patients
with severe COPD: the PROMETE study. Respir Med.
108(3):453-62. 2014. PMID: 24433744. IF: 2,917. DOI:
10.1016/j.rmed.2013.12.003.
http://dx.doi.org/10.1016/j.rmed.2013.12.003
– 64 –
Alba Guiu, Buenaventura Buendía, Laura Llorca, Rosa
María Gómez Punter, Rosa Girón. Chryseobacterium
spp., ¿nuevo patógeno oportunista asociado a fibrosis
quística?. Enferm Infecc Microbiol Clin. 32(8):497-501.
2014. PMID: 24656793. IF: 1,881. DOI: 10.1016/
j.eimc.2013.08.003.
Lerín M, Prados C, Martínez MT, Maíz L, Girón R, Solé
A, Cabanillas JJ, Alvarez-Sala R. Cystic fibrosis in adult
age. Rev Clin Esp. 214(6):289-295. 2014. PMID:
24948579. IF: 1,314. DOI: 10.1016/j.rce.2014.05.001.
http://dx.doi.org/10.1016/j.rce.2014.05.001
Martínez-Moragón E, Palop M, de Diego A, Serra J,
Pellicer C, Casán P, Caloto MT, Nocea G. ASMACOST
Study Group. Estudio corporativo. Factors affecting
quality of life of asthma patients in Spain: The importance of patient education. Allergol Immunophatol
(Madr). 42(5):476-84. 2014. PMID: 24094444. IF: 1,58.
DOI: 10.1016/j.aller.2013.06.006.
http://dx.doi.org/10.1016/j.aller.2013.06.006
García-Rio F, Soriano JB, Miravitlles M, Muñoz L,
Duran-Tauleria E, Sánchez G, Sobradillo V, Ancochea
J. Impact of obesity on the clinical profile of a population-based sample with chronic obstructive pulmonary
disease. PLos One. 9(8):e105220. 2014. PMID:
25153331.
IF:
3,534.
DOI:
10.1371/journal.pone.0105220.
http://dx.doi.org/10.1371/journal.pone.0105220
Tamara Alonso Pérez, Claudia Valenzuela, Rosa María
Girón Moreno, Julio Ancochea Bermúdez. Interstitial
lung diseases. Pneumoconiosis. Hypersensitivity pneumonitis. Medicine. 11(64):3789-98. 2014. IF: 4,867.
DOI: 10.1016/S0304-5412(14)70846-7.
http://dx.doi.org/10.1016/S0304-5412(14)70846-7
Olveira C, Olveira G, Espildora F, Girón RM, Vendrell M,
Dorado A, Martínez-García MA. Mediterranean diet is
associated on symptoms of depressionand anxiety in
patients with bronchiectasis. Gen Hosp Psychiatry.
36(3):277-83. 2014. PMID: 24602964. IF: 2,898. DOI:
10.1016/j.genhosppsych.2014.01.010.
http://dx.doi.org/10.1016/j.genhosppsych.2014.01.010
AREA 1
Girón-Moreno RM, Justicia JL, Yamamoto S,
Valenzuela C, Cisneros C, Gómez-Púnter RM,
Fernandes-Vasconcelos G, Ancochea J. Role of Creactive protein as a biomarker for prediction of the
severity of pulmonary exacerbations in patients with
cystic fibrosis. BMC Pulm Med. 14(1):150. 2014.
PMID: 25248567. IF: 2,489. DOI: 10.1186/14712466-14-150.
http://dx.doi.org/10.1186/1471-2466-14-150
Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J,
Almagro P, Quintano JA, Riesco JA, Trigueros JA,
Piñera P, Simón A, Rodríguez-Hermosa JL, Marco
E, López D, Coll R, Coll-Fernández R, Lobo MÁ,
Díez J, Soriano JB, Ancochea J. Spanish guideline
for COPD (GesEPOC). Update 2014. Arch
Bronconeumol. 50 Suppl 1:1-16. 2014. PMID:
24507959. IF: 1,816. DOI: 10.1016/S03002896(14)70070-5.
http://dx.doi.org/10.1016/S0300-2896(14)70070-5
Olveira C, Olveira G, Espildora F, Giron RM, Muñoz
G, Quittner AL, Martinez-Garcia MA. Validation of a
Quality of Life Questionnaire for Bronchiectasis: psychometric analyses of the Spanish QOL-B-V3.0. Qual
Life Res. 23(4):1279-92. 2014. PMID: 24142190. IF:
2,864. DOI: 10.1007/s11136-013-0560-0.
http://dx.doi.org/10.1007/s11136-013-0560-0
Somiedo Gutiérrez MD, Girón Moreno R, Moreno
Balsalobre R. Mucoepidermoid Carcinoma in a Bone
Marrow Transplant Patient. Arch Bronconeumol.
50(3):125. 2014. PMID: 24486048. IF: 1,816. DOI:
10.1016/j.arbres.2013.06.002.
http://dx.doi.org/10.1016/j.arbres.2013.06.002
14(1):197. 2014. PMID: 25495677. IF: 2,489. DOI:
10.1186/1471-2466-14-197.
http://dx.doi.org/10.1186/1471-2466-14-197
López-Campos JL, Hartl S, Pozo-Rodriguez F,
Roberts CM; European COPD Audit team (Ancochea
J). Variability of hospital resources for acute care of
COPD patients: the European COPD Audit. Eur
Respir J. 43(3):754-62. 2014. PMID: 23988775. IF:
7,125. DOI: 10.1183/09031936.00074413.
http://dx.doi.org/10.1183/09031936.00074413
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK,
Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y,
Kim DS, Kolb M, Nicholson AG, Noble PW, Selman M,
Taniguchi H, Brun M, Le Maulf F, Girard M, Stowasser
S, Schlenker-Herceg R, Disse B, Collard HR; INPULSIS
Trial Investigators (Ancochea J). Efficacy and safety of
nintedanib in idiopathic pulmonary fibrosis. N Engl J
Med. 370(22):2071-82. 2014. PMID: 24836310. IF:
54,42. DOI: 10.1056/NEJMoa1402584.
http://dx.doi.org/ 10.1056/NEJMoa1402584
Girón Moreno RM, Caballero P, Friera A. Multidetector
computed tomography angiography for pre-embolization assessment in cystic fibrosis patients with massive
haemoptysis. Respir Med. 108(5):816-7. 2014. PMID:
24613210. IF: 2,917. DOI: 10.1016/j.rmed.2013.12.010.
BOOKS
Girón RM. Comentarios bibliográficos. Biblioteca de las
bronquiectasias. Enfoque Editorial. ISBN: 978-8415905-13-4
Carolina Cisneros. La importancia de la medición de la
hiperrespuesta bronquial en asma. La neumología que
viene II. Marge Médica Books (ICG Marge, SL)
Barcelona. ISBN: 978-84-15340-99-7
– 65 –
Xaubet A, Serrano-Mollar A, Ancochea J. Pirfenidone
for the treatment of idiopathic pulmonary fibrosis.
Expert Opin Pharmacother. 15(2):275-81. 2014.
PMID: 24308635. IF: 3,085. DOI: 10.1517/
14656566.2014.867328.
http://dx.doi.org/10.1517/14656566.2014.867328
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ANCOCHEA BERMÚDEZ,
JULIO
Parámetros que hay que medir en el subestudio de
EPOC y Riesgo Cardiovascular (aditivos a los de la
cohorte CHAIN).
PRINCIPAL RESEARCHER: CISNEROS SERRANO,
CAROLINA
Características del asma grave mal controlada en la
Comunidad de Madrid (AsmaCoM); (Versión NEUMOMADRID). ASMACOM
– 66 –
PRINCIPAL RESEARCHER: GIRÓN MORENO, ROSA
MARÍA
Estudio HUTIQOL: Utilidades en salud y calidad de
vida, en pacientes españoles con fibrosis quÍstica;
(Versión 1: 05-06-14). DR. LUIS MAIZ CARRO (Sº
NEUMOLOGIA, H.RAMON-CAJAL) MAI-FQ-2014-01
(HUTIQOL)
PRINCIPAL RESEARCHER: GOMEZ PUNTER, ROSA
MARÍA
La atención médica de la EPOC en consultas de neumología; (Versión 1: marzo 2014). SOCIEDAD
ESPAÑOLA DE NEUMOLOGÍA Y CIRUGÍA TORÁCICA
ESTUDIO EPOCONSUL
AREA 1
Line 1.8
Inflammatory response
in hepatic diseases
es-related pathogenesis of progressive liver disease.
We believe that this ambitious project could identify
molecular targets involved in HCV infection and it could
improve the management of the chronic infected
patients.
GROUP 24
MAJOR GRANTS
GROUP MEMBERS
• Virgínia Manuela Gondar de Sousa e Silva
• Francisca Molina Jiménez
RESEARCH INTEREST
Hepatotropic viruses, including Hepatitis C virus (HCV),
chronically infect millions of people worldwide. Infection
can lead to fibrosis, cirrhosis and hepatocellular carcinoma, and is the major reason for liver transplantation.
Current standard-of-care therapy against chronic hepatitis C, pegylated IFN-α in combination with ribavirina
and HCV NS3/4A protease inhibitor, is frequently not
effective depending on viral and host factors.
In our group we are interested in understanding how
HCV interacts with target cells, with particular emphasis on the role of the cellular factors implicated in different steps of the viral life cycle including entry, assembly,
egress and spread. Our recently published studies
have determined that HCV egress is a clathrin-dependent process. We are studying 1) cellular factors implicated in HCV entry in highly polarized cultures; 2) the
role of apolipoproteins in HCV spread; 3) changes in
hepatocyte proteome after HCV infection. Finally, we
are also exploring whether dendrimer-based therapies
could be used to inhibit HCV infection.
In overall, these studies may provide new insights for
our understanding of virus-host interactions and the
molecular mechanisms underlying hepatotropic virus-
Majano Rodríguez, Pedro Lorenzo. Estudio de la interacción entre el virus de la hepatitis c y sus células
diana: papel del "microambiente hepático", la asociación con lipoproteínas y el modo de diseminación en
distintas fases del ciclo viral. ISCIII. PI13/00159. 20142016.
PUBLICATIONS (3)
Reglero-Real N, Alvarez-Varela A, Cernuda-Morollón E,
Feito J, Marcos-Ramiro B, Fernández-Martín L,
Gómez-Lechón MJ, Muntané J, Sandoval P, Majano
PL, Correas I, Alonso MA, Millán J. Apicobasal polarity
controls lymphocyte adhesion to hepatic epithelial
cells. Cell Reports. 8(6):1879-1893. 2014. PMID:
25242329.
IF:
7,027.
DOI:
10.1016/j.celrep.2014.08.007.
http://dx.doi.org/10.1016/j.celrep.2014.08.007
Pisonero-Vaquero S, García-Mediavilla MV, Jorquera F,
Majano PL, Benet M5, Jover R, González-Gallego J,
Sánchez-Campos S. Modulation of PI3K-LXRα-dependent lipogenesis mediated by oxidative/nitrosative stress
contributes to inhibition of HCV replication by quercetin.
Lab Invest. 94(3):262-74. 2014. PMID: 24492281. IF:
3,828. DOI: 10.1038/labinvest.2013.156.
http://dx.doi.org/10.1038/labinvest.2013.156
Martín-Vílchez S, Rodríguez-Muñoz Y, LópezRodríguez R, Hernández-Bartolomé A, Borque-Iñurrita
MJ, Molina-Jiménez F, García-Buey L, Moreno-Otero
R, Sanz-Cameno P. Inhibition of Tyrosine Kinase
Receptor Tie2 Reverts HCV-Induced Hepatic Stellate
Cell Activation. PLoS One. 9(10):e106958. 2014.
– 67 –
HEAD OF LABORATORY
Pedro Lorenzo Majano Rodríguez
PMID: 25302785. IF: 3,534. DOI: 10.1371/journal.
pone.0106958.
GROUP 23
HEAD OF LABORATORY
Ricardo Moreno Otero
GROUP MEMBERS
• María Jesús Alonso Martín
• María Jesús Borque Iñurrita
• Luisa Consuelo García Buey
• Asunción García Sánchez
• Leticia González Moreno
• Ángel Hernández Bartolomé
• Rosario López Rodríguez
• Jorge Mendoza Jiménez-Ridruejo
• Yolanda Real Martínez
• María Paloma Sanz Cameno
RESEARCH INTEREST
During recent years our research group has been particularly focused on identifying non-invasive prognostic
biomarkers of chronic liver diseases (CLD) progression
to cirrhosis and hepatocellular carcinoma (HCC).
HCC is the second leading cause of cancer death
worldwide and has a high mortality rate because it is
only diagnosed in advanced stages, at which available
treatments are no longer effective. Therefore, new tools
that improve the diagnosis and treatment of HCC
patients are needed.
The altered expression of angiogenic and fibrogenicrelated factors during the course of CLD to HCC may
provide a valuable tool for the non-invasive assessment
of liver fibrosis, key for clinical decision-making. Among
– 68 –
other clinical and demographic variables, we found that
peripheral levels of angiopoietins significantly correlated
with hepatic fibrosis in patients with chronic hepatitis C
(CHC). Such finding allowed us to develop a novel
index for non-invasive evaluation of liver fibrosis,
AngioScore, which was further validated in an independent series of patients.
In addition, our group reported a significant increment
of TIE2-expressing monocytes (TEMs) in the peripheral
blood of patients with CHC. Monocytes, essential precursors of antigen-presenting cells, notably contribute
to the pathogenesis of chronic inflammatory diseases
and cancer. We proposed that chronic expansion of
TEMs, which are characterized by their marked proangiogenic properties and notable immunosuppressive
nature, might prevent proper immune response and
promote mechanisms that cause liver damage. The
expression of the angiopoietin’s receptor, Tie2, in the
surface of this subtype of monocytes might serve as
useful "tag" for the non-invasive monitoring of CLD progression in a simple blood test. Moreover, we believe
that a more in depth understanding of TEMs regulation
can lead to important therapeutic advances.
Interestingly, in the meantime, other authors described
that TEMs might work as useful cellular diagnostic and
prognostic biomarker for HCC.
Furthermore, we have also characterized the significance of certain genetic variants of HDACs and of
other angiogenic factors, receptors and mediators, in
relation to fibrosis progression.
Based on such evidences, our research group is currently focused on addressing the role of all the above
mentioned humoral, cellular and genetic factors
together as liquid biopsy for diagnosis, prognosis and
monitoring of CLD progression to HCC.
MAJOR GRANTS
• Sanz Cameno, María Paloma. Modulación epigenética de la progresión de la hepatitis crónica c a carcinoma hepatocelular: papel de las variantes genéticas
AREA 1
PUBLICATIONS (4)
Rodríguez-Grau MC, Jusué V, Fiera A, Castaño C,
García-Buey LC. Acute pancreatitis as fatal complication after chemoembolization of hepatocellular carcinoma. Rev Esp Enferm Dig. 106(2):146-7. 2014. PMID:
24852743. IF: 1,317
Vidal-Castiñeira JR, López-Vázquez A, Martínez-Borra
J, Martínez-Camblor P, Prieto J, López-Rodríguez R,
Sanz-Cameno P, de la Vega J, Rodrigo L, Pérez-López
R, Pérez-Álvarez R, López-Larrea C. Diversity of killer
cell immunoglobulin-like receptor (KIR) genotypes and
KIR2DL2/3 variants in HCV treatment outcome. PLoS
One. 9(6):e99426. 2014. PMID: 24927414. IF: 3,534.
DOI: 10.1371/journal.pone.0099426.
http://dx.doi.org/ 10.1371/journal.pone.0099426
Martín-Vílchez S, Rodríguez-Muñoz Y, LópezRodríguez R, Hernández-Bartolomé A, Borque-Iñurrita
MJ, Molina-Jiménez F, García-Buey L, Moreno-Otero
R, Sanz-Cameno P. Inhibition of Tyrosine Kinase
Receptor Tie2 Reverts HCV-Induced Hepatic Stellate
Cell Activation. PLoS One. 9(10):e106958. 2014.
PMID:
25302785.
IF:
3,534.
DOI:
10.1371/journal.pone.0106958.
Cabaleiro T, Ochoa D, López-Rodríguez R, Román
M, Novalbos J, Ayuso C, Abad-Santos F. Effect of
polymorphisms on the pharmacokinetics, pharmacodynamics, and safety of risperidone in healthy volunteers. Hum Psychopharmacol. 29(5):459-69.
2014. PMID: 25042870. IF: 1,854. DOI:
10.1002/hup.2420.
http://dx.doi.org/10.1002/hup.2420
CLINICAL TRIALS
PRINCIPAL RESEARCHER: GARCÍA BUEY, LUISA
CONSUELO
Estudio de fase III, aleatorizado, doble ciego, controlado con simulación de ThermoDox® (doxorubicina liposomal liso-termosensible-LTLD) en carcinoma hepatocelular (HCC) utilizando un tiempo de tratamiento de
ablación con radiofrecuencia estandarizado (RFA) 45
minutos para lesiones solitarias de 3 cm a 7 cm;
(Versión 2.1E: 04-08-14). CELSION CORPORATION
104-13-302
EudraCT: 2014-000934-53
PRINCIPAL RESEARCHER: GONZÁLEZ MORENO,
LETICIA
Estudio aleatorizado, internacional, doble ciego, controlado con placebo de grupos paralelos para evaluar
la eficacia y seguridad de avatrombopag por vÍa oral
una vez al día para el tratamiento de adultos con trombocitopenia asociada a enfermedad hepática antes de
un procedimiento programado; (Versión 4.0:12-11-13).
EISAI LIMITED E5501-G000-311
EudraCT: 2013-000934-36
PRINCIPAL RESEARCHER: REAL MARTINEZ,
YOLANDA
Adherencia en triple terapia para la Hepatitis C (Estudio
AdHoC); (Versión2.0:5-11-13). FUNDACIÓ IMIM IMITRI-2013-01
– 69 –
de las histonaa deacetilasas. Fundación Mutua
Madrileña. 2012-2015.
• Sanz Cameno, María Paloma. Influencia de las histonas desacetilasas en la progresión de la hepatitis
crónica c a carcinoma hepatocelular: polimorfimos
genéticos, niveles de expresión y funcionalidad.
Fundación Mutua Madrileña. 2011-2014.
• Sanz Cameno, María Paloma. Implicación de polimorfismos genéticos de factores angiogénicos en la
etiopatogenia de la hepatitis crónica c y su evolución a
carcinoma hepatocelular. AECC. 2010-2015.
Line 1.9
Mechanisms and
mediators of endocrine
diseases
GROUP 25
HEAD OF LABORATORY
Mónica Marazuela Azpíroz
GROUP MEMBERS
• Susanna Leskelä
• Rebeca Martínez Hernández
• Andrés Pérez Casas
• Ana María Ramos Leví
• Ana Rodríguez Muñoz
• Miguel Antonio Sampedro Núñez
• Ana Serrano Somavilla
RESEARCH INTEREST
Our current and future work involves different research
fields in endocrine diseases. First, we are studying the
role of galectins and other immunoregulatory molecules
in patients with autoimmune thyroid diseases (AITD)
including Hashimoto’s thyroiditis (HT), Graves’ disease
(GD) and Graves’ ophtalmopathy (GO). During the last
years, we have discovered that patients with AITD have
altered populations of regulatory T cells, augmented
Th17 cells, diminished levels of plasmacytoid dendritic
cells, and a defective expression of the immune regulatory molecule galectin-9 in antigen-presenting dendritic cells. We are planning to study additional regulatory
molecules such as VIP in these patients. These abnormalities in immunoregulatory molecules may contribute
to the pathogenesis and/or auto perpetuation of AITD.
In the course of 2013, we have initiated new projects in
this field. One project aims to characterize the expression of miRNAs (miRNAome) in samples of thyroid in
– 70 –
patients with AITD and healthy controls and to study
the potential use of the selected miRNAs as biomarkers in serum samples of AITD patients. We also participate in a collaborative project in the study of
immunoregulatory molecules and miRNAs in different
immune-mediated inflammatory diseases (IMID) including rheumatoid arthritis, psoriasis, inflammatory bowel
disease and AITD to try to find new predictive biomarkers (immuno-regulatory molecules) of IMID severity and
responsiveness to biological therapies. We are developing novel approaches of analysis using exosomes as
target containers of these relevant biomarkers. The aim
of this study is to improve the selectivity and efficacy in
the use of biological therapies in IMID.
Another area of investigation of the group is the
process of angiogenesis in neuroendocrine gastroentero-pancreatic tumors and its relation to the somatostatin receptors. We are studying the role of angiopoietins-1 and -2 and their receptor Tie-2 in the tumor
cells, as well as their association with somatostatin
receptors and also clinical and pathological factors.
Furthermore, we are studying the role of key molecules
in GH secreting tumours, especially those related to
treatment response with the GH antagonist pegvisomant. These studies will include techniques of molecular biology, including their characterization through qRTPCR, genotyping and sequencing with association
studies with the clinical data available.
MAJOR GRANTS
• Marazuela Azpiroz, Mónica. Identificación y caracterización de microrRNAs implicados en la etiopatogenia de las enfermedades tiroideas autoinmunes.
ISCIII. PI13/01414. 2014-2016.
• Marazuela Azpíroz, Mónica. Study of “escape” to
pegvisomant (peg) therapy in acromegalic patients:
its definition, prevalence and determinants. Pfizer.
2013-2014.
• Marazuela Azpiroz, Monica. Immunoregulatory molecules and biomarkers predicting response to biological therapies and disease severity in immune-medi-
AREA 1
ated inflamatory disorders. BIOIMID PROJECT. ISCIII. PIE13/00041.Coordinador. 2014-2016.
10.1111/1753-0407.12127.
http://dx.doi.org/10.1111/1753-0407.12127
.
PUBLICATIONS (3)
CLINICAL TRIALS
Marazuela M, Ramos-Leví A, Sampedro-Núñez M,
Bernabeu I. Cabergoline treatment in acromegaly:
pros. Endocrine. 46(2):215-2014. PMID: 24532103. IF:
3,527. DOI: 10.1007/s12020-014-0206-1.
http://dx.doi.org/10.1007/s12020-014-0206-1
PRINCIPAL RESEARCHER: MARAZUELA AZPIROZ,
MÓNICA
Estudio 110933: Albiglutida frente a placebo en sujetos
con diabetes mellitus tipo 1 de nueva aparición tratados con insulina; (Versión 0.0: 29-05-14). GLAXOSMITHKLINE ESPAÑA, S.A. GLP110933
EudraCT: 2014-001825-33
Ramos-Levi AM, Matia P, Cabrerizo L, Barabash A,
Sanchez-Pernaute A, Calle-Pascual AL, Torres AJ,
Rubio MA. Statistical models to predict type 2 diabetes
remission after bariatric surgery. J Diabetes. 6(5):4727. 2014. PMID: 24433454. IF: 2,349. DOI:
PRINCIPAL RESEARCHER: RAMOS LEVÍ, ANA
MARÍA
Estudio PEGASO: Estudio observacional, transversal y
multicéntrico para valorar el cumplimiento terapéutico
con Somavert® en pacientes con acromegalia en
condiciones de práctica clínica habitual; (Versión 1.1,
31- -10-14). LABORATORIOS PFIZER S.L.U. PFI-PEG2014-01 (A6291043)
Ramos-Levi AM, Duran Rodriguez-Hervada A,
Mendez-Bailon M, Marco-Martinez J. Drug-induced
hyponatremia: an updated review. Minerva Endocrinol.
39(1):1-12. 2014. PMID: 24513599. IF: 1,323
– 71 –
Line 1.10
Children´s development
(obesity and growth)
GROUP 26
HEAD OF LABORATORY
Jesús Argente Oliver
GROUP MEMBERS
• Pilar Argente Arizón
• Eva Baquedano Caballero
• Vicente Barrios Sabador
• Emma Burgos Ramos
• Sandra Canelles Ortiz
• David Castro González
• Julie Ann Chowen King
• Esther de la Fuente Martín
• Francisca Díaz González
• Laura María Frago Fernández
• Cristina García Cáceres
• Gabriel Ángel Martos Moreno
• María Teresa Muñoz Calvo
• Jesús Pozo Román
• Oscar Rubio Cabezas
• Silvia Tapia González
RESEARCH INTEREST
How the genetic make-up of an individual interacts with
the early maternal/neonatal and postnatal environments to culminate in obesity and its secondary complications, is being studied with both clinical and basic
approaches. Genetic studies are performed to identify
mutations in genes involved in monogenic obesity, to
identify new candidate genes and to analyze polygenic
and epigenetic causes of obesity. Diverse new candidate genes have been identified and are being further
investigated, as well as the interaction genotype/phe-
– 72 –
notype and ethnic influences. Metabolomic studies are
underway to better understand the processes involved
in the development of insulin resistance and type-2 diabetes in obese children. Metabolites that may be
involved in this process have been identified and will be
further studied. In addition, it appears that this process
may differ between males and females even prepubertally and this will be further explored. We have recently
identified a new monogenic cause of pathological
human growth that courses with skeletal abnormalities.
The underlying cause is the affectation of the insulin-like
growth factor (IGF) system and this new syndrome will
be thoroughly analyzed and new concepts of the physiological functioning of the IGF system pursued.
Animal models are employed to analyze how poor
maternal and/or neonatal nutrition, stress or changes
in specific hormones during neonatal life affect adult
metabolism, with special attention focused on the differential responses of males and females. Studies analyzing the effect of increased central leptin levels on
insulin signaling in the CNS and adipose tissue
demonstrate a relationship between insulin resistance,
hypothalamic inflammation and energy homeostasis.
Hypothalamic glial cells are a main focus of investigation for their newly recognized role in metabolic control. We have shown them to respond to weight gain
and metabolic hormones such as leptin. Current interest includes analysis of glial responses to specific
nutrients and how this could influence the metabolic
outcome to weight gain. The implications of weight
gain and abnormal circulating levels of leptin and
insulin have also been implicated in increased susceptibility to neurodegenerative diseases, with this susceptibility being different between males and females.
Future studies are planned to determine the role of
astrocytes in mediating the protective and/or detrimental responses to high fat diet intake on neurodegeneration.
MAJOR GRANTS
• Argente Oliver, Jesús. Obesidad infantil grave de
comienzo precoz: fundamentos metabólicos, hor-
AREA 1
PUBLICATIONS (13)
Flanagan SE, De Franco E, Lango Allen H, Zerah M,
Abdul-Rasoul MM, Edge JA, Stewart H, Alamiri E,
Hussain K, Wallis S, de Vries L, Rubio-Cabezas O,
Houghton JA, Edghill EL, Patch AM, Ellard S,
Hattersley AT. Analysis of transcription factors key for
mouse pancreatic development establishes NKX2-2
and MNX1 mutations as causes of neonatal diabetes in
man. Cell Metab. 19(1):146-154. 2014. PMID:
24411943.
IF:
16,747.
DOI:
10.1016/j.cmet.2013.11.021.
http://dx.doi.org/10.1016/j.cmet.2013.11.021
Argente J, Flores R, Gutiérrez-Arumí A, Verma B,
Martos-Moreno GÁ, Cuscó I, Oghabian A, Chowen JA,
Frilander MJ, Pérez-Jurado LA. Defective minor
spliceosome mRNA processing results in isolated
familial growth hormone deficiency. EMBO Mol Med.
6(3):299-306. 2014. PMID: 24480542. IF: 8,245. DOI:
10.1002/emmm.201303573.
http://dx.doi.org/10.1002/emmm.201303573
Sáenz de Pipaón M, Martínez-Biarge M, Dorronsoro I,
Salas S, Madero R, Martos GÁ, Argente J, Quero J.
Growth in preterm infants until 36 weeks' postmenstrual age is close to target recommendations.
Neonatology. 106(1):30-36. 2014. PMID: 24776717.
IF: 2,369. DOI: 10.1159/000358479.
http://dx.doi.org/10.1159/000358479
Kim JG, Suyama S, Koch M, Jin S, Argente-Arizon P,
Argente J, Liu ZW, Zimmer MR, Jeong JK, SzigetiBuck K, Gao Y, Garcia-Caceres C, Yi CX, Salmaso N,
Vaccarino FM, Chowen J, Diano S, Dietrich MO,
Tschöp MH, Horvath TL. Leptin signaling in astrocytes
regulates hypothalamic neuronal circuits and feeding.
Nat Neurosci. 17(7):908-10. 2014. PMID: 24880214.
IF: 14,976. DOI: 10.1038/nn.3725.
http://dx.doi.org/10.1038/nn.3725
Rubio-Cabezas O, Codner E, Flanagan SE, Gómez JL,
Ellard S, Hattersley AT. Neurogenin 3 is important but
not essential for pancreatic islet development in
humans. Diabetologia. 57(11):2421-2424. 2014. PMID:
25120094. IF: 6,88. DOI: 10.1007/s00125-014-3349y.
http://dx.doi.org/10.1007/s00125-014-3349-y
Villanueva C, Argente J. Pathology or normal variant:
what constitutes a delay in puberty?. Horm Res
Paediatr. 82(4):213-221. 2014. PMID: 25011467. IF:
1,713. DOI: 10.1159/000362600.
http://dx.doi.org/10.1159/000362600
Martos-Moreno GÁ, Barrios V, Muñoz-Calvo MT, Pozo
J, Chowen JA, Argente J. Principles and pitfalls in the
differential diagnosisand management of childhood
obesities. Adv Nutr. 14(5):299-305. 2014. PMID:
24829481. IF: 4,891. DOI:
http://dx.doi.org/ 10.3945/an.113.004853
Martos-Moreno GÁ, Argente J. The "glacier crevice"
sign, from image to diagnosis. J Pediatr. 164(5):12371237. 2014. PMID: 24565426. IF: 3,736. DOI:
10.1016/j.jpeds.2014.01.026.
http://dx.doi.org/10.1016/j.jpeds.2014.01.026
Baquedano E, Ruiz-Lopez A, Sustarsic E, Herpy J, List
E, Chowen J, Frago L, Kopchick J, Argente J. The
absence of GH signaling affects the susceptibility to
high fat diet induced hypothalamic inflammation in male
mice. Endocrinology. 155(12):4856-67. 2014. PMID:
25237935. IF: 4,664. DOI: 10.1210/en.2014-1367.
http://dx.doi.org/10.1210/en.2014-1367
Rubio-Cabezas O, Hattersley AT, Njølstad PR,
Mlynarski W, Ellard S, White N, Chi DV, Craig ME. The
diagnosis and management of monogenic diabetes in
children and adolescents. Pediatr Diabetes. 15 Suppl
20:47-64. 2014. PMID: 25182307. IF: 2,129. DOI:
10.1111/pedi.12192.
http://dx.doi.org/10.1111/pedi.12192
– 73 –
monales, genéticos, genómicos y metabolómicos.
PI13/02195. ISCIII. 2014-2016.
• Chowen King, Julie Ann. Regulación de los astrocitos
hipotalámicos por la leptina: implicaciones en el control metabólico sistémico. BFU2011-27492. MICINN.
2012-2014.
Granado M, Diaz F, Fuente-Martín E, García-Cáceres C,
Argente J, Chowen JA. The metabolic response to postnatal leptin in rats varies with age and may be litter dependent.
Horm Metab Res. 46(7):462-470. 2014. PMID: 24446159.
IF: 2,038. DOI: 10.1055/s-0033-1363226.
http://dx.doi.org/10.1055/s-0033-1363226
García-Cáceres C, Fuente-Martín E, Díaz F, Granado
M, Argente-Arizón P, Frago LM, Freire-Regatillo A,
Barrios V, Argente J, Chowen JA. The opposing effects
of ghrelin on hypothalamic and systemic inflammatory
processes are modulated by its acylation status and
food intake in male rats. Endocrinology. 155(8):28682880. 2014. PMID: 24848869. IF: 4,664. DOI:
10.1210/en.2014-1074.
http://dx.doi.org/ 10.1210/en.2014-1074
Martos-Moreno GÁ, Serra-Juhé C, Pérez-Jurado
LA, Argente J. Underdiagnosed BeckwithWiedemann syndrome among early onset obese
children. Arch Dis Child. 99(10):965-967. 2014.
PMID: 25085994. IF: 2,905. DOI: 10.1136/archdischild-2014-307097.
http://dx.doi.org/10.1136/archdischild-2014-307097
BOOKS
Martos-Moreno GÁ. Obesidad y Síndrome Metabólico.
Tratado de Pediatría (11ªEd.). Editorial Panamericana.
ISBN: 978-84-9835-723-3
J. Argente Oliver, L. Soriano Guillén. Manual de
Endocrinología Pediátrica. Manual de Endocrinología
Pediátrica (2ª ed.). Ergon. ISBN: 978-84-15950-73-8
Martos-Moreno GA, Pozo J, Argente J. Obesidad en el
niño y adolescente: Etiopatogenia. Trastornos de la
Conducta Alimentaria y Obesidad. Un enfoque integral.
Editorial Panamericana. ISBN: 978-84-98357-41-7
Martos-Moreno GÁ, Muñoz MT, Argente J. Obesidad
en el niño y adolescente: Clínica y evaluación.
– 74 –
Trastornos de la conducta alimentaria y obesidad un
enfoque integral. Editorial Panamericana. ISBN: 97884-98357-41-7
Martos-Moreno GÁ, Muñoz MT, Argente J. Obesidad
en el niño y adolescente: Complicaciones médicas.
Trastornos de la Conducta Alimentaria y Obesidad. Un
Martos-Moreno GÁ, Madruga M, Argente J. Obesidad
en el niño y adolescente: Tratamiento dietético.
Trastornos de la Conducta Alimentaria y Obesidad. Un
Argente J, Martos-Moreno GÁ, Soriano L, Ros P,
Lapunzina P. Investigación clínica, radiológica y molecular de las displasias óseas más relevantes y síndromes específicos en el niño con talla baja. IV
Symposium Nacional de Endocrinología Pediátrica.
Momento Médico.
Argente J, Martos-Moreno GÁ. Fundamentos
endocrinológicos y bases moleculares de las obesidades. Tratado de Pediatría (11ªEd.). Editorial
Panamericana. ISBN: 978-84-9835-723-3
Martos-Moreno GÁ. Desarrollo y exploración del
tiroides. Tratado de Pediatría (11ªEd.). Editorial
Panamericana. ISBN: 978-84-9835-723-3
Martos-Moreno GÁ, Pozo J. Hipocrecimiento. Tratado
de Pediatría (11ªEd.). Editorial Panamericana. ISBN:
978-84-9835-723-3
Martos-Moreno GÁ. Diabetes insípida y SIADH.
Tratado de Pediatría (11ªEd.). Panamericana. ISBN:
978-84-9835-723-3
Martos-Moreno GÁ. Diabetes insípida. Tratado de
Pediatría (11ªEd.). Editorial Panamericana. ISBN: 97884-9835-723-3
AREA 1
GROUP 27
HEAD OF LABORATORY
Raffaele Carraro Casieri
GROUP MEMBERS
• Andrea Azcárate Villalón
• Elena Cercas Alonso
• Lourdes Martínez-Piñeiro Muñoz
• Erika Palacios Rosas
• María Concepción Peiró Vallejo
• Tania del Mar Romacho Romero
• Carlos Félix Sánchez Ferrer
• Isabelle Sharmiashvili
• Iñigo Tejado Elviro
• Marta Vázquez Bella
• Laura Alicia Villalobos Rodríguez
RESEARCH INTEREST
1) Obesity, insulin resistance, adipokines, and vascular dysfunction
Obesity, insulin resistance and type 2 diabetes mellitus are considered a major threat to worldwide
public health. Their pathogenic implication in cardiovascular disease has been largely acknowledged. The adipose tissue has been recognized as
an endocrine organ that actively secretes a number
of molecules potentially implicated in vascular
pathophysiology for their proinflammatory or
vasoactive properties. That is the case of IL1 beta,
IL6, TNF alpha, Ang (1-7), leptin, adiponectin or
visfatin. Our working hypothesis has been that in a
state such as obesity and/or diabetes, there is a
dysbalance in adipokines production that can
directly produce vascular inflammation and damage. Adipokines may act as the link between metabolic diseases and cardiovascular complications.
2) Mechanisms of human vascular ageing
We have confirmed the age-related endothelial dysfunction in humans, proposing the involvement of
several mechanisms: (1) NO-related endotheliumdependent relaxations are well preserved even in
very old subjects, including the expression and
activity of endothelial nitric oxide synthase (eNOS).
There is, however, a higher destruction of NO with
age, likely due to the enhancement of reactive oxygen species and peroxynitrite. (2) Vascular ageing
is associated to a loss of vasodilator prostanoids,
as well as to the presence of vasoconstrictor
prostanoids. Nevertheless, cyclooxigenase expression (both COX-1 and COX-2) was not affected by
age. (3) Although eNOS expression is well preserved, a marked increase in the expression of the
inducible isoform of the NO synthase (iNOS), associated to inflammatory processes, and able to synthesize greater amounts of NO and, therefore, producing peroxynitrite,may also contribute to
endothelial dysfunction. (4) The sources of superoxide radicals required for peroxynitrite formation
are the NOS uncoupling as well as the enhanced
expression of the enzyme NADPH oxidase. (5) We
have demonstrated the in situ activation of NF-kB
in the vascular wall of older subjects lacking clinical
cardiovascular diseases, and associated to
endothelial dysfunction. Therefore, we propose that
age-dependent endothelial dysfunction can be the
consequence of the inflammatory processes developed into the vascular wall.
3) Future directions: Adipokines and vascular ageing: mechanistic insights and pharmacological
modulation
Our working hypothesis is that the over-production
of adipokines such as visfatin/Nampt, soluble
dipeptidyl peptidase-4 (sDPP-4), or interleukin (IL)1β, can be mediators of the accelerated vascular
ageing. We aim to analyze the mechanistic insight
by these adipokines that may lead to age-related
vascular alterations, with focus on endothelial dys-
– 75 –
Line 1.11
Metabolic syndrome
and vascular risk
function, oxidative stress and inflammation, cell
senescence, extracellular matrix turnover and calcification. For this purpose, this translational study
will include experimental approaches using human
cell cultures of both vascular endothelial and
smooth muscle cells, experimental animal models
for different pathophysiological conditions, as well
as selected groups of patients for in vivo or in vitro
determinations. The validity of the adipokines as
biomarkers of vascular ageing will be determined.
Moreover, as pharmacologists, we aim to characterize targets that could be relevant to prevent or
delay vascular ageing, particularly through the
pharmacological blockade of the pro-ageing action
of adipokines. This could be achieved by specific
adipokine blockers or broader regulators of vascular function.
GROUP 5
HEAD OF LABORATORY
Carmelo García Monzón
GROUP MEMBERS
• Enrique Chávez Jiménez
• Elvira Del Pozo Maroto
• Faustino Manuel La Banda Brusi
• María Eugenia Miquilena Colina
• Javier Rodríguez de Cía
• Alicia Sáez Sáez
• Rodolfo Javier Vargas Castrillón
RESEARCH INTEREST
PUBLICATIONS
(1)
Lean ME, Carraro R, Finer N, Hartvig H, Lindegaard
ML, Rössner S, Van Gaal L, Astrup A. Tolerability of
nausea and vomiting and associations with weight
loss in a randomized trial of liraglutide in obese,
non-diabetic adults. Int J Obes (Lond). 38(5):68997. 2014. PMID: 23942319. IF: 5,386. DOI:
10.1038/ijo.2013.149.
http://dx.doi.org/10.1038/ijo.2013.149
CLINICAL TRIALS
PRINCIPAL RESEARCHER: CARRARO, RAFFAELLE
Ensayo de fase II, aleatorizado, doble ciego, de
grupos paralelos, multicéntricos e internacional, de
12 semanas de duración para evaluar el efecto
sobre el control glucémico de cinco dosis de
HM11260C comparado con placebo o liraglutida
en abierto, en pacientes con diabetes de tipo 2;
(Versión 1.1: 25-09-13). HANMI PHARMACEUTICAL CO., LTD HM-EXC-203
EudraCT: 2013-003625-29
– 76 –
Nonalcoholic fatty liver disease (NAFLD) is an increasingly
common chronic liver disease around the world with a
diverse histopathological spectrum ranging from simple
steatosis without significant inflammation to steatohepatitis (NASH) with varying stages of fibrosis and, ultimately,
cirrhosis and hepatocellular carcinoma. It is well known
that NAFLD occurs more frequently in obese and diabetics, being currently considered as the hepatic manifestation of the metabolic syndrome. Although the molecular
mechanisms involved in the pathogenesis of NAFLD and
progression to NASH remain incompletely defined, most
investigations indicate that insulin resistance plays a pivotal role in NAFLD setup. Since NASH is becoming one of
the most frequent causes of cirrhosis and liver transplantation in the developed countries, it is crucial to identify
populations at risk for NASH in order to prioritize the diagnostic and therapeutic interventions on those patients with
an increased risk for liver disease progression.
Our group seeks three main research lines for the next
five years. 1) To unravel the molecular mechanisms
involved in the pathogenesis of NASH searching for
potential therapeutic targets. We are exploring the role of
autophagy in the development of NASH. We recently
reported that autophagic flux is impaired in hepatocytes
from NASH patients and murine models of NASH and
AREA 1
other chronic liver diseases as well as for the noninvasive
diagnosis of NASH.
MAJOR GRANTS
García Monzón, Carmelo. Papel de la hipoxia intermitente del síndrome de apnea-hipopnea obstructiva del
sueño en la patogenia del hígado graso no alcohólico.
ISCIII. PI13/01299. 2014-2016.
PUBLICATIONS (3)
Sheedfar F, Sung MM, Aparicio-Vergara M, Kloosterhuis
NJ, Miquilena-Colina ME, Vargas-Castrillón J, Febbraio
M, Jacobs RL, de Bruin A, Vinciguerra M, GarcíaMonzón C, Hofker MH, Dyck JR, Koonen DP. CD36
expression with age is associated with enhanced susceptibility to nonalcoholic fatty liver disease. Aging
(Albany NY). 6(4):281-95. 2014. PMID: 24751397. IF:
4,886
González-Rodríguez A, Mayoral R, Agra N, Valdecantos
MP, Pardo V, Miquilena-Colina ME, Vargas-Castrillón J,
Lo Iacono O, Corazzari M, Fimia GM, Piacentini M,
Muntané J, Boscá L, García-Monzón C, Martín-Sanz P,
Valverde ÁM. Impaired autophagic flux is associated with
increased endoplasmic reticulum stress during the
development of NAFLD. Cell Death Dis. 17;5:e1179.
2014.
PMID:
24743734.
IF:
5,177.
DOI:
10.1038/cddis.2014.162.
http://dx.doi.org/10.1038/cddis.2014.162
García-Monzón C, Lo Iacono O, Crespo J, RomeroGómez M, García-Samaniego J, Fernández-Bermejo M,
Domínguez-Díez A, Rodríguez de Cía J, Sáez A, Porrero
JL, Vargas-Castrillón J, Chávez-Jiménez E, SotoFernández S, Díaz A, Gallego-Durán R, Madejón A,
Miquilena-Colina ME. Increased soluble CD36 is linked
to advanced steatosis in non-alcoholic fatty liver disease.
Eur J Clin Invest. 44(1):65-73. 2014. PMID: 24134687.
IF: 2,834. DOI: 10.1111/eci.12192.
http://dx.doi.org/10.1111/eci.12192
– 77 –
we are, therefore, proposing to investigate in the next
future whether therapies aimed to restore the autophagic flux might prevent or attenuate the progression of
NAFLD. We are also addressing the role of intermittent
hypoxia in the pathogenesis of NAFLD by analyzing the
expression levels of hypoxia-inducible factors 1 and 2 in
liver biopsies and serum of NASH patients and murine
models of NASH as well as the impact of hypoxia on the
mitochondrial function in human hepatocytes under
experimental conditions of lipid overload. 2) Identification
of biomarkers able to be used for noninvasive diagnosis
of NASH. We have shown that genetic variants of
SLC2A1 are associated with NAFLD and that circulating
levels of soluble CD36 is an independent factor associated with advanced steatosis in NAFLD but not in
patients with chronic hepatitis C virus (HCV) infection.
More recently, we have reported that the combination of
ultrasound and HOMA score is useful for noninvasive
diagnosis of patients with NASH. We are now pursuing
diagnostic tools based on ELISA multiplex using proteins
of pathogenic relevance in chronic liver diseases. 3)
Impact of the new direct-acting antivirals on carbohydrate and lipid metabolism in patients with chronic hepatitis C treated with these highly effective antiviral drugs:
Implications for the cardiovascular morbidity and mortality. It is well known that chronic HCV infection is associated with insulin resistance and type 2 diabetes mellitus
together with alterations in hepatic lipid metabolism. The
discovery of new direct-acting antiviral agents has
become a huge advance in the treatment of HCV infection. Among them, sofosbuvir and other new antivirals in
combination with ribavirin have improved considerably
the sustained virological response of HCV infection.
However, little is known about their effects on carbohydrate and lipid metabolic profiles in patients treated with
these new direct-acting agents and their potential mechanistic actions. On that basis, we propose to determine
the effects of sofosbuvir and other direct-acting antivirals
on HCV-induced metabolic complications such as
insulin resistance, hyperglycemia and dyslipidemia.
Moreover, the impact of therapy with sofosbuvir and
other related agents on metabolic disturbances induced
by the impairment of autophagic flux in HCV infection will
be analyzed. In summary, we believe that our lines of
investigation could shed light, in the next future, on key
aspects for the pathogenesis and therapy of NAFLD and
AREA 2
NEUROTRANSMISSION, PHARMACOLOGICAL
NEUROPROTECTION AND NEURODEGENERATIVE
AND NEUROPSYCHIATRIC DISEASES
Line 2.1
Neuropharmacology and neuroprotection.
Line 2.2
Neurotransmission in the hippocampus.
Line 2.3
Clinical pharmacology and pharmacogenetics.
Line 2.4
Diagnostic and therapeutic advances in affective disorders.
Line 2.5
Neurosurgery of epilepsy.
Line 2.6
Cerebrovascular diseases.
– 79 –
AREA 2
NEUROTRANSMISSION,
PHARMACOLOGICAL NEUROPROTECTION
AND NEURODEGENERATIVE AND
NEUROPSYCHIATRIC DISEASES
– 80 –
AREA 2
NEUROTRANSMISSION, PHARMACOLOGICAL
NEUROPROTECTION AND NEURODEGENERATIVE
AND NEUROPSYCHIATRIC DISEASES
GROUP 28
HEAD OF LABORATORY
GROUP MEMBERS
• Juan Alberto Arranz Tagarro
• Enrique Calvo Gallardo
• María Francisca Cano Abad
• Cristóbal de los Ríos Salgado
• Ricardo de Pascual y del Castillo
• José Carlos González San Frutos
• María Rocío Lajarín Cuesta
• Marcos Maroto Pérez
• Ana José Moreno Ortega
• Juan Fernando Padín Nogueira
• Ana Ruiz Nuño
• Aneta Wojnicz
RESEARCH INTEREST
1) Exocytosis-neurotransmission-calcium signalling
Our research line is established since almost 40
years on basic ionic and receptor mechanisms
involved in the regulation of exocytotic neurotransmitter release. We mostly use adrenal medullary
chromaffin cell as a model to perform electrophysiological, pharmacological and neurosecretory studies, by the use of calcium imaging techniques with
patch-clamp and amperometric techniques. We are
particularly interested in going forward with my
hypothesis that the functional triad formed by voltage-dependent calcium channels, the endoplasmic
reticulum and the mitochondria, shape the cytosolic calcium signals required to regulate pre-exocytotic and exocytotic steps. We are trying to project
this hypothesis into pathogenic mechanisms of
three disorders, i.e. Alzheimer´s disease, amyotrophic lateral sclerosis and hypoxia survival in
early life.
2) Design, synthesis and Pharmacology of neuroprotective compounds with potential therapeutic
application in neurodegenerative diseases and
stroke.
In 1994, We published our first paper, trying to link
sodium and calcium channels to basic mechanisms
of neuronal death, using the chromaffin cell as a
model. In subsequent years, we developed this
area, focusing on neurotoxicity mechanisms looking for targets to develop new chemical entities
with potential neuroprotective effects and therapeutic applications to neurodegenerative diseases
(particularly Alzheimer´s disease) and cerebrovascular diseases (stroke)
During the next 5 years we will focus on the understanding of neurotransmitter release, exocytosis
and endocytosis in neurodegenerative diseases.
Also, we will try to develop newly synthesised compounds as neuroprotective medicine for
Alzheimer’s disease
MAJOR GRANTS
• de los Ríos Salgado, Cristóbal. The calhm1
channel and its Alzheimer's disease-linked
mutated form p86l-calhm1. A new biological target for the finding of neuroprotective drugs.
CP10/00531. ISCIII. 2011-2014.
– 81 –
AREA 3AREA 2 AREA 1
Line 2.1
Neuropharmacology
and neuroprotection
Neurotransmission, pharmacological neuroprotection and
neurodegenerative and neuropsychiatric diseases
• de los Ríos Salgado, Cristóbal. La proteína fosfatasa 2a como diana terapéutica para el desarrollo
de nuevos fármacos para el tratamiento de enfermedades neurodegenerativas. ISCIII. PI13/00789.
2014-2016.
Granted 2014:
• Ríos Salgado, Cristóbal de los. La proteína fosfatasa 2a como diana terapéutica para el desarrollo
de nuevos fármacos para el tratamiento de enfermedades neurodegenerativas. PI13/00789. ISCIII.
2014-2016.
PUBLICATIONS
(8)
Gomez-Pinedo U, Yáñez M, Matías-Guiu J, Galán L,
Guerrero-Sola A, Benito-Martin MS, Vela A, ArranzTagarro JA, García AG. Cellular changes in motor
neuron cell culture produced by cytotoxic cerebrospinal fluid from patients with amyotrophic lateral sclerosis. Neurologia. 29(6):346-352. 2014.
PMID:
24144827.
IF:
1,289.
DOI:
10.1016/j.nrl.2013.08.001.
http://dx.doi.org/10.1016/j.nrl.2013.08.001
10.1128/MCB.00360-13.
Fernández-Morales JC, Padín JF, Arranz-Tagarro JA,
Vestring S, García AG, de Diego AM. Hypoxia-elicited
catecholamine release is controlled by L-type as well as
N/PQ types of calcium channels in rat embryo chromaffin cells. Am J Physiol. 307(5):C455-65. 2014.
PMID: 24990647. IF: 3,674. DOI: 10.1152/ajpcell.00101.2014.
http://dx.doi.org/10.1152/ajpcell.00101.2014
González JC, Lignani G, Maroto M, Baldelli P,
Hernández-Guijo JM. Presynaptic muscarinic receptors reduce synaptic depression and facilitate its recovery at hippocampal gabaergic synapses. Cereb Cortex.
24(7):1818-31. 2014. PMID: 23425889. IF: 8,305. DOI:
10.1093/cercor/bht032.
http://dx.doi.org/10.1093/cercor/bht032
Arranz-Tagarro JA, de los Ríos C, García AG, Padín JF.
Recent patents on calcium channel blockers: emphasis
on CNS diseases. Expert Opin Ther Pat. 24(9):959977. 2014. PMID: 25118673. IF: 3,441. DOI:
10.1517/13543776.2014.940892.
http://dx.doi.org/10.1517/13543776.2014.940892
Rodríguez, J.Q.D, Da Silva Jr., E.D., Galvao, K.M.,
Miranda-Ferreira, R., Caricati-Neto, A., Jurkiewicz,
N.H., García, A.G. and Jurkiewicz, A. Differential
regulation of atrial contraction by P1 and P2
purinoceptors in normotensive and spontaneously
hypertensive rats. Hypertens Res. 37(3):210-9.
2014. PMID: 24285249. IF: 2,936. DOI:
10.1038/hr.2013.146.
http://dx.doi.org/10.1038/hr.2013.146
Yáñez M, Matías-Guiu J, Arranz-Tagarro JA, Galán
L, Viña D, Gómez-Pinedo U, Vela A, Guerrero A,
Martínez-Vila E, García AG. The neuroprotection
exerted by memantine, minocycline and lithium,
against neurotoxicity of CSF from patients with
amyotrophic lateral sclerosis, is antagonized by riluzole. Neurodegener Dis. 13(2-3):171-179. 2014.
PMID:
24356417.
IF:
3,454.
DOI:
10.1159/000357281.
http://dx.doi.org/10.1159/000357281
Mellström B, Sahún I, Ruiz-Nuño A, Murtra P, GomezVillafuertes R, Savignac M, Oliveros JC, Gonzalez P,
Kastanauskaite A, Knafo S, Zhuo M, Higuera-Matas A,
Errington ML, Maldonado R, DeFelipe J, Jefferys JG,
Bliss TV, Dierssen M, Naranjo JR. DREAM controls the
on/off switch of specific activity-dependent transcription pathways. Mol Cell Biol. 34(5):877-887. 2014.
PMID:
24366545.
IF:
5,036.
DOI:
Egea J, Parada E, Gómez-Rangel V, Buendia I,
Negredo P, Montell E, Ruhí R, Vergés J, Roda JM,
García AG, López MG. Small synthetic hyaluronan disaccharides afford neuroprotection in brain ischemiarelated models. Neuroscience. 265:313-22. 2014.
PMID: 24486437. IF: 3,327. DOI: 10.1016/j.neuroscience.2014.01.032.
http://dx.doi.org/10.1016/j.neuroscience.2014.01.032
– 82 –
AREA 2
GROUP 16
HEAD OF LABORATORY
GROUP MEMBERS
• Izaskun Buendía Abaitua
• Francisco Javier Egea Máiquez
• Vanessa Gómez Rangel
• Laura González Lafuente
• Rafael León Martínez
• María Nares Yustas
• Elisa Navarro González de Mesa
• Esther Parada Pérez
• Mercedes Villarroya Sánchez
RESEARCH INTEREST
Neurodegenerative disorders like Alzheimer’s disease,
Parkinson’s disease and stroke present an appalling
cost, both in financial and human terms. Treatments for
neurodegenerative diseases (NDDs) are destined to
become the most significant health challenge for this
generation. To date, no therapeutic strategy has proven
effective and millions have been invested in therapeutic
trials that have failed. There is therefore a most urgent
and pressing need to identify novel therapeutic strategies that might protect or rescue vulnerable neurons in
these dreadful diseases. Our research group is interested in developing pre-clinical models “in vitro” and “in
vivo” that may be more relevant to NDDs in human
pathology and to evaluate new therapeutics for NDDs
diseases based on new targets that involve control of the
redox balance and neuroinflammation. We are also interested in the combination therapy approach by using
commercial drugs with complementary mechanisms of
action: this strategy is working well in diseases like cancer and AIDS and we believe that they could become an
interesting approach in the future treatment of NDDs.
Furthermore, we are interested in the search of biomarkers for early diagnosis, monitoring neurodegenerative disease progression and gauging responses to
therapies. In ischemic stroke, the prediction of outcome after suffering an ischemic stroke is important for
clinicians, patients, and researchers. In that sense, we
try to define protein changes associated with acute
ischemic brain damage that might help us to identify
new biomarker candidates for stroke prognosis.
From a medicinal chemistry point of view, our group is
developing new chemical entities as potential drugs for
the treatment of neurodegenerative diseases. Our
approach is based in the use of multitarget ligands, i.e.
the design, synthesis and biological evaluation of one
molecule that integrates two or more activities for biological targets implicated in neurodegeneration, like the
mitochondrial sodium/calcium exchanger, the calcium
homeostasis modulator-1 or the phosphatase 2A, new
Nrf2 inducers combined with scavenger effect, the inhibition of several enzymes related to neurological disorders and agonist of the nicotinic acetylcholine receptors, and thus assessing the real contribution of these
targets to physiopathological pathways of neuronal
death/survival.
MAJOR GRANTS
• León Martinez, Rafael. NRF2-are pathway upregulation combined with gsk3-beta inhibition as
key targets for a novel disease modifying multitarget drug development program for neurodegenerative diseases. CP11/00165. ISCIII. 20122014.
• León Martinez, Rafael. Non-conventional target
approach for drug discovery against neurodegenerative diseases: NRF2 upregulation. CIG322156. EU/PRG. MARCO. MARIE CURIE
CAREER INTEGRATION GRANT (CIG) 2012.
FP7-People-2012. 2012-2016.
– 83 –
AREA 3AREA 2 AREA 1
Line 2.2
Neurotransmission
in the hippocampus
Granted 2014:
• León Martínez, Rafael. Compuestos multidiana
quirales para el tratamiento de enfermedades
neurodegenerativas: ligandos de receptores
nicotínicos, inductores de NRF2 y antiinflamatorios. PI14/00372. ISCIII. 2015-2017.
PUBLICATIONS (10)
Cunha MP, Martín-de-Saavedra MD, Romero A, Egea
J, Ludka FK, Tasca CI, Farina M, Rodrigues AL, López
MG. Both creatine and its product phosphocreatine
reduce oxidative stress and afford neuroprotection in
an in vitro Parkinson's model. ASN Neuro. 2014: 1–16.
2014. PMID: 25424428. IF: 4,436. DOI:
10.1177/1759091414554945.
http://dx.doi.org/10.1177/1759091414554945
Balsera B, Mulet J, Fernández-Carvajal A, de la TorreMartínez R, Ferrer-Montiel A, Hernández-Jiménez JG,
Estévez-Herrera J, Borges R, Freitas AE, López MG,
García-López MT, González-Muñiz R, Pérez de Vega
MJ, Valor LM, Svobodová L, Sala S, Sala F, Criado M.
Chalcones as positive allosteric modulators of α7 nicotinic acetylcholine receptors: a new target for a privileged structure. Eur J Med Chem. 86:724-39. 2014.
PMID:
25232969.
IF:
3,432.
DOI:
10.1016/j.ejmech.2014.09.039.
http://dx.doi.org/10.1016/j.ejmech.2014.09.039
González-Muñoz GC, Arce MP, Pérez C, Romero A,
Villarroya M, López MG, Conde S, Rodríguez-Franco
MI. Dibenzo [1,4,5]thiadiazepine: a hardly-known heterocyclic system with neuroprotective properties of
potential usefulness in the treatment of neurodegenerative diseases. Eur J Med Chem. 81:350-8. 2014.
PMID:
24858540.
IF:
3,432.
DOI:
10.1016/j.ejmech.2014.04.075.
http://dx.doi.org/10.1016/j.ejmech.2014.04.075
Romero A, Egea J, González-Muñoz GC, Martín de
Saavedra MD, del Barrio L, Rodríguez-Franco MI,
Conde S, López MG, Villarroya M, de los Ríos C.
ITH12410/SC058: a new neuroprotective compound
– 84 –
with potential in the treatment of Alzheimer's disease.
ACS Chem Neurosci. 17;5(9):770-5. 2014. PMID:
25008046. IF: 4,21. DOI: 10.1021/cn500131t.
http://dx.doi.org/10.1021/cn500131t
Egea J, Romero A, Parada E, León R, Dal-Cim T,
López MG. Neuroprotective effect of dimebon against
ischemic neuronal damage. Neuroscience. 267:11-21.
2014. PMID: 24607349. IF: 3,327. DOI: 10.1016/j.neuroscience.2014.02.025.
Tenti G, Parada E, León R, Egea J, Martínez-Revelles
S, Briones AM, Sridharan V, López MG, Ramos MT,
Menéndez JC. New 5-unsubstituted dihydropyridines
with improved CaV1.3 selectivity as potential neuroprotective agents against ischemic injury. J Med Chem.
57(10):4313-23. 2014. PMID: 24754640. IF: 5,48. DOI:
10.1021/jm500263v.
http://dx.doi.org/10.1021/jm500263v
López-Iglesias B, Pérez C, Morales-García JA, AlonsoGil S, Pérez-Castillo A, Romero A, López MG, Villarroya
M, Conde S, Rodríguez-Franco MI. New melatonin-N,
N-dibenzyl(N-methyl)amine hybrids: potent neurogenic
agents with antioxidant, cholinergic, and neuroprotective properties as innovative drugs for Alzheimer's disease. J Med Chem. 57(9):3773-85. 2014. PMID:
24738476. IF: 5,48. DOI: 10.1021/jm5000613.
http://dx.doi.org/10.1021/jm5000613
Rojo AI, McBean G, Cindric M, Egea J, López MG,
Rada P, Zarkovic N, Cuadrado A. Redox control of
microglial function: molecular mechanisms and functional significance. Antioxid Redox Signal. 21(12):1766801. 2014. PMID: 24597893. IF: 7,667. DOI:
10.1089/ars.2013.5745.
http://dx.doi.org/10.1089/ars.2013.5745
Egea J, Parada E, Gómez-Rangel V, Buendia I,
Negredo P, Montell E, Ruhí R, Vergés J, Roda JM,
García AG, López MG. Small synthetic hyaluronan disaccharides afford neuroprotection in brain ischemiarelated models. Neuroscience. 265:313-22. 2014.
PMID: 24486437. IF: 3,327. DOI: 10.1016/j.neuroscience.2014.01.032.
AREA 2
Cherif O, Allouche F, Chabchoub F, Chioua M, Soriano E,
Yañez M, Cacabelos R, Romero A, López MG, Marco-
Contelles J. Isoxazolotacrines as non-toxic and selective
butyrylcholinesterase inhibitors for Alzheimer's disease.
Future Med Chem 6(17):1883-1891. 2014. PMID:
25495982. IF: 4. DOI: 10.4155/fmc.14.115.
http://dx.doi.org/: 10.4155/fmc.14.115
AREA 3AREA 2 AREA 1
http://dx.doi.org/10.1016/j.neuroscience.2014.
01.032
– 85 –
Line 2.3
Clinical pharmacology
and pharmacogenetics
GROUP 32
HEAD OF LABORATORY
GROUP MEMBERS
• Elizabeth Barreto Quiñones
• Carmen Belmonte Campillo
• María Teresa Cabaleiro Ocampo
• María Fagoaga Torija
• Esperanza González Rojano
• Juan Diego López de la Reina Maroto
• Igone Marrodán Remírez
• María Isabel Moreno Arza
• Dolores Ochoa Mazarro
• Concepción Pérez Hernández
• Rocío María Prieto Pérez
• Angela Rivas Acosta
• Irene Román Martínez
• Manuel Román Martínez
• Sergio Daniel Sánchez Rojas
• Javier Soriano Ventura
• María Talegón García
• Ana María Tello Miller
• Sarahi Elizabeth Valdez Acosta
• Carmen Verge González
RESEARCH INTEREST
The aim of the investigation performed in this group is to
evaluate pharmacokinetics, pharmacodynamics and
pharmacogenetics in order to predict the response of the
patients to drugs, in terms of efficacy and safety.
Our group has wide experience conducting numerous
phase I, II and III clinical trials. We have available a Clinical
Trials Unit, with capacity for 14 subjects (7th floor,
– 86 –
Hospital Universitario de la Princesa). The Clinical trials
performed include safety, pharmacokinetics, pharmacodynamics, interaction and bioequivalence studies in
healthy volunteers, and studies in patients to probe the
efficacy of new drugs in collaboration with several specialists in the hospital and primary care. Our group performed more than 20 clinical trials each year, and this
number is anticipated to increase due to the demand
from the pharmaceutical industry.
Our pharmacogenetic research is related with various
clinical diseases, trying to search for new pharmacogenetic markers to predict drug responses, both therapeutic and toxic, that could help physicians to decide the
best treatment for every patient. In 2014, 217 patients
benefited from pharmacogenetic testing. We are already
increasing the number of pharmacogenetic tests performed in our Service to better support the physicians on
the decision about therapeutic strategies. In addition, in
2014 we participated in 7 projects, one of them about
epigenetic biomarkers predicting response to biological
drugs in psoriasis, which is the continuation of another
project analyzing pharmacogenetic biomarkers.
MAJOR GRANTS
• Abad Santos, Francisco. Plataforma de unidades de
investigación clínica y ensayos clínicos. ISCIII.
PT13/0002/0027. 2014-2017.
• Abad Santos, Francisco. Estudio de marcadores exigenticos asociados a la respuesta a fármacos biológicos en
el tratamiento de la psoriasis. ISCIII. PI13/01598. 20142016.
• Abad Santos, Francisco. Nuevos medicamentos genéricos para el tratamiento de patologías de alto impacto.
MINECO. IPT-2011-1663-900000. 2012-2015.
• Abad Santos, Francisco. CAIBER.CAIBER. 2009-2014.
PUBLICATIONS (4)
Cabaleiro T, Ochoa D, López-Rodríguez R, Román M,
Novalbos J, Ayuso C, Abad-Santos F. Effect of poly-
AREA 2
Kress HG, Ahlbeck K, Aldington D, Alon E, Coaccioli S,
Coluzzi F, Huygen F, Jaksch W, Kalso E, Kocot-Kępska
M, Mangas AC, Margarit Ferri C, Morlion B, MüllerSchwefe G, Nicolaou A, Pérez Hernández C, Pergolizzi
J, Schäfer M, Sichère P. Managing chronic pain in elderly patients requires a CHANGE of approach. Curr
Med Res Opin. 30(6):1153-64. 2014. PMID:
24450746.
IF:
2,372.
DOI:
10.1185/03007995.2014.887005.
http://dx.doi.org/10.1185/03007995.2014.887005
Darbà J, Kaskens L, Pérez C, Alvarez E, NavarroArtieda R, Sicras-Mainar A. Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy
from a spanish perspective. Adv Ther. 31(1):1-29.
2014. PMID: 24390901. IF: 2,438. DOI:
10.1007/s12325-013-0088-2.
http://dx.doi.org/10.1007/s12325-013-0088-2
Román M, Ochoa D, Sánchez-Rojas SD, Talegón M,
Prieto-Pérez R, Rivas Â, Abad-Santos F, Cabaleiro T.
Evaluation of the relationship between polymorphisms
in CYP2C19 and the pharmacokinetics of omeprazole,
pantoprazole and rabeprazole. Pharmacogenomics.
15(15):1893-901. 2014. PMID: 25495411. IF: 3,425.
DOI: 10.2217/pgs.14.141.
http://dx.doi.org/10.2217/pgs.14.141
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ABAD SANTOS, FRANCISCO
Ensayo clínico cruzado y aleatorizado de bioequivalencia de
dos formulaciones de ezetimiba de 10 mg comprimidos de
recubiertos con película, tras su administración oral en
dosis £nica a voluntarios sanos en ayunas (Versión 1:0302-14). LABORATORIOS ALTER, S.A. UECHUP-EZT/14-3
EudraCT: 2014-000375-18
PRINCIPAL RESEARCHER: OCHOA MAZARRO,
DOLORES
Ensayo clínico pivotal, aleatorizado, cruzado y replicado de
bioequivalencia de dos formulaciones de barnidipino 20
mg capsulas de liberación modificada tras su administración oral en dosis única a voluntarios sanos en ayunas;
(Versión 1: 14-11-13). CHEMO RESEARCH S.L.
ESPAÑACHR1-CR-BARN-0159-CT-B-04-13
EudraCT: 2013-004880-29
DOLORES
Ensayo clínico cruzado y aleatorizado de bioequivalencia
de dos formulaciones de amlodipino/valsartán 10 mg/160
mg comprimidos recubiertos, tras su administración oral
en dosis única a voluntarios sanos en ayunas con diseño
cruzado replicado; (Versión 1: 15-01-14). LABORATORIOS NORMON, S.A. N-AMLVAL-13-196
EudraCT: 2013-004147-23
DOLORES
Ensayo clínico cruzado aleatorizado para evaluar la bioequivalencia entre couldina ibuprofeno (ibuprofeno lisina
400 mg + clorfenamina 2 mg + fenilefrina 7,5 mg) comprimidos efersvescentes y Couldina® (ácido acetilsalicílico
500 mg + clorfenamina 2 mg + fenilefrina 7,5 mg) comprimidos efervescentes más Algifast® (ibuprofeno 400 mg)
suspensión oral, tras su administración en dosis única a
voluntarios sanos en ayunas; (Versión 1:05-02-14). LABORATORIOS ALTER, S.A. UECHUP-COU-IBU/14-1
EudraCT: 2014-000188-42
DOLORES
Ensayo clínico cruzado, aleatorizado de bioequivalencia de
dos formulaciones de olmesartán/hidroclorotiazida comprimidos recubiertos de 40/25 mg, tras su administración
en dosis única a voluntarios sanos en ayunas (Versión 1:
19-03-14). LABORATORIOS NORMON, S.A. N-OLMHID14-199
EudraCT: 2014-000607-27
DOLORES
Ensayo clínico cruzado y aleatorizado de bioequivalencia
– 87 –
AREA 3AREA 2 AREA 1
morphisms on the pharmacokinetics, pharmacodynamics, and safety of risperidone in healthy volunteers.
Hum Psychopharmacol. 29(5):459-69. 2014. PMID:
25042870. IF: 1,854. DOI: 10.1002/hup.2420.
http://dx.doi.org/10.1002/hup.2420
de dos formulaciones de rasagilina comprimidos de
1 mg, tras su administración en dosis única a voluntarios sanos en ayunas; (Versión 1: 28-4-14). LABORATORIOS ALTER, S.A. UECHUP-RAS/14-4
EudraCT: 2014-001123-77
DOLORES
Ensayo clínico aleatorizado de bioequivalencia de
dos formulaciones de voriconazol comprimidos
recubiertos de 200 mg, tras su administración en
dosis única a voluntarios sanos en ayunas con un
diseño cruzado en dos etapas; (Versión 1: 11-0714). LABORATORIOS KERN PHARMA S.L. KPVOR-71
2014-001964-36
DOLORES
Estudio farmacocinético aleatorizado, abierto,
cruzado de dos brazos, para la evaluación de la
seguridad sistémica de dos formulaciones de
budesonida/formoterol 320/9 microgramos polvo
inhalado administrado como una dosis única de
640/18 microgramos a voluntarios sanos en ayunas; (Versión 1: 23-7-14). CHEMO RESEARCH S.L.
ESPAÑA CHR1-CR-BUDF-0202-CTP-01-14
EudraCT: 2014-003016-37
DOLORES
Ensayo clínico cruzado, aleatorizado de bioequivalencia de dos formulaciones de roflumilast comprimidos
recubiertos de 500 mcg, tras su administración en
dosis única a voluntarios sanos en ayunas; (Versión 1:
– 88 –
29-7-14). LABORATORIOS CINFA S.A. CFA-1080-P
EudraCT: 2014-002662-71
DOLORES
Ensayo clínico aleatorizado de bioequivalencia de dos
formulaciones de comprimidos recubiertos con película de tadalafilo de 20 mg, tras su administración oral en
dosis única a voluntarios sanos con comida en un diseño cruzado de dos etapas; (Versión 1: 21-07-14).
LABORATORIOS KERN PHARMA S.L. KP-TDF-67
EudraCT: 2014-001073-13
PRINCIPAL RESEARCHER: PÉREZ HERNÁNDEZ,
CONCEPCIÓN
Estudio observacional transversal para determinar la
prevalencia y repercusión del dolor en pacientes del
Hospital Universitario de la Princesa (Madrid, España);
(Versión 1: 05-11-13). DOL-PRIN-14
PRINCIPAL RESEARCHER: PÉREZ HERNÁNDEZ,
CONCEPCIÓN
Estudio multicéntrico con grupos cruzados, aleatorizado, doble ciego y doble enmascaramiento para
demostrar la equivalencia en la eficacia analgésica y función intestinal de dosis equivalentes de oxicodona de
120 y160 mg al día, utilizando las presentaciones de
comprimidos de mayor dosis OXN PR (OXN60/30 mg
PR, OXN80/40 mg PR) dos veces al día, en comparación con la dosis idéntica diaria utilizando una combinación de comprimidos de menor dosis en individuos
con dolor oncológico que requiere un tratamiento continuo con opiáceos; (Versión 06-03-14). MUNDIPHARMA RESEARCH GMBH & CO. KG OXN3508
EudraCT: 2013-004888-31
AREA 2
GROUP 33
HEAD OF LABORATORY
GROUP MEMBERS
• Montserrat Alcañiz Rodríguez
• Celia Anaya Suárez
• Francisco Félix Caballero Díaz
• María Cabello Salmerón
• Elena Ezquiaga Terrazas
• Luis Miguel García Olmos
• Eduardo García-Camba de la Muela
• Kaloyan Kamenov Kamenov
• Itziar Leal Leturia
• Pilar López García
• Natalia Martín María
• Herminio Martínez Cano
• Blanca Mellor Marsá
• Marta Miret García
• María Provencio Ortega
• Laura Alejandra Rico Uribe
• María del Mar Rivas Rodríguez
• Jesús Valle Fernández
RESEARCH INTEREST
Our team has been devoted to researching the nosology of mental disorders, the study of the efficacy and
efficiency of clinical interventions in affective disorders
and the assessment of the health status, quality of life
and well-being by means of analysing large populations data. We maintain our collaboration with the
WHO and have contributed to the revision of the
International Classification of Diseases 10th edition
(ICD-10). We are currently conducting a randomized
clinical trial to verify the efficacy of methylphenidate in
patients with acute bipolar mania (MEMAP study). In
addition we are conducting a multi-approach study
for the identification of the available interventions for
targeting psychosocial difficulties in major depression
(meta-analyses and expert consultation) (MARATONE
project).
Following H2020 strategic plan, we are consolidating
our research line on active aging and wellbeing. In
2014 we presented two European proposals that
received funding for the upcoming years: ATHLOS Ageing Trajectories of Health: Longitudinal
Opportunities and Synergies,
and PATHWAYS PArticipation To Healthy Workplaces And inclusive
Strategies in the Work Sector . In addition, we are part
of the consortiums leading two other H2020 projects
that have been selected by the European Commission
for the second stage of the evaluation. Both projects
(IMPACD and EU-PATIO) aim to improve mental health
in the older population by means of a comprehensive
and integrated approach to health and well-being.
The ROAMER project, an important European project
in which we participate, is almost finished and by the
end of March 15 the main gaps of knowledge in mental health research and the priorities for mental health
and well-being research in Europe are going to be
presented in a final report.
During the next years, we intend to continue to contribute to the promotion of mental health not only at a
European level but also in Low and middle income
countries (LAMICs) and focus in improvement of
health systems. We are already participating in an
international project (EMERALD project) funded by the
EU aimed to enhance mental health in LAMICs by
means of improvement of all the systems related to
health care.
Our research staff has been publishing numerous scientific works from a health survey comprising representative sample of adults from Poland, Finland, and Spain
(COURAGE in Europe project). Our team has also com-
– 89 –
AREA 3AREA 2 AREA 1
Line 2.4
Diagnostic and
therapeutic advances
in affective disorders
pared these data to make other cross-national comparisons with other available datasets from other countries (e.g. India, Mexico) and validating new tools to
measure the well-being at population level. In addition,
the team has received funding from Carlos III National
health institute to conduct the second wave of this
health survey including the Spanish population.
Finally, we maintain our interest in the study of the
environmental and genetic risk factors for the development of psychotic episodes and we currently collaborate with 5 Hospital in Madrid in the identification
of some of the risk factors for first psychotic episodes.
This is part of a multi-center longitudinal study (AGESCM project).
MAJOR GRANTS
• Ayuso Mateos, José Luis. Depresión, bienestar
subjetivo, salud y mortalidad: un estudio longitudinal en población general. ISCIII. PI13/00059. 20142016
• Ayuso Mateos, José Luis. Mental health training
through research network in Europe. MARATONE.
FP7-31795. Comisión Europea. 2013-2017.
• Miret García, Marta. Desarrollo y validación de un
instrumento para evaluar calidad de vida en personas de edad avanzada. 13INT. Convocatoria
intramural CIBERSAM. 2013-2014.
• Ayuso Mateos, José Luis. Emerging mental health
systems in low- and middle-income countries.
EMERALD. FP7-305968. Comisión Europea. 20122017.
• Ayuso Mateos, José Luis. Bienestar y salud mental
y física en población general: un análisis longitudinal. PI11/02915. ISCIII. 2012-2014.
• Ayuso Mateos, José Luis. Ambiente y genes en
esquizofrenia-grupos de investigación de la comunidad de Madrid. S2010/BMD-2422. CAM. 20112015.
• Ayuso Mateos, José Luis. A roadmap for mental
health research in Europe (ROAMER). Health - F3 2011 - 282586. Comisión Europea. VII Programa
Marco. 2011-2014.
– 90 –
PUBLICATIONS (21)
Torres CV, Sola RG, Pastor J, Pedrosa M, Navas M,
García-Navarrete E, Ezquiaga E, García-Camba E.
Aggressive behavior. response. J Neurosurg.
120(1):287-288. 2014. PMID: 24520574. IF: 3,227
Kamenov K, Mellor-Marsá B, Leal I, Ayuso-Mateos JL,
Cabello M. Analysing Psychosocial Difficulties in
Depression: A Content Comparison between
Systematic Literature Review and Patient Perspective.
Biomed Res Int. 2014:319634. 2014. PMID:
25009814. IF: 1,579. DOI: 10.1155/2014/319634.
http://dx.doi.org/10.1155/2014/319634
Leonardi M, Chatterji S, Koskinen S, Ayuso-Mateos JL,
Haro JM, Frisoni G, Frattura L, Martinuzzi A, TobiaszAdamczyk B, Gmurek M, Serrano R, Finocchiaro C, on
behalf of COURAGE in Europe Project's Consortium.
Determinants of Health and Disability in Ageing
Population: The COURAGE in Europe Project
(Collaborative Research on Ageing in Europe). Clinical
psychology & psychotherapy. 21(3):193-8. 2014.
PMID: 23881690. IF: 2,59. DOI: 10.1002/cpp.1856.
http://dx.doi.org/10.1002/cpp.1856
Caballero FF, Miret M, Olaya B, Perales J, López-Ridaura
R, Haro JM, Chatterji S, Ayuso-Mateos JL. Evaluation of
Affect in Mexico and Spain: Psychometric Properties and
Usefulness of an Abbreviated Version of the Day
Reconstruction Method. Journal of Happiness Studies.
15:915-935. 2014. IF: 1,772. DOI: 10.1007/s 10902-0139456-5.
http://dx.doi.org/10.1007/s 10902-013-9456-5
Perales J, Martin S, Ayuso-Mateos JL, Chatterji S, Garin
N, Koskinen S, Leonardi M, Miret M, Moneta V, Olaya B,
Tobiasz-Adamczyk B, Haro JM. Factors associated with
active aging in Finland, Poland, and Spain. Int
Psychogeriatr. 26(8):1363-75. 2014. PMID: 24735743. IF:
1,892. DOI: 10.1017/S1041610214000520.
http://dx.doi.org/10.1017/S1041610214000520
Miret M, Caballero FF, Huerta-Ramírez R, Moneta MV,
Olaya B, Chatterji S, Haro JM, Ayuso-Mateos JL.
Factors associated with suicidal ideation and attempts
AREA 2
Raggi A, Quintas R, Russo E, Martinuzzi A, Costardi D,
Frisoni GB, Franco MG, Andreotti A, Ojala M, Fajuri SP,
Perales J, Chatterji S, Miret M, Tobiasz-Adamczyk B,
Koskinen S, Frattura L, Leonardi M. Mapping SAGE
questionnaire to the International Classification of
Functioning, Disability and Health (ICF). Clinical psychology & psychotherapy. 21(3):199-203. 2014. PMID:
23861299. IF: 2,59. DOI: 10.1002/cpp.1857.
Garin N, Olaya B, Perales J, Moneta MV, Miret M, AyusoMateos JL, Haro JM. Multimorbidity patterns in a national representative sample of the Spanish adult population.
PLoS One. 9(1):e84794. 2014. PMID: 24465433. IF:
3,534. DOI: 10.1371/journal.pone. 0084794.
Hartley S, McArthur M, Coenen M, Cabello M, Covelli
V, Roszczynska-Michta J, Pitkänen T, Bickenbach J,
Cieza A. Narratives Reflecting the Lived Experiences of
People with Brain Disorders: Common Psychosocial
Difficulties and Determinants. PLoS One. 9(5):e96890.
2014. PMID: 24805128. IF: 3,534. DOI: 10.1371/journal.pone.0096890.
Haro JM, Ayuso-Mateos JL, Bitter I, Demotes-Mainard
J, Leboyer M, Lewis SW, Linszen D, Maj M, McDaid D,
Meyer-Lindenberg A, Robbins TW, Schumann G,
Thornicroft G, Van Der Feltz-Cornelis C, Van Os J,
Wahlbeck K, Wittchen HU, Wykes T, Arango C,
Bickenbach J, Brunn M, Cammarata P, Chevreul K,
Evans-Lacko S, Finocchiaro C, Fiorillo A, Forsman AK,
Hazo JB, Knappe S, Kuepper R, Luciano M, Miret M,
Obradors-Tarragó C, Pagano G, Papp S, Walker-Tilley
T. ROAMER: roadmap for mental health research in
Europe. Int J Methods Psychiatr Res. 23 Suppl 1:1-14.
2014. PMID: 24375532. IF: 3,421. DOI:
10.1002/mpr.1406.
http://dx.doi.org/10.1002/mpr.1406
Valiente C, Cantero D, Sánchez A, Provencio M,
Wickham S. Self-esteem and evaluative beliefs in paranoia. J Behav Ther Exp Psychiatry. 45(2):297-302.
2014. PMID: 24561901. IF: 2,232. DOI:
10.1016/j.jbtep.2014.01.002.
http://dx.doi.org/10.1016/j.jbtep.2014.01.002
Quintas R, Raggi A, Bucciarelli P, Franco MG, Andreotti
A, Caballero FF, Olaya B, Chatterji S, Galas A,
Meriläinen-Porras S, Frisoni G, Russo E, Minicuci N,
Power M, Leonardi M. The COURAGE Built
Environment Outdoor Checklist: An Objective Built
Environment Instrument to Investigate the Impact of the
Environment on Health and Disability. Clin Psychol
Psychother. 21(3):204-214. 2014. PMID: 23897864.
IF: 2,59. DOI: 10.1002/cpp.1858.
Evans-Lacko S, Courtin E, Fiorillo A, Knapp M, Luciano
M, Park AL, Brunn M, Byford S, Chevreul K, Forsman
AK, Gulacsi L, Haro JM, Kennelly B, Knappe S, Lai T,
Lasalvia A, Miret M, O'Sullivan C, Obradors-Tarragó C,
Rüsch N, Sartorius N, Svab V, van Weeghel J, Van
Audenhove C, Wahlbeck K, Zlati A; ROAMER
Consortium, McDaid D, Thornicroft G. The state of the
art in European research on reducing social exclusion
and stigma related to mental health: a systematic mapping of the literature. Eur Psychiatry. 29(6):381-389.
2014. PMID: 24726533. IF: 3,21. DOI: 10.1016/j.eurpsy.2014.02.007.
http://dx.doi.org/10.1016/j.eurpsy.2014.02.007
Zawisza K, Galas A, Tobiasz-Adamczyk B, Chatterji S,
Haro JM, Miret M, Koskinen S, Power M, Leonardi M.
The Validity of the Instrument to Evaluate Social
Network in the Ageing Population: The Collaborative
Research on Ageing in Europe Social Network Index.
Clin Psychol Psychother. 21(3):227-241. 2014. PMID:
23939715. IF: 2,59. DOI: 10.1002/cpp.1860.
Raggi A, Quintas R, Bucciarelli P, Franco MG, Andreotti
A, Miret M, Zawisza K, Olaya B, Chatterji S, Sainio P,
Frisoni GB, Martinuzzi A, Minicuci N, Power M,
Leonardi M. Validation of the COURAGE Built
Environment Self-Reported Questionnaire. Clinical psy-
– 91 –
AREA 3AREA 2 AREA 1
in Spain for different age groups. Prevalence before
and after the onset of the economic crisis. J Affect
Disord. 163:1-9. 2014. PMID: 24836081. IF: 3,705.
DOI: 10.1016/j.jad.2014.03.045.
http://dx.doi.org/10.1016/j.jad.2014.03.045
chology & psychotherapy. 21(3):215-26. 2014. PMID:
23861306. IF: 2,59. DOI: 10.1002/cpp.1859.
Garin N, Olaya B, Lara E, Moneta MV, Miret M, AyusoMateos JL, Haro JM. Visual impairment and multimorbidity in a representative sample of the Spanish population. BMC Public Health. 14(815). 2014. PMID:
25103270. IF: 2,321. DOI: 10.1186/1471-2458-14815.
http://dx.doi.org/10.1186/1471-2458-14-815
Miret M, Caballero FF, Chatterji S, Olaya B, TobiaszAdamczyk B, Koskinen S, Leonardi M6, Haro JM,
Ayuso-Mateos JL. Health and happiness: cross-sectional household surveys in Finland, Poland and
Spain. Bull World Health Organ. 92(10):716-25. 2014.
PMID: 25378725. IF: 5,112. DOI: 10.2471/
BLT.13.129254.
http://www.who.int/bulletin/volumes/92/10/13-129254.pdf
Cabello M, Caballero F, Chatterji S, Cieza A, AyusoMateos JL. Risk factors for incidence and persistence
of disability in chronic major depression and alcohol
use disorders: longitudinal analyses of a populationbased study. Health Qual Life Outcomes. 17;12:186.
2014. PMID: 25516069. IF: 2,099. DOI:
10.1186/s12955-014-0186-0.
http://www.hqlo.com/content/12/1/186
Garin N, Olaya B, Moneta MV, Miret M, Lobo A, AyusoMateos JL, Haro JM. Impact of multimorbidity on disability and quality of life in the Spanish older population.
– 92 –
PLoS One. 9(11):e111498. 2014. PMID: 25375890. IF:
3,534.
DOI:
10.1371/journal.pone.0111498.
http://journals.plos.org/plosone/article?id=10.1371/jou
rnal.pone.0111498
Koyanagi A, Garin N, Olaya B, Ayuso-Mateos JL,
Chatterji S, Leonardi M, Koskinen S, TobiaszAdamczyk B, Haro JM. Chronic conditions and sleep
problems among adults aged 50 years or over in nine
countries: a multi-country study. PLoS One.
9(12):e114742. 2014. PMID: 25478876. IF: 3,534.
http://journals.plos.org/plosone/article?id=10.1371/jou
rnal.pone.0114742
Ezquiaga E, García-López A, de Dios C, Agud JL,
Albillo D, Vega-Piris L. Seasonality, Smoking and
History of Poor Treatment Compliance are Strong
Predictors of Dropout in a Naturalistic 6 Year Follow-Up
of Bipolar Patients. Psychiatr Q. 85(4):467-77. 2014.
PMID: 24986371. IF: 1,347. DOI: 10.1007/s11126014-9303-9.
http://dx.doi.org/10.1007/s11126-014-9303-9
CLINICAL TRIALS
PRINCIPAL RESEARCHER: AYUSO MATEOS, JOSE
LUIS
Depresión, bienestar subjetivo, salud y mortalidad: Un
estudio longitudinal en población general. INSTITUTO DE
SALUD CARLOS III ISCIII (EXPEDIENTE: PI13/00059)
AREA 2
GROUP 34
HEAD OF LABORATORY
GROUP MEMBERS
• Angela Adgyan de Abreu Arvelo
• Eva de Dios Tomás
• Luís Domínguez Gadea
• Eduardo García Navarrete
• Oscar Garnés-Camarena Estruch
• José Luís Martínez-Chacón Crespo
• María Luisa Meilán Paz
• Marta Navas García
• Guillermo Ortega Rabbione
• Jesús Pastor Gómez
• Paloma Pulido Rivas
• Cristina Virginia Torres Díaz
• Lorena Vega Zelaya
• Rybel Wix Ramos
RESEARCH INTEREST
Partial epileptic seizures were traditionally thought
to originate in specific areas of the cortex known as
“seizure onset zones”, before spreading to other
areas known as “epileptogenic zones”. These areas
are essential for seizures to propagate. Surgical
approaches, as the ones routinely practiced in our
neurosurgery service, to this condition include
resection or disconnection of these areas, from the
rest of the brain. This “single focus” model, however, fails in explaining the appearance of post-operative seizures in a significant minority of patients
where the suspected epileptogenic areas were correctly localized and excised during the surgery. In
view of that, our group has embarked in an interdisciplinary research program oriented toward a
broader perspective, considering the epilepsy as a
truly cortical network disease instead of “single
area” pathology. Several new lines of basic
research has been opened under this objective,
including definition of the epileptogenic network,
identification of critical network nodes and their
relationship with seizure onset areas. Since most of
the work done during these years was performed
with interictal recordings, that is, out of the seizure
stage, we are facing now a critical incremental step
in the future work.Taking advantage of the fact that
subdural and depth electrodes are now routinely
implanted in the Neurosurgery Service, we are now
ready to tackle the problem of understanding how
and why seizure appears, spread and perhaps
most important, terminate.
In order to do that, two straightforward objectives
will be:
a) Analyzing subdural recordings to understand
seizure spread, both in temporal lobe epilepsy and
in extra-temporal lobe patients. We will analyze
these recordings using similar methodology as the
one used in the analysis of interictal recordings.
b) Construction of a numerical model of cortical
activity, based in already existing mean field models, which allows to understand the role played by
the high synchronization areas in the propagation
and/or magnification of the epileptogenic activity.
Both objectives are in fact interrelated because
information provided by the analysis of the subdural electrodes will be included in the numerical
model and conversely, the numerical model, we
hope, will be used as a guide to analyze particular
aspects of the neurophysiological recordings.
MAJOR GRANTS
Pastor Gómez, Jesús. Tratamiento radioquirúrgico de
alta precisión en epilepsia temporal mesial. ISCIII.
PI12/02839. 2012-2014.
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AREA 3AREA 2 AREA 1
Line 2.5
Neurosurgery of epilepsy
PUBLICATIONS (6)
Vega-Zelaya L, Torres CV, Garnes-Camarena O, Ortega
GJ, García-Navarrete E, Navas M, Sola RG, Pastor J.
Electrocorticographicevidence and surgical implications of different physiopathologic subtypes of temporal epilepsy. Clin Neurophysiol. 125(12):2349-57. 2014.
PMID: 24820005. IF: 2,979. DOI: 10.1016/j.clinph.
2014.03.027.
http://dx.doi.org/10.1016/j.clinph.2014.03.027
Pastor J, Sola RG, Ortega GJ. Influence of paroxysmal
activity on background synchronization in epileptic
recordings. J Neurosci Methods. 223:69-73. 2014.
PMID: 24333290. IF: 1,959. DOI: 10.1016/
j.jneumeth.2013.11.027.
http://dx.doi.org/10.1016/j.jneumeth.2013.11.027
Torres CV, Manzanares R, Sola RG. Integrating diffusion tensor imaging-based tractography into deep
brain stimulation surgery: a review of the literature.
– 94 –
Stereotact Funct Neurosurg. 92(5):282-90. 2014.
PMID: 25248076. IF: 1,477. DOI: 10.1159/000362937.
http://dx.doi.org/10.1159/000362937
Vega-Zelaya L, Ortega GJ, Sola RG, Pastor J. Plasma
albumin induces cytosolic calcium oscilations and DNA
synthesis in human cultured astrocytes. Biomed Res
Int. 2014:539140. 2014. PMID: 24967376. IF: 1,579.
DOI: 10.1155/2014/539140.
http://dx.doi.org/10.1155/2014/539140
Navas M, Sola RG, Torres CV, Shakur SF, Manzanares
R, Gordillo C, Jimenez JA. Primary central neurocytoma of the mesencephalic tectum in a pediatric
patient. Childs Nerv Syst 30(5):945-951. 2014. PMID:
23958899. IF: 1,163.
Torres CV, Sola RG, Pastor J, Pedrosa M, Navas M,
García-Navarrete E, Ezquiaga E, García-Camba E.
Aggressive behavior. response. J Neurosurg.
120(1):287-288. 2014. PMID: 24520574. IF: 3,227
AREA 2
GROUP 35
HEAD OF LABORATORY
José Aurelio Vivancos Mora
GROUP MEMBERS
• Teresa Carreras Rodríguez
• Ana Beatriz Gago Veiga
• Lydia López Manzanares
• Virginia Meca Lallana
• Noemí Mora Pérez
• Florentino Nombela Merchán
• Gemma Reig Roselló
• Mónica Sobrado Sanz
• Álvaro Ximenez-Carrillo Rico
- Mild Cognitive impairment and dementia in very old
patients
- Cognitive impairment and dementia in Down syndrome
• Multiple Sclerosis.
- Outcome markers and new therapies
• Cephaleas.
- Botulinum toxin in chronic migraine
- Occipital nerve block for the treatment of cephaleas.
The future research of the group will be aimed at:
• Innovation projects in Migraine and Stroke: Integrated
device for multivariable and ambulatory monitoring of
clinical and environmental parameters (FIS, TEC and
Horizon H2020)
• Translational Study: Role of Toll-like receptors in
Myasthenia gravis.
• New biomarkers in drug refractory epilepsy and
Multiple Sclerosis.
• Clinical trials with private funding. Phase III studies.
Multiple sclerosis, cerebral infarction, Parkinson's,
Alzheimer's disease and Epilepsy.
• EEG monitoring in Stroke acute phase patients.
• New devices for capture of parameters by telemetry
in the stroke Unit
RESEARCH INTEREST
MAJOR GRANTS
The main research lines of this group are:
• Stroke and Cerebrovascular Diseases,
- Biomolecular markers of ischemia and new therapeutic targets
- Interventional neuroradiology and emerging therapies
- Population-based health services delivery / stroke
code system
- Telemedicine
• Epilepsy
- Drug-refractory Epilepsy
• Movement Disorders
- Parkinson disease in young patients
- Parkinson disease. Follow up and control helped by
new technologies
• Cognitive impairment and dementia
• Vivancos Mora, José Aurelio. Programa I2M2-"Imagen
molecular multimodal de la inflamacion". MINECO.
S2010/BMD-2349. 2012-2015.
• Vivancos Mora, José Aurelio. Estudio de viabilidad y
seguridad, abierto, aleatorizado y controlado, para evaluar el efecto neuroprotector de la diálisis de glutamato
plasmático en la fase aguda del infarto cerebral. EC11109. MSPSI. 2012-2015.
PUBLICATIONS (7)
Vivancos J, Gilo F, Frutos R, Maestre J, García-Pastor A,
Quintana F, Roda JM, Ximénez-Carrillo A; por el
– 95 –
AREA 3AREA 2 AREA 1
Line 2.6
Cerebrovascular
diseases
Comitéad hoc del grupo de Estudio de Enfermedades
Cerebrovasculares de la SEN:, Díez Tejedor E, Fuentes
B, Alonso de Leciñana M, Alvarez-Sabin J, Arenillas J,
Calleja S, Casado I, Castellanos M, Castillo J, Dávalos A,
Díaz-Otero F, Egido JA, Fernández JC, Freijo M, Gállego
J, Gil-Núñez A, Irimia P, Lago A, Masjuan J, MartíFábregas J, Martínez-Sánchez P, Martínez-Vila E, Molina
C, Morales A, Nombela F, Purroy F, Ribó M, RodríguezYañez M, Roquer J, Rubio F, Segura T, Serena J, Simal
P, Tejada J. Clinical management guidelines forsubarachnoid haemorrhage. Diagnosis and treatment.
Neurologia. 29(6):353-70. 2014. PMID: 23044408. IF:
1,289. DOI: 10.1016/j.nrl.2012.07.009.
Fuentes B, Gállego J, Gil-Nuñez A, Morales A, Purroy F,
Roquer J, Segura T, Tejada J, Lago A, Díez-Tejedor E; por
el Comité ad hoc del grupo de Estudio de Enfermedades
Cerebrovasculares de la SEN:, Alonso de Leciñana M,
Alvarez-Sabin J, Arenillas J, Calleja S, Casado I, Castellanos
M, Castillo J, Dávalos A, Díaz-Otero F, Egido JA, LópezFernández JC, Freijo M, García Pastor A, Gilo F, Irimia P,
Maestre J, Masjuan J, Martí-Fábregas J, Martínez-Sánchez
P, Martínez-Vila E, Molina C, Nombela F, Ribó M,
Rodríguez-Yañez M, Rubio F, Serena J, Simal P, Vivancos J.
Guidelines for the preventive treatment of ischaemic stroke
and TIA (II). Recommendations according to aetiological
sub-type. Neurologia. 29(3):168-183. 2014. PMID:
21937151. IF: 1,289. DOI: 10.1016/j.nrl.2011.06.003.
Alonso de Leciñana M, Egido JA, Casado I, Ribó M,
Dávalos A, Masjuan J, Caniego JL, Martínez Vila E, Díez
Tejedor E; por el Comitéad hoc del grupo de Estudio de
Enfermedades Cerebrovasculares de la SEN:, Fuentes
Secretaría B, Alvarez-Sabin J, Arenillas J, Calleja S,
Castellanos M, Castillo J, Díaz-Otero F, LópezFernández JC, Freijo M, Gállego J, García-Pastor A, GilNúñez A, Gilo F, Irimia P, Lago A, Maestre J, MartíFábregas J, Martínez-Sánchez P, Molina C, Morales A,
Nombela F, Purroy F, Rodríguez-Yañez M, Roquer J,
Rubio F, Segura T, Serena J, Simal P, Tejada J, Vivancos
J. Guidelines for the treatment of acute ischaemic
stroke. Neurologia. 29(2):102-122. 2014. PMID:
22152803. IF: 1,289. DOI: 10.1016/j.nrl.2011.09.012.
– 96 –
Camós S, Gubern C, Sobrado M, Rodríguez R,
Romera VG, Moro MA, Lizasoain I, Serena J, Mallolas
J, Castellanos M. Oct-2 Transcription Factor binding
activity and ExpressioN Up-Regulation In Rat Cerebral
Ischaemia Is Associated With a DIminution Of
Neuronal Damage In Vitro. Neuromolecular Med.
16(2):332-49. 2014. PMID: 24282026. IF: 3,885. DOI:
10.1007/s12017-013-8279-1.
http://dx.doi.org/10.1007/s12017-013-8279-1
J, Castellanos M. The high-mobility group I-Y transcription factor is involved in cerebral ischemia and
modulates the expression of angiogenic proteins.
Neuroscience. 269:112-30. 2014. PMID: 24680881.
IF: 3,327. DOI: 10.1016/j.neuroscience.2014.03.036.
Ballesteros I, Cuartero MI, Pradillo JM, de la Parra J,
Pérez-Ruiz A, Corbí A, Ricote M, Hamilton JA,
Sobrado M, Vivancos J, Nombela F, Lizasoain I, Moro
MA. Rosiglitazone-induced CD36 up-regulation
resolves inflammation by PPARγ and 5-LO-dependent
pathways. J Leukoc Biol. 95(4):587-98. 2014. PMID:
24338629. IF: 4,304. DOI: 10.1189/jlb.0613326.
http://dx.doi.org/10.1189/jlb.0613326
Gubern C, Camós S, Hurtado O, Rodríguez R,
Romera VG, Sobrado M, Cañadas R, Moro MA,
Lizasoain I, Serena J, Mallolas J, Castellanos M.
Characterization of Gcf2/Lrrfip1 in experimental cerebral ischemia and its role as a modulator of Akt, mTOR
and β-catenin signaling pathways. Neuroscience.
268:48-65. 2014. PMID: 24637094. IF: 3,327. DOI:
CLINICAL TRIALS
PRINCIPAL
RESEARCHER:
CARRERAS
RODRÍGUEZ, MARÍA TERESA
Estudio 18 semanas, aleatorizado, controlado con
AREA 2
PRINCIPAL RESEARCHER: LÓPEZ MANZANARES,
LYDIA
Estudio multicéntrico observacional para evaluar la
efectividad del tratamiento combinado con Neupro®
(parche transdérmico de rotigotina) y levodopa en
pacientes con Enfermedad de Parkinson. (NEUPART); PD0013
PRINCIPAL RESEARCHER: MECA LALLANA, VIRGINIA
Estudio observacional retrospectivo en esclerosis
múltiple remitente-recurrente para comparar la efectividad de los fármacos de segunda línea fingolimod
y natalizumab en la práctica clínica habitual. Estudio
MS 2ndline GATE; (Versión final: 1-7-14). NOVARTIS
FARMACEUTICA, S.A. NOV-FIN-2014-03
PRINCIPAL RESEARCHER: VIVANCOS MORA,
AURELIO
Estudio aleatorizado, doble ciego, multinacional,
para la prevención de episodios vasculares mayores
con ticagrelor comparado con aspirina (AAS) en
pacientes con ictus isquémico agudo o AIT
(SOCRATES Acute Stroke Or transient IsChaemic
Attack TReated with Aspirin or Ticagrelor and Patient
OutcomES); (Versión 1: 21-08-13). ASTRAZENECA
AB D5134C00001
EudraCT: 2012-003895-38
PRINCIPAL RESEARCHER: VIVANCOS MORA,
AURELIO
Ensayo sobre inhibición plaquetaria en el AIT y el
accidente cerebrovascular isquémico leve de
reciente aparición (POINT), un ensayo aleatorizado,
doble ciego, multicéntrico; Versión 5.029-10-13).
UNIVERSIDAD DE SAN FRANCISCO POINT
EudraCT: 2013-001185-41
GROUP ASSOCIATED 1
HEAD OF LABORATORY
Ignacio Lizasoain Hernández
GROUP MEMBERS
• Tamara Atanes Pérez
• Iván Ballesteros Martín
• Roberto Cañadas Martín
• María Isabel Cuartero Desviat
• Isaac García de Yébenes y Castro
• Víctor Manuel González Romera
• Macarena Hernández Jiménez
• Olivia Hurtado Moreno
• Ana Moraga Yébenes
• María Ángeles Moro Sánchez
RESEARCH INTEREST
The Neurovascular Research Unit (UIN), located at the
Department of Pharmacology of the School of Medicine
at the Universidad Complutense is an associated group
of the “Instituto de Investigación Sanitaria La Princesa
(IIS IP)”. It was formed in 1996 and since then our team
has been studying the pathophysiology and pharmacology of stroke. Our unit is devoted to the study of the
cerebrovascular disease (stroke) from a basic point of
view but also with a strong translational projection, a
vocation due to our location in a School of Medicine and
developed through a tight partnership with IIS IP.
MAJOR GRANTS
• Moro Sánchez, María Ángeles. Brain dysfunction during
aging: relevance for Alzheimer’s disease. CSD201000045. MICINN. 2011-2015.
• Lizasoain
Hernández,
Ignacio.
INVICTUS.
RD12/0014/0003. ISCIII. 2013-2016.
• Lizasoain Hernández, Ignacio. CITI-SIRCTUS. Ferrer
Internacional SA. 2012-2014.
– 97 –
AREA 3AREA 2 AREA 1
placebo, doble ciego, con grupos paralelos para
evaluar la seguridad y eficacia de PF-05212377
(SAM-760) en pacientes con Enfermedad de
Alzheimer de leve a moderada que presentan síntomas neuropsiquiátricos con una dosis diaria
estable de donepezilo; (Versión final: 2-1-14). PFIZER INC B2081011
EudraCT: 2014-000830-42
• Moro Sánchez, María Ángeles. BRAINFATE (el destino del cerebro): modulación de la respuesta neuroinflamatoria en el ictus. SAF2012-33216.
MINECO. 2013-2015.
• Lizasoain Hernández, Ignacio. Proyecto APTLR:
desarrollo de aptámeros moduladores de la actividad de receptorestlr-4, enfermedad cerebro-vascular (ICTUS). Aptus-Biotech. 2013-2014.
• Moro Sánchez, María Ángeles. Estudio de la
biología de células madre neurales para su empleo
en terapia celular en enfermedades neurodegenerativas (neurostem-cm). S2010/BMD-2336. CAM.
2012-2015.
• Lizasoain Hernández, Ignacio. Doble función de los
receptores "Toll-Like" en el ictus: reguladores de
daño y reparación. SAF2011-23354. MICINN.
2011-2014.
PUBLICATIONS (8)
Gubern C, Camós S, Hurtado O, Rodríguez R,
Romera VG, Sobrado M, Cañadas R, Moro MA,
Lizasoain I, Serena J, Mallolas J, Castellanos M.
Characterization of Gcf2/Lrrfip1 in experimental cerebral ischemia and its role as a modulator of Akt,
mTOR and β-catenin signaling pathways.
Neuroscience. 268:48-65. 2014. PMID: 24637094.
IF: 3,327. DOI:
02.051
Domínguez-Soto A, de Las Casas-Engel M, Bragado
R, Medina-Echeverz J, Aragoneses-Fenoll L, MartínGayo E5, van Rooijen N6, Berraondo P, Toribio ML,
Moro MA, Cuartero I, Castrillo A, Sancho D, SánchezTorres C, Bruhns P, Sánchez-Ramón S, Corbí AL.
Intravenous immunoglobulin promotes antitumor
responses by modulating macrophage polarization. J
Immunol. 193(10):5181-2014. PMID: 25326025. IF:
5,362. DOI: 10.4049/jimmunol.1303375.
Cuartero MI, Ballesteros I, de la Parra J, Harkin AL,
Abautret-Daly A, Sherwin E, Fernández-Salguero P,
– 98 –
Corbí AL, Lizasoain I, Moro MA. L-Kynurenine/Aryl
Hydrocarbon Receptor Pathway Mediates Brain
Damage After Experimental Stroke. Circulation.
130(23):2040-51. 2014. PMID: 25359166. IF: 14,948.
DOI: 10.1161/CIRCULATIONAHA.114.011394.
http://dx.doi.org/10.1161/CIRCULATIONAHA.114.
011394
Ballesteros I, Cuartero MI, Pradillo JM, de la Parra J,
Pérez-Ruiz A, Corbí A, Ricote M, Hamilton JA,
Sobrado M, Vivancos J, Nombela F, Lizasoain I, Moro
MA. Rosiglitazone-induced CD36 up-regulation
resolves inflammation by PPARγ and 5-LO-dependent pathways. J Leukoc Biol. 95(4):587-98. 2014.
PMID:
24338629.
IF:
4,304.
DOI:
10.1189/jlb.0613326.
http://dx.doi.org/10.1189/jlb.0613326
Moraga A, Pradillo JM, Cuartero MI, HernándezJiménez M, Oses M, Moro MA, Lizasoain I. Toll-like
receptor 4 modulates cell migration and cortical neurogenesis after focal cerebral ischemia. FASEB J.
28(11):4710-8. 2014. PMID: 25063846. IF: 5,48. DOI:
10.1096/fj.14-252452.
http://dx.doi.org/10.1096/fj.14-252452
J, Castellanos M. Oct-2 Transcription Factor binding
activity and ExpressioN Up-Regulation In Rat Cerebral
Ischaemia Is Associated With a DIminution Of
Neuronal Damage In Vitro. Neuromolecular Med.
16(2):332-49. 2014. PMID: 24282026. IF: 3,885. DOI:
10.1007/s12017-013-8279-1.
http://dx.doi.org/10.1007/s12017-013-8279-1
Romera VG, Moro MA, Lizasoain I, Serena J,
Mallolas J, Castellanos M. The high-mobility group IY transcription factor is involved in cerebral ischemia
and modulates the expression of angiogenic proteins. Neuroscience. 269:112-30. 2014. PMID:
24680881. IF: 3,327. DOI: 10.1016/j.neuroscience.2014.03.036.
03.036
AREA 2
initiate inflammation. Science. 346(6214):1234-8.
2014. PMID: 25477463. IF: 31,477 DOI: 10.1126/science.1256478.
http://dx.doi.org/10.1126/science.1256478
AREA 3AREA 2 AREA 1
Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero
MI, Rossaint J, Bilbao I, Nácher M, Pitaval C,
Radovanovic I, Fukui Y, McEver RP, Filippi MD,
Lizasoain I, Ruiz-Cabello J, Zarbock A, Moro MA,
Hidalgo A. Neutrophils scan for activated platelets to
– 99 –
AREA 3
ADVANCED THERAPIES AND
INDIVIDUALIZED MEDICINE
Line 3.1
Prognostic and predictor markers in autoimmune diseases.
Line 3.2
Esophagogastrointestinal inflammatory diseases.
Line 3.3
Progenitors and cell therapy.
Line 3.4
Advanced therapies in oncohematology.
Line 3.5
Biological, cellular and molecular monitoring in oncohematology.
Line 3.6
New diagnostic and therapeutic advances in cardiovascular diseases.
Line 3.7
New therapies in infectious pathologies.
Line 3.8
Individualized medicine in solid tumors.
– 101 –
AREA 3
– 102 –
AREA 3
GROUP 36
HEAD OF LABORATORY
GROUP MEMBERS
• José María Álvaro-Gracia Álvaro
• Santos Castañeda Sanz
• Vanessa Centeno Talayero
• Belén Díaz Sánchez
• Carlos Gamallo Amat
• Rosario García de Vicuña Pinedo
• Jesús Alberto García Vadillo
• María de las Nieves Gómez León
• Amalia Lamana Domínguez
• Ana María Ortiz García
• Esther Patiño Ruiz
• Eva Gloria Tomero Muriel
• Teresa Velasco Ripoll
RESEARCH INTEREST
The main goal for our group is personalized medicine
in the field of autoimmune/inflammatory rheumatic disorders (mainly rheumatoid arthritis, spondyloarthritis,
systemic lupus erythematous, giant cell arteritis and
scleroderma). Our efforts are focused on providing
new knowledge about two unmet needs for rheumatologists: severity biomarkers and predictors of
response to biological therapy. For the last five years,
to achieve these objectives, we have consolidated our
collaborations both at a local level in our Institute and
at national level.
Regarding the first, in 2013 we were involved in the
development of BioIMID project that was granted by
the PIE program (Integrated Projects for Excellence at
Health Research Institutes) from the Instituto de Salud
Carlos III (ISCIII). This is a project that intends to deepen in personalized medicine in the field of biological
therapies for immune mediated inflammatory diseases. BioIMID involves 8 groups of our Institute coordinated by Dr Monica Marazuela and the Biological
Therapies Unit, directed by Dr Alvaro-Gracia, plays a
key role in this project.
On the other hand, we maintain an intense collaborative effort with groups of the Network of Inflammation
and Rheumatic Diseases (RIER) that belongs to the
RETICS program from the ISCIII. Our research is mainly focused on the detection of prognostic and cardiovascular risk factor in rheumatoid arthritis, as well as
the study of security aspects in biological therapies.
However, many other rheumatologic diseases such as
scleroderma, systemic lupus erythematosus, systemic
vasculitis, osteoporosis, osteoarthritis, are objectives
of the research work conducted by our researchers.
As a result of the intense activity of the group, some of
its members have been called to participate in several
documents to establish consensus guidelines for the
rational use of biological therapies or imaging techniques in which the establishment of proper cost/benefit ratio is of great importance in the current economic situation. In addition, members of the group have
developed two patents.
For the next years, our efforts continue to focus on discovering new biomarkers allowing us to treat patients
more efficiently. The main objective is to find applications for the findings protected by our patents and
– 103 –
AREA 3AREA 2 AREA 1
Line 3.1
Prognostic and
predictor markers in
autoimmune diseases
Advanced therapies and individualized medicine
transfer them to the industry. Thus, we could offer to
the society some tools that may help to establish more
efficient therapeutic schedules for the diseases of our
interest.
MAJOR GRANTS
• González Álvaro, Isidoro. Immunoregulatory molecules as biomarkers predicting response to biological
therapies and disease severity in immune-mediated
inflamatory
disorders.
BIOMID
PROJECT.
• García Vadillo, Jesús Alberto. El TBS en mujeres
postmenopáusicas con fractura de antebrazo por
traumatismo de baja energía. SEIOMM. 2014-2015.
• Castañeda Sanz, Santos. Observar (observancia al
tratamiento con FAMES en artritis reumatoide).
Laboratorio ROCHE. 2014-2015.
• Tomero Muriel, Eva Gloria. Relesser-pro. Registro
prospectivo español de pacientes con lupus eritematoso sistémico. SER. 2014-2019.
• González Álvaro, Isidoro. Red de investigación en
inflamación y enfermedades reumáticas. ISCIII.
RD12/0009/0017. 2013-2016.
• García Vadillo, Jesús Alberto. Proyecto Sjöngreser:
registro de pacientes con síndrome de Sjörgren primario. SER y FER. 2013-2014.
• Castañeda Sanz, Santos. Valor predictivo de la
variación mineral ósea cortical en manos determinada mediante densitometría dual como marcador
pronostico en pacientes con artritis de inicio. ISCIII.
PI12/01578. 2013-2015.
• Castañeda Sanz, Santos. Estrategias en el
tratamiento de la osteoporosis. Proyecto estratos.
Lilly. 2013-2014.
• Castañeda Sanz, Santos. Estudio de marcadores de
respuesta en artritis psosiásica. Proyecto
INNPACTO. 2013-2014.
• González Álvaro, Isidoro. Factores genéticos asociados a niveles elevados de interleuquina 15 en sangre
de pacientes con artritis reumatoide. Papel modulador de cd69 en la gravedad de esta enfermedad.
– 104 –
ISCIII. PI11/00551. 2012-2014.
• Gómez León, María de las Nieves. Evaluación de la
técnica TC multidetector 64 frente a la PET/CT en el
estudio clínico de pacientes con linfoma y su estudio
de coste-efectividad: estudio multicéntrico.
ISCIII.PI11/01800. 2012-2014.
• González Álvaro, Isidoro. Factores genéticos asociados a niveles elevados de Il-15 en sangre de
pacientes con artritis reumatoide. Estudio preliminar
para el desarrollo de un kit marcador de mal pronóstico. UCB PHARMA. 2011• García de Vicuña Pinedo, Rosario. Análisis prospectivo de los factores predictivos de evolución clínica
desfavorable en una corte multicéntrica española de
pacientes con lupus eritematoso sistémico.
PI11/02857. ISCIII. 2012-2014.
• García de Vicuña Pinedo, Rosario. Determinación de
los niveles séricos de interleuquina 6 como posible
marcador de gravedad en pacientes con artritis de
reciente comienzo. Instituto Roche. 2012-.
• Ortiz García, Ana María. Estudio de los niveles de
expresión de VIP y sus receptores en pacientes con
artritis de reciente comienzo. Determinación de su
potencial como biomarcador pronostico. ISCIII.
PI11/00505. 2012-2014.
• Ortiz García, Ana María. Factores genéticos asociados a niveles elevados de Il15 en sangre de
pacientes con artritis reumatoide. Estudio preliminar
para el desarrollo de un kit marcador de mal pronóstico. UCB. 2012-2014.
• García de Vicuña Pinedo, Rosario. Proyecto
CARMA: estudio sobre el riesgo cardiovascular (CV)
en los pacientes con enfermedades reumáticas
inflamatorias crónicas. Fundación Española de
Reumatología con el patrocinio de Abbott
Laboratories. 2010-2021.
Granted 2014:
• González Álvaro, Isidoro. Desarrollo de un sistema de
apoyo a las decisiones basado en técnicas de
inteligencia artificial para el manejo rutinario de la
artritis reumatoide. PI14/00442. ISCIII. 2015-2017.
• Lamana Domínguez, Amalia. Estudio de la expresión
génica y mecanismos de regulación de VIP y sus
receptores en artritis de reciente comienzo.
AREA 3
PUBLICATIONS (33)
Roman-Blas JA, Castañeda S, Largo R, Lems WF,
Herrero-Beaumont G. An OA phenotype may obtain
major benefit from bone-acting agents. Semin Arthritis
Rheum. 43(4):421-8. 2014. PMID: 24016748. IF:
3,629. DOI: 10.1016/j.semarthrit.2013.07.012.
http://dx.doi.org/10.1016/j.semarthrit.2013.07.012
Márquez A, Solans R, Hernández-Rodríguez J, Cid
MC, Castañeda S, Ramentol M, Morado IC,
Rodriguez-Rodriguez L, Narváez J, Gómez-Vaquero C,
Miranda-Filloy JA, Martínez-Taboada VM, Ríos R,
Sopeña B, Monfort J, García-Villanueva MJ, MartínezZapico A, Marí-Alfonso B, Sánchez-Martín J,
Unzurrunzaga A, Raya E, de Miguel E, Hidalgo-Conde
A, Blanco R, González-Gay MÁ, Martín J; Spanish
GCA Consortium. Analysis of two autoimmunity genes,
IRAK1 and MECP2, in giant cell arteritis. Clin Exp
Rheumatol. 32(3 Suppl 82):S30-3. 2014. PMID:
24709033. IF: 2,973
Gónzalez-Álvaro I, Ortiz AM, Seoane IV, García-Vicuña
R, Martínez C, Gomáriz RP. Biomarkers predicting a
need for intensive treatment in patients with early arthritis. Curr Pharm Des. 21(2):170-81. 2014. PMID:
25163741. IF: 3,288
Márquez A, Solans R, Hernández-Rodríguez J, Cid
MC, Castañeda S, Ramentol M, Rodriguez-Rodriguez
L, Narváez J, Blanco R, Ortego-Centeno N; Spanish
GCA Consortium, Palm O, Diamantopoulos AP, Braun
N, Moosig F, Witte T, Beretta L, Lunardi C, Cimmino
MA, Vaglio A, Salvarani C, González-Gay MA, Martín J.
A. Candidate Gene Approach Identifies an IL33
Genetic Variant as a Novel Genetic Risk Factor for
Giant Cell Arteritis. PLoS One. 9(11):e113476. 2014.
pone.0113476.
María A. Martín-Martínez, Santos Castañeda, Carlos
González-Juanatey, Javier Llorca, Federico DíazGonzalez, Miguel A. González-Gay. Cardiovascular risk
assessment in rheumatoid arthritis: What goals should
be achieved?. Seminars Arthritis Rheum. 44(1):1-8.
2014. IF: 3,629
Saketkoo LA, Mittoo S, Huscher D, Khanna D,
Dellaripa PF, Distler O, Flaherty KR, Frankel S, Oddis
CV, Denton CP, Fischer A, Kowal-Bielecka OM, LeSage
D, Merkel PA, Phillips K, Pittrow D, Swigris J, Antoniou
K, Baughman RP, Castelino FV, Christmann RB,
Christopher-Stine L, Collard HR, Cottin V, Danoff S,
Highland KB, Hummers L, Shah AA, Kim DS, Lynch
DA, Miller FW, Proudman SM, Richeldi L, Ryu JH,
Sandorfi N, Sarver C, Wells AU, Strand V, Matteson EL,
Brown KK, Seibold JR; CTD-ILD Special Interest Group
(Rosario García de Vicuña). Connective tissue disease
related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and
instruments for use in clinical trials. Thorax. 69(5):428436. 2014. PMID: 24368713. IF: 8,562. DOI:
10.1136/thoraxjnl-2013-204202.
http://dx.doi.org/10.1136/thoraxjnl-2013-204202
Ortiz-Sanjuán F, Blanco R, Calvo-Rio V, Narvaez J,
Rubio Romero E, Olivé A, Castañeda S, Gallego Flores
A, Hernández MV, Mata C, Ros Vilamajo I, Sifuentes
Giraldo WA, Caracuel MA, Freire M, Gómez Arango C,
Llobet J, Manrique Arija S, Marras C, Moll-Tuduri C,
Plasencia-Rodriguez C, Roselló R, Urruticoechea A,
Velloso-Feijoo ML, Del Blanco J, González-Vela MC,
Rueda-Gotor J, Pina T, Loricera J, González-Gay MA.
Efficacy of tocilizumab in conventional treatmentrefractory adult-onset Still's disease: multicenter retrospective open-label study of thirty-four patients.
Arthritis Rheumatol. 66(6):1659-65. 2014. PMID:
24515813. IF: 7,871. DOI: 10.1002/art.38398.
Conde-Jaldón M, Montes-Cano MA, García-Lozano
JR, Ortiz-Fernández L, Ortego-Centeno N, GonzálezLeón R, Espinosa G, Graña-Gil G, Sánchez-Bursón J,
González-Gay MA, Barnosi-Marín AC, Solans R, Fanlo
P, Carballeira MR, Camps T, Castañeda S, Martín J,
– 105 –
AREA 3AREA 2 AREA 1
Validación como marcador pronóstico. PI14/01236.
ISCIII. 2015-2017.
González-Escribano MF. Epistatic interaction of ERAP1
and HLA-B in Behçet disease: a replication study in the
Spanish population. PLoS One. 9(7):e102100. 2014.
pone.0102100.
Ortiz-Fernández L, Conde-Jaldón M, García-Lozano JR,
Montes-Cano MA, Ortego-Centeno N, Castillo-Palma
MJ, Espinosa G, Graña-Gil G, Sánchez-Bursón J,
González-Gay MA, Barnosi-Marín AC, Solans R, Fanlo P,
Rodríguez Carballeira M, Camps T, Castañeda S, Martín
J, González-Escribano MF. GIMAP and Behçet disease:
no association in the European population. Ann Rheum
Dis. 73(7):1433-4. 2014. PMID: 24625627. IF: 9,27.
DOI: 10.1136/annrheumdis-2013-205156.
http://dx.doi.org/10.1136/annrheumdis-2013-205156
Márquez A, Hernández-Rodríguez J, Cid MC, Solans
R, Castañeda S, Fernández-Contreras ME, Ramentol
M, Morado IC, Narváez J, Gómez-Vaquero C,
Martínez-Taboada VM, Ortego-Centeno N, Sopeña B,
Monfort J, García-Villanueva MJ, Caminal-Montero L,
de Miguel E, Blanco R; Spanish GCA Consortium,
Palm O, Molberg O, Latus J, Braun N, Moosig F, Witte
T, Beretta L, Santaniello A, Pazzola G, Boiardi L,
Salvarani C, González-Gay MA8, Martín J. Influence of
the IL17A locus in giant cell arteritis susceptibility. Ann
Rheum Dis. 73(9):1742-5. 2014. PMID: 24919468. IF:
9,27. DOI: 10.1136/annrheumdis-2014-205261.
García-Bermúdez M, López-Mejías R, Genre F,
Castañeda S, Llorca J, González-Juanatey C, Corrales
A, Ubilla B, Miranda-Filloy JA,Pina T, Gómez-Vaquero
C, Rodríguez-Rodríguez L, Fernández-Gutiérrez B,
Balsa A, Pascual-Salcedo D, López-Longo FJ, Carreira
P, Blanco R, Martín J, González-Gay MA. Interferon
regulatory factor 5 genetic variants are associated with
cardiovascular disease in patients with rheumatoid
arthritis. Arthritis Res Ther. 16(4):R146. 2014. PMID:
25011482. IF: 4,117.
DOI: http://dx.doi.org/10.1186/ar4608
López-Mejías R, Genre F, Corrales A, GonzálezJuanatey C, Ubilla B, Llorca J, Miranda-Filloy JA, Pina
– 106 –
T, Blanco R, Castañeda S, Martín J, González-Gay MA.
Investigation of a PON1 gene polymorphism (rs662
polymorphism) as predictor of subclinical atherosclerosis in patients with rheumatoid arthritis. Ann Rheum
Dis. 73(9):1749-50. 2014. PMID: 24833785. IF: 9,27.
DOI: 10.1136/annrheumdis-2014-205543.
Castañeda S, Roman-Blas JA, Cohen-Solal M, Largo
R, Herrero-Beaumont G. Is lecturing in Rheumatology
Satellite Symposia a male attribute?. Rheumatol Int.
34(2):287-8. 2014. PMID: 23588408. IF: 1,627. DOI:
10.1007/s00296-013-2747-7.
http://dx.doi.org/10.1007/s00296-013-2747-7
López-Mejías R, Genre F, García-Bermúdez M, Ubilla
B, Castañeda S, Llorca J, González-Juanatey C,
Corrales A, Miranda-Filloy JA, Pina T, Gómez-Vaquero
P, Blanco R, Martín J, González-Gay MA. Lack of association between ABO, PPAP2B, ADAMST7, PIK3CG,
and EDNRA and carotid intima-media thickness,
carotid plaques, and cardiovascular disease in patients
with rheumatoid arthritis. Mediators Inflamm.
2014;2014:756279. 2014. PMID: 24795506. IF: 2,417.
DOI: 10.1155/2014/756279.
http://dx.doi.org/10.1155/2014/756279
Ferreiro-Iglesias A, Calaza M, Pérez-Pampin E, López
Longo FJ, Marenco JL, Blanco FJ, Narvaez J, Navarro F,
Cañete JD, de la Serna AR, González-Álvaro I, HerreroBeaumont G, Pablos JL, Balsa A, Fernández-Gutiérrez
B, Cáliz R, Gómez-Reino JJ, González A. Lack of replication of interactions between polymorphisms in
rheumatoid arthritis susceptibility: case control study.
Arthritis Res Ther. 16(5):436. 2014. PMID: 25260880. IF:
4,117. DOI: 10.1186/s13075-014-0436-x.
http://dx.doi.org/10.1186/s13075-014-0436-x.
Castañeda S, Roman-Blas JA, Largo R, HerreroBeaumont G. Osteoarthritis: a progressive disease with
changing phenotypes. Rheumatology (Oxford). 53(1):13. 2014. PMID: 23878311. IF: 4,435. DOI:
10.1093/rheumatology/ket247.
http://dx.doi.org/10.1093/rheumatology/ket247
Genre F, López-Mejías R, García-Bermúdez M,
Castañeda S, González-Juanatey C, Llorca J, Corrales
A, Ubilla B, Miranda-Filloy JA, Pina T, Gómez-Vaquero
P, Blanco R, González-Álvaro I, Martín J, González-Gay
MA. Osteoprotegerin CGA haplotype protection
against cerebrovascular complications in anti-CCP
negative patients with rheumatoid arthritis. PLoS One.
9(9):e106823. 2014. PMID: 25184828. IF: 3,534. DOI:
10.1371/journal.pone.0106823.
Saketkoo LA, Mittoo S, Frankel S, LeSage D, Sarver C,
Phillips K, Strand V, Matteson EL; OMERACT
Connective Tissue Disease–Interstitial Lung Diseases
Working Group; OMERACT Connective Tissue
Disease-Interstitial Lung Diseases Working Group
(Rosario García de Vicuña). Reconciling healthcare professional and patient perspectives in the development
of disease activity and response criteria in connective
tissue disease-related interstitial lung diseases. J
Rheumatol. 41(4):792-798. 2014. PMID: 24488412. IF:
3,173. DOI: 10.3899/jrheum.131251.
http://dx.doi.org/10.3899/jrheum.131251
Julià A, Rodríguez J, Fernández-Sueiro JL, Gratacós J,
Queiró R, Montilla C, Torre-Alonso JC, Pérez-Venegas
JJ, Manrique-Arija S, Muñoz-Fernández S, González
C, Roig D, Zarco P, Erra A, Castañeda S, García A,
Salvador G, Díaz-Torne C, Blanco R, Domínguez AW,
Mosquera JA, Vela P, Tornero J, Sánchez-Fernández S,
Corominas H, Ramírez J, Avila G, Alonso A, Tortosa R,
López-Lasanta M, Cañete JD, Marsal S. PDE3ASLCO1C1 locus is associated with response to antitumor necrosis factor therapy in psoriatic arthritis.
Pharmacogenomics. 15(14):1763-1769. 2014. PMID:
25493569. IF: 3,425
Martínez C, Ortiz AM, Juarranz Y, Lamana A, Seoane
IV, Leceta J, García-Vicuña R, Gomáriz RP, GonzálezÁlvaro I. Serum levels of vasoactive intestinal peptide
as a prognostic marker in early arthritis. PLoS One. 7 9
(1) e85248. 2014. PMID: 24409325. IF: 3,534. DOI:
10.1371/journal.pone.0085248.
Tomero E, Mulero J, de Miguel E, Fernández-Espartero
C, Gobbo M, Descalzo MA, Collantes-Estévez E, Zarco
P, Muñoz-Fernández S, Carmona L. Performance of
the Assessment of Spondyloarthritis International
Society criteria for the classification of spondyloarthritis
in early spondyloarthritis clinics participating in the
ESPERANZA programme. Rheumatology (Oxford).
53(2):353-60. 2014. PMID: 24196385. IF: 4,435. DOI:
10.1093/rheumatology/ket359.
http://dx.doi.org/10.1093/rheumatology/ket359
Martín-Martínez MA, González-Juanatey C, Castañeda
S, Llorca J, Ferraz-Amaro I, Fernández-Gutiérrez B,
Díaz-González F, González-Gay MA. Recommendations for the management of cardiovascular risk in
patients with rheumatoid arthritis: scientific evidence
and expert opinion. Semin Arthritis Rheum. 44(1):1-8.
2014. PMID: 24560170. IF: 3,629. DOI:
10.1016/j.semarthrit.2014.01.002.
http://dx.doi.org/10.1016/j.semarthrit.2014.01.002
Fernández-Nebro A, Marenco JL, López-Longo F,
Galindo M, Hernández-Cruz BE, Narváez J, RúaFigueroa I, Raya-Alvarez E, Zea A, Freire M, SánchezAtrio AI, García-Vicuña R, Pego-Reigosa JM,
Manrique-Arija S, Nieves-Martín L, Carreño L; LESIMAB GROUP (Dra Eva Tomero miembro de LESIMAB
GROUP). The effects of rituximab on the lipid profile of
patients with active systemic lupus erythematosus:
results from a nationwide cohort in Spain (LESIMAB).
Lupus. 23(10):1014-1022. 2014. PMID: 24833667. IF:
2,481. DOI: 10.1177/0961203314534909.
http://dx.doi.org/10.1177/0961203314534909
González-Gay MA, González-Juanatey C, Llorca J,
Castañeda S. The influence of inflammation in the
development of subclinical atherosclerosis in psoriatic
arthritis: comment on 'Cardiovascular comorbidities in
patients with psoriatic arthritis: a systematic review' by
Jamnistki et al. Ann Rheum Dis. 73(5):e27. 2014.
PMID: 24442882. IF: 9,27. DOI: 10.1136/
annrheumdis-2013-205154.
Gomáriz RP, González-Álvaro I. Thematic issue:
optimizing treatment in rheumatoid arthritis. Curr
– 107 –
AREA 3AREA 2 AREA 1
AREA 3
Pharm Des. 21(2):129. 2014. PMID: 25163733. IF:
3,288
Loricera J, Blanco R, Castañeda S, Humbría A, OrtegoCenteno N, Narváez J, Mata C, Melchor S, Aurrecoechea
E, Calvo-Alén J, Lluch P, Moll C, Mínguez M, HerreroBeaumont G, Bravo B, Rubio E, Freire M, Peiró E,
González-Vela C, Rueda-Gotor J, Pina T, Palmou-Fontana
N, Calvo-Río V, Ortiz-Sanjuán F, González-Gay MÁ.
Tocilizumab in refractory aortitis: study on 16 patients and
literature review. Clin Exp Rheumatol. 32(3 Suppl 82):S7989. 2014. PMID: 24854377. IF: 2,973
Naredo E, Uson J, Jiménez-Palop M, Martínez A, Vicente E,
Brito E, Rodríguez A, Cornejo FJ, Castañeda S, Martínez
MJ, Sanz J, Möller I, Batlle-Gualda E, Garrido J, Pascual E.
Ultrasound-detected musculoskeletal urate crystal deposition: which joints and what findings should be assessed for
diagnosing gout?. Ann Rheum Dis. 73(8):1522-8. 2014.
PMID: 23709244. IF: 9,27. DOI: 10.1136/annrheumdis2013-203487.
Pérez-García S, Carrión M, Jimeno R, Ortiz AM, GonzálezÁlvaro I, Fernández J, Gomáriz RP, Juarranz Y. Urokinase
plasminogen activator system in synovial fibroblasts from
osteoarthritis patients: modulation by inflammatory mediators and neuropeptides. J Mol Neurosci. 52(1):18-27. 2014.
PMID: 24318839. IF: 2,757. DOI: 10.1007/s12031-0130189-z.
http://dx.doi.org/10.1007/s12031-013-0189-z
Fernández-Espartero C, de Miguel E, Loza E, Tomero E,
Gobbo M, Descalzo MA, Collantes-Estévez E, Mulero J,
Muñoz-Fernández S, Zarco P, Carmona L; ESPERANZA
Study Group (Tomero, E). Validity of the Ankylosing
Spondylitis Disease Activity Score (ASDAS) in patients with
early spondyloarthritis from the Esperanza programme. Ann
Rheum Dis. 73(7):1350-5. 2014. PMID: 23709245. IF:
9,27. DOI: 10.1136/annrheumdis-2012-202976.
Carrión M, Juarranz Y, Seoane IV, Martínez C, GonzálezÁlvaro I, Pablos JL, Gutiérrez-Cañas I, Gomáriz RP. VIP
modulates IL-22R1 expression and prevents the contribution of rheumatoid synovial fibroblasts to IL-22-medi-
– 108 –
ated joint destruction. J Mol Neurosci. 52(1):10-17.
2014.
PMID:
24254222.
IF:
2,757.
DOI:
10.1007/s12031-013-0177-3.
http://dx.doi.org/10.1007/s12031-013-0177-3
Castañeda S, Gamallo- Amat C, Fraga J, García-García C,
Muñoz-Calleja C, García-Diez A, Urzainqui A. Development
of an autoimmune syndrome affecting the skin and internal
organs in P-Selectin Glycoprotein Ligand-1 deficient mice.
Arthritis and Rheumatology. 66(11):3178-89. 2014. PMID:
25132671. IF: 7,871. DOI: 10.1002/art.38808.
Campo LD, León NG, Palacios DC, Lagana C, Tagarro D.
Abdominal Complications Following Hematopoietic Stem
Cell Transplantation. RadioGraphics. 34(2):396-412. 2014.
PMID: 24617687. IF: 2,729. DOI: 10.1148/rg.342135046.
http://dx.doi.org/ 10.1148/rg.342135046
Concha-Garzón MJ, Solano-López G, García-García C,
García-Vicuña R, Daudén E. Lupus erythematosus induced
by terbinafine in a patient with systemic lupus erythematosus. Rev Clin Esp. 214(6):353-354. 2014. PMID:
24880185. IF: 1,314. DOI: 10.1016/j.rce. 2014.04.002.
BOOKS
Martín Millán M, Castañeda S. Sex hormones and related
compounds, including hormonal contraceptives. Side
Effects of Annual Drugs (SEDA) 36. 10040-SEDA36C
Rosario García de Vicuña y Eva Tomero Muriel. Amiloidosis
y otras enfermedades de depósito. Manual de enfermedades Reumáticas (6ª edición). Elsevier España, S.L.,
Barcelona. ISBN: 978-84-9022-903-3
S Castañeda, EF Vicente Rabaneda. Clínica, diagnóstico y
diagnóstico diferencial de la artrosis. Manual SER de
Diagnóstico de las Enfermedades Reumáticas
Autoinmunes Sistémicas. Elsevier España, S.L., Barcelona.
ISBN: 978-84-9022-857-9
AREA 3
CLINICAL TRIALS
PRINCIPAL RESEARCHER: CASTAÑEDA SANZ, SANTOS
Estudio multicéntrico del efecto metabólico y sobre biomarcadores de daño endotelial del tratamiento con tocilizumab
en pacientes con artritis reumatoide refractarios a terapia
convencional y que estén ya en tratamiento con este fármaco por indicación clínica. MIGUEL ANGEL GONZÁLEZ
GAY-MANTECON (IFIMAV) BIO-ANTI-IL6-2013-01/BIOANT-2013-01
PRINCIPAL RESEARCHER: CASTAÑEDA SANZ, SANTOS
Estudio aleatorizado, doble ciego, controlado con placebo,
de prueba de concepto sobre la eficacia del gevokizumab
en el tratamiento de pacientes con arteritis de células
gigantes; (Versión final: 18-07-13). LABORATORIOS
SERVIER, S.L. CL2-78989-012
EudraCT: 2013-002778-38
PRINCIPAL RESEARCHER: GARCÍA DE VICUÑA PINEDO, ROSARIO
Estudio no controlado para evaluar la eficacia de tocilizumab en pacientes con artritis reumatoide moderada o grave
y candidatos a monoterapia con un biológico; (Versión 1.0:
4-10-13). FUNDACION ESPAÑOLA DE REUMATOLOGIA
FER-TOC-2013-01
EudraCT: 2013-004051-20
Estudio de extensión fase 2, multicéntrico, y abierto (EEA)
en pacientes con artritis reumatoide que han completado el
estudio controlado y aleatorizado (ECA) en fase 2 con ABT494 precedente; (Versión 2: 30-09-13). ABBVIE INC M13538
EudraCT: 2013-003530-33
Estudio aleatorizado, doble ciego, controlado con placebo
en fase 2 para investigar la seguridad y la eficacia ABT-494
administrado con metotrexato (MTX) en pacientes con artritis reumatoide (AR) activa moderada o grave que han
tenido una respuesta insuficiente o que no han tolerado el
tratamiento biológico anti-TNF; (Versión amendment1: 1912-13). ABBVIE INC M13-550
EudraCT: 2013-002358-57
PRINCIPAL RESEARCHER: ORTIZ GARCÍA, ANA MARÍA
Ensayo clínico aleatorizado sobre la prevención de la progresión radiológica con ácido zoledrónico en pacientes con
artritis reumatoide de inicio y baja actividad de la enfermedad; (Versión 1.0: 15-12-13). H. U. DE BELLVITGE
(SERVICIO DE REUMATOLOGIA) CGV222
EudraCT: 2013-005001-31
PRINCIPAL RESEARCHER: ORTIZ GARCÍA, ANA MARÍA
Estudio sobre cumplimiento terapéutico en pacientes con
artritis reumatoide en tratamientos con fármacos biológicos
de administración subcutánea. Estudio ARCO; (Versión 1:
27-11-13). MERCK SHARP & DOHME DE ESPAÑA, S.A.
MSD-ART-2013-01
PRINCIPAL RESEARCHER: VICENTE RABANEDA,
ESTHER
Estudio ecográfico de inflamación subclínica articular en
pacientes con gota aguda HG ALICANTE, HGU GREGORIO MARAÑON, H. MOSTOLES. GOTA SUBCLINICA
GRUPO 37
HEAD OF LABORATORY
Esteban Daudén Tello
GROUP MEMBERS
• Maximiliano Aragüés Montañés
• María José Concha Garzón
• Diego de Argila Fernández-Durán
• Javier Fraga Fernández
• María Carmen García García
– 109 –
AREA 3AREA 2 AREA 1
Rosario García de Vicuña. Mononeuritis múltiple. Manual
SER de Diagnóstico de las Enfermedades Reumáticas
Autoinmunes Sistémicas. Elsevier España, S.L., Barcelona.
ISBN: 978-84-9022-857-9
•
•
•
•
María Jesús Gómez Gago
María del Mar Llamas Velasco
Javier Sánchez Pérez
Fátima Tudelilla Fernández
RESEARCH INTEREST
The investigation activity of the Group at present and
for the following 5 years is focused on:
1) Immune-mediated inflammatory diseases (IMID),
particularly psoriasis. The main lines of investigation
are: a) Immunoregulatory molecules as biomarkers
predicting response to biological therapies and disease severity in IMIDs. These are a group of diseases
that display inflammation as a major pathogenic
mechanism. Their long-term impact has been alleviated by the implementation of biological therapy.
Despite the growing knowledge on the etiopathogenesis of these diseases and the marked improvement
in their management represented by biologic therapy,
markers of the severity of the disease or to predict
whether patients will be refractory to treatment are
lacking. We are searching for new predictive biomarkers of IMID severity and responsiveness to biologics.
b) Gene Expression Profile in patients with moderateto-severe psoriasis. c) Epigenetic biomarkers as predictors of therapeutic response to biologic drugs in
psoriasis. d) Immunoregulatory molecules and their
therapeutical potential. We investigate the possible
role of GADD45, ICOSL, TSP-1, and galectins in the
immunopathogenesis of psoriasis, and the possibility
of finding new therapeutic targets for the treatment of
this disease. e) Survival analysis of conventional systemic therapies and biologics in psoriasis. f) Factors
associated with receiving biologics or classic systemic therapy for moderate to severe psoriasis. g)
Study of paradoxical psoriasiform reactions with
change of morphology induced by biologics in
patients with psoriasis. Determination of the prevalence, clinical and histopathological features, possible
trigger or associated factors. Assessment of the therapeutic management. h) Identification of CopyNumber Variants associated with the risk to develop
– 110 –
psoriasis and psoriatic arthritis using a genome-wide
analysis approach. i) Study of optimization strategies
(dose reduction, increase of the administration interval) in the treatment of moderate-to-severe psoriasis
with systemic agents.
2) Eczematous dermatitis. Study on the prevalence of
allergens as responsible of allergic contact dermatitis in
the Spanish population
3) Connective Tissue Diseases. Determination of the
association between myositis-specific autoantibodies
and myositis-associated autoantibodies with clinically
amyopathic dermatomyositis.
MAJOR GRANTS
• Daudén Tello, Esteban. Immunoregulatory molecules as biomarkers predicting response to biological therapies and disease severity in immunemediated inflamatory disorders. BIOMID PROJECT. PIE13/00041. ISCIII. 2014-2016.
• Daudén Tello, Esteban. INNPACTO. ESTUDIO DE
BIOMARCADORES EN PSORIASIS. 2013-2015.
• Daudén Tello, Esteban. El papel de GADD45alpha,
GADD45-beta
y
TSP-1
en
la
inmunopatogénesis de la psoriasis. JanssenDerma. 2013-.
Granted 2014
• Daudén Tello, Esteban. Identificación de
microRNAs como biomarcadores de gravedad y
respuesta al tratamiento en pacientes con psoriasis. PI14/01751. ISCIII. 2015-2017.
.
PUBLICATIONS (18)
Solano-López G, De Argila D, Fraga J, Daudén E.
Actinic lichen nitidus in a Caucasian European patient.
J Eur Acad Dermatol Venereol. 28(10):1403-4. 2014.
PMID: 24393535. IF: 3,105. DOI: 10.1111/jdv.12356.
http://dx.doi.org/10.1111/jdv.12356
Llamas-Velasco M, Requena L, Podda M,
Weidenthaler-Barth B, Rütten A. Apocrine intraductal
carcinoma in situ in nevus sebaceus: two case reports.
J Cutan Pathol. 41(12):944-9. 2014. PMID: 25302933.
IF: 1,56. DOI: 10.1111/cup.12394.
http://dx.doi.org/10.1111/cup.12394
use of the fixed combination calcipotriol and
betamethasone dipropionate gel for the topical treatment of psoriasis. J Eur Acad Dermatol Venereol. 28
Suppl 2:22-32. 2014. PMID: 24684740. IF: 3,105. DOI:
10.1111/jdv.12443.
Carrascosa JM, Vilavella M, Garcia-Doval I, Carretero
G, Vanaclocha F, Daudén E, Gómez-García FJ,
Herrera-Ceballos E, De la Cueva Dobao P, Belinchón I,
Sánchez-Carazo JL, Alsina M, López-Estebaranz JL,
Ferrán M, Peral F, Torrado R, Rivera R, Jiménez-Puya
R, Mendiola MV, Ferrándiz C. Body mass index in
patients with moderate-to-severe psoriasis in Spain
and its impact as an independent risk factor for therapy withdrawal: results of the Biobadaderm Registry. J
Eur Acad Dermatol Venereol. 28(7):907-2014. PMID:
23848131. IF: 3,105. DOI: 10.1111/jdv.12208.
http://dx.doi.org/ 10.1111/jdv.12208
Llamas-Velasco M, Requena L, Kutzner H, Schärer
L, Rütten A, Hantschke M, Paredes BE, Mentzel T.
Fumarate hydratase immunohistochemical staining
may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and
hereditary leiomyomatosis and renal cell cancer
(HLRCC) syndrome. J Cutan Pathol. 41(11):859-65.
2014. PMID: 25292446. IF: 1,56. DOI: 10.1111/
cup.12396.
García-Martín P, Fraga J, Hashimoto T, García-Diez A.
Brunsting-perry type cicatricial pemphigoid with IgG
autoantibodies to LAD-1. Br J Dermatol. 170(3):743-5.
2014. PMID: 24124894. IF: 4,1. DOI: 10.1111/bjd.12677.
http://dx.doi.org/10.1111/bjd.12677
Llamas-Velasco M, Solano-López Morel GE, GruberWackernagel A, Concha-Garzón MJ, Requena L,
Cerroni L. Comedonal graft-vs-host disease: a distinct
clinical expression of a lichenoid follicular GVHD. J
Cutan Pathol. 41(11):853-8. 2014. PMID: 25264218.
IF: 1,56. DOI: 10.1111/cup.12391.
Torre-Alonso JC, Gratacós J, Rey-Rey JS, Valdazo de
Diego JP, Urriticoechea-Arana A, Daudén E, Moreno
M, Zarco-Montejo P, Collantes-Estévez E, FernándezLópez JA. Development and validation of a new instrument to measure health-related quality of life in patients
with psoriatic arthritis: the VITACORA-19. J Rheumatol.
41(10):2008-17. 2014. PMID: 25179846. IF: 3,173.
DOI: 10.3899/jrheum.131021.
http://dx.doi.org/10.3899/jrheum.131021
Daudén E, Bewley A, Lambert J, Girolomoni G,
Cambazard F, Reich K. Expert recommendations: the
Llamas-Velasco M, Pérez-Gónzalez YC, Requena L,
Kutzner H. Histopathologic clues for the diagnosis of
Wiesner nevus. J Am Acad Dermatol. 70(3):549-54.
2014. PMID: 24373783. IF: 5,004. DOI:
10.1016/j.jaad.2013.10.032.
http://dx.doi.org/10.1016/j.jaad.2013.10.032
Llamas-Velasco M, Fraga J, Kutzner H, Steegmann JL,
García-Diez A, Requena L. Hypopigmented macules
secondary to imatinib for the treatment of chronic
myeloid leukemia: a histopathologic and immunohistochemical studyleukemia: a histopathologic and
immunohistochemical study. J Cutan Pathol.
41(5):417-426. 2014. PMID: 24467724. IF: 1,56. DOI:
10.1111/cup.12298.
Sánchez-Moya AI, Daudén E. Isoniazid therapy for
latent tuberculosis in psoriasis patients receiving biological agents: is it safe and efficacious?. Int J
Dermatol. 53 (3) e211–e212. 2014. PMID: 23786208.
IF: 1,227. DOI: 10.1111/ijd.12127.
http://dx.doi.org/ 10.1111/ijd.12127
Concha-Garzón MJ, Solano-López G, García-García C,
García-Vicuña R, Daudén E. Lupus erythematosus induced
by terbinafine in a patient with systemic lupus erythematosus. Rev Clin Esp. 214(6):353-354. 2014. PMID:
– 111 –
AREA 3AREA 2 AREA 1
AREA 3
24880185. IF: 1,314. DOI: 10.1016/j.rce. 2014.04.002.
Llamas-Velasco M, Fraga J, Solano-López GE, Steegmann
JL, García Diez A, Requena L. Multiple eruptive dermatofibromas related to imatinib treatment. J Eur Acad Dermatol
Venereol. 28(7):979-981. 2014. PMID: 24321053. IF:
3,105. DOI:
Augustin M, Blome C, Costanzo A, Daudén E, Ferrandiz C,
Girolomoni G, Gniadecki R, Iversen L, Menter A, MichaelisWittern K, Morita A, Nakagawa H, Reich K. Nail
Assessment in Psoriasis and Psoriatic Arthritis (NAPPA):
Development and Validation of a Tool for Assessment of
Nail Psoriasis Outcomes. Br J Dermatol. 170(3):591-8.
2014. PMID: 24117393. IF: 4,1. DOI: 10.1111/bjd.12664.
http://dx.doi.org/10.1111/bjd.12664
Navarro R, Concha-Garzón MJ, Castaño C, Casal C, Guiu
A, Daudén E. Outcome of patients with serology suggestive
of past hepatitis B virus infection during antitumor necrosis
factor therapy for psoriasis. Int J Dermatol. 53(7):909-11.
2014. PMID: 24673290. IF: 1,227. DOI: 10.1111/ijd.12313.
http://dx.doi.org/10.1111/ijd.12313
Concha-Garzón MJ, Solano-López Morel G, Pérez-Plaza
A, de Argila D. Pyoderma gangrenosum following a hip surgical procedure. Rev Clin Esp. 214(5):283-284. 2014.
PMID:
24698002.
IF:
1,314.
DOI:
10.1016/j.rce.2014.02.008
Llamas-Velasco M, Sanchez-Perez J, Fraga J, Garcia-Diez
A. Reply: Macular lymphocytic arteritis. J Cutan Pathol.
41(5):481. 2014. PMID: 24606034. IF: 1,56. DOI:
10.1111/cup.12307.
Reich K, Daudén E. Treatment adherence: a hurdle for reallife effectiveness in psoriasis?. J Eur Acad Dermatol
Venereol. 28 Suppl 2:1-3. 2014. PMID: 24684737. IF:
3,105. DOI: 10.1111/jdv.12442.
http://dx.doi.org/ 10.1111/jdv.12442
– 112 –
CLINICAL TRIALS
PRINCIPAL RESEARCHER: DAUDÉN TELLO, ESTEBAN
Estudio multicéntrico, aleatorizado, doble ciego de 52
semanas de seguimiento de secukinumab subcutáneo
para demostrar la eficacia evaluada mediante el Índice de
Severidad y Área de la psoriasis a las 16 semanas de
tratamiento comparado con ustekinumab y para evaluar
la seguridad, tolerabilidad y eficacia a largo plazo en
pacientes con psoriasis en placas de moderada a grave;
(Versión 00: 21-10-13). NOVARTIS FARMACEUTICA,
S.A. CAIN457A2317
EudraCT: 2013-003434-32
PRINCIPAL RESEARCHER: DAUDÉN TELLO, ESTEBAN
Estudio multicéntrico de fase 3, aleatorizado, doble
ciego, controlado con placebo y fármaco activo, para
evaluar la eficacia y la seguridad de guselkumab en el
tratamiento de pacientes con psoriasis en placa de
moderada a grave en los que se retira y reinicia el
tratamiento de forma aleatoria; (Versión A0: 10-07-14).
JANSSEN-CILAG INTERNATIONAL NV CNTO
1959PSO3002
EudraCT: 2014-000720-18
PRINCIPAL RESEARCHER: DELGADO JIMENEZ,
YOLANDA
Estudio de registro de enfermedades de tipo observacional, multicéntrico para evaluar las tendencias y resultados en la práctica clínica habitual en pacientes adultos
con hidradenitis supurativa: UNITE; (Versión cambio
administrativo 1: 08-11-13). ABBVIE INC H13-147/ABBANT-2014-01
PRINCIPAL RESEARCHER: SANCHEZ PÉREZ, ABILIO
JAVIER
Estudio aleatorizado, en doble ciego y controlado con
placebo, para demostrar la eficacia y la seguridad a largo
plazo de dupilumab en pacientes adultos con dermatitis
atópica de grado moderado a severo; (Versi¢n1.0: 1112-13). REGENERON PHARMACEUTICALS, INC.
R668-AD-1224
EudraCT: 2013-003254-24
AREA 3
GRUPO 38
HEAD OF LABORATORY
GROUP MEMBERS
• María José Beceiro Pedreño
• María José Casanova González
• María Chaparro Sánchez
• Almudena Durán Vegue
• Alicia Marín Gómez
• José Maté Jiménez
• Adrián Gerald Mcnicholl
• Pablo Muñoz Linares
• Mercedes Ramas López
• Cecilio Santander Vaquero
RESEARCH INTEREST
Our Group leads a CIBERehd (Networked
Biomedical Research Centre on Hepatic and
Digestive Diseases) research team focused on the
understanding and management of Helicobacter
pylori infection and Inflammatory Bowel Diseases
(IBD). Different projects have been developed in
collaboration with several services of La Princesa
Hospital, research institutions and universities, and
a network of digestive diseases services throughout Spain.
In 2014 the group has continued its focus in
European and international contexts:
• Coordinates the ‘Pan-European Registry on H.
pylori infection management’ in which 300 gastroenterologists from 30 European countries participate, making it the largest study on an infectious agent.
• The United European Gastroenterology has
granted this team a long-term educational aiming
to improve the knowledge and implementation of
the European Consensus on H. pylori infection in
9 European countries.
Our group’s strategic plan for the next five years will
be framed under three key elements: Collaboration,
Internationalization, and “Bench to bedside” translation.
The European Registry has made an open call for
collaboration that will increase our network of collaboration, both nationally and internationally. We
have promoted a stable strategic consortium in
IBD, between the Spanish Society of IBD (GETECCU), the Biomedical Research Network (CIBER)
and the Spanish Network of Clinical Trial Units.
This agreement has created a central scientific
unit, supervised by our team, to coordinate, sponsor and monitor investigator driven clinical
research on IBD. Our group has also promoted
and is directing the consortium created between
the Spanish Society of Gastroenterology (AEG)
and the REDCap platform that will provide a free
and potent online system for Data Capture, surveys and coordination of multicentre digestive diseases projects.
The group has been selected by the European
Helicobacter Study Group to coordinate an international project on microbiota alterations related to H.
pylori infection and its eradication treatment.
In order to increase Translational Research, we
have reached agreements with different basic
research groups (Microbiology Service, Molecular
Biology, etc.) for long-term synergistic collaboration, and a new Researcher has been incorporated
to coordinate our basic research with accredited
expertise on translational science on digestive
immunological response, genetics and microbiota.
– 113 –
AREA 3AREA 2 AREA 1
Line 3.2
Esophagogastrointestinal
inflammatory diseases
MAJOR GRANTS
PUBLICATIONS (34)
• Pérez Gisbert, Javier. Immunoregulatory molecules
as biomarkers predicting response to biological
therapies and disease severity in immune-mediated inflamatory disorders. BIOMID PROJECT.
PIE13/00041. ISCIII. 2014-2016.
• Pérez Gisbert, Javier. Cátedra de patrocinio de
investigación en enfermedad inflamatoria intestinal
ABBVIE – UAM. Departamento de Medicina de la
Universidad Autónoma de Madrid. 2014-2016.
• Pérez Gisbert, Javier. Optimal h. Pylori management in primary care. United European
Gastroenterology (UEG) (Long-term Projects).
2013-2015.
• Pérez Gisbert, Francisco Javier. Asesoramiento en
la realización de protocolos y procedimientos de
investigación del área de enfermedades inflamatorias esofago-gastro-intestinales y análisis de resultados. CASEN FLEET. 2013-2014.
• Pérez Gisbert, Javier. European registry on the
management of helicobacter pylori infection.
European Helicobacter Study Group. 2013-2015.
• Pérez Gisbert, Francisco Javier. ENSAYO CLINICO
COMVIB. CAIBER. 2013-2014.
• María Chaparro Sánchez. Desarrollo de un método
basado en ELISA para la medición de los niveles
séricos de anti-TNFy anticuerpos contra el fármaco. PRE-PREDICROHN. PI 618. MSD. 2013-2015.
• Chaparro Sánchez, María. Predicción de respuesta
a corto y largo plazo al tratamiento con fármacos
anti-tnf en pacientes con enfermedad de Crohn.
ESTUDIO PREDICROHN. ISCIII. PI12/02557.
2012-2015
• Gerald McNicholl, Adrián. Detección de h. Pylori
mediante RT-PCR e inmunohistoquímica en el
paciente con linfoma MALT gástrico h. Pylori negativo por métodos convencionales (estudio multicéntrico nacional). Asociación Española de
Gastroenterología. 2009-2014.
A Julià, E Domènech, M Chaparro, V García-Sánchez,
F Gomollón, J Panés, M Mañosa, M Barreiro-de
Acosta, A Gutiérrez, E Garcia-Planella, M Aguas, F
Muñoz, M Esteve, JL Mendoza, M Vera, L Márquez, R
Tortosa, M López-Lasanta, A Alonso, JLluís Gelpí, AC
García-Montero, J Bertanpetit, D Absher, R Myers, JP
Gisbert, S Marsal. A genome-wide association study
identifies a novel locus at 6q22.1 associated with
ulcerative colitis. Hum Mol Genet. 23(25):6927-34.
2014. PMID: 25082827. IF: 6,677. DOI:
10.1093/hmg/ddu398.
http://dx.doi.org/10.1093/hmg/ddu398
Granted 2014
• Bernardo Ordiz, David. Compartimentalización de
las células dendríticas intestinales humanas en
enfermedad de Crohn. SAF2014-56642-JIN.
MINECO. 2015-2017.
– 114 –
McNicholl AG, Forné M, Barrio J, De la Coba C,
González B, Rivera R, Esteve M, Fernandez-Bañares
F, Madrigal B, Gras-Miralles B, Perez-Aisa A, Viver-PiSunyer JM, Bory F, Rosinach M, Loras C, Esteban C,
Santolaria S, Gomollon F, Valle J, Gisbert JP;
Helicobacter pylori Study Group of Asociación
Española de Gastroenterología (AEG). Accuracy of
GastroPanel for the diagnosis of atrophic gastritis. Eur
J Gastroenterol Hepatol. 26(9):941-948. 2014. PMID:
25014624. IF: 2,152. DOI: 10.1097/MEG.
0000000000000132.
http://dx.doi.org/10.1097/MEG.0000000000000132
Linares PM, Chaparro M, Gisbert JP. Angiopoietins in
inflammation and their implication in the development
of inflammatory bowel disease. A review. J Crohns
Colitis. 8(3):183-190. 2014. PMID: 23859759. IF:
3,562. DOI: 1016/j.crohns.2013.06.013.
http://dx.doi.org/1016/j.crohns.2013.06.013
Miehlke S, Madisch A, Kupcinskas L, Petrauskas
D, Böhm G, Marks HJ, Neumeyer M, Nathan T,
Fernández-Bañares F, Greinwald R, Mohrbacher R,
Vieth M, Bonderup OK; BUC-60/COC Study
Group. Colaborador Gisbert JP. Budesonide is
more effective than mesalamine or placebo in
short-term treatment of collagenous colitis.
Gastroenterology. 146(5):1222-30.e1-2. 2014.
PMID: 24440672. IF: 13,926. DOI: 10.1053/j.gastro.2014.01.019.
http://dx.doi.org/10.1053/j.gastro.2014.01.019
AREA 3
Calvet X, Panés J, Alfaro N, Hinojosa J, Sicilia B,
Gallego M, Pérez I, Lázaro y de Mercado P, Gomollón
F; Members of Consensus Group, Aldeguera X, Alós
R, Andreu M, Barreiro M, Bermejo F, Casis B,
Domenech E, Espín E, Esteve M, García-Sánchez V,
López-Sanromán A, Martínez-Montiel P, Luis Mendoza
J, Gisbert JP, Vera M, Dosal A, Sánchez E, Marín L,
Sanromán L, Pinilla P, Murciano F, Torrejón A, Ramón
García J, Ortega M, Roldán J. Delphi consensus statement: Quality Indicators for Inflammatory Bowel
Disease Comprehensive Care Units. J Crohns Colitis.
8(3):240-251. 2014. PMID: 24295646. IF: 3,562. DOI:
10.1016/j.crohns.2013.
http://dx.doi.org/10.1016/j.crohns.2013
Vergara M, Bennett C, Calvet X, Gisbert JP.
Epinephrine injection versus epinephrine injection and
a second endoscopic method in high-risk bleeding
ulcers. Cochrane Database Syst Rev. 10:CD005584.
2014. PMID: 25308912. IF: 5,939. DOI:
10.1002/14651858.CD005584.pub3.
http://dx.doi.org/10.1002/14651858.CD005584.pub3
M. Andreu, L. Marquez, E. Domènech, J.P. Gisbert, V.
García, I. Marín, M. Peñalva, F. Gomollón, X. Calvet, O.
Merino, E. García-Planella, N. Vazquez-Romero, M.
Esteve, P. Nos, A. Gutierrez, I. Vera, JL. Cabriada, MD.
Martín, N. Vázquez, J Panés on behalf of Spanish
GETECCU grupo ENEIDA project. Disease severity in
familial cases of Inflammatory Bowel Disease. J Crohn
Colitis. 8(3):234-9. 2014. PMID: 24016462. IF: 3,562.
DOI: 10.1016/j.crohns.2013.08.010.
http://dx.doi.org/10.1016/j.crohns.2013.08.010
C. Loras, J.P. Gisbert, M.C. Saro, M. Piqueras, C.
Sánchez-Montes, J. Barrio, I. Ordás, A. Montserrat, R.
Ferreiro, Y. Zabana, M. Chaparro, F. FernándezBañares, M. Esteve, for the REPENTINA study, GETECCU group (GROUP Español de Enfermedades de Crohn
y Colitis Ulcerosa). Impact of surveillance of hepatitis b
and hepatitis c in patients with inflammatory bowel disease under anti-TNF therapies: Multicenter prospective
observational study REPENTINA 3. J Crohns Colitis.
8(11):1529-38. 2014. PMID: 25052345. IF: 3,562. DOI:
10.1016/j.crohns.2014. 06.009.
http://dx.doi.org/10.1016/j.crohns.2014.06.009.
Bujanda L, Sarasqueta C, Lanas Á, Quintero E,
Cubiella J, Hernandez V, Morillas JD, Perez-Fernández
T, Salas D, Andreu M, Carballo F, Bessa X, Portillo I,
Jover R, Balaguer F, Cosme A, Castells A; COLONPREV study investigators (Chaparro M, Gisbert JP,
Santancer C). Effect of oral anticoagulants on the outcome of faecal immunochemical test. Br J Cancer.
110(5):1334-7. 2014. PMID: 24496455. IF: 4,817.
DOI: 10.1038/bjc.2014.38.
http://dx.doi.org/10.1038/bjc.2014.38
Barreiro-de Acosta M, Gisbert JP. Letter: acute severe
ulcerative colitis - should all patients be treated equally?. Aliment Pharmacol Ther. 39(1):113. 2014. PMID:
24299325. IF: 5,478. DOI: 10.1111/apt.12537.
http://dx.doi.org/ 10.1111/apt.12537
Molina-Infante J, Gisbert JP. Letter: Bismuth quadruple therapy with Pylera for H. pylori infection. Aliment
Pharmacol Ther. 40(6):735-736. 2014. PMID:
25123391. IF: 5,478. DOI: 10.1111/apt.12876.
http://dx.doi.org/10.1111/apt.12876
Molina-Infante J, Dellon ES, Gisbert JP. Letter: distinguishing PPI-responsive oesophageal eosinophilia
from eosinophilic oesophagitis - still a long way to go.
Aliment Pharmacol Ther. 39(10):1248-1249. 2014.
PMID: 24735150. IF: 5,478. DOI: 10.1111/apt.12711.
– 115 –
AREA 3AREA 2 AREA 1
Cano-Martínez D, Román ID, T Lobo MV, Pastor O,
Moreno-Villena I, Paradela A, Hernández-Breijo B,
Fernández-Moreno MD, Monserrat J, SanmartínSalinas P, Gisbert JP, Guijarro LG. Effect of Infliximab
in oxidised serum albumin levels during experimental
colitis. Biomarkers. 19(8):693-701. 2014. PMID:
25382460.
IF:
2,522.
DOI:
10.3109/1354750X.2014.982189.
http://dx.doi.org/10.3109/1354750X.2014.982189
Chaparro M, Gisbert JP. How safe is infliximab therapy during pregnancy and lactation in inflammatory
bowel disease?. Expert Opin Drug Saf. 13(12):174962. 2014. PMID: 25244582. IF: 2,735. DOI:
10.1517/14740338.2014.959489.
http://dx.doi.org/10.1517/14740338.2014.959489
Chaparro M, Gisbert JP. Letter: Limitations of studies to evaluate the significance of anti-tumour
necrosis factor serum levels in Crohn's disease.
Aliment Pharmacol Ther. 40(1):120-121. 2014.
PMID: 24903436. IF: 5,478. DOI: 10.1111/
apt.12799.
González Lama Y, Gisbert JP. Letter: metabolite monitoring for thiopurines in Crohn's disease - still not fully
understood. Aliment Pharmacol Ther. 39(6):642. 2014.
PMID: 24588251. IF: 5,478. DOI: 10.1111/apt.12632.
Fernández-Bañares, Gisbert JP. Letter: Persisting clinical symptoms in microscopic colitis in remission.
Aliment Pharmacol Ther. 40(1):117-118. 2014. PMID:
24903432. IF: 5,478. DOI: 10.1111/apt.12776.
Molina-Infante J, Gisbert JP. Letter: PPI-responsive
oesophageal eosinophilia--from initial scepticism to
consistent prospective data. Aliment Pharmacol Ther.
39(2):229-30. 2014. PMID: 24330241. IF: 5,478. DOI:
10.1111/apt.12548.
Barreiro-de-Acosta M, Gisbert JP. Letter: predictors of
severe disease in ulcerative colitis the same or different in Crohn's disease?. Aliment Pharmacol Ther.
40(9):1120-1121. 2014. PMID: 25280260. IF: 5,478.
DOI: 10.1111/apt.12916.
Barreiro-de Acosta M, Gisbert JP. Letter: psychological remission - a future endpoint in inflammatory bowel
disease?. Aliment Pharmacol Ther. 39(12):1436. 2014.
PMID: 24849160. IF: 5,478. DOI: 10.1111/apt.12766.
Molina-Infante J, Calvet X, Gisbert JP. Letter: the irony
of oral iron - not an underdog for post-gastrointestinal
bleeding anaemia. Aliment Pharmacol Ther. 39(5):550551. 2014. PMID: 24494851. IF: 5,478. DOI:
10.1111/apt.12617.
– 116 –
Guerra I, Chaparro M, Bermejo F, Gisbert JP.
Measurement of Anti-TNF Agents and anti-Drug
Antibodies Serum Levels in Patients with Inflammatory
Bowel Disease. Curr Drug Metab. 15(9): 875-881.
2014. PMID: 25373884. IF: 3,487
Molina-Infante J, Gisbert JP. Optimizing clarithromycin-containing therapy for Helicobacter pylori in
the era of antibiotic resistance. World J Gastroenterol.
20(30):10338-10347. 2014. PMID: 25132750. IF:
2,433. DOI: 10.3748/wjg.v20.i30.10338.
http://dx.doi.org/ 10.3748/wjg.v20.i30.10338
Cabré E, Mañosa M, García-Sánchez V, Gutiérrez A,
Ricart E, Esteve M, Guardiola J, Aguas M, Merino O,
Ponferrada A, Gisbert JP, Garcia-Planella E, Ceña G,
Cabriada JL, Montoro M, Domènech E; ENEIDA Project
of the Spanish Working Group in Crohn's Disease and
Ulcerative Colitis (GETECCU). Phenotypic concordance
in familial inflammatory bowel disease (IBD). Results of a
nationwide IBD Spanish database. J Crohns Colitis.
8(7):654-661. 2014. PMID: 24388046. IF: 3,562. DOI:
10.1016/j.crohns.2013. 12.005.
McNicholl AG, Marin AC, Molina-Infante J, Castro M,
Barrio J, Ducons J, Calvet X, de la Coba C, Montoro
M, Bory F, Perez-Aisa A, Forné M, Gisbert JP; On
behalf of the participant centres. Randomised clinical
trial comparing sequential and concomitant therapies
for Helicobacter pylori eradication in routine clinical
practice. Gut. 63(2):244-9. 2014. PMID: 23665990. IF:
13,319. DOI: 10.1136/gutjnl-2013-304820.
http://dx.doi.org/10.1136/gutjnl-2013-304820
Castells A, Quintero E, Álvarez C, Bujanda L, Cubiella
J, Salas D, Lanas A, Carballo F, Morillas JD,
Hernández C, Jover R, Hijona E, Portillo I, EnríquezNavascués JM, Hernández V, Martínez-Turnes A,
Menéndez-Villalva C, González-Mao C, Sala T, Ponce
M, Andrés M, Teruel G, Peris A, Sopeña F, GonzálezRubio F, Seoane-Urgorri A, Grau J, Serradesanferm A,
Pozo À, Pellisé M, Balaguer F, Ono A, Cruzado J,
Pérez-Riquelme F, Alonso-Abreu I, Carrillo-Palau M, de
la Vega-Prieto M, Iglesias R, Amador J, Blanco JM,
Sastre R, Ferrándiz J, González-Hernández MJ,
AREA 3
Bermejo F, Algaba A, Guerra I, Gisbert JP. Response
to letter: folate deficiency in Crohn's disease. Scand J
Gastroenterol.
49(2):255-256.
2014.
PMID:
24328943. IF: 2,329. DOI: 10.3109/00365521.
2013.869829.
http://dx.doi.org/10.3109/00365521.2013.869829
Cañas-Ventura A, Márquez L, Ricart E, Domènech E,
Gisbert JP, García-Sanchez V, Marín-Jiménez I,
Rodriguez-Moranta F, Gomollón F, Calvet X, Merino O,
Garcia-Planella E, Vázquez-Romero N, Esteve M,
Iborra M, Gutiérrez A, Vera M, Andreu M; Spanish
GETECCU group (ENEIDA project). Risk of colectomy
in patients with ulcerative colitis under thiopurine treatment. J Crohns Colitis. 8(10):1287-1293. 2014. PMID:
24726696. IF: 3,562. DOI: 10.1016/j.crohns.2014.
03.014.
Medrano LM, Taxonera C, Márquez A, Barreiro-de
Acosta M, Gómez-García M, González-Artacho C,
Pérez-Calle JL, Bermejo F, Lopez-Sanromán A, Martín
Arranz MD, Gisbert JP, Mendoza JL, Martín J, Urcelay
E, Núñez C. Role of TNFRSF1B polymorphisms in the
response of Crohn's disease patients to infliximab.
Hum Immunol. 75(1):71-5. 2014. PMID: 24121042. IF:
2,282. DOI: 10.1016/j.humimm.2013.09.017.
http://dx.doi.org/10.1016/j.humimm.2013.09.017
cancer in ulcerative colitis. Aliment Pharmacol Ther.
39(7):645-659. 2014. PMID: 24612141. IF: 5,478
Algaba A, Linares PM, Encarnación FernándezContreras M, Figuerola A, Calvet X, Guerra I, de Pousa I,
Chaparro M, Gisbert JP, Bermejo F. The effects of infliximab or adalimumab on vascular endothelial growth factor and angiopoietin 1 angiogenic factor levels in inflammatory bowel disease: serial observations in 37 patients.
Inflamm Bowel Dis. 20(4):695-702. 2014. PMID:
24562175.
IF:
5,475.
DOI:
10.1097/MIB.
0000000000000004.
http://dx.doi.org/10.1097/MIB.0000000000000004
Gisbert JP, Perez-Aisa A, Rodrigo L, Molina-Infante J,
Modolell I, Bermejo F, Castro-Fernández M, Antón R,
Sacristán B, Cosme A, Barrio J, Harb Y, GonzalezBarcenas M, Fernandez-Bermejo M, Algaba A, Marín
AC, McNicholl AG; On behalf of the H. pylori Study
Group of the Spanish Gastroenterology Association.
Third-Line Rescue Therapy with Bismuth-Containing
Quadruple Regimen After Failure of Two Treatments with
Clarithromycin and Levofloxacin for H. pylori Infection.
Dig Dis Sci. 59(2):383-9. 2014. PMID: 24126798. IF:
2,55. DOI: 10.1007/s10620-013-2900-x.
http://dx.doi.org/10.1007/s10620-013-2900-x
O'Connor A, Vaira D, Gisbert JP, O'Morain C.
Treatment of Helicobacter pylori Infection 2014.
Helicobacter. 19(1):38-45. 2014. PMID: 25167944. IF:
2,993. DOI: 10.1111/hel.12163.
http://dx.doi.org/10.1111/hel.12163
BOOKS
Gisbert JP, Chaparro M. Systematic review with metaanalysis: inflammatory bowel disease in the elderly.
Aliment Pharmacol Ther. 39(5):459-477. 2014. PMID:
24405149. IF: 5,478. DOI: 10.1111/apt.12616.
JP Gisbert, ER Greenberg, IARC Helicobacter pylori
working Group. Potential regimens for the mass
eradication of Helicobacter pylori infection.
International Agency for Research on Cancer (IARC
Working Group Reports, No. 8. ISBN: 978-92-8322454-9
Castaño-Milla C, Chaparro M, Gisbert JP. Systematic
review with meta-analysis: the declining risk of colorectal
M Chaparro, JP Gisbert. Dudas frecuentes sobre el
embarazo y la lactancia en pacientes con colitis
– 117 –
AREA 3AREA 2 AREA 1
Andreu M, Bessa X; COLONPREV Study Investigators
(Chaparro M, Gisbert JP, Santancer C). Rate of detection of advanced neoplasms in proximal colon by simulated sigmoidoscopy vs fecal immunochemical tests.
Clin Gastroenterol Hepatol. 12(10):1708-16.e4. 2014.
PMID:
24681078.
IF:
6,534.
DOI:
10.1016/j.cgh.2014.03.022.
http://dx.doi.org/10.1016/j.cgh.2014.03.022
ulcerosa. Todo sobre la Colitis Ulcerosa. Manual de
ayuda para el paciente. M Chaparro, S Gómez-Senent
Eds. ISBN: 978-84-695-8644-0
Javier Pérez Gisbert. Enfermedad por Reflujo
Gastroesofágico. AEGASTRUM. Asociación Española de
Gastroenterología (AEG). ISBN: 978-84-933345-8-1
M Chaparro, JP Gisbert. Aspectos relacionados con la fertilidad, el embarazo y la lactancia en los pacientes con enfermedad inflamatoria intestinal. Tratado de terapéutica en
Enfermedad Inflamatoria Intestinal. F Gomollón Eds. 2014
Nature Publishing Group I. ISBN: 978-84-940238-3-5
JP Gisbert. Ustekinumab. Tratado de terapéutica en
Enfermedad Inflamatoria Intestinal. En: F Gomollón Eds.
Nature Publishing Group I. ISBN: 978-84-940-238-3-5
JP Gisbert. Tioguanina. Tratado de terapéutica en
Enfermedad Inflamatoria Intestinal. F Gomollón Eds.
Nature Publishing Group I. ISBN: 978-84-940-238-3-5
JP Gisbert. Azatioprina. Tratado de terapéutica en
Enfermedad Inflamatoria Intestinal. F Gomollón Eds.
Nature Publishing Group I. ISBN: 978-84-940238-3-5
M Chaparro, JP Gisbert. Dudas frecuentes sobre el
embarazo y la lactancia en pacientes con enfermedad de
Crohn. Todo sobre la enfermedad de Crohn. Manual de
ayuda para el Paciente. M Chaparro, S Gómez-Senent
Eds. ISBN: 978-84-695-8644-0
JP Gisbert. The Contribution of Meta-Analyses to the
Treatment of Helicobacter pylori. Helicobacter pylori: A
Worldwide Perspective 2014. 280-315. Buzás György
Miklós (Ed.).ISBN: 978-60805-738-2-5
CLINICAL TRIALS
PRINCIPAL RESEARCHER: PÉREZ GISBERT,
FRANCISCO JAVIER
Estudio comparativo prospectivo multicéntrico
aleatorizado del tratamiento endoscópico de la
estenosis en la Enfermedad de Crohn: Prótesis
– 118 –
metálica autoexpandible vs dilatación con balón
(Versión 3: Marzo 2013). PRODILAT-3-2013
FRANCISCO JAVIER
Registro no intervencionista a largo plazo para evaluar la seguridad y la efectividad de HUMIRA® (adalimumab) en pacientes con colitis ulcerosa (CU) de
actividad moderada a grave; (Versión enmienda 1:
23-10-12). Estudio Legacy. ABBVIE DEUTSCHLAND
GMBH & CO. KG ABB-ADAEudraCT: 2013-01/P11-282
FRANCISCO JAVIER
Estudio observacional retrospectivo para describir
los patrones de tratamiento y la utilización de recursos sanitarios asociados a la terapia con los
inhibidores del factor de necrosis tumoral (TNF) en
pacientes con diagnóstico de Enfermedad de Crohn
(EC) o colitis ulcerosa (CU); (Versión 1: 17-02-14).
TAKEDA PHARMACEUTICALS INTERNATIONAL
INC. MLN0002-5001
FRANCISCO JAVIER
Estudio de fase III multicéntrico, doble ciego y controlado con placebo de la eficacia y seguridad de
etrolizumab durante la inducción y el mantenimiento
en pacientes con colitis ulcerosa activa de moderada a grave resistentes o intolerantes a los
inhibidores del FNT; (Versión 3: 11-03-14). ROCHE
FARMA, S.A. GA28950
EudraCT: 2013-004278-88
FRANCISCO JAVIER
Estudio postautorización, observacional y multicéntrico para confirmar que el almagato no interfiere en
el resultado del test del aliento para el diagnóstico
de infección por Helicobacter pylori; (Versión 2:242-14) ALMIRALL S.A. ALM-ALM-2014-01
FRANCISCO JAVIER
Evolución tras la suspensión del tratamiento anti-tnf
AREA 3
FRANCISCO JAVIER
Evaluación de la exactitud diagnostica de un método
de medición de los niveles séricos de anti-TNF y anticuerpos contra el fármaco para la predicción de actividad endoscópica en la enfermedad inflamatoria intestinal; (Versión 1.0: junio 2014). GIS-EDNA-ANTI-TNF
FRANCISCO JAVIER
Estudio comparativo y prospectivo en el que se
compara la exactitud de dos pruebas distintas de
antígenos en las heces (Premier Platinum HpSA
PLUS y el nuevo ImmunoCard STAT!HpSA HD) para
el diagnóstico de la infección por Helicobacter
pylori; (Versión 3.0: 30-06-14). MERIDIAN BIOSCIENCES INC ESTUDIO MERIDIAN/HP-STOOLAG
FRANCISCO JAVIER
Registro de pacientes con colitis colágena tratados
con azatioprina y/o mercaptopurina; (Versión abril
de 2014). AZA/MP CC-01-2014
FRANCISCO JAVIER
Prevalencia de desnutrición y características nutricionales de pacientes con enfermedad inflamatoria
intestinal; Versión 1: julio 2014. GIS-NUTRICIÓN2014
FRANCISCO JAVIER
Un estudio doble ciego, aleatorizado, multicéntrico
sobre una pauta posológica más alta de adalimumab en comparación con una pauta estándar para el
tratamiento de inducción y mantenimiento en
pacientes con colitis ulcerosa moderada o muy activa; (Versión enmienda 1: 02-06-14). ABBVIE
DEUTSCHLAND GMBH & CO. KG M14-033
EudraCT: 2013-001682-16
FRANCISCO JAVIER
Estudio de fase 2, aleatorizado, multicéntrico y controlado con placebo para investigar la eficacia y la
seguridad de aprmilast (CC-10004) para el
tratamiento de pacientes con colitis ulcerosa activa;
(Versión 1: 13-08-14). CELGENE CORPORATION
CC-10004-UC-001 2014-002981-64
– 119 –
AREA 3AREA 2 AREA 1
en pacientes con enfermedad inflamatoria intestinal;
(Versión junio 2014). JAVIER P. GISBERT (DIGESTIVO) GIS-2014-01-SUSPENSION
Line 3.3
Progenitors and
cell therapy
GRUPO 39
HEAD OF LABORATORY
Luis Madero López
GROUP MEMBERS
• Beatriz Aguado Bueno
• Isabel Colmenero Blanco
• Miguel Ángel Díaz Pérez
• Lucía Fernández Casanova
• Ana María Gómez García
• África González Murillo
• Marta González Vicent
• Álvaro Lassaletta Atienza
• Evangelina Muñoz Mayoral
• Antonio Pérez Martínez
• Manuel Ramírez Orellana
• Julián Sevilla Navarro
• Jaime Valentín Quiroga
• Isabel Vicuña Andres
RESEARCH INTEREST
Although more than half of children diagnosed with cancer survive, yet cancer remains the leading cause of
death by disease in children under 14 years. The reality
for patients with metastasis at diagnosis or those who
have genetic markers of poor prognosis or in cases of
relapsed / refractory tumors, is very negative. Therefore,
new treatment options are much needed to bail out all
these patients. Our interest is trying to develop treatment strategies for children with poor prognosis, based
on strategies of immunotherapy against cancer.
We propose to develop treatment strategies for children with malignant tumors of poor prognosis, based
– 120 –
on the use of immune cells, able to attack and kill the
cancer cells. This is a project that has both a clinical
aspect and a preclinical one, and which is oriented
both towards hematological malignancies and solid
tumors. For children with leukemia, we aim to evaluate
the administration of NK cells from the donor 1 month
after receiving haploidentical transplantation. Our current experience has allowed us to identify that the
reconstitution of an insufficient number of NK cells 1
month after transplant is a factor significantly associated with leukemic relapse, so that administration of NK
cells in this group of children may increase the clinical
benefit of transplantation. In the case of solid tumors,
we aim at evaluating a treatment that is not experienced in childhood cancer, but it has proven antitumor
capacity especially in melanomas. It is the use of
tumor infiltrating lymphocytes (TILs) as an anti-tumor
therapy. This clinical investigation plan is accompanied
by a parallel experimental research plan, which aims to
prepare a product of cellular immunotherapy able to
overcome the barriers imposed by the tumor on the
effector cells, known as tolerance. Of the various
mechanisms known to produce tolerance, we will
begin to address the soluble molecules that induce a
decrease in the cytotoxic capacity of both NK cells
and TILs. We aim at making effector cells resistant to
the action of these immunoregulatory molecules, and
also setting up protocols that may have immediate
clinical translation. These strategies of cell manipulation want to be a proof of concept, and therefore will
be evaluated in preclinical models, serving as a “master protocol” to apply to other known molecules or
from which new knowledge is generated. The results
should serve for the design of new clinical trials for the
continuation of the project.
The team is a multidisciplinary group, with proven experience in the diagnosis and treatment of childhood cancer, and in developing research projects in advanced
therapies applied to refractory pediatric cancer, and the
development of clinical trials in pediatric oncology. It
also has all the technical means and infrastructure for
the development of the project, ensuring their implementation to the patients, which tries to deal with
potential impact for all children being treated in any of
the pediatric oncology units in Spain.
AREA 3
• Ramírez Orellana, Manuel. Estudio de los mecanismos de acción de la terapia con CELVIR en tumores
infantiles: hacia la optimización de los resultados
clínicos. PI13/02487. ISCIII. 2014-2016
• Madero López, Luis. Identificación y validación de
biomarcadores de recaída infantil LLA leucemia.
PI13/02475. ISCIII. 2014-2016.
• Ramírez Orellana, Manuel. Una nueva generación
de medicamentos celulares más eficaces y
seguros. CELLCAM. S2010/BMD-2420. CAM.
2012-2015.
PUBLICATIONS (7)
Carceller F, Oñoro G, Buitrago MJ, Herrero B,
Lassaletta A, Pérez-Martínez A, González-Vicent M,
Madero L. Cunninghamella bertholletiae Infection in
Children: Review and Report of 2 Cases With
Disseminated Infection. J Pediatr Hematol Oncol.
36(2):e109-14. 2014. PMID: 23887023. IF: 1,97. DOI:
10.1097/MPH.0b013e31829eec5a.
http://dx.doi.org/10.1097/MPH.0b013e31829eec5a
Menezes J, Acquadro F, Wiseman M, Gómez-López G,
Salgado RN, Talavera-Casañas JG, Buño I, Cervera JV,
Montes-Moreno S, Hernández-Rivas JM, Ayala R,
Calasanz MJ, Larrayoz MJ, Brichs LF, Gonzalez-Vicent
M, Pisano DG, Piris MA, Alvarez S, Cigudosa JC.
Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm. Leukemia. 28(4):823-9. 2014.
PMID: 24072100. IF: 9,379. DOI: 10.1038/leu.
2013.283.
http://dx.doi.org/10.1038/leu.2013.283
Carceller Lechón F, Duat Rodríguez A, Sirvent Cerdá
SI, Khabra K, de Prada I, García-Peñas JJ, Madero
López L. Hemicerebellitis: Report of three paediatric
cases and review of the literature. Eur J Paediatr
Neurol. 18(3):273-281. 2014. PMID: 24423631. IF:
1,934. DOI: 10.1016/j.ejpn.2013. 12.004.
http://dx.doi.org/10.1016/j.ejpn.2013.12.004
Ruiz-Hernández E, Hess M, Melen GJ, Theek B, Talelli
M, Shi Y, Ozbakir B, Teunissen EA, Ramírez M,
Moeckel D, Kiessling F, Storm G, Scheeren AW, Hennik
WWE, Szalay AA, Stritzker J, Lammers T. PEGpHPMAm-based polymeric micelles loaded with doxorubicin-prodrugs in combination antitumor therapy
with oncolytic vaccinia viruses. Polym Chem.
7;(5):1674-1681. 2014. PMID: 24518685. IF: 5,368
López Villar E, Wu D, Cho WC, Madero L, Wang X.
Proteomics-based discovery of biomarkers for paediatric acute lymphoblastic leukaemia: challenges and
opportunities. J Cell Mol Med. 18(7):1239-46. 2014.
PMID:
24912534.
IF:
3,698.
DOI:
10.1111/jcmm.12319.
http://dx.doi.org/ 10.1111/jcmm.12319
Oñoro G, de Lama G, Pérez-Martínez A, GonzálezVicent M. Severe hyperphosphoremia and hypocalcemia after the administration of a hypertonic sodium
phosphate enema. Med Intensiva. 38(4):263-4. 2014.
PMID:
23890987.
IF:
1,24.
DOI:
10.1016/j.medin.2013.01.011.
http://dx.doi.org/10.1016/j.medin.2013.01.011
Piñana JL, Sanz J, Picardi A, Ferrá C, Martino R, Barba
P, Gonzalez-Vicent M, Pascual MJ, Martín C,
Verdeguer A, Diaz de Heredia C, Montesinos P, Ribera
JM, Sanz M, Arcese W, Sanz G. Umbilical cord blood
transplantation from unrelated donors in patientswith
PH-positive
acute
lymphoblastic
leukemia.
Haematologica. 99(2):378-84. 2014. PMID: 24097633.
IF: 5,868. DOI: 10.3324/haematol.2013.091009.
http://dx.doi.org/10.3324/haematol.2013.091009
CLINICAL TRIALS
PRINCIPAL RESEARCHER: MADERO LÓPEZ, LUIS
Fase 2 de Aprepitant para Vomitos post
Quimioterapia. 0869-134.
PRINCIPAL RESEARCHER: RAMÍREZ ORELLANA,
MANUEL
Estudio fase 1 con viroterapia oncolitica. CELYVIR.
– 121 –
AREA 3AREA 2 AREA 1
MAJOR GRANTS
PRINCIPAL RESEARCHER: SEVILLA NAVARRO,
JULIÁN
A Single Arm, Open-label, Long-term Efficacy and
Safety Study of Romiplostim in Thrombocytopenic
Pediatric Subjects with Immune Thrombocytopenia
(ITP). AMGEN. 20101221 (Romiplostim)
EudraCT: 2011-005019-96
JULIÁN
Open Label Study Comparing Efficacy and Safety
of Dabigatran Etexilate to Standard of Care in
Paediatric Patients With Venous Thromboembolism
(VTE). BOEHRINGER INGELHEIM. 1160.106
EudraCT: 2013-002114-12
JULIÁN
Estudio fase 2 Dabigatran en Trombosis. 1160.109
JULIÁN
FANCOSTEM-1: Clinical Phase II Trial to evaluate
efficacy and safety of CD34+ cells mobilization and
collection after treatment with plerixafor and filgrastim in patients with Fanconi anemia for subsequent
transduction with a lentiviral vector carring FANCA
– 122 –
gene and reinfusion in the patient – ES.
FANCOSTEM-1
EudraCT: 2011-006197-88
JULIÁN
A Combined Study in Pediatric Cancer Patients for
Dose Ranging and Efficacy/Safety of Plerixafor Plus
Standard Regimens for Mobilization Versus
Standard
Regimens
Alone.
GENZYME.
MOZ15609/DFI12860 (MOZAIC).
EudraCT: 2010-019340-40
JULIÁN
A Study to Investigate the Safety and Efficacy of an
Anti-IFNγ mAb in Children Affected by Primary
Haemophagocytic Lymphohistiocytosis.
NovImmune SA. NI-0501-04
EudraCT: 2012-003632-23
JULIÁN
Pediatric
Disease
Registry
in
Essential
Thrombocythaemia (ET). SHIRE. SPD422-404
EudraCT: 2004-004061-15
AREA 3
GRUPO 44
HEAD OF LABORATORY
Juan Luis Steegmann Olmedillas
GROUP MEMBERS
• Adrián Alegre Amor
• Eva Arranz Muñoz
• María Reyes Arranz Sáez
• María Jimena Cannata Ortiz
• Ángela Figuera Álvarez
• Ana María García-Noblejas Moya
• Valle Gómez García de Soria
• Jimena Jiménez Braña
• Javier Loscertales Pueyo
• María Ángeles Sanz de Benito
RESEARCH INTEREST
The Group of Advanced Therapies in Oncohematology
of the Research Institute of the Hospital de la Princesa
has the mission of promoting clinical, epidemiological
and translational research in hematologic malignancies.
The scope of the group is broad, reflecting the variegated nature of each member’s interests, and spans from
genetic studies to the commitment in the development
of new drugs.
The Group has a differential interest in:
• Epidemiological studies on chronic myeloid leukemia.
• Study of the efficacy and safety of new drugs in
hematologic malignancies.
• Immunological and genetic studies in hematologic
malignancies.
• Analysis of conditioning regimes in bone marrow
transplants (BMT)
• Analysis of infectious complications of BMT.
During the past 5 years, our clinical research has
focused his activity in two fields. The first, as Spanish IP
of the European Leukemia Net EUTOS projects, in epidemiological studies and good clinical practice recommendations. Secondly, as president of the Spanish
CML group (GELMC), to foster clinical research in this
group. One multicentric clinical trial is currently running,
and other is on its way of approval. We have constructed a mobile app for IOS, Windows, and Android for
exchanging information between GELMC members.
On the other hand, locally, our aim is to establish common projects which could cover all the hematologic
malignancies cared by our group. In this regard the plan
is to set studies of quality of life, comorbidities, and
pharmacology.
MAJOR GRANTS
Steegmann Olmedillas, Juan Luis. European treatment
and otucome study for cml. Comisión Europea. EUTOS.
2008-.
PUBLICATIONS (18)
García-Noblejas, C. Martínez Chamorro, B. Navarro
Matilla, TJ.González-Lopez, R. Oña Navarrete; MJ
Ramírez Sánchez, P. Martínez Barranco, JJ Sanchez
Blanco, C. Nicolás, R. Pérez, B. Sánchez González,
AM. Ruedas López, Domingo-Domenech, C. Panizo,
S. Macia, E. Fernandez-Fonseca, J. Cannata-Ortiz, C.
Da Silva Rodriguez and R. Arranz. Bendamustine as
salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective
study of the Spanish experience. Annals of
Hematology. 93(9):1551-8. 2014. PMID: 24782117. IF:
2,396. DOI: 10.1007/s00277-014-2077-1.
http://dx.doi.org/10.1007/s00277-014-2077-1
– 123 –
AREA 3AREA 2 AREA 1
Line 3.4
Advanced therapies
in oncohematology
García-Gutiérrez V, Puerta JM, Maestro B, Casado
Montero LF, Muriel A, Molina Hurtado JR, PerezEncinas M, Moreno Romero MV, Suñol PB, Sola Garcia
R, De Paz R, Ramirez Sanchez MJ, Osorio S, Mata
Vazquez MI, Martinez López J, Sastre JL, Portero MD,
Bautista G, Duran Nieto MS, Giraldo P, Jimenez
Jambrina M, Burgaleta C, Ruiz Aredondo J, Peñarrubia
MJ, Requena MJ, Fernández Valle MD, Calle C, Paz
Coll A, Hernández-Rivas JA, Franco Osorio R, Cano P,
Tallón Pérez D, Fernández de la Mata M, Garrido PL,
Steegmann JL. Do chronic myeloid leukemia patients
with late "warning" responses benefit from "watch and
wait" or switching therapy to a second generation tyrosine kinase inhibitor?. Am J Hematol. 89(11):E206-11.
2014. PMID: 25059397. IF: 3,477. DOI:
10.1002/ajh.23816.
http://dx.doi.org/10.1002/ajh.23816
Jabbour E, Kantarjian HM, Saglio G, Steegmann JL,
Shah NP, Boqué C, Chuah C, Pavlovsky C, Mayer J,
Cortes J, Baccarani M, Kim DW, Bradley-Garelik MB,
Mohamed H, Wildgust M, Hochhaus A. Early response
with dasatinib or imatinib in chronic myeloid leukemia:
3-year follow-up from a randomized phase 3 trial
(DASISION). Blood. 123(4):494-500. 2014. PMID:
24311723. IF: 9,775. DOI: 10.1182/blood-2013-06511592.
http://dx.doi.org/10.1182/blood-2013-06-511592
Vetro C, Romano A, Amico I, Conticello C, Motta G,
Figuera A, Chiarenza A, Di Raimondo C, Giulietti G,
Bonanno G, Palumbo GA, Di Raimondo F. Endoscopic
features of gastro-intestinal lymphomas: from diagnosis
to
follow-up.
World
J
Gastroenterol.
28;20(36):12993-3005. 2014. PMID: 25278693. IF:
2,433. DOI: 10.3748/wjg.v20.i36.12993.
http://dx.doi.org/10.3748/wjg.v20.i36.12993
López Rubio M, Da Silva C, Loscertales J, Seri C,
Baltasar P, Colado E, Pérez Fernández I, Osma M,
Gomis F, González M, Jarque I, Vargas M, Monzó E,
Monteagudo D, Orts MI, Pardal E, Carbonell F, Perez
Calvo C, Garcia-Marco JA. Hairy cell leukemia treated
initially with purine analogs: a retrospective study of
107 patients from the Spanish Cooperative Group on
Chronic Lymphocytic Leukemia (GELLC). Leuk
– 124 –
Lymphoma. 55(5):1007-12. 2014. PMID: 23885799.
IF: 2,605. DOI: 10.3109/10428194.2013.827187.
http://dx.doi.org/10.3109/10428194.2013.827187
Redondo AM, Pomares H, Vidal MJ, Pascual MJ,
Quereda B, Sancho JM, Polo M, López J, Conde E,
Jarque I, Alonso N, Ramírez MJ, Fernández P, Sayas MJ,
Requena MJ, Salar A, González JD, González-Barca E,
Arranz R, Caballero D, Martín A. Impact of prior rituximab
on outcomes of autologous stem-cell transplantation in
patients with relapsed or refractory aggressive B-cell
lymphoma: a multicentre retrospective Spanish group of
lymphoma/autologous bone marrow transplant study.
Br J Haematol. 164(5):668-74. 2014. PMID: 24274082.
IF: 4,959. DOI: 10.1111/bjh.12676.
http://dx.doi.org/10.1111/bjh.12676
Onida F, Brand R, van Biezen A, Schaap M, von dem
Borne PA, Maertens J, Beelen DW, Carreras E,
Alessandrino EP, Volin L, Kuball JH, Figuera A, Sierra J,
Finke J, Kröger N, de Witte T; MDS subcommittee of
the EBMT-CMWP. Impact of the International
Prognostic Scoring System cytogenetic risk groups on
the outcome of patients with primary myelodysplastic
syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings:
a retrospective analysis of the European Society for
Blood
and
Marrow
Transplantation-Chronic
Malignancies Working Party. Haematologica.
99(10):1582-90. 2014. PMID: 25085359. IF: 5,868.
DOI: 10.3324/haematol.2014.106880.
http://dx.doi.org/10.3324/haematol.2014.106880
Piñana JL, Montesinos P, Martino R, Vazquez L, Rovira
M, López J, Batlle M, Figuera Á, Barba P, Lahuerta JJ,
Debén G, Perez-Lopez C, García R, Rosique P, Lavilla
E, Gascón A, Martínez-Cuadrón D, Sanz MÁ.
Incidence, risk factors, and outcome of bacteremia following autologous hematopoietic stem cell transplantation in 720 adult patients. Ann Hematol. 93(2):299-307.
2014. PMID: 23995612. IF: 2,396. DOI:
10.1007/s00277-013-1872-4.
http://dx.doi.org/10.1007/s00277-013-1872-4
Pardal E, Coronado M, Martín A, Grande C, MarínNiebla A, Panizo C, Bello JL, Conde E, Hernández MT,
AREA 3
Duarte RF, Boumendil A, Onida F, Gabriel I, Arranz R,
Arcese W, Poiré X, Kobbe G, Narni F, Cortelezzi A,
Olavarría E, Schmitz N, Sureda A, Dreger P. Long-term
outcome of allogeneic hematopoietic cell transplantation for patients with mycosis fungoides and sézary
syndrome: a European society for blood and marrow
transplantation lymphoma working party extended
analysis. J Clin Oncol. 32(29):3347-3348. 2014. PMID:
25154828.
IF:
17,96.
DOI:
10.1200/JCO.2014.57.5597.
http://dx.doi.org/10.1200/JCO.2014.57.5597
Muñoz-Linares C, Ojeda E, Forés R, Pastrana M,
Cabero M, Morillo D, Bautista G, Baños I, Monteserín
C, Bravo P, Jaro E, Cedena T, Steegmann JL, Villegas
A, Cabrera JR. Paroxysmal nocturnal hemoglobinuria:
a single Spanish center's experience over the last 40
yr. Eur J Haematol. 93(4):309-319. 2014. PMID:
24758317. IF: 2,414. DOI: 10.1111/ejh.12346.
http://dx.doi.org/10.1111/ejh.12346
Llamas-Velasco M, Steegmann JL, Carrascosa R,
Fraga J, García Diez A, Requena L. Perforating
Folliculitis in a Patient Treated With Nilotinib: A Further
Evidence of C-kit Involvement. Am J Dermatopathol.
36(7):592-3. 2014. PMID: 23612033. IF: 1,426. DOI:
10.1097/DAD.0b013e31828cf3b7.
http://dx.doi.org/10.1097/DAD.0b013e31828cf3b7
Weisser M, Yeh RF, Duchateau-Nguyen G, Palermo G,
Nguyen TQ, Shi X, Stinson SY, Yu N, Dufour A, Robak T,
Salogub GN, Dmoszynska A, Solal-Celigny P, Warzocha
K, Loscertales J, Catalano J, Larratt L, Rossiev VA,
Bence-Bruckler I, Geisler CH, Montillo M, Fischer K, Fink
AM, Hallek M, Bloehdorn J, Busch R, Benner A, Döhner
H, Valente N, Wenger MK, Stilgenbauer S, Dornan D.
PTK2 expression and immunochemotherapy outcome in
chronic lymphocytic leukemia. Blood. 124(3):420-425.
2014. PMID: 24916506. IF: 9,775. DOI: 10.1182/blood2013-12-538975.
http://dx.doi.org/10.1182/blood-2013-12-538975
Alegre A, Gironella M, Bailén A, Giraldo P. Zoledronic
acid in the management of bone disease as a consequence of multiple myeloma: a review. Eur J Haematol.
92(3):181-8. 2014. PMID: 24330023. IF: 2,414. DOI:
10.1111/ejh.12239.
http://dx.doi.org/10.1111/ejh.12239
Awan FT, Hillmen P, Hellmann A, Robak T, Hughes SG,
Trone D, ShannonM, Flinn IW, Byrd JC; LUCID trial
investigators (Loscertales J). A randomized, openlabel, multicentre, phase 2/3 study to evaluatethe safety and efficacy of lumiliximab in combination withfludarabine, cyclophosphamide and rituximab versus fludarabine,cyclophosphamide and rituximab alone in
subjects with relapsed chroniclymphocytic leukaemia.
Br J Haematol 167(4):466-477. 2014. PMID:
25130401. IF: 4,959. DOI: 10.1111/bjh.13061.
Llamas-Velasco M, Fraga J, Kutzner H, Steegmann JL,
García-Diez A, Requena L. Hypopigmented macules
secondary to imatinib for the treatment of chronic
myeloid leukemia: a histopathologic and immunohistochemical study. J Cutan Pathol. 41(5):417-426. 2014.
PMID: 24467724. IF: 1,56. DOI: 10.1111/cup.12298.
Muñoz-Cobo B, Giménez E, Solano C, de la Cámara
R, Nieto J, López J, Amat P, Garcia-Noblejas A,
Navarro D. An evaluation of the role of NKG2C+ natural killer cells in protection from cytomegalovirus
DNAemia early following allogeneic stem cell transplantation. J Med Virol. 86(5):806-11. 2014. PMID:
24105728. IF: 2,217. DOI: 10.1002/jmv.23742.
http://dx.doi.org/10.1002/jmv.23742
Llamas-Velasco M, Fraga J, Solano-López GE,
Steegmann JL, García Diez A, Requena L. Multiple
eruptive dermatofibromas related to imatinib treatment.
J Eur Acad Dermatol Venereol. 28(7):979-981. 2014.
PMID: 24321053. IF: 3,105.
DOI: http://dx.doi.org/10.1111/jdv.12328
– 125 –
AREA 3AREA 2 AREA 1
Arranz R, Bargay J, González-Barca E, Pérez-Ceballos
E, Montes-Moreno S, Caballero MD. Intensification
treatment based on early FDG-PET in patients with
high-risk diffuse large B-cell lymphoma: a phase II
GELTAMO trial. Br J Haematol. 167(3):327-36. 2014.
PMID: 25066542. IF: 4,959. DOI: 10.1111/bjh.13036.
BOOKS
Juan Luis Steegmann, María Teresa Gómez-Casares y
Manuel Pérez Encinas. Manual para el control y el
tratamiento de los pacientes con leucemia mieloide
crónica. EUROMEDICE, Ediciones Médicas, S.L. ISBN:
978-84-16269-01-3
Juan Luis Steegmann Olmedillas, Luis Felipe Casado
Montero. Tratamiento de primera línea de la leucemia
mieloide crónica en fase crónica. Manual para el control y el tratamiento de los pacientes con leucemia
mieloide crónica. EUROMEDICE, Ediciones Médicas,
S.L. ISBN: 978-84-16269-01-3
A Alegre, JM Fernandez. Terapia en Oncohematología.
IV Edición. Terapia en Oncohematología. IV Edición.
Editorial Aymon. Madrid. ISBN: 978-84-617-2444-4
A Alegre, C Burgaleta. Manual del Residente Médico
residente en Hematología y Hemoterapia. EDIMSA.
Madrid. ISBN: 978-84-7714-409-0
Tomás Martínez, José Francisco; Raquel de Oña,
Alegre Amor, Adrián, y Fernández-Rañada de la
Gándara, José Mª. Fundamentos de la quimioterapia
antineoplásica. Terapia en Oncohematología. IV
Edición. Editorial Aymon. Madrid. ISBN: 978-84-6172444-4
Loscertales Pueyo, Javier; Aguado Bueno, Beatriz;
Villanueva-Forero, Miguel y Alegre Amor, Adrián.
Nuevas terapias biológicas no citostáticas en oncohematología. Terapia en Oncohematología. IV Edición.
Editorial Aymon. Madrid. ISBN: 978-84-617-2444-4
Alegre Amor, Adrián; Aguado Bueno, Beatriz; Vicuña
Andrés, Isabel; González Pardo, Miriam, y Martínez
Chamorro, Carmen. Tratamiento del mieloma múltiple.
Terapia en Oncohematología. IV Edición. Editorial
Aymon. Madrid. ISBN: 978-84-617-2444-4
Concepción Aláez Usó; Nistal Gil, Sara; Nvas Elorza,
Begoña; Alegre Amor, Adrián. Tratamiento de la
Amiloidosis
Primaria,
Macroglobulinemia
de
Waldenstrom y otras Gammpatías Monoclonales.
– 126 –
Terapia en Oncohematología. IV Edición. Editorial
Aymon. Madrid. ISBN: 978-84-617-2444-4
Vicuña Andrés, Isabel, Alegre Amor, Adrián; Aguado
Bueno, Beatriz; Lorenzo Jambrina; Alicia; Veramendi
Zabala, Susi. Transfusión sanguínea en el paciente
neoplásico y en el trasplante de progenitores
hematopoyéticos. Terapia en Oncohematología. IV
Edición. Editorial Aymon. Madrid. ISBN: 978-84-6172444-4
Fernández-Rañada, J. Alegre, A. Tratamiento de los linfomas agresivos. Terapia en Oncohematología. Elsevier
(4ª Edición). ISBN: 978-84-617-2444-4
Miguel Villanueva Forero, Sonia Guijarro Montoro, Alicia
Lorenzo Jambrina, Gabriela Silva Carreras, Javier
Loscertales Pueyo. Leucemia linfocítica crónica y otros
síndromes linfoproliferativos crónicos. Manual del
Residente Médico residente en Hematología y
Hemoterapia. EDIMSA. Madrid. ISBN: 978-84-7714409-0
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ALEGRE AMOR, ADRIÁN
Ensayo clínico aleatorizado en fase IIIB de Revlimid®
(lenalidomida) en comparación con placebo como
tratamiento de mantenimiento tras la terapia de inducción con melfalán, prednisona y Velcade® (bortezomib)
en el mieloma múltiple de nuevo diagnóstico; (Versión
enmienda1 final: 27-11-13) CELGENE CORPORATION
CC-5013-MM-026
EudraCT: 2013-001729-26
PRINCIPAL RESEARCHER: ALEGRE AMOR, ADRIÁN
Estudio fase III nacional, multicéntrico, abierto, aleatorizado, de tratamiento de mantenimiento con lenalidomida y dexametasona versus lenalidomida, dexametasona y MLN9708 tras trasplante autólogo de progenitores hematopoyéticos para pacientes con mieloma
múltiple sintomático de nuevo diagnóstico; (Versión 1:
24-03-14). FUNDACION PETHEMA GEM2014MAIN
EudraCT: 2014-000554-10
AREA 3
PRINCIPAL RESEARCHER: ARRANZ SAEZ, MARÍAREYES
Estudio de fase 3 doble ciego, aleatorizado, controlado con placebo y multicéntrico para comparar la eficacia y seguridad de lenalidomida (CC-5013) más
quimioterapia con R-CHOP (R-CHOP) frente a placebo
más quimioterapia con R-CHOP en sujetos con linfoma
difuso de células B grandes activadas que no han
recibido tratamiento con anterioridad; (Versión final:
16-05-14). CELGENE CORPORATION CC-5013-DLC002
EudraCT: 2013-004054-21
PRINCIPAL RESEARCHER: LOSCERTALES PUEYO,
JAVIER
Estudio de fase 3, aleatorizado, doble ciego, controlado con placebo, en el que se evalúa la eficacia y
seguridad de idelalisib en combinación con bendamustina y rituximab, en pacientes con leucemia linfocítica crónica previamente sin tratar; (Versión
amend1: 19-02-14). GILEAD SCIENCES, INC GS-US312-0123
EudraCT: 2013-003313-17
PRINCIPAL RESEARCHER: STEEGMANN OLMEDILLAS, JUAN LUIS
Estudio fase I, multicéntrico, abierto, de ABL001 oral,
en pacientes con leucemia mieloide crónica o con
leucemia linfoblástica aguda Cromosoma Filadelfia
positivo; (Versión 00: 18-11-13). NOVARTIS FARMACEUTICA, S.A. CABL001X2101
EudraCT: 2013-004491-36
Estudio de fase IV para evaluar la seguridad y la eficacia de bosutinib (Bosulif ) en pacientes con leucemia
mieloide crónica con cromosoma Filadelfia positivo
tratados previamente con uno o más inhibidores de la
tirosina quinasa; (Versión final: 21-1-14). PFIZER INC
B1871039
EudraCT: 2013-003250-25
Tratabilidad en mielofibrosis. Estudio observacional
prospectivo para identificar los aspectos clínicos que
conducen a la toma de decisiones terapéuticas en
pacientes con mielofibrosis; (Versión final: 29-01-14).
GEMFIN GEM-MIE-2014-01
. AVILLIAN DEVELOPMENT 1 LIMITED AV001
EudraCT: 2013-005101-31
– 127 –
AREA 3AREA 2 AREA 1
PRINCIPAL RESEARCHER: ARRANZ SAEZ, MARÍA
REYES
Estudio de fase 1/3, aleatorizado, doble ciego, de
grupos paralelos y controlado con fármaco activo
para demostrar la equivalencia en la farmacocinética
y la no inferioridad en la eficacia de CT-P10 en comparación con rituxán, cada uno de ellos administrado
en combinación con ciclofosfamida, vincristina y
prednisona (CVP), en pacientes con linfoma folicular
avanzado; (Versión 1.0: 04-11-13). CELLTRION INC.
CT-P10-3.3
EudraCT: 2013-004493-96
Line 3.5
Biological, cellular and
molecular monitoring in
oncohematology
GRUPO 45
HEAD OF LABORATORY
GROUP MEMBERS
• Irene Bodega Mayor
• Álvaro Cuesta Domínguez
• Mónica Sala Valdés
• Matilde Santos Roncero
model as a relevant preclinical tool to validate new therapeutic approaches with JAK2 inhibitors. This therapy
warrants further investigation for use alone or in combination with standard chemotherapy in treating human
cancer with elevated JAK2 activity. Recently, it has been
reported that 10% of high risk pediatric acute lymphoblastic leukemia (ALL) cases bear activated JAK2
mutations and could be potential candidates for JAK2
inhibitor therapeutic intervention. ALL is the most common neoplasm in childhood and although most cases
respond to treatment, 20% relapse, shortening survival.
Therefore, we want to analyze high risk ALL samples
with next generation sequencing (NGS) to determine the
percentage of JAK-family receptor mutations in the
Spanish population. For this purpose ALL samples will
be obtained from hospitals throughout the country. The
mutational analysis will be correlated with clinical parameters to assess their prognostic value. Furthermore,
those mutations that may alter the function of the receptor will be analyzed in in vitro assays with mutated-constructs and deficient cells to describe their effect on
downstream signaling pathways.
RESEARCH INTEREST
Chromosomal translocations that give rise to fusion proteins are frequently associated with the etiology of hematologic neoplasm. The search for small tyrosine-kinase
inhibitors specific for fusion protein leading to leukemia is
an active area of research after the success of imatinib
based therapy. We have described the transforming and
tumorigenic activity of a new fusion protein, BCR-JAK2,
obtained from a patient with acute lymphoblastic
leukemia. This chimeric protein involves the BCR
oligomerization domain fused to the JAK2 tyrosinekinase domain. JAK2 is a non-receptor tyrosine-kinase
that mediates signaling of different cytokine receptors
and is crucial to normal hematopoiesis through the
recruitment of downstream effectors of cell proliferation
and survival. Our group successfully proved that cells
expressing BCR-JAK2 developed tumors when injected
subcutaneously into immunodeficient mice. In addition,
using transduced bone marrow progenitors in a mouse
transplantation model, we demonstrated BCR-JAK2 as
the driving force of a myeloproliferative disorder with a
fatal outcome. These findings support the use of this
– 128 –
MAJOR GRANTS
• Fernández Ruiz, Elena. Preclinical study of the efficacy of
TG101348 inhibitor on ex-vivo cells from high-risk BCRABL negative adult and childhood acute lymphoblastic
leukaemia with JAK2 mutations and CRLF2 overexpression: assessment of disease reversion in vivo in immunodefic. Sanofi-Aventis. 2013-2014.
• Fernández Ruiz, Elena. Implicación de JAK2 en el
reconocimiento de patógenos y en la respuesta inmune
innata. ISCIII. PI11/00128. 2012-2014.
PUBLICATIONS (1)
Cruz-Adalia A, Ramirez-Santiago G, Calabia-Linares
C, Torres-Torresano M, Feo L, Galán-Díez M,
Fernández-Ruiz E, Pereiro E, Guttmann P, Chiappi
M, Schneider G, Carrascosa JL, Chichón FJ,
AREA 3
GRUPO 46
HEAD OF LABORATORY
Cecilia Muñoz Calleja
GROUP MEMBERS
• Beatriz Colom Fernández
• Carlos Cuesta Mateos
• Anna Sofia Kreutzman
I• txaso Portero Sainz
• Beatriz Somovilla Crespo
RESEARCH INTEREST
Lymphocyte migration is involved in the pathogenesis of
many diseases. Its control constitutes a target for different forms of immunotherapy. Conversely, other forms of
immunotherapy can affect lymphocyte migration, leading
to secondary effects, either desirable or not.
Chemokines mediate recirculation of lymphocytes. The
chemokine receptor CCR7 is involved in the homing of
lymphocytes through secondary lymphoid organs and
mediates the ganglionar dissemination of lymphoid
malignancies and inflammatory processes. CCR7 is
highly expressed on different lymphoid malignancies and
several proofs of concept have demonstrated the therapeutic benefit of targeting either the molecule or the signaling downstream.
Among the inflammatory conditions, the recirculation of
CCR7+ naïve T lymphocytes plays a key role in the graft-
vs-host disease (GVHD), which represents a major complication of allogeneic stem cell transplantation.
Receiving high numbers of CCR7+ T-cells from the
donor increases the probability of migration through
recipient´s lymphoid organs and the incidence of GVHD.
Therefore, the proportion of CCR7+ T-cells in the allograft might provide a predictive indicator of GVHD and
supports the approaches of selective T-cell depletion to
prevent GVHD.
Dasatinib is a tyrosin kinase inhibitor for the treatment of
chronic myeloid leukemia which has immunomodulatory
effects, including a lymphocytosis occurring in most
patients which has been associated to a better outcome
of the patients.
Our group aims at three objectives:
1.The efficacy of CCR7 immunotherapy.
We are testing humanized versions of anti-CCR7 antibodies to treat ex vivo different lymphoid cancers, including B and T cell leukemias. We are analyzing their cytolytic activity dependent on complement or cells. Animal
models of primary human T cell leukemias or GVHD are
being used to evaluate the in vivo efficacy of targeting
CCR7.
2. Identification of biomarkers of GVHD.
A better characterization of the CCR7+ T cells in the
apheresis product of the donor is being performed to
identify those subpopulations responsible for the
development and severity of GVHD. This would allow
the identification of those recipients with special
needs of GVHD profilaxis. We will also perform in vitro
functional experiments of migration to evaluate
whether the migratory ability of the lymphocytes in the
apheresis is a better predictor than the expression of
CCR7 itself.
3. Characterization of the immunomodulatory effects of
dasatinib.
We are evaluating the migratory response to different
chemokines of lymphocytes obtained from patients
immediately after their daily uptake of the drug. In vitro
experiments are being performed to address whether
dasatinib has direct effects in the adhesive and migratory abilities of lymphocytes.
– 129 –
AREA 3AREA 2 AREA 1
Martínez Del Hoyo G, Sánchez-Madrid F, Veiga E. T
cells kill bacteria captured by transinfection from
dendritic cells and confer protection in mice. Cell
Host Microbe. 15(5):611-22. 2014. PMID:
24832455.
IF:
12,194.
DOI:
10.1016/j.chom.2014.04.006.
MAJOR GRANTS
Muñoz Calleja, Cecilia. Estudio de dianas terapéuticas
novedosas en modelos preclínicos de linfoma y de
trasplantes de progenitores hematopoyeticos. ISCIII.
PI12/00494. 2012-2015.
PUBLICATIONS (2)
Sanmamed MF, Carranza-Rua O, Alfaro C, Oñate C,
Martín-Algarra S, Perez G, Landazuri SF, Gonzalez A,
Gross S, Rodriguez I, Muñoz-Calleja C, Rodríguez-Ruiz
M, Sangro B, López-Picazo JM, Rizzo M, Mazzolini G,
Pascual JI, Andueza MP, Perez-Gracia JL, Melero.
Serum Interleukin-8 Reflects Tumor Burden and
– 130 –
Treatment Response across Malignancies of Multiple
Tissue Origins. Clin Cancer Res. 20(22):5697-707. 2014.
PMID: 25224278. IF: 8,193. DOI: 10.1158/10780432.CCR-13-3203.
http://dx.doi.org/10.1158/1078-0432.CCR-13-3203
Castañeda S, Gamallo- Amat C, Fraga J, García-García
C, Muñoz-Calleja C, García-Diez A, Urzainqui A.
Development of an autoimmune syndrome affecting the
skin and internal organs in P-Selectin Glycoprotein
Ligand-1 deficient mice. Arthritis and Rheumatology.
66(11):3178-89. 2014. PMID: 25132671. IF: 7,871. DOI:
10.1002/art.38808.
AREA 3
GRUPO 58
HEAD OF LABORATORY
Fernando Alfonso Manterola
GROUP MEMBERS
• Amparo Benedicto Buendía
• Rosa María Moreno Carriles
• Guillermo Reyes Copa
• Antonio Reyes García
• Fernando Rivero Crespo
• Bernhard Seidelberger
RESEARCH INTEREST
Cardiovascular diseases represent the leading cause of
mortality in developed countries including Spain.
Coronary artery disease constitutes the main disease
burden for these patients and this explains why major
preventive, diagnostic and therapeutic research efforts
are being developed to address this highly prevalent and
challenging clinical condition. Percutaneous coronary
intervention, with stent implantation, remains the most
widely used method of revascularization in these
patients.
Our group pursues several lines of investigation.
”Stent failure” constitutes our main research interest.
Stent failure includes both “in-stent restenosis” and
“stent thrombosis”. Recently it has been suggested
that neoatherosclerosis might provide an elusive link
between these conditions. Specifically, we sought to
assess the value on novel generation drug-eluting
stents in the treatment of patients with different clinical
and anatomic characteristics. We are also developing
strategies to optimize stent implantation. In these
regard, head-to-head randomized clinical studies comparing different therapeutic devices are of major interest. In addition, we are deeply interested in the healing
and vascular repair process after stent implantation. In
this regard, a detailed assessment of the target coronary segment using sophisticated intracoronary imaging techniques (optical coherence tomography,
intravascular ultrasound) and a functional evaluation of
the physiology of the vessel wall (pressure wire and
fractional flow reserve), are of major value. These techniques unravel novel information on vessel healing,
endothelization, neointimal hyperplasia response, and
may also disclose risk markers for stent thrombosis.
We are leading multicenter controlled initiatives in our
country to establish the relative value of different coronary interventions for patients suffering from in-stent
restenosis. Likewise, we are actively involved in several
international initiatives focused on the dreadful problem
of stent thrombosis.
On the other hand, new intracoronary diagnostic techniques provide novel insights on the “vulnerable plaque”
and may also help to understand mechanisms implicated in the pathophysiology of acute coronary syndromes
and in coronary atherosclerosis progression and regression. In this regard, our group is actively involved in
research projects on disease progression and in establishing further criteria to define lesion severity.
The diagnosis and clinical management of patients with
acute coronary syndrome represents a major work-load
of our daily clinical activity and, therefore, also stimulates
many of our research projects. Different strategies are
being evaluated in patients with ST-segment elevation
acute myocardial infarction. This includes studies
assessing preventive strategies, diagnosis and management initiatives in these patients.
New and potent antiplatelet and antithrombotic drugs
and lipid lowering agents are currently available and we
are studying their value in several subsets of patients
with coronary artery disease requiring coronary revascularization or just medical management.
– 131 –
AREA 3AREA 2 AREA 1
Line 3.6
New diagnostic and
therapeutic advances in
cardiovascular diseases
Last but not least, structural heart disease is another
important evolving field. We are deeply interested in
defining the role of some emerging interventional techniques as transcatheter aortic valve implantation in elderly patients with severe aortic stenosis, and the value of
other new devices aiming to correct diverse structural
heart diseases.
MAJOR GRANTS
Alfonso Manterola, Fernando. Prevention of late stent
thrombosis by an interdisciplinary global EUROPEAN
effort. PRESTIGE. 2014-.
PUBLICATIONS (27)
Authors/Task Force members (Alfonso F), Elliott PM,
Anastasakis A, Borger MA, Borggrefe M, Cecchi F,
Charron P, Hagege AA, Lafont A, Limongelli G,
Mahrholdt H, McKenna WJ, Mogensen J,
Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B,
Rapezzi C, Rutten FH, Tillmanns C, Watkins H. 2014
ESC Guidelines on diagnosis and management of
hypertrophic cardiomyopathy: The Task Force for the
Diagnosis and Management of Hypertrophic
Cardiomyopathy of the European Society of Cardiology
(ESC). Eur Heart J. 35(39):2733-79. 2014. PMID:
25173338.
IF:
14,723.
DOI:
10.1093/eurheartj/ehu284.
http://dx.doi.org/10.1093/eurheartj/ehu284
Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J,
Falk V, Filippatos G, Hamm C, Head SJ, Jüni P,
Kappetein AP, Kastrati A, Knuuti J, Landmesser U,
Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa
Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli
M, Wijns W, Witkowski A; ESC Committee for Practice
Guidelines, Zamorano JL, Achenbach S, Baumgartner
H, Bax JJ, Bueno H, Dean V, Deaton C, Erol Ç, Fagard
R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J,
Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P,
Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL,
– 132 –
Tendera M, Torbicki A, Wijns W, Windecker S; EACTS
Clinical Guidelines Committee, Sousa Uva M,
Achenbach S, Pepper J, Anyanwu A, Badimon L,
Bauersachs J, Baumbach A, Beygui F, Bonaros N, De
Carlo M, Deaton C, Dobrev D, Dunning J, Eeckhout E,
Gielen S, Hasdai D, Kirchhof P, Luckraz H, Mahrholdt
H, Montalescot G, Paparella D, Rastan AJ, Sanmartin
M, Sergeant P, Silber S, Tamargo J, ten Berg J8, Thiele
H, van Geuns RJ, Wagner HO, Wassmann S, Wendler
O, Zamorano JL. 2014 ESC/EACTS Guidelines on
myocardial revascularization: the Task Force on
Myocardial Revascularization of the European Society
of Cardiology (ESC) and the European Association for
Cardio-Thoracic Surgery (EACTS). Developed with the
special contribution of the European Association of
Percutaneous Cardiovascular Interventions (EAPCI).
Eur J Cardiothorac Surg. 46(4):517-92. 2014. PMID:
25173601. IF: 2,814. DOI: 10.1093/ejcts/ezu366.
http://dx.doi.org/10.1093/ejcts/ezu366
Authors/Task Force members (Alfonso F), Windecker
S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V,
Filippatos G, Hamm C, Head SJ, Jüni P, Kappetein AP,
Kastrati A, Knuuti J, Landmesser U, Laufer G,
Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M,
Stefanini GG, Taggart DP, Torracca L, Valgimigli M,
Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on
myocardial revascularization: The Task Force on
Myocardial Revascularization of the European Society
of Cardiology (ESC) and the European Association for
Cardio-Thoracic Surgery (EACTS) Developed with the
special contribution of the European Association of
Percutaneous Cardiovascular Interventions (EAPCI).
Eur Heart J. 35(37):2541-619. 2014. PMID: 25173339.
IF: 14,723. DOI: 10.1093/eurheartj/ehu278.
http://dx.doi.org/10.1093/eurheartj/ehu278
López Mínguez JR, Nogales Asensio JM, Doncel
Vecino LJ, Sandoval J, Romany S, Martínez Romero
P, Fernández Díaz JA, Fernández Portales J,
González Fernández R, Martínez Cáceres G, Merchán
Herrera A, Alfonso Manterola F; BABILON
Investigators. A prospective randomised study of the
paclitaxel-coated balloon catheter in bifurcated coronary lesions (BABILON trial): 24-month clinical and
angiographic results. EuroIntervention. 10(1):50-7.
AREA 3
Alfonso F, Pérez-Vizcayno MJ, Cárdenas A, García
Del Blanco B, Seidelberger B, Iñiguez A, GómezRecio M, Masotti M, Velázquez MT, Sanchís J, GarcíaTouchard A, Zueco J, Bethencourt A, Melgares R,
Cequier A, Dominguez A, Mainar V, López-Mínguez
JR, Moreu J, Martí V, Moreno R, Jiménez-Quevedo P,
Gonzalo N, Fernández C, Macaya C; RIBS V Study
Investigators, under the auspices of the Working
Group on Interventional Cardiology of the Spanish
Society of Cardiology. A randomized comparison of
drug-eluting balloon versus everolimus-eluting stent in
patients with bare-metal stent-in-stent restenosis: the
RIBS V Clinical Trial (Restenosis Intra-stent of Bare
Metal Stents: paclitaxel-eluting balloon vs.
everolimus-eluting stent). J Am Coll Cardiol.
63(14):1378-86. 2014. PMID: 24412457. IF: 15,343.
DOI: 10.1016/j.jacc.2013.12.006.
http://dx.doi.org/10.1016/j.jacc.2013.12.006
Alfonso F, Benedicto A, Bastante T, Diego G, Rivero F.
Comment on: "a multicenter randomized comparison
of paclitaxel-coated balloon catheter with conventional
balloon angioplasty in patients with bare-metal stent
restenosis and drug-eluting stent restenosis". Am
Heart J. 167(3):e9. 2014. PMID: 24576529. IF: 4,555.
DOI: 10.1016/j.ahj.2013.11.007.
http://dx.doi.org/10.1016/j.ahj.2013.11.007
de la Torre Hernández JM, Alfonso F, Martin Yuste V,
Sánchez Recalde A, Jimenez Navarro MF, Pérez de
Prado A, Hernández F, Abdul-Jawad Altisent O, Roura
G, García Camarero T, Elizaga J, Calviño R, Moreu J,
Bosa F, Jimenez Mazuecos J15, Ruiz-Arroyo JR,
Garcia Del Blanco B, Rumoso JR; ESTROFA-IM study
group. Comparison of Paclitaxel and Everolimus-eluting Stents in ST-segment Elevation Myocardial
Infarction and Influence of Thrombectomy on
Outcomes. ESTROFA-IM Study. Rev Esp Cardiol (Engl
Ed). 67(12):999-1006. 2014. PMID: 25432710. IF:
3,342. DOI: 10.1016/j.rec.2014.01.019.
http://dx.doi.org/10.1016/j.rec.2014.01.019
Ferrera C, Echavarría-Pinto M, Nuñez-Gil I, Alfonso F.
Bikram yoga and acute myocardial infarction. J Am Coll
Cardiol. 63(12):1223. 2014. PMID: 24509268. IF:
15,343. DOI: 10.1016/j.jacc.2013. 10.091.
Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. J Am Coll Cardiol.
63(24):2659-73. 2014. PMID: 24632282. IF: 15,343.
DOI: 10.1016/j.jacc.2014.02.545.
Valcárcel de Laiglesia MÁ, Alfonso F, Miró Ò,
Casademont J, Burbano Santos P, Burillo-Putze G,
Fernández
Pérez
C,
Martín-Sánchez
FJ.
Characteristics and longevity of electronic citations in
four25432710 leading biomedical journals in Spain.
Rev Esp Cardiol (Engl Ed). 67(10):837-43. 2014. PMID:
25262130. IF: 3,342. DOI: 10.1016/j.rec.2014.01.029.
Alfonso F, Pan M. Do we know how to treat bifurcation
coronary lesions?. Rev Esp Cardiol (Engl Ed).
67(10):790-3. 2014. PMID: 25262124. IF: 3,342. DOI:
10.1016/j.rec.2014.05.017.
Alfonso F, Cuevas C, Jimenez-Quevedo P, Gonzalo N,
Escribano N. Combined in vivo insights unraveling the
underlying substrate of an acute myocardial infarction
treated with a bioabsorbable vascular scaffold: from
imaging to pathology. JACC Cardiovasc Interv.
7(3):e17-8. 2014. PMID: 24650414. IF: 7,44. DOI:
10.1016/j.jcin.2013.05.035.
http://dx.doi.org/10.1016/j.jcin.2013.05.035
Byrne RA, Joner M, Alfonso F, Kastrati A. Drugcoated balloon therapy in coronary and peripheral
artery disease. Nat Rev Cardiol. 11(1):13-23. 2014.
PMID: 24189405. IF: 10,154. DOI: 10.1038/nrcardio.2013.165.
http://dx.doi.org/10.1038/nrcardio.2013.165
Das Neves BC, Núñez-Gil IJ, Alfonso F, Hernández
R, Cuevas C, Jimenez Quevedo P, Gomez de Diego
JJ, Escaned J, Macaya C, Fernández Ortiz A.
Evolutive recanalization of spontaneous coronary
– 133 –
AREA 3AREA 2 AREA 1
2014. PMID: 24832638. IF: 3,758. DOI:10.4244/
EIJV10I1A10.
http://dx.doi.org/10.4244/EIJV10I1A10
artery dissection: insights from a multimodality imaging
approach. Circulation. 129(6):719-20. 2014. PMID:
24515959. IF: 14,948. DOI: 10.1161/CIRCULATIONAHA.112.000101. http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000101
Alfonso F, Gonçalves L, Pinto F, Timmis A, Ector H,
Ambrosio G, Vardas P; Editors' Network European
Society of Cardiology Task Force. Fostering diffusion of
scientific contents of National Society Cardiovascular
Journals: the new ESC search engine. Heart.
100(6):450-5. 2014. PMID: 23899784. IF: 6,023. DOI:
10.1136/heartjnl-2013-304596.
http://dx.doi.org/10.1136/heartjnl-2013-304596
Bastante T, Alfonso F. Insights of optical coherence
tomography in renal artery fibromuscular dysplasia in a
patient with spontaneous coronary artery dissection.
Arq Bras Cardiol. 103(1):e18. 2014. PMID: 25120090.
IF: 1,124
Echavarría-Pinto M, Gonzalo N, Ibañez B, Petraco R,
Jimenez-Quevedo P, Sen S, Nijjer S, Tarkin J, Alfonso
F, Núñez-Gil IJ, Bañuelos C, Quirós A, Fernández-Ortiz
A, Macaya C, Koo BK, Davies J, Escaned J. Low coronary microcirculatory resistance associated with profound hypotension during intravenous adenosine infusion: implications for the functional assessment of
coronary stenoses. Circ Cardiovasc Interv. 7(1):35-42.
2014. PMID: 24399244. IF: 6,982.
DOI:
http://dx.doi.org/10.1161/CIRCINTERVENTIONS.113.000659
Alfonso F, Jimenez-Quevedo P, Gonzalo N, Medina M,
Bañuelos C. Neoatherosclerosis after paclitaxel-coated
balloon angioplasty for in-stent restenosis. Circulation.
129(8):923-5. 2014. PMID: 24566068. IF: 14,948.
DOI:
http://dx.doi.org/10.1161/CIRCULATIONAHA.112.000800
Alfonso F, Gonzalo N, Benedicto A. New Insights on
Plaque Erosion and Calcified Nodules: Seeing is
Believing. J Am Coll Cardiol. 63(14):1458-9. 2014.
PMID: 24315900. IF: 15,343. DOI: 10.1016/j.jacc.
2013.08.1653.
– 134 –
Windecker S, Stortecky S, Stefanini GG, da Costa BR,
Rutjes AW, Di Nisio M, Silletta MG, Maione A, Alfonso
F, Clemmensen PM, Collet JP, Cremer J, Falk V,
Filippatos G, Hamm C, Head S, Kappetein AP, Kastrati
A, Knuuti J, Landmesser U, Laufer G, Neumann FJ,
Richter D, Schauerte P, Sousa Uva M, Taggart DP,
Torracca L, Valgimigli M, Wijns W, Witkowski A, Kolh P,
Jüni P. Revascularisation versus medical treatment in
patients with stable coronary artery disease: network
meta-analysis. BMJ. 348:g3859. 2014. PMID:
24958153. IF: 16,378. DOI: 10.1136/bmj.g3859.
http://dx.doi.org/10.1136/bmj.g3859
Rivero F, Cuesta J, Benedicto A, Bastante T, Alfonso F.
Ruptured neoatherosclerosis presenting as a large
intrastent neointimal dissection. JACC Cardiovasc
Interv. 7(11):e169-70. 2014. PMID: 25459046. IF: 7,44.
DOI: 10.1016/j.jcin.2014.04.028.
http://dx.doi.org/10.1016/j.jcin.2014.04.028
Méndez I, Pozo E, Benedicto A, Olivera MJ, Ascensión A,
Jiménez-Borreguero LJ, Alfonso F. Searching for the culprit
vessel in acute myocardial infarction beyond angiography:
role of cardiac magnetic resonance. Circulation. 130(5):e324. 2014. PMID: 25070554. IF: 14,948. DOI: 10.1161/CIRCULATIONAHA.114.009739.
http://dx.doi.org/10.1161/CIRCULATIONAHA.114.
009739
Jimenez-Quevedo P, Gonzalez-Ferrer JJ, Sabate M,
Garcia-Moll X, Delgado-Bolton R, Llorente L, Bernardo
E, Ortega-Pozzi A, Hernandez-Antolin R, Alfonso F,
Gonzalo N, Escaned J, Bañuelos C, Regueiro A, Marin
P, Fernandez-Ortiz A, Neves BD, Del Trigo M,
Fernandez C, Tejerina T, Redondo S, Garcia E, Macaya
C. Selected CD133+ Progenitor Cells to Promote
Angiogenesis in Patients With Refractory Angina: Final
Results of the PROGENITOR Randomized Trial. Circ
Res. 115(11):950-60. 2014. PMID: 25231095. IF:
11,089. DOI: 10.1161/CIRCRESAHA.115.303463.
http://dx.doi.org/10.1161/CIRCRESAHA.115.303463
Alfonso F, Bastante T, Rivero F, Cuesta J, Benedicto A,
Saw J, Gulati R. Spontaneous coronary artery dissection. Circ J. 78(9):2099-110. 2014. PMID: 25131524.
IF: 3,685
AREA 3
Lozano A, Bastante T, Salamanca J, Aguilar R, Montes
de Oca R, Rodríguez D, Alfonso F. Tako-tsubo cardiomyopathy triggered by Influenza A virus infection. Int
J Cardiol. 174(2):e52-3. 2014. PMID: 24768388. IF:
6,175. DOI: 10.1016/j.ijcard.2014.04.033
Alfonso F, Nuccio J, Cuevas C, Cárdenas A,
Gonzalo N, Jimenez-Quevedo P. Treatment of coronary in-stent restenosis with bioabsorbable vascular
scaffolds. J Am Coll Cardiol. 63(25 Pt A):2875.
2014. PMID: 24969756. IF: 15,343. DOI: 10.1016/
j.jacc.2013.05.107.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ALFONSO MANTEROLA,
FERNANDO
Administración precoz de B-bloqueantes antes de la
repercusión en pacientes con infarto agudo de miocardio con elevación de ST sometidos a angioplastia
priMARÍA; (Versión 1.0: 07-10-13). MAATSCHAP CARDIOLOGIE ISALA KLINIEKEN 9129/ESTUDIO EARLYBAMI
EudraCT: 2010-023394-19
PRINCIPAL RESEARCHER: ALFONSO MANTEROLA,
FERNANDO
Ensayo multinacional, aleatorizado, doble ciego, controlado con placebo, para evaluar el efecto de ticagrelor 90 mg dos veces al día sobre la incidencia de
muerte cardiovascular, infarto de miocardio o ictus en
pacientes con diabetes mellitus tipo 2; (Versión 1: 2510-13) ASTRAZENECA AB D513BC00001
EudraCT: 2013-003519-23
PRINCIPAL RESEARCHER: BENEDICTO BUENDÍA,
AMPARO
Efecto de la infusión intracoronaria de células madre
mononucleares derivadas de la médula ósea (CMNMO) sobre la mortalidad por cualquier caso en el infarto agudo de miocardio; (Versión 1.3: 12-10-12).
QUEEN MARY UNIVERSITY LONDON BAMI-01
EudraCT: 2012-001495-11
GRUPO 48
HEAD OF LABORATORY
Luis Jesús Jiménez Borreguero
GROUP MEMBERS
• Río Jorge Aguilar Torres
• Fernando Alfonso Manterola
RESEARCH INTEREST
Preclinical and translational cardiovascular research
Our work has been developed in cardiovascular imaging technology for translational research, in coordination with basic scientists at the Hospital de La
Princesa and the National Center for Cardiovascular
Research (CNIC). In collaboration with basic scientists
we have contributed by our translational scientific
vision and by the application of cardiovascular (CV)
imaging technology for both, preclinical and clinical
research. Our collaborations include work on several
mouse and zebrafish models of myocardial regeneration, atherosclerosis, heart aging, systolic, diastolic
and diabetic heart failure, non-compacted cardiomyopathy, left ventricular hypertrophy, aortic aneurysm,
degenerative aortic valve, aortic annular ectasia,
mitral insufficiency, coronary aneurysm, acute pulmonary hypertension, and chronic pulmonary hypertension. In many of these projects our basic CV imag-
– 135 –
AREA 3AREA 2 AREA 1
Alfonso F, Bastante T. Spontaneous coronary artery
dissection: novel diagnostic insights from large series
of patients. Circ Cardiovasc Interv. 7(5):638-41. 2014.
PMID: 25336602. IF: 6,982. DOI: 10.1161/CIRCINTERVENTIONS.114.001984.
http://dx.doi.org/10.1161/CIRCINTERVENTIONS.114.001984
ing analysis and our clinical expertise have led to identifying the clinical translation to human disease.
Clinical Cardiovascular Research
In the Hospital de la Princesa, our main line of clinical
research is focused in the characterization of the heart
phenotype of patients with hypertrophic cardiomyopathy
and its prognostic association, by identifying new goals
in cardiovascular imaging technology.
In collaboration with CNIC, we have contributed to the
design of the trials, Progression of Early Subclincial
Atherosclerosis (PESA) and Aragon Workers’ Health Study
(AWHS). We are coordinating the imaging aspects of these
projects, which are two large population trials focused in
the study of early detection and progression of subclinical
atherosclerosis in middle aged adult populations.
We have consolidated our collaboration with basic scentists for the translation of basic research to clinical scenario
by using cardiovascular imaging technology. Our work on
several mouse and zebrafish models is currently carrying
on in the focus of myocardial regeneration, atherosclerosis, heart aging, systolic, diastolic and diabetic heart failure, non-compacted cardiomyopathy, left ventricular
hypertrophy, aortic aneurysm, degenerative aortic valve,
aortic annular ectasia, mitral insufficiency, coronary
aneurysm, acute pulmonary hypertension, and chronic
pulmonary hypertension. In many of these projects our
basic CV imaging analysis and our clinical expertise have
led to identifying the clinical translation to human disease.
In the clinical research scenario we are currently
coordinating a myocardiopathies study at Hospital
de La Princesa and the imaging focus of PESA
study at CNIC until June 2019.
MAJOR GRANTS
• Moldenhauer Díaz, Fernando. Estudio clínico,
neuroanatómico y funcional mediante técnicas
de neuroimagen en adultos con SD y sin demencia: patrones predictivos para el desarrollo de
demencia. PI12/01695. ISCIII. 2013-2015.
– 136 –
• García Polo, Iluminada. Efectos de los nitratos
orales sobre la presión de pulso y la elasticidad
arterial en pacientes mayores de 65 años con
hipertensión sistólica aislada refractaria. EC11111. MSPSI. 2012-2014.
• Jiménez Borreguero, Luis Jesús. FCNIC. 2009- .
PUBLICATIONS
(10)
Domingo E, Grignola JC, Aguilar R, Arredondo C,
Bouteldja N, Messeguer ML, Roman A. Impairment of
pulmonary vascular reserve and right ventricular systolic
reserve in pulmonary arterial hypertension. BMC Pulm
Med. 14:69. 2014. PMID: 24762000. IF: 2,489. DOI:
10.1186/1471-2466-14-69.
http://dx.doi.org/10.1186/1471-2466-14-69
López-Olañeta MM, Villalba M, Gómez-Salinero JM,
Jiménez-Borreguero LJ, Breckenridge R, Ortiz-Sánchez
P, García-Pavía P, Ibáñez B, Lara-Pezzi E. Induction of the
calcineurin variant CnAβ1 after myocardial infarction
reduces post-infarction ventricular remodelling by promoting infarct vascularization. Cardiovasc Res.
102(3):396-406. 2014. PMID: 24667850. IF: 5,808. DOI:
10.1093/cvr/cvu068.
http://dx.doi.org/10.1093/cvr/cvu068
Sánchez SA, Méndez-Barbero N, Santos-Beneit AM,
Esteban V, Jiménez-Borreguero LJ, Campanero MR,
Redondo JM. Nonlinear optical 3-dimensional method for
quantifying atherosclerosis burden. Circ Cardiovasc
Imaging. 7(3):566-9. 2014. PMID: 24847011. IF: 6,752.
DOI: 10.1161/CIRCIMAGING.114.001753.
http://dx.doi.org/10.1161/CIRCIMAGING.114.001753
Lorenzo N, Restrepo JA, Aguilar R. Pulmonary embolism,
where are the thrombi?. Eur J Intern Med. 25(8):e91-2.
2014.
PMID:
25044095.
IF:
2,3.
DOI:
10.1016/j.ejim.2014.06.024.
http://dx.doi.org/10.1016/j.ejim.2014.06.024
Ibanez B, Macaya C, Sánchez-Brunete V, Pizarro G,
Fernández-Friera L, Mateos A, Fernández-Ortiz A,
García-Ruiz JM, García-Álvarez A, Iñiguez A, Jiménez-
AREA 3
González-Rosa JM, Guzmán-Martínez G, Marques IJ,
Sánchez-Iranzo H, Jiménez-Borreguero LJ, Mercader N.
Use of Echocardiography Reveals Reestablishment of
Ventricular Pumping Efficiency and Partial Ventricular Wall
Motion Recovery upon Ventricular Cryoinjury in the
Zebrafish. PLoS One. 9(12):e115604. 2014. PMID:
25532015. IF: 3,534. DOI: 10.1371/journal.pone. 0115604.
García-Prieto J, García-Ruiz JM, Sanz-Rosa D, Pun A,
García-Alvarez A, Davidson SM, Fernández-Friera L,
Nuno-Ayala M, Fernández-Jiménez R, Bernal JA,
Izquierdo-Garcia JL, Jimenez-Borreguero J, Pizarro G,
Ruiz-Cabello J, Macaya C, Fuster V, Yellon DM, Ibanez B.
β3 adrenergic receptor selective stimulation during
ischemia/reperfusion improves cardiac function in translational models through inhibition of mPTP opening in
cardiomyocytes. Basic Res Cardiol. 109(4):422. 2014.
PMID: 24951958. IF: 5,955. DOI: 10.1007/s00395-0140422-0.
http://dx.doi.org/10.1007/s00395-014-0422-0
Méndez I, Pozo E, Benedicto A, Olivera MJ, Ascensión A,
Jiménez-Borreguero LJ, Alfonso F. Searching for the culprit vessel in acute myocardial infarction beyond angiography: role of cardiac magnetic resonance. Circulation.
130(5):e32-4. 2014. PMID: 25070554. IF: 14,948. DOI:
10.1161/CIRCULATIONAHA.114.009739.
h t t p : / / d x . d o i . o r g / 1 0 . 1 1 6 1 / C I R C U L AT I O N A HA.114.009739
Lozano A, Bastante T, Salamanca J, Aguilar R, Montes
de Oca R, Rodríguez D, Alfonso F. Tako-tsubo cardiomyopathy triggered by Influenza A virus infection. Int J
Cardiol. 174(2):e52-3. 2014. PMID: 24768388. IF: 6,175.
DOI: 10.1016/j.ijcard.2014.04.033
Lucas E, Jurado-Pueyo M, Fortuño MA, FernándezVeledo S, Vila-Bedmar R, Jiménez-Borreguero LJ,
Lazcano JJ, Gao E, Gómez-Ambrosi J, Frühbeck G,
Koch WJ, Díez J, Mayor F Jr, Murga C Biochim Biophys
Acta. Downregulation of G protein-coupled receptor
kinase 2 levels enhances cardiac insulin sensitivity and
switches on cardioprotective gene expression patterns.
Biochim Biophys Acta. 1842(12 Pt A):2448-56. 2014.
PMID:
25239306.
IF:
5,089.
DOI:
10.1016/j.bbadis.2014.09.004.
AREA 3AREA 2 AREA 1
Borreguero J, López-Romero P, Fernández-Jiménez R,
Goicolea J, Ruiz-Mateos B, Bastante T, Arias M, IglesiasVázquez JA, Rodriguez MD, Escalera N, Acebal C,
Cabrera JA, Valenciano J, de Prado AP, FernándezCampos MJ, Casado I, García-Rubira JC, García-Prieto
J, Sanz-Rosa D, Cuellas C, Hernández-Antolín R,
Albarrán A, Fernández-Vázquez F, de la Torre-Hernández
JM, Pocock S, Sanz G, Fuster V. Response to letter
regarding article, "effect of early metoprolol on infarct size
in ST-segment-elevation myocardial infarction patients
undergoing primary percutaneous coronary intervention:
the Effect of Metoprolol in Cardioprotection During an
Acute Myocardial Infarction (METOCARD-CNIC) trial".
Circulation. 130(3):e19-20. 2014. PMID: 25024129. IF:
14,948. DOI: 10.1161/CIRCULATIONAHA.114.009352.
h t t p : / / d x . d o i . o r g / 1 0 . 1 1 6 1 / C I R C U L AT I O N A HA.114.009352
GRUPO 57
HEAD OF LABORATORY
Carmen Suárez Fernández
GROUP MEMBERS
• Juan Mariano Aguilar Mulet
• Paloma Caballero Sánchez-Robles
• Carmen del Arco Galán
• Alfonsa Friera Reyes
• Iluminada García Polo
• Paloma Gil Martínez
• Patricia Ibáñez Sanz
• Fernando Moldenhauer Díaz
• Diego Real de Asúa Cruzat
• Isabel Rivas Pollmar
• Nuria Ruiz-Giménez Arrieta
• Gema Vega González
– 137 –
RESEARCH INTEREST
Cardiovascular diseases (CVD) are the main cause of
mortality in developed countries. The prevalence and
incidence of CVD are increasing. There are a great variety of new cardiovascular drugs that are targeted to
dyslipidaemia, arterial and venous thrombosis and diabetes, and can modify the natural history of CVD.
Age is an important determinant of arterial and venous
outcomes. However, usual clinical practice in a general
setting reveals a disproportionately low use of cardiovascular medications and intensive treatment in elderly
patients that could otherwise benefit from their use. On
the other hand, there probably is an excessive use of
these medications in patients with cognitive impairment
and short life expectancy. There is not enough information about cardiovascular therapies in very elderly
patients with multiple comorbidities/diseases.
The purpose of this group is:
1) To investigate the efficacy of new cardiovascular
treatments in different settings
2) To evaluate the risks and benefit obtained from
antithrombotic treatment in elderly patients with venous
thromboembolic disease and atrial fibrillation.
3) To describe the natural history of CVD in very elderly patients (over 90).
MAJOR GRANTS
• Suarez Fernández, Carmen. Red de innovación en tecnologías médicas y sanitarias. ISCIII. PT13/0006/0016.
2014-2017.
• Suarez Fernández, Carmen. Proyecto MASCERCA con
kit de telebiometria autónomo. Compra publica innovadora. MASCERCA. 2014-2014.
• Moldenhauer Diaz, Fernando. Estudio clínico, neuroanatomico y funcional mediante técnicas de neuroimagen en adultos con SD y sin demencia: patrones predictivos para el desarrollo de demencia. ISCIII.
PI12/01695. 2012-2015.
• Caballero Sánchez-Robles, María Paloma. RM para la
arteroesxclerosis de la aorta y arterias carótidas de
– 138 –
pacientes con hipercolesterolemia familiar de acuerdo a
protocolo. FUNJIM. 2009-.
PUBLICATIONS (10)
Martínez-Castelao A, Górriz JL, Segura-de la Morena
J, Cebollada J, Escalada J, Esmatjes E, Fácila L,
Gamarra J, Gràcia S, Hernánd-Moreno J, Llisterri-Caro
JL, Mazón P, Montañés R, Morales-Olivas F, MuñozTorres M, de Pablos-Velasco P, de Santiago A,
Sánchez-Celaya M, Suárez C, Tranche S. Consensus
document for the detection and management of chronic kidney disease. Nefrologia. 34(2):243-62. 2014.
PMID:
24658201.
IF:
1,442.
DOI:
10.3265/Nefrologia.pre2014.Feb.12455.
http://dx.doi.org/10.3265/Nefrologia.pre2014.Feb.124
55
M Hernández Olmedo, P Gil Martínez, V de la Cuesta
Esteban, JJ Curbelo García, M Forero, J Iglesias
Franco. Dificultad respiratoria en un varón tratado con
heparina. Emergencias. (26):238-239. 2014. IF: 2,583
Real de Asua D, Parra P, Costa R, Moldenhauer F,
Suárez C. Evaluation of the impact of abdominal obesity on glucose and lipid metabolism disorders in adults
with Down syndrome. Res Dev Disabil. 35(11):29422949. 2014. PMID: 25108610. IF: 2,735. DOI:
10.1016/j.ridd.2014.07.038.
http://dx.doi.org/ 10.1016/j.ridd.2014.07.038
D Mesado, P Gil, L Prósper, C Sáez. Insuficiencia
Cardiaca terminal: último acto. Medicina Paliativa.
21(2):55-61. 2014. IF: 0,162. DOI: 10.1016/j.medipa.2012.09.006.
http://dx.doi.org/10.1016/j.medipa.2012.09.006
Girón Moreno RM, Caballero P, Friera A. Multidetector
computed tomography angiography for pre-embolization assessment in cystic fibrosis patients with massive
haemoptysis. Respir Med. 108(5):816-7. 2014. PMID:
24613210. IF: 2,917. DOI: 10.1016/j.rmed.2013.
12.010.
AREA 3
Pérez-Rodon J, Martínez-Alday J, Barón-Esquivias G,
Martín A, García-Civera R, Del Arco C, Cano-Gonzalez
A, Moya-Mitjans A. Prognostic value of the electrocardiogram in patients with syncope: Data from the Group
for Syncope Study in the Emergency Room (GESINUR). Heart Rhythm. 11(11):2035-44. 2014. PMID:
24993462. IF: 4,918. DOI: 10.1016/j.hrthm.2014.
06.037.
http://dx.doi.org/10.1016/j.hrthm.2014.06.037
Suárez C, Galgo A, Mantilla T, Leal M, Escobar C.
Variables associated with change in blood pressure
control status after 1-year follow up in primary care: a
retrospective analysis: the TAPAS study. Eur J Prev
Cardiol. 21(1):12-20. 2014. PMID: 23572479. IF:
2,675. DOI: 10.1177/2047487313483609.
http://dx.doi.org/10.1177/2047487313483609
Gómez-Huelgas R, Giner-Galvañ V, Mostaza JM,
Cuende JI, de Miguel-Yanes JM, Rovira E, SánchezFuentes D, Suárez Fernández C, Román Sánchez P;
SEMI Working Group. Unanswered clinical questions in
the management of cardiometabolic risk in the elderly:
a statement of the Spanish society of internal medicine.
BMC Cardiovascular Disorders 14:193. 2014. PMID:
25519433. IF: 1,5.
Rodríguez Salvanes F, Arnalich B, Luquero Bueno
S, Díaz López A, de la Fuente H, Suárez C,
Ancochea J, Aspa J. The incidence of cardiovascular events after hospitalization due to CAP and their
association with different inflammatory markers.
BMC Pulm Med. 14(1):197. 2014. PMID:
25495677. IF: 2,489. DOI: 10.1186/1471-246614-197.
http://dx.doi.org/10.1186/1471-2466-14-197
BOOKS
Galván Román JM, Real de Asúa D, Suárez C.
Dislipemia. Protocolos “Manejo diagnóstico y terapéutico de las comorbilidades en la EPOC”. Elsevier
Doyma. ISBN: 978-84-752-7626
CLINICAL TRIALS
PRINCIPAL RESEARCHER: GIL MARTINEZ, PALOMA
MARÍA
Estudio multicéntrico, prospectivo, aleatorizado, abierto para evaluar el efecto de serelaxina comparado con
el tratamiento de referencia en pacientes con insuficiencia cardiaca aguda (ICA), Versión: 13-09-13.
NOVARTIS FARMACEUTICA, S.A. CRLX030A3301
2013-002513-35
PRINCIPAL RESEARCHER: MOLDENHAUER DÍAZ,
FERNANDO
Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo fase 2 para evaluar la eficacia,
seguridad y tolerancia de RO5186582 en adultos y
adolescentes con síndrome de Down (CLEMATIS);
Versión 1:08-11-13 F. HOFFMANN-LA ROCHE LTD.
BP27832
EudraCT: 2013-001263-23
PRINCIPAL RESEARCHER: SUÁREZ FERNÁNDEZ,
CARMEN
Estudio aleatorizado, multicéntrico, doble ciego, de
grupos paralelos y controlado con placebo de los efectos de canagliflozina en los criterios de valoración
renales en sujetos adultos con diabetes mellitus de tipo
2 ("CANVAS-R"); (Versión INT1: 16-10-13). JANSSENCILAG INTERNATIONAL NV 28431754DIA4003
EudraCT: 2013-003050-25
CARMEN
PREFER EN TEV: Prevención de episodios de tromboembolia-Registro europeo sobre tromboembolia
venosa; (Versión 2.0: 6-11-13). DAIICHI SANKYO
EUROPE GMBH DAI-VTE-2013-02
– 139 –
AREA 3AREA 2 AREA 1
Sanclemente C, Yeste M, Suárez C, Coll R, Aguilar E,
Sahuquillo JC, Lerma R, Monreal M; FRENA investigators. Predictors of outcome in stable outpatients with
peripheral artery disease. Intern Emerg Med. 9(1):6977. 2014. PMID: 23054402. IF: 2,41. DOI:
10.1007/s11739-012-0854-1.
http://dx.doi.org/10.1007/s11739-012-0854-1
CARMEN
Validación del cuestionario ACTS en pacientes con fibrilación auricular (FA) tratados con anticoagulantes
orales (ACOs) en consultas de medicina interna y neurología de España. Estudio ALADIN. (Versión 3.1:2802-14). BAYER HISPANIA S.L. BAY-ACO-2014-01
GRUPO 49
HEAD OF LABORATORY
Blanca Novella Arribas
GROUP MEMBERS
• Ana Cubillo Serna
• María Jesús Fernández Luque
• Ángela Gallego Arenas
• Amelia González Gamarra
• María del Pilar Loeches Belinchón
• Javier López González
• M. Soledad Mayayo Vicente
• Francisco José Rodríguez Salvanés
• María Lourdes Ruiz Díaz
• Rosa María Sánchez Alcalde
• Luis María Sánchez Gómez
• Belén Sierra García
RESEARCH INTEREST
Our investigation addresses the genesis of scientific evidence on cardiovascular risk (CVR) in general and in specific populations, as well as evaluating the transfer of evidence to both the professionals and the population.
Our research projects addressing these issues are:
"Development, implementation and evaluation of a guide
of clinical practice in global cardiovascular risk";
"Evaluation, in Terms of Morbimortality and control of
CVR factors, of the implementation of an adaptation of a
– 140 –
guide of clinical practice in CVR"; and "A Clinical Trial Of
Two Educational Strategies In Cardiovascular Health In
Child Population (SAVINHEARTS)".
We collaborate with other groups of the Institute in the
projects: "Effect of oral nitrates on pulse pressure and
arterial elasticity in patients older than 65 years with
refractory isolated systolic hypertension”. Funded by a
grant for non-commercial clinical trials from Spanish
Ministry of Health. We also collaborate in projects from
other institutions related to the CVR: "Project Prevention
of Early Complications of Diabetes in Europe. European
Project e-PREDICT" with Hospital La Paz as a member of
a node of the Cardiovascular Diseases Network (ISCIII);
and "CARDIORISK / MAPAPRES Project” with the
Hospital 12 October. Dr Novella is a member of the international group RISC (research in insulin resistance).
We promote the investigation of the other group members in these lines. Thus, we have participated in the projects: "Control of blood pressure in diabetic patients: a
comparative study between treatment based on BP
measured in the doctor´s practice and treatment based
on self-measurement of BP by the patient at home";
“Development from primary care of a risk stratification
model in patients with heart failure to predict disability and
hospitalization", within the network of Health in Chronic
Disease; the studies “PREDIMERC” and “CHAMBS”,
with the research network Diabetes AP (GEDAPS); and
the “FOCUS” trial aimed at the fixed-dose combination of
drugs for secondary prevention of IHD, with the IASB. .
Over the next five years, thanks to the experience gained
in these projects, we plan to start a project to establish a
tool for the assessment of doctor-patient communication
addressed to the measurement and control of CVR. We
also plan to analyze and publish the results of studies
launched over the years and to continue cooperating with
other groups of the Institute.
MAJOR GRANTS
Novella Arribas, Blanca. A clinical trial of two educational
strategies in cardiovascular health in child population
(SAVINHEARTS). PI11/00798. ISCIII. 2012-2014.
AREA 3
Castellano JM, Sanz G, Peñalvo JL, Bansilal S,
Fernández-Ortiz A, Alvarez L, Guzmán L, Linares JC,
García F, D’Aniello F, Arnáiz JA, Varea S, Martínez F,
Lorenzatti A, Imaz I, Sánchez-Gómez LM,
Roncaglioni MC, Baviera M, Smith Jr. SC, Taubert K,
Pocock S, Brotons C, Farkouh ME, Fuster V. A polypill strategy to improve adherence: results from
FOCUS (Fixed-dose Combination Drug for
Secondary Cardiovascular Prevention) Project.
Journal of the American College of Cardiology.
64(20):2071-82. 2014. PMID: 25193393. IF: 15,343.
DOI: 10.1016/j.jacc.2014.08.021.
Monje A, Monje F, González-García R, GalindoMoreno P, Rodriguez-Salvanes F, Wang HL.
Comparison between microcomputed tomography
and cone-beam computed tomography radiologic
bone to assess atrophic posterior maxilla density
and microarchitecture. Clin Oral Implants Res.
25(6):723-8. 2014. PMID: 23442126. IF: 3,123.
DOI: 10.1111/clr.12133.
http://dx.doi.org/10.1111/clr.12133
Amado Rivero-Santana; Leticia Cuellar-Pompa; Luis M
Sánchez-Gómez; Lilisbeth Perestelo-Pérez; Pedro
Serrano-Aguilar. Effectiveness And Cost-Effectiveness
Of Different Immunization Strategies Against Whooping
Cough To Reduce Child Morbidity And Mortality.
Health Policy. 115(1):82-91. 2014. PMID: 24444703.
IF: 1,725. DOI: 10.1016/j.healthpol.2013.12.007.
http://dx.doi.org/10.1016/j.healthpol.2013.12.007
de Ulíbarri Pérez JI, Fernández G, Rodríguez Salvanés
F, Díaz López AM. Nutritional screening; control of clinical undernutrition with analytical parameters. Nutr
Hosp. 29(4):797-811. 2014. PMID: 24679020. IF:
1,25. DOI: 10.3305/nh.2014.29.4.7275.
http://dx.doi.org/10.3305/nh.2014.29.4.7275
Rajas O, Ortega-Gómez M, Galván Román JM, Curbelo
J, Fernández Jiménez G, Vega Piris L, Rodríguez
Salvanes F, Arnalich B, Luquero Bueno S, Díaz López A,
de la Fuente H, Suárez C, Ancochea J, Aspa J. The incidence of cardiovascular events after hospitalization due
to CAP and their association with different inflammatory
markers. BMC Pulm Med. 14(1):197. 2014. PMID:
25495677. IF: 2,489. DOI: 10.1186/1471-2466-14-197.
http://dx.doi.org/10.1186/1471-2466-14-197
– 141 –
AREA 3AREA 2 AREA 1
PUBLICATIONS (5)
Line 3.7
New therapies in
infectious pathologies
GRUPO 50
HEAD OF LABORATORY
GROUP MEMBERS
• José Rafael de la Cámara de Llanza
• Ana Salas Aparicio
• María Teresa Sánchez Casasola
• Jesús Sanz Sanz
• Cristina Sarriá Cepeda
RESEARCH INTEREST
Our group has been working on the study of HIV infection for more than 20 years. We have participated in
several clinical trials and international research projects.
Currently, we continue working in the Research
Network on AIDS (CoRIS) collecting data from patients
with HIV infection who come to our clinic for the first
time, for epidemiological studies, and sending blood
samples periodically to the Biobank Network of AIDS,
for virological and immunological studies. This project
will keep going for years, and will also continue collecting the data necessary for these studies. We have hired
a doctor for two years with funds from the Network,
and hopefully we can continue employing her in the
future.
We are also involved in clinical trials of new drugs for
HIV, including the combination of Darunavir and cobicistat and the new nonnucleoside, Doravirine, both
drugs for naive and pretreated patients. These trials will
begin in 2015 and will last three years.
In addition, another field of interest, in which we have
more than ten years of experience, is the HIV / HCV
– 142 –
coinfection. This aspect of the HIV infection is currently having a major projection, due to the appearance of
new drugs to treat hepatitis C, direct antiviral agents,
that have revolutionized the treatment, with the greatest effectiveness until now (more than 90%) and few
side effects. We are collaborating with the HEPAVIR
cohort of coinfected patients, along with various centres in Spanish territory, where we have a number of
more than 600 patients treated so far. The study of new
drugs in real life is very important because it can reveal
side effects not seen before in clinical trials.
In this sense, and also in a multicenter group, we are
studying the impact of sustained viral response in cardiovascular risk and inflammation markers, and look
forward to the first data in late 2015.
MAJOR GRANTS
de los Santos Gil, Ignacio. RED DE SIDA (RIS).
RD12/0017/0011. ISCIII. 2013-2016.
PUBLICATIONS (26)
Diez M, Garriga C, Pons M, Ten A, Marcos H, Gutiérrez
G, Moreno S, González-García J, Barrios AM, Arponen
S, García MT, Royo MC, Toledo J, González G,
Aranguren R, Izquierdo A, Viloria LJ, Martínez E,
Elizalde L, Castrillejo D, López I, Redondo C, Cano A,
the Hospital Survey Study Group (collaborator Sanz J
et al). A low-cost, sustainable,second generation system for surveillance of people living with HIV in Spain:
10-year trends in behavioural and clinical indicators,
2002 to 2011. Euro Surveill. 2014 May 22;19(20). pii:
20805. 2014. PMID: 24871758. IF: 4,659
Muñoz-Cobo B, Giménez E, Solano C, de la Cámara
R, Nieto J, López J, Amat P, Garcia-Noblejas A,
Navarro D. An evaluation of the role of NKG2C+ natural killer cells in protection from cytomegalovirus
DNAemia early following allogeneic stem cell transplantation. J Med Virol. 86(5):806-11. 2014. PMID:
AREA 3
Monge S, Guillot V, Alvarez M, Chueca N, Stella N,
Peña A, Delgado R, Córdoba J, Aguilera A, Vidal C,
García F; CoRIS (de los Santos I, Sanz J). Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations.
PLoS One. 9(3):e90710. 2014. PMID: 24637804. IF:
3,534. DOI: 10.1371/journal.pone.0090710.
Olmos C, Vilacosta I, Fernández C, Sarriá C, López J,
Del Trigo M, Ferrera C, Vivas D, Maroto L, Hernández
M, Rodríguez E, San Román JA. Comparison of clinical
features of left-sided infective endocarditis involving
previously normal versus previously abnormal valves.
Am J Cardiol. 114(2):278-83. 2014. PMID: 24878130.
IF: 3,425. DOI: 10.1016/j.amjcard.2014.04.036.
http://dx.doi.org/10.1016/j.amjcard.2014.04.036
Suárez-García I, Sobrino-Vegas P, Tejada A et al.
(Colaborador I. de los Santos). Compliance with national guidelines for HIV treatment and its association with
mortality and treatment outcome: a study in a Spanish
cohort. HIV Medicine. 15(2):86-97. 2014. PMID:
24007468. IF: 3,454. DOI: 10.1111/hiv.12078.
http://dx.doi.org/10.1111/hiv.12078
Ljungman P, Brand R, Hoek J, de la Camara R,
Cordonnier C, Einsele H, Styczynski J, Ward KN,
Cesaro S, for the Infectious Diseases Working Party of
the European Group for B, Marrow T. Donor
Cytomegalovirus Status Influences the Outcome of
Allogeneic Stem Cell Transplant: A Study by the
European
Group
for
Blood
and
Marrow
Transplantation. Clinical Infectious Diseases.
59(4):473-481. 2014. PMID: 24850801. IF: 9,416. DOI:
10.1093/cid/ciu364.
http://dx.doi.org/10.1093/cid/ciu364
Martinez E, Gonzalez-Cordon A, Ferrer E, Domingo P,
Negredo E, Gutierrez F, Portilla J, Curran A,
Podzamczer D, Murillas J, Bernardino JI, Santos I,
Carton JA, Peraire J, Pich J, Perez I, Gatell JM;
ATADAR Study Group (collaborator Sanz J et al). Early
lipid changes with atazanavir/ritonavir or darunavir/
ritonavir. HIV Med. 15(6):330-338. 2014. PMID:
24417772. IF: 3,454. DOI: 10.1111/hiv.12121.
http://dx.doi.org/10.1111/hiv.12121
Berenguer J, Zamora FX, Carrero A, Von Wichmann
MA, Crespo M, López-Aldeguer J, Aldámiz-Echevarría
T, Montes M, Quereda C, Téllez MJ, Galindo MJ, Sanz
J, Santos I, Guardiola JM, Esteban H, Bellón JM,
González-García J; GESIDA HIVHCV Cohort Study
Group. Effects of sustained viral response in patients
with HIV and chronic hepatitis C and nonadvanced liver
fibrosis. J Acquir Immune Defic Syndr. 66(3):280-287.
2014. PMID: 25157646. IF: 4,394. DOI:
10.1097/QAI.0000000000000156.
http://dx.doi.org/10.1097/QAI.0000000000000156
Domingo P, Gutierrez Mdel M, Gallego-Escuredo JM,
Torres F, Mateo GM, Villarroya J, de los Santos I,
Domingo JC, Villarroya F, Del Rio L, Estrada V, Giralt M.
Effects of switching from stavudine to raltegravir on
subcutaneous adipose tissue in HIV-infected patients
with HIV/HAART-associated lipodystrophy syndrome
(HALS). A clinical and molecular study. PLoS One.
9(2):e89088. 2014. PMID: 24586518. IF: 3,534. DOI:
10.1371/journal.pone.0089088.
De Los Santos I, Montes M, Sanz-Moreno J, De Miguel
J, Sanz-Sanz J, Gaspar G, Perez-Caballero L. Efficacy
and tolerability of telaprevir (TVR)-based triple therapy
in HIV/HCV-coinfected patients. J Int AIDS Soc. 17(4
Suppl 3):19633. 2014. PMID: 25394137. IF: 4,207.
DOI: 10.7448/IAS.17.4.19633
http://dx.doi.org/10.7448/IAS.17.4.19633.
Ramirez ML, Vargas FX, González-Garcia J, Quereda
C, Pérez-Elías MJ, de Cea AM, Barros C, Condés E,
Moreno JS, Santos I, Torralba M, Aldamiz-Echevarria T,
Moreno A. Etravirine-based antiretroviral therapy in
HIV/hepatitis C virus coinfected advanced fibrosis
patients receiving triple therapy against hepatitis C virus
with telaprevir. AIDS. 28(16):2487-2489. 2014. PMID:
25265233.
IF:
6,557.
DOI:
10.1097/QAD.
0000000000000425.
http://dx.doi.org/10.1097/QAD.0000000000000425
– 143 –
AREA 3AREA 2 AREA 1
24105728. IF: 2,217. DOI: 10.1002/jmv.23742.
http://dx.doi.org/10.1002/jmv.23742
Expert Panel of GeSIDA and the National Aids Plan,
Berenguer J, Polo R, Lozano F, López Aldeguer J,
Antela A, Arribas JR, Asensi V, Blanco JR, Clotet B,
Domingo P, Galindo MJ, Gatell JM, González-García J,
Iribarren JA, Locutura J, López JC, Mallolas J, Martínez
E, Miralles C, Miró JM, Moreno S, Palacios R, Pérez
Elías MJ, Pineda JA, Podzamczer D, Portilla J, Pulido
F, Ribera E, Riera M, Rubio R, Santos J, Sanz J, Tuset
M, Vidal F, Rivero A. Executive summary of the
GeSIDA/National AIDS Plan consensus document on
antiretroviral therapy in adults infected by the human
immunodeficiency virus (updated January 2014).
Enferm Infecc Microbiol Clin. 32(7):447-58. 2014.
PMID: 24986715. IF: 1,881. DOI: 10.1016/j.eimc.
2014.02.018.
Borges AH, O'Connor JL, Phillips AN, Baker JV, Vjecha
MJ, Losso MH, Klinker H, Lopardo G, Williams I,
Lundgren JD; INSIGHT SMART Study Group; ESPRIT
Study Group (collaborator Sanz J et al) ; SILCAAT
Scientific Committee. Factors associated with D-dimer
levels in HIV-infected individuals. PLoS One.
9(3)e90978. 2014. PMID: 24626096. IF: 3,534. DOI:
10.1371/journal.pone.0090978.
IeDEA and ART Cohort Collaborations, Avila D, Althoff
KN, Mugglin C, Wools-Kaloustian K, Koller M, Dabis F,
Nash D, Gsponer T, Sungkanuparph S, McGowan C,
May M, Cooper D, Chimbetete C, Wolff M, Collier A,
McManus H, Davies MA, Costagliola D, CrabtreeRamirez B, Chaiwarith R, Cescon A, Cornell M, Diero L,
Phanuphak P, Sawadogo A, Ehmer J, Eholie SP, Li PC,
Fox MP, Gandhi NR, González E, Lee CK, Hoffmann
CJ, Kambugu A, Keiser O, Ditangco R, Prozesky H,
Lampe F, Kumarasamy N, Kitahata M, Lugina E,
Lyamuya R, Vonthanak S, Fink V, d'Arminio Monforte A,
Luz PM, Chen YM, Minga A, Casabona J, Mwango A,
Choi JY, Newell ML, Bukusi EA, Ngonyani K, Merati TP,
Otieno J, Bosco MB, Phiri S, Ng OT, Anastos K,
Rockstroh J, Santos I, Oka S, Somi G, Stephan C,
Teira R, Wabwire D, Wandeler G, Boulle A, Reiss P,
Wood R, Chi BH, Williams C, Sterne JA, Egger M.
IeDEA
and
ART
Cohort
Collaboration.
Immunodeficiency at the start of combination antiretro-
– 144 –
viral therapy in low-, middle-, and high income countries. J Acquir Immune Defic Syndr. 1(65):e8-e16.
2014. PMID: 24419071. IF: 4,394. DOI:
10.1097/QAI.0b013e3182a39979.
http://dx.doi.org/10.1097/QAI.0b013e3182a39979
Fernández-Ruiz M, Aguado JM, Almirante B, LoraPablos D, Padilla B, Puig-Asensio M, Montejo M,
García-Rodríguez J, Pemán J, Ruiz Pérez de Pipaón M,
Cuenca-Estrella M; CANDIPOP Project; GEIH-GEMICOMED (SEIMC); REIPI (colaborador I de los Santos).
Initial Use of Echinocandins Does Not Negatively
Influence Outcome in Candida parapsilosis
Bloodstream Infection: A Propensity Score Analysis.
Clin Infect Dis. 58(10):1421-1431. 2014. PMID:
24642553. IF: 9,416. DOI: 10.1093/cid/ciu158.
http://dx.doi.org/10.1093/cid/ciu158
Guinea J, Zaragoza Ó, Escribano P, Martín-Mazuelos
E, Pemán J, Sánchez-Reus F, Cuenca-Estrella M;
CANDIPOP Project, GEIH-GEMICOMED (SEIMC), and
REIPI (colbs. De los Santos I, Buendía B). Molecular
identification and antifungal susceptibility of yeast isolates causing fungemia collected in a population-based
study in Spain in 2010 and 2011. Antimicrob Agents
Chemother. 58(3):1529-1537. 2014. PMID: 24366741.
IF: 4,451. DOI: 10.1128/AAC.02155-13.
http://dx.doi.org/10.1128/AAC.02155-13
Olmos C, Vilacosta I, Pozo E, Fernández C, Sarriá C,
López J, Ferrera C, Maroto L, González I, Vivas D,
Palacios J, San Román JA. Prognostic implications of
diabetes in patients with left-sided endocarditis: findings from a large cohort study. Medicine (Baltimore).
93(2):114-9. 2014. PMID: 24646468. IF: 4,867. DOI:
10.1097/MD.0000000000000023.
http://dx.doi.org/10.1097/MD.0000000000000023
Portolés-Pérez J, Marques-Vidas M, Picazo JJ,
González-Romo F, García-Rojas A, Pérez-Trallero E,
Gil-Gregorio P, de la Cámara R, Morató ML, Rodríguez
A, Barberán J, Domínguez-Hernández V, Linares-Rufo
M, Jimeno-Sanz I, Sanz-Herrero F, Espinosa-Arranz J,
García-Sánchez V, Galindo-Izquierdo M, MartínezCastelao A. Recommendations for vaccination against
pneumococcus in kidney patients in Spain. Nefrologia.
34(5):545-51. 2014. PMID: 25036264. IF: 1,442. DOI:
http://dx.doi.org/10.3265/Nefrologia.pre2014.May.125
34.
122(6):526-9. 2014. PMID: 24106887. IF: 1,922. DOI:
10.1111/apm.12189.
http://dx.doi.org/10.1111/apm.12189
Hernando V, Alejos B, Álvarez D, Montero M, PérezElías MJ, Blanco JR, Masiá M, Del Romero J, de los
Santos I, Rio I, Llácer A; CoRIS. Reproductive desire in
women with HIV infection in Spain, associated factors
and motivations: a mixed-method study. BMC
Pregnancy Childbirth. 14:194. 2014. PMID: 24902487.
IF: 2,152. DOI: 10.1186/1471-2393-14-194.
http://dx.doi.org/10.1186/1471-2393-14-194
Puig-Asensio M, Pemán J, Zaragoza R, GarnachoMontero J, Martín-Mazuelos E, Cuenca-Estrella M,
Almirante B; Prospective Population Study on
Candidemia in Spain (CANDIPOP) Project; Hospital
Infection Study Group (GEIH); Medical Mycology Study
Group (GEMICOMED) of the Spanish Society of
Infectious Diseases and Clinical Microbiology (SEIMC);
(colbs. De los Santos I, Buendía B. Sanz J) Spanish
Network for Research in Infectious Diseases. Impact of
therapeutic strategies on the prognosis of candidemia
in the ICU. Crit Care Med. 42(6):1423-1432. 2014.
PMID:
24557426.
IF:
6,147.
DOI:
10.1097/CCM.0000000000000221.
http://dx.doi.org/10.1097/CCM.0000000000000221
Nordell AD, McKenna M, Borges ÁH, Duprez D,
Neuhaus J, Neaton JD; INSIGHT SMART, ESPRIT
Study Groups (collaborator Sanz J et al); SILCAAT
Scientific Committee. Severity of cardiovascular disease outcomes among patients with HIV is related to
markers of inflammation and coagulation. J Am Heart
Assoc. 3(3):e000844. 2014. PMID: 24870935. IF:
2,882. DOI: 10.1161/JAHA.114.000844.
http://dx.doi.org/10.1161/JAHA.114.000844
González I, Sarriá C, López J, Vilacosta I, San Román
A, Olmos C, Sáez C, Revilla A, Hernández M, Caniego
JL, Fernández C. Symptomatic peripheral mycotic
aneurysms due to infective endocarditis: a contemporary profile. Medicine (Baltimore). 93(1):42-52. 2014.
PMID:
24378742.
IF:
4,867.
DOI:
10.1097/MD.0000000000000014.
http://dx.doi.org/10.1097/MD.0000000000000014
Monge S, Diez M, Pulido F, Iribarren JA, Campins AA,
Arazo P, Montero M, Miro JM, Moreno S, Del Amo J;
Spanish AIDS Research Network Cohort (CoRIS) (de
los Santos I, Sanz J). Tuberculosis in a cohort of HIVpositive patients: epidemiology, clinical practice and
treatment outcomes. Int J Tuberc Lung Dis. 18(6):7008. 2014. PMID: 24903942. IF: 2,756. DOI:
10.5588/ijtld.13.0778.
http://dx.doi.org/10.5588/ijtld.13.0778
Bustamante J, Arévalo A, Tamayo E, Sarria C, AguilarBlanco EM, Heredia M, Almansa R, Rico L, Iglesias V,
Bermejo-Martin JF. Cytokine profiles linked to fatal outcome in infective prosthetic valve endocarditis. APMIS.
Panel of experts from the AIDS Working Group (GESIDA) of the Spanish Society of Infectious Diseases and
Clinical Microbiology (SEIMC), the Spanish Society of
Nephrology (S.E.N.), and the Spanish Society of
Clinical Chemistry and Molecular Pathology (SEQC),
Górriz JL, Gutiérrez F, Trullas JC, Arazo P, Arribas JR,
Barril G, Cervero M, Cofan F, Domingo P, Estrada V,
Fulladosa X, Galindo MJ, Gracia S, Iribarren JA, Knobel
H, Lopez-Aldeguer J, Lozano F, Martínez-Castelao A,
Martinez E, Mazuecos MA, Miralles C, Montañes R,
Praga M, Quereda C, Rivero A, Santamaria JM, Sanz J,
Sanz J, Miró JM. Executive summary of the consensus
document on the management of renal disease in HIVinfected patients. Nefrologia. 34(6):768-788. 2014.
PMID:
25415577.
IF:
1,442.
DOI:
10.3265/Nefrologia.pre2014.Sep.12745.
http://dx.doi.org/10.3265/Nefrologia.pre2014.Sep.127
45
Gorriz JL, Gutiérrez F, Trullàs JC, Arazo P, Arribas JR,
Barril G, Cervero M, Cofán F, Domingo P, Estrada V,
Fulladosa X, Galindo MJ, Gràcia S, Iribarren JA, Knobel
H, López-Aldeguer J, Lozano F, Martínez-Castelao A,
Martínez E, Mazuecos MA, Miralles C, Montañés R,
Praga M, Quereda C, Rivero A, Santamaría JM, Sanz J,
– 145 –
AREA 3AREA 2 AREA 1
AREA 3
Sanz J, Miró JM. Executive summary of the recommendations on the evaluation and management of
renal disease in human immunodeficiency virus-infected patients. Enferm Infecc Microbiol Clin. 32(9):583-97.
2014. PMID: 25303781. IF: 1,881. DOI:
10.1016/j.eimc.2014.09.002.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: DE LOS SANTOS GIL,
IGNACIO
Estudio multicéntrico, aleatorizado, doble ciego y
controlado con placebo para evaluar el efecto de
CR8020 y CR6261 en pacientes hospitalizados por
infección de gripE A; (Versión v1: 02-10-13). CRUCELL HOLLAND B.V. CR6261CR8020FLZ2001
EudraCT: 2013-003341-41
IGNACIO
Seguridad hepática de Eviplera® en pacientes coinfectados con HIV/virus de la Hepatitis C (VHC) sin
tratamiento para HVC en el estudio de cohortes de
HEPAVIR de seguridad hepática. Estudio hEPAtic.
(Versión 1.1:22- -10-13). FUNDACION PROGRESO Y
SALUD IN-ES-264-1260(HEPATIC) FPA-RIL-2014-01
IGNACIO
Estudio de fase 3, aleatorizado, controlado con
tratamiento activo y abierto para evaluar el cambio de
tratamiento a un régimen en un solo comprimido
administrado
una
vez
al
día
de
darunavir/cobicistat/emtricita-bina/tenofovir alafenamida (D/C/F/TAF) frente a la continuación del régimen actual formado por un inhibidor de la proteasa
potenciado (IPp) combinado con emtricitabina/tenofovir disoproxil fumarato (FTC/TDF) en sujetos infectados por el virus de la inmunodeficiencia humana de
tipo 1 (VIH 1) con supresión virológica; (Ve0si¢n
CTPA1: 25-09-14). JANSSEN R&D IRELAND
TMC114IFD3013
EudraCT: 2014-003052-31
– 146 –
GRUPO 51
HEAD OF LABORATORY
Javier Aspa Marco
GROUP MEMBERS
• José Juan Curbelo García
• Gilda Fernandes Vasconcelo
• Guillermo Fernández Jíménez
• José María Galván Román
• Sergio Luquero Bueno
• María del Mar Ortega Gómez
• Olga Rajas Naranjo
• María del Valle Somiedo Gutiérrez
• Lorena Vega Piris
RESEARCH INTEREST
The community acquired pneumonia (CAP) is an
infectious disease with high prevalence and great
morbid-mortality rate. Our group has been working
on different collaborative research lines, mainly: A)
Clinical indicators related to the safe management
of patients with CAP. We participated as collaborators in several projects of the Spanish Society of
Pneumology and Thoracic Surgery, funded by
grants. B) Our group maintains an open line of collaboration with several groups, mainly with
Immunology Service, Hospital Dr Negrin (Gran
Canaria, Spain). We collaborate in several topics,
mainly mannose-binding lectin and surfactant protein, related to different aspects of host defense in
pneumonia. The financial support of this research
has been possible by FISS and grants of scientific
societies in which we have participated as collaborating researchers. These two lines are active.
Our current research project aims at the incidence
of cardiovascular events following hospitalization for
CAP in adults, and its association with different
markers of inflammation. In this project we just try
to quantify the incidence of cardiovascular disease
AREA 3
The preliminary results are very promising: we have
found a link between long-term mortality and occurrence of cardiovascular events, besides being able
to select some biomarkers to improve forecasts
admission scores. We need a longer time monitoring to ensure the relationship between biomarkers
and development of cardiovascular events.
MicroRNAs (miRNAs) are a family of endogenous,
small, noncoding RNA molecules that modulate
physiological and pathological processes by posttranscriptional inhibition of gene expression. Recent
studies have also begun to reveal that altered
miRNA expression profiles may be associated with
pathological processes within the lung and lead to
the development of various pulmonary diseases,
ranging from inflammatory diseases to lung cancers. Also miRNAs are pivotal to both adaptive and
innate immunity, with regulatory effects on cell differentiation and immunological function. The
expression of different miRNAs in patients with cardiovascular events also had been published recently. We propose to explore the role of different
miRNAs in the development of heart failure in
patients with CAP and the regulation of the inflammatory response in CAP patients.
MAJOR GRANTS
• Aspa Marco, Javier. Incidencia de episodios cardiovasculares tras un ingreso hospitalario por neumonía
adquirida. 089/2013. SEPAR. 2014-2015.
• Ortega Gómez, María del Mar. RED NACIONAL DE
BIOBANCOS. PT13/0010/0058. ISCIII. 2014-2017.
• Aspa Marco, Francisco Javier. Incidencia de episodios cardiovasculares tras un ingreso hospitalario por
neumonía adquirida en la comunidad en pacientes
adultos y su asociación con diferentes marcadores
de inflamación. PI12/01142. ISCIII. 2013-2015
• Rajas Naranjo, Olga. Determinación del papel de los
proteoglicanos en la interacción entre microorganismos y el tejido respiratorio. 125/2012. SEPAR. 20132015.
• Olga Rajas Naranjo. Análisis de la estructura haplotípica de genes de citocinas inflamatorias en
relación con la evolución de la neumonía adquirida
en la comunidad. Sociedad madrileña de
Neumologia-Neumomadrid. 2012-2014.
PUBLICATIONS (8)
Ezquiaga E, García-López A, de Dios C, Agud JL,
Albillo D, Vega-Piris L. Seasonality, Smoking and
History of Poor Treatment Compliance are Strong
Predictors of Dropout in a Naturalistic 6 Year Follow-Up
of Bipolar Patients. Psychiatr Q. 85(4):467-77. 2014.
PMID: 24986371. IF: 1,347. DOI: 10.1007/s11126014-9303-9.
http://dx.doi.org/10.1007/s11126-014-9303-9
Herrera-Ramos E, López-Rodríguez M, RuízHernández JJ, Horcajada JP, Borderías L, Lerma E,
Blanquer J, Pérez-González MC, García-Laorden MI,
Florido Y, Mas-Bosch V, Montero M, Ferrer JM, Sorlí L,
Vilaplana C, Rajas O, Briones M, Aspa J, LópezGranados E, Solé-Violán J, de Castro FR, RodríguezGallego C. Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic
influenza A virus infection. Crit Care. 18(3):R127. 2014.
PMID: 24950659. IF: 5,035. DOI: 10.1186/cc13934.
http://dx.doi.org/10.1186/cc13934
– 147 –
AREA 3AREA 2 AREA 1
in adult patients, in the year after hospital admittance due to CAP and to establish its possible relationship with mortality. Moreover, we will try to
describe the distribution of a wide spectrum of
immune response mediators upon the admittance
to and release from hospital. This will allow characterizing an inflammatory profile for these patients
and determining a possible relationship with the
incidence of cardiovascular disease.
14(1):197. 2014. PMID: 25495677. IF: 2,489. DOI:
10.1186/1471-2466-14-197.
http://dx.doi.org/10.1186/1471-2466-14-197
Bello S, Menéndez R, Torres A, Reyes S, Zalacain
R, Capelastegui A, Aspa J, Borderías L, MartinVillasclaras JJ, Alfageme I, Rodríguez de Castro F,
Rello J, Molinos L, Ruiz-Manzano J. Tobacco
smoking increases the risk for death from pneumococcal pneumonia. Chest. 146(4):1029-1037.
2014. PMID: 24811098. IF: 7,132. DOI: 10.1378/
chest.13-2853.
http://dx.doi.org/10.1378/chest.13-2853
Balsalobre R. Mucoepidermoid Carcinoma in a Bone
Marrow Transplant Patient. Arch Bronconeumol.
50(3):125. 2014. PMID: 24486048. IF: 1,816. DOI:
10.1016/j.arbres.2013.06.002.
Girón-Moreno RM, Justicia JL, Yamamoto S,
Valenzuela C, Cisneros C, Gómez-Púnter RM,
Fernandes-Vasconcelos G, Ancochea J. Role of Creactive protein as a biomarker for prediction of the
severity of pulmonary exacerbations in patients with
cystic fibrosis. BMC Pulm Med. 14(1):150. 2014.
PMID: 25248567. IF: 2,489. DOI: 10.1186/1471-246614-150.
http://dx.doi.org/10.1186/1471-2466-14-150
Real de Asua D, Galván JM, Filigheddu MT, Trujillo D,
Costa R, Cadiñanos J. Systemic AA amyloidosis: epidemiology, diagnosis and management. Clinical
Epidemiology. 6:369-77. 2014. PMID: 25378951. DOI:
10.2147/CLEP.S39981.
http://dx.doi.org/ 10.2147/CLEP.S39981
M Hernández Olmedo, P Gil Martínez, V de la Cuesta
Esteban, JJ Curbelo García, M Villanueva Forero, J
Iglesias Franco. Dificultad respiratoria en un varón
tratado con heparina. Emergencias. (26):238-239.
2014. IF: 2,583
– 148 –
BOOKS
Galván Román JM, Real de Asúa D, Suárez C.
Dislipemia. Protocolos “Manejo diagnóstico y terapéutico de las comorbilidades en la EPOC”. Elsevier
Doyma. ISBN: 978-84-752-7626
GRUPO 52
HEAD OF LABORATORY
Teresa Alarcón Cavero
GROUP MEMBERS
• María Luz Balsalobre Arenas
• Ana Blanco Suárez
• Buenaventura Buendía Moreno
• Laura María Cardeñoso Domingo
• Ana Correa Ruiz
• Carmen De las Cuevas Torresano
• Diego Domingo García
• Marina Espínola Docio
• María Dolores Guerrero Torres
• Alba Guiu Martínez
• Laura Llorca Otero
• Elisea Lomas Lomas
• Justo Martiáñez Rodríguez
• María Josefa Martínez Gómez
• Sandra Rodrigo Gil
• Cristina Santa olalla Peralta
• Carmen María Serrano Morago
RESEARCH INTEREST
A great interest in the role of human microbiome in health
and disease exists due to the accesible high throughput
sequencing methods. Several studies indicate that the
human microbiome may contribute to the regulation of
multiple neuro-chemical and neuro-metabolic pathways
through a complex series of highly interactive and sym-
AREA 3
Helicobacter pylori infects 50% of the population worldwide and colonizes the gastric mucosa causing many
gastrointestinal diseases such as severe gastritis, peptic
ulcer disease, gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. It is identified as
a Group I carcinogen by the International Agency for
Research on Cancer from the World Health Organization.
Several treatment regimens have been used to eradicate
this microorganism. Resistance to the antibiotics is considered the main cause of treatment failure.
This group includes members of the Microbiology
Department with interest in diagnosis and treatment of
several infectious diseases such as fungi,
Mycobacterium spp or CMV infection, as well as infections in cystic Fibrosys patients.
The main lines of research at present time and for the
near future are: (1) the study of gastric microbiome and
its relationship with H. pylori infection but also with other
human diseases with potential therapeutic applications.
The role of human microbiome in H. pylori infections but
also in other diseases is going to be an exciting research
area for the next few years. (2) We are interested in
antimicrobial resistance in H. pylori (national and international surveys) and in molecular methods for detection of
clarithromycin resistance and heteroresistance. (3) We
are also interested in the in vitro activity of wine phenolic
compounds against H. pylori. (4) The role of phages and
CRISPR in H. pylori strains and their relationship with the
transfer of resistance genes is also an area of interest.
MAJOR GRANTS
• López-Brea Calvo, Manuel. International health management association (INC). EPI252.2012. 2012-.
• Alarcon Cavero, Teresa. International health management association (INC). EPI252.2013. 2014• Alarcon Cavero, Teresa. International health management association (INC). EPI252.2014. 2014-
PUBLICATIONS (4)
Puig-Asensio M, Padilla B, Garnacho-Montero J,
Zaragoza O, Aguado JM, Zaragoza R, Montejo M,
Muñoz P, Ruiz-Camps I, Cuenca-Estrella M, Almirante
B; CANDIPOP Project; GEIH-GEMICOMED (SEIMC);
REIPI. Epidemiology and predictive factors for early
and late mortality in Candida bloodstream infections:
a population-based surveillance in Spain. Clin
Microbiol Infect. 20(4):0245-0254. 2014. PMID:
24125548. IF: 5,197. DOI: 10.1111/14690691.12380.
http://dx.doi.org/10.1111/1469-0691.12380
Puig-Asensio M, Pemán J, Zaragoza R, GarnachoMontero J, Martín-Mazuelos E, Cuenca-Estrella M,
Almirante B; Prospective Population Study on
Candidemia in Spain (CANDIPOP) Project; Hospital
Infection Study Group (GEIH); Medical Mycology
Study Group (GEMICOMED) of the Spanish Society of
Infectious Diseases and Clinical Microbiology
(SEIMC); Spanish Network for Research in Infectious
Diseases. Impact of therapeutic strategies on the
prognosis of candidemia in the ICU. Crit Care Med.
42(6):1423-1432. 2014. PMID: 24557426. IF: 6,147.
DOI: 10.1097/CCM.0000000000000221.
http://dx.doi.org/10.1097/CCM.0000000000000221
Alba Guiu, Buenaventura Buendía, Laura Llorca, Rosa
María Gómez Punter, Rosa Girón. Chryseobacterium
spp., ¿nuevo patógeno oportunista asociado a fibrosis quística?. Enferm Infecc Microbiol Clin. 32(8):497501. 2014. PMID: 24656793. IF: 1,881. DOI:
10.1016/j.eimc.2013.08.003.
Guinea J, Zaragoza Ó, Escribano P, Martín-Mazuelos E,
Pemán J, Sánchez-Reus F, Cuenca-Estrella M; CANDIPOP Project, GEIH-GEMICOMED (SEIMC), and REIPI
– 149 –
AREA 3AREA 2 AREA 1
biotic host-microbiome signalling systems that mechanistically interconnect the gastrointestinal tract, skin, liver,
and other organs with the central nervous system.
Several studies suggest that the stomach contains an
unexpected diversity of microorganisms but the relationship with H. pylori and with other human diseases are
not well established.
(colbs. De los Santos I, Buendía B). Molecular identification and antifungal susceptibility of yeast isolates causing
fungemia collected in a population-based study in Spain
in 2010 and 2011. Antimicrob Agents Chemother.
58(3):1529-1537. 2014. PMID: 24366741. IF: 4,451.
DOI: 10.1128/AAC.02155-13.
http://dx.doi.org/10.1128/AAC.02155-13
– 150 –
BOOKS
Marina Espinola Teresa Alarcón. La historia evolutiva de
Helicobacter pylori. Medicina Evolucionista II:
Aportaciones pluridisciplinares. Editor Álvaro Daschner,
JL Gómez Pérez, MJ Trujillo Tiebas. ISBN: 978-84617-0375-3
AREA 3
GRUPO 40
HEAD OF LABORATORY
GROUP MEMBERS
• Concepción Alonso Cerezo
• Ana Isabel Ballesteros García
• Ana Collazo Lorduy
• Pablo Costas Rojo
• Lourdes del Campo del Val
• Yolanda Delgado Jiménez
• Beatriz Doblado Cardellach
• Olga Donnay Candil
• Julia Fernández Bueno
• José Luis García Fernández
• Iñigo García Sanz
• Jesús González Cajal
• María Mercedes Guijarro Rojas
• Eugenia Jareño Dorrego
• José Antonio Jiménez Heffernan
• Elena Martín Pérez
• Santiago Martínez San Martín
• Ramón Moreno Balsalobre
• José Andrés Moreno Monteagudo
• Antonio José Pita Carranza
• Yat Wah Pun Tam
• José Miguel Sánchez Torres
• Natalia Torres Waldhaus
• Erich Alberto Vargas Díez
• Francisco E. Viamontes Ugalde
RESEARCH INTEREST
Our line of clinical research in focused on the development of new cancer therapies for breast cancer, partic-
ularly in the fields of monoclonal antibodies against
HER2 and on biomarker of human breast cancer. We
have contributed to the clinical evaluation of threeweekly trastuzumab, currently the standard of therapy
in HER2+ breast cancer, or the HER2 tyrosine kinase
inhibitor neratinib in advanced breast cancer. Also, we
have evaluated novel drug combinations including
antiangiogenic drugs such as nintedanib or dovitinib in
phase I and phase II trials.
Our line of laboratory research is focused on the interactions of fatty acids and oncogenes. We have demonstrated in the past the in vitro and in vivo therapeutic
effects of the pharmacological or RNA-interference
inhibition of the enzyme fatty acid synthase (FASN) in
breast cancer. Our preliminary data in immortalized
MEFS generated from a conditional FASN knockout
mouse model suggest that FASN is necessary for
transformation. In wild-type embryonal fibroblasts, the
effects of genetic ablation of FASN does not impact in
cell cycle, cell survival or cell metabolism; however, the
deletion of FASN severely impairs the ability of gaining
the metabolic hallmark of cancer, the Warburg effect, if
exposed to a transformation-driver stimulus. We have
now hypothesized that the genetic ablation of FASN
using a conditional inducible FASN knockout model will
prevent the development of breast carcinomas in vivo
due to its role in eliciting the connection between the
Warburg effect and the anaplerotic shift of the Krebs
cycle. Our experiments will generate and characterize
three multi-transgenic animal models of breast cancer
(representing the ER+, HER-2+ and triple-negative
subtypes) that will allow us to establish whether there is
a crucial role of FASN during and after breast tumourigenesis. We will also determine which are the metabolic mechanisms underlying the rate-limiting nature of
FASN in breast transformation. Finally, we will establish
the validity of FASN as a safe target by evaluating the
effects of systemic FASN deletion in the adult mouse.
Our project will establish whether FASN is a new and
druggable metabolic target for the chemoprevention of
breast cancer.
Finally, we have been involved in public policy involving
the National Cancer Strategy organized by the Spanish
Ministry of Health, which has included the development
– 151 –
AREA 3AREA 2 AREA 1
Line 3.8
Individualized medicine
in solid tumors
of indicators for the care of breast and colon cancer,
and the evaluation of these indicators in Spain.
MAJOR GRANTS
• Ramón Colomer Bosch. Desestabilización estructural de la adicción a oncogenes en cáncer de mama
mediante el bloqueo de la sintasa de ácidos grasos.
PI11-00832. ISCIII. 2012-2014.
• Pun Tam, Yatwah. TORACICA. 2010-
PUBLICATIONS (10)
Campo LD, León NG, Palacios DC, Lagana C,
Tagarro D. Abdominal Complications Following
Hematopoietic Stem Cell Transplantation. Radio
Graphics. 34(2):396-412. 2014. PMID: 24617687.
IF: 2,729. DOI: 10.1148/rg.342135046.
http://dx.doi.org/ 10.1148/rg.342135046
Cañizares MA, Matilla JM, Cueto A, Algar J,
Muguruza I, Moreno-Mata N, Moreno-Balsalobre R,
Guijarro R, Arrabal R, Garcia-Fontan E, GonzalezPiñeiro A, Garcia-Yuste M; EMETNE-SEPAR
Members. Atypical carcinoid tumours of the lung:
prognostic factors and patterns of recurrence.
Thorax. 69(7):648-53. 2014. PMID: 24603194. IF:
8,562. DOI: 10.1136/thoraxjnl-2013-204102.
http://dx.doi.org/10.1136/thoraxjnl-2013-204102
González-Peramato P, Jiménez-Heffernan JA,
Vicandi B, López-Ferrer P, Bárcena C, AlvarezRodríguez F, Picazo ML, Viguer JM. Micropapillary
carcinoma of the urinary tract: a cytologic study of
urine and fine-needle aspirate samples. Acta Cytol.
58(3):269-74. 2014. PMID: 24556948. IF: 1,562.
DOI: 10.1159/000358506.
http://dx.doi.org/10.1159/000358506
Jiménez-Heffernan JA, Alvarez F, Salas C. Mitotic
activity in subependymal giant cell astrocytoma.
Diagn Cytopathol. 42(7):643. 2014. PMID:
– 152 –
23239637. IF: 1,52. DOI: 10.1002/dc.22939.
http://dx.doi.org/10.1002/dc.22939
Balsalobre R. Mucoepidermoid Carcinoma in a
Bone
Marrow
Transplant
Patient.
Arch
Bronconeumol. 50(3):125. 2014. PMID: 24486048.
IF: 1,816. DOI: 10.1016/j.arbres.2013.06.002.
Salido S, Gómez-Ramírez J, Bravo JM, MartínPérez E, Fernández-Díaz G, Múñoz de Nova JL,
Auza J, Larrañaga E. Parathyroid adenoma in third
pharyngeal pouch cyst as a rare case of primary
hyperparathyroidism. Ann R Coll Surg Engl.
96(7):e8-10. 2014. PMID: 25245714. IF: 1,223.
DOI: 10.1308/003588414X13946184900804.
http://dx.doi.org/10.1308/003588414X139461849
00804
Quintela-Fandino M, Urruticoechea A, Guerra J, Gil
M, Gonzalez-Martin A, Marquez R, HernandezAgudo E, Rodriguez-Martin C, Gil-Martin M, Bratos
R, Escudero MJ, Vlassak S, Hilberg F, Colomer R.
Phase I clinical trial of nintedanib plus paclitaxel in
early HER-2-negative breast cancer (CNIO-BR-012010/GEICAM-2010-10 study). Br J Cancer.
111(6):1060-4. 2014. PMID: 25058346. IF: 4,817.
DOI: 10.1038/bjc.2014.397.
http://dx.doi.org/10.1038/bjc.2014.397
Quintela-Fandino M, Bueno MJ, Lombardia L, Gil
M, Gonzalez-Martin A, Marquez R, Bratos R,
Guerra J, Tan E, Lopez A, Colomer R, Salazar R.
Selective activity over a constitutively active RETvariant of the oral multikinase inhibitor dovitinib:
Results of the CNIO-BR002 phase I-trial. Mol
Oncol. 8(8):1719-28. 2014. PMID: 25103625. IF:
5,935. DOI: 10.1016/j.molonc.2014.07.005.
http://dx.doi.org/10.1016/j.molonc.2014.07.005
Guinea-Viniegra J, Jiménez M, Schonthaler HB,
Navarro R, Delgado Y, Concha-Garzón MJ,
Tschachler E, Obad S, Daudén E, Wagner EF.
Targeting miR-21 to treat psoriasis. Sci Transl Med.
6(225):225re1. 2014. PMID: 24574341. IF: 14,414.
AREA 3
Sanz AB, Aroeira LS, Bellon T, del Peso G,
Jimenez-Heffernan J, Santamaria B, Sanchez-Niño
MD, Blanco-Colio LM, Lopez-Cabrera M, RuizOrtega M, Egido J, Selgas R, Ortiz A. TWEAK promotes peritoneal inflammation. PLoS One.
9(3):e90399. 2014. PMID: 24599047. IF: 3,534.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ALONSO CEREZO,
MARÍA CONCEPCIÓN
Estudio multicéntrico abierto para la evaluación de la
frecuencia de mutaciones en genes accionables asociados al Cáncer Hereditario: (Versión1.0: 30-06-14).
MYRIAD GENETICS ESPAÑA S.L.U. FAMOSA
PRINCIPAL RESEARCHER: BALLESTEROS GARCÍA,
ANA-ISABEL
Estudio de fase III, abierto, aleatorizado, paralelo, con
2 brazos y multicéntrico sobre BMN 673 en comparación con la elección del médico en pacientes con
mutaciones en la línea germinal de BRCA con cáncer
de mama localmente avanzado y/o metastásico, que
han recibido no más de 2 regímenes de quimioterapia
previos para la enfermedad metastásica; (Versión
Original: 17-07-13). BIOMARIN PHARMACEUTICAL
INC. 673-301
EudraCT: 2013-002716-28
ANA ISABEL
Predictores de respuesta a la quimioterapia neoadyuvante con docetaxel-carboplatino en pacientes con
cáncer de mama triple negativo en etapas II y III;
(Versión 2.0). HOSPITAL GENERAL UNIVERSITARIO
GREGORIO MARAÑÓN. GOMHGUGM022011
ANA ISABEL
Ensayo clínico fase III para analizar la preferencia de
la paciente por el uso de trastuzumab subcutáneo
(SC) vs intravenoso (IV) en pacientes con cáncer de
mama diseminado HER2-positivo en tratamiento con
trastuzumab intravenoso (IV) durante al menos 4
meses y sin progresión de la enfermedad; (Versión 3:
14-02-14). GEICAM GEICAM/2012-07
EudraCT: 2012-004928-38
ANA ISABEL
Estudio fase III, aleatorizado, doble ciego, controlado
con placebo de BKM1220 con fulvestrant, en mujeres
postmenopáusicas con cáncer de mama metastásico
o localmente avanzado con receptores hormonales
positivos HER2 negativo, tratadas con IA, que han
progresado durante o después del tratamiento con
un inhibidor de mTOR; (Versión 02: 19-12-13).
NOVARTIS FARMACEUTICA, S.A. CBKM120F2303
EudraCT: 2012-002571-34
PRINCIPAL RESEARCHER: COLOMER BOSCH,
RAMÓN
Estudio de fase II multicéntrico, multinacional, de
evaluación de pertuzumab en combinación con
trastuzumab y quimioterapia neoadyuvante basada
en antraciclinas en pacientes con cáncer de mama
HER2 positivo localmente avanzado, inflamatorio o
precoz; (Versión 2: 26-02-14). ROCHE FARMA, S.A.
WO29217
EudraCT: 2014-000156-28
PRINCIPAL RESEARCHER: MARTÍN PÉREZ,
MARÍAELENA
Ultrasonido focalizado de alta intensidad (HAIFU tm)
en pacientes con cáncer de páncreas no resecable;
(Versión 1.0: 28-04-14). IMAGO DIAGNOSTICS S.L.
PANHAIFU-2014 / CNIO-BR-003
PRINCIPAL RESEARCHER: SÁNCHEZ TORRES,
JOSÉ MIGUEL
Estudio de fase III multicéntrico, abierto, randomizado
de alectinib frente a crizotinib en pacientes con
cáncer de pulmón no microcítico avanzado quinasa
del linfoma anaplásico positivo, no tratados previamente; (Versión 1: 10-02-2014). F. HOFFMANN-LA
– 153 –
AREA 3AREA 2 AREA 1
DOI: 10.1126/scitranslmed.3008089.
http://dx.doi.org/10.1126/scitranslmed.3008089
ROCHE LTD BO28984(ES EL 2479)
EudraCT: 2013-004133-33
JOSÉ MIGUEL
Estudio de fase 3, aleatorizado, controlado con
placebo, en doble ciego, multicéntrico y de dos
partes, de patritumab (U3-187) en combinación con
erlotinib en sujetos con EGFR de tipo salvaje con
cáncer de pulmón no microcítico (CPNM) localmente
avanzado o metastásico en los que su enfermedad ha
progresado con al menos un tratamiento sistémico
previo; (Versión 2: 24-2-14). DAIICHI SANKYO
EUROPE GMBH U31287-A-U301
EudraCT: 2013-004371-12
JOSÉ MIGUEL
Ensayo clínico fase II para evaluar la eficacia y la
seguridad del tratamiento con crizotinib en pacientes
con adenocarcinoma de pulmón avanzado traslocado
para ROS1; (Versión 3.0-F: 26-3-14). UNIVERSIDAD
DE COLONIA EUCROSS/UNI-KOELN-1659
EudraCT: 2013-002737-38
GRUPO 53
HEAD OF LABORATORY
Almudena Zapatero Laborda
GROUP MEMBERS
• María Magdalena Adrados de Llano
• Ramón Cristóbal Arellano Gañán
• José Alfonso Cruz Conde
• Feliciano García Vicente
• María del Carmen Martín de Vidales Cervantes
• Leopoldo Pérez González
RESEARCH INTEREST
JOSÉ MIGUEL
Estudio internacional multicéntrico de fase III, aleatorizado, doble ciego controlado con placebo, de
MEDI4736 como tratamiento secuencial en pacientes
con cáncer pulmonar de células no pequeñas, localmente avanzado, no resecable (estadio III) que no han
progresado después de una terapia de quimiorradiación concurrente definitiva con base de platino
(PACIFIC); (Versión 1: 19-02-14). ASTRAZENECA AB
D4191C00001
EudraCT: 2014-000336-42
In Europe, prostate cancer (PCa) is the most common solid neoplasm, with an incidence rate of 214
cases per 1000 men, outnumbering lung and colorectal cancer. PCa affects elderly men more often
and therefore is a bigger health concern in developed
countries. The therapeutic management of PCa has
become increasingly complex because of the various
stage-specific therapeutic options available. One relevant issue is the discrimination between favourable
and unfavourable intermediate-risk disease. And
especially important is the identification of high-risk
patients (based on clinical and molecular patterns)
susceptible of more intensive radical treatment or
their inclusion in clinical trials. Since advanced PCa
can be considered a chronic disease, the evaluation
of quality of life and the control of toxic effects
induced by treatment has become a priority in the
global approach of PCa patients.
JOSÉ MIGUEL
Ensayo en fase III, aleatorizado, de ganetespib en
combinación con docetaxel frente a docetaxel solo en
pacientes con adenocarcinoma de pulmón no
microcítico avanzado; (Versión Am 2: 10-03-14).
SYNTA PHARMACEUTICALS CORP. 9090-14
EudraCT: 2012-004349-34
This group is focused on three lines of investigation: 1)
the identification of clinical and biological markers as
risk and predictive factors. We work in a cooperative
project with the CNIO to determine the prognostic
value of expression of molecular markers (hif1a, pak-6,
and psmb4) in the biopsy specimens of intermediateand high-risk localized prostate cancer patients treated with androgen deprivation and dose escalation
– 154 –
AREA 3
MAJOR GRANTS
Zapatero Laborda, Almudena. Valor pronóstico de
los niveles de células tumorales circulantes (CTCS)
en sangre periférica en pacientes con cáncer de
próstata de alto riesgo (estadios IIb-III) sometidos a
tratamiento radical con radioterapia y hormonoterapia. Janssen-Radio. Onco. 2013-.
PUBLICATIONS (3)
Zapatero A, Gómez-Huelgas R, González N, Canora J,
Asenjo A, Hinojosa J, Plaza S, Marco J, Barba R.
Frequency of hypoglycemia and its impact on length of
stay, mortality, and short-term readmission in patients
with diabetes hospitalized in internal medicine wards.
Endocr Pract. 20(9):870-5. 2014. PMID: 24641928. IF:
2,588. DOI: 10.4158/EP14006.OR.
http://dx.doi.org/10.4158/EP14006.OR
J. López Torrecilla, A. Zapatero, I. Herruzo, F. A. Calvo,
M. A. Cabeza, A. Palacios, A. Guerrero, A. Hervás, P.
Lara, B. Ludeña Martínez, E. del Cerro Peñalver, G.
Nagore, G. Sancho, J. L. Mengual, M. Mira, A. Mairiño,
P. Samper, S. Pérez, I. Castillo, J. C. Martínez Cedrés, E.
Ferrer, S. Rodriguez, X. Maldonado, A. Gómez
Caamaño, C. Ferrer. Infrastructures, treatment modalities, and workload of radiation oncology departments in
Spain with special attention to prostate cancer. Clinical
and Translational Oncology. 16(5):447-54. 2014. PMID:
24682792. IF: 1,6. DOI: 10.1007/s12094-013-1121-2.
http://dx.doi.org/10.1007/s12094-013-1121-2
Zapatero A, Morente M, Nieto S, Martín de Vidales C,
Lopez C, Adrados M, Arellano R, Artiga MJ, GarciaVicente F, Herranz LM, Leaman O. Predictive value of
PAK6 and PSMB4 expression in patients with localized
prostate cancer treated with dose-escalation radiation
therapy and androgen deprivation therapy. Urol Oncol.
32(8):1327-32. 2014. PMID: 24946957. IF: 3,363. DOI:
10.1016/j.urolonc.2014.05.004.
http://dx.doi.org/10.1016/j.urolonc.2014.05.004
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ZAPATERO LABORDA,
MARÍA ALMUDENA
Tratamiento radioterápico en pacientes con cáncer de
próstata conforme a la práctica clínica habitual en los
servicios de oncología radioterápica españoles; (Versión
final 1.0: 18-12-13). GICOR GIC-RAD-2014-01
PRINCIPAL RESEARCHER: ZAPATERO LABORDA,
MARÍA ALMUDENA
Estudio multinacional, de fase III, aleatorizado, con doble
enmascaramiento y controlado con placebo, de la eficacia y la seguridad de la enzalutamida en los pacientes
– 155 –
AREA 3AREA 2 AREA 1
radiation therapy. We also participate in an international project with a cell cycle progression (CCP) gene
panel, a test for risk assessment of localized PCa
patients. The test combines the gene expression levels of 31 genes related to cell cycle progression and
15 housekeeping genes into a cell cycle progression
(CCP) score that is used to predict 10-year prostate
cancer specific disease progression and mortality. 2)
Randomized trials done during the past two decades
have shown that androgen deprivation combined with
conventional-dose radiotherapy improves overall survival, mainly in patients with intermediate-risk and
high-risk prostate cancer. Similarly, clinical outcomes
have also improved substantially with high-dose radiotherapy. In view of the absence of specific randomized
trials, we designed a phase III clinical trial to determine
the optimum duration of androgen deprivation alongside high-dose raditotherapy in localized intermediate
and high-risk PCa patiens (EudraCT 2005-00041736). 3) The androgen receptor remains the main driver
of prostate cancer progression in CRPC. We participate in 2 international clinical trials with Enzalutamide.
Enzalutamide is a potent androgen receptor inhibitor
that significantly prolonged overall survival in men with
metastatic CRPC. These 2 trials will evaluate enzalutamide in 2 scenarios: non-metastatic castration
resistant PCa and treatment of biochemical progression following primary local therapy.
con cáncer de próstata no metastatizante, resistente a la
castración; (Versión enmienda1 2.0: 16-05-13). MEDIVATION INC. MDV3100-14
EudraCT: 2012-005665-12
GRUPO 54
HEAD OF LABORATORY
Laura Cerezo Padellano
GROUP MEMBERS
• Adolfo Hinojar Gutiérrez
• Consuelo López Elzaurdia
• Mario López Rodríguez
• Rafael Manzanares Soler
• Alicia Marín Palomo
• Margarita Martín Martín
• Mario Fernando Muñoz Guerra
• Eduardo Raboso García-Baquero
• Francisco José Rodríguez Campo
RESEARCH INTEREST
Advances in head and neck cancer include new knowledge on etiology and progress on organ preservation
treatments modalities. Head and neck cancer (HNC) is
mainly related to smoking, however, another risk factor,
the human papillomavirus (HPV), has emerged in recent
years. HPV related carcinoma constitutes a distinct entity
which presents in young adults, not heavy smokers, usually presenting as regionally advanced disease and with
better prognosis, probably due to their different molecular
profile. On the other hand, organ preservation with
chemoradiation is feasible in locally advanced head and
neck cancer without compromising survival.
Our group pursues four lines of investigation: 1) Monitor the
evolving incidence of HPV-induced OPSCC in our region
and identify new molecular mechanisms in these tumors,
related to increased radiosensitivity. For the next years we
– 156 –
are planning to expand this research, analyzing all patients
with oropharyngeal cancer treated from 2011 to 2015 from
six large hospitals in Madrid and studying the percentage
of HPV positive. Thus, we will have a clear picture of the
incidence of oropharyngeal cancer related to HPV infection
in our region. We have applied for a grant to study the gene
expression profile of HPV positive and HPV negative
oropharyngeal cancer, with potential implications on treatment choices. 2) Advance in organ preservation treatment
in locally advanced head and neck within a multidisciplinary
approach of chemotherapy, radiotherapy and immunotherapy. We will participate in a phase III, randomized, study of
the effects of leukocyte interleukin injection plus radiotherapy in patients with advanced squamous cell carcinoma of
the oral cavity. 3) Test new drugs that can reduce acute
and late toxicity derived from chemoradiation, such as
mucositis and xerostomia. Our multicentric phase III study
on the benefit of Clonidine for the prevention of oral
mucositis in head and neck cancer patients has completed accrual now, and statistical analysis is planned for this
year. Also, the study on intranasal Fentanyl for the treatment of pain associated with oral mucositis, has completed its accrual now. 4) We are also working in surgical
rehabilitation, including dental implants and mandibular
reconstruction in order to improve quality of life of head and
neck cancer patients. A review on neck dissection after
chemoradiation for head and neck cancer has been done,
in collaboration with the E.N.T. department, and the
Radiology department to establish which patients undergoing a conservative treatment need to be operated.
MAJOR GRANTS
Hinojar Gutiérrez, Adolfo Carlos. Papel de las células
madre tumorales en la evolución clínica del carcinoma
escamoso de laringe. Estudio de la expresión de
podoplanin A, CD44 Y ALDH-1. Fundación Mutua
Madrileña. 2011-2014.
PUBLICATIONS
(4)
Cerezo L, López C, de la Torre A, Suárez D, Hervás
AREA 3
Cerezo L, de la Torre A, Hervás A, Ruiz A, Liñán O,
López M, Villar K, Martín M. Oropharyngeal cancer
related to Human Papilloma Virus: Incidence and
Prognosis in Madrid, Spain. Clin Transl Oncol.
16(3):301-6. 2014. PMID: 23828503. IF: 1,6. DOI:
10.1007/s12094-013-1074-5.
http://dx.doi.org/10.1007/s12094-013-1074-5
Navas M, Sola RG, Torres CV, Shakur SF,
Manzanares R, Gordillo C, Jimenez JA. Primary
central neurocytoma of the mesencephalic tectum
in a pediatric patient. Childs Nerv Syst 30(5):945951. 2014. PMID: 23958899. IF: 1,163.
Zapatero A, Morente M, Nieto S, Martín de Vidales
C, Lopez C, Adrados M, Arellano R, Artiga MJ,
Garcia-Vicente F, Herranz LM, Leaman O. . Urol
Oncol. 32(8):1327-32. 2014. PMID: 24946957. IF:
3,363. DOI: 10.1016/j.urolonc.2014.05.004.
http://dx.doi.org/10.1016/j.urolonc.2014.05.004
CLINICAL TRIALS
PRINCIPAL RESEARCHER: MUÑOZ GUERRA,
MARIO FERNANDO
Ensayo clínico en fase III, multicéntrico, aleatorizado, doble ciego, con doble simulación, de grupos
paralelos, controlado con comparador activo y
placebo, para evaluar la eficacia analgésica y
seguridad de ibuprofeno arginina/tramadol
400/37,5 mg comparado con ibuprofeno arginina
400 mg, tramadol 50 mg sólo y placebo en
pacientes con dolor moderado a intenso tras
cirugía dental; (Versión 1: 22-02-14). LABORATORIOS FARMALIDER, S.A. FMLD-IOTRA-20_FIIIA
EudraCT: 2013-004637-33
GRUPO 59
HEAD OF LABORATORY
Carlos Manuel Olivier Gómez
GROUP MEMBERS
• Marco Antonio Acosta Reveles
• Eduardo Mariano Albers Acosta
• Gloria Bocardo Fajardo
• Ricardo Brime Menéndez
• Guillermo Celada Luis
• Victoria Diego García
• Inmaculada Fernández González
• María José Galán Sánchez-Heredero
• Renán Javier Otta Oshiro
• Estefanía Romero Selas
• Luis Alberto San José Manso
RESEARCH INTEREST
Our group focused on different research areas.
Erectile dysfunction: Endothelial dysfunction is one
of the first symptoms of erectile dysfunction (ED) and
is closely related to atherosclerosis and risk factors
such as diabetes mellitus (DM), both of them characterized by inflammatory and oxidative advanced
state. Vardenafil is one of the more effective 5-phosphodiesterase inhibitors in patients with ED and DM.
We have determined plasma proteome of patients
with DM and the effect of vardenafil administration in
the expression of proteins related to inflammatory
oxidative stress and cellular homeostasis. We have
observed a significant negative correlation between
plasma levels of beta-tropomyosin and IIEF-EF
score. Elevated levels of beta-tropomyosin in plasma
indicate cell damage and loss of cellular regenerative
capacity.
Urothelial cancer: Exosome extracellular vesicles
are potent intercellular mediators containing membrane and cytosolic proteins, mRNA and specific
– 157 –
AREA 3AREA 2 AREA 1
A, Ruiz A, Ballestín C, Martín M, Sandoval P.
Incidence of HPV-related oropharyngeal cancer
and outcomes after chemoradiation in a population
of heavy smokers. Head Neck. 36(6):782-6. 2014.
PMID:
23616290.
IF:
3,006.
DOI:
10.1002/hed.23366.
http://dx.doi.org/10.1002/hed.23366
miRNA, which in turn can be obtained from fluids
such as urine. We have analyzed urinary exosomes,
miRNA and protein content in order to find diagnostic markers for bladder urothelial cancer. Some of
the miRNAs that are involved in tumor cell proliferation, inhibition of tumor suppressor genes, activation
of EMT and metastatic state, are significantly
reduced in urinary exosomes from patients with
bladder urothelial carcinoma and may be useful as
non-invasive diagnostic biomarkers in bladder cancer.
With regard to surgical techniques, we have optimized the diagnosis and therapeutic endourologic
approach to the upper urothelial tract cancer.
• Fernando Ramasco Rueda
• Fernando Teba del Pino
PUBLICATIONS (1)
Gómez-Barrena E, Padilla-Eguiluz NG, García-Rey E,
Cordero-Ampuero J, García-Cimbrelo E. Factors influencing regional variability in the rate of total knee
arthroplasty. Knee. 21(1):236-41. 2014. PMID:
23528444. IF: 1,702.
DOI: http://dx.doi.org/10.1016/j.knee.2013.01.003
CLINICAL TRIALS
GROUP ASSOCIATED 3
HEAD OF LABORATORY
José Cordero Ampuero
GROUP MEMBERS
• Enrique Alday Muñoz
• Vicente Casa de Pantoja
• Francisco Clement Fernández
• José Cordero Ampuero
• Jacobo González Guijarro
• Emilio Marín Aráez
• Mar Orts Rodríguez
• Antonio Planas Roca
– 158 –
PRINCIPAL RESEARCHER: ALDAY MUÑOZ,
ENRIQUE
Efecto de la revisión del bloqueo neuromuscular con
sugammadex frente a neoestigmina en la función
pulmonar postoperatoria. Estudio aleatorizado y controlado; (Versión 1: 19-11-14). ENRIQUE ALDAY (Sº
ANESTESIOLOGIA HUP) PRIN-SUGAR-2014
EudraCT: 2014-005156-26
PRINCIPAL RESEARCHER: RAMASCO RUEDA,
FERNANDO
Reducción de las complicaciones postoperatorias
y de la estancia hospitalaria con una estrategia
perioperatoria individualizada de ventilación de
protección pulmonar. Estudio comparativo,
prospectivo, multicéntrico, aleatorizado y controlado. INCLIVA ESTUDIO IPROVE
www.iis-princesa.org

AREA 1 - IIS LA PRINCESA

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