AREA 1 - IIS LA PRINCESA

Transcripción

2012
ANNUAL REPORT OF
SCIENTIFIC ACTIVITY
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2012
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.
Etiopathogenic and immunological mechanisms of
dermatological diseases.
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 . . . . . . . . . . . . . . . . . . . . . .27
2012 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
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AREA 3 · Advanced therapies and individualized medicine . . . . . . . . . . . . . .107
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Diego de León, 62
28006 Madrid
Phone 91 520 25 08
e-mail: [email protected]
Web: www.iis-princesa.org
–3–
PRÓLOGO FOREWORD
Prólogo IP
Foreword IP
IIS-Princesa 2012
–5–
Carta del director científico
Letter from the Scientific Director
Francisco Sánchez Madrid
Director Científico / Scientific Director
La producción
científica del IP
durante el año
2012 muestra una
consolidación de
su tendencia
creciente durante
los últimos años,
con 340
publicaciones que
suponen un factor
de impacto de
1672.99
–6–
E
s una enorme satisfacción poder
presentar un año más la memoria
científica del Instituto de Investigación Sanitaria del Hospital Universitario de
la Princesa (IP).
La difusión de la actividad de investigación que se lleva a cabo en el IP es un elemento de gran importancia. En primer lugar
resulta esencial para dar a conocer la actividad investigadora que se desarrolla dentro
del propio IP, como reconocimiento expreso del esfuerzo llevado a cabo por todos y
cada uno de los investigadores que trabajamos en él, dentro de un año particularmente complicado, como fuera de él poniendo de manifiesto ante otras instituciones la gran capacidad de investigación del
IP. Para ello intentaremos en esta memoria
recoger la actividad científica del IP durante
el pasado 2012.
La producción científica del IP durante
el año 2012 muestra una consolidación de
su tendencia creciente durante los últimos
años, con 340 publicaciones que suponen
un factor de impacto de 1672.99. Estos
datos evidencian la tendencia creciente del
IP no sólo en número de publicaciones,
sino en la calidad de los mismos. Durante el
último año el número de publicaciones en
revistas en primer quartil se ha incrementado en más de un 45% respecto al año
2011.
Desde el punto de vista económico y a
pesar de las dificultades del momento actual, la capacidad de captación de fondos
para la investigación a diferentes niveles, ha
seguido su tendencia ascendente. En este
nce again, it is a great pleasure
to present the Annual Scientific
Report of the Instituto de Investigación Sanitaria Hospital Universitario de La Princesa (La Princesa Hospital Institute for Health Research, IP).
The research activity of our Institute is
the result of the combined effort of our
professionals who have worked with
strong commitment and great dedication during 2012. To acknowledge the
effort of our researches, after a year
specially difficult for our institution, and
to show to the Public the outstanding
research capacity of the IP it is particularly important to communicate the results of our research. In the present report we will gather and present the research activity of IP during 2012.
The scientific output during
2012, with 340 publications and a total
impact factor of 1672.99, confirms the
steady tendency to increase in recent
years. Our scientific output has improved both in the number of publications and their quality. During the last
year the number of publications in fist
quartile journal was augmented 45%
compared to 2011.
Despite the great difficulties
faced in the current economic environment, the capacity of IP to attract research funds has maintained an increasing trend. In this scenario, it is important to emphasize the crucial role of
the Biomedical Research Foundation
(FIB) and its great effort dedicated to
O
punto, es importante resaltar el importante
papel de la Fundación para la Investigación Biomédica y el gran esfuerzo de
gestión que realiza para intentar mantener las complicadas condiciones económicas actuales, y así mantener los compromisos adquiridos y las prestaciones
ofrecidas a los investigadores del IP.
Sin duda, es esencial realizar un gran
esfuerzo para mantener la capacidad investigadora del IP al menos en los mismos
parámetros en años previos, por lo que el
trabajo en equipo resulta un pilar fundamental para ello. Como prueba de ello, resaltar que el pasado año 2012 se puso en
marcha la Unidad de Terapias Biológicas
que tiene como participantes a investigadores del IP de los servicios de Reumatología, Digestivo, Neurología, Dermatología y
Farmacia. Esta Unidad (la primera de la comunidad de Madrid) tiene como objetivo la
aplicación de una terapia individualizada
para los pacientes con enfermedades crónicas de base inmunológica, mejorando así
las enfermedades asociadas; favoreciendo
con ello la optimización de los recursos
hospitalarios,
Desde aquí quiero agradecer a los todos los jefes de áreas, jefes de líneas y grupos de investigación, a todos los investigadores así como a las plataformas de apoyo,
su comprometida participación que desde
hace años vienen realizando y no siempre
bajo unas condiciones fáciles. Es por ello
que los resultando obtenidos durante el
año 2012 resultan aún más gratificantes.
the management of resources to keep
up with the services provided to all the
IP researches.
Our institution has pioneered in
2012 the formation of the multidisciplinary Biological Therapies Unit. In this
new unit (the first of this nature in
Madrid) participate IP researchers from
the Rheumatology, Neurology, Gastroenterology, Dermatology and Pharmacy services of la Princesa Hospital in
a project aimed to integrate and optimize the use of Biological Therapies in
immune mediated inflammatory disorders. The main goal of this Unit is the integration of the use of these treatments
from the perspective of increasing efficiency, safety, and cost effectiveness.
The new Unit is an excellent example of
joint collaborative effort that will foster
further research projects.
Finally, I would like to express
here my gratitude to all personnel for
their great effort and committed dedication working for IP during the last few
years. It makes it more gratifying to
present the results of our activity during
2012.
The scientific
output during
2012, with 340
publications and
a total impact
factor of 1672.99,
confirms the
steady tendency
to increase in
recent years
–7–
PRÓLOGO IP / FOREWORD IP
ESTRUCTURA ORGANIZATIVA
ORGANISATIONAL CHART
CONSEJO RECTOR
GOVERNING COUNCIL
PRESIDENTE / CHAIRMAN
Patricia Flores Cerdán
Viceconsejera de Asistencia Sanitaria de la Comunidad de Madrid
Deputy Minister of Health Care, Comunidad de Madrid
VICEPRESIDENTE / VICE-CHAIRMAN
José Mª Sanz Martínez
Vicerector de la UAM
Vice-chancelor of UAM
MIEMBROS / MEMBERS
Miguel Ángel Andrés Molinero
Director Gerente, Hospital U. La Princesa
General Manager, Hospital U. La Princesa
Margarita González Grande
Director Gerente, Hospital U. Niño Jesús
Managing Director Hospital U. Niño Jesús
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,
Consejería de Sanidad de la Comunidad de Madrid
Rosar Mª Ramos Pérez
Director Gerente, Hospital U. Santa Cristina
Managing Director Hospital U. Santa Cristina
Alfonso Garrigós Garnica
Dirección de Gestión, Hospital U. La Princesa
José Antonio Gutierrez Fuentes
Director de la Fundación Lilly
Director of Lilly Foundation
Miguel López-Bravo Bascán
Director General de Planificación, Infraestructuras y Equipamientos
Sanitarios de la Comunidad de Madrid
Federico Mayor Menéndez
Centro Biología Molecular Severo Ochoa, Madrid
Severo Ochoa Molecular Biology Centre, Madrid
Julio Ancochea Bermúdez
Servicio de Neumología, Hospital U. La Princesa
Respiratory Department, Hospital U. La Princesa
Director Científico, Instituto Investigación Sanitaria IP
Scientific Director of IP
SECRETARIA / SECRETARY
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
Miguel Ángel Andrés Molinero
Director Gerente, Hospital U. La Princesa
General Manager, Hospital U. La Princesa
VICEPRESIDENTE / VICE-CHAIRMAN
Antonio García García
Director del Instituto Teófilo Hernando, UAM
Servicio de Frmacología Clínica, Hospital U. La Princesa.
Director of Instituto Teófilo Hernando, UAM
Clinical Farmacology Department, Hospital U. La Princesa
MIEMBROS / MEMBERS
Alfonso Garrigós Garnica
Director de Gestión Y SS.GG, Hospital U. La Princesa
Gustavo Casero Balboa
Subdirector de Gestión/RR.HH, Hospital U. La Princesa
–9–
Manuel Fresno Escudero
Emilio Úcar Corral
Subdirector Médico, Hospital U. Santa Cristina
Medical Sub-director, Hospital U. Santa Cristina
Luis Madero López
Servicio de Hematología, Hospital U. Niño Jesús
Hematology Department, Hospital. U. Niño Jesús
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,
Consejería de Sanidad de la Comunidad de Madrid.
Javier Aspa Marco
Director Médico, Hospital U. La Princesa
Medical Director, Hospital U. La Princesa
SECRETRIA / SECRETARY
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
COMITÉ CIENTÍFICO EXTERNO / EXTERNAL SCIENTIFIC COMMITTEE
Carlos López Otín
Departamento de Bioquímica y Biología Molecular, Universidad de
Oviedo.
Department of Biochemistry and Molecular Biology, University of Oviedo
Miguel López-Botet Arbona
Director Científico del IMIN, Barcelona
Scientific Director of IMIN, Barcelona
Jaime Bosch Genover
Director Científico del CIBERHED
Scientific Director of CIBEREHD
Xosé R. Bustelo
Centro de Investigación del Cáncer, Salamanca
Cancer Research Center, Salamanca
– 10 –
Felipe Rodriguez de Castro,
Decano de la Facultad de Medicina, Universidad de Las Palmas de
Gran Canaria.
Dean of Medical School, University of Las Palmas de Gran Canaria
José López Barneo
Director del Instituto de Investigación Biomédica, Sevilla
Director of Biomedical Research Institute, Sevilla
COMISIÓN DE INVESTIGACIÓN
RESEARCH COMMITTEE
Manuel Ortiz de Landázuri
Servicio de Inmunología, Hospital U. La Princesa
Immunology Department, Hospital U. La Princesa
Servicio de Neumología, Hospital U. La Princesa
Respiratory Department, Hospital U. La Princesa
Ricardo Moreno Otero
Servicio de Digestivo, Hospital U. La Princesa
Gastroenterology Department, Hospital U. La Princesa
Amaro García Díez
Servicio de Dermatología, Hospital U. La Princesa
Dermatology Department, Hospital U. La Princesa
Servicio de Farmacología Clínica, Hospital U. La Princesa
Isidoro González Álvaro
Servicio de Reumatología, Hospital U. La Princesa
Rheumatology Department, Hospital U. La Princesa
Mónica Marazuela Azpiroz
Servicio de Endocrinología, Hospital U. La Princesa
Endocrinology Department, Hospital U. La Princesa
Adrián Alegre Amor
Servicio de Hematología, Hospital U. La Princesa
Hematology Department, Hospital U. La Princesa
Francisco Abad Santos
Servicio de Farmacología Clínica, Hospital U. La Princesa
Carmelo García Monzón
Servicio de Medicina Interna, Hospital U. Santa Cristina
Internal Medicine Department, Hospital U. Santa Cristina
Jesús Argente Oliver
Servicio de Endocrinología, Hospital U. Niño Jesús
Endocrinology Department, Hospital U. Niño Jesús
Luis García Olmos
Coordinador de Docencia e Investigación, Atención Primaria,
Madrid
Teaching and Research Coordinator, Atención Primaria, Madrid
Ramón Colomer Bosch
Servicio de Oncología Médica, Hospital U. La Princesa
Medical Oncolgy Department, Hospital U. La Princesa
Carmen Súarez Fernández
Servicio de Medicina Interna, Hospital U. La Princesa
Internal Medicine Department, Hospital U. La Princesa
Dolores Ochoa Mazarro
Igor Pinedo García
Carolina Pozuelo González
Eduardo Sánchez Sánchez
Alberto Sebastián Palomino
Alba Serrano Ruiz
Tania Tineo Drove
Mara Ortega Gómez
FUNDACIÓN INVESTIGACIÓN BIOMÉDICA (FIB)
FOUNDATION FOR BIOMEDICAL RESEARCH (FBR)
DIRECTOR / DIRECTOR
Mª Ángeles Vallejo
COMITÉ ÉTICO DE INVESTIGACIÓN CLÍNICA
CLINICAL RESEARCH ETHICS COMMITTEE
VICEPRESIDENTE/ DEPUTY CHAIRMAN
MIEMBROS / MEMBERS
Enrique Alday Muñoz
Ramón Colomer Bosch
Carmen del Arco Galán
Mª José Galán Sánchez Heredero
D. Carmelo García-Monzón
Jesús González Cajal
Andrés López Romero
Elena Martín Pérez
Concepción Martínez Nieto
Licinio Medina Moreno
– 11 –
PRODUCCIÓN CIENTÍFICA
SCIENTIFIC OUTPUT
SCIENTIFIC OUTPUT
El análisis de la producción científica del IP medido por el factor de
impacto (IF) de las revistas académicas, es uno de los indicadores
bibliométricos más utilizados que muestran la calidad de los trabajos publicados. Este índice, es una medida que se calcula anualmente y refleja el número de veces que los artículos son citados,
referidos al total de las publicaciones “citables” de una revista concreta. Consideraremos como Factor de Impacto (FI) de las revistas
el indicado en el Journal Citation Report (JCR) 2011.
Cada publicación será computada una sola vez cuando sean
referidos al total de las publicaciones y del factor de impacto acumulado del IP. Sin embargo aquellas que involucren a diferentes
grupos de investigación se computan individualmente a cada uno
de ellos y así se muestra con detalle en la actividad científica de
cada grupo. Sólo se mostrarán las publicaciones publicadas en
revistas con factor de impacto superior a 0,9.
Impact factor (IF) of the academic journals in which articles are
published is one of the indicators used most frequently to show the
quality of published articles. This index is calculated yearly and
reflects for each journal the number of times that its articles are
cited, referred to the total number of cited articles in a particular
field. In this report we have used for our analysis the IF indicated in
Journal Citation Report (JCR) 2011.
Each article is counted only once when referred to the total
number of publications and the accumulated impact factor of the
IP. However, those involving different research groups are ascribed
to each of the groups and are shown in detail in the scientific output of the groups. Only the publications in journals with IF higher
than 0.9 are shown
En 2012 un total de 340 artículos fueron publicados en revistas indexadas con FI superior a 0,9; este dato supone un incremento del 15% respecto al año 2011. El factor de impacto acumulado fue de 1672.99. Esto significa que el factor de impacto medio
por artículo fue de 4.92, implicando un aumento significativo respecto al 4.7 del año 2011.
In 2012, a total of 340 articles were published in indexed journals with IF higher than 0,9, representing a 15% increased from
2011. The accumulated IF was 1672.99. These data resulted in a
mean IF per article of 4.92 which represented a significant
increase from the 4.7 of 2011.
– 12 –
En el siguiente gráfico se muestran los artículos del IP distribuidos por quartiles. Durante el año 2012 se ha producido un
incremento en los artículos publicados en revistas de quartil 1, lo
que supone un 57% de todas de las publicaciones.
The following graphic shows distribution of IP articles in different quartiles. In 2012 the number of articles published in quartile
1 journal has increased. Articles in quartile 1 represent 55% of
total.
LISTADO REVISTAS
JOURNAL INDEX
JOURNAL
Articles
6,8
1
CEREB CORTEX
6,544
1
ANN ONCOL
6,425
1
HAEMATOL-HEMATOL J
6,424
3
J INFECT DIS
6,41
1
JACC-CARDIOVASC INTE
The tables listed below shows the fifty high impact factor journal in
which IP researchers published articles during 2012.
The tables listed below show the fifty high impact factor journals in which IP researchers published articles during 2012.
JOURNAL
IF
IF
Articles
NEW ENGL J MED
53,298
3
ONCOGENE
6,373
1
NAT REV MOL CELL BIO
39,123
1
J PATHOL
6,318
1
LANCET
38,278
3
AIDS
6,245
4
ANN INTERN MED
16,733
1
MOL CELL
14,178
1
WORLD PSYCHIATRY
6,233
2
CELL METAB
13,668
1
J CELL SCI
6,111
1
J CLIN INVEST
13,069
1
CARDIOVASC RES
6,064
1
GASTROENTEROLOGY
11,675
1
CANCER TREAT REV
6,054
1
HEPATOLOGY
11,665
1
PLOS BIOL
11,452
1
J CLIN ENDOCR METAB
5,967
2
GUT
10,111
1
EUR RESPIR J
5,895
1
BLOOD
9,898
4
J IMMUNOL
5,788
3
J AM SOC NEPHROL
9,663
1
J THROMB HAEMOST
5,731
2
J HEPATOL
9,264
1
EMBO J
9,205
1
STROKE
5,729
2
CLIN INFECT DIS
9,154
3
FASEB J
5,712
1
PLOS PATHOG
9,127
1
BBA-MOL CELL RES
5,538
1
8,8
1
J INTERN MED
5,483
1
ANN RHEUM DIS
8,727
4
CLIN CHEM
7,905
1
INTENS CARE MED
5,399
1
CLIN CANCER RES
7,742
1
CHEST
5,25
1
HUM MOL GENET
7,636
2
ENDOSCOPY
5,21
1
SCI SIGNAL
7,499
2
MOL CELL PROTEOMICS
7,398
1
TRENDS PARASITOL
5,144
1
AM J GASTROENTEROL
7,282
3
CURR DRUG METAB
5,113
4
SCHIZOPHRENIA BULL
– 13 –
GUÍAS CLÍNICAS
CLINICAL GUIDELINES
Uno de los retos de nuestra investigación, es poder trasladar los
avances desarrollados en nuestro al IP al beneficio de los pacientes. Este hecho se materializa en la creación de guías de Práctica
Clínica. A continuación, se listan las guías publicadas durante el
año 2012.
TITLE
One of our biggest challenges is to translate our research to
the benefit of patients. Our researchers contribute to this effort participating actively in the elaboration of clinical guidelines. The
guidelines published during 2012 are listed below.
AUTHORS
JOURNAL
AREA
GROUP
Latex allergy: Position Paper
Cabañes N, Igea JM, de la Hoz B, Agustín P, Blanco
C, Domínguez J, Lázaro M, Lleonart R, Méndez J,
Nieto A, Rodríguez A, Rubia N, Tabar A, Beitia JM,
Dieguez MC, Martínez-Cócera C, Quirce S.
J Investig Allergol Clin Immunol
22(5):313-30. 2012. PMID:
23101306.
1
20
Guía de Práctica Clínica para el
Tratamiento de Pacientes con Enfermedad
Pulmonar Obstructiva Crónica (EPOC)
Julio Ancochea Bermúdez.
MSC 2012
1
22
COPD Guidelines (GesEPOC): pharmacological treatment of stable COPD
Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J,
Almagro P, Quintano JA, Riesco JA, Trigueros JA,
Piñera P, Simón A, López-Campos JL, Soriano JB,
Ancochea J.
Arch Bronconeumol. 48(7):247257. 2012. PMID: 22561012.
1
22
Recommendations for the prevention and
management of suicidal behavior. Guía clínica para el manejo de la conducta suicida
derivada de un proyecto Subvencionado
por la Comunidad de Madrid.
Ayuso-Mateos JL, Baca-García E, Bobes J, Giner J,
Giner L, Pérez V, Sáiz PA, Saiz Ruiz J; Grupo
RECOMS
Rev Psiquiatr Salud Ment 5(1):823. 2012. PMID: 22854500.
2
33
Guidelines for the preventive treatment of
ischaemic stroke and TIA (I). update of risk
factors and life style
Fuentes B, Gállego J, Gil-Nuñez A, Morales A,
Purroy F, Roquer J, Segura T, Tejada J, Lago A,
Díez-Tejedor E; por el Comitéad 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, Maestre J, Masjuan J, MartíFábregas J, Martínez-Sánchez P, Martínez-Vila E,
Molina C, Nombela F, Ribó M, Rodríguez-Yañez M,
Rubio F, Serena J, Simal P, Vivancos J.
Neurologia
27(9):560-574.
2012. PMID: 21890241.
2
35
Ultrasound measurement of carotid stenosis: recommendations from the Spanish
Society of Neurosonology.
Serena J, Irimia P, Calleja S, Blanco M, Vivancos J,
Ayo-Martín O
Neurologia. 2012 Oct 4. pii:
S0213-4853(12)00251-4.
2012. PMID: 23040716. doi:
10.1016/j.nrl.2012.07.011
2
35
– 14 –
TITLE
AUTHORS
JOURNAL
AREA
GROUP
Clinical management guidelines for subarachnoid haemorrhage. Diagnosis and
treatment.
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, AlvarezSabin 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, MartínezSánchez 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).
Neurologia. 2012 Oct 6. pii:
S0213-4853(12)00249-6.
2012. PMID: 23044408. doi:
10.1016/j.nrl.2012.07.009.
2
35
Validation of a new tool to assess healthrelated quality of life in psoriasis: the PSOLIFE questionnaire
Dauden E, Herrera E, Puig L, Sánchez-Carazo JL,
Toribio J, Caloto MT, Nocea G, Roset M, Lara N.
Health Qual Life Outcomes. 10:56.
2012. PMID: 22624984. doi:
10.1186/1477-7525-10-56.
3
37
Clinical practice guideline for an integrated
approach to comorbidity in patients with
psoriasis.
Daudén E, Castañeda S, Suárez C, GarcíaCampayo J, Blasco AJ, Aguilar MD, Ferrándiz C,
Puig L, Sánchez-Carazo JL; on behalf of the
Working Group on Comorbidity in Psoriasis.
J Eur Acad Dermatol Venereol.
[Epub ahead of print]. 2012.
PMID: 23134338. doi: 10.1111/
jdv.12024
3
37
Clinical practice guideline on the management of patients with dyspepsia.
Gisbert JP, Calvet X, Ferrándiz J, Mascort J, AlonsoCoello P, Marzo M.
Aten Primaria. 44(12):727.e1727.e38.
2012.
PMID:
23036729.
3
38
Managing of the patient with dyspepsia.
Gisbert JP, Calvet Calvo X, Ferrándiz Santos J,
Mascort Roca JJ, Alonso-Coello P, Marzo Castillejo
M.
Aten Primaria. 44(12):728-33.
2012. PMID:23089244. doi:
10.1016/j.aprim.2012.07.008
3
38
Management of Helicobacter pylori infection--the Maastricht IV/ Florence
Consensus Report.
P. Malfertheiner, F. Megraud, C. A. O'Morain, J.
Atherton, A. T. Axon, F. Bazzoli, G. F. Gensini, J. P.
Gisbert, D. Y. Graham, T. Rokkas, E. M. El-Omar y E.
J. Kuipers & the European Helicobacter Study
Group (EHPSG).
Gut 61(5):646-664. 2012.
PMID:22491499. DOI: 10.1136/
gutjnl-2012-302084.
3
38
Guías españolas de diagnóstico y tratamiento de los síndromes mielodisplásicos y
la leucemia mielomonocítica crónica.
Grupo
Español
de
Síndromes
Mielodisplásicos (GESMD)
Valle Gómez García de Soria (colaboradora).
Haematologica 97(supl 5). 2012.
ISSN 1138-0381.
3
44
Comparative study of talc poudrage versus
pleural abrasion for the treatment of primary spontaneous pneumothorax
Moreno-Merino S, Congregado M, Gallardo G,
Jimenez-Merchan R, Trivino A, Cozar F, LopezPorras M, Loscertales J.
Interact Cardiovasc Thorac Surg.
15(1):81-5. 2012. Entidad:
Sponsor: European Soc Thorac
Surg (ESTS). PMID: 22514256.
DOI: 10.1093/icvts/ivs027
3
44
– 15 –
SCIENTIFIC OUTPUT
INNOVACIÓN Y TRANSFERENCIA
DE RESULTADOS
INNOVATION AND TRANSFERENCE
Es esencial para el IP potenciar todos los trabajos llevados a cabo
en materia de innovación. Como prueba de ellos es la Unidad de
terapias Biológicas de nuestro centro, siendo la primera de la
Comunidad de Madrid. La creación de esta unidad es un reto para
la aplicación de los avances en áreas de Neurología, Reumatología,
Dermatología, Digestivo y Farmacia, que favorece no sólo la posibilidad de instaurar terapias personalizadas para los pacientes,
sino también para optimizar los recursos existentes.
Por otro lado los trabajos de innovación de los investigadores
del IP han dado lugar a la solicitud de 5 nuevas patentes y a la concesión durante el pasado año 2012 de otras 7. A continuación se
muestras los detalles de cada grupo.
TITLE
REF. NUMBER
One of the great achievements of our Institute in the area of
innovation in health care has been the multidisciplinary Biological
Therapies Unit. This new unit (the first of this nature in Madrid) was
established in 2012 by the collaborative effort of researchers from
the Rheumatology, Neurology, Gastroenterology, Dermatology and
Pharmacy services of la Princesa Hospital within IP. It aims to integrate the use of Biological Therapies in immune mediated inflammatory disorders, trying to optimize the use of these treatments
from the perspective of increasing efficiency, safety, and cost effectiveness.
During 2012 seven new patent applications have been filed by
researchers of IP and seven applications were granted. Details for
each group are listed below.
AUTHORS
COUNTRY
ENTIDAD
GROUP
Secuencias nucleotídicas motivo que
dirigen la localización de los ácidos
nucleicos
P201231503
Villarroya-Beltri, C., Mittelbrunn, M.,
Gutierrez-Vazquez, C., Sanchez-Cabo,
F. and Sanchez-Madrid, F
España
CNIC / UAM
1
Uso de al menos una molécula de ADN
para preparar un medicamento destinado
al tratamiento del cáncer
P201231393
Julián Aragones, Ainara Elorza,
Manuel O. Landazuri
España
UAM
9, 6
Método in vitro de pronóstico de fibrosis
hepática grave
P201230368
Ricardo Moreno Otero, Rosario López
Rodríguez, Paloma Sanz Cameno
España
UAM /
CIBERehd
23
Método in vitro de pronóstico de cirrosis
hepática
P201230365
Ricardo Moreno Otero, Rosario López
Rodríguez, Paloma Sanz Cameno
España
UAM /
CIBERehd
23
P201230827
Rosa Perez Gomariz, Mª Carmen
Martínez Mora, Yasmina Juarranz,
Javier Leceta, Isidoro González Álvaro
y Ana Mª Ortiz
España
FIB del HUP/
Universidad
Complutense
de Madrid
36
Uso de VIP como marcador pronóstico de
enfermedades autoinmunes
– 16 –
ENTIDAD
ENTIDAD
EXPLOTADORA
GROUP
España
Instituto
Biomar, S.L
Instituto Biomar,
S.L
12, 39
María Yañez Mo, Francisco SánchezMadrid, Francisco Domínguez Hernández,
Carlos Simón Vallés
España
CNIC/UAM/
IVI
3,1
P200900085
Piqueras, J.F., Hernández, S., Villa-Morales,
M, González-Sanchez, Laura, Fresno, M. &
Fernández-Navarro
España
UAM
12
P200930936
Rodríguez Franco, Mª Isabel, Conde Ruzafa,
Santiago, López Iglesias, Beatriz, Pérez
Martín, Concepción, Villarroya Sánchez,
Mercedes, García López, Manuela, García
García, Antonio
España
UAM / CSIC
28
P200930931
Rodríguez Franco, Mª Isabel, Conde Ruzafa,
Santiago, López Iglesias, Beatriz, Pérez
Martín, Concepción, Villarroya Sánchez,
Mercedes, García López, Manuela, García
García, Antonio
España
UAM / CSIC
28
Compuestos derivados de
1,8-naftiridinas y su uso en el
tratamiento de enfermedades
neurodegenerativas
P200930903
PCT/ES2010/
070687
Cristóbal de los Ríos Salgado, Alejandro
Romero Martínez, Javier Egea Máiquez,
Rafael León Martínez, Mercedes Villarroya
Sánchez, Manuela García López, Antonio
García García, José Luis Marco Contelles,
Elena Soriano Santamaría, Abdelouahid
Samadi, Chioua Mourad
España
UAM / CSIC
28
Utilização de cromonas, seus
derivados, seus sais farmaceuticamente aceitáveis e
seus pró-fármacos com
actividade inibidora da
monoamina oxidase e
aplicações
terapêuticas
relacionadas
PT104487
Borges, M.F.M., Gaspar, A.M.N., Garrido,
J.M.P.J., Milhazes, N.J.S.P., Uriarte, E.,
Yáñez, M., Orallo, F
España
UAM
28
P201030762
Manuel López-Brea Calvo, Teresa Alarcón
Cavero, Sandra Rodrigo Gil, Alfonso-Vicente
Carrascosa Santiago, Adolfo José Martínez
Rodríguez
España
CSIC / UAM
52
TITLE
REF. NUMBER
AUTHORS
Hexacyclic polyketides as
kinase inhibitors
PCT/EP2011/
062379
Sánchez López, José Mª, Martínez Insua,
Marta, Romero Millán, Francisco,
Fernández-Medarde, Antonio, Fernández
Chimeno, Rosa Isabel, Fresno Escudero,
Manuel, Sánchez Valdepeñas, María del
Carmen, Ramírez Orellana, Manuel
Uso de CD98 como marcador
de receptividad endometrial
P200902193
Prostaglandina E2 para la
prevención o el tratamiento
de linfomas linfoblásticos
Derivados de bis(aralquil
amino y sistemas [6+5]heteroaromáticos y su uso en
el tratamiento de patologías
neurodegenerativas, incluida
la
enfermedad
de
Alzheimer
Derivados de bis(aralquil)
amino y sistemas (hetero)
aromáticos de seis miembros y
su uso en el tratamiento de
patologías neurodegenerativas,
incluida la enfermedad de
Alzheimer
Uso de compuestos fenólicos
para el tratamiento de
patologías causadas por
Helicobacter pylori
COUNTRY
– 17 –
SCIENTIFIC OUTPUT
TESIS DOCTORALES
DOCTORAL THESES
Para potenciar la calidad de los trabajos de investigación es fundamental tener personal bien formado, por lo que este aspecto es
fundamental dentro del IP. Como prueba de ellos durante el pasado año se ha dado lectura a 14 tesis doctorales que se detallan a
continuación.
DOCTORATE
THESIS READER
Training of PhD students is fundamental for IP. As a result of
this effort, during 2012 seven theses have been defended by
members of IP. Details are listed below:
TITLE
DIRECTOR/S
AREA
GROUP
Itziar Leal Leturia
Espectroscopia por resonancia magnética de protón del cíngulo anterior en
pacientes diagnosticados de esquizofrenia y trastorno bipolar
José Luis Ayuso Mateos,
Roberto Nuevo Benítez
2
33
María Cabello
Salmerón
Discapacidad laboral y depresión: prevalencia, evolución y factores relacionados
desde una aproximación multiple
José Luis Ayuso Mateos,
Marta Miret García, Roberto
Nuevo Benítez
2
33
Yolanda Rodríguez
Muñoz
Caracterización de subpoblaciones monocíticas en sangre periférica de pacientes con hepatitis crónica C: implicación de monocitos proangiogénicos
Tie-2 en el establecimiento y progreso de la enfermedad
1
23
Ángela Somodevilla
Solís
Factores de virulencia, aspectos inmunológicos y patrones de sensibilidad en
aislamientos clínicos de Helicobacter pylori
Manuel López-Brea Calvo,
Teresa Alarcón Cavero
3
52
Iván Ballesteros
Martín
Acciones antiinflamatorias del receptor nuclear PPARgamma en isquemia
cerebral: Papel de la 5-lipoxigenasa en la neuroprotección por rosiglitazona
María
Ángeles
Moro
Sánchez, Ignacio Lizasoain
Hernández, Olivia Hurtado
Moreno
3
Assoc.
3
Ana María Gómez
García
Estudio de quemoquinas en la Leucemia Linfoblástica Aguda infantil. Papel
del eje CXCR3/CXCL10 en la recaída del Sistema Nervioso Central
Manuel Ramírez Orellana
3
39
Ana I. Sánchez Moya
Infección y enfermedad tuberculosa en el paciente con psoriasis en tratamiento
biológico
Esteban Daudén Tello
3
37
Paloma Guillem
Llobat
Efectos de los ligandos de receptores LXR sobre la activación de macrófagos y
el desarrollo de aneurismas aórticos abdominales
Miguel Ángel Íñiguez Peña
1
18
Inés Claire Osma
García
Prostaglandinas dependientes de ciclooxigenasa-2: Moléculas clave en el
conrol funcional de los macrófagos
1
12
Elba Alonso Álvarez
Las concentraciones nanomolares de ouabaína activan la vía intrínseca de la
apoptosis en las células HeLa
Antonio García García, María
Francisca Cano Abad
2
28
– 18 –
DOCTORATE
THESIS READER
TITLE
DIRECTOR/S
AREA
GROUP
Eva María Pérez
Sacristán
La Escuela de Farmacología de Madrid: de Teófilo Hernando al Instituto de I+D
del Medicamento en la UAM
2
28
Liliana González
Espinosa
Bases clínicas y moleculares para el uso de la Pentoxifilina como tratamiento
del estado microinflmatorio y de la disfunción endotelial de pacientes en
diálisis
Abelardo Isaac Aguilera
Peralta, José Antonio
Sánchez Tomero
1
21
Felipe de La Morena
Utilidad de la aplicación de lidocaína como anestesia tópica faríngea en las
esofagogastroduodenoscopias realizadas bajo sedación con propofol
Cecilio Santander Vaquero
3
55
Eduardo Balsa
Martínez
Regulación de la cadena de transporte de electrones bajo condiciones de
hipoxia
Manuel Ortiz de Landázuri
Busca
1
6
COMUNICACIÓN Y DIFUSIÓN
COMMUNICATION AND DIFUSSION
En el momento actual es de vital importancia contar con las nuevas herramientas para divulgar cualquier actividad la actividad
científica. Desde la página Web de nuestro IP (www.iis-princesa.org), no sólo se hace difusión de los avances y novedades en el
ámbito científico, sino también convocatorias, ofertas de empleo,
cursos, congresos y noticias de relevancia para el IP. En la siguiente gráfica se muestran los datos del año 2012 y su comparativa
con el año 2011. Como se observa el número de visitas tuvo un
incremento del 26,6% respecto al año 2011 y los nuevos usuarios
que consultaban la Web se incrementaron en un 21,6%.
La difusión de las actividades del IP no sólo tiene alcance en
nuestro país, a continuación se muestra la distribución de las visitas a la Web por países y una tabla con los que más nos visitan.
It is currently of vital importance to use the new information
tools to widely communicate the scientific activity. From the IP website (www.iis-princesa.org), we communicate not only the new scientific discoveries, but also research calls, courses, scientific congresses and news relevant to IP. The following graphic shows data
from 2012 and their comparison to 2011. As depicted, the number
of visits to the website increased 26.6% compared to 2011 with a
21.6% raise in the number of new users.
The diffusion of our activities goes beyond our country. A distribution of the number of visits to the Web by countries is shown
together with a table listing the nationalities most frequently consulting the Web.
– 19 –
SCIENTIFIC OUTPUT
COUNTRY
ESPAÑA
2012
2011
IMPROVEMENT
24295
19008
+26.67%
COLOMBIA
390
281
+38.79%
REINO UNIDO
321
196
+68.78%
NO DETERMINADO
300
87
+244.83%
ALEMANIA
207
86
+140.70%
En el siguiente gráfico, se muestra la distribución del número
de visitas de las noticias por trimestres.
The following graphic shows a quarterly distribution of the
number of visits.
PLATAFORMAS CIENTÍFICAS
SCIENTIFIC PLATFORMS
BIOBANCO
BIOBANK
Responsable Científica
Scientifc Coordinator
Dra. Mara Ortega Gómez
El Biobanco Hospital Universitario de La Princesa (acreditado por la
Comunidad de Madrid) se organiza como una Plataforma de apoyo
– 20 –
a la investigación dentro del Instituto de Investigación Sanitaria
Hospital de La Princesa (IIS-IP). Constituye un banco de muestras
biológicas de interés científico, procesadas para su explotación,
cuyos principales objetivos son 1). Coordinar la recopilación, el procesamiento, el almacenamiento y la transferencia de muestras biológicas humanas para promover la investigación biomédica de más
alto nivel. 2). Estandarizar las colecciones de muestras de investigación del Instituto (de conformidad con el artículo 67 de la LIB
14/2007 y RD 1716/2011 relacionados con la Investigación
Biomédica con muestras humanas).3). Optimizar los recursos
humanos y materiales, ofreciendo una gama de servicios para el
procesamiento y análisis de las muestras recogidas por los grupos
de investigación.
Con el objetivo de optimizar los recursos humanos y materiales el Biobanco ofrece una amplia gama de servicios para el procesamiento y análisis de las muestras recogidas por los grupos de
investigación.
El Biobanco dispone de muestras de ADN, PBMCs, suero, plasma, sangre, orina y tejidos procedentes de las siguientes colecciones:
• Patología Oncológica Genitourinaria.
• Carcinoma tiroideo primario.
• Hiperparatiroidismo Primario.
• Controles sanos.
Biobank Hospital Universitario de La Princesa (accredited by
the Comunidad de Madrid) is organized as a platform to support
research within the Instituto de Investigación IP.
It is a biological sample bank with great scientific interest,
processed for their use, whose main objectives are 1). Coordinate
the collection: processing, storage and transfer of human biological samples to promote high-level research. 2). Standardize sample collections of the Institute (in accordance with article 67 of LIB
14/2007 and RD 1716/2011, about research with human samples). 3). Optimize human and material resources, offering a range
of services for the processing and analysis of samples collected by
the research groups.
With the aim of optimizing the human and material resources,
Biobank offers a wide range of services for the processing and
analysis of samples collected by the research groups.
Biobank has samples of DNA, PBMCs, serum, plasma, blood,
urine and tissues from the following collections:
• Oncology Genitourinary Pathology.
• Primary thyroid carcinoma.
• Primary Hyperparathyroidism.
• Healthy controls .
UNIDAD ENSAYOS CLÍNICOS
CLINICAL RESEARCH AND CLINICAL TRIALS UNIT
Coordinador
Coordinator
Dr. Francisco Abad Santos
Es un servicio de apoyo a la investigación acreditado por la
Comunidad de Madrid, dirigido a todos los investigadores que
requieran apoyo para la realización de investigación clínica. Sus
principales funciones son:
• Proporcionar asistencia los investigadores tanto en recursos humanos y materiales como en procedimientos operativos y funcionales.
• Dar soporte en la gestión de la documentación para evaluación de CEIC y autoridades competentes.
• Asesorar y apoyar en la elaboración de la documentación
vinculada a la investigación clínica.
• Coordinar, asesorar la puesta en marcha de los ensayos clínicos y mantener el seguimiento de los mismos .
Clinical Trials Unit (accredited by the Comunidad de Madrid) is
a service aimed at all researchers who need support for conducting clinical trials. The main functions are:
• Provide assistance to researchers, both in human and
material resources and operating and functional procedures
• Provide management support of documentation by the Clinical
Research Ethics Committee and competent authorities.
• Advising and support in the preparation of documentation
related to clinical research.
• Coordinate the start-up and follow up clinical trials.
UNIDAD METODOLOGÍA
METHODOLOGICAL UNIT
Coordinador
Coordinator
Dr. Francisco Rodríguez Salvanés
En coherencia con los objetivos generales del IP, la Unidad de
Apoyo Metodológico (UM) tiene como fin proporcionar a los equi-
pos 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. Las prioridades de la UM son:
• Asesorar en el diseño de protocolos de investigación de
calidad que puedan resultar competitivos en las distintas
convocatorias.
• Asesoramiento para la preparación de comunicaciones y
publicación de artículos originales en revistas científicas de
amplia difusión.
• Análisis de resultados de investigación que puedan trasladarse a la práctica clínica.
According with main objectives of IP, Methodological Support
Unit (UM) is designed to provide support to the researchers of IP so
the making and implementation of scientific projects, in order to
increase the excellence of the scientific activity of the IP. UM's priorities are:
• Advising of quality protocols designs in order to be competitive in all different calls.
• Advising and development of communications and original
articles in order to publish them in scientific journals of
large diffusion.
• Research results analysis to be translated into clinical practice.
PLATAFORMAS TÉCNICAS DE APOYO
SCIENTIFIC PLATFORMS
Coordinadora
Coordinator
Dra. María Yañez Mó
El principal objetivo de esta Unidad es la coordinación de todos servicios científico-técnicos del Instituto de Investigación Sanitaria
Hospital Universitario de La Princesa. Las principales funciones
son:
• Proporcionar soporte tecnológico a todos los grupos de
investigación y planificar la cartera de servicios de las plataformas.
• Desarrollar y mejorar las instalaciones en cuanto a infraestructuras científicas, asegurando la adecuada renovación y
actualización del equipo científico-tecnológico disponible.
– 21 –
SCIENTIFIC OUTPUT
• Mejorar los servicios prestados optimizando el uso de instalaciones científicas y tecnológicas.
• Gestionar el mantenimiento de las infraestructuras científicas y la relación con las plataformas tecnológicas de ámbito autonómico y estatal.
Las plataformas gestionadas desde esta unidad son las
siguientes:
The main objective of this Unit is coordinating all scientific and
technical services of IP. The main functions are:
• Provide technical support to all research groups and plan
platforms activity.
• Develop and improve scientific infrastructure facilities,
ensuring appropriate renewal and updating of scientific and
technological equipment available.
• Optimizing use of scientific and technological facilities.
• Manage the maintenance of scientific infrastructure and
related technology platforms regional and state level.
Platforms managed from this unit are:
Sala Blanca IP (Hospital U. Niño Jesús)
Clean Room IP (Hospital U. Niño Jesús)
Director Técnico
Technical Director
Dra. Maria Antonia Varela-Portas San Juan
Servicio de Citometría
Cytometry Service
Coordinadora
Coordinator
Dra. Cecilia Muñoz Calleja
Servicio de Genómica CBMSO IP
Genomic Unit CBMSO IP
Director Técnico
Technical Director
Dr. Fernando Carrasco Ramiro
Servicio Microscopía Electrónica CBMSO IP
Electronic Microscope Service CBMSO IP
Director Técnico
Technical Director
Dra María Teresa Rejas Marco
Servicio de Proteómica CBMSO IP
Proteomic Unit CBMSO IP
– 22 –
Coordinador
Coordinator
Ana Isabel Marina Ramirez
Servicio de Videomicroscopía Confocal
Confocal Microscopy Service
Coordinador
Coordinator
Dra. María Yáñez Mó
Gabinete Veterinario UAM
Animal Facility UAM
Directora
Director
Carmen Fernández Criado
ÁREAS DE INVESTIGACIÓN
RESEARCH AREAS
EL IP se estructura en tres áreas prioritarias que poyan la actividad
investigadora del personal del Instituto. A continuación se desglosa la actividad de cada una de ellas mostrando el número de publicaciones con su factor de impacto acumulado y medio, así como
su evolución en los 3 últimos años.
The research groups are organized in three main areas that
cover all the research activity of IP. The scientific output of these
areas is presented bellow, showing the number of articles, mean
and accumulated impact factor and their evolution in the last three
years.
AREA 1: Cellular and Molecular Etiopathogenic Mechanisms
in Inflammatory and Autoimmune Diseases
Coordinator: Francisco Sánchez Madrid
LINE
NAME
DIRECTOR
1.1
Intercellular communication In the
inflammatory response
Francisco
Sánchez Madrid
1.2
Cellular and molecular responses to
hypoxia
Manuel Ortiz De
Landázuri Busca
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
Ricardo Moreno
Otero
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
Carmelo García
Monzón
– 23 –
SCIENTIFIC OUTPUT
AREA 2: Neurotransmission, Pharmacological Neuroprotection
and Neurodegenerative and Neuropsychiatric Diseases
Coordinator: Antonio García García
LINE
NAME
DIRECTOR
2.1
Neuropharmacology and neuroprotection
Antonio García
García
2.2
Neurotransmission in the hippocampus
Luis Gandía Juan
2.3
Clinical pharmacology and pharmacogenetics
Francisco Abad
Santos
2.4
Diagnostic and therapeutic advances in
affective disorders
José Luis Ayuso
Mateos
2.5
Neurosurgery of epilepsy
Rafael García de
Sola
2.6
Cerebrovascular diseases
José Aurelio
Vivancos Mora
– 24 –
AREA 3: Advanced Therapies and Individualized Medicine
Coordinator: Isidoro González Álvarez
LINE
NAME
DIRECTOR
3.1
Prognostic and predictor markers in
autoimmune diseases
Isidoro González
Álvaro
3.2
Esophagogastrointestinal
inflammatory diseases
Javier Pérez
Gisbert
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
Elena Fernández Ruiz
3.6
New diagnostic and therapeutic
advances in cardiovascular diseases
Luis Jesús Jiménez
Borreguero
3.7
New therapies in infectious
pathologies
Ignacio de los Santos
Gil
3.8
Individualized medicine in solid
tumors
Almudena Zapatero
Laborda
– 25 –
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 1.4
Etiopathogenic and immunological mechanisms of dermatological diseases.
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.
– 27 –
AREA 1
CELLULAR AND MOLECULAR
ETIOPATHOGENIC MECHANISMS IN
INFLAMMATORY AND
AUTOIMMUNE DISEASES
– 28 –
AREA 1
CELLULAR AND MOLECULAR ETIOPATHOGENIC
MECHANISMS IN INFLAMMATORY AND
AUTOIMMUNE DISEASES
Line 1.1
Intercellular
Communication in the
Inflammatory Response
HEAD OF LABORATORY
Francisco Sánchez-Madrid.
Scientific Director, Inmmunology.
GROUP MEMBERS
• Olga Barreiro del Río
• Noa Beatriz Martín Cófreces
• Gloria Martínez del Hoyo Cañizares
• María Mittelbrunn Herrero
• Vera Rocha Perugini
• Hortensia de la Fuente Flores
• Adela Matesanz Marín
• Emilio Tejera Puente
• Francesc Baixauli Celda
• Cristina Gutiérrez Vázquez
• Noelia Blas Rus
• Carolina Villarroya Beltri
• Olga Moreno Gonzalo
• Mª Ángeles Ursa Pecharromán
• María José López Campos
• Marta Esther Ramírez Huesca
The immune synapse acts as a platform facilitating the passage of genetic material between cells. During immune synapse, the molecules
involved in antigen recognition (such as T cell receptor (TCR) and peptide-loaded major histocompatibility complex (pMHC) molecules)
move to a central cluster surrounded by a peripheral ring enriched in
adhesion molecules (such as the integrin leukocyte function-associated antigen 1 (LFA-!) and intercellular cell adhesion molecules (ICAMs)
and the actin cytoskeleton. The T lymphocyte orients its microtubuleorganizing center (MTOC) and secretory compartments (such as the
Golgi apparatus and multivesicular bodies (MVBs), towards the antigen presenting cell (APC).
izing complex (MTOC), by controlling cytoskeletal
rearrangements at the immune synapse (IS), provides a
mechanism for macromolecular transport and the concentration of signaling molecules during synaptic contact. This research program has the potential to reveal
how transfer of miRNA between the T cell and the cognate antigen presenting cell (APC) regulates the early initiation of immunity. We are also developing methodologies for the in vivo imaging of immune cell infiltration, the
inflammatory response and the role of immunoregulatory molecules (galectins and tetraspanins) in animal models of inflammation and human diseases.
RESEARCH INTEREST
The group’s present work focuses on key cell-to-cell
communication events during cognate immune interactions. A key goal is to define how the microtubule organ-
Our current specific objectives are the following:
1. To assess the role of MTOC polarization as a signaling and structural platform for the control of secretion during IS formation.
– 29 –
AREA 3 AREA 2 AREA 1
GROUP 1
Cellular and molecular etiopathogenic mechanisms
in inflammatory and autoimmune diseases
2. To investigate the mechanisms and functional consequences of intercellular transfer of miRNA via the IS.
3. To image immune-inflammatory responses in vivo in
order to define the role of immunoregulatory molecules in autoimmune inflammatory diseases.
Martín-Cófreces NB, Baixauli F, López MJ, Gil D, Monjas
A, Alarcón B, Sanchez-Madrid F. End-binding protein 1
controls signal propagation from the T cell receptor.
EMBO J. 31(21):4140-52. 2012. PMID: 22922463. IF:
9,205. DOI: 10.1038/emboj.2012.242
MAJOR GRANTS
de la Fuente H, Cibrián D, Sanchez-Madrid F.
Immunoregulatory molecules are master regulators of
inflammation during the immune response. FEBS Lett.
586(18):2897-2905. 2012. PMID: 22819828. IF: 3,538.
DOI: 10.1016/j.febslet.2012.07.032
• Francisco Sánchez Madrid. Plataforma de análisis
genético y proteínas. ISCIII. PI10/03659. Duration: 2011
- 2012.
• Francisco Sánchez Madrid. Red temática de enfermedades cardiovasculares (RECAVA). ISCIII. RD060014-0030. Duration: 2011 - 2012.
• Francisco Sánchez Madrid. Nuevos mecanismos de
inmunomodulación: moléculas reguladoras, polaridad
celular y transferencia de información genética en la
comunicación intercelular. MICINN. SAF-2011-25834.
Duration: 2012 - 2014.
• Proyecto Coordinado. Redes moleculares y celulares
en enfermedades inflamatorias. Programa Biomedicina.
CAM. INDISNET S2011/BMD-2332. Duration: 2012 2015.
• Francisco Sánchez Madrid. Mechanisms of MTOC
guidance and Genetic Transfer at the Immune Synapse:
novel modes of Immuno-modulation. European
Research Council. ERCEA-AdG-2011-294340_GENTRIS. Duration: 2012 - 2017.
PUBLICATIONS (13) [IF: 121,394]
YEAR
Total IF
Publication No.
Q1
2010
77,391
11
11
2011
74,667
12
11
1
2012
121,394
13
10
3
Fernández-Pisonero I, Dueñas AI, Barreiro O, Montero O,
Sanchez-Madrid
F,
García-Rodríguez
C.
Lipopolysaccharide and sphingosine-1-phosphate cooperate to induce inflammatory molecules and leukocyte
adhesion in endothelial cells. J Immunol. 188(11):54025410. 2012. PMID: 23089395. IF: 5,788. DOI:
10.4049/jimmunol.1201309
Gordón-Alonso M, Sala-Valdés M, Rocha-Perugini V,
Pérez-Hernández D, López-Martín S, Ursa A, Alvarez S,
Kolesnikova TV, Vázquez J, Sanchez-Madrid F, YáñezMó M. EWI-2 association with -actinin regulates T cell
immune synapses and HIV viral infection. J Immunol.
189(2):689-700. 2012. PMID: 22689882. IF: 5,788. DOI:
10.4049/jimmunol.1103708
Q2
Sanchez-Cuellar S, de la Fuente H, Cruz-Adalia A,
Lamana A, Cibrian D, Giron RM, Vara A, Sanchez-Madrid
F, Ancochea J. Reduced expression of galectin-1 and
galectin-9 by leucocytes in asthma patients. Clin Exp
Immunol. 170(3):365-374. 2012. PMID: 23121677. IF:
3,36. DOI: 10.1111/j.1365-2249.2012.04665.x
– 30 –
Sala-Valdés M, Gordón-Alonso M, Tejera E, Ibáñez A,
Cabrero JR, Ursa A, Mittelbrunn M, Lozano F, SanchezMadrid F, Yáñez-Mó M. Association of syntenin-1 with
M-RIP polarizes Rac-1 activation during chemotaxis and
immune interactions. J Cell Sci. 125(Pt 5):1235-46. Epub
2012 Feb 20. 2012. PMID: 22349701. IF: 6,111. DOI:
10.1242/jcs.094912
Fuente HD, Perez-Gala S, Bonay P, Cruz-Adalia A,
Cibrian D, Sanchez-Cuellar S, Dauden E, Fresno M,
García-Diez A, Sanchez-Madrid F. Psoriasis in humans is
associated with downregulation of galectins in dendritic
cells. J Pathol. 228: 193-203. 2012. PMID: 22271227. IF:
6,318. DOI: 10.1002/path.3996
Gordón-Alonso M, Rocha-Perugini V, Álvarez S, MorenoGonzalo O, Ursa A, López-Martín S, Izquierdo-Useros N,
Martínez-Picado J, Muñoz-Fernández MÁ, Yáñez-Mó M,
AREA 1
Elorza A, Soro-Arnáiz I, Meléndez-Rodríguez F,
Rodríguez-Vaello V, Marsboom G, de Cárcer G, AcostaIborra B, Albacete-Albacete L, Ordóñez A, SerranoOviedo L, Giménez-Bachs JM, Vara-Vega A, Salinas A,
Sánchez-Prieto R, Martín Del Río R, Sanchez-Madrid F,
Malumbres M, Landázuri MO, Aragonés J. HIF2 Acts as
an mTORC1 Activator through the Amino Acid Carrier
SLC7A5. Molecular Cell. 48(5):681-91. 2012. PMID:
23103253.
IF:
14,178.
DOI:
10.1016/j.molcel.2012.09.017
Mittelbrunn M, Sanchez-Madrid F. Intercellular communication: diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol. 13(5):328-335. 2012.
PMID: 22510790. IF: 39,123
Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P,
Askenase P, Bond VC, Borràs FE, Breakefield X, Budnik
V, Buzas E, Camussi G, Clayton A, Cocucci E, FalconPerez JM, Gabrielsson S, Gho YS, Gupta D, Harsha HC,
Hendrix A, Hill AF, Inal JM, Jenster G, Krämer-Albers EM,
Lim SK, Llorente A, Lötvall J, Marcilla A, MinchevaNilsson L, Nazarenko I, Nieuwland R, Nolte-'t Hoen EN,
Pandey A, Patel T, Piper MG, Pluchino S, Prasad TS,
Rajendran L, Raposo G, Record M, Reid GE, SanchezMadrid F, Schiffelers RM, Siljander P, Stensballe A,
Stoorvogel W, Taylor D, Thery C, Valadi H, van Balkom
BW, Vázquez J, Vidal M, Wauben MH, Yáñez-Mó M,
Zoeller M, Mathivanan S. Vesiclepedia: a compendium
for extracellular vesicles with continuous community
annotation. PLoS Biol. 10(12):e1001450. 2012. PMID:
23271954.
IF:
11,452.
DOI:
10.1371/
journal.pbio.1001450
de Andrés C, Teijeiro R, Alonso B, Sanchez-Madrid F,
Martínez ML, Guzmán de Villoria J, Fernández-Cruz E,
Sánchez-Ramón S. Long-term decrease in VLA-4
expression and functional impairment of dendritic cells
during natalizumab therapy in patients with multiple sclerosis. PLoS One. 7(4):e34103. 2012. PMID: 22496780.
IF: 4,092. DOI: 10.1371/journal. pone.0034103
Citterio C, Menacho-Márquez M, García-Escudero R,
Larive RM, Barreiro O, Sanchez-Madrid F, Paramio JM,
Bustelo XR. The rho exchange factors vav2 and vav3
control a lung metastasis-specific transcriptional program
in breast cancer cells. Sci Signal 5(244):ra71. 2012.
PMID: 23033540. IF: 7,499. DOI: 10.1126/scisignal.2002962
GROUP 2
HEAD OF LABORATORY
Esteban Veiga Chacón
GROUP MEMBERS
• Carmen Calabia Linares
• Aranzazu Cruz Adalia
• Guillermo Ramírez Santiago
• Mónica Torres Torresano
MAJOR GRANTS
Esteban Veiga Chacón. Sinapsis inmunológica y control
bacteriano del sistema inmune. MICINN. BFU201129450. Duration: 2012 - 2014.
YEAR
Total IF
Publication No.
Q1
Q2
2010
13,114
3
2
1
2011
20,235
3
2
1
2012
9,678
2
1
1
Lamana A, Cibrian D, Giron RM, Vara A, SanchezMadrid F, Ancochea J. Reduced expression of
galectin-1 and galectin-9 by leucocytes in asthma
patients. Clin Exp Immunol. 170(3):365-374. 2012.
– 31 –
Sanchez-Madrid F. The PDZ-adaptor protein syntenin-1
regulates HIV-1 entry. Mol Biol Cell 23(12):2253-2263.
2012.
PMID:
22535526.
IF:
4,942.
DOI:
10.1091/mbc.E11-12-1003
PMID: 23121677. IF: 3,36. DOI: 10.1111/j.13652249.2012.04665.x
García-Diez A, Sanchez-Madrid F. Psoriasis in
humans is associated with downregulation of
galectins in dendritic cells. J Pathol. 228: 193-203.
2012. PMID: 22271227. IF: 6,318. DOI:
10.1002/path.3996
GROUP 3
Syntenin-1 is polarized in migrating lymphocytes. T lymphoblastic
HSB2 cells were transfected with GFP–syntenin-1 and monitored at 30
second intervals after stimulation with 100 ng/ml SDF-1a. Representative pseudocolored maximal projections are shown. Scale bar: 5
mm. Arrows indicate the uropod (U) and leading edge (LE).
HEAD OF LABORATORY
María Yáñez Mó
GROUP MEMBERS
• Soraya López Martín
RESEARCH INTEREST
Tetraspanin-enriched microdomains (TEM) are ubiquitous specialized membrane platforms formed by the
engagement of tetraspanins in molecular associations
with lipids and selected transmembrane proteins,
mostly integrins, immunoglobulin-superfamily receptors and metalloproteinases. Most studies on
tetraspanins have emphasized their role as scaffolds
of membrane microdomains, however, emerging evidence suggests that tetraspanins might also connect
receptors to signalling cascades and the cytoskeleton. We analyzed the connection of TEM with the
actin cystoskeleton via actinin and syntenin-1. We
demonstrated that actinin regulates the immune
synapse formation and is required for efficient T cell
activation. We extended these observations to virological synapses induced by HIV and so that our data
suggest that the TEM-actinin complex is involved in
the regulation of the actin cytoskeleton at T cell
– 32 –
Syntenin-1–M-RIP regulates F-actin polymerization at the immune
synapse. (A) Relocalization of endogenous syntenin-1 and M-RIP in
antigen-induced conjugates. Maximal projections of the confocal image stacks are shown, together with the corresponding DIC images.
Scale bars: 5 mm.
immune and virological synapses, providing a link
between membrane microdomains and the formation
of polarized membrane structures involved in T cell
recognition. On the other hand, syntenin-1 controls
cell asymmetry. We found that syntenin-1 controls
actin polymerization through a specific association
with the myosin phosphatase Rho interacting protein
(M-RIP), which occurs in response to phosphorylation
of syntenin-1 by Src. Our data provide a novel mechanistic link between receptor activation and actin
polymerization and accumulation in response to
extracellular stimulation.
AREA 1
María Yañez Mó. 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.
Duration: 2012 - 2015.
YEAR
Total IF
Publication No.
Q1
Q2
2010
16,562
3
3
2011
19,372
4
2
1
2012
28,293
4
3
1
Sala-Valdés M, Gordón-Alonso M, Tejera E, Ibáñez
A, Cabrero JR, Ursa A, Mittelbrunn M, Lozano F,
Sánchez-Madrid F, Yáñez-Mó M. Association of syntenin-1 with M-RIP polarizes Rac-1 activation during
chemotaxis and immune interactions. J Cell Sci.
125(Pt 5):1235-46. Epub 2012 Feb 20. 2012. PMID:
22349701. IF: 6,111. DOI: 10.1242/jcs.094912
Gordón-Alonso M, Sala-Valdés M, Rocha-Perugini V,
Pérez-Hernández D, López-Martín S, Ursa A,
Alvarez S, Kolesnikova TV, Vázquez J, SánchezMadrid F, Yáñez-Mó M. EWI-2 association with actinin regulates T cell immune synapses and HIV
viral infection. J Immunol. 189(2):689-700. 2012.
PMID: 22689882. IF: 5,788. DOI: 10.4049/jimmunol.1103708
Gordón-Alonso M, Rocha-Perugini V, Álvarez S,
Moreno-Gonzalo O, Ursa A, López-Martín S,
Izquierdo-Useros N, Martínez-Picado J, MuñozFernández MÁ, Yáñez-Mó M, Sánchez-Madrid F.
The PDZ-adaptor protein syntenin-1 regulates HIV-1
entry. Mol Biol Cell 23(12):2253-2263. 2012. PMID:
22535526. IF: 4,942. DOI: 10.1091/mbc.E11-121003
Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P,
Askenase P, Bond VC, Borràs FE, Breakefield X,
Budnik V, Buzas E, Camussi G, Clayton A, Cocucci
E, Falcon-Perez JM, Gabrielsson S, Gho YS, Gupta
D, Harsha HC, Hendrix A, Hill AF, Inal JM, Jenster G,
Krämer-Albers EM, Lim SK, Llorente A, Lötvall J,
Marcilla A, Mincheva-Nilsson L, Nazarenko I,
Nieuwland R, Nolte-'t Hoen EN, Pandey A, Patel T,
Piper MG, Pluchino S, Prasad TS, Rajendran L,
Raposo G, Record M, Reid GE, Sánchez-Madrid F,
Schiffelers RM, Siljander P, Stensballe A, Stoorvogel
W, Taylor D, Thery C, Valadi H, van Balkom BW,
Vázquez J, Vidal M, Wauben MH, Yáñez-Mó M,
Zoeller M, Mathivanan S. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 10(12):e1001450.
2012. PMID: 23271954. IF: 11,452. DOI:
10.1371/journal.pbio.1001450
GROUP 4
HEAD OF LABORATORY
Miguel Vicente Manzanares
GROUP MEMBERS
• Álvaro Ortega Carrión
• Cristina Delgado Arévalo
• Lidia Feo Lucas
• Rocío Aguilar Cuenca
• Irene Ríos Guillén
• Alba Juanes García
RESEARCH INTEREST
During 2012, the Mechanotransduction group at the
IIS-IP has incorporated one PhD student and two
Masters students as well as one Research Specialist.
The group has obtained new funding from the Ramón
Areces Foundation and from Wimasis S.L. through the
Invest in Spain Program. Scientifically, the
Mechanotransduction group has continued evaluating
the role of phosphorylation of the force-generating mol-
– 33 –
MAJOR GRANTS
Under the auspices of 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.
Scheme for preparation of traction force microscopy substrates. Images are obtained using the confocal microscope Leica SP5 that belongs
to the IIS-IP. A detailed protocol can be found in the lab webpage
(http://web.uam.es/personal_pdi/medicina/mvicente/default.html)
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.
The group has set in the Institute and has been heavily
involved in the research to acquire a new, state-of-theart TIRF microscope that will widen the capabilities of
the microscopy unit. We have also established collaborations with other groups in and out of the IIS-IP,
including that of Prof. Sanchez-Madrid (IP), Dr. YáñezMó (IP), Prof. Juan Manuel García Aznar (out of IP, U.
Zaragoza), Prof. Carlos Ortiz de Solorzano (out of IP, U.
Navarra) and Dr. Brenton Hoffman (U. Duke, USA).
MAJOR GRANTS
Super-quantitative maps of force exerted by tumor cells. Force is quantified by displacement of fluorescent beads lying on the substrate.
ecule 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.
– 34 –
• Miguel Vicente Manzanares. 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. MICINN.
SAF2011-24953. Duration: 2012 - 2014.
• Miguel Vicente Manzanares. Estudio de la función de
la miosina no muscular de clase II en inflamación.
Marie Curie Career Reintegration Grant (CIG).
Duration: 2011 - 2014.
• Miguel Vicente Manzanares. La miosina II integra las
señales mecánicas del microentorno celular y controla la migración y diferenciación de las células
madre. Fundación Ramon Areces CIVP16A1831.
Duration: 2012 – 2015.
AREA 1
PUBLICATIONS 2) [IF: 7,745]
YEAR
Total IF
Publication No.
Q1
Q2
2012
7,745
2
1
1
Toplak T, Pandzic E, Chen L, Vicente-Manzanares
M, Horwitz AR, Wiseman PW. STICCS reveals
matrix-dependent adhesion slipping and gripping in
migrating cells. Biophys J. 103(8):1672-82. 2012.
PMID:
23083710.
IF:
3,653.
DOI:
10.1016/j.bpj.2012.08.060
1-/- mice have reduced thymic CD4+ Treg population
and more immunogenic DCs. Recently, we reported
that PSGL-1 interacts with the metalloproteinase
ADAM8, whose activation cuts PSGL-1 regulating its
membrane expression. In a mouse model of experimental ulcerative colitis, we found that PSGL-1 is implicated in maintaining the mice colonic lamina propria
tolerance, indicating that homeostatic PSGL-1/PSelectin interactions during leukocyte recirculation are
important for maintaining the peripheral tolerance.
Chen L, Vicente-Manzanares M, Potvin-Trottier L,
Wiseman PW, Horwitz AR. The integrin-ligand interaction regulates adhesion and migration through a
molecular clutch. PLoS One. 7(7):e40202. 2012.
PMID: 22792239. IF: 4,092. DOI: 10.1371/journal.pone.0040202
HEAD OF LABORATORY
Ana Carmen Urzainqui Mayayo
GROUP MEMBERS
• Alicia Pérez Frías
• Rafael González Tajuelo
RESEARCH INTEREST
PSGL-1 leukocyte adhesion receptor is responsible for
the initial interactions of leukocytes with the activated
endothelium and their recruitment to sites of inflammation. PSGL-1 is also important for the homeostatic
homing and entry of leukocytes into different tissues
and organs such as skin, thymus or lymph nodes. We
described that PSGL-1 signaling makes human monocyte-derived DC become tolerogenic and drive the differentiation of naïve T cells to Treg. Accordingly, PSGL-
Figure 1. PSGL-1 KO mice develop skin fibrosis and spontaneously generate autoantibodies related with connective tissue autoimmune diseases. A) Photographs of a 4 month-old and an aged female PSGL-1
deficient mice showing skin lesions. B) Hematoxilin/Eosin (H/E) and
Masson´s trichrome staining 5x microphotographs showing representative skin samples of young and aged WT and PSGL-1 deficient mice.
C) Percentage of PSGL-1 deficient mice with fibrotic skin from 1.5 to 24
months after birth. D) and E) Hypodermis width (D) and Dermis width
(E) of WT and PSGL-1 deficient mice. F) Dermis/hypodermis ratios in
WT and PSGL-1 deficient mice from 1.5 to 24 months after birth. C to
F:At least 10 mice per group of age were analyzed. Bars represent the
mean plus SD.Statistical significance was determined by Mann-Whitney U test.G) Immunofluorescence microphotographs of Hep-2 cells
incubated with blood serum of either WT or PSGL-1 KO mice. H) Percentage of mice positive for Scl-70, U3-RNP, Sm, Jo-1 and SSA-Ro autoantibodies. G and H: 25 mice per group of age were analyzed.
– 35 –
GROUP 56
activation with production of auto-antibodies, widespread fibrosis in the skin and internal organs –including kidneys and lungs-and vascular damage.
Regarding the vascular damage, we have found that
the small arterioles have the light of vessel reduced
and the media wall layer increased, suggesting that
they could develop pulmonary arterial hypertension.
Our findings indicate that this could be an accurate
mouse model for human scleroderma.
MAJOR GRANTS
Figure 2.A) 5x representative microphotographs of H/E stained
kidney sections of WT and PSGL-1 KO mice.B) and C): 20x and 40x
representative microphotographs of H/E (B) and Masson´s trichrome stained (C) kidney samples of WT and PSGL-1 KO mice.D
and E): 10x, 20x, 40x microphotrographsof H/E (D) and Masson’s
trichromic (E) stained representative sections of lung parenchimal areas from WT and PSGL-1-/- mice.F)anti-αSMA staining of
lung sections. 40x immunohistochemistry microphotographs of
alveolar parenchyma showing 10-30 μm-diameter arterioles in
lungs of WT and PSGL-1-/- mice.
Our present work focuses on a recent observation of
our laboratory that adult PSGL-1 deficient mice present lesions in their back skin. We have found
thatPSGL-1 deficiency develops an autoimmune disease that recapitulates the main hallmarks of the
human diffuse systemic sclerosis: immune system
– 36 –
• Ana Carmen Urzainqui Mayayo. Caracterización de
una enfermedad espontánea autoinmune desarrollada en ratones deficientes en PSGL-1. Contribución
de PSGL-1 al desarrollo de enfermedades autoinmunes en humanos. ISCIII. PI11/01418. Duration:
2012 - 2014.
• Ana Carmen Urzainqui Mayayo. Estudio del papel de
PSGL-1 en el control del desarrollo de enfermedades
autoinmunes. Fundación Ramón Areces. Duration:
2012 - 2015.
PUBLICATIONS (0) [IF: 0]
YEAR
Total IF
Publication No.
Q1
2010
9,273
1
1
2011
17,735
3
3
Q2
AREA 1
Line 1.2
Cellular and molecular
responses to Hypoxia
GROUP 6
HEAD OF LABORATORY
Manuel Ortiz de Landázuri Busca
Model showing the involvement of NDUFA4L2 induction by HIF-1a in
hypoxic adaptation. HIF-1α stabilization by hypoxia upregulates NDUFA4L2, which inhibits ETC Complex I activity. As a result, oxygen consumption decreases and ROS production is abrogated, thereby allowing cells to adapt to the hypoxic conditions. In addition, hypoxia decreases Complex IV levels, which represents a further regulatory point
in hypoxic adaptation.
RESEARCH INTEREST
1) Electron transport chain adaptations to low oxygen
tensions
Fine regulation of the mitochondrial electron transport chain (ETC) has proven to be an essential regulatory point under hypoxia.
Over the last years our work have been focused on
how the different complexes within the ETC are modulated by low oxygen availability. Specifically, we have
found that hypoxic stabilization of HIF-1 controls
Complex I inhibition and reactive oxygen species
(ROS) abrogation. This is mediated by the induction
of the new HIF-1 target gene: NDUFA4L2.
Our later results showed how reduction in oxygen availability is sensed by the mitochondria and rapidly trigger
a degradation response over Complex IV subunits. The
final outcome is that Complex IV is reduced while its
subunit composition is gradually altered, adjusting the
ETC to better fit to low oxygen tensions.
2) Role of the ubiquitin ligate SART-1 in the progression of renal cell carcinomas
SART-1 is a novel E3 ubiquitin ligase able to degrade
HIF-1 but not HIF-2 .
We are exploring the role of this ubiquitin ligase in the
regulation of HIF transcription factors in renal cell carcinoma.
HIF-1 is considered to have tumor suppressor
activities whereas HIF-2 is a promoter of tumor progression. Therefore it is important to study new players that may regulate the expression of the HIF transcription factors. Preliminary data of our lab indicate
that depending of the mutation of VHL protein, the
ubiquitin ligase SART-1 may play an important role in
the degradation of HIF-1 in these tumors.
Progression of renal cell carcinoma tumors has been
shown to be dependent on the loss of HIF-1 and
the maintenance of HIF-2 , and studies indicate that
SART-1 may negatively regulate the levels of HIF-1 .
Therefore, the ubiquitin ligase SART-1 might play
and important role in the malignancy of renal cell
carcinomas, eliminating HIF-1 and preserving HIF2 .
– 37 –
GROUP MEMBERS
• Ángel Ordóñez Navadijo
• Bárbara Acosta Iborra
• Eduardo Balsa Martínez
• Esther Fuertes Yebra
• Alicia Vara Vega
MAJOR GRANTS
• Manuel Ortiz de Landázuri Busca. Sensores de
oxigeno: reprogramación metabólica y supervivencia celular. MICINN. SAF2010-14851. Duration:
2010 - 2012.
• Manuel Ortiz de Landázuri Busca. Red temática de
enfermedades cardiovasculares (RECAVA). ISCIII.
RD06-0014-0031. Duration: 2011 - 2012.
• Manuel Ortiz de Landázuri Busca. Inflamación e
hipoxia: Mecanismos de desarrollo y progresión en
EPOC y SAHS. Programa Biomedicina. CAM.
S2011/BMD-2542. Duration: 2012 - 2015.
YEAR
Total IF
Publication No.
Q1
2010
10.462
2
2
Q2
2011
21,077
3
2
1
2012
43,04
5
4
1
Balsa E, Marco R, Perales-Clemente E, Szklarczyk R,
Calvo E, Landázuri MO, Enríquez JA. NDUFA4 is a
subunit of complex IV of the mammalian electron transport chain. Cell Metab. 16(3):378-86. Epub 2012 Aug
16. 2012. PMID: 22902835. IF: 13,668. DOI:
Palazon A, Aragones Lopez J, Morales-Kastresana A,
Ortiz De Landázuri M, Melero IJ. Molecular Pathways:
Hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res 18(5):1207-13. Epub 2011
Dec 28. 2012. PMID: 22205687. IF: 7,742. DOI:
10.1158/1078-0432.CCR-11-1591
Lamana A, Cibrian D, Giron RM, Vara A, SanchezMadrid F, Ancochea J. Reduced expression of galectin1 and galectin-9 by leucocytes in asthma patients. Clin
Exp Immunol. 170(3):365-374. 2012. PMID:
23121677. IF: 3,36. DOI: 10.1111/j.13652249.2012.04665.x
Rodríguez-Vaello V, Marsboom G, de Cárcer G,
– 38 –
Acosta-Iborra B, Albacete-Albacete L, Ordóñez A,
Serrano-Oviedo L, Giménez-Bachs JM, Vara-Vega A,
Salinas A, Sánchez-Prieto R, Martín Del Río R,
Sánchez-Madrid F, Malumbres M, Landázuri MO,
Aragonés J. HIF2 Acts as an mTORC1 Activator
through the Amino Acid Carrier SLC7A5. Molecular
Cell. 48(5):681-91. 2012. PMID: 23103253. IF: 14,178.
DOI: 10.1016/j.molcel.2012.09.017
Conde E, Alegre L, Blanco-Sánchez I, Sáenz-Morales
D, Aguado-Fraile E, Ponte B, Ramos E, Sáiz A,
Jiménez C, Ordoñez A, López-Cabrera M, del Peso L,
de Landázuri MO, Liaño F, Selgas R, Sanchez-Tomero
JA, García-Bermejo ML. Hypoxia inducible factor 1alpha (HIF-1 alpha) is induced during reperfusion after
renal ischemia and is critical for proximal tubule cell
survival. PLoS One 7(3):e33258. 2012. PMID:
22432008. IF: 4,092. DOI: 10.1371/ournal
.pone.0033258
GROUP 7
HEAD OF LABORATORY
Antonio Martínez Ruiz
GROUP MEMBERS
• Alicia Izquierdo Álvarez
• Pablo Hernansanz Agustín
• Elena Ramos Serrano
RESEARCH INTEREST
Non-enzymatic post-translational modifications in vascular pathophysiology
The research of the group is centred on the study of
non-enzymatic
post-translational
modifications
induced by reactive oxygen and nitrogen species,
especially cysteine reversible oxidative modifications.
We also study their relevance in cell function and
AREA 1
pathophysiology, mainly in the molecular and cellular
responses to hypoxia.
We have developed new proteomic methodologies for analyzing these modifications (simultaneously with protein
abundance changes), both with two-dimensional electrophoresis (“redox fluorescence switch”, RFS), and second-generation proteomic techniques (“GELSILOX”
method, in collaboration with Dr. Jesús Vázquez, from the
CBMSO and CNIC).
We have reviewed the role of S-nitrosylation in the immune
system, including the mechanistic and therapeutic
approaches of nitrosothiols in autoimmune diseases. We
have also reviewed the particularities of S-nitrosylation as a
short-distance nonclassical NO signalling mechanism.
MAJOR GRANTS
Short-range and long-range NO signaling. Classical NO signaling, such as
sGC activation, can be exerted at a relatively long distance from NO sources (NOS enzymes), even if NO concentration diminishes while targets
are farther from the NOS. We postulate that S-nitrosylation of target proteins (TP) or interacting proteins (IP) is essentially a short-range mechanism, limited to a tiny sphere around NOS. Among other factors, RNS formation requires higher NO concentrations, which are easier to achieve in
the NOS surroundings, and denitrosylases such as Trx or GSNOR with GSH
can narrow the range of action by reducing target protein S-nitrosylation.
• Antonio Martínez Ruiz. Papel funcional del estrés
oxidativo y nitrosativo en grandes sistemas biológicos
(consorcio ROSAS - “Reactive Oxygen Species And
Systems”). MEC. Consolider-Ingenio 2010. CSD200700020. Duration: 2007 - 2012.
• Antonio Martínez Ruiz. Papel de las especies reactivas
de oxígeno y nitrógeno y de las modificaciones oxidativas de proteínas en la respuesta a hipoxia en fisiopatología cardiovascular. ISCIII. PS09/00101. Duration:
2010 - 2012.
• Antonio Martínez Ruiz. Identificación proteómica de
proteínas vegetales S-nitrosiladas en la respuesta a
– 39 –
2DE gels of endothelial cells extracts subjected to the Redox Fluorescence Switch (RFS). The green fluorescent signal corresponds to reversibly oxidised proteins; the red signal corresponds to total protein
staining in the same gel. Differential green spots are the proteins reversibly oxidised in hypoxia (2 h, 1% O2). Nine more differential spots
can be found; the solution is in Izquierdo-Álvarez et al., 2012.
We have applied both techniques to analyze differential
reversible cysteine oxidations in the acute response of
endothelial cells subjected to hypoxia. We have
observed a number of proteins that are oxidized after 2
hours in hypoxia, which is reverted by a 30-minutes
reoxygenation. We have identified some of these proteins, among which we have found several proteins that
take part in different protein signalling pathways, as well
as metabolic enzymes that could have their function
altered. The latter could be part of the acute responses
to hypoxia before the transcriptional response by the
canonical HIF pathway is initiated.
auxina. MICINN. PRI-AIBAR-2011-0782. Duration:
2011 - 2013.
• Antonio Martínez Ruiz. Identificación de dianas de Snitrosilación en la estimulación de la neurogénesis
endógena. MICINN. PRI-AIBPT-2011-1015. Duration:
2011 - 2013.
I
YEAR
Total IF
Publication No.
Q1
2010
6,051
1
1
2011
44,908
5
5
2012
12,276
2
2
Q2
RESEARCH INTEREST
Our research interests have centered on the mechanisms that regulate TSP-1 and its counter receptor
CD47, in particular the role of hypoxia and how this
regulation is important in different pathophysiological
aspects. In renal carcinomas, hypoxic conditions
enhance the expression of angiogenic factors that help
adapt tumour cells to their hostile environment.
Conversely, we proved that hypoxia stimulates multiple
signals that independently contribute to diminish
thrombospondin-1 in ccRCC and proved to be important for ccRCC cell migration and invasion (Bienes R. et
al. Nature Scintific Reports 2012). Another pathophysi-
Izquierdo-Álvarez A, Ramos E, Villanueva J, HernansanzAgustín P, Fernández-Rodríguez R, Tello D, Carrascal M,
Martínez-Ruiz A. Differential redox proteomics allows
identification of proteins reversibly oxidized in cysteines in
endothelial cells during acute response to hypoxia. J
Proteomics 75(17):5449-5462. 2012. PMID: 22800641.
IF: 4,878. DOI: 10.1016/j.jprot.2012.06.035
Martínez-Acedo P, Núñez E, Sánchez-Gómez FJ,
Moreno M, Ramos E, Izquierdo-Álvarez A, MiróCasas E, Mesa R, Rodriguez P, Martínez-Ruiz A,
Garcia-Dorado D, Lamas S, Vázquez J. A novel
strategy for the global analysis of the dynamic thiol
redox proteome. Mol Cell Proteomics 11(9):800813. 2012. PMID: 22647871. IF: 7,398. DOI:
10.1074/mcp.M111.016469
TSP1 regulation by hypoxia in ccRCC cell lines. Hypoxia stimulates
multiple signals that contribute to the decrease in TSP-1 in ccRCC.
TSP1 suppression by hypoxia elicits an autocrine stimulation of
ccRCC migration.
GROUP 8
HEAD OF LABORATORY
María Josefa Calzada García
GROUP MEMBERS
• Raquel Bienes Martínez
• Cristina Sánchez Corzo
– 40 –
CD47 activation promotes PAH through suppressing constituative Caveolin-1 inhibtion of eNOS. Under hypoxia, the CD47 ligand TSP1 is
upregualted. On binding with TSP1 the cell receptor CD47 is activated
leading to disrruption of the constitutive interaction between CD47
and membrane caveolin-1 (Cav-1). This in turn leads to decreased
Cav-1 and increased eNOS activity. Monomeric hyperactive eNOS then
produces superoxide rather than NO resulting in tissue oxidation and
nitration.
AREA 1
ological aspect we were interested in was the role of
TSP-1/CD47 in promoting pulmonary aortic hypertension (PAH) since TSP1 and CD47 null mice are protected in a classic murine hypoxia model of PAH. It has
been previously shown that activation of CD47 by TSP1 inhibits eNOS. In this respect, our studies in animals
and hypoxic cell cultures demonstrated that activation
of CD47 by TSP1, inhibits caveolin-1 (Cav-1), promoting eNOS-dependent superoxide production, oxidative
stress and PAH (Bauer PM et al. Cardiovascular Res.
2012). However it is not completely clear whether this
is a unique mechanism or there are other pathways
regulated by the TSP-1/CD47 nexus involved in the
onset and maturation of PAH and whether hypoxia
could be a condition of these phenomena trigger.
Ongoing areas of interest also include the implications
of this new paradigm in relation to cardiac function and
inflammatory diseases.
2012. PMID: 22215724.
10.1093/cvr/cvr356
MAJOR GRANTS
GROUP 9
6,064.
DOI:
Fernández-Sánchez R, Berzal S, Sánchez-Niño MD,
Neria F, Gonçalves S, Calabia O, Tejedor A, Calzada
MJ, Caramelo C, Deudero JJ, Ortiz A. AG490 promotes HIF-1 accumulation by inhibiting its hydroxylation. Curr Med Chem 19(23):4014-4023. 2012. PMID:
22709000. IF: 4,859
Fernández-Barral A, Orgaz JL, Gomez V, del Peso L,
Calzada MJ, Jiménez B. Hypoxia negatively regulates
antimetastatic PEDF in melanoma cells by a hypoxia
inducible factor-independent, autophagy dependent
mechanism. PloS One 7(3):e32989. 2012. PMID:
22457728.
IF:
4,092.
DOI:
10.1371/journal.pone.0032989
HEAD OF LABORATORY
Julián Aragonés López
GROUP MEMBERS
• Ainara Elorza Peregrina
• Inés Soro Arnaíz
• Florinda Meléndez Rodríguez
RESEARCH INTEREST
YEAR
Total IF
Publication No.
Q1
Q2
2010
1,254
1
2011
16,603
2
1
1
2012
15,015
3
3
Philip M. Bauer, Eileen M. Bauer, Mingyi Yoa, Xiaojun
Huang, Monica Feijoo-Cuaresma, Joesph M. Pilewski,
Hunter C. Champion, Brian S. Zuckerbraun, Maria J.
Calzada, Jeff S. Isenberg. Activated CD47 Promotes
Pulmonary Arterial Hypertension Through Suppression
of Caveolin-1. Cardiovascular Research 93(4):682-93.
The HIF oxygen-sensing pathway in tumor biology
Local O2 supply to cells or tissues becomes limited
during the development of numerous pathological
scenarios such cardiac ischemia, inflammation, solid
tumor formation (malignant cells localized in the
inner core of the tumour). Cell respond to these O2
fluctuations by activating the hypoxia-inducible factors HIF-1 and HIF-2 . We have implemented loss
or gain of function animal models to assess the role
of these two oxygen-sensing pathways in vivo.
– 41 –
• María Josefa Calzada García. TSP1 in
Pathophysiology: Role in Renal Cancer and Ischemic
Tissue Damage and Regeneration. MICINN.
SAF2009-11113.
• María Josefa Calzada García. TSP1-CD47 in
Promotion of PAH-Associated Vasoconstriction and
Vascular Overgrowth. NIH. FOA: PA10-067, period
2011-2015
IF:
MAJOR GRANTS
mTORC1 activation by the HIF2α-SLC7A5 pathway. The HIF2α oxygen pathway upon Vhl gene inactivation or hypoxia in vivo induces
the expression of the amino acid carrier SLC7A5, which facilitates
the amino acid-dependent mTORC1 activity. This HIF2α-SLC7A5mTORC1 axis mediates tumor progression of Vhl deficient tumors
and provide molecular basis of proliferative responses in non-tumoral scenarios as hypoxic lung.
In particular, our research has been focused on the
role of the HIF-dependent rewiring of cell metabolism and autonomous tumour cell proliferation. We
recently found that the pro-proliferative activity of
HIF2 can be explained by its effects on amino acid
metabolism. Indeed, we found that HIF2 induces
the expression of the amino acid carrier SLC7A5
(Solute carrier family 7A5), a protein that mediates
the uptake of extracellular amino acids, and it also
activates mTORC1, a central element in the growth
and proliferation of cells driven by amino acid availability and the energy status of the cell (Figure 1)
(Elorza et al. Molecular Cell 2012). Therefore these
studies are aimed to unravel the molecular mechanisms by which HIFs factors contribute to tumour
development and open new opportunities for therapeutic intervention.
Overall our aim is to understand the molecular pathways executed by the HIF oxygen sensing pathways, which are critical (i) to understand the molecular bases of numerous pathologies and (ii) to design
novel therapeutical and efficient interventions.
– 42 –
• Julián Aragonés López. Gaining sage on the
Epoetins' saga: assessing long term risks and
advancing towards better Epoetin driven treatment
modalities. European Comission. 282551.
Duration: 2011 - 2014.
• Julián Aragonés López. Rutas de señalización del
oxÍgeno mediadas por los factores de respuesta a
hipoxia, HIF1 and HIF2, en obesidad y enfermedad
cardiaca isquémica. MICINN. SAF2011-29716.
Duration: 2012 - 2013.
• Julián Aragonés López. Inflamación e hipoxia:
mecanismos en desarrollo y progresión en EPOC y
SAHS. CAM. P2010 / BMD-2542. Duration: 2012 2015.
YEAR
Total IF
Publication No.
Q1
2010
35,531
5
5
2011
21,077
3
2
2012
21,92
2
2
Q2
1
Palazon A, Aragones Lopez J, Morales-Kastresana
A, Ortiz Del Landazuri M, Melero IJ. Molecular
Pathways: Hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res
18(5):1207-13. Epub 2011 Dec 28. 2012. PMID:
22205687. IF: 7,742. DOI: 10.1158/10780432.CCR-11-1591
Rodríguez-Vaello V, Marsboom G, de Cárcer G,
Acosta-Iborra B, Albacete-Albacete L, Ordóñez A,
Serrano-Oviedo L, Giménez-Bachs JM, Vara-Vega
A, Salinas A, Sánchez-Prieto R, Martín Del Río R,
Sánchez-Madrid F, Malumbres M, Landázuri MO,
Aragonés J. HIF2 Acts as an mTORC1 Activator
through the Amino Acid Carrier SLC7A5.
Molecular Cell. 48(5):681-91. 2012. PMID:
23103253.
IF:
14,178.
DOI:
10.1016/j.molcel.2012.09.017
AREA 1
GROUP 10
HEAD OF LABORATORY
Susana Cadenas Álvarez
GROUP MEMBERS
• Andrea Anedda
• Elia López Bernardo
Research in our group is focused on the function of
mitochondria within cells and their implication in the
development of pathological conditions. We have followed several lines of research as described below.
1) We studied the ability of intact mitochondria to generate nitric oxide (NO) and the effect of mitochondrial
NO on respiration in skeletal muscle mitochondria
from control mice and mice injected with E. coli
lipopolysaccharide (LPS). Mitochondria from LPStreated mice had lower respiration rates and higher
P50 values than control mitochondria, suggesting that
mitochondrially derived NO is generated by an LPSinducible NO synthase protein that modulates oxygen
consumption. Aguirre et al. (2012) Mitochondrion,
12:126-131.
2) In collaboration with Dr. F. Díaz-González (Hospital
Universitario de Canarias, La Laguna) and Dr. F.
Sánchez-Madrid (Hospital Universitario de La
Princesa, Madrid), we analyzed the involvement of
reactive oxygen species in the down-regulation of Lselectin induced by non-steroidal anti-inflammatory
drugs in human neutrophils. We reported the implication of superoxide anion generated by plasma
membrane NADPH-oxidase in this effect.
Dominguez-Luis et al. (2013) Biochem. Pharmacol.,
85:245-256.
3) We have also studied the regulation of mitochondrial uncoupling protein 3 (UCP3) expression and function under oxidative stress. We found that hydrogen
H2O2 increases UCP3 expression via Nrf2 promoting cell survival under
conditions of oxidative stress. Model showing the activation and nuclear translocation of Nrf2 induced by H2O2-generated oxidative stress.
The binding of Nrf2 to an ARE within the UCP3 promoter increases UCP3
expression, while superoxide and 4-HNE increase UCP3 activity. Increased UCP3 expression together with protein activation induces a slight
decrease in the membrane potential (mild uncoupling), and an ensuing
decrease in superoxide production. This mechanism promotes cell survival under conditions of oxidative stress. Anedda et al. (2013) Free Radic. Biol. Med., 61:395-407.
peroxide (H2O2) treatment increases both UCP3
mRNA and protein in C2C12 and HL-1 cells, and that
this effect is mediated by the transcription factor Nrf2,
an essential regulator of the cellular redox homeostasis. UCP3 up-regulation increases proton leak and
promotes survival, suggesting a role for this protein in
attenuating ROS-induced damage. Anedda et al.
(2013) Free Radic. Biol. Med., 61:395-407.
MAJOR GRANTS
• Susana Cadenas Álvarez. Desacoplamiento mitocondrial en isquemia experimental y clínica. ISCIII.
PS09/00116. Duration: 2009 - 2012.
• Susana Cadenas Álvarez. La mitocondria y su implicación en patología humana. Programas de actividades de I+D entre grupos de investigación de la
Comunidad
de
Madrid
en
Biomedicina.
S2010/BMD-2402. Duration: 2012 - 2015.
– 43 –
RESEARCH INTEREST
– 44 –
YEAR
Total IF
Publication No.
Q1
2010
16,315
3
3
2011
19,091
2
2
2012
3,615
1
Q2
1
Aguirre E, López-Bernardo E, Cadenas S. Functional
evidence for nitric oxide production by skeletal-muscle
mitochondria from lipopolysaccharide-treated mice.
Mitochondrion 12(1):126-31. Epub 2011 Jun 12. 2012.
PMID:
21664300.
IF:
3,615.
DOI:
10.1016/j.mito.2011.05.010.
AREA 1
Line 1.3
Animal models of
and intercellular signalling
GROUP 11
HEAD OF LABORATORY
GROUP MEMBERS
• Catalina Ribas Núñez
• Petronila Penela Márquez
• Guzmán Sánchez Fernández
• Laura Nogués Vera
• Susana Rojo Berciano
• Verónica Rivas Guerrero
• Julia Palacios García
• Almudena Inés Santos Bajo
• Adolfo Molejón García
• Paula Ramos Barbeito
• Clara Reglero Gómez
• Sofía Cabezudo Violero
Pathophysiological implications of the GRK2 interactome.
RESEARCH INTEREST
G protein-coupled-receptor kinase 2 (GRK2) is
emerging as a key integrative node in many signaling
networks. GRK2 displays a complex network of functional interactions (“interactome”) that underlies a variety of novel physiological roles. Changes in GRK2
expression occur in several relevant inflammatory,
metabolic, cardiovascular or cancer diseases, suggesting that those alterations may contribute to the
development of these pathologies. In order to assess
the feasibility of GRK2 as a useful biomarker and/or
therapeutic target, our main objectives are the identification of the relevant GRK2 interactome in specific
physiopathological contexts and the evaluation of the
functional impact of alterations in GRK2 levels using
cellular and animal models. During 2011, we have:
a) Revealed the existence of multiple scaffolding functions in the degradation of GRK2 by the proteasome
pathway, and identified a direct interaction between
GRK2 and the Mdm2 E3-ubiquitin ligase (Nogués L et
al., J. Biol. Chem. 2011)
b) Identified a novel Galpha-q/ PKCzeta/ ERK5 pathway that has an important role in angiotensin-mediated
heart hypertrophy in vivo (Garcia-Hoz C , SanchezFernández G et al. , J. Biol. Chem. 2012)
c) In collaboration with Dr. J. De Celis (CBM Madrid),
revealed the participation of Drosophila GRKs and
– 45 –
The complex GRK2 interactome (adapted from Penela et al., Brit J. Pharmacol. 2010).
arrestin homologs in the control of the Smoothened
signaling pathway (Molnar C et al., Plos Genetics 2011)
d) In collaboration with the group of Dr. Cristina Murga
(UAM-IISLP), further developed a new type of p38
MAPK inhibitors based on the mechanism of regulation
of p38MAPK by GRK2 (two patents filed)
e) Also in collaboration with the group of Dr. Cristina
Murga (UAM-IISLP), continued investigating the role of
GRK2 in obesity and insulin resistance as well as in cardioprotection.
f) Discovered that GRK2 modulates tubulin acetylation
in a HDAC6-dependent manner in order to regulate key
cellular processes relying on cytoskeletal rearrangements such as migration, polarity and cell spreading
(Lafarga V et al., EMBO Journal, 2011)
MAJOR GRANTS
• Catalina Ribas Núñez. Señalización a través de receptores acoplados a Proteínas G. Interacciones funcionales
entre las vías Mapk, G Q Y GRKS y su relación con
enfermedades cardiovasculares. ISCIII. PI080461.
Duration: 2009 - 2012.
• Federico Mayor Menéndez. GRK2(G protein-coupled
receptor kinase 2) as a key node in signal transduction
networks. Role in physiopathology. MICINN. SAF201123800. Duration: 2012 - 2014.
• Federico Mayor Menéndez. La quinasa GRK2(G proteincoupled receptor kinase 2) como un nodo central en las
redes de señalización celular. Papel en fisiopatología.
MICINN. SAF2011-23800. Duration: 2012 - 2014.
• Federico Mayor Menéndez. Redes Moleculares y
Celulares en Enfermedades Inflamatorias. CAM. S2010/BMD-2332 - Programa de Actividades I+D en BIOMEDICINA. Duration: 2012 - 2015.
• Catalina Ribas Núñez. Nuevas vías de señalización iniciadas por interacción entre proteínas GALFAQ y PKCZ
tras activación por GPCRS: su regulación e implicación
en enfermedades cardiovasculares. ISCIII. PI11/00126.
Duration: 2012 - 2014.
• Petronila Penela Márquez. Repercusiones de la regu-
– 46 –
lación de Mdm2 y p53 por la quinasa GRK2 en cáncer
de mama: estabilidad genómica y quimioresistencia.
ISCIII. PI11/ 00859. Duration: 2012 - 2014.
YEAR
Total IF
Publication No.
Q1
2010
23,585
3
3
2011
36.765
5
5
2012
27,961
6
5
Q2
Lafarga V, Mayor F Jr, Penela P. The interplay between G
protein-coupled receptor kinase 2 (GRK2) and histone
deacetylase 6 (HDAC6) at the crossroads of epithelial cell
motility. Cell Adh Migr. 6(6):495-501. 2012. PMID:
23076141. IF: 1,816. DOI: 10.4161/cam.21585
García-Zaragoza E, Pérez-Tavarez R, Ballester A, Lafarga V,
Jiménez-Reinoso A, Ramírez A, Murillas R, Gallego MI.
Intraepithelial paracrine Hedgehog signaling induces the
expansion of ciliated cells that express diverse progenitor
cell markers in the basal epithelium of the mouse mammary gland. Dev. Biol. 372(1):28-44. 2012. PMID: 23000969.
IF: 4,069. DOI: 10.1016/j.ydbio.2012.09.005
Vila-Bedmar R, Garcia-Guerra L, Nieto-Vazquez I, Mayor F
Jr,, Lorenzo M, Murga C, Fernández-Veledo S. GRK2 contribution to the regulation of energy expenditure and brown
fat function. FASEB J 26(8):3503-3514. 2012. PMID:
22516294. IF: 5,712. DOI: 10.1096/fj.11-202267
García-Hoz C, Sánchez-Fernández G, García-Escudero R,
Fernández-Velasco M, Palacios-García J, Ruiz-Meana M,
Díaz-Meco MT, Leitges M, Moscat J, García-Dorado D,
Boscá L, Mayor F Jr, Ribas C. Protein kinase C (PKC) mediated G q stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts. J Biol Chem.
287(10):7792-7802. 2012. PMID: 22232556. IF: 4,773.
DOI: 10.1074/jbc.M111.282210
Buitrago-Pérez Á, Hachimi M, Dueñas M, Lloveras B,
Santos A, Holguín A, Duarte B, Santiago JL, Akgül B,
Rodríguez-Peralto JL, Storey A, Ribas C, Larcher F, del Rio
M, Paramio JM, García-Escudero R. A humanized mouse
AREA 1
model of HPV-associated pathology driven by E7 expression. PLoS One 7(7):e41743. 2012. PMID: 22911850. IF:
4,092. DOI: 10.1371/journal.pone.0041743
Penela P, Lafarga V, Tapia O, Rivas V, Nogués L, Lucas E,
Vila-Bedmar R, Murga C, Mayor F Jr,. Roles of GRK2 in cell
signaling beyond GPCR desensitization: GRK2-HDAC6
interaction modulates cell spreading and motility. Sci Signal
5(224):pt3. 2012. PMID: 22589388. IF: 7,499. DOI:
10.1126/scisignal.2003098
PMEPA1, a downstream target of Cox-2 may control epithelial mesechymal transition of ovarian carcinoma cells Skov3. Cells stained
with phalloidin to visualize actin filaments.
GROUP 12
GROUP MEMBERS
• Nuria Gironés Pujol
• Ruth Álvarez Díaz
• Isabel M. Chico-Calero
• Natalia Cuesta Rubio
• Carmen Mª Sánchez-Valdepeñas
• María Gema Marín Alberca
• Inés Claire Osma García
• Carmen Punzón Gálvez
• Beatriz Barrocal López
• Carlos Chillón Marinas
• Mª de los Ángeles de Chorro y de Villa• Konstantinos Stamatakis Andriani
• Alberto Jiménez Buiza
• Marta Jiménez Martínez
• Alba Jiménez Segovia
RESEARCH INTEREST
There are similarities between recognition of pathogens
by Toll-like receptors (TLR), the immune response to
infection and chronic inflammation. We are analysing the
involvement of TLR/NFAT/Cox-2/prostaglandins (PGs) in
novel functions of the immune system and in inflammato-
Different types of myocarditis induced by three different T. cruzi
strains.
ry pathologies as Atherosclerosis, Obesity and Cancer.
We have unravelled a link between TLRs and NFAT activation that regulates Cox-2, increasing inflammatory
responses. Besides, PGs trigger migration activation of
macrophages and T lymphocytes, including the duration
of antigen presenting cell interaction with T lymphocytes.
TLR2-TLR4/NFATc4 induces expression of some adipogenic and repressed the antiadipogenic genes in
adipocytes, promoting or preventing Obesity. Finally, we
have identified PMEPA1 and DUSP10 as Cox-2 induced
molecules that control differentiation and stress response,
respectively, key in promoting tumorogenicity on colon or
ovarian carcinoma.
Different genetic lineages have been defined in
Trypanosoma cruzi, the causative agent of Chagas’ dis-
– 47 –
HEAD OF LABORATORY
ease. However, understanding of their comparative biology and pathogenesis is fragmentary. We have defined
the protective immune mechanism and the double-edge
role of NO. Th1/Th17/Treg/MDSC (myeloid derived suppressor
cells)
balance
determines
resistance/susceptibility in murine Chagas’s disease, depending on both host genetics and parasite strain. In general,
Th1 are protective but need to be counterbalanced by
Tregs to avoid excessive inflammatory damage. Th17
effect depends on host genetic and parasite background. Arginase I+ MDSC play a detrimental role.
Besides, we are studying how the parasite enters, infects
and escapes destruction by myeloid cells, defining Slamf1
as a new T. cruzi receptor. All intended for improved
understanding and prevention of Chagas’ disease.
MAJOR GRANTS
• Manuel Fresno Escudero. Estudios para el tratamiento
sintomático de la inflamación y el dolor. Neogenius
Pharma AIE (Lab Almirall). CENIT-E 2009. Duration: 2010
- 2012.
• Manuel Fresno Escudero. Receptores toll-like,
prostanoides y redes de señalización en enfermedades
inflamatorias. MICINN. SAF2010-18733. Duration: 2011
- 2013.
• Manuel Fresno Escudero. Redes Moleculares y Celulares
en Enfermedades Inflamatorias. CAM. S-2010/BMD2332 - Programa de Actividades I+D en BIOMEDICINA.
Duration: 2012 - 2015.
YEAR
Total IF
Publication No.
Q1
Q2
2010
47,566
8
5
2
2011
23,852
5
4
1
2012
44,972
8
7
1
Díaz-Muñoz MD, Osma-García IC, Fresno M, Iñiguez MA.
Involvement of PGE2 and the cAMP signalling pathway in
the up-regulation of COX-2 and mPGES-1 expression in
LPS-activated macrophages. Biochem. J 443(2):451-461.
– 48 –
2012.
PMID:
22268508.
10.1042/BJ20111052
IF:
4,897.
DOI:
Sreeramkumar V, Fresno M, Cuesta N. Prostaglandin E2
and T cells: friends or foes?. Immunol Cell Biol 90(6):579586. 2012. PMID: 21946663. IF: 3,661. DOI:
10.1038/icb.2011.75
Wang G, Abadía-Molina AC, Berger SB, Romero X,
O'Keeffe MS, Rojas-Barros DI, Aleman M, Liao G,
Maganto-García E, Fresno M, Wang N, Detre C, Terhorst C.
Cutting edge: Slamf8 is a negative regulator of Nox2 activity in macrophages. J Immunol. 188(12):5829-5832. 2012.
PMID: 22593622. IF: 5,788. DOI: 10.4049/jimmunol.1102620
Fuente HD, Perez-Gala S, Bonay P, Cruz-Adalia A, Cibrian
D, Sanchez-Cuellar S, Dauden E, Fresno M, García-Diez A,
Sanchez-Madrid F. Psoriasis in humans is associated with
downregulation of galectins in dendritic cells. J Pathol. 228:
193-203. 2012. PMID: 22271227. IF: 6,318. DOI:
10.1002/path.3996
Donnini S, Finetti F, Terzuoli E, Giachetti A, Iñiguez MA,
Hanaka H, Fresno M, Rådmark O, Ziche M. EGFR signaling upregulates expression of microsomal prostaglandin E
synthase-1 in cancer cells leading to enhanced tumorigenicity. Oncogene 31(29):3457-3466. 2012. PMID:
22081067. IF: 6,373. DOI: 10.1038/onc.2011.503
Calvo-Álvarez E, Guerrero NA, Alvarez-Velilla R, Prada CF,
Requena JM, Punzón C, Llamas MÁ, Arévalo FJ, Rivas L,
Fresno M, Pérez-Pertejo Y, Balaña-Fouce R, Reguera RM.
Appraisal of a Leishmania major strain stably expressing
mCherry fluorescent protein for both in vitro and in vivo
studies of potential drugs and vaccine against cutaneous
leishmaniasis. PLoS Negl Trop Dis. 6(11):e1927. 2012.
PMID: 23209866. IF: 4,716. DOI: 10.1371/journal.pntd.0001927
Aquilino C, Gonzalez Rubio ML, Seco EM, Escudero L,
Corvo L, Soto M, Fresno M, Malpartida F, Bonay P.
Differential trypanocidal activity of novel macrolide antibiotics; correlation to genetic lineage. PLoS One 7(7):e40901.
2012. PMID: 22859958. IF: 4,092. DOI: 10.1371/journal.pone.0040901
AREA 1
Calderón J, Maganto-Garcia E, Punzón C, Carrión J,
Terhorst C, Fresno M. The receptor Slamf1 on the surface
of myeloid lineage cells controls susceptibility to infection by
Trypanosoma cruzi. PLoS Pathog 8(7):e10027. 2012.
PMID: 22807679. IF: 9,127. DOI: 10.1371/journal.ppat.1002799
GROUP 17
HEAD OF LABORATORY
Cristina Murga Montesinos
The effects of GRK2 levels on insulin signalling and adiposity add up to
the previously described regulation of G protein-coupled effects and
other intracellular pathways by this kinase.
GROUP MEMBERS
• Rocío Vila Bedmar
• Elisa Lucas Fernández
During the past year 2012, the group has developed
the following lines of research:
1.- Establishment of a proof of concept that a deletion
of GRK2 could hamper the development of obesity
and/or insulin resistance when deleted during an
established condition of weight gain or insulin resistance (in collaboration with the groups of Dr. Federico
Mayor and Dr. Annemieke Kavelaars and Dr. Cobi
Heijnen in MD Anderson Cancer Center, University of
Texas at Houston).
2.- Analysis of the cellular, molecular and systemic
mechanisms by which lower levels of GRK2 protect
from the development obesity and/or insulin resistance
(following previous publications of our group).
2.- Studies on the gene expression analysis and transcriptional profile of the cardiac tissue of adult (9
months-old) mice hemizygous for GRK2 as well as the
status of key cardioprotective signaling routes with age
in this mice model.(Lucas E et al, manuscript submitted
Decreased lipid accumulation and increased core temperature in hemizygous GRK2 mice.(A) Representative microscopy images of paraffinembedded sections of BAT stained with hematoxylin and eosin from WT
and GRK2+/- 9-month-old mice (magnification 10x). Individual adipocyte areas were determined using image analysis software (ImageJ).(B)BAT from3 and9 month-oldWT and GRK2+/- mice was isolated
and the expression of GRK2 as well as GAPDH was examined by Western
blot. (C) Core temperature (expressed as ºC) was measured in WT and
GRK2+/- 9-month-old mice maintained at room temperature (24±2°C).
(D) BAT of 9 month oldWT and GRK2+/- mice was weighted after sacrifice and results expressed as BAT weight (g)/mouse weight (g).
in collaboration with the groups of Dr. W.J.KochTemple University-and Dr. Javier Díez-CIMA-).
3.- Analysis of the vascular response to vasodilatatory and vasoconstrictory neurohumoral stimuli, structure and biomechanics of the vasculature and the
development of hypertension by chronic infusion of
angiotensin II in mice hemizygous for the GRK2 protein (Lucas E et al, manuscript submitted in collaboration with the group of Dr. Mercedes Salaíces/Dr. Ana
Briones).
– 49 –
RESEARCH INTEREST
4.- In silico identification of candidate small molecule
compounds for p38MAPK based on virtual screening
of molecules and peptidomimetic approaches, followed by in vitro validation, and further characterization
in cells and in animal models of autoimmune diseases
and hyperalgesia.(Willhemen et al, manuscript submitted in collaboration with the group of of Dr. Annemieke
Kavelaars and Dr. Cobi Heijnen and Dr. Federico
Mayor). Also, derived from this line of research are the
following registered patents:
• ES P201031673 (2010) & PCT /ES2011/070774
(2011): "Péptido inhibidor de p38 y sus aplicaciones"
• ES 201131754 (2011) & PCT/ES2012/070762
(2012). "Fármacos inhibidores de p38 y sus apicaciones"
MAJOR GRANTS
• Cristina Murga Montesinos. Evaluación de compuestos
neuroprotectores. Neuron BIOPHARMA, S.L. 409.
Duration: 2010 - 2012.
• Cristina Murga Montesinos. Caracterización de las rutas
de señalización de GRK2 y MAPK en hipertrofia y disfunción cardiaca: desarrollo de inhibidores farmacológicos y
validación de biomarcadores diagnósticos. ISCIII - MSC.
Proyectos de Cooperación Interuniversitaria UAM Banco Santander con Estados Unidos. PS09/01208.
Duration: 2010 - 2012.
YEAR
Total IF
Publication No.
Q1
2010
13,814
2
2
2011
12,714
2
2
2012
13,211
2
2
Q2
Vila-Bedmar R, Garcia-Guerra L, Nieto-Vazquez I,
Mayor F Jr, Lorenzo M, Murga C, Fernández-Veledo
S. GRK2 contribution to the regulation of energy
expenditure and brown fat function. FASEB J
26(8):3503-3514. 2012. PMID: 22516294. IF: 5,712.
DOI: 10.1096/fj.11-202267
– 50 –
Penela P, Lafarga V, Tapia O, Rivas V, Nogués L,
Lucas E, Vila-Bedmar R, Murga C, Mayor F Jr. Roles
of GRK2 in cell signaling beyond GPCR desensitization: GRK2-HDAC6 interaction modulates cell spreading and motility. Sci Signal 5(224):pt3. 2012. PMID:
22589388. IF: 7,499. DOI: 10.1126/scisignal.2003098
GROUP 18
HEAD OF LABORATORY
Miguel Ángel Iñiguez Peña
GROUP MEMBERS
• Elena Hernández Subirá
• Paloma Guillem Llobat
• Raquel Nieto Pintado
• Ana Renshaw Calderón
RESEARCH INTEREST
Lipid mediators as prostanoids and cholesterol
derivatives play an essential role in inflammatory
processes associated to the onset and development
of a number of pathologies as cardiovascular diseases. Prostanoids participate in the inflammatory
response and exert important actions in the cardiovascular system, modulating vascular homeostasis
and participating in the pathogenesis of vascular diseases. Their importance in inflammation and in maintaining cardiovascular homeostasis is highlighted by
clinical experience with drugs inhibiting their production as NSAIDs. In spite of their well-known properties as anti-inflammatory drugs, recent studies have
shown that cyclooxygenase -2 selective NSAIDs
inhibitors increase the risk of adverse cardiovascular
side effects. On the other hand, oxysterols and
drugs acting as LXR ligands play a central regulatory role in lipid uptake, metabolism and efflux through
their properties as transcriptional regulators of gene
AREA 1
and investigation of the contribution of prostanoid
–mediated events and LXR ligands to the progression of abdominal aortic aneurysm, by the use of
cellular models and an experimental model of this
disease in Apo-E null mice and Cox-2 null mice.
Research on the molecular and cellular basis of the
actions of prostanoids and LXRs in the cardiovascular pathophysiology is required to clearly understand the benefits and risks of pharmaceutical
intervention with COX inhibitors as NSAIDs or synthetic LXR ligands on cardiovascular diseases.
MAJOR GRANTS
Miguel Ángel Íñiguez Peña. Acciones de
prostanoides y ligandos del receptor LXR en procesos inflamatorios y sus implicaciones en la fisiopatología cardiovascular. MICINN. SAF2011-23971.
Duration: 2012 - 2014.
PUBLICATIONS
(2)
[IF: 11,231]
YEAR
Total IF
Publication No.
Q1
Q2
2010
13,906
3
1
1
2011
3,536
1
1
2012
11,27
2
2
expression. In addition to their function in lipid
metabolism, LXRs have also been found to modulate
the immune response and inflammation. These
properties have made them particularly attractive
targets for intervention in human cardiovascular diseases.
Díaz-Muñoz MD, Osma-García IC, Fresno M,
Iñiguez MA. Involvement of PGE2 and the cAMP
signalling pathway in the up-regulation of COX-2
and mPGES-1 expression in LPS-activated
macrophages. Biochem. J 443(2):451-461. 2012.
PMID:
22268508.
IF:
4,897.
DOI:
10.1042/BJ20111052
Based on these observations and our previous
studies, the main objectives of our line of research
include:analysis of the effects of prostanoids and
LXR ligands in different cell types as leukocytes
and cardiomyocytes, among others; study of the
signal transduction pathways mediating hypertrophic effects of prostanoids on cardiomyocytes;
Donnini S, Finetti F, Terzuoli E, Giachetti A, Iñiguez
MA, Hanaka H, Fresno M, Rådmark O, Ziche M.
EGFR signaling upregulates expression of microsomal prostaglandin E synthase-1 in cancer cells
leading to enhanced tumorigenicity. Oncogene
31(29):3457-3466. 2012. PMID: 22081067. IF:
6,373. DOI: 10.1038/onc.2011.503
– 51 –
Coordinated regulation of the expression of COX-2 and mPGES1 in macrophages. Our group have presented evidences indicating that COX-2 and mPGES-1 share common signaling pathways and transcription factors (NF-κB, Egr-1 and CREBP) that
drive a coordinated expression of both genes in LPS-activated
macrophages. The figure shows a model integrating these signaling pathways for the coordinated expression of COX-2 and
mPGES-1 in macrophages. LPS treatment triggers NF-κB activation and Egr-1 expression. These transcription factors are involved in the early induction of COX-2 and mPGES-1. PGE2 produced at this stage promotes an autocrine positive feedback
resulting in increased COX-2 and mPGES-1 expression through
a signaling pathway involving an EP2-dependent increase of
intracellular cAMP. This second messenger leads to the sequential activation of PKA and CREB that, in turns, promote an
induction in the synthesis of COX-2 and mPGES-1, and hence in
PGE2 production.
Line 1.4
Etiopathogenic
and immunological
mechanisms of
dermatological diseases
Dermatol. 148(6):755-60. 2012. PMID: 22710460. IF:
3,888. DOI: 10.1001/archderm.148.6.755-b
Fernandez-Peñas P, Jones-Caballero M, Espallardo O,
García-Díez A. Comparison of Skindex-29, Dermatology
Life Quality Index, Psoriasis Disability Index and Medical
Outcome Study Short Form 36 in patients with mild to
severe psoriasis. Br J Dermatol. 166(4):884-7. 2012.
PMID: 22229951. IF: 3,666. DOI: 10.1111/j.13652133.2012.10806.x
GROUP 19
HEAD OF LABORATORY
Amaro García Díez
Gallo E, Llamas-Velasco M, Navarro R, Fraga J, GarcíaDíez A. Eccrine squamous syringometaplasia secondary
to cutaneous extravasation of docetaxel: report of three
cases. J Cutan Pathol. 2012 Nov 21. [Epub ahead of
print]. 2012. PMID: 23170995. IF: 1,561. DOI:
10.1111/cup.12041
GROUP MEMBERS
• Maximiliano Aragüés Montañés
• Silvia Pérez Gala
• Javier Fraga Fernández
García-Díez A, Sanchez-Madrid F. Psoriasis in humans is
associated with downregulation of galectins in dendritic
cells. J Pathol. 228: 193-203. 2012. PMID: 22271227. IF:
6,318. DOI: 10.1002/path.3996
MAJOR GRANTS
Amaro García Díez. Estudio Epidemiológico Psoriasis.
Schering Plough. Duration: 2008 - 2012.
YEAR
Total IF
Publication No.
Q1
Q2
2010
32,326
11
4
7
2011
5,846
3
1
1
2012
23,542
7
5
1
Llamas-Velasco M, Sánchez-Pérez J, Gallo E, Fraga
J. Hyperpigmented asymptomatic macule in a fingertip with suspicious dermoscopic pattern--quiz case.
Arch Dermatol. 148(2):247-252. 2012. PMID:
22351829. IF: 3,888. DOI: 10.1001/archdermatol.2011.1073a
Pedraz J, Onate MJ, García-García C, Fraga J, Daudén
E. Long-term nasal plaque with nasal obstruction. Arch
– 52 –
García-Martín P, De Argila D, To-Figueras J, LlamasVelasco M, Fraga J, García-Díez A. Phototolerance
induced by narrow-band UVB phototherapy in severe
erythropoietic
protoporphyria.
Photodermatol
Photoimmunol Photomed. 28(5):261-3. 2012. PMID:
22971192. IF: 1,305. DOI: 10.1111/j.16000781.2012.00677.x
Navarro R, Daudén E, Gallo E, Santiago Sánchez-Mateos
D, García-Díez A. Alopecia areata during treatment of
psoriasis with adalimumab and leflunomide: a case and
review of the literature. Skin Pharmacol Physiol.
25(2):107-10. 2012. PMID: 22301842. IF: 2,916. DOI:
10.1159/000335264
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: ARAGUES MONTAÑES,
MAXIMILIANO
AREA 1
con psoriasis en placas de moderada a grave: AMAGINE2; (versión 20-02-12). AMGEN INC. 20120103.
EudraCT: 2012-000656-34
Estudio de fase 3 para evaluar la eficacia y la seguridad de
las pautas de inducción y mantenimiento de brodalumab
en comparación con placebo y ustekinumab en sujetos
– 53 –
Line 1.5
Cellular mechanisms and
molecular determinants of
allergy-based diseases
GROUP 20
HEAD OF LABORATORY
Carlos Blanco Guerra
GROUP MEMBERS
• Álvaro Daschner
• Francisco Félix Vega de la Osada
• Consolación de Frutos Moreno
• Ana Valls Sánchez
• M. Paloma Las Heras Almazán
• Tania María Ramos García
This figure shows the proposed immunologic mechanisms leading to different clinical outcome after an acute parasitism by
Anisakis simplex. GA: gastric Anisakiasis. GAA: Gastro-allergic
Anisakiasis. CU+: A. simplex sensitization associated chronic urticaria. (Trends in Parasitology 2012)
RESEARCH INTEREST
Our group has focused on three different research
areas throughout 2012:
- Anisakis simplex allergy: Within the project on
characterizing Anisakis simplex sensitization associated chronic urticaria as a differential phenotype,
leaded be Dr. A. Daschner, we published the results
on the use of recombinant allergens for the differentiation of clinical entities associated with Anisakis
simplex sensitization Whereas anti- Ani s 7 IgE is
able to confirm a previous parasitic episode by this
nematode in patients with urticaria, in chronic
urticaria anti- Ani s 1 IgE is detected in less than
50% of patients and is thus not a major allergen.
Our pluri-disciplinary teaching and research activities in Evolutionary medicine have further contributed to a high impact publication in the field of
Parasitology, in which a model has been proposed
explaining necessary immunologic features leading
– 54 –
Co-sensitization graph of lipid transfer protein (LTP) allergens.
Each node represents one allergen (LTP, white ovals; non-LTP
allergens, blue squares) and the links represent co-sensitization
of one or more sera for the linked allergens. The weight of each
link, between 0 and 1, measures the degree of co-sensitization.
(PLoS One. 2012).
AREA 1
Clin Immunol 22(5):313-30.
23101306. IF: 2,269
- Food allergy: we have collaborated with Centro
de Biotecnología y Genómica de Plantas (UPMINIA), to deepen sensitization mechanisms to lipid
transfer proteins (LTP). Sensitization profiles have
been checked by protein microarrays and co-sensitization graph approach, demonstrating that LTP
are relevant allergens (Fig. 2). Now we are focusing
on kiwi and plane tree allergy.
Palacín A, Gómez-Casado C, Rivas LA, Aguirre J,
Tordesillas L, Bartra J, Blanco C, Carrillo T, CuestaHerranz J, de Frutos C, Alvarez-Eire GG,
Fernández FJ, Gamboa P, Muñoz R, SánchezMonge R, Sirvent S, Torres MJ, Varela-Losada S,
Rodríguez R, Parro V, Blanca M, Salcedo G, DíazPerales A. Graph based study of allergen crossreactivity of plant lipid transfer proteins (LTPs)
using microarray in a multicenter study. Plos One
7(12):e50799. 2012. PMID: 23272072. IF: 4,092.
DOI: 10.1371/journal.pone.0050799
- Respiratory allergy: in the context of the MEICA
research project formerly funded by Fundación
Genoma España, a phase IV clinical trial has been
finished, and a 2 yr study prolongation has been
approved, to check immunological changes
induced by grass-pollen immunotherapy. A new
placebo controlled clinical trial has been also
designed, in collaboration with ALK laboratory and
the CNB (Biotechnological National Centre).
PUBLICATIONS
(5)
[IF: 17,876]
YEAR
Total IF
Publication No.
Q1
Q2
2010
18,62
6
2
2
2011
4,87
2
2012
17,876
5
3
1
Cuéllar C, Daschner A, Valls A, De Frutos C,
Fernández-Fígares V, Anadón AM, Rodríguez E,
Gárate T, Rodero M, Ubeira FM. Ani s 1 and Ani s
7 recombinant allergens are able to differentiate
distinct Anisakis simplex-associated allergic clinical
disorders. Arch Dermatol Res 304(4):283-288.
2012. PMID: 22249742. IF: 2,279. DOI:
10.1007/s00403-012-1206-8
Cabañes N, Igea JM, de la Hoz B, Agustín P,
Blanco C, Domínguez J, Lázaro M, Lleonart R,
Méndez J, Nieto A, Rodríguez A, Rubia N, Tabar A,
Beitia JM, Dieguez MC, Martínez-Cócera C, Quirce
S. Latex allergy: Position Paper. J Investig Allergol
2012.
PMID:
Palacín A, Rivas LA, Gómez-Casado C, Aguirre J,
Tordesillas L, Bartra J, Blanco C, Carrillo T,
Cuesta-Herranz J, Bonny JA, Flores E, GarcíaAlvarez-Eire MG, García-Nuñez I, Fernández FJ,
Gamboa P, Muñoz R, Sánchez-Monge R, Torres M,
Losada SV, Villalba M, Vega F, Parro V, Blanca M,
Salcedo G, Díaz-Perales A. The involvement of
thaumatin-like proteins in plant food cross-reactivity: a multicen ter study using a specific protein
microarray. PLOS One 7(9):e44088. 2012. PMID:
22970164. IF: 4,092. DOI: 10.1371/journal.
pone.0044088
Daschner A, Cuéllar C, Rodero M. The Anisakis
allergy debate: dose an evolutionary approach
help?. Trends in Parasitology 28(1):9-15. 2012.
PMID:
22079162.
IF:
5,144.
DOI:
10.1016/j.pt.2011.10.001
BOOKS
Carlos Blanco Guerra. Alergia al látex. Libro de las
enfermedades alérgicas de la Fundación BBVA.
2012. Nerea S.A. ISBN: 978-84-92937-15-8.
Alvaro Daschner. Una visión evolucionista de la
hipótesis de la higiene en alergia y las enfermedades
inflamatorias
crónicas.
Medicina
– 55 –
to a different outcome after parasitism by A. simplex (Fig.1).
Evolucionista: Aportaciones pluridisciplinares.
2012. MedEvo. ISBN: 978-84-695-3141-9.
Alvaro Daschner. Consideraciones evolucionistas
en las enfermedades alérgicas. Medicina
Evolucionista: Aportaciones pluridisciplinares.
2012. MedEvo. ISBN: 978-84-695-3141-9.
Alvaro Daschner, José Luis Gómez Pérez,
Editores. Medicina Evolucionista: Aportaciones
pluridisciplinares. 2012. MedEvo. ISBN: 978-84695-3141-9.
– 56 –
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: BLANCO GUERRA,
CARLOS
Estudio multicéntrico, aleatorizado, doble ciego, de
grupos paralelos, para evaluar la eficacia y la
seguridad de cuatro concentraciones de Depigoid«
Phleum en pacientes con Rinitis Alérgica y/o
Rinoconjuntivitiscon o sin Asma Intermitente;
(Versión 2.0: 15-03-12). LETI PHARMA GMBH.
6043-PG-PSC-192.
EudraCT: 2012-000416-28
AREA 1
Line 1.6
Inflammatory processes in
nephrological diseases
GROUP 21
•
•
•
•
•
•
•
•
•
•
GROUP MEMBERS
Carmen Bernis Carro
Vicente Álvarez Chiva
Guillermina Barril Cuadrado
Carmen Sánchez González
Abelardo Isaac Aguilera Peralta
Antonio Carlos Fernández Perpén
Isabel Herráez Jiménez
Martín Giorgi González
Pablo Ruano Suárez
Laura Salanova Villanueva
RESEARCH INTEREST
These are the most relevant areas of interest during 2012.
1. Renal Nutrition: Multidisciplinary consensus on the
approach to hospital malnutrition in Spain. Influence of
endogenous testosterone, muscle strength and fat-free
mass in men with chronic kidney disease (CKD).
Organization of the Annual National Meeting on Nutrition in
CKD. 2. Virology and CKD: Hepatitis C haemodialysis, epidemiology and prevention of virus transmission. Long-term
virological follow up of patients with occult hepatitis C virus
infection. 3. Peritoneal Dialysis: Studies about more biocompatible fluids and evaluation of peritoneal membrane
response: Influence of bicarbonate/low-GDP peritoneal
dialysis fluid on in vitro and ex vivo epithelial-to-mesenchymal transition of mesothelial cells. 4. Mechanisms associated with Acute Renal Failure: Hypoxia inducible factor 1alpha (HIF-1 alpha) is induced during reperfusion after renal
ischemia and is critical for proximal tubule cell survival. 5.
Haemodialysis procedures and complications manage-
Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival. HIF-1a is expressed exclusively in non-damaged proximal tubules
of human post-transplant renal biopsies. (a) PAS staining for renal
structure and immunohistochemistry for HIF-1a in paraffin-embedded
human renal biopsies. HIF-1 a is expressed in non-damaged proximal
tubules (biopsy nu4). Images of representative biopsies are presented:
severe ATN (biopsies nu6 and nu14) and ATN regeneration (biopsy nu4).
Magnification:6400. (b) Spearman Rho-Correlation coefficient between
ATN grade and HIF-1a expression in all biopsies, with statistical significance p#0.01.doi:10.1371/journal.pone.0033258.g009
ment: Spanish study of anticoagulation in haemodialysis.
Successful treatment with sodium thiosulfate for calcific
uraemic arteriolopathy. Inflammation and resistance to erythropoietin in patients with tuberous sclerosis on haemodialysis. 6. Mechanisms and treatment of glomerular diseases:
– 57 –
HEAD OF LABORATORY
José Antonio Sánchez Tomero
MAJOR GRANTS
Influence of bicarbonate/low-gdp peritoneal dialysis fluid (bicavera)
on in vitro and ex vivo epithelial-to-mesenchymal transition of mesothelial cells. Effects of peritoneal dialysis (PD) fluids on mesothelial
cells (MCs) in vitro. (A) Effects on MC morphology at 48 and 72 hours.
Images are representative of 5 independent experiments. (B) Western
blot results show expression of E-cadherin in exposed MCs. Tubulin
was used as a loading control. Images are representative of 5 independent experiments. (C) Levels of E-cadherin messenger RNA (mRNA)
analyzed by quantitative reverse transcription polymerase chain reaction [for MCs treated with PD fluids or with transforming growth factor
β1 (TGF-β1) relative to untreated cells]. Results are mean ± standard
error of 5 experiments. (D) Production of vascular endothelial growth
factor (VEGF) in supernatant (picograms per milligram of cell pro¬tein)
by omentum-derived MCs treated with PD fluids or with TGF-β1. The
box plots show 75th percentile, 25th percentile, median, maximum,
and minimum values from 5 experiments. BicaVera: solution from Fresenius Medical Care, Bad Homburg, Germany. R.U. = relative units.
Long-Term Outcomes of IA Nephropathy presenting with
minimal or no-proteinuria. A Randomized Trial to study the
effect of dual blockade of the Renin-Angiotensin System on
the progression of type 2 diabetic nephropathy. 7. Ethical
aspects and Nephrology: Exploring the opinion of CKD
patients on dialysis regarding end-of-life and advance care
planning¸ Unplanned start of dialysis and instruction protocols. 8. Economical Studies: Advantages of the peritoneal
dialysis procedure for the public health system sustainability; Cost comparison between haemodialysis and peritoneal
dialysis outsourcing agreements.
– 58 –
• José Antonio Sánchez Tomero. Mecanismos moleculares
que regulan el daño renal provocado por isquemia-reperfusión. Amgen SA. IRSIN 2322006. Duration: 2010 - 2012.
• Guillermina Barril Cuadrado. Infección silente por virus C
de la hepatitis en unidades de diálisis: análisis de la
respuesta inmunoserológica y repercusiones diagnósticas. Fundacion Mutua Madrileña. Duration: 2010 - 2012.
• Abelardo Isaac Aguilera Peralta. Looking for a new, more
biocompatible peritoneal dialysis solution based in glicosides as osmotic agent. Fresenius Medical Care.
Duration: 2010 - 2012.
• Abelardo Isaac Aguilera Peralta. Validación de la
Transición Epitelio Mesenquimal de Células Mesoteliales
como Herramienta para el Diagnóstico y Pronóstico del
Fracaso de la Membrana Peritoneal en Pacientes en
Diálisis Peritoneal. Sociedad Española de Nefrología.
Duration: 2010 - 2012.
• Abelardo Isaac Aguilera Peralta. Modulación de la transición epitelio mesenquimal (EMT) de las células
mesoteliales (CM) como aproximación para mejorar la
función peritoneal de pacientes en diálisis peritoneal.
ISCIII. FIS: 009/00774. Duration: 2010-2012
YEAR
Total IF
Publication No.
Q1
Q2
2010
32,685
11
4
3
2011
33,655
12
5
2012
27,84
11
3
1
Sánchez-Fructuoso AI, Ruiz JC, Torregrosa JV, González E,
Gómez E, Gallego RJ, Troya MI, Jimenez C, Llamas F,
Romero R, Bernis C, Crespo JF, Guirado L; AnemiaTrans
Study Group. Anemia control in renal transplant recipients
receiving continuous erythropoietin receptor activator
(C.E.R.A.) treatment: the AnemiaTrans Study. Adv Ther
29(11):979-991. 2012. PMID: 23160946. IF: 2,105. DOI:
10.1007/s12325-012-0063-3
Jadoul M, Barril G. Hepatitis C in hemodialysis: epidemiology and prevention of hepatitis C virus transmission. Contrib
Nephrol. 176:35-41. Epub 2012 Jan 30. 2012. PMID:
22310779. IF: 1,487. DOI: 10.1159/000333761
AREA 1
Herrero-Calvo JA, González-Parra E, Pérez-García R,
Tornero-Molina F; Grupo de Estudio Español Sobre
Anticoagulación en Hemodiálisis (..,Barril G, ..). Spanish
study of anticoagulation in haemodialysis. Nefrologia
32(2):143-152. 2012. PMID: 22425796. IF: 1. DOI:
10.3265/Nefrologia.pre2011.Nov.11106
Arrieta J, Rodríguez-Carmona A, Remón C, Pérez-Fontán
M, Ortega F, Sánchez-Tomero JA, Selgas R. Cost comparison between haemodialysis and peritoneal dialysis outsourcing agreements. Nefrologia 32(2):247-248. 2012.
PMID: 22466267. IF: 1. DOI: 10.3265/Nefrologia.pre2011
.Dec.11311
Bernis-Carro C. What happens to the specialty of nephrology?. Nefrología 32(4):535-6. 2012. PMID: 22806289. IF: 1.
DOI: 10.3265/Nefrologia.pre2012.Apr.11467
Selgas R, López-Cabrera M, Sánchez-Tomero JA.
Influence of bicarbonate/low-GDP peritoneal dialysis fluid
(BicaVera) on in vitro and ex vivo epithelial-to-mesenchymal
transition of mesothelial cells. Perit Dial Int 32(3):292-304.
2012.
PMID:
22215656.
IF:
2,097.
DOI:
10.3747/pdi.2010.00315
Conde E, Alegre L, Blanco-Sánchez I, Sáenz-Morales D,
Aguado-Fraile E, Ponte B, Ramos E, Sáiz A, Jiménez C,
Ordoñez A, López-Cabrera M, del Peso L, de Landázuri
MO, Liaño F, Selgas R, Sánchez-Tomero JA, GarcíaBermejo ML. Hypoxia inducible factor 1-alpha (HIF-1 alpha)
is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival. PLoS One 7(3):e33258.
BOOKS
Aguilera A, Loureiro J, Gónzalez-Mateo G, Selgas R,
López-Cabrera M. The mesothelial to mesenchymal transition a pathogenic and therapeutic key for peritoneal membrane failure. Text book of Peritoneal Dialysis. 2012. Boston,
USA.
Fernández-Perpén A, Sánchez-Tomero JA. Unplanned
start of dialysis and instruction protocols. Nefrologia Suppl
Ext 3(3):8-11. 2012. IF: 1. DOI: 10.3265/Nefrologia
SuplementoExtraordinario.pre2012.Feb.11406
Barril Caudrado G. Infecciones víricas en pacientes en
Hemodiálisis. Manual de Nefrología al día. 2012. Plus
Medical, Badalona. ISBN: 978-84-96727-97-7.
Giorgi M, Jerico S. Paciente con esclerosis tuberosa en
Hemodiálisis. Inflamación y resistencia a la eritropoyetina.
Nefrología. Suppl Extra 3(5):63-66. 2012. IF: 1
CLINICAL TRIALS
Del Peso G, Bajo MA, Perez Fontán M, Martínez J, Marrón
B, Selgas R, Group of Study on ‘Bemidextrin’. Fernandez
Perpen A. Effect of self-administered intraperitoneal bemiparin on peritoneal transport and ultrafiltration capacity in
peritoneal dialysis patients with membrane dysfunction. A
randomized, multi-centre open clinical trial. Nephrol Dial
Transplant. 27(5):2051-2058. Epub 2011 Oct 12. 2012.
PMID: 21993377. IF: 3,396. DOI: 10.1093/ndt/gfr546
Fernández-Perpén A, Pérez-Lozano ML, Bajo MA, AlbarVizcaino P, Correa PS, del Peso G, Castro MJ, Aguilera A,
Ossorio M, Peter ME, Passlick-Deetjen J, Aroeira LS,
PRINCIPAL INVESTIGATOR: BARRIL CUADRADO,
GUILLERMINA
Estudio de la mejora de la tolerancia intrahemodialisis asociada al control de la volemia. "EMTIACO"; (versión 26-0612). EMTIACO
PRINCIPAL INVESTIGATOR: SANCHEZ TOMERO, JOSE A.
Biodisponibilidad de tres formulaciones de hierro tras su
administración oral a pacientes en hemodiálisis en ayunas;
(versión 1: 13-07-12). LABORATORIOS ZAMBON S.A.U.
FIFERJ01.
EudraCT: 2012-003419-71
– 59 –
Gutiérrez E, Zamora I, Ballarín JA, Arce Y, Jiménez S,
Quereda C, Olea T, Martínez-Ara J, Segarra A, Bernis C,
García A, Goicoechea M, García de Vinuesa S, RojasRivera J, Praga M. Long-Term Outcomes of IA
Nephropathy Presenting with Minimal or No Proteinuria. J
Am Soc Nephrol 23(10):1753-1760. 2012. PMID:
22956820. IF: 9,663. DOI: 10.1681/ASN.2012010063
Line 1.7
Inflammatory mechanisms
in pulmonary diseases
GROUP 22
HEAD OF LABORATORY
GROUP MEMBERS
• Rosa María Girón Moreno
• Carolina Cisneros Serrano
• Enrique Domingo Zamora García
• Silvia Sánchez Cuéllar
• Ana Martínez Meca
RESEARCH INTEREST
COPD (chronic obstructive pulmonary disease) is a
major problem worldwide. In 2012, the GesEPOC
(Spanish Guide of COPD) was developed as an initiative of SEPAR (Spanish Society of Respiratory
Disease), in which many scientific societies, and
various services, including the Pneumology
Department of Hospital de La Princesa have participated. This guide describes the classification of
the severity and pharmacotherapy of stable COPD.
GesEPOC is a new approach to more individualized
treatment of COPD according to the clinical characteristics of patients.
Our group also participated in a national study
where the objective was to determine the frequency, severity, geographical variability and determinants of individual consequences of a restrictive
ventilatory defect measured by spirometry in the
Spanish population.
We have worked with the Immunology Department
of the Hospital to study the role that galectins as
– 60 –
Surface expression of galectin (gal)-1 and gal-9 is reduced in
leucocytes from induced sputum of asthma patients. (a) cells
from sputum samples were stained as in Fig.2 and galectin expression was analysed on macrophages (CD16* HLA-DR*). Representative histograms from a healthy donor and an asthma
patient are shown. Isotype control (dotted line), gal expression
(solid line). (b) Gal-1, gal-3 and gal-9 expression on leucocytes
grom asthma (n=15) and healthy donors (n=10). Bars represent
mean +- standard error of the mean of mean fluorescence intestity (MFI) of galectins expression. Differences were tested
by Mann-Whitney U-test. (c) gal expression according to allergic state. Differences between atopy and non-atopy against healthy donors were tested by Mann-Whitney U-test.
immunoregulatory molecules in controlled stable
asthma.
In addition, our group is involved with the ConsEPOC
consortium of the Community of Madrid to identify
genetic variations that alter HIF-mediated response in
patients with COPD/ Sleep Apnea Hypopnea Syndrome
(SAHS) and analyze their correlation with disease progression.
AREA 1
• Rosa María Girón Moreno. Estudio multicéntrico de
la estructura poblacional de P. aeruginosa en primocolonización y cololonización patogénica crónica broncopulmonar y la dinámica del microbioma
en fibrosis quística. PI12/00734. Duration: 2012 2015.
MAJOR GRANTS
• Julio Ancochea Bermúdez. Desarrollo de nuevas estrategias terapéuticas en la LAM: estudio sobre su origen
celular y diseminación. SEPAR. Duration: 2011 - 2013.
• Julio Ancochea Bermúdez. Programa de I+D
Biomedicina. CONSEPOC-CM. Inflamación e hipoxia:
mecanismos de desarrollo y progresión en EPOC y
SAHS. Consejería de Educación - CAM. Duration: 2011
- 2014.
• Rosa María Girón Moreno. Prevalencia de la
Miocardiopatía Dilatada en pacientes con Fibrosis
Quística y estudio de posibles factores etiológicos. Beca
Pablo Motos. Duration: 2011 - 2013.
• Silvia Sánchez Cuéllar. El papel de las Galectinas como
molécula de inmunoregulación en el asma.
Neumomadrid. Duration: 2011 - 2013.
• Julio Ancochea Bermúdez. Inflamación e hipoxia:
mecanismos en desarrollo y progresión en EPOC y
SAHS. CAM. P2010 / BMD-2542. Duration: 2012 2015.
• Rosa María Girón Moreno. Estudio Dayca. SEPAR.
Duration: 2012 - 2014.
YEAR
Total IF
Publication No.
Q1
Q2
2010
26,616
7
3
1
2011
54,608
3
3
2012
16,936
4
2
2
Yañez AM, Guerrero D, Pérez de Alejo R, GarciaRio F, Alvarez-Sala JL, Calle-Rubio M, Malo de
Molina R, Valle Falcones M, Ussetti P, Sauleda J,
Zamora García E, Rodríguez-González-Moro JM,
Franco Gay M, Torrent M, Agustí A. Monitoring
breathing rate at home allows early identification of
COPD exacerbations. Chest 142(6):1524-9. 2012.
PMID: 22797131. IF: 5,25. DOI: 10.1378/chest.112728
Lamana A, Cibrian D, Giron RM, Vara A, SanchezMadrid F, Ancochea J. Reduced expression of
galectin-1 and galectin-9 by leucocytes in asthma
patients. Clin Exp Immunol. 170(3):365-374. 2012.
PMID: 23121677. IF: 3,36. DOI: 10.1111/j.13652249.2012.04665.x
García-Diez A, Sanchez-Madrid F. Psoriasis in
humans is associated with downregulation of
galectins in dendritic cells. J Pathol. 228: 193-203.
2012. PMID: 22271227. IF: 6,318. DOI:
10.1002/path.3996
Cisneros C. A female patient with asthma in the
emergency room. Rev Clín Esp. 212(11):540-544.
2012. PMID: 23092746. IF: 2,008. DOI:
10.1016/j.rce.2012.08.001
– 61 –
Induced sputum cells of asthma patients show altered mRNA expression of galectins (gal) and Th2 cytokines. Total RNA was isolated from induced sputum of asthma patients (n=16) and healthy donors (n=11), and real-time reverse transcription-polymerase chain
reaction (RT-PCR) was performed. (a) Gal-1, gal-3 and gal-9 mRNA
expression. (b) Interlukin (IL)-5 and IL-13 mRNA expression. mRNA
levels are expressed as arbitrary units respect to B-actin expression. Differences between groups were tested by Mann-Whitney Utest. Bars correspond to mean +- standard error of the mean.
BOOKS
Carolina Cisneros Serrano. Módulo: Asma. Proyecto
SEPAR: Pulmón Virtual. 2012. WEB Online SEPAR.
Carolina Cisneros Serrano. Pruebas de provocación bronquial. Programa AGER: Módulo de pruebas funcionales.
2012. WEB Online SEPAR.
A. Xaubet Mir, F. Morell Brotad, J. Ancochea Bermúdez.
Enfermedades Difusas del Pulmón. Medicina InternaFarreras/Rozman. 2012. Elsevier España. ISBN: 978-848086-896-9.
Carolina Cisneros Serrano, Gonzalo Segrelles Calvo, Ana
Martínez Meca. Provocación bronquial inespecífica.
Monografía de Neumomadrid: “Exploración funcional respiratoria". 2012. Ergon. ISBN: 978-84-8473-983-8.
Madruga D, Girón R. Alteración de la densidad Mineral
ósea. Tratado de Fibrosis Quística. 2012. Editorial Justim.
ISBN: 978-84-695-0562-5.
Girón R, Antelo C. Terapia inhalada. Tratado de Fibrosis
Quística. 2012. Editorial Justim. ISBN: 978-84-695-0562-5.
Carolina Cisneros Serrano. De la sospecha al diagnóstico
de Asma. Curso de formación continuada de
Neumomadrid sobre Asma. 2012. Acceso WEB
Neumomadrid.
Salcedo A, Gartner S, Girón R, García-Novo D. Tratado de
Fibrosis Quística. 2012. Editorial Justim. ISBN: 978-84695-0562-5.
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: ANCOCHEA BERMUDEZ,
JULIO
Estudio clínico aleatorizado, doble ciego, controlado con
placebo para evaluar el efecto sobre la función endotelial de
roflumilast en pacientes con enfermedad pulmonar
obstructiva crónica; (versión 1.0:28-9-11). CIBERES. CIBROF-2011-01.
EudraCT: 2011-005047-27
– 62 –
JULIO
Ensayo clínico de extensión, abierto, para evaluar la seguridad a largo plazo de BIBF 1120 administrado por vía oral
en pacientes con Fibrosis Pulmonar Idiopática; (versión
1.0:27-1-12). BOEHRINGER INGELHEIM ESPAÑA, S.A.
1199.33.
EudraCT: 2011-002766-21
PRINCIPAL INVESTIGATOR: CISNEROS SERRANO,
CAROLINA
Estudio multicéntrico aleatorizado, doble ciego, de doble
enmascaramiento, grupos paralelos, controlado con placebo, sobre la eficacia y la seguridad del tratamiento complementario con mepolizumab, en sujetos con asma grave no
controlada, refractaria al tratamiento; (versión 00: 18-0512). GLAXOSMITHKLINE ESPAÑA, S.A. MEA115588.
EudraCT: 2012-001251-40
JULIO
Estudio aleatorizado multicéntrico de 52 semanas de
duración para evaluar la monitorización remota de
pacientes utilizando el cuestionario EXACT de resultados
notificados por el paciente en la reducción de hospitalizaciones por exacerbaciones en pacientes con Enfermedad
Pulomonar Obstructiva Crónica en comparación con
pacientes controlados según práctica clínica habitual; (versión V00:20-01-12). NOVARTIS FARMACEUTICA, S.A.
CIDD001D2401
JULIO
Estudio aleatorizado, doble ciego y de grupos paralelos de
12 semanas de tratamiento para evaluar la eficacia y la
seguridad de QMF149 (150micro gramos/160 microgramos 1 vez al día) en comparación con xinafoato de salmeterol/propionato de fluticasona (50 microgramos/500
microgramos 2 veces al día) en pacientes con enfermedad
pulmonar obstructiva crónica; (versión 00: 04-04-12).
NOVARTIS PHARMA SERVICES AG. CQMF149F2202.
EudraCT: 2012-001172-12
PRINCIPAL INVESTIGATOR: GIRON MORENO, ROSAMARIA
Estudio de la eficacia del tratamiento a largo plazo con
ácido docosahexanóico sobre la inflamación pulmonar,
AREA 1
PRINCIPAL INVESTIGATOR: GIRON MORENO, ROSAMARIA
Estudio observacional de calidad de vida relacionada con la
salud y cumplimiento terapéutico en pacientes con fibrosis
quística e infección pulmonar crónica por Pseudomonas
aeruginosa que reciben tratamiento anti-biótico crónico
nebulizado (estudio CAPA-FQ); (versión 1:29-02-12).
AMPARO SOLER JOVER (H.U. LA FE DE VALENCIA).
AMP-AZT-2012-01
sistémica e intestinal en pacientes con fibrosis quística; (versión 6:29-06-12). FUNDACION INVESTIGACION BIOMEDICA H. RYC. DHA-FQ-1
PRINCIPAL INVESTIGATOR: CISNEROS SERRANO,
CAROLINA
Evaluación transversal y longitudinal internacional
sobre el control del asma (LIAISON); (Versión 1.0:0603-12). CHIESI FARMACEUTICI, S.P.A. DFIDM1101/CHI-ANT-2012-01
– 63 –
Line 1.8
Inflammatory response
in hepatic diseases
GROUP 23
HEAD OF LABORATORY
GROUP MEMBERS
• Luisa Consuelo García Buey
• María Trapero Marugán
• Jorge Mendoza Jiménez-Ridruejo
• Leticia González Moreno
• Asunción García Sánchez
• Ángel Hernández Bartolomé
• María Jesús Borque Iñurrita
• María Jesús Alonso Martín
• María Paloma Sanz Cameno
• Samuel Martín Vílchez
• Yolanda Rodríguez Muñoz
• Rosario López Rodríguez
• Yolanda Real Martínez
Our previous results showed the significant involvement of the Angiopoietin/Tie-2 axis on CHC progression and therapy response, finding a notable unbalance
of peripheral blood expression of Angiopoietin 1 and 2
(Ang1 and Ang2). Interestingly, we could observe the
relative increase of TEMs in the blood of CHC patients,
monocytes that express the tyrosine kinase receptor of
angiopoietins, Tie-2. This subtype of circulating
myeloid cells, with marked proangiogenic properties
but notable immunosuppressive nature, was also
found at CHC inflamed portal tracts (Figure 1) and has
recently been proposed as a diagnostic biomarker for
HCC by other authors.
Monocytes are essential precursors of antigen-presenting cells, such as macrophages and dendritic cells, and
notably contribute to the pathogenesis of chronic
inflammatory diseases and cancer; thus, we aimed to
analyze the expression of Tie2 and Angs throughout
monocyte differentiation and maturation. Such
approach pointed out to the sustained expression of
Ang2 by macrophages and dendritic cells derived from
CHC monocytes, which additionally resulted poorly dif-
RESEARCH INTEREST
During last years our research group has been particularly focused on identifying useful non invasive prognostic biomarkers of chronic hepatitis C (CHC) progression to cirrhosis and hepatocellular carcinoma
(HCC).
The infection by hepatitis C virus often becomes chronic
due to the inefficacy of immune system to eradicate the
virus; consequently, the inflammatory response is continuously stimulated, altering the self-limiting nature of tissue
repairing mechanisms. Therefore, the expression of multiple angiogenic and fibrogenic-related factors is deeply
modified, behaving as useful markers of disease evolution.
– 64 –
Intrahepatic identification of TEMs in livers from CHC patients.
Immunofluorescence experiments were performed on cryostat
sections from CHC liver biopsies. Image acquisition of single fluorescence identified in the same section CD14, CD31 and Tie-2 (AC and E-G, respectively) of different representative CHC patients.
Their combined immunofluorescences are also shown (D & H).
Tie-2 expression was observed surrounding the hepatic infiltrates, in which TEMs could be distinguished (A-D, arrows). Intrahepatic Tie-2 expressing cells were frequently associated with endothelial CD31 positive cells (E-H). Original magnifications: x400.
Left bottom squares denote amplified sections.
AREA 1
ferentiated, in contrast to healthy subjects (Figure 2).
These findings might highlight the relevant role of the
Angiopoietin/Tie-2 system on the regulation of inflammatory response during the progression of chronic diseases throughout its influence on functionality of antigen presenting cells.
• Proyecto Coordinado. Estimulación pan-poblacional
de la respuesta de los linfocitos T frente a epítopos
CD8 conservados del virus de la hepatitis C.
MICINN. SAF 2009/08103. Duration: 2009 - 2012.
• Ricardo Moreno Otero. Implicación de polimorfismos
genéticos de factores angiogénicos en la etiopatogenia de la hepatitis crónica C y su evolución a carcinoma hepatocelular. Fundación Mutua Madrileña.
Duration: 2010 - 2013.
• Ricardo Moreno Otero. Implicación del Sistema
Angiopoyetinas/Tie2 en los procesos angiogénicos y
fibrogénicos asociados a la hepatitis crónica C.
MEC. SAF2010-21805. Duration: 2010 - 2013.
Tie2 and angiopoietins 1 and 2 expression in peripheral blood monocytes and Mo-DCs from healthy volunteers and CHC patients.
Points represent the median fold-induction of Tie2-expressing cells
(A and B) and the median concentrations of Ang1, Ang2 and
Ang2/Ang1 ratio (C-H) in the supernatants of peripheral blood monocytes, MDDCs (A, C, E, & G) and MDMs (B, D, F and H) from CHC patients (black line) and controls (grey line). The concentration of
Ang1 was lower in monocytes and mature MDDDs supernatants
from CHC patients (C, p<0.001 and D, p<0.05). Ang2 levels notably
fell after differentiation of control monocytes to MDDC and MDM
(p<0.001, both) but persisted during the differentiation of CHC cells
(E & F). Thus, Ang2 release was significantly higher in the supernatants from immature MDDCs, mature MDDCs (p <0.05 and p <0.01,
respectively, E), and MDMs (p <0.05, F) of CHC patients compared
with controls. Ang2/Ang1 values in supernatants of CHC mature
MDDCs and MDMs were quite similar to those of CHC monocytes (G
& H). Statistical significance was calculated by Mann-Whitney test,
represented as # p< 0.05 or ## p< 0.01 and *p< 0.05 or ***p< 0.001,
where # represents CHC versus controls and * shows statistical significance during differentiation/maturation.
YEAR
Total IF
Publication No.
Q1
Q2
2010
82,467
16
10
4
2011
66,493
18
8
6
2012
23,378
9
2
2
Santander C, Moreno-Otero R. Commentary:
ursodeoxycholic acid as chemoprevention in inflammatory bowel disease and primary sclerosing cholangitis.
Aliment Pharmacol Ther 35(7):846-846. 2012. PMID:
22404405. IF: 3,769. DOI: 10.1111/j.13652036.2012.05019.x
Casals-Seoane F, Arberas-Diez B, Moreno-Otero R.
Letter: acute hepatitis B - to treat or not to treat?.
22650494. IF: 3,769. DOI: 10.1111/j.13652036.2012.05123.x
– 65 –
MAJOR GRANTS
Moreno-Otero R, García-Buey L, Trapero-Marugán M.
Safety of methotrexate for inflammatory bowel disease.
Dig Liver Dis 44(8):706-707. 2012. PMID: 22538205.
IF: 3,054. DOI: 10.1016/j.dld.2012.03.012
Moreno-Otero R, Trapero-Marugan M. Antioxidant
agents in the prevention of hepatocellular carcinoma.
Eur J Cancer Prev 21(4):323-5. 2012. PMID:
22044850. IF: 2,13. DOI: 10.1097/CEJ.0b013e32834
dbc6d
Rodziewicz M, Moreno-Otero R. Role of percutaneous
liver biopsy. Hepat Mon 12(4):294-295. 2012. PMID:
22690239. IF: 2,19. DOI: 10.5812/hepatmon.854
Miranda-García P, López-Martín MC, Alvarez-Malé T,
Casanova-González MJ, Santander C, Bañares R,
Moreno-Otero R, Trapero-Marugán M. Idiopathic portal
hypertension complicated by ischemic hepatitis: the
diagnostic importance of hemodynamics and liver
biopsy. Rev Esp Enferm Dig 104(1):45-47. 2012.
PMID: 22300122. IF: 1,548
Benedicto I, Molina-Jiménez F, García-Buey L, Gondar
V, López-Cabrera M, Moreno-Otero R, Majano PL. Role
of tight junctions in hepatitis C virus infection. Rev Esp
Enferm Dig 104(5):255-263. 2012. PMID: 22662778.
IF: 1,548
Barbero-Villares A, Mendoza J, Taxonera C, LópezSanromán A, Pajares R, Bermejo F, Pérez-Calle J,
Mendoza J, Algaba A, Moreno-Otero R, Maté J,
Gisbert J. Evaluation of liver fibrosis by transient elastography (Fibroscan®) in patients with inflammatory
bowel disease treated with methotrexate: a multicentric
trial. Scand J Gastroenterol 47(5):575-579. 2012.
PMID: 22229701. IF: 2,019. DOI: 10.3109/00365521.
2011.647412
Molina-Jimenez F, Benedicto I, Dao Thi VL, Gondar V,
Lavillette D, Marin JJ, Briz O, Moreno-Otero R, Aldabe
R, Baumert TF, Cosset FL, Lopez-Cabrera M, Majano
PL. Matrigel-embedded 3D culture of Huh-7 cells as a
hepatocyte-like polarized system to study hepatitis C
virus cycle. Virology 425(1):31-39. 2012. PMID:
22280897. IF: 3,351. DOI: 10.1016/j.virol.2011.12.021
– 66 –
BOOKS
Moreno-Otero R. Patogénesis de las hepatitis crónicas víricas. Hepatitis Víricas. 2012. Juan GonzálezLahoz y Vicente Soriano.
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: GARCIA BUEY, LUISACONSUELO
Estudio observacional retrospectivo para evaluar la
eficacia y la seguridad a largo plazo de la monoterapia con entecavir en la práctica clínica habitual en
pacientes con Hepatitis B Crónica naive al tratamiento con análogos de núcleos(T)Idos. Estudio Oriente 2;
(versión 1:08-03-12). FUNDACIO DE LLUITA CONTRA LA SIDA-UNIDAD VIH. FLS-ENT-2012-01
GROUP 24
HEAD OF LABORATORY
Pedro Lorenzo Majano Rodríguez
GROUP MEMBERS
• Ignacio Benedicto Español
• Francisca Molina Jiménez
• Virgínia Manuela Gondar de Sousa e Silva
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-alpha in combination with ribavirina, is frequently not
effective depending on both viral and host factors.
AREA 1
These three dimensional cultures supported the entire HCV
infection cycle and produced infective viral particles. In
overall, these studies may provide new insights for our
understanding of virus-host interactions and the molecular
mechanisms underlying hepatotropic viruses-related
pathogenesis of progressive liver disease.
MAJOR GRANTS
Human hepatocyte-derived cells (Huh7) stably transfected with
MAV-GFP protein. Cells were infected with HCVcc. MAV-GFP protein (green): nuclei stained with DAPI (blue). Nuvlear translocation of protein indicates viral infection.
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, replication, morphogenesis and egress.
Our studies have demonstrated that HCV promotes structural and functional alterations of intercellular junctions and
that occludin, a tigh junction associated protein, plays an
essential role in HCV infection. We have also described a
novel use of Matrigel-embedded hepatocytes cultures to
study the HCV infection in a more polaryzed context.
YEAR
Total IF
Publication No.
Q1
2010
23,67
3
3
Q2
2011
12,134
2
1
1
2012
16,724
5
3
1
García-Mediavilla MV, Pisonero-Vaquero S, LimaCabello E, Benedicto I, Majano PL, Jorquera F,
González-Gallego J, Sánchez-Campos S. Liver X
receptor -mediated regulation of lipogenesis by core
and NS5A proteins contributes to HCV-induced liver
steatosis and HCV replication. Laboratory Investigation
92(8):1191-1202. 2012. PMID: 22641099. IF: 3,641.
DOI: 10.1038/labinvest.2012.88
Martin Caballero J, Garzón A, González-Cintado L,
Kowalczyk W, Jimenez Torres I, Calderita G, Rodriguez
M, Gondar V, Bernal JJ, Ardavín C, Andreu D, Zürcher
– 67 –
Immunohistochemical detection of MRP2 in liver sections. An intense immunoreactivity to MRP2 (brown) was observed within
the canalicular membrane of the hepatocytes.
• Pedro Lorenzo Majano Rodríguez. Estudio de la
interrelación entre la polaridad celular y la infección
por el virus de la hepatitis C: Posible implicación en
el hepatocarcinoma. ISCIII. PI10/00101. Duration:
2011 - 2013.
• Pedro Lorenzo Majano Rodríguez. Papel en el
hepatocarcinoma de la alteración en las uniones
intercelulares provocadas por la infección por el
virus hepatitis c. Fundación Mutua Madrileña. VIII
Convocatoria de Becas y Ayudas a la Investigación
Médica de la Fundación Mutua Madrileña. Duration:
2011 - 2013.
T, von Kobbe C. Chimeric infectious bursal disease
virus-like particles as potent vaccines for eradication of
established HPV-16 E7-dependent tumors. PLoS One
7(12):e52976. 2012. PMID: 23300838. IF: 4,092. DOI:
10.1371/journal.pone.0052976
Benedicto I, Molina-Jiménez F, García-Buey L, Gondar
V, López-Cabrera M, Moreno-Otero R, Majano PL. Role
of tight junctions in hepatitis C virus infection. Rev Esp
Enferm Dig 104(5):255-263. 2012. PMID: 22662778.
IF: 1,548
Strippoli R, Benedicto I, Perez Lozano ML, Pellinen T,
Sandoval P, Lopez-Cabrera M, del Pozo MA. Inhibition
of transforming growth factor-activated kinase 1 (TAK1)
blocks and reverses epithelial to mesenchymal transition of mesothelial cells. PLoS One 7(2):e31492. 2012.
PMID: 22384029. IF: 4,092. DOI: 10.1371/journal.pone.0031492
Molina-Jimenez F, Benedicto I, Dao Thi VL, Gondar V,
Lavillette D, Marin JJ, Briz O, Moreno-Otero R, Aldabe
R, Baumert TF, Cosset FL, Lopez-Cabrera M, Majano
PL. Matrigel-embedded 3D culture of Huh-7 cells as a
hepatocyte-like polarized system to study hepatitis C
virus cycle. Virology 425(1):31-39. 2012. PMID:
22280897. IF: 3,351. DOI: 10.1016/j.virol.2011.12.021
– 68 –
AREA 1
Line 1.9
Mechanisms and
mediators of endocrine
diseases
GROUP 25
GROUP MEMBERS
• Manuel Luque Ramírez
• Susanna Leskelä
• Ana Rodríguez Muñoz
• Javier Riveiro Villanueva
• Ana Serrano Somavilla
RESEARCH INTEREST
Our current and future work involves different
research fields in endocrine diseases.
First, we are studying the role of (tolerogenic) dendritic cells (DCs) in patients with autoimmune thyroid
diseases
(AITD)
including
primarily
Hashimoto’s thyroiditis (HT) and Graves’ disease
(GD). During last year, we have discovered that
patients with AITD have diminished levels of plasmacytoid DCs in their peripheral blood and these
cells show both an enhanced production of IFNand defective expression of different immunoregulatory receptors. This abnormal proportion and
phenotype of pDCs may contribute to the pathogenesis of AITD.
In the course of 2012, we have initiated new projects in this field, One aiming to characterize the
regulatory T cells and the other the role of
galectins, both in AITD and healthy controls.
Quantitative and phenotypic analysis of pDCs in thyroid tissue
from patients with AITD. A-E) Hematopoeitic mononuclear cells
were isolated from thyroid tissue (TMC) and blood samples
(PBMC) of five patients with HT (black) and five with GD (red,
dashed line). The percent of pDCs (A) or the MFI values of the
expression of the indicated immunoregulatory receptors (B-E)
was determined by multiparametric flow cytometry analysis.
Results from Paired t-tests, *p<0.05. F) Immunofluorescence
analysis of CD123+ (pDCs, red fluorescence) cells expressing
ILT2 (F) or PSGL-1 (G) (green fluorescence) in thyroid tissue
sections from a representative patient with HT. Cell nuclei were
stained with the Hoechst 33342 dye (blue fluorescence). Original magnification x400.
Another area of investigation is the process of
angiogenesis in neuroendocrine gastroentero-pancreatic tumors (TNE-GP) and their relation to the
somatostatin receptors. We are studying the role of
angiopoietins-1 and -2 and their receptor Tie-2 in
the tumoral 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 tumors, especially those related
to treatment response with the GH antagonist pegvisomant. These studies will include techniques of
molecular biology, including their characterization
through qRT-PCR, genotyping and sequencing with
association studies with the clinical data available.
– 69 –
HEAD OF LABORATORY
Mónica Marazuela Azpíroz
ción con células T reguladoras y linfocitos Th17
en pacientes con enfermedad tiroidea autoinmune. ISCIII. PI 10-2521. Duration: 2011 - 2013.
PUBLICATIONS
(3)
[IF: 13,15]
YEAR
Total IF
Publication No.
Q1
Q2
2010
33,692
6
5
1
2011
14,934
4
1
2
2012
13,15
3
1
1
Escobar-Morreale HF, Samino S, Insenser M,
Vinaixa M, Luque-Ramírez M, Lasunción MA,
Correig X. Metabolic heterogeneity in polycystic
ovary syndrome is determined by obesity: plasma
metabolomic approach using GC-MS. Clin Chem.
58(6):999-1009. 2012. PMID: 22427353. IF: 7,905.
DOI: 10.1373/clinchem.2011.176396
% IGF-I evolution (a) and percentage of change of IGF-I level (b)
during combination therapy with pegvisomant and cabergoline
for each individual patient (Female: blue dot lines and blue bars;
Male: brown lines and bars).
Dr. M. Luque-Ramirez has been studying the role of
different inflammatory markers in hyperandrogenic
disorders in women, in particular in polycystic ovary
syndrome.
MAJOR GRANTS
• Mónica Marazuela Azpíroz. Pilot study of the
influence of truncated GH receptor isoforms,
related to polymorphisms in exon 9 on GHR, on
clinical expressivity and on response to pegvisomant treatment in acromegaly. Laboratorios
Pfizer S.L.U. Duration: 2010 - 2012.
• Mónica Marazuela Azpíroz. Estudio del potencial
tolerogénico de células dendríticas y su interac-
– 70 –
Roset M, Merino-Montero S, Luque-Ramírez M,
Webb SM, López-Mondéjar P, Salinas I, Soto A,
Bernal C, Villabona C, De Luis D, Donnay S,
Pascual H, Pérez-Luis J; Spanish group of the
OASIS study. Cost of clinical management of
acromegaly in Spain. Clin Drug Investig. 32(4):23545. 2012. PMID: 22397307. IF: 1,822. DOI:
10.2165/11599680-000000000-00000
Oriola J, Lucas T, Halperin I, Mora M, Perales MJ,
Alvarez-Escolá C, Paz de MN, Díaz Soto G, Salinas
I, Julián MT, Olaizola I, Bernabeu I, Marazuela M,
Puig-Domingo M. Germline mutations of AIP gene
in somatotropinomas resistant to somatostatin
analogues. Eur J Endocrinol. 168(1):9-13. 2012.
PMID: 23038625. IF: 3,423. DOI: 10.1530/EJE-120457
CLINICAL TRIALS
PRINCIPAL
INVESTIGATOR:
MARAZUELA
AZPIROZ, MONICA
Caracterización de la expresión génica en tumores
AREA 1
ESPAÑOL DE TUMORES NEUROENDOCRINOS
(GETNE).
GETNE1105_GENEX
neuroendocrinos gastro-enteropancreáticos y su
correlación con aspectos clínicos y de comportamiento del tumor; (versión 2: 7-06-12). GRUPO
– 71 –
Line 1.10
Children´s development
(obesity and growth)
GROUP 26
HEAD OF LABORATORY
Jesús Argente Oliver
GROUP MEMBERS
• Julie Ann Chowen King
• Vicente Barrios Sabador
• Laura María Frago Fernández
• Gabriel Ángel Martos Moreno
• Oscar Rubio Cabezas
• Jesús Pozo Román
• María Teresa Muñoz Calvo
• Emma Burgos Ramos
• Silvia Tapia González
• Eva Baquedano Caballero
• Esther de la Fuente Martín
• Cristina García Cáceres
• Pilar Argente Arizón
• David Castro González
• Sandra Canelles Ortiz
• Francisca Díaz 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
new 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 geno-
– 72 –
Effects of maternal diet on glial coverage and glucose sensitivity of proopiomelanocortin (POMC) neurons in the hypothalamic arcuate nucleus. Electron micrographs showing astroglial
coverage (in green) of POMC neurons from male mice born to
mothers on A)a control diet or B)high fat diet (HFD). Offspring of
HFD mothers have a higher percentage of somal membrane
ensheathed by astrocytes (C). The frequency of resting mIPSCs
was significantly decreased with no change in mEPSC frequency in HFD offspring. D) The response to changes in glucose
concentration was also modified in HFD offspring, with a reduction in the concentration of glucose decreasing action potential frequency in POMC neurons. *p<0.05, **p<0.001, ***
p<0.0001. (Fuente-Martín et al., JCI, 2012).
type/phenotype and ethnic influences. Metabolomic
studies are underway to better understand the
processes involved in the development of insulin resistance and type 2 diabetes.
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, inflammation and energy homeostasis. Hypothalamic glial
cells are a main focus of investigation for their important
AREA 1
• Jesús Argente Oliver. Fisiopatología de la Obesidad.
ISCIII. CIBER: CB06/03/0022. Duration: 2006 indefinido.
• Jesús Argente Oliver. Obesidad infantil grave de
comienzo precoz: fundamentos metabólicos, genéticos y proteomicos. ISCIII. PI10/00747. Duration:
2011 - 2013.
• Julie Ann Chowen King. Regulación de los astrocitos
hipotalámicos por la leptina: implicaciones en el control metabólico sistémico. MICINN. BFU2011-27492.
Duration: 2012 - 2014.
The metabolic hormone leptin directly modifies glutamate and
glucose uptake in hypothalamic astrocytes. A) Levels of the
glutamate trasporter GLAST in primary hypothalamic astrocyte
cultures treated with saline (control) or leptin (Lep, 100 ng/ml)
for 1 or 24 hours. B) Glutamate uptake in response to leptin at
30 min and 24 hours. C) Leptin modifies the levels of glucose
transporter (GLUT)-2 in hypothalamic astrocytes and D) glucose up-take. (Fuente-Martín et al., JCI, 2012). # p<0.0005.
role in metabolic control. We have recently shown them
to respond to dietary changes and metabolic hormones, both pre and postnatally, and that astrocytes
are most likely involved in controlling metabolic neuronal function (Fig. 1 & 2).
MAJOR GRANTS
• Vicente Barrios Sabador. Red de centros de Genética
clínica y molecular. Integración de la investigación clínica, molecular y epidemiológica en Genética humana.
ISCIII. C03/07. Duration: 2002 - Actualidad.
YEAR
Total IF
Publication No.
Q1
Q2
2010
83,646
21
10
9
2011
57,965
16
7
4
2012
90,732
22
12
9
Fuente-Martín E, García-Cáceres C, Granado M,
Sánchez-Garrido MA, Tena-Sempere M, Frago LM,
Argente J, Chowen JA. Early postnatal overnutrition
increases adipose tissue accrual in response to a
sucrose-enriched diet. Am J Physiol Endocrinol
Metab. 302(12):E1586-E1598. 2012. PMID:
22510708. IF: 4,746. DOI: 10.1152/ajpendo.00618.2011
Bang P, Ahmed SF, Argente J, Backeljauw P,
Bettendorf M, Bona G, Coutant R, Rosenfeld RG,
Walenkamp MJ, Savage MO. Identification and management of poor response to growth-promoting therapy in children with short stature. Clin Endocrinol
(Oxf). 77(2):169-181. 2012. PMID: 22540980. IF:
3,168. DOI: 10.1111/j.1365-2265.2012.04420.x
Stucchi P, Gil-Ortega M, Merino B, Guzmán-Ruiz R,
Cano V, Valladolid-Acebes I, Somoza B, Le Gonidec
S, Argente J, Valet P, Chowen JA, Fernández-Alfonso
M, Ruiz-Gayo M. Circadian Feeding Drive of
Metabolic Activity in Adipose Tissue and not
Hyperphagia Triggers Overweight in Mice: Is There a
Role of the Pentose-Phosphate Pathway?.
Endocrinology 153(2):690-9. Epub 2011 Dec 6. 2012.
– 73 –
PMID: 22147018. IF: 4,459. DOI: 10.1210/en.20111023
Burgos-Ramos E, González-Rodríguez A, Canelles S,
Baquedano E, Frago LM, Revuelta-Cervantes J,
Gómez-Ambrosi J, Frühbeck G, Chowen JA, Argente J,
Valverde AM, Barrios V. Differential Insulin Receptor
Substrate-1 (IRS1)-Related Modulation of Neuropeptide
Y and Proopiomelanocortin Expression in Nondiabetic
and Diabetic IRS2-/- Mice. Endocrinology 153(3):112940. Epub 2011 Dec 30. 2012. PMID: 22210743. IF:
4,459. DOI: 10.1210/en.2011-1278
Fraser CS, Rubio-Cabezas O, Littlechild JA, Ellard S,
Hattersley AT, Flanagan SE. Amino acid properties
may be useful in predicting clinical outcome in
patients with Kir6.2 neonatal diabetes. Eur J
Endocrinol 167(3):417-421. 2012. PMID: 22648966.
IF: 3,423. DOI: 10.1530/EJE-12-0227
Coutant R, Dörr HG, Gleeson H, Argente J.
Limitations of the IGF-I generation test in children with
short stature. Eur J Endocrinol. 166(3):351-7. Epub
2011 Nov 2. 2012. PMID: 22048966. IF: 3,423. DOI:
10.1530/EJE-11-0618
Linglart A, Fryssira H, Hiort O, Holterhus PM, Perez
de Nanclares G, Argente J, Heinrichs C, Kuechler A,
Mantovani G, Leheup B, Wicart P, Chassot V,
Schmidt D, Rubio-Cabezas Ó, Richter-Unruh A,
Berrade S, Pereda A, Boros E, Muñoz-Calvo MT,
Castori M, Gunes Y, Bertrand G, Bougnères P,
Clauser E, Silve C. PRKAR1A and PDE4D mutations
cause acrodysostosis but two distinct syndromes
with or witho ut GPCR-signaling hormone resistance.
J Clin Endocrinol Metab 97(12):2328-2338. 2012.
PMID: 23043190. IF: 5,967. DOI: 10.1210/jc.20122326
Perez-Nanclares G, Romanelli V, Mayo S, Garin I,
Zazo C, Fernandez-Rebollo E, Martínez F, Lapunzina
P, de Nanclares GP; Spanish PHP Group. Detection
of hypomethylation syndrome among patients with
epigenetic alterations at the GNAS locus. J Clin
Endocrinol Metab. 97(6):E1060-1067. 2012. PMID:
22492776. IF: 5,967. DOI: 10.1210/jc.2012-1081
– 74 –
Mela V, Díaz F, Gertler A, Solomon G, Argente J,
Viveros MP, Chowen JA. Neonatal treatment with a
pegylated leptin antagonist has a sexually dimorphic
effect on hypothalamic trophic factors and neuropeptide levels. J Neuroendocrinol 24(5):756-765. 2012.
PMID: 22236109. IF: 3,138. DOI: 10.1111/j.13652826.2012.02279.x
Fuente-Martín E, García-Cáceres C, Granado M, de
Ceballos ML, Sánchez-Garrido MA, Sarman B, Liu ZW, Dietrich MO, Tena-Sempere M, Argente-Arizón P,
Diaz F, Argente J, Horvath TL, Chowen JA. Leptin
regulates glutamate and glucose transporters in
hypothalamic
astrocytes.
J.
Clin.
Invest.
122(11):3900-13. 2012. PMID: 23064363. IF: 13,069.
DOI: 10.1172/JCI64102
Burgos-Ramos E, Sackmann-Sala L, Baquedano E,
Cruz-Topete D, Barrios V, Argente J, Kopchick JJ.
Central leptin and insulin administration modulates
serum cytokine- and lipoprotein-related markers.
Metabolism 61(11):1646-57. 2012. PMID: 22658937.
IF: 2,664. DOI: 10.1016/j.metabol.2012.05.001
Fuente-Martín E, Granado M, García-Cáceres C,
Sanchez-Garrido MA, Frago LM, Tena-Sempere M,
Argente J, Chowen JA. Early nutritional changes induce
sexually dimorphic long-term effects on body weight
gain and the response to sucrose intake in adult rats.
Metabolism 61(6):812-822. 2012. PMID: 22209665. IF:
2,664. DOI: 10.1016/j.metabol.2011.11.003
Perianes-Cachero A, Burgos-Ramos E, PueblaJiménez L, Canelles S, Viveros MP, Mela V, Chowen
JA, Argente J, Arilla-Ferreiro E, Barrios V. Leptininduced downregulation of the rat hippocampal
somatostatinergic system may potentiate its anorexigenic effects. Neurochem Int. 61(8):1385-96. 2012.
PMID:
23073237.
IF:
2,857.
DOI:
10.1016/j.neuint.2012.09.019
Granado M, Fuente-Martín E, García-Cáceres C,
Argente J, Chowen JA. Leptin in early life: a key factor for the development of the adult metabolic profile.
Obes Facts 5(1):138-150. 2012. PMID: 22433625. IF:
1,856. DOI: 10.1159/000336967
AREA 1
Rachmiel M, Rubio-Cabezas O, Ellard S, Hattersley
AT, Perlman K. Early-onset, severe lipoatrophy in a
patient with permanent neonatal diabetes mellitus
secondary to a recessive mutation in the INS gene.
Pediatr Diabetes 13(6):26-29. 2012. PMID:
21910811. IF: 2,16. DOI: 10.1111/j.13995448.2011.00809.x
García-Herrero CM, Rubio-Cabezas O, Azriel S,
Gutierrez-Nogués A, Aragonés A, Vincent O,
Campos-Barros A, Argente J, Navas MA. Functional
characterization of MODY2 mutations highlights the
importance of the fine-tuning of glucokinase and its
role in glucose sensing. PLoS One 7(1):e30518.
Burgos-Ramos E, Canelles S, Perianes-Cachero A,
Arilla E, Argente J, Barrios V. Adipose tissue promotes
a serum cytokine profile related to lower insulin sensitivity after chronic central infusion. Plos One
7(10):e46893. 2012. PMID: 23056516. IF: 4,092.
23251400. IF: 4,092. DOI: 10.1371/journal.pone.
0050894
Fernández O, Agüera E, Izquierdo G, Millán-Pascual
J, Ramió I Torrentà L, Oliva P, Argente J, Berdei Y,
Soler JM, Carmona O, Errea JM, Farrés J; Group on
Adherence to IFNb-1b in Spain. Adherence to interferon -1b treatment in patients with multiple sclerosis in Spain. PLoS One 7(5):e35600. 2012. PMID:
0035600
Sáinz N, Rodríguez A, Catalán V, Becerril S, Ramírez
B, Lancha A, Burgos-Ramos E, Gómez-Ambrosi J,
Frühbeck G. Leptin reduces the expression and
increases the phosphorylation of the negative regulators of GLUT4 traffic TBC1D1 and TBC1D4 in muscle
of ob/ob mice. PLoS One. 7(1):e29389. 2012. PMID:
22253718. IF: 4,092. DOI: 10.1371/journal.
pone.0029389
Mela V, Llorente-Berzal A, Díaz F, Argente J, Viveros
MP, Chowen JA. Maternal deprivation exacerbates
the response to a high fat diet in a sexually dimorphic
manner. PLOS One. 7(11):e48915. 2012. PMID:
23145019. IF: 4,092. DOI: 10.1371/journal.
pone.0048915
BOOKS
Granell S, Serra-Juhé C, Martos-Moreno GÁ, Díaz F,
Pérez-Jurado LA, Baldini G, Argente J. A novel
melanocortin-4 receptor mutation MC4R-P272L
associated with severe obesity has increased propensity to be ubiquitinated in the ER in the face of correct
folding. PLoS One 7(12):e50894. 2012. PMID:
Burgos-Ramos E, Martos-Moreno GA, Argente J,
Barrios V. Multiplexed bead immunoassays: advantages and limitations in Pediatrics. Advances in
Immunoassay Technology. 2012. ISBN: 978-95351-0440-7.
– 75 –
Rubio-Cabezas O, Flanagan SE, Damhuis A,
Hattersley AT, Ellard S. KATP channel mutations in
infants with permanent diabetes diagnosed after 6
months of life. Pediatr Diabetes 13(4):315-18. 2012.
PMID: 21981029. IF: 2,16. DOI: 10.1111/j.13995448.2011.00824.x
Line 1.11
Metabolic syndrome
and vascular risk
receptor subtype agonists on endothelial vasodilation in
human microvessels. Exp Gerontol. 47(9):734-40. 2012.
PMID: 22776133. IF: 3,741. DOI: 10.1016/j.exger.2012
06.014
Kozakova M, Palombo C, Eng MP, Dekker J, Flyvbjerg A,
Mitrakou A, Gastaldelli A, Ferrannini E; RISC Investigators (..,
Carraro R, Friera A, Novella B, ..). Fatty liver index, gammaglutamyltransferase, and early carotid plaques. Hepatology.
55(5):1406-15. 2012. PMID: 22334565. IF: 11,665. DOI:
10.1002/hep.25555
GROUP 27
HEAD OF LABORATORY
Raffaele Carraro
Astrup A, Carraro R, Finer N, Harper A, Kunesova M,
Lean ME, Niskanen L, Rasmussen MF, Rissanen A,
Rössner S, Savolainen MJ, Van Gaal L. Safety, tolerability and sustained weight loss over 2 years with the
once-daily human GLP-1 analog, liraglutide. Int J Obes
(Lond). 36(6):890. 2012. PMID: 21844879. IF: 4,691.
DOI: 10.1038/ijo.2011.158
GROUP MEMBERS
• María Concepción Peiró Vallejo
• Carlos Félix Sánchez Ferrer
• Isabelle Sharmiashvili
• Andrea Azcárate Villalón
• Iñigo Tejado Elviro
• Tania del Mar Romacho Romero
• Marta Vázquez Bella
• Laura Alicia Villalobos Rodríguez
• Erika Palacios Rosas
• Elena Cercas Alonso
• Lourdes Martínez-Piñeiro Muñoz
Handberg A, Højlund K, Gastaldelli A, Flyvbjerg A, Dekker
JM, Petrie J, Piatti P, Beck-Nielsen H; RISC Investigators (..,
Carraro R, Friera A, Novella B, ..). Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and
fatty liver in a nondiabetic healthy population. J Intern Med.
271(3):294-304. 2012. PMID: 21883535. IF: 5,483. DOI:
10.1111/j.1365-2796.2011.02442.x
MAJOR GRANTS
Carmelo García Monzón. Análisis comparativo de los mediadores moleculares relacionados con el síndrome metabólico en pacientes con enfermedad hepática grasa no alcohólica y en pacientes con hepatitis crónica C. ISCIII.
PI10/00067
Bobbioni-Harsch E, Pataky Z, Makoundou V, Laville M,
Disse E, Anderwald C, Konrad T, Golay A; RISC
Investigators(.., Carraro R, Friera A, Novella B,..). From
metabolic normality to cardiometabolic risk factors in
subjects with obesity. Obesity (Silver Spring).
20(10):2063-9. 2012. PMID: 22421925. IF: 4,284.
DOI: 10.1038/oby.2012.692011. PMID: 20888662. IF:
9,334
YEAR
Total IF
Publication No.
Q1
2010
36,377
6
6
2011
39,347
7
5
2012
29,864
5
5
Q2
2
Angulo J, Vallejo S, El Assar M, García-Septiem J, SánchezFerrer CF, Rodríguez-Mañas L. Age-related differences in
the effects of and peroxisome proliferator-activated
– 76 –
GROUP 5
HEAD OF LABORATORY
Carmelo García Monzón
AREA 1
GROUP MEMBERS
• Rodolfo Javier Vargas Castrillón
• Alicia Sáez Sáez
• María Eugenia Miquilena Colina
• Faustino Manuel La Banda Brusi
• Enrique Chávez Jiménez
• Javier Rodríguez de Cía
RESEARCH INTEREST
Triglyceride accumulation in nonalcoholic fatty liver
(NAFL) results from unbalanced lipid metabolism
which, in the liver, is controlled by several transcription factors, such as the Foxa subfamily. In the
mouse liver, unlike Foxa2, the role of Foxa1 has not
yet been investigated in detail. Therefore, we wanted
to evaluate the role of Foxa1 in two human liver cell
models, primary cultured hepatocytes and HepG2
cells, by adenoviral infection. Moreover, human and
rat livers were analyzed to determine Foxa1 regulation in NAFL. Our findings demonstrated that Foxa1
is a potent inhibitor of hepatic triglyceride synthesis,
accumulation and secretion by repressing the
expression of multiple target genes of these pathways. Moreover, Foxa1 repressed the fatty acid
transporter protein FATP2 and lowered fatty acid
uptake. We also found that human and rat NAFL
have a reduced Foxa1 expression, possibly through a
Analysis of autophagy levels in liver biopsies of HCV patients.
(A) Immunoblotting analysis of total protein extracts from liver
biopsies of HCV patients using an anti-LC3 antibody. (B) Signal
intensities of LC3-I and -II bands have been measured and used
for the correlation analysis with microvesicular steatosis and
other clinical parameters (see table 1). Glyceraldehyde-3phosphate dehydrogenase (GAPDH) was analyzed as a protein
loading control.
protein kinase C-dependent pathway. The results of
our work (2) demonstrate that Foxa1 is an antisteatotic factor that coordinately tunes several lipid
metabolic pathways to block triglyceride accumulation in hepatocytes.
Evidence links increased hepatic fatty acid translocase (FAT)/CD36 protein amount and gene expression with hyperinsulinemia in animal models and
patients with fatty liver, but whether insulin regulates
FAT/CD36 expression, amount, distribution, and
function in hepatocytes is currently unknown. To
investigate this, FAT/CD36 protein content and FA
uptake was analyzed in isolated hepatocytes from
obese and lean Zucker rats. We found that
FAT/CD36 protein amount at the plasma membrane
(PM) was higher in hepatocytes from obese rats than
from lean controls. Interestingly, increased amount of
FAT/CD36 protein at the PM and enhanced FA
uptake of obese Zucker rat hepatocytes were maintained only when exposed to hyperinsulinemic conditions. Thus, we showed in this work (3) that high
insulin levels are required for FAT/CD36 translocation
– 77 –
Despite the growing number of studies linking nonalcoholic fatty liver disease (NAFLD) with altered serum
metabolite levels, an obstacle to the development of
metabolome-based NAFLD predictors has been the
lack of large cohort data from biopsy-proven patients
matched for key metabolic features such as obesity.
In order to shed light on this matter, we studied 467
biopsied individuals with normal liver histology or
diagnosed with NAFLD. We showed in this study (1)
that body mass index-dependent serum metabolic
profile may be able to reliably distinguish nonalcoholic steatohepatitis (NASH) from simple steatosis
patients, and could have significant implications for
the development of NASH biomarkers and potential
novel targets for therapeutic intervention.
otic cells, occur during infection of cells with hepatitis C
virus (HCV), but the clinical relevance of this process is
not clear. In order to gain insight on this issue, levels of
autophagy were analyzed in liver biopsy samples from
patients with HCV infection. We found that there was an
inverse correlation between microvesicular steatosis
and level of autophagy. In addition, we observed that
HCV selectively induced autophagy of lipids in virusinfected and replicon cells as well as autophagosomes
frequently colocalized with lipid deposits, mainly formed
by unesterified cholesterol. Interestingly, inhibition of the
autophagic process in these cells significantly increased
the induction of cholesterol accumulation by HCV. The
findings of our work (4) indicate that autophagy counteracts the alterations in lipid metabolism induced by HCV,
suggesting that disruption of the autophagic process
might contribute to development of steatosis in patients
with HCV.
MAJOR GRANTS
Cholesterol synthesis is required for autophagy induction in
hCV replicon cells. (A) Reduced LC3 cleavage in mevastatintreated HCV replicon cells. Protein extracts were prepared from
HuH7 and Rep Blast cells treated with mevastatin for 36 h and
subjected to immunoblotting to determine LC3 and nonstructural protein 5A (NS5A) protein levels. Tubulin was used as a protein loading control. (B) Reduced number of autophagosomes
in mevastatin-treated cells. GFP-LC3-expressing Rep Blast
cells were treated with mevastatin for 36 h, fixed, and stained
with Filipin (blue signal). Scale bar=10 um.
to the PM in obese rat hepatocytes to enhance FA
uptake and triglyceride synthesis.
• Carmelo García Monzón. Análisis comparativo de
los mediadores moleculares relacionados con el
síndrome metabólico en pacientes con enfermedad hepática grasa no alcohólica y en
pacientes con hepatitis crónica C. ISCIII.
PI10/00067. Duration: 2011 - 2013.
• Carmelo García Monzón. Valor de la determinación sérica de la fracción soluble de la ácido
graso translocasa CD36 (FAT/CD36) para el diagnóstico no invasivo de la enfermedad hepática
grasa no alcohólica: Papel de la insulina en la regulación de la expresión y función de FAT/CD36 en
el hepatocito humano. Fundación Mutua
Madrileña. Duration: 2012 - 2013.
YEAR
On the other hand, high levels of autophagy, a lysosome-mediated catabolic process that mediates degradation and recycling of all major components of eukary-
– 78 –
Total IF
Publication No.
Q1
2010
6,115
1
1
2011
23,692
3
3
2012
25,626
4
4
Q2
AREA 1
Buqué X, Cano A, Miquilena-Colina ME, GarcíaMonzón C, Ochoa B, Aspichueta P. High insulin levels are required for FAT/CD36 plasma membrane
translocation and enhanced fatty acid uptake in
obese Zucker rat hepatocytes. Am J Physiol
Endocrinol Metab 303(9):E504-E514. 2012. PMID:
22693206. IF: 4,746. DOI: 10.1152/ajpendo.00653.2011
Reduces
Lipid
Accumulation
in
Human
Hepatocytes
and
Is
Down-Regulated
in
Nonalcoholic Fatty Liver. PLoS ONE 7(1):e30014.
2012. PMID: 22238690. IF: 4,092. DOI: 10.1371/
journal.pone.0030014
BOOKS
Vescovo T, Romagnoli A, Perdomo AB, Corazzari M,
Ciccosanti F, Alonzi T, Nardacci R, Ippolito G, Tripodi
M, García-Monzón C, Lo Iacono O, Piacentini M,
Fimia GM. Autophagy Protects Cells From HCVInduced
Defects
in
Lipid
Metabolism.
Gastroenterology 142(3):644-653.e3. 2012. PMID:
22155365.
IF:
11,675.
DOI:
10.1053/j.gastro.2011.11.033
Carmelo García Monzón. Enfermedad hepática grasa
no alcohólica. Gastroenterología y Hepatología.
Problemas comunes en la práctica clínica. 2012.
Jarpyo Editores S.A. ISBN: 978-84-92982-31-8.
Moya M, Benet M, Guzmán C, Tolosa L, GarcíaMonzón C, Pareja E, Castell JV, Jover R. Foxa1
PRINCIPAL INVESTIGATOR: GARCIA MONZON,
CARMELO
Estudio para evaluar la eficacia y la seguridad de
GFT505 una vez al día para esteatohepatitis en
pacientes con esteatohepatitis no alcohólica (EHNA).
Estudio multicéntrico, aleatorizado, doble ciego y controlado con placebo, con un diseño adaptativo para
permitir la administración inicial de GFT505 80 mg
frente a placebo, seguido de una segunda fase en la
que se incluirá una dosis de GFT505 de 120 mg, tras
la revisión del análisis de la seguridad a los seis meses,
de los datos de 80 mg en al menos el 50% de los
pacientes; (Versión 3.0: 01-08-12). GENFIT. GFT505212-7.
EudraCT: 2012-000295-42
– 79 –
CLINICAL TRIALS
Barr J, Caballería J, Martínez-Arranz I, DomínguezDíez A, Alonso C, Muntané J, Pérez-Cormenzana M,
García-Monzón C, Mayo R, Martín-Duce A, RomeroGómez M, Lo Iacono O, Tordjman J, Andrade RJ,
Pérez-Carreras M, Le Marchand-Brustel Y, Tran A,
Fernández-Escalante C, Arévalo E, García-Unzueta
M, Clement K, Crespo J, Gual P, Gómez-Fleitas M,
Martínez-Chantar ML, Castro A, Lu SC, VázquezChantada M, Mato JM. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver
disease progression. Journal of Proteome Research
11(4):2521-2532. 2012. PMID: 22364559. IF: 5,113.
DOI: 10.1021/pr201223p
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.
– 81 –
AREA 2
NEUROTRANSMISSION,
PHARMACOLOGICAL NEUROPROTECTION
AND NEURODEGENERATIVE AND
NEUROPSYCHIATRIC DISEASES
– 82 –
AREA 2
NEUROTRANSMISSION, PHARMACOLOGICAL
NEUROPROTECTION AND NEURODEGENERATIVE
AND NEUROPSYCHIATRIC DISEASES
Line 2.1
Neuropharmacology
and neuroprotection
GROUP 28
GROUP MEMBERS
• Manuela García López
• Mercedes Villarroya Sánchez
• Cristóbal de los Ríos Salgado
• Manuel Alejandro Romero Martínez
• Matilde Yáñez Jato
• Elba Alonso Álvarez
• Laura del Barrio Díaz
• José Carlos Fernández Morales
• Antonio Miguel García de Diego
• María Dolores Martín de Saavedra
• Lorena Cortés Gil
• Francisco Javier Egea Máiquez
• Santos Morais Nicolau
• Patricia Velasco Jurado
• Marcos Maroto Pérez
• Esther Parada Pérez
RESEARCH INTEREST
For the last two decades, most efforts on new drug
development to treat neurodegenerative diseases
have been done. However, all these compounds
have so far failed in clinical trials or have not contributed to ameliorate the disease advance. It
seems therefore desirable to explore new concepts
Fig. 1. Multitarget compounds acting on VDCCs of soma of vulnerable neurons (A; a DHP-like moiety to mitigate excess Ca2+
entry) and on the MNCX (B; benzothiazepine moiety to abort the
futile MCC) as well as on oxidative stress linked to distorted
Ca2+ homeostasis (C; a polyphenol-like moiety to sequester
excess free radicals) could be a more efficacious strategy to
rescue neurons from death in neurodegenerative diseases. In
this scheme, we propose that a trifunctional compound (i.e., a
hybrid molecule with dihydropyridine benzothiazepine, and
polyphenol moieties) could effectively mitigate the augmented
neuronal (NCC) and mitochondrial Ca2+ cycling (MCC), thereby
exerting a protective survival effects on vulnerable neurons in
neurodegenerative diseases.
and strategies in the field of drug development for
neurodegenerative diseases. We analyze in our
project the hypothesis that a trifunctional chemical
entity acting on the L subtype of voltage-dependent Ca2+ channels (VDCCs) and on the mitochondrial Na+/Ca2+ exchanger (MNCX), and having
additional antioxidant properties, may efficiently
delay or stop the death of vulnerable neurons in the
brain of patients with neurodegenerative diseases
(see figure 1). In the last year, we have published
– 83 –
AREA 3AREA 2 AREA 1
HEAD OF LABORATORY
Neurotransmission, pharmacological neuroprotection and
neurodegenerative and neuropsychiatric diseases
Fig. 2. Exocytotic response to high K+ depolarization measured
with amperometry. Graph depicted the average of control and
APP/PS1 spikes.
four review articles focused on the functional triad
hypothesis, the mitochondrial importance on the
regulation of cytosolic Ca2+, and new strategies for
drug development [1-4].
In this context of drug design and development, we
have published two original articles; one of them is
about the mechanism of action of the neuroprotective and natural drug resveratrol. Here, we have proposed that resveratrol is able to mitigate the catecholamine surge occurring during stress, through its
ability to elicit mild local [Ca2+]c transients and
enhanced NO production, that blocks the last steps
of exocytosis [5]. The other article is about a new
class of neuroprotective agents based on 4,6diaryl-1,4-dihydropyridines chemical structure.
These compounds lack the structural features
needed for vascular activity, were found to prevent
calcium overload and behave as neuroprotective
agents. One of the compounds, bearing a 2-thienyl
substituent at C-4, showed the highest neuroprotective activity and was also a moderate antioxidant, being a good compound for further studies in
this area [6].
In addition to new drug development, we have tested our hypothesis of the homeostatic control of
cytosolic Ca2+ by the functional triad in transgenic
– 84 –
mice models of Alzheimer disease (AD). We have
assessed how homeostatic Ca2+ imbalance affect
to exocytosis machinery in chromaffin cells as
periphery neuronal model in this transgenic mouse.
Obviously, the search for synaptic dysfunctions in
AD has been focused on the brain. However, the
analysis of the last steps of exocytosis in the millisecond-time range has been best studied in
peripheral chromaffin cells, using amperometry. This
technique provides information on subtle differences in fast exocytotic mechanisms, which have
not been possible to study in CNS. In this study, we
have compared the kinetic parameters of singlevesicle amperometric events in chromaffin cells from
control C57 mice and the APP/PS1 transgenic
mouse model of AD. Given that cholinergic neuron
loss is prominent in AD brains, we used the AChE
activity technique to assess alterations in both, the
cholinergic innervations and the activity of the
enzyme itself which is substantially depleted in the
brains of patients with AD. Finally we assayed the
presence of amyloid plaque deposition in the adrenal medullae and brain of these mice. In this study,
we have described alterations in the last steps of
regulated exocytosis in a peripheral neuroendocrine
cell of a mouse model of AD. Due to accessibility
and available methodological approaches to study
minute changes of the kinetics of the last steps of
exocytosis, chromaffin cells may become invaluable
models to study the potential changes of exocytotic machine in the various mouse models of AD available (see figure 2). These studies would aid to shed
light on other central pathophysiological alterations
produced by the disease [7].
Finally, we aimed to investigate the effects of chondroitin sulphate (CS) on voltage- and currentclamped rat embryo hippocampal neurons in primary cultures. We found that CS elicited a wholecell Na+-dependent inward current (ICS) that produced drastic cell depolarization, and a cytosolic
calcium transient ([Ca2+]c). Those effects were
mediated
throughout
-amino-3-hydroxy-5methylisoxazole-4-propionate (AMPA) and kainite
receptors. Because CS proteoglicanes have been
attributed Ca2+-dependent roles, such as neural
AREA 2
MAJOR GRANTS
• Antonio García García. Modulación farmacológica
del intercambiador sodio-calcio mitocondrial: una
nueva estrategia para tratar la enfermedad de
Alzheimer. Proyecto Fundación CIEN Instituto de
Salud Carlos III. PI 016/09. Duration: 2009 2012.
• Antonio García García. Neurotoxicidad del líquido
cefalorraquídeo de pacientes con esclerosis lateral amiotrófica (ELA): una nueva estrategia para la
búsqueda de fármacos neuroprotectores.
Agencia Laín Entralgo-Consejería de Sanidad.
NDG09/8. Duration: 2010 - 2012.
• Antonio García García. Perturbación de la liberación cuantal de adrenalina en la hipertensión
arterial. Cooperación Interunivesitaria UAMBanco de Santander. Duration: 2011 - 2012.
• Antonio García García. Tríada funcional y especialización de los subtipos de canales de calcio
para controlar la exocitosis en la célula cromafín.
MICINN. SAF2010-21795. Duration: 2011 2013.
• Cristóbal de los Ríos Salgado. The CALHM1
channel and its Alzheimer's disease-linked mutated form P86L-CALHM1. A new biological target
for the finding of neuroprotective drugs. MICINN.
CP10/00531. Duration: 2011 - 2013.
• Antonio García García. Esclerosis lateral amiotrófica: neuroprotección basada en la regulación farmacológica de la circulación neuronal del calcio.
Fundación Eugenio Rodríguez Pascual. Duration:
2012 - 2013.
PUBLICATIONS
(8)
YEAR
Total IF
2010
2011
2012
[IF: 30,209]
Publication No.
Q1
Q2
45,614
12
6
4
45,763
14
5
7
30,209
8
3
4
Fernández-Morales, J.C. Arranz-Tagarro, J.A.
Calvo-Gallardo, E. Maroto, M. Padin, J.F. García,
A.G. Stabilisers of neuronal and mitochondrial calcium cycling as a strategy for developing a medicine
for
Alzheimer´s
disease.
ACS
Chemical
Neuroscience. 2012. IF: 3,676
González-Lafuente, L. Egea, J. León, R. MartínezSanz, F.J. Monjas, L. Perez, C. Merino, C. GarcíaDe-Diego, A.M. Rodríguez-Franco, M.I. García, A.G.
Villarroya, M. López, M.G. De Los Ríos, C.
Benzothiazepine CGP37157 and its isosteric 2’methyl analogue provide neuroprotection and block
cell calcium entry. ACS Chemical Neuroscience
3(7):519-529. 2012. PMID: 22860221. IF: 3,676.
DOI: 10.1021/cn300009e
de Diego AM, Lorrio S, Calvo-Gallardo E, García,
A.G. Smaller quantal size and faster kinetics of single exocytotic events in chromaffin cells from the
APP/PS1 mouse model of Alzheimer's disease.
Biochem Biophys Res Commun. 428(4):482-6.
2012. PMID: 23123627. IF: 2,484. DOI:
10.1016/j.bbrc.2012.10.082
García, A.G. Padin, J.F. Fernández-Morales, J.C.
Maroto, M. García-Sancho, J. Cytosolic organelles
shape calcium signals and exo-endocytotic
responses of chromaffin cells. Cell Calcium 51(34):309-320. 2012. PMID: 22209033. IF: 3,766. DOI:
10.1016/j.ceca.2011.12.004
– 85 –
AREA 3AREA 2 AREA 1
network development, axon pathfinding, plasticity
and regeneration after central nervous system
injury, CS action after extracellular matrix degradation could be contributing to the mediation of these
effects through its interaction with AMPA and
kainate receptors [8]. We have also presented the
development, characterization and functional validation of a new polymeric support able to induce
neuronal differentiation in both PC12 cell line and
adult primary skin-derived precursor cells (SKPs) in
vitro. This support is based in the combination of a
photolithographic technique with use of neural
extracellular matrix as a substrate, and a biocompatible and efficient microenvironment for neuronal
differentiation [9]
Padín J.F. De Diego, A.M.G. Fernández-Morales,
J.C. Merino, C. Maroto, M. Calvo-Gallardo, E.
Arranz, J.A. Yáñez, M. García, A.G. Resveratrol augments nitric oxide generation and causes store calcium reléase in chromaffin cells. European Journal of
Pharmacology 685(1-3):99-107. 2012. PMID:
22498000.
IF:
2,516.
DOI:
10.1016/j.ejphar.2012.03.040
Egea, F.J. Martín de Saavedra, M.D. Parada, E.
Romero, A. Del Barrio,L. Rosa, A.O. García, A.G.
López, M.G. Galantamine elicits neuroprotection by
inhibiting iNOS, NADPH oxidase and ROS in hippocampal
slices
stressed
with
anoxia/reoxygenation. Neuropharmacology 62(2):10821090. 2012. PMID: 22085833. IF: 4,814. DOI:
10.1016/j.neuropharm.2011.10.022
Lorrio, S. Gómez-Rangel, V. Negredo, P. Egea, J.
León, R. Romero, A. Dal-Cim, T. Villarroya, M.
Rodríguez-Franco, M.I. Conde, S. Arce, M. Roda,
J.M. García, A.G. López, M.G. Novel multitarget ligand ITH33/IQM9.21 provides neuroprotection in in
vitro and in vivo models related to brain ischemia.
Neuropharmacology 67:403-411. 2012. PMID:
23228428.
IF:
4,814.
DOI:
10.1016/j.neuropharm.2012.12.001
García-Sancho, J. García, A.G. De Diego, A.M.G.
Mitochondria and chromaffin cell function. Pflügers
Archiv European Journal of Physiology 464(1):33-41.
2012. PMID: 22278417. IF: 4,463. DOI:
10.1007/s00424-012-1074-2
GROUP 29
HEAD OF LABORATORY
María Francisca Cano Abad
GROUP MEMBERS
• Ana Ruiz Nuño
• Ana José Moreno Ortega
MAJOR GRANTS
Ana Ruiz Nuño. Estudio del potencial efecto neuroprotector del nuevo compuesto ITH12233 en modelos TDP-43
in vitro e in vivo de esclerosis lateral amiotrófica. ISCIII.
FIS.10/01426. Duration: 2011 - 2013.
YEAR
Total IF
Publication No.
Q1
2010
2,595
1
6
2011
10,593
3
1
2012
8,61
2
2
Q2
1
Hernández-Vivanco A, Pérez-Alvarez A, Caba-González
JC, Alonso MT, Moreno-Ortega AJ, Cano-Abad M,
Ruiz-Nuño A, Carmona-Hidalgo B, Albillos A. Selectivity
of action of pregabalin on Ca(2+) channels but not on
fusion pore, exocytotic machinery, or mitochondria in
chromaffin cells of the adrenal gland. J Pharmacol Exp
Ther. 342(2):263-72. 2012. PMID: 22537772. IF: 3,828.
DOI: 10.1124/jpet.111.190652
BOOKS
De Diego, A.M.G. Lorrio, S. Hernández-Guijo, J.M.
Gandia, L. García, A.G. Multitarget drugs for
Stabilization of Calcium Cycling and Neuroprotection
in Neurodegenerative Diseases and Stroke.
Therapeutic Targets: Modulation, Inhibition and
Activation. 2012. Wiley & Sons, Inc. ISBN: 978-0470-58719-5.
– 86 –
Paredes-Gamero EJ, Casaes-Rodrigues RL, Moura
GE, Domingues TM, Buri MV, Ferreira VH, Trindade ES,
Moreno-Ortega AJ, Cano-Abad MF, Nader HB,
Ferreira AT, Miranda A, Justo GZ, Tersariol IL. Cell-permeable gomesin peptide promotes cell death by intracellular Ca(2+) overload. Mol Pharm. 9(9):2686-97.
2012. PMID: 22873645. IF: 4,782. DOI:
10.1021/mp300251j
AREA 2
GROUP 31
Line 2.2
Neurotransmission
in the hippocampus
HEAD OF LABORATORY
Jesús Miguel Hernández Guijo
GROUP 30
GROUP MEMBERS
• José Carlos González San Frutos
• Elisa Albiñana Durá
HEAD OF LABORATORY
Luis Gandía Juan
MAJOR GRANTS
• Luis Gandía Juan. Receptores nicotínicos alfa7 e
inflamación en un modelo animal de distrofia
muscular. CEAL-SANTANDER. Duration: 2011 2012.
• Luis Gandía Juan. Receptores nicotínicos y liberación
de
neurotransmisores.
MICINN.
SAF2010-18837. Duration: 2011 - 2013.
• Luis Gandía Juan. Receptores nicotínicos alfa7 e
inflamación en un modelo animal de distrofia muscular. MECD. PHB2011-0031-PC. Duration: 2012 2013.
YEAR
Total IF
Publication No.
Q1
Q2
2010
11,994
4
1
2011
10,933
3
1
2
2012
7,582
2
1
1
MSegura-Chama P, Rivera-Cerecedo CV, GonzálezRamírez R, Felix R, Hernández-Guijo JM, HernándezCruz A. Atypical Ca2+ currents in chromaffin cells from
SHR and WKY rat strains result from the deficient
expression of a splice variant of the 1D Ca2+ channel.
Am. J. Physiol. Heart and Circulatory Physiology
302(2):467-478. 2012. PMID: 22081701. IF: 3,708.
DOI: 10.1152/ajpheart.00849.2011
Lopez-Jimenez ME, González JC, Lizasoain I,
Sánchez-Prieto J, Hernández-Guijo JM, Torres M.
Functional cGMP-gated channels in cerebellar granule
cells. J Cell Physiol. 227(5):2252-63. 2012. PMID:
21809342. IF: 3,874. DOI: 10.1002/jcp.22964
YEAR
Total IF
Publication No.
Q1
Q2
2010
16,783
5
2
3
2011
12,287
4
2
1
2012
– 87 –
AREA 3AREA 2 AREA 1
GROUP MEMBERS
• Ángela Orozco Alarcón
• Carmen Pérez de Nanclares Fernández
• Ricardo de Pascual y del Castillo
• Inés Colmena Crespo
Line 2.3
Clinical pharmacology
and pharmacogenetics
GROUP 32
HEAD OF LABORATORY
GROUP MEMBERS
• Dolores Ochoa Mazarro
• María Isabel Moreno Arza
• Manuel Román Martínez
• Sergio Daniel Sánchez Rojas
• María Fagoaga Torija
• María Talegón García
• María Teresa Cabaleiro Ocampo
• Ana María Tello Miller
• Igone Marrodán Remírez
• Javier Soriano Ventura
• Rocío María Prieto Pérez
• Angela Rivas Acosta
• Carmen Verge González
Comparison of TPMT genotype frequencies obtained by LightSNiP and
sequencing methods, and differences by gender.
Reference: Román M, Cabaleiro T, Ochoa D, Novalbos J, Chaparro M,
Gisbert JP, Abad-Santos F. Validation of a genotyping method for analysis of TPMT polymorphisms. Clin Ther. 2012; 34(4): 878-84.
the efficacy of new drugs in collaboration with several specialists in the hospital and primary care. During 2012, 15
clinical trials (phase I to IV) were performed.
Pharmacogenetic research is related with various clinical
diseases, trying to look for new pharmacogenetic markers
to predict drug response, both therapeutic and toxic, that
could help physicians to decide the best treatment for
every patient. In 2012, 524 patients benefited from pharmacogenetic testing.
During 2012, our group published 6 articles related to
pharmacogenetics and clinical trials (Agúndez et al., 2012;
Cabaleiro et al., 2012; Carcas et al., 2012; Gallo et al.,
2012; González-Vacarezza et al., 2012; Román et al.,
2012).
RESEARCH INTEREST
The aim of the investigation performed in this group is to
evaluate the pharmacokinetics, pharmacodynamics and
pharmacogenetics of drugs in order to predict the
response of patients to drugs, in terms of both efficacy
and safety.
Our group has wide experience in the performance of
numerous phase I, II and III clinical trials, with Dr. AbadSantos and Dolores Ochoa as principal investigators. We
have available a Clinical Trials Unit, with capacity for 14
patients (7th floor, Hospital Universitario de la Princesa).
Clinical trials performed include safety, pharmacokinetics,
pharmacodynamics, interaction and bioequivalence studies in healthy volunteers, and studies in patients to probe
– 88 –
In addition, we are participating in 2 projects: Búsqueda
de marcadores genéticos predictores de respuesta a fármacos biológicos en el tratamiento de la psoriasis, supported by the Instituto de Salud Carlos III (Ref.
PI10/01740); Nuevos medicamentos genéricos para el
tratamiento de patologías de alto impacto socioeconómico supported by the Ministerio de Ciencia e Innovación
(Ref. IPT-2011-1663-900000).
MAJOR GRANTS
• Francisco Abad Santos. Búsqueda de marcadores
genéticos predictores de respuesta a fármacos
AREA 2
YEAR
Total IF
Publication No.
Q1
Q2
2010
14,591
5
2
3
2011
13,854
4
2
1
2012
9,93
3
1
2
M Román, T Cabaleiro, J Novalbos, M Chaparro, JP
Gisbert, F Abad-Santos. Validation of a genotyping
method for analysis of TPMT polymorphisms. Clin Ther
34(4):878-884. 2012. PMID: 22421577. IF: 2,321. DOI:
10.1016/j.clinthera.2012.02.017
Cabaleiro T, Roman M, Gisbert JP, Abad-Santos F.
Utility of assesing thiopurine S-methyltransferase polymorphism before azathioprine therapy. Current Drug
Metabol. 13(9):1277-93. 2012. PMID: 22493988. IF:
5,113
Carcas AJ, Borobia AM, Velasco M, Abad-Santos F,
Díaz MQ, Fernández-Capitán C, Ruiz-Giménez N,
Madridano O, Sillero PL; PGX-ACE Spanish
Investigators Group (..., Ochoa D, Marrodan I, Moreno
I, Román M, Verge C,...). Efficiency and effectiveness of
the use of an acenocoumarol pharmacogenetic dosing
algorithm versus usual care in patients with venous
thromboembolic disease initiating oral anticoagulation:
study protocol for a randomized controlled trial. Trials
13:239. 2012. PMID: 23237631. IF: 2,496. DOI:
10.1186/1745-6215-13-239
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: ABAD SANTOS, FRANCISCO
Ensayo clínico cruzado y aleatorizado de bioequivalencia de dos formulaciones de comprimidos de aripiprazol 10 mg, tras su administración oral en dosis única a
voluntarios sanos; (versión 1: 02-10-12). LABORATORIOS ALTER, S.A. ITHUEC-ARI/12-4.
EudraCT: 2012-004241-32
PRINCIPAL INVESTIGATOR: OCHOA MAZARRO,
DOLORES
Ensayo clínico cruzado aleatorizado de bioequivalencia
de dos formulaciones de clopidogrel comprimidos de
75mg, tras su administración en dosis única a voluntarios sanos en ayunas; (Versión 1:16-04-12). LABORATORIOS ALTER, S.A. ITHUEC-CLO/12-1.
EudraCT: 2012-000702-30
DOLORES
Ensayo clínico aleatorizado, abierto y cruzado de tres
vías de bioequivalencia de tres formulaciones de
ibuprofeno 400mg (ibuprofene en suspensión
100mg/5ml e ibuprofeno suspensión 200mg/5ml)
frente a junifen suspensión 100mg/5ml) tras su administración oral en dosis única a voluntarios sanos; (versión 1.0:16-05-12). LABORATORIOS FARMALIDER,
S.A. FMLD-CALISTO 2%4%-15.
EudraCT: 2012-002310-40
Ensayo clínico cruzado y aleatorizado de bioequivalencia de dos formulaciones de diclofenaco de 50mg
comprimidos gastrorresistentes, tras su administración
oral en dosis única con comida a voluntarios sanos;
(Versión 1:17-04-12). LABORATORIOS NORMON,
S.A. N-DIC-11-176.
EudraCT: 2012-000176-41
DOLORES
Ensayo clínico cruzado y aleatorizado de bioequivalencia de dos formulaciones de amlodipino/atorvastatina
10mg/10mg comprimidos recubiertos, tras su administración oral en dosis única a voluntarios sanos en
ayunas con diseño cruzado replicado; (Versión 1:1605-12). LABORATORIOS NORMON, S.A. N-AMLATO-
– 89 –
AREA 3AREA 2 AREA 1
biológicos en el tratamiento de la psoriasis. ISCIII.
PI10/01740. Duration: 2010 - 2013.
• Francisco Abad Santos. Nuevos medicamentos
genéricos para el tratamiento de patologías de alto
impacto socioeconómico. MEC. IPT-2011-1663900000. Duration: 2011 - 2014.
12-178.
EudraCT: 2012-001846-16
DOLORES
Ensayo clínico cruzado y aleatorizado de bioequivalencia de tres formulaciones de efavirenz comprimidos
recubiertos de 600mg, tras su administración oral en
dosis única a voluntarios sanos; (Versión 1: 03-10-12).
LABORATORIOS KERN PHARMA S.L. KP-EFA-53.
EudraCT: 2012-004402-96
Ensayo clínico cruzado y aleatorizado de bioequivalencia de dos formulaciones de comprimidos bucodispersables de aripiprazol 10mg, tras su administración
oral en dosis única a voluntarios sanos en ayunas; (versión 1:16-07-12). LABORATORIOS KERN PHARMA
S.L. KP-ARI-51.
EudraCT: 2012-003196-19
DOLORES
Ensayo clínico cruzado y aleatorizado de bioequivalencia de dos formulaciones en comprimidos de aripiprazol 10mg, tras su administración oral en dosis única a
voluntarios sanos en ayunas; (Versión 1:16-05-12).
LABORATORIOS KERN PHARMA S.L. KP-ARI-46.
EudraCT: 2012-002016-97
DOLORES
Ensayo clínico cruzado y aleatorizado de bioequivalencia de dos formulaciones de diclofenaco 50mg comprimidos gastrorresistentes, tras su administración oral
en dosis única a voluntarios sanos en ayunas; (Versión
1: 29-02-12). LABORATORIOS NORMON, S.A. N-DIC11-175.
EudraCT: 2012-000189-40
DOLORES
Ensayo clínico cruzado y aleatorizado para evaluar la
biodisponibilidad y tolerabilidad de una nueva formulación de ibuprofeno arginato comparada con la formu-
– 90 –
lación estándar oral de ibuprofeno arginina administrada en dosis única a voluntarios sanos en ayunas; (versión 1.0: 16-07-12). LABORATORIOS FARMALIDER,
S.A. FMLD-FEBE-17.
EudraCT: 2012-003264-53
DOLORES
de dos formulaciones de quetiapina comprimidos de
liberación prolongada de 50mg, tras su administración
oral en dosis única con comida a voluntarios sanos
seguido de dosis múltiple; (versión 1: 20-09-12). LABORATORIOS ALTER, S.A. ITHUEC-QUE50/12-5.
EudraCT: 2012-004287-22
DOLORES
Estudio piloto cruzado, aleatorizado para evaluar la farmacocinética tras la administración de dosis única de
progesterona (tres formulaciones de EF800 y
Utrogestan« 200mg) por vía oral en mujeres postmenopáusicas o mujeres con ovarectomía bilateral;
(versión 1: 31-10-12). EFFIK GROUP. 2013001_ORAL.
EudraCT: 2012-005011-10
DOLORES
Ensayo clínico cruzado y aleatorizado de bioequivalencia
de dos formulaciones de metformina comprimidos recubiertos de 850mg, tras su administración en dosis única
con comida a voluntarios sanos;(Versión1:8-5-12). LABORATORIOS KERN PHARMA S.L. KP-MET-47.
EudraCT: 2012-002006-48
Ensayo clínico aleatorizado, abierto y cruzado de bioequivalencia de dos formulaciones de ibuprofeno
400mg (ibuprofeno 400mg polvo oral frente a dalsy
400 mg comprimidos recubiertos con película) tras su
administración oral en dosis única a voluntarios sanos;
(versión 1.0: 12-07-12). LABORATORIOS FARMALIDER, S.A. FMLD-SINOPE-16.
EudraCT: 2012-003263-21
AREA 2
Ensayo clínico pivotal, aleatorizado, cruzado y replicado de bioequivalencia de dos formulaciones de barnidipino 20mg capsulas de liberación modificada tras su
administración oral en dosis única a voluntarios sanos
en ayunas; (versión 1: 17-10-12). LABORATORIOS
LICONSA S.A., SPAIN. LIE1-CH-BARN-0159-CT-B02-12.
EudraCT: 2012-004843-59
QUE50/12-2.
EudraCT: 2012-002986-36
DOLORES
Ensayo clínico cruzado, replicado y aleatorizado de
biodisponibilidad comparada de dos formulaciones de
albendazol comprimidos de 400mg, tras su administración en única dosis a voluntarios sanos, junto con un
desayuno estándar y un desayuno rico en grasas; (versión 2:11-01-12). FUNDACION TEOFILO HERNANDO.
ITHUEC-ALB/10-6.
EudraCT: 2010-021006-38
DOLORES
de dos formulaciones de rasagilina comprimidos de 1mg,
tras su administración oral en dosis única a voluntarios
sanos en ayunas; (versión 1: 15-10-12). LABORATORIOS
NORMON, S.A. N-RAS-12-184.
EudraCT: 2012-004433-17
DOLORES
Ensayo clínico aleatorizado de bioequivalencia de dos formulaciones de Telmisartán/hidroclorotiazida comprimidos
de 80/25 mg, tras su administración en dosis única a voluntarios sanos en ayunas con diseño cruzado replicado;
(Versión 1: 20-09-12). LABORATORIOS ALTER, S.A.
ITHUEC-TEL-HTZ/12-3.
EudraCT: 2012-004242-14
– 91 –
AREA 3AREA 2 AREA 1
DOLORES
de dos formulaciones de quetiapina comprimidos de
liberación prolongada de 50mg, tras su administración
en dosis única a voluntarios sanos en ayunas; (versión
1:21-06-12). LABORATORIOS ALTER, S.A. ITHUEC-
de dos formulaciones de comprimidos bucodispersables
de aripiprazol 10mg, tras su administración oral en dosis
única a voluntarios sanos en ayunas; (versión 1: 03-1212). LABORATORIOS ALTER, S.A. ITHUEC-ARI/12-6.
EudraCT: 2012-005274-60
Line 2.4
Diagnostic and
therapeutic advances
in affective disorders
GROUP 33
HEAD OF LABORATORY
José Luis Ayuso Mateos
GROUP MEMBERS
• Marta Miret García
• Matilde Hernández Álvarez
• Celia Anaya Suárez
• María del Mar Rivas Rodríguez
• María Cabello Salmerón
• Eduardo García-Camba de la Muela
• Jesús Valle Fernández
• Elena Ezquiaga Terrazas
• Miguel Ángel Gorriti Irigai
• Itziar Leal Leturia
• Luis Miguel García Olmos
• Herminio Martínez Cano
• Pilar López García
• Blanca Mellor Marsá
• Francisco Félix Caballero Díaz
• José David Albillo Labarra
Clinicians ’ organization of mental disorders by 2 dimensions: internalizing/externalizing disorders and Functional/Organic disorders.
Figure taken from: Roberts MC, Reed GM, Medina-Mora ME, Keeley JW,
Sharan P, Johnson DK, Mari Jde J, Ayuso-Mateos JL, Gureje O, Xiao Z,
Maruta T, Khoury B, Robles R, Saxena S. A global clinicians' map of
mental disorders to improve ICD-11: analysing meta-structure to enhance clinical utility.Int Rev Psychiatry. 2012 Dec;24(6):578-90.
•
•
RESEARCH INTEREST
In 2012 our group conducted research in the following
key areas:
• 1. Study of the risk factors for psychotic disorders: Our
team started working in a multi-center study to clarify
the role of genes, social environment, and other clinical
variables in the onset of psychotic episodes.
• 2. Application and assessment of interventions in
affective disorders: Clinical researchers of our team
were involved in testing the effectiveness of new ther-
– 92 –
•
•
apeutic agents in bipolar disorders and treatment
resistant depression.
3. Nosology of mental disorders. Members of our
team have participated in the working groups for the
revision of ICD-10th chapter for mental and behavioral disorders. Currently, our team also leads the
implementation of the field studies in Spanish speaking countries.
4. Analysis and prevention of suicidal behaviour,
mental disorders and promotion of mental health:
Our group leads studies in the analysis of suicidal
behaviour in different settings and organizes training
workshops addressed to mental health professionals
and other non-specialized mental health professionals to prevent suicidal behavior in Madrid.
5. Improvement of mental health services performance in LAMICs countries. Clinicians and researchers
are working to identify key health system barriers to,
and solutions for, the scaled-up delivery of mental
health services in low- and middle-income countries
(LAMICs).
6. Analysis of health status and well-being: Our
group published in 2012 the validation of a short
version of an instrument for measuring subjective
well-being in large population samples. In addition;
researchers worked in the elaboration a roadmap
for mental health and well-being research in
Europe.
• 7. Evaluation of common psychosocial problems in
mental disorders: Our team collected a sample of 80
depressive patients from primary care centers to validate a new generic tool for gathering psychosocial
difficulties in day-to-day clinical practice.
MAJOR GRANTS
• José Luis Ayuso Mateos. Centros de investigación
biomédica en Red CIBER de Salud Mental. FIS.
Acciones CIBER. CB07TEMP/003. Duration: 2008 2012.
• José Luis Ayuso Mateos. Collaborative Research on
AGEing in Europe. COURAGE. CE. VII Programa
Marco Union Europea. Convocatoria FP7 HEALTH2007- 3.2-6: Health outcome measures and population ageing. FP7 HEALTH-2007-3.2-6. Duration:
2008 - 2012.
• José Luis Ayuso Mateos. Centro de Investigación
Biomédica en Red de Salud Mental: CIBER-SAM.
ISCIII. CIBER CB07/09/0013. Duration: 2008 - 2012.
• José Luis Ayuso Mateos. Capacidad de reserva cognitiva en el trastorno bipolar eutímico: impacto en el
funcionamiento y en el rendimiento cognitivo.
Ministerio de Educación y cultura. concesión de una
beca FPU para la realización del proyecto de tesis de
Celia Anaya dirigida por Jose Luis Ayuso Mateos.
AP2008-00915. Duration: 2009 - 2012.
• José Luis Ayuso Mateos. Estudio Colaborativo del
Envejecimiento en Europa (COURAGE in Europe).
MCINN. Programa de Internacionalización de la I+D.
Fomento de la Cooperación Científica Internacional.
Modalidad
ACI-Promociona.
ACI2009-2010.
Duration: 2010 - 2012.
• José Luis Ayuso Mateos. Psycho-social Aspects
Relevant to Brain Disorders in Europe. PARADISE. VII
Programa Marco de la Unión Europea. Convocatoria:
FP7-HEALTH-2009-single-stage. FP7-HEALTH2009-241572. Duration: 2010 - 2012.
• José Luis Ayuso Mateos. Scaling up services for
mental, neurological and substance use (MNS) disorders within WHO mental health Gap Action
Programme (mhGAP). Unión Europea. Convocatoria:
EuropeAid/129197/C/ACT/Multi. 129197/C/ACT/
Multi. Duration: 2010 - 2012.
• José Luis Ayuso Mateos. Estado de Salud, Calidad
de Vida y Bienestar de la Población Española de
Edad Avanzada: un Estudio Epidemiológico. ISCIII.
PS09/00295. Duration: 2010 - 2012.
• José Luis Ayuso Mateos. Metilfenidato de liberación
inmediata en la mejoría sintomática de la Manía
aguda: un estudio frente a placebo. Ministerio de
Sanidad y Política Social. EC10-110. Duration: 2011
- 2012.
• José Luis Ayuso Mateos. Psycho-social Aspects
Relevant to Brain Disorders in Europe. PARADISE.
Comisión Europea. VII Programa Marco. FP7/20072013-241572. Duration: 2011 - 2012.
• José Luis Ayuso Mateos. Use of antidepressants in
the last decade and its relation to mortality and suicide-related events, with special focus on children
and adolescents. CIBERSAM. Convocatoria
Intramural. 11INT1. Duration: 2011 - 2013.
• José Luis Ayuso Mateos. Long-term Safety and
Tolerability of BMS-820836 in the Treatment of
Patients With Treatment Resistant Major Depression.
Bristol-Myers Squibb. CN162-010. Duration: 2011 2013.
• José Luis Ayuso Mateos. Efficacy and Safety of Fixed
Doses of BMS 820836 in the Treatment of Patients
With Treatment Resistant Major Depression. BMS.
C162-007. Duration: 2011 - 2013.
• José Luis Ayuso Mateos. Una hoja de ruta para la
investigación en salud mental y bienestar en Europa:
ROAMER. MICINN. ACI Promociona. ACI-PRO2011-1080. Duration: 2011 - 2013.
• Proyecto Coordinado. Metilfenidato de liberación
inmediata en la mejoría sintomática de la Manía aguda:
un estudio frente a placebo. CAIBER. 1392-D-079EudraCT 2010-023992-24. Duration: 2011 - 2013.
• Proyecto Coordinado. An age-friendly city for successful ageing. Caixa Reserca. Duration: 2011 2013.
• José Luis Ayuso Mateos. Metilfenidato de liberación
inmediata en la mejoría sintomática de la Manía
– 93 –
AREA 3AREA 2 AREA 1
AREA 2
aguda: un estudio frente a placebo. CIBERSAM.
Convocatoria Intramural. 11INT2. Duration: 2011 2013.
• Proyecto Coordinado. A Roadmap for Mental Health
Research in Europe (ROAMER). Comisión Europea.
VII Programa Marco. Health - F3 - 2011 - 282586.
Duration: 2011 - 2014.
• José Luis Ayuso Mateos. Ambiente y genes en
esquizofrenia-grupos de investigacion de la comunidad de Madrid. CAM. S2010/BMD-2422. Duration:
2011 - 2015.
• José Luis Ayuso Mateos. Emerging mental health
systems in low- and middle-income countries.
EMERALD. VI Programa marco de la UE. FP7305968. Duration: 2012 - 2017.
YEAR
Total IF
Publication No.
Q1
Q2
2010
2011
91,793
14
6
7
60,29
12
8
2012
3
56,606
16
9
7
Avila CC, Cieza A, Anaya C, Ayuso-Mateos JL. The
patients' perspective on relevant areas and problems
in the bipolar spectrum disorder: individual interviews
using the international classification of functioning,
disability and health as a reference tool. Am J Phys
Med Rehabil 91(13):S181-S188. 2012. PMID:
22193328. IF: 1,581. DOI: 10.1097/PHM.0b013e318
23d54db
Leonardi M, Ayuso-Mateos JL, Hollenweger J, Pessina
A, Bickenbach JE. Multidisciplinary research and training network on health and disability in Europe: the
MURINET project. Am J Phys Med Rehabil 91(13):S1S4. 2012. PMID: 22193330. IF: 1,581. DOI:
10.1097/PHM.0b013e31823d699e
Veronese A, Ayuso-Mateos JL, Cabello M, Chatterji S,
Nuevo R. Work disability and depressive disorders:
impact on the European population. Am J Phys Med
Rehabil 91(13):S62-S68. 2012. PMID: 22193312. IF:
1,581. DOI: 10.1097/PHM.0b013e31823d4f02
– 94 –
Rodríguez MR, Nuevo R, Chatterji S, Ayuso-Mateos JL.
Definitions and factors associated with subthreshold
depressive conditions: a systematic review. BMC
Psychiatry 12:181. 2012. PMID: 23110575. IF: 2,552.
DOI: 10.1186/1471-244X-12-181
Almaraz MC, González-Romero S, Bravo M, Caballero
FF, Palomo MJ, Vallejo R, Esteva I, Calleja F, Soriguer F.
Incidence of lower limb amputations in individuals with
and without diabetes mellitus in Andalusia (Spain) from
1998 to 2006. Diabetes Res Clin Pract 95(3):399-405.
2012.
PMID:
22133651.
IF:
2,754.
DOI:
10.1016/j.diabres.2011.10.035
Roberts MC, Reed GM, Medina-Mora ME, Keeley JW,
Sharan P, Johnson DK, Mari Jde J, Ayuso-Mateos JL,
Gureje O, Xiao Z, Maruta T, Khoury B, Robles R, Saxena S.
A global clinicians' map of mental disorders to improve ICD11: analysing meta-structure to enhance clinical utility. Int
Rev Psychiatry 24(6):578-590. 2012. PMID: 23244613. IF:
1,798. DOI: 10.3109/09540261.2012.736368
Bonnín CM, Sánchez-Moreno J, Martínez-Arán A, Solé
B, Reinares M, Rosa AR, Goikolea JM, Benabarre A,
Ayuso-Mateos JL, Ferrer M, Vieta E, Torrent C.
Subthreshold symptoms in bipolar disorder: Impact on
neurocognition, quality of life and disability. J Affect
Disord 136(3):650-9. Epub 2011 Nov 3. 2012. PMID:
22051075. IF: 3,517. DOI: 10.1016/j.jad.2011.10.012
Anaya C, Martinez Aran A, Ayuso-Mateos JL, Wykes T,
Vieta E, Scott J. A systematic review of cognitive remediation for schizo-affective and affective disorders. J Affect
Disord 142(1-3):13-21. 2012. PMID: 22840620. IF:
3,517. DOI: 10.1016/j.jad.2012.04. 020
Reinares M, Papachristou E, Harvey P, Mar Bonnín C,
Sánchez-Moreno J, Torrent C, Ayuso-Mateos JL,
Ploubidis GB, Vieta E, Frangou S. Towards a clinical
staging for bipolar disorder: Defining patient subtypes
based on functional outcome. J Affect Disord 144(12):65-71. 2012. PMID: 22862890. IF: 3,517. DOI:
10.1016/j.jad.2012.06.005
Cabello M, Mellor-Marsá B, Sabariego C, Cieza A,
Bickenbach J, Ayuso-Mateos JL. Psychosocial features
AREA 2
of depression: A systematic literature review. J Affect
Disord. 141(1):22-33. 2012. PMID: 22209189. IF: 3,517.
DOI: 10.1016/j.jad.2011.12.009
De Dios C, Ezquiaga E, Agud JL, Vieta E, Soler B, GarcíaLópez A. Subthreshold symptoms and time to
relapse/recurrence in a community cohort of bipolar disorder outpatients. J Affect Disord. 143(1-3):160-5. 2012.
PMID: 22925351. IF: 3,517. DOI: 10.1016/j.jad.2012.
05.047
Nuevo R, Chatterji S, Verdes E, Naidoo N, Arango
C, Ayuso-Mateos JL. The Continuum of Psychotic
Symptoms in the General Population: A Crossnational Study. Schizophr Bull. 38(3):475-85. Epub
2010 Sep 13. 2012. PMID: 20841326. IF: 8,8. DOI:
10.1093/schbul/sbq099
AAyuso-Mateos JL. Prototype diagnosis of psychiatric
syndromes and the ICD-11. World Psychiatry 11(1):3031. 2012. PMID: 22295005. IF: 6,233
Miret M, Caballero FF, Mathur A, Naidoo N, Kowal P, AyusoMateos JL, Chatterji S. Validation of a measure of subjective well-being: an abbreviated version of the day reconstruction method. PLoS One 7(8):e43887. 2012. PMID:
22952801. IF: 4,092. DOI: 10.1371/journal.pone. 0043887
Ayuso-Mateos JL, Lopez-Garcia P. Severity of depressive disorders: considerations for ICD-11. World
Psychiatry 11(Suppl. 1):48-52. 2012. IF: 6,233
De Dios C, Agud JL, Ezquiaga E, García-López A, Soler
B, Vieta E. Syndromal and subsyndromal illness status
and five-year morbidity using criteria of the International
Society for Bipolar Disorders compared to alternative criteria. Psychopathology. 45(2):102-8. 2012. PMID:
22269982. IF: 1,816. DOI: 10.1159/000329740
BOOKS
AREA 3AREA 2 AREA 1
Ayuso-Mateos JL, Saiz-Ruiz J, Morant C, Baca-García E,
Miret M, Nuevo R. Estudio de la Conducta Suicida en la
Comunidad de Madrid. 2012. Comunidad de Madrid.
Libro online en http://www.madrid.org.
– 95 –
Line 2.5
Neurosurgery of epilepsy
GROUP 34
HEAD OF LABORATORY
Rafael García de Sola
GROUP MEMBERS
• Jesús Pastor Gómez
• Guillermo Ortega Rabbione
• Luís Domínguez Gadea
• Desislava Panova Tzonova
• Rybel Wix Ramos
• María Luisa Meilán Paz
• José Luís Martínez-Chacón Crespo
• Eva de Dios Tomás
• Eduardo García Navarrete
• Paloma Pulido Rivas
Localization of coefficient of variation for electrodes 1 [CV(1)] to 5
[CV(5)] and resected tissue in each patient (Pearson correlation coefficient). (A) Cortical grid electrodes: Gray areas represent the approximate lateral cortical tissue resected during surgery. Superimposed, CV
minima are displayed according to the key bar (right): CV(1) = 1st,
CV(2) = 2nd, CV(3) = 3rd, CV(4) = 4th, and CV(5) = 5th. Patients with
postoperative seizures are highlighted in blue. G1 is always at the bottom left and G20 at the top right position. (B) Mesial strip electrodes:
Same schematic diagram as in panel (A).
RESEARCH INTEREST
The groups included in this line are focused on epilepsy, one of the most prevalent and sometimes devastating neurologic diseases in humans. We address the
problem from different aspects, ranging from basic
mechanisms of epileptogenesis, to new analytical and
pharmacological diagnostic tools. There are three different Programs in the group:
Temporal lobe epilepsy is commonly associated with
synchronous, hyper-synchronous and des-synchronous activity. However, in patients suffering from temporal lobe epilepsy there exist a clear tendency in the
mesial area of the epileptic side to be organized as isolated clusters of electrical activity as compared with the
contra-lateral side, which is organized in the form of
large clusters of synchronous activity. We addressed
the synchronization and the stability of highly synchronized areas in a group of patients. Our results show the
– 96 –
Ca2+ signal in human astrocytes in situ. (A) Pseudocolor images of
fluo-4-filled hippocampal and cortical slices, and representative Ca2+
levels showing spontaneous Ca2+ elevations from hippocampal and
cortical astrocytes. Scale bar: 60 µm (left), 40 µm (right). (B) Relative
number of active astrocytes and oscillation frequency in control and
TTX (n=46 and 39 astrocytes for the hippocampus and the cortex, respectively; n ≥ 6 slices for each bar). (C) Fluorescence images of a fluo4-loaded hippocampal slice depicting the experimental arrangement
(left), and Ca2+ levels 10 s before and after ATP application. Scale bar
60 µm. (D) Astrocyte Ca2+ responses (at the regions shown in C) to 2 s
application of WIN (300 µM), glutamate (0.8 mM), or ATP (20 mM). (E)
Astrocyte Ca2+ wave extension and speed in control and TTX (n ≥ 4 slices for each bar). Error bars indicate SEM. *P<0.05.
AREA 2
MAJOR GRANTS
• Guillermo Ortega Rabbione. Identificación, caracterización y papel de los clusters de sincronización
sobre la actividad epileptogénica en pacientes con
epilepsia del lóbulo temporal. Fundación Mutua
Madrileña. Duration: 2008 - 2012.
• Jesús Pastor Gómez. Papel de la albúmina y de la
permeabilidad de la barrera hematoencefálica, en la
activación de los astrocitos en la epilepsia focal
humana. ISCIII. PS09/02116. Duration: 2010 - 2012.
• Guillermo Ortega Rabbione. Análisis de registros de
EEG-EFO por medio de redes complejas en
pacientes con epilepsia del lóbulo temporal y sus
aplicaciones clínicas. MICINN. SAF2009-09406.
Duration: 2010 - 2013.
• Guillermo Ortega Rabbione. Análisis de los registros
EEG-EFO por medio de redes complejas en pacientes
con epilepsia del lóbulo temporal y sus aplicaciones
clínicas. ISCIII. PI10/00160. Duration: 2010 - 2013.
YEAR
Total IF
Publication No.
Q1
Q2
2010
13,676
8
1
2
2011
5,824
2
2012
5,89
2
1
1
Palmigiano A, Pastor J, Sola RG, Ortega GJ. Stability
of synchronization clusters and seizurability in temporal
lobe epilepsy. PLoS One. 7(7):e41799. 2012. PMID:
0041799
Navarrete EG, Torres C, Gallego I, Navas M, Pastor J,
Sola RG. Long-term results of vagal nerve stimulation
for adults with medication-resistant epilepsy, who have
been on unchanged antiepileptic medication. Seizure
22(1):9-13. 2012. PMID: 23041031. IF: 1,798. DOI:
10.1016/j.seizure.2012.09.008
BOOKS
Pastor J, Sola RG, Ortega GJ. Hyper-synchronization,
de-synchronization, synchronization and seizures.
Epileptic seizures. 2012. InTech. ISBN: 978-953-307737-6.
Pastor J. Estudios neurofisiológicos durante el postoperatorio inmediato. Manual de cuidados postoperatorios de
pacientes neuroquirúrgicos. 2012. Ergon SA. ISBN: 97884-1551-40-5.
Pascual JM, Carrasco R, Navas M, Pastor J. Cirugía
de la fosa posterior: técnica quirúrgica, complicaciones y cuidados perioperatorios. Manual de cuidados postoperatorios de pacientes neuroquirúrgicos.
2012. Ergon SA. ISBN: 978-84-1551-40-5. Págs.:
527-582.
de Dios Tomás E, Meilán ML, Hernando Requejo V.
Utilidad de la monitorización con BIS en el paciente neurológico/neuroquirúrgico. Manual de cuidados postoperatorios de pacientes neuroquirúrgicos. 2012. Ergon SA.
ISBN: 978-84-1551-40-5.
– 97 –
AREA 3AREA 2 AREA 1
existence of highly localized and stable synchronization
areas in both the lateral and the mesial areas of the
temporal lobe ipsilateral to the clinical seizures.
Synchronization areas seem to play a central role in the
capacity of the epileptic network to generate clinical
seizures. Resection of stable synchronization areas is
associated with elimination of seizures; nonresection of
synchronization clusters is associated with the persistence of seizures after surgery (Figure 1). We suggest
that synchronization clusters and their stability play a
central role in the epileptic network, favoring seizure
onset and propagation. We further speculate that the
stability distribution of these synchronization areas
would differentiate normal from pathologic cases.
On the other hand, continuing with the previous work,
we have shown that human astrocytes are able to
release the gliotransmitter glutamate, which affects
neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of
reciprocal signaling between neurons and astrocytes in
human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in
human brain function (Figure 2).
Pulido P. Monitorización de la PIC. Técnicas, dispositivos,
indicaciones. Manual de cuidados postoperatorios de
pacientes neuroquirúrgicos. 2012. Ergon SA. ISBN: 97884-1551-40-5.
– 98 –
Torres CV, García de Sola R. Consideraciones quirúrgicas
en el postoperatorio en la cirugía estereotáxica y de
estimulación profunda. Manual de cuidados postoperatorios de pacientes neuroquirúrgicos. 2012. Ergon SA.
ISBN: 978-84-1551-40-5.
AREA 2
GROUP 35
HEAD OF LABORATORY
José Aurelio Vivancos Mora
GROUP MEMBERS
• Florentino Nombela Merchán
• Mónica Sobrado Sanz
• Gemma Reig Roselló
• Lydia López Manzanares
• Virginia Meca Lallana
• Teresa Carreras Rodríguez
• Álvaro Ximenez-Carrillo Rico
• Noemí Mora Pérez
GROUP ASSOCIATED 1
HEAD OF LABORATORY
Ignacio Lizasoain Hernández
GROUP MEMBERS
• María Ángeles Moro Sánchez
• Olivia Hurtado Moreno
• Macarena Hernández Jiménez
• Ana Moraga Yébenes
• ván Ballesteros Martín
• Isaac García de Yébenes y Castro
• María Isabel Cuartero Desviat
• Víctor Manuel González Romera
• Tamara Atanes Pérez
• Roberto Cañadas Martín
RESEARCH INTEREST (G.35 & G.ASSOC 1)
The Neurological Service And Stroke Unit Of Hospital
Universitario De La Princesa is a medical service of the
Spanish public health system specialized in neurological diseases. It is public provider of neurological medical care for the entire health district #2 (metropolitan
population of Madrid, 320.744 people). For the rest of
the population of health district #2: Hospital de
Henares (164.810 people) and throughout health district #3 (Hospital Universitario Principe de Asturias
380.757 people), we are the reference Center for specific processes and special procedures such as stroke
center and stroke unit, Madrid region stroke code system, thrombolysis and emerging therapies and interventional neuroradiology unit. We are doing 17.000
outpatient visits and more than 700 admissions per
year. The Neurology Service of Hospital Universitario de
la Princesa has a neurology teaching program certified
for pre and post-degree, assigned to Universidad
Autonoma de Madrid and an accredited clinical
research tradition for nearly 50 years.
The main research lines of The Neurology Service of
Hospital Universitario de la Princesa 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
- Mild Cognitive impairment and dementia in very old
patients
- Cognitive impairment and dementia in Down syndrome
• Multiple Sclerosis.
- Outcome markers and new therapies
– 99 –
AREA 3AREA 2 AREA 1
Line 2.6
Cerebrovascular
diseases
Neuronal excitotoxicity after carotid angioplasty and stent placement
procedures. Graph shows glutamate plasma levels in patients subjected to Carotid Angioplasty and Stenting (CAS) and control groups (cerebral angiography without carotid stenosis and coronary angioplasty
stenting). Increased Glu levels in plasma decreased into the baseline
range at 24 hours, unrelated to stroke, and remained stable up to 72
hours after CAS. Glutamate concentrations remained unchanged over
time in both control groups. Nombela et al., Radiology, 2013.
The results obtained by our group during 2012
include: 6 papers published in international journals
belonging to the Neurosciences field and directly
related to stroke (J. Vasc. Int. Rad., Stroke Res.
Treat., Radiology, Cerebrovasc. Dis., Eur. J. Neurol.);
1 guideline in Stroke; 2 book chapters (Neurology;
Cerebrovascular diseases); 3 epidemiological studies in stroke. Extension of a competitive project (clinical trial and translational study in Stroke) and about
10 ongoing clinical trials (in Stroke, Multiple Sclerosis
and Alzheimer´s and Parkinson´s disease -private
companies).
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 Investigacion 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
– 100 –
Cannabinoid type 2 receptor activation downregulates stroke-induced
classic and alternative brain macrophage/microglial activation concomitant to neuroprotection. Effects of JWH-133 on microglial activation after pMCAO. A, Representative images of Iba1+ cells in the contralateral healthy and the ipsilateral peri-infarct hemispheres I untreated or JWH-133-treated animals. B, Densitometry of peri-infarct microglia in pMCAO mice treated either with vehicle or JWH-133. Sq dashed lines show the ROIs (Regions of interest) where the images were
taken. N=4 in each group. Data were expressed as mean±SD, *P<0.05
vs MCAO contralesional+vehicle, #P<0.05 vs MCAO+vehicle. ANOVA
and Bonferroni post hoc test. Zarruk et al., Stroke 2012.
Medicine and developed through a tight partnership
with IIS IP.
The results obtained by our group during 2012, include
more than 10 papers published in international journals
belonging to the Neurosciences field and directly related to cerebral ischemia (Stroke, J Neuroinflammation,
Biochim Biophys Acta, etc…) and 1 PhD Thesis.
AREA 2
• José Aurelio Vivancos Mora. Estudio doble ciego aleatorizado, controlado con placebo de dosis escaladas de
deferoxamina intravenosa en pacientes con ictus
isquémico agudo tratados con activador tisular de plasminógeno. MEC. ISCIII. FIS. EC 07/90793. Duration:
2008 - 2012.
• José Aurelio Vivancos Mora. Open, randomized and controlled study of safety and viability, to evaluate the neuroprotective effect of plasma glutamate dialysis in acute
ischemic stroke. MSPSI. EC11-109 (SAS/2885/2011).
Duration: 2012 - 2013.
• José Aurelio Vivancos Mora. Imagen molecular multimodal de la inflamación. S2010/BMD-23494. Duration:
2012 - 2015.
MAJOR GRANTS GR.AS.1
• María Ángeles Moro Sánchez. Papel de los
Receptores Nucleares PPARgamma y LXR en la
isquemia cerebral: De la inflamación a la neurorreparación. MICINN. SAF2009-08145 (Subprograma
NEF). Duration: 2010 - 2012.
• María Ángeles Moro Sánchez. Estudio del efecto neuroprotector de compuestos de origen marino en los
daños causados por la isquemia cerebral. MICINN.
Consorcio DENDRIA. Subproyecto 10/DEN005.
Duration: 2010 - 2013.
• Ignacio Lizasoain Hernández. Doble función de los
receptores "Toll-like" en el ictus: reguladores de daño
y reparación. MICINN. SAF2011-23354. Duration:
2011 - 2014.
• María Ángeles Moro Sánchez. Brain dysfunction during aging: relevance for Alzheimer’s disease. MICINN.
CSD2010-00045. Duration: 2011 - 2015.
• María Ángeles Moro Sánchez. Grupo de Investigación
962088. Unidad de Investigación Neurovascular (UIN).
Santander-Universidad Complutense. Convocatoria
GR42/10. Duration: 2012 - 2012.
• María Ángeles Moro Sánchez. Estudio de la biología
de células madre neurales para su empleo en terapia celular en enfermedades neurodegenerativas
(NEUROSTEM-CM). Comunidad de Madrid.
S2010/BMD-2336, Programas de Actividades de
I+D entre Grupos de Investigación en Biomedicina
de la Comunidad de Madrid. Duration: 2012 2015.
• Olivia Hurtado Moreno. Estudio de la sirtuina1 como
diana terapéutica en la neuroprotección y en la neurorreparación tras isquemia cerebral. MEC. SAF201237008. Duration: 2012 - 2013.
PUBLICATIONS GR.35 (8) [IF GR35: 5,890]
YEAR
Total IF
Publication No.
Q1
Q2
2010
6,974
2
1
2011
23,427
5
4
1
2012
26,977
8
3
4
Matute MC, Masjuan J, Egido JA, Fuentes B, Simal P,
Díaz-Otero F, Reig G, Díez-Tejedor E, Gil-Nuñez A,
Vivancos J, Alonso de Leciñana M. Safety and outcomes following thrombolytic treatment in stroke
patients who had received prior treatment with anticoagulants. Cerebrovasc Dis. 33(3):231-239. 2012.
PMID: 22261670. IF: 2,723. DOI: 10.1159/000334662
Fuentes B, Martínez-Sánchez P, Alonso de Leciñana
M, Simal P, Reig G, Díaz-Otero F, Masjuán J, Egido J,
Vivancos J, Gil-Nuñez A, Díez-Tejedor E, Madrid Stroke
Network. Diabetes and previous stroke: hazards for
intravenous thrombolysis?. Eur J Neurol 19(4):587593. 2012. PMID: 22050315. IF: 3,692. DOI:
10.1111/j.1468-1331.2011.03576.x
Fuentes B, Martínez-Sánchez P, de Leciñana MA,
Egido J, Reig-Roselló G, Díaz-Otero F, Sánchez V,
Simal P, Ximenez-Carrillo A, García-Pastor A, Ruiz-Ares
G, García-García A, Masjuan J, Vivancos-Mora J, GilNuñez A, Díez-Tejedor E. Efficacy of intravenous thrombolysis according to stroke subtypes: the Madrid
Stroke Network Data. Eur J Neurol. 19(12):1568-1574.
2012. PMID: 22742869. IF: 3,692. DOI:
10.1111/j.1468-1331.2012.03790.x
de Leciñana MA, Fuentes B, Masjuan J, Simal P, DíazOtero F, Reig G, Díez-Tejedor E, Gil-Nuñez A, Vivancos
J, Egido JA. Thrombolytic therapy for acute ischemic
stroke after recent transient ischemic attack. Int J
– 101 –
AREA 3AREA 2 AREA 1
MAJOR GRANTS GR.35
Stroke. 7(3):213-8. Epub 2011 Nov 9. 2012. PMID:
22098785. IF: 2,382. DOI: 10.1111/j.17474949.2011.00690.x
Sobrado M, Ramirez BG, Neria F, Lizasoain I, Arbonés
ML, Minami T, Redondo JM, Moro MA, Cano E.
Regulator of Calcineurin 1 (Rcan1) has a protective role
in brain ischemia/reperfusion injury. J Neuroinflammation 9:48. 2012. PMID: 22397398. IF: 3,827. DOI:
10.1186/1742-2094-9-48
Cristobo I, Brea D, Blanco M, Vázquez F, RodríguezYáñez M, Vivancos J, Silva Y, de la Ossa NP, Pumar
JM, Forteza J, Castillo J. Usefulness of material recovered from distal embolic protection devices after
carotid angioplasty for proteomic studies. J Vasc Interv
Radiol. 23(6):818-824. 2012. PMID: 22626270. IF:
2,075. DOI: 10.1016/j.jvir.2012.02.004
García-Yébenes I, Sobrado M, Moraga A, Zarruk JG,
Romera VG, Pradillo JM, Perez de la Ossa N, Moro
MA, Dávalos A, Lizasoain I. Iron overload, measured as
serum ferritin, increases brain damage induced by focal
ischemia and early reperfusion. Neurochem Int
61(8):1364-9. 2012. PMID: 23036361. IF: 2,857. DOI:
10.1016/j.neuint.2012.09.014
Zarruk JG, Fernández-López D, García-Yébenes I,
García-Gutiérrez MS, Vivancos J, Nombela F, Torres M,
Burguete MC, Manzanares J, Lizasoain I, Moro MA.
Cannabinoid type 2 receptor activation downregulates
stroke-induced classic and alternative brain
macrophage/microglial activation concomitant to neuroprotection. Stroke 43(1):211-219. 2012. PMID:
22020035. IF: 5,729. DOI: 10.1161/STROKEAHA.111.631044
PUBLICATIONS GR.AS.1 (9)
[IF GRAS1: 37,137]
YEAR
Total IF
Publication No.
Q1
Q2
2010
17,911
4
3
1
2011
33,486
5
5
2012
37,137
9
4
4
Hernández-Jiménez M, Ayuso MI, Pérez-Morgado MI,
García-Recio EM, Alcázar A, Martín ME, González VM.
– 102 –
eIF4F complex disruption causes protein synthesis inhibition during hypoxia in nerve growth factor (NGF)-differentiated PC12 cells. Biochim Biophys Acta 1823(2):4308. 2012. PMID: 22178387. IF: 5,538. DOI:
10.1016/j.bbamcr.2011.11.008
Redondo M, Zarruk JG, Ceballos P, Pérez DI, Pérez C,
Perez-Castillo A, Moro MA, Brea J, Val C, Cadavid MI,
Loza MI, Campillo NE, Martínez A, Gil C.
Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental
stroke model. Eur J Med Chem 47(1): 175-185. 2012.
PMID:
22100138.
IF:
3,346.
DOI:
10.1016/j.ejmech.2011.10.040
Lopez-Jimenez ME, González JC, Lizasoain I, SánchezPrieto J, Hernández-Guijo JM, Torres M. Functional
cGMP-gated channels in cerebellar granule cells. J Cell
Physiol. 227(5):2252-63. 2012. PMID: 21809342. IF:
3,874. DOI: 10.1002/jcp.22964
Sobrado M, Ramirez BG, Neria F, Lizasoain I, Arbonés
ML, Minami T, Redondo JM, Moro MA, Cano E.
Regulator of Calcineurin 1 (Rcan1) has a protective role
in brain ischemia/reperfusion injury. J Neuroinflammation 9:48. 2012. PMID: 22397398. IF: 3,827. DOI:
10.1186/1742-2094-9-48
Hurtado O, Ballesteros I, Cuartero MI, Moraga A, Pradillo
JM, Ramírez-Franco J, Bartolomé-Martín D, Pascual D,
Torres M, Sánchez-Prieto J, Salom JB, Lizasoain I, Moro
MA. Daidzein has neuroprotective effects through ligand-binding-independent PPAR activation. Neurochem
Int 61(1):119-127. 2012. PMID: 22521773. IF: 2,857.
DOI: 10.1016/j.neuint.2012. 04.007
García-Yébenes I, Sobrado M, Moraga A, Zarruk JG,
Romera VG, Pradillo JM, Perez de la Ossa N, Moro MA,
Dávalos A, Lizasoain I. Iron overload, measured as
serum ferritin, increases brain damage induced by focal
ischemia and early reperfusion. Neurochem Int
61(8):1364-9. 2012. PMID: 23036361. IF: 2,857. DOI:
10.1016/j.neuint.2012.09.014
Fernández-López D, Faustino J, Derugin N, Wendland
M, Lizasoain I, Moro MA Vexler ZS. Reduced infarct size
AREA 2
Zarruk JG, Fernández-López D, García-Yébenes I,
García-Gutiérrez MS, Vivancos J, Nombela F,
Torres M, Burguete MC, Manzanares J, Lizasoain I,
Moro MA. Cannabinoid type 2 receptor activation
downregulates stroke-induced classic and alternative brain macrophage/microglial activation concomitant to neuroprotection. Stroke 43(1):211-219.
2012. PMID: 22020035. IF: 5,729. DOI:
10.1161/STROKEAHA.111.631044
ElAli A, Urrutia A, Rubio-Araiz A, HernandezJimenez M, Colado MI, Doeppner TR, Hermann
DM.
Apolipoprotein-E
Controls
Adenosine
Triphosphate-Binding Cassette Transporters
ABCB1 and ABCC1 on Cerebral Microvessels After
Methamphetamine Intoxication. Stroke 43(6):16471653. 2012. PMID: 22426312. IF: 5,729. DOI:
10.1161/STROKEAHA.111.648923
BOOKS GR.35
G. Reig Roselló, L. López Manzanares, F. Nombela
Merchán y J. Vivancos Mora. Enfermedades
venosas. Tratado de Neurología. 2012. Luzan 5 SA.
ISBN: 978-84-7989-698-0.
F. Nombela Merchán, J. Vivancos Mora.
Mecanismos de producción. Factores de riesgo.
Etiologías. Fisiopatología. Enfermedades vasculares cerebrales. 2012. Mayo. ISBN: 978-84-9905156-7.
BOOKS GR.AS.1
Lorenzo P, Moreno A, Leza JC, Lizasoain I, Moro MA,
Portolés A. (Eds.). Velázquez. Manual de Farmacología
Básica y Clínica. 2012. Panamericana. ISBN: 978-849835-437-9.
CLINICAL TRIALS GR.35
PRINCIPAL INVESTIGATOR: MECA LALLANA, VIRGINIA
Registro REDEM: Registro de pacientes con esclerosis
múltiple (EM) tratados con natalizumab en España; (Versión
1:28-10-11). ACADEM. ACA-NAT-2011-02
Registro español de pacientes tratados con Gilenya
(Fingolimod); (Versión enmienda 1: 20-02-12). ACADEM.
ACA-FIN-2011-01
PRINCIPAL INVESTIGATOR: VIVANCOS MORA, AURELIO
Efecto del tratamiento con F2695 (75mg una vez al día)
durante 3 meses en la mejoría de la recuperación funcional
de pacientes con accidente cerebrovascular isquémico.
Estudio multicéntrico, aleatorizado, doble ciego, en grupos
paralelos y controlado con placebo. Estudio LIFE; (Versión
2: 16-05-12). PIERRE FABRE MEDICAMENT. F02695 LP 2
05.
EudraCT: 2012-001592-37
PRINCIPAL INVESTIGATOR: CARRERAS RODRIGUEZ,
MARIA-TERESA
Eficacia y seguridad de 3 dosis de S38093 (2,5y 20 mg/día)
frente a placebo asociado a donepezilo (10mg/día) en
pacientes con Enfermedad de Alzheimer moderada.
Estudio de fase IIb, internacional, multicéntrico, aleatorizado, doble ciego, controlado frente a placebo, de 24 semanas de duración (Versión final:27-03-12). LABORATORIOS SERVIER, S.L. CL2-38093-012.
EudraCT: 2011-005862-40
MARIA-TERESA
Estudio multicéntrico, aleatorizado y controlado para evaluar la eficacia y seguridad de intercambio de plasmático a
corto plazo seguido de plasmaféresis con infusión de
albúmina humana combinada con inmunoglobulina intravenosa en pacientes con Enfermedad de Alzheimer de
leve-moderada; (Versión 1.6: 01-04-12). INSTITUTO GRIFOLS S.A. IG1002.
EudraCT: 2011-001598-25
Efectividad a largo plazo de Copaxone« en la práctica clíni-
– 103 –
AREA 3AREA 2 AREA 1
and accumulation of microglia/macrophages in rats
treated with WIN55,212-2 after neonatal stroke.
Neuroscience
207:307-315.
2012.
PMID:
22285309.
IF:
3,38.
DOI:
10.1016/j.neuroscience.2012.01.008
ca habitual. Estudio observacional (Xperiencia-5); (Versión
final:21-03-12). TEVA PHARMA S.L.U. TEV_ACE_2012_01
MITRA: Estudio observacional retrospectivo y transversal
de adherencia al tratamiento con interferón beta 1a subcutáneo en pacientes con esclerosis múltiple en brotes
mediante el dispositivo electrónico RebiSmart« y el software
MITRA; (versión 1.0: 06-07-12). MERCK S.L. MER-INT2012-01
MARIA-TERESA
Estudio de los biomarcadores en LCR para el diagnóstico
de EA prodrómica en pacientes con deterioro cognitivo
ligero. Estudio PREDEM; (versión final: 21-12-11). NOVARTIS FARMACEUTICA, S.A. NOV-SNC-2011-01
MARIA-TERESA
Estudio de fase IIa para evaluar el efecto del rilapladib (SB
659032) sobre los biomarcadores relacionados con la patogenia y progresión de la Enfermedad de Alzheimer; (Versión
00:11-03-11). GLAXOSMITHKLINE, S.A. LPZ114458.
EudraCT: 2010-020993-41
– 104 –
PRINCIPAL INVESTIGATOR: VIVANCOS MORA, 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; (versión 1: 14-02-12). FUNDACION INVESTIGACION BIOMEDICA H. LA PRINCESA. JVM-GLU-12.
EudraCT: 2012-000791-42
Estudio observacional, transversal, multicéntrico, nacional
para evaluar el cumplimiento terapéutico y la satisfacción de
los pacientes con esclerosis múltiple remitente-recurrente
en tratamiento con fingolimod. Estudio Compliance in MS
II;(versión final: 08-06-12, enmienda 1:02-08-12). NOVARTIS FARMACEUTICA, S.A. NOV-FIN-2012-002
Estudio observacional prospectivo para evaluar la
influencia del resultado del test de anticuerpos antivirus JC sobre la percepción del riesgo en el
tratamiento con natalizumab (Tysabri«) en pacientes
con esclerosis múltiple y sus neurólogos; (versión
final: 27-04-12). BIOGEN IDEC IBERIA. BIO-NAT2012-01/PERCEPT
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.
– 105 –
AREA 3
– 106 –
AREA 3
Line 3.1
Prognostic and
predictor markers in
autoimmune diseases
GROUP 36
been granted by ISCIII for the next four years. 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, etc. are objectives of the research work conducted by our
HEAD OF LABORATORY
Isidoro González Álvaro
AREA 3AREA 2 AREA 1
GROUP MEMBERS
• Rosario García de Vicuña Pinedo
• Ana María Ortiz García
• Jesús Alberto García Vadillo
• Santos Castañeda Sanz
• José María Álvaro-Gracia Álvaro
• Carlos Gamallo Amat
• Eva Gloria Tomero Muriel
• Esther Patiño Ruiz
• Amalia Lamana Domínguez
• Esther Francisca Vicente Rabaneda
• Isabel Castrejón Fernández
• Teresa Velasco Ripoll
• María de las Nieves Gómez León
• Belén Díaz Sánchez
RESEARCH INTEREST
During year 2012, once more our main source of
publications comes from the intense collaborative
effort with groups of the Network of Inflammation
and Rheumatic Diseases (RIER) that belongs to
the RETICS program from the Instituto de Salud
Carlos III (ISCIII). Interestingly, this year RIER has
Lamana A, Balsa A, Rueda B, Ortiz AM, Nuno L, Miranda-Carus ME, Gonzalez-Escribano MF, Lopez-Nevot MA, Pascual-Salcedo D, Martin J et
al: The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early
Arthritis. PLoS One 2012, 7(8):e43661.
– 107 –
Advanced therapies and individualized medicine
Luis Fernandez Sueiro who died suddenly in
November 2012 during the ACR Meeting.
MAJOR GRANTS
Lamana A, Balsa A, Rueda B, Ortiz AM, Nuno L, Miranda-Carus ME, Gonzalez-Escribano MF, Lopez-Nevot MA, Pascual-Salcedo D, Martin J et
al: The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early
Arthritis. PLoS One 2012, 7(8):e43661.
researchers. Once again, as a result of this intense
activity of the group, some of its members have
been requested to participate in the drafting of 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.
For second consecutive year, a research project of
one of our investigators (Dr Santos Castañeda
Sanz) has been granted in the last call for Health
Research Grants from the ISCIII three projects. This
means that currently our group has four active
research proyect in the FIS program of ISCIII.
We would like to acknowledge the generous collaboration of our patients in our research projects.
Their willingness to participate in our studies support the notion that they support our efforts to discover new biomarkers allowing us to treat them
more efficiently.
The figures accompanying this summary represent
two good examples of this kind of research. The
figure related to biomarkers in psoriasis is in
memoriam of our collegue from A Coruña Dr Jose
– 108 –
• Isidoro González Álvaro. Red de Investigación en
Inflamación y Enfermedades Reumáticas. ISCIII.
RD08/0075/0004. Duration: 2009 - 2012.
• Santos Castañeda Sanz. Valor predictivo de la pérdida mineral ósea cortical determinada mediante radiogrametría como marcador pronóstico en pacientes
con artritis de inicio. PFIZER España. Duration: 2011
- 2012.
• Santos Castañeda Sanz. Valor predictivo de la radiogrametría de manos como factor pronóstico en
una cohorte de artritis de inicio. Financiado por
Pfizer a través de la FIB del HUP. Duration: 2011 2012.
• Isabel Castrejón Fernández. Relative efficiencies of 7
RA core data set measures and 3 indices to distinguish between tight control in the GUEPARD cohort
(DAS28-ESR-driven therapy with anti-TNF agents)
versus routine care in the ESPOIR cohort. NYUHospital for Joint Diseases and Hospital Cochin,
Paris. Duration: 2011 - 2012.
• Isabel Castrejón Fernández. Evaluation of the proposed
ACR/EULAR criteria and traditional DAS28, CDAI and
RAPID3 definitions of remission in Rheumatoid Arthritis
in routine clinical care. Internal support (NYU-Hospital
for Joint Dise ases). Duration: 2011 - 2012.
• Isabel Castrejón Fernández. Development of an online
“toolbox” including indices and measures in rheumatology with special emphasis on Patient Reported
Outcomes (PRO). EULAR. Duration: 2011 - 2013.
• Isidoro González Álvaro. 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.
PI11/00551. Duration: 2012 - 2014.
• Rosario García de Vicuña Pinedo. Proyecto VALORA: “Estudio de la Variablidad en el Hospital de Día
en Reumatología”. Sociedad Española Reumatología
- Roche. Duration: 2012 - 2013.
AREA 3
• Ana María Ortiz García. 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. Financiado por UCB a través de la FIB del HUP.
Duration: 2012 - 2014.
• Ana María Ortiz García. Estudio de los niveles de VIP
y sus receptores en pacientes con artritis de reciente
comienzo. Determinación de su potencial como biomarcador pronóstico. ISCIII. PI11/00505. Duration:
2012 - 2014.
Total IF
Publication No.
Q1
2010
2011
116,956
29
14
8
151,416
36
15
14
2012
138,584
31
15
8
Bykerk VP, Ostör AJ, Alvaro-Gracia J, Pavelka K, Ivorra
JA, Graninger W, Bensen W, Nurmohamed MT, Krause
A, Bernasconi C, Stancati A, Sibilia J. Tocilizumab in
patients with active rheumatoid arthritis and inadequate
responses to DMARDs and/or TNF inhibitors: a large,
open-label study close to clinical practice. Ann Rheum
Dis. 71(12):1950-4. 2012. PMID: 22615456. IF: 8,727.
DOI: 10.1136/annrheumdis-2011-201087
Q2
Ruiz-Tovar J, Gamallo C. Duodenitis associated with
non-steroidal anti-inflammatory drug use causing
mesenteric panniculitis. Am Surg. 78(3):E137-8. 2012.
PMID: 22524738. IF: 1,285
Pincus T, Castrejon I, Yazici Y. Low-dose prednisone
inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis. Ann Intern Med.
157(4):299. 2012. PMID: 22910946. IF: 16,733. DOI:
10.7326/0003-4819-157-4-201208210-00018
Gómez-Reino JJ, Rodríguez-Lozano C, CamposFernández C, Montoro M, Descalzo MÁ, Carmona L;
BIOBADASER 2.0 Study Group (..,Tomero E, Ortiz
AM,..). Change in the discontinuation pattern of tumor
necrosis factor antagonist in rheumatoide arthritis over
10 years: data from the Spanish registry BIOBADASER
2.0. Ann Rheum Dis 71(3):382-5. Epub 2011 Oct 13.
2012. PMID: 21998116. IF: 8,727. DOI:
10.1136/annrheumdis-2011-200302
Carmona FD, Gutala R, Simeón CP, Carreira P, OrtegoCenteno N, Vicente-Rabaneda E, García-Hernández
FJ, García de la Peña P, Fernández-Castro M,
Díaz-Gallo LM, Garcia S, Ortego-Centeno N, JiménezAlonso J, Sánchez-Román J, de Ramón E, GonzálezEscribano MF, Balsa A, Fernández-Gutierrez B,
González-Alvaro I, González-Gay MA, Martin J.
Association study of BAK1 gene polymorphisms in
Spanish rheumatoid arthritis and systemic lupus erythematosus cohorts. Ann Rheum Dis. 71(2):314-6.
Epub 2011 Aug 17. 2012. PMID: 21852253. IF: 8,727.
DOI: 10.1136/annrheumdis-2011-200062
Descalzo MÁ, Carbonell J, González-Alvaro I Sanmartí R,
Balsa A, Hernandez-Barrera V, Román-Ivorra JA, IvorraCortés J, Lisbona P, Alperi M, Jiménez-Garcia R, Carmona
L; SERAP (.., Ortiz AM, Garcia-Vicuña R,..) and PROAR
Study Groups (.., Garcia-Vicuña R,..). Effectiveness of a
clinical practice intervention in early rheumatoid arthritis.
Arthritis Care Res (Hoboken). 64(3):321-30. 2012. PMID:
22052599. IF: 4,851. DOI: 10.1002/acr.20682
Castrejon I, McCollum L, Tanriover MD, Pincus T.
Importance of patient history and physical examination
in rheumatoid arthritis compared to other chronic diseases: Results of a physician survey. Arthritis Care Res
(Hoboken). 64(8):1250-1255. 2012. PMID: 22371298.
IF: 4,851. DOI: 10.1002/acr.21650
Celis R, Planell N, Fernández-Sueiro JL, Sanmartí R,
Ramírez J, González-Alvaro I, Pablos JL, Cañete JD.
– 109 –
AREA 3AREA 2 AREA 1
YEAR
Martínez-Estupiñán L, Egurbide MV, Tsao BP, Gourh P,
Agarwal SK, Assassi S, Mayes MD, Arnett FC, Tan FK,
Martín J; Spanish Scleroderma Group. Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemi c sclerosis. Ann
Rheum Dis. 71(1):114-9. 2012. PMID: 21926187. IF:
8,727. DOI: 10.1136/annrheumdis-2011-200275
Synovial cytokine expression in psoriatic arthritis and
associations with lymphoid neogenesis and clinical features. Arthritis Res Ther. 14(2):R93. 2012. PMID:
22541888. IF: 4,445. DOI: 10.1186/ar3817
López-Mejías R, García-Bermúdez M, GonzálezJuanatey C, Castañeda S, Miranda-Filloy JA, GómezVaquero C, Fernández-Gutiérrez B, Balsa A, PascualSalcedo D, Blanco R, González-Álvaro I, Llorca J,
Martín J, González-Gay MA. NFKB1-94ATTG ins/del
polymorphism (rs28362491) is associated with cardiovascular disease in patients with rheumatoid arthritis.
Atherosclerosis. 224(2):426-9. 2012. PMID: 22742859.
IF: 3,794. DOI: 10.1016/j.atherosclerosis.2012.06.008
Castañeda S, Roman-Blas JA, Largo R, HerreroBeaumont G. Subchondral bone as a key target for
osteoarthritis treatment. Biochem Pharmacol.
83(3):315-23. Epub 2011 Sep 22. 2012. PMID:
21964345. IF: 4,705. DOI: 10.1016/j.bcp.2011.09.018
Lamana A, Cibrian D, Giron RM, Vara A, SanchezMadrid F, Ancochea J. Reduced expression of galectin1 and galectin-9 by leucocytes in asthma patients. Clin
Exp Immunol. 170(3):365-374. 2012. PMID:
23121677. IF: 3,36. DOI: 10.1111/j.13652249.2012.04665.x
Garcia-Bermudez M, González-Juanatey C, LopezMejias R, Rodriguez-Rodriguez L, Pérez-Esteban S,
Castañeda S, Urcelay E, Miranda-Filloy JA, GómezVaquero C, Fernández-Gutierrez B, Balsa A, GonzálezAlvaro I, Blanco R, Llorca J, Martín J, Gonzalez-Gay MA.
Influence of MHCIITA rs3087456 and rs4774 polymorphisms in the susceptibility to cardiovascular disease of
patients with rheumatoid arthritis. Clin Exp Rheumatol.
30(1):51-7. 2012. PMID: 22272574. IF: 2,148
Pincus T, Castrejón I, Bergman MJ, Yazici Y. Treat-totarget: not as simple as it appears. Clin Exp Rheumatol.
30(4 Suppl 73):S10-20. 2012. PMID: 23072741. IF:
2,148
Castrejón I, Pincus T. Patient self-report outcomes to
guide a treat-to-target strategy in clinical trials and
– 110 –
usual clinical care of rheumatoid arthritis. Clin Exp
Rheumatol. 30(4 Suppl 73):S50-55. 2012. PMID:
23079199. IF: 2,148
García-Bermúdez M, López-Mejías R, GonzálezJuanatey C, Castañeda S, Miranda-Filloy JA, Blanco R,
Fernández-Gutiérrez B, Balsa A, González-Alvaro I,
Gómez-Vaquero C, Llorca J, Martín J, González-Gay
MA. Lack of association between TLR4 rs4986790
polymorphism and risk of cardiovascular disease in
patients with rheumatoid arthritis. DNA Cell Biol.
31(7):1214-20. 2012. PMID: 22360682. IF: 2,072. DOI:
10.1089/dna.2011.1582
García-Bermúdez M, López-Mejías R, GonzálezJuanatey C, Corrales A, Castañeda S, Miranda-Filloy
JA, Gómez-Vaquero C, Fernández-Gutiérrez B, Balsa
A, Pascual-Salcedo D, Blanco R, González-Álvaro I,
Llorca J, Martín J, González-Gay MA. Association
Study of MIA3 rs17465637 Polymorphism with
Cardiovascular Disease in Rheumatoid Arthritis
Patients. DNA Cell Biol. 31(8):1412-7. 2012. PMID:
22577832. IF: 2,072. DOI: 10.1089/dna.2012.1672
Martin JE, Carmona FD, Broen JC, Simeón CP, Vonk
MC, Carreira P, Ríos-Fernández R, Espinosa G,
Vicente-Rabaneda E, Tolosa C, García-Hernández FJ,
Castellví I, Fonollosa V, González-Gay MA, SáezComet L, Portales RG, de la Peña PG, FernándezCastro M, Díaz B, Martínez-Estupiñán L, Coenen M,
Voskuyl AE, Schuerwegh AJ, Vanthuyne M, Houssiau F,
Smith V, de Keyser F, De Langhe E, Riemekasten G,
Witte T, Hunzelmann N, Kreuter A, Palm Ø, Chee MM,
van Laar JM, Denton C, Herrick A, Worthington J,
Koeleman BP, Radstake TR, Fonseca C, Martín J;
Spanish Scleroderma Group. The autoimmune disease-associated IL2RA locus is involved in the clinical
manifestations of systemic sclerosis. Genes Immun.
13(2):191-6. 2012. PMID: 22012429. IF: 3,872. DOI:
10.1038/gene.2011.72
López-Mejías R, García-Bermúdez M, GonzálezJuanatey C, Castañeda S, Miranda-Filloy JA, GómezVaquero C, Fernández-Gutiérrez B, Balsa A, PascualSalcedo D, Blanco R, González-Álvaro I, Llorca J,
Martín J, González-Gay MA. Lack of association
AREA 3
Martin JE, Broen JC, Carmona FD, Teruel M,
Simeon CP, Vonk MC, van 't Slot R, RodriguezRodriguez L, Vicente E, Fonollosa V, OrtegoCenteno N, González-Gay MA, García-Hernández
FJ, de la Peña PG, Carreira P; Spanish Scleroderma
Group, Voskuyl AE, Schuerwegh AJ, van Riel PL,
Kreuter A, Witte T, Riemekasten G, Airo P, Scorza R,
Lunardi C, Hunzelmann N, Distler JH, Beretta L, van
Laar J, Chee MM, Worthington J, Herrick A, Denton
C, Tan FK, Arnett FC, Assass i S, Fonseca C, Mayes
MD, Radstake TR, Koeleman BP, Martin J.
Identification of CSK as a systemic sclerosis genetic risk factor through Genome Wide Association
Study follow-up. Hum Mol Genet. 21(12):2825-35.
2012. PMID: 22407130. IF: 7,636. DOI:
10.1093/hmg/dds099
Castelblanco E, Gallel P, Ros S, Gatius S, Valls J, DeCubas AA, Maliszewska A, Yebra-Pimentel MT,
Menarguez J, Gamallo C, Opocher G, Robledo M,
Matias-Guiu X. Thyroid paraganglioma. Report of 3
cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary
thyroid carcinoma, based on complementary DNA
array results. Hum Pathol. 43(7):1103-12. 2012. PMID:
22209341. IF: 2,876. DOI: 10.1016/j.humpath.2011.
08.022
Augustin M, Alvaro-Gracia JM, Bagot M, Hillmann O,
van de Kerkhof PC, Kobelt G, Maccarone M, Naldi L,
Schellekens H. A framework for improving the quality of
care for people with psoriasis. J Eur Acad Dermatol
Venereol. 26(Supl 4):1-16. 2012. PMID: 22725729. IF:
2,98. DOI: 10.1111/j.1468-3083.2012.04576.x
Robledo G, González-Gay MA, Fernández-Gutiérrez B,
Lamas JR, Balsa A, Pascual-Salcedo D, Castañeda S,
Blanco R, González-Alvaro I, García A, Raya E,
Gómez-Vaquero C, Delgado M, Martín J. NPSR1 gene
is associated with reduced risk of rheumatoid arthritis.
J Rheumatol. 39(6):1166-70. 2012. PMID: 22548958.
IF: 3,695. DOI: 10.3899/jrheum.111205
Carmona FD, Serrano A, Rodríguez-Rodríguez L,
Callejas JL, Simeón CP, Carreira P, Castañeda S,
Solans R, Blanco R; The Spanish Scleroderma Group;
The Spanish Giant Cell Arteritis Group, González-Gay
MA, Martín J. Evaluation of a Shared Autoimmune
Disease-associated Polymorphism of TRAF6 in
Systemic Sclerosis and Giant Cell Arteritis. J
Rheumatol. 39(6):1275-1279. 2012. PMID: 22589256.
IF: 3,695. DOI: 10.3899/jrheum.120038
Fernández-Nebro A, de la Fuente JM, Carreño L,
Izquierdo MG, Tomero E, Rúa-Figueroa I, HernándezCruz B, Narváez J, Ucar E, Olivé A, Zea A, FernándezCastro M, Raya-Álvarez E, Pego-Reigosa J, Freire M,
Martínez-Taboada V, Pérez-Venegas J, Sánchez-Atrio A,
Villa-Blanco I, Manrique-Arija S, López-Longo F, Carreira
P, Martínez-Pérez R, García-Vicuña R. Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study. Lupus.
21(10):1063-76. 2012. PMID: 22786985. IF: 2,337. DOI:
10.1177/0961203312446627
García-Bermúdez M, López-Mejías R, GonzálezJuanatey C, Corrales A, Robledo G, Castañeda S,
Miranda-Filloy JA, Blanco R, Fernández-Gutiérrez B,
Balsa A, González-Alvaro I, Gómez-Vaquero C, Llorca
J, Martín J, González-Gay MA. Analysis of the interferon gamma (rs2430561, +874T/A) functional gene variant in relation to the presence of cardiovascular events
in rheumatoid arthritis. PLoS One. 7(10):e47166. 2012.
PMID: 23077565. IF: 4,092. DOI: 10.1371/journal.
pone.0047166
García-Bermúdez M, González-Juanatey C, LópezMejías R, Teruel M, Corrales A, Miranda-Filloy JA,
Castañeda S, Balsa A, Fernández-Gutierrez B,
González-Álvaro I, Gómez-Vaquero C, Blanco R, Llorca
J, Martín J, González-Gay MA. Study of association of
CD40-CD154 gene polymorphisms with disease susceptibility and cardiovascular risk in Spanish rheumatoid arthritis patients. PLoS One. 7(11):e49214. 2012.
PMID: 23166616. IF: 4,092. DOI: 10.1371/journal.
pone.0049214
– 111 –
AREA 3AREA 2 AREA 1
between the CXCL12 rs501120 polymorphism and
cardiovascular disease in Spanish patients with
rheumatoid arthritis. Hum Immunol. 73(5):543-6. 2012.
PMID: 22386691. IF: 2,837. DOI: 10.1016/j.humimm.
2012.02.012
Lamana A, Balsa A, Rueda B, Ortiz AM, Nuño L,
Miranda-Carus ME, Gonzalez-Escribano MF, LopezNevot MA, Pascual-Salcedo D, Martin J, GonzálezÁlvaro I. The TT Genotype of the STAT4 rs7574865
Polymorphism Is Associated with High Disease Activity
and Disability in Patients with Early Arthritis. PLoS One.
7(8):e43661. 2012. PMID: 22937072. IF: 4,092. DOI:
10.1371/journal.pone.0043661
K Shum, I Castrejón, C-E Tseng, A Askanase. Authors'
reply. Scand J Rheumatol. 41(5):409-410. 2012. IF:
2,472. DOI: 10.3109/03009742.2012.676808
Ruiz-Tovar J, Gamallo C. Streptococcus salivarius
causing multiple liver abscesses in a patient with
situs inversus. Surg Infect (Larchmt). 13(2):130-1.
2012.
PMID:
22439778.
IF:
1,8.
DOI:
10.1089/sur.2011.082
Cénit MC, Simeón CP, Fonollosa V, Espinosa G,
Beltrán E, Sáez-Comet L, Vicente-Rabaneda E,
García-Hernández FJ, Martínez-Estupiñán L,
Rodríguez-Carballeira M, Hernández V, de la Peña
PG, Fernández-Castro M, Narváez FJ, Pros A,
Gallego M, Ríos-Fernández R, Camps MT,
Fernández-Nebro A, Egurbide MV, Carreira P,
González-Gay MA, Martín J; Spanish Scleroderma
Group. No evidence of association between functional polymorphisms located within IL6R and IL6ST
genes and systemic sclerosis. Tissue Antigens.
80(3):254-8. 2012. PMID: 22742541. IF: 2,588. DOI:
10.1111/j.1399-0039.2012.01915.x
BOOKS
Esther F. Vicente Rabaneda, Santos Castañeda Sanz.
Diagnóstico diferencial de la artrosis tipo II de la mujer
menopáusica. Módulo 2. Curso virtual para ginecólogos y generalistas 2012-13. 2012.
Santos Castañeda, Gabriel Herrero-Beaumont. Futuro
en la atención y abordaje de la artrosis. Módulo 4.
Curso virtual para ginecólogos y generalistas 2012-13.
2012.
– 112 –
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: GARCIA DE VICUÑA PINEDO, ROSARIO
Estudio sobre el perfil y el manejo clínico de los
pacientes con artritis reumatoide tratados con terapias
biológicas en monoterapia. "EstudioBIO MONO; (versión 9.00:22-12-11). ROCHE FARMA, S.A. ROC-BIO2011-01
Inmunogenicidad de las terapias Anti-TNF en los
pacientes con enfermedades reumáticas. Estudio REASON; (versión 4: 21-02-12). LABORATORIOS PFIZER
ESPAÑA, S.A. PFI-ANT-2012-01
PRINCIPAL INVESTIGATOR: ALVARO-GRACIA ALVARO,
JOSE M.
Estudio multicéntrico, aleatorizado, en doble ciego y controlado con placebo, para evaluar la eficacia y la seguridad de certolizumab pegol en combinación con
metotrexato en la inducción y el mantenimiento de la
respuesta clínica en adultos con artritis reumatoide activa
en fase inicial no tratados previamente con Farme; (versión enmienda: 25-10-11). UCB PHARMA, S. A.
RA0055.
EudraCT: 2011-001729-25
Estudio observacional, comparativo, global, en pacientes
con artritis reumatoide (AR) tratados con un inhibidor de
TNF o tocilizumab como primera terapia biológica;
(Versión 3.0:25-11-11). F. HOFFMANN-LA ROCHE LTD.
MA27950/FHO-TOC-2011-01
PRINCIPAL INVESTIGATOR: GARCIA VADILLO, JESUS
Proyecto Sjögren-SER: Creación de un registro de
pacientes con Síndrome de Sjögren primario; (versión
marzo 2012). SOCIEDAD ESPAÑOLA DE REUMATOLOGIA. SER-TRA-2012-01
Estudio multicéntrico, internacional, aleatorizado, doble
AREA 3
PRINCIPAL INVESTIGATOR: GARCIA VADILLO, JESUS
Estudio aleatorizado, doble ciego y con control activo
para evaluar la eficacia y seguridad de denosumab comparado con risedronato en pacientes tratados con glucocorticoides; (Versión 06-12-11). AMGEN INC. 20101217.
EudraCT: 2010-024393-19
PRINCIPAL INVESTIGATOR: ORTIZ GARCIA, ANAMARIA
Estudio de extensión de cuatro años de seguimiento
para evaluar la eficacia, seguridad y tolerabilidad a largo
plazo de secukinumab en pacientes con artritis reumatoide activa; (versión V00:29-06-12). NOVARTIS FARMACEUTICA, S.A. CAIN457F2309E1.
EudraCT: 2012-002760-27
GRUPO 37
HEAD OF LABORATORY
Esteban Daudén Tello
GROUP MEMBERS
• María Carmen García García
• Diego de Argila Fernández-Durán
• Javier Sánchez Pérez
• Fátima Tudelilla Fernández
• María Jesús Gómez Gago
MAJOR GRANTS
Esteban Daudén Tello. Estudio sobre comorbilidad
en Psoriasis. Laboratorio PFIZER y Cátedra de
Psoriasis de la UAM. Duration: 2010 - 2012.
YEAR
Total IF
Publication No.
Q1
Q2
2010
28,877
10
5
4
2011
31,284
12
6
4
2012
39,348
10
8
1
Sánchez-Moya AI, Daudén E. Peripheral lymph node
recurrence of tuberculosis after ustekinumab treatment. Arch Dermatol. 148(11):1332-3. 2012. PMID:
23165852. IF: 3,888. DOI: 10.1001/archdermatol.2012.2958
Llamas-Velasco M, Sánchez-Pérez J, Gallo E, Fraga
J. Hyperpigmented asymptomatic macule in a fingertip with suspicious dermoscopic pattern--quiz case.
22351829. IF: 3,888. DOI: 10.1001/archdermatol.2011.1073a
Garcia-Doval I, Carretero G, Vanaclocha F, Ferrandiz
C, Daudén E, Sánchez-Carazo JL, Alsina M, HerreraCeballos E, Gómez-García FJ, Ferrán M, LópezEstebaranz JL, Hernanz JM, Belinchón-Romero I,
Vilar-Alejo J, Rivera R, Carrascosa JM, Carazo C. Risk
of serious adverse events associated with biologic
and nonbiologic psoriasis systemic therapy: patients
ineligible vs eligible for randomized controlled trials.
22508869. IF: 3,888. DOI: 10.1001/archdermatol.2011.2768
Pedraz J, Onate MJ, García-García C, Fraga J,
Daudén E. Long-term nasal plaque with nasal
obstruction. Arch Dermatol. 148(6):755-60. 2012.
PMID: 22710460. IF: 3,888. DOI: 10.1001/archderm.148.6.755-b
Uter W, Aberer W, Armario-Hita JC, FernandezVozmediano JM, Ayala F, Balato A, Bauer A, BallmerWeber B, Beliauskiene A, Fortina AB, Bircher A,
Brasch J, Chowdhury MM, Coenraads PJ,
Schuttelaar ML, Cooper S, Czarnecka-Operacz M,
Zmudzinska M, Elsner P, English JS, Frosch PJ,
Fuchs T, García-Gavín J, Fernández-Redondo V,
Gawkrodger DJ, Giménez-Arnau A, Green CM, Horne
– 113 –
AREA 3AREA 2 AREA 1
ciego, controlado con alendronato para determinar la eficacia y seguridad de AMG 785en el tratamiento de
mujeres con osteoporosis postmenopáusica; (versión
22-12-11). AMGEN INC. 20110142.
EudraCT: 2011-003142-41
HL, Johansen JD, Jolanki R, Pesonen M, King CM,
Krêcisz B, Chomiczewska D, Kiec-Swiercz ynska M,
Larese F, Mahler V, Ormerod AD, Peserico A,
Rantanen T, Rustemeyer T, Sánchez-Pérez J, Sansom
JE, Silvestre JF, Simon D, Spiewak R, Statham BN,
Stone N, Wilkinson M, Schnuch A. Current patch test
results with the European baseline series and extensions to it from the 'European Surveillance System on
Contact Allergy' network, 2007-2008. Contact
Dermatitis. 67(1):9-19. 2012. PMID: 22500724. IF:
3,509. DOI: 10.1111/j.1600-0536.2012.02070.x
Daudén E, Herrera E, Puig L, Sánchez-Carazo JL,
Toribio J, Caloto MT, Nocea G, Roset M, Lara N.
Validation of a new tool to assess health-related quality of life in psoriasis: the PSO-LIFE questionnaire.
Health Qual Life Outcomes. 10:56. 2012. PMID:
22624984. IF: 2,112. DOI: 10.1186/1477-7525-10-56
Julià A, Tortosa R, Hernanz JM, Cañete JD, Fonseca
E, Ferrándiz C, Unamuno P, Puig L, Fernández-Sueiro
JL, Sanmartí R, Rodríguez J, Gratacós J, Daudén E,
Sánchez-Carazo JL, López-Estebaranz JL, MorenoRamírez D, Queiró R, Montilla C, Torre-Alonso JC,
Pérez-Venegas JJ, Vanaclocha F, Herrera E, MuñozFernández S, González C, Roig D, Erra A, Acosta I,
Fernández-Nebro A, Zarco P, Alonso A, LópezLasanta M, García-Montero A, Gelpí JL, Absher D,
Marsal S. Risk variants for psoriasis vulgaris in a large
case-control collection and association with clinical
subphenotypes. Hum Mol Genet. 21(20):4549-57.
2012. PMID: 22814393. IF: 7,636. DOI:
10.1093/hmg/dds295
Cibrian D, Sanchez-Cuellar S, Daudén E, Fresno M,
García-Diez A, Sanchez-Madrid F. Psoriasis in humans
is associated with downregulation of galectins in dendritic cells. J Pathol. 228: 193-203. 2012. PMID:
22271227. IF: 6,318. DOI: 10.1002/path.3996
García-Martín P, De Argila D, To-Figueras J, LlamasVelasco M, Fraga J, García-Diez A. Phototolerance
– 114 –
induced by narrow-band UVB phototherapy in severe
erythropoietic protoporphyria. Photodermatol
Photoimmunol Photomed. 28(5):261-3. 2012. PMID:
22971192. IF: 1,305. DOI: 10.1111/j.16000781.2012.00677.x
Navarro R, Daudén E, Gallo E, Santiago SánchezMateos D, García-Diez A. Alopecia areata during treatment of psoriasis with adalimumab and leflunomide: a
case and review of the literature. Skin Pharmacol
Physiol. 25(2):107-10. 2012. PMID: 22301842. IF:
2,916. DOI: 10.1159/000335264
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: DAUDEN TELLO, ESTEBAN
Efecto de la inmunogenicidad de las terapias anti-TNF
sobre la respuesta terapéutica obtenida en los pacientes
con psoriasis en placas moderada agrave. Estudio
PREDIR, (Versión final:20-02-12). LABORATORIOS PFIZER S.L.U. PFI-ETA-2012-01
Estudio observacional de los efectos hepáticos del ustekinumab; versión septiembre-octubre 2012. AAHUP
Estudio epidemiológico observacional para evaluar la
retención en el tratamiento de los pacientes con psoriasis de moderada a grave en la práctica clínica; (versión
ESP/CGL/CNTO1275PSO4024/Protocolo/v1.0:29-1111). Estudio SAHARA. JANSSEN-CILAG, S.A. JANPSO-2011-01
PRINCIPAL INVESTIGATOR: SANCHEZ PEREZ, ABILIO
JAVIER
El uso de alitretinoina oral en el tratamiento del eczema
crónico de manos en el ámbito sanitario público español:
descripción y análisis de la práctica clínica actual; (Versión
04: enero 2012). ALMIRALL S.A. 11-ALL-04-RETRO
AREA 3
Line 3.2
Esophagogastrointestinal
GRUPO 38
GROUP MEMBERS
• José Maté Jiménez
• María Encarnación Fernández Contreras
• María Chaparro Sánchez
• Adrián Gerald Mcnicholl
• Pablo Muñoz Linares
• Carlos Castaño Milla
• Alicia Marín Gómez
• María José Beceiro Pedreño
• Almudena Durán Vegue
• Mercedes Ramas López
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 Disease (IBD). Clinical and epidemiological projects are performed coordinating
networks of gastroenterologists from hospitals all
over Spain. Different projects have been developed in
collaboration with the Pathology service, the
Immunology service and the Clinical Pharmacology
service of La Princesa Hospital, the Research Unit of
Guadalajara’s
Hospital,
the
Pharmaceutical
Technology Department and the Organic Chemistry
department of the Complutense University of Madrid,
the Biochemistry and Molecular Biology Department
of Alcalá de Henares University, the Oncology
Institute of Catalunya, the Galician Genomics
Foundation, and numerous Digestive Services
throughout Spain.
In 2012 the group has focused on increasing its
activity in European and international contexts:
• Dr. Gisbert (Group Leader) has been elected
President of the European Helicobacter Study Group.
• Our team leads the organization of the International
Workshop on Helicobacter to be hold in Madrid,
September 2013.
• Coordinates the ‘Pan-European Registry on
Helicobacter 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 and research
– 115 –
AREA 3AREA 2 AREA 1
HEAD OF LABORATORY
Javier Pérez Gisbert
project entitled ‘Optimal H. pylori management in
Primary Care’ aiming to improve the knowledge
and implementation of the ‘Maastricht IV European
Consensus on Helicobacter pylori infection’ in 8
European countries.
Main research Topics
• Gastric H. pylori induced proliferation/apoptosis
- Effect of infection status, bacterial strain,
patients’ genotype and the type and severity of
gastric lesions
- Comparison pre and post H. pylori eradication
- Genetic and epidemiological factors in the progression of pre-cancerous lesions
• Angiogenesis and lymphangiogenesis in IBD
- Ulcerative colitis vs. Crohn’s disease
- Pathological behavior of the disease
- Effect of the therapy
• Immunity in IBD
- Vaccination optimization in IBD patients
- Immunological alterations after Hepatitis B virus
(HBV) vaccination
- Predictive variables to HBV vaccination response
- Mechanisms of production of antibodies against
anti-TNF treatments
• New diagnostic methods
- Serologic diagnosis of Duodenal Ulcer
- Diagnosis of H. pylori infection with novel monoclonal fecal kits
- Clinical utility of biological markers like fecal calprotectin as well as azathioprine metabolites
- Theragnosis (Genetic/Pharmacogenetic) and individualized medicine in IBD
- Improved diagnosis of concomitant diseases in
IBD
• New therapies
- Routine-data-based studies on the efficacy and
safety of novel and traditional treatments on H.
pylori eradication
- New antibiotic combinations and formulations
(hydrogels) for H. pylori treatment
- Photodynamic therapy applied to the inactivation
of H. pylori
- Identification of new therapeutic targets in IBD
(PSGL-1, MT1-MMP, IFG-1, ER , CB1 and
CB2)
– 116 –
MAJOR GRANTS
• Javier Pérez Gisbert. Registro de colitis
microscópica nacional (proyecto RECOMINA):
estudio de factores ambientales de riesgo de colitis microscópica y creación de un banco de ADN.
ISCIII. PI061577. Duration: 2009 - 2012.
• Javier Pérez Gisbert. Implicación de los factores
angiogénicos y linfangiogénicos en la enfermedad
inflamatoria intestinal. ISCIII. PS09/02369.
Duration: 2010 - 2012.
• Javier Pérez Gisbert. Biobanco IMIDs diferencial
permite identificar biomarcadores y nuevas terapias. Subprograma INNPACTO MICINN. IPT010000-2010-036. Duration: 2010 - 2013.
• Javier Pérez Gisbert. Estudio genético en
pacientes con Enfermedad Inflamatoria Intestinal
con mielotoxicidad por tiopurinas con actividad
de la TPMT normal. Asociación Castellana de
Aparato Digestivo. Duration: 2011 - 2012.
• Javier Pérez Gisbert. Centro de Investigación
Biomédica en Red de Enfermedades Hepáticas y
Digestivas (CIBEREHD). Ministerio de Sanidad y
Consumo (ISCIII). ISCIII. Duration: 2012 - .
• Javier Pérez Gisbert. Desarrollo de un método
basado en ELISA par la medición de los niveles
séricos de anti-TNF y anticuerpos contra el fármaco. PRE-PREDICROHN. MSD. Duration: 2012 - .
• María Encarnación Fernández Contreras.
Involvement of estrogen receptor beta (ER ) and
thymidylate syntase polymorphisms in inflammatory bowel disease. Duration: 2012 - .
• María Chaparro Sánchez. Impacto de la vacuna
frente al virus de la hepatitis B en el sistema
inmune. GETTECCU-Otsuka. Duration: 2012 2013.
PUBLICATIONS (47) [IF: 313,775
YEAR
Total IF
Publication No.
Q1
Q2
2010
76,409
21
8
10
2011
172,025
34
22
9
2012
313,775
47
32
11
AREA 3
M Barreiro-de Acosta, JP Gisbert. Letter: surgery for
ulcerative colitis mostly follows anti-TNF drugs - a new
'therapeutic package'?. Aliment Pharmacol Ther 2012
36(3):297-298. 2012. PMID: 22747458. IF: 3,769. DOI:
10.1111/j.1365-2036.2012.05158.x
JP Gisbert, L Menchén, V García-Sánchez, I Marín, JR
Villagrasa, M Chaparro. Comparison of the effectiveness
of two protocols for vaccination (standard and double
dosage) against hepatitis B virus in patients with inflammatory bowel disease. Aliment Pharmacol Ther
35(12):1379-1385. 2012. PMID: 22530631. IF: 3,769.
DOI: 10.1111/j.1365-2036.2012.05110.x
JP Gisbert on behalf of the H. pylori Study Group of the
Spanish Gastroenterology Association. Letter: third-line
rescue therapy with levofloxacin after failure of two treatments to eradicate Helicobacter pylori infection. Aliment
Pharmacol Ther 35(12):1484-1485. 2012. PMID:
22582841. IF: 3,769. DOI: 10.1111/j.13652036.2012.05117.x
JP Gisbert, X Calvet. Review article: Rifabutin in the
treatment of refractory Helicobacter pylori infection.
22129228. IF: 3,769. DOI: 10.1111/j.13652036.2011.04937.x
M Chaparro, P Burgueño, E Iglesias, J Panés, F Muñoz,
P Nos, L Castro, C Jiménez, JL Mendoza, M Barreiro, S
Gómez Senent, F Gomollón, X Calvet, E García-Planella,
M Gómez, V Hernández, J Hinojosa, M Mañosa, O
Pérez Nyssen, JP Gisbert. Infliximab salvage therapy
after failure of ciclosporin in corticosteroid-refractory
ulcerative colitis: a multicentre study. Aliment Pharmacol
Ther 35(2):275-283. 2012. PMID: 22142227. IF: 3,769.
DOI: 10.1111/j.1365-2036.2011.04934.x
Y González-Lama, JP Gisbert. Why Thiopurine metabolites are relevant: authors’ reply. Aliment Pharmacol Ther
35(3):401-402. 2012. IF: 3,769. DOI: 10.1111/j.13652036.2011.04957.x
JP Gisbert. The ethics of using inferior regimens in H.
pylori randomised trials - invited comment. Aliment
Pharmacol Ther 35(7):856-857. 2012. PMID: 22404413.
IF: 3,769. DOI: 10.1111/j.1365-2036.2011.04985.x
JP Gisbert, M Castro-Fernandez, A Perez Aisa, A
Cosme, J Molina-Infante, L Rodrigo, I Modolell, JL
Cabriada, JL Gisbert, E Lamas, E Marcos, X Calvet.
Fourth-line rescue therapy with rifabutin in patients with
three H. pylori eradication failures. Aliment Pharmacol
Ther 35(8):941-947. 2012. PMID: 22372560. IF: 3,769.
DOI: 10.1111/j.1365-2036.2012.05053.x
M Chaparro, I Guerra, PM Linares, JP Gisbert.
Systematic review: Antibodies and anti-TNF-a levels in
inflammatory bowel disease. Aliment Pharmacol Ther
35(9):971-986. 2012. PMID: 22443153. IF: 3,769. DOI:
10.1111/j.1365-2036.2012.05057.x
J Sánchez-Delgado, P García-Iglesias, M CastroFernández, F Bory, M Barenys, L Bujanda, J Lisozain,
MM Calvo, S Torra, JP Gisbert, X Calvet. High-dose, tenday esomeprazole, amoxicillin and metronidazole triple
therapy achieves high H. pylori eradication rates. Aliment
IF: 3,769. DOI: 10.1111/j.1365-2036.2012.05137.x
Y Gonzalez-Lama, JP Gisbert. Letter: TPMT - not all that
glitters is gold. Aliment Pharmacol Ther 36(2):208-209.
2012. PMID: 22703467. IF: 3,769. DOI: 10.1111/j.13652036.2012.05148.x
A McNicholl, PM Linares, OP Nyssen, X Calvet, JP
Gisbert. Meta-analysis: esomeprazole or rabeprazole vs.
first generation pump inhibitors in the treatment of
Helicobacter pylori infection. Aliment Pharmacol Ther
36(5):414-425. 2012. PMID: 22803691. IF: 3,769. DOI:
10.1111/j.1365-2036.2012.05211.x
I Guerra, JP Gisbert. Anti-TNFs and psoriasis: friends or
foes?. Aliment Pharmacol Ther 36(5):497. 2012. PMID:
22860613. IF: 3,769. DOI: 10.1111/j.13652036.2012.05136.x
– 117 –
AREA 3AREA 2 AREA 1
AG McNicholl, JP Gisbert. Commentary: comparators in
H. pylori eradication - stating the ethics of statins.
Aliment Pharmacol 36(4):400-401. 2012. PMID:
22803647. IF: 3,769. DOI: 10.1111/j.13652036.2012.05191.x
A Lopez-Sanroman, JP Gisbert. Infliximab and adalimumab in the management of Crohn’s disease: are they
really comparable?. Aliment Pharmacol Ther 36(5):498499. 2012. PMID: 22860615. IF: 3,769. DOI:
10.1111/j.1365-2036.2012.05185.x
X Calvet, JP Gisbert. Letter: are idiopathic (non-NSAID,
non-Helicobacter pylori) ulcers really increasing?. Aliment
IF: 3,769. DOI: 10.1111/j.1365-2036.2012.05218.x
F Fernández-Bañares, JP Gisbert. Are lymphocytic colitis and collagenous colitis really the same disease?.
Aliment Pharmacol Ther 36(6):606. 2012. PMID:
22913854. IF: 3,769. DOI: 10.1111/j.13652036.2012.05230.x
E Domenech, JP Gisbert. Letter: real-life management of
new onset ulcerative colitis and proctitis. Aliment
IF: 3,769. DOI: 10.1111/apt.12003
JP Gisbert, X Calvet, A Cosme, P Almela, F Feu, F Bory,
S Santolaria, R Aznárez, M Castro, N Fernández, R
García-Grávalos, A Benages, N Cañete, M Montoro, F
Borda, A Pérez-Aisa, JM Piqué. Long-Term Follow-Up
of 1,000 Patients Cured of Helicobacter pylori Infection
Following an Episode of Peptic Ulcer Bleeding. Am J
Gastroenterol 107(8):1197-1204. 2012. PMID:
22613904. IF: 7,282. DOI: 10.1038/ajg.2012.132
Gisbert JP, Villagrasa JR, Rodríguez-Nogueiras A,
Chaparro M. Efficacy of hepatitis B vaccination and
revaccination and factors impacting on response in
patients with inflammatory bowel disease. Am J
Gastroenterol. 107(10):1460-6. 2012. PMID: 23034605.
IF: 7,282. DOI: 10.1038/ajg.2012.79
Curr Drug Metab. 13(9):1266. 2012. PMID: 22998087.
IF: 5,113
Guijarro LG, Román ID, Fernández-Moreno MD, Gisbert
JP, Hernández-Breijo B. Is the autophagy induced by
thiopurines beneficial or deleterious?. Current Drug
Metabol. 13(9):1267-76. 2012. PMID: 22493985. IF:
5,113
Cabaleiro T, Roman M, Gisbert JP, Abad-Santos F. Utility
of assesing thiopurine S-methyltransferase polymorphism
before azathioprine therapy. Current Drug Metabol.
13(9):1277-93. 2012. PMID: 22493988. IF: 5,113
DR Serrano, S Torrado, S Torrado-Santiago, JP Gisbert.
The influence of CYP2C19 genetic polymorphism on the
pharmacokinetics/pharmacodynamics of proton pump
inhibitor-containing Helicobacter pylori treatments.
Current Drug Metabol. 13(9):1303-12. 2012. PMID:
22493986. IF: 5,113
B Velayos, L Fernández-Salazar, F Pons-Renedo, MF
Muñoz, A Almaraz, R Aller, L Ruíz, L Del Olmo, JP
Gisbert, JM González-Hernández. Accuracy of urea
breath test performed immediately after emergency
endoscopy in peptic ulcer bleeding. Dig Dis Sci
57(7):1880-1886. 2012. PMID: 22453995. IF: 2,117.
DOI: 10.1007/s10620-012-2096-5
Y González-Lama, C Taxonera, A López-Sanromán, JL
Pérez-Calle, F Bermejo, R Pajares, AG McNicholl, V
Opio, JL Mendoza, P López, A Algaba, J Estelles, A
Barbero, JL Mendoza, J Maté, JP Gisbert. Methotrexate
in inflammatory bowel disease: A multicenter retrospective study focused on long-term efficacy and safety. The
Madrid experience. Eur J Gastroenterol Hepatol
24(9):1086-1091. 2012. PMID: 22713509. IF: 1,757.
DOI: 10.1097/MEG.0b013e3283556db5
M Román, T Cabaleiro, J Novalbos, M Chaparro, JP
Gisbert, F Abad-Santos. Validation of a genotyping
method for analysis of TPMT polymorphisms. Clin Ther
34(4):878-884. 2012. PMID: 22421577. IF: 2,321. DOI:
10.1016/j.clinthera.2012.02.017
JP Gisbert. Rescue therapy for Helicobacter pylori infection 2012. Gastroenterol Res Pract. 2012:974594.
2012.
PMID:
22536225.
IF:
0,978.
DOI:
10.1155/2012/974594
JP Gisbert. Drugs and the Upper and Lower
Gastrointestinal Tract: From Inflammation to Malignancy.
P. Malfertheiner, F. Megraud, C. O'morain, J. Atherton, A.
Axon, F. Bazzoli, E. El-omar, G. Gensini, JP Gisbert, D.
– 118 –
AREA 3
JP Gisbert, AG McNicholl. Maintenance of Helicobacter
pylori eradication rates with triple therapy over 12 years
in a Spanish hospital. Helicobacter 17(2):160-161. 2012.
PMID: 22404448. IF: 3,151. DOI: 10.1111/j.15235378.2011.00922.x
J Molina-Infante, C Pazos-Pacheco, G VinagreRodriguez, B Perez-Gallardo, C Dueñas-Sadornil, M
Hernandez-Alonso, G Gonzalez-Garcia, JM MateosRodriguez, M Fernandez-Bermejo, JP Gisbert. Non-bismuth quadruple (concomitant) therapy: empirical and tailored efficacy versus standard triple therapy for clarithromycin-susceptible Helicobacter pylori and vs.
sequential therapy for clarithromycin-resistant strains.
Helicobacter 17(4):269-276. 2012. PMID: 22759326. IF:
3,151. DOI: 10.1111/j.1523-5378.2012.00947.x
B Tepes, A O'Connor, JP Gisbert, CA O'Morain.
Treatment of Helicobacter pylori infection 2012.
Helicobacter. 17 Suppl 1:36-42. 2012. PMID:
22958154. IF: 3,151. DOI: 10.1111/j.15235378.2012.00981.x
M Chaparro, J Panés, V García, O Merino, P Nos, E
Domènech, M Peñalva, E García-Planella, M Esteve, J
Hinojosa, M Andreu, F Muñoz, A Gutiérrez, JL Mendoza,
J Barrio, M Barreiro, I Vera, P Vilar, JL Cabriada, MA
Montoro, X Aldeguer, C Saro, JP Gisbert. Long-term
durability of response to adalimumab in Crohn’s disease.
Inflamm Bowel Dis 18(4):685-690. 2012. PMID:
21618353. IF: 4,855. DOI: 10.1002/ibd.21758
F Bermejo, E Garrido, M Chaparro, J Gordillo, M
Mañosa, A Algaba, A López-Sanromán, JP Gisbert, E.
García-Planella, E Doménech, I Guerra. Efficacy of different therapeutic options for spontaneous abdominal
abscesses in Crohn’s disease: are antibiotics enough?.
Inflamm Bowel Dis 18(8):1509-1514. 2012. PMID:
22674826. IF: 4,855. DOI: 10.1002/ibd.21865
L Katz, JP Gisbert, B Manoogian, L Kirk, C Steenholdt,
GJ Mantzaris, A Atreja, Y Ron, A Swaminath, S Shah, A
Harts, PL Lakatos, P Ellul, E Israeli, MN Svendsen, J van
der Woude, KH Katsanos, L Yun, EV Tsianos, T Nathan,
M Abreu, I Dotan, B Lashner, J Brynskov, JP Terdiman,
P Higgins, M Chaparro, S Ben-Horin. Doubling the infliximab dose versus halving the infusion intervals in
Crohn's disease patients with loss of response. Inflamm
Bowel Dis. 18(11):2026-33. 2012. PMID: 22294554. IF:
4,855. DOI: 10.1002/ibd.22902
Gisbert JP, Villagrasa JR, Rodríguez-Nogueiras A,
Chaparro M. Kinetics of anti-hepatitis B surface antigen
titers after hepatitis B vaccination in patients with inflammatory bowel disease. Inflamm Bowel Dis. 19(3):554-8.
2012.
PMID:
23380936.
IF:
4,855.
DOI:
10.1097/MIB.0b013e31827febe9
G de la Poza, A Lopez-Sanroman, C Taxonera, I Marín,
JP Gisbert, F Bermejo, V Opio, A Muriel. Genital fistulas
in female Crohn’s disease patients. Clinical characteristics and response to therapy. J Crohn Colitis 6(3):276280. 2012. PMID: 22405162. IF: 2,566. DOI:
10.1016/j.crohns.2011.08.015
I. Guerra, A. Algaba, J. Pérez-Calle, M. Chaparro, I.
Marín-Jiménez, A. López-Sanromán, R. GarcíaCastellanos, Y. González-Lama, N. Manceñido, P.
Martínez, E. Quintanilla, C. Taxonera, M. Villafruela,
A. Romero, P. López-Serrano, JP Gisbert, F. Bermejo.
Induction of psoriasis with anti-TNF agents in
patients with inflammatory bowel disease: a report of
21 cases. J Crohn Colitis 6(5):518-523. 2012. PMID:
22398059. IF: 2,566. DOI: 10.1016/j.crohns.
2011.10.007
J Hinojosa, JP Gisbert, F Gomollon, AL San Roman.
Adherence of gastroenterologists to European Crohn’s
and Colitis Organisation consensus on Crohn’s disease:
A real-life survey in Spain. J Crohn Colitis 6(7):763-770.
2012.
PMID:
22398092.
IF:
2,566.
DOI:
10.1016/j.crohns.2011.12.013
P Marticorena-Álvarez, M Chaparro, A Pérez-Casas, MA
Muriel-Herrero, JP Gisbert. Probable diffuse retinopathy
caused by adalimumab in a patient with Crohn’s dis-
– 119 –
AREA 3AREA 2 AREA 1
Graham, T. Rokkas, E. Kuipers & the European
Helicobacter Study Group (EHPSG). Management of
Helicobacter pylori infection--the Maastricht IV/ Florence
Consensus Report. Gut 61(5):646-664. 2012. PMID:
22491499. IF: 10,111. DOI: 10.1136/gutjnl-2012302084
ease. J Crohn Colitis 6(9):950-953. 2012. PMID:
22537636. IF: 2,566
M Chaparro, P Martínez-Montiel, M Van-Domselaar, F
Bermejo, JL Pérez-Calle, B Casis, A López-SanRomán, A
Algaba, J Maté, JP Gisbert. Intensification of infliximab therapy in Crohn’s disease: efficacy and safety. J Crohn’s Colitis
6(1):62-67. 2012. PMID: 22261529. IF: 2,566. DOI:
10.1016/j.crohns.2011.07.005
Casanova MJ, Chaparro M, Martínez S, Vicuña I, Gisbert
JP. Severe adalimumab-induced thrombocytopenia in a
patient with Crohn’s disease. J Crohn's Colitis. 6(10):10347. 2012. PMID: 22534313. IF: 2,566. DOI:
10.1016/j.crohns.2012.04.001
D Laharie, A Bourreille, J Branche, M Allez, Y Bouhnik, J
Filippi, F Zerbib, M Nachury, G Savoye, J Moreau, JC
Delchier, E Ricart, J Cosnes, A López-Sanroman, O Dewit,
JL Dupas, F Carbonnel, G Bommelaer, B Coffin, X Roblin,
G Van Assche, M Esteve, M Färkkilä, JP Gisbert, P
Marteau, S Nahon, M de Vos, D Franchimont, JY Mary, JF
Colombel, M Lémann. Ciclosporin versus infliximab in
patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet. 380(9857):1909-15. 2012. PMID:
23063316. IF: 38,278. DOI: 10.1016/S01406736(12)61084-8
Rutgeerts, S Ghosh, WJS de Villiers,R Panaccione, G
Greenberg, S Schreiber, S Lichtiger, BG Feagan, for the
CERTIFI Study Group (..., Pérez Gisbert, J, ...).
Ustekinumab Induction and Maintenance Therapy in
Refractory Crohn's Disease. N Engl J Med.
367(16):1519-1528. 2012. PMID: 23075178. IF:
53,298. DOI: 10.1056/NEJMoa1203572
Barbero-Villares A, Mendoza J, Taxonera C, LópezSanromán A, Pajares R, Bermejo F, Pérez-Calle J,
Mendoza J, Algaba A, Moreno-Otero R, Maté J, Gisbert
J. Evaluation of liver fibrosis by transient elastography
(Fibroscan®) in patients with inflammatory bowel disease treated with methotrexate: a multicentric trial.
Scand J Gastroenterol 47(5):575-579. 2012. PMID:
22229701. IF: 2,019. DOI: 10.3109/00365521.2011.
647412
Chaparro M, Andreu M, Barreiro-de Acosta M,
García-Planella E, Ricart E, Domènech E, Esteve M,
Merino O, Nos P, Peñalva M, JP Gisbert.
Effectiveness of infliximab after adalimumab failure in
Crohn's disease. World J Gastroenterol. 18(37):521924. 2012. PMID: 23066316. IF: 2,471. DOI:
10.3748/wjg.v18.i37.5219
BOOKS
Quintero E, Castells A, Bujanda L, Cubiella J, Salas D,
Lanas Á, Andreu M, Carballo F, Morillas JD, Hernández C,
Jover R, Montalvo I, Arenas J, Laredo E, Hernández V,
Iglesias F, Cid E, Zubizarreta R, Sala T, Ponce M, Andrés M,
Teruel G, Peris A, Roncales MP, Polo-Tomás M, Bessa X,
Ferrer-Armengou O, Grau J, Serradesanferm A, Ono A,
Cruzado J, Pérez-Riquelme F, Alonso-Abreu I, de la VegaPrieto M, Reyes-Melian JM, Cacho G, Díaz-Tasende J,
Herreros-de-Tejada A, Poves C, Santander C, GonzálezNavarro A; COLONPREV Study Investigators (...,Mª
Chaparro, Gisbert JP,...). Colonoscopy versus Fecal
Immunochemical Testing in Colorectal-Cancer Screening.
N Engl J Med 366(8):697-706. 2012. PMID: 22356323. IF:
53,298. DOI: 10.1056/NEJMoa1108895
WJ Sandborn, C Gasink, LL Gao, MA Blank, J Johanns,
C Guzzo, BE Sands, SB Hanauer, St Targan, P
– 120 –
M Chaparro, JP Gisbert. Antimetabolite therapy in
ulcerative colitis: Azathioprine, mercaptopurine and
methotrexate. 2012. Editores: Lichtestein G.
M Chaparro, JP Gisbert, I Marín, L Menchén, F
Gomollón. Diagnóstico diferencial de las estenosis
intestinales y su manejo en los pacientes con enfermedad de Crohn. Diagnóstico diferencial de la enfermedad inflamatoria intestinal. 2012. Eds. Elsevier
Doyma. ISBN: 978-84-75927-466.
M Chaparro, JP Gisbert. Desintensificación de la dosis
de adalimumab en pacientes con enfermedad de
Crohn. Casos clínicos en Enfermedad de Crohn. 2012.
Publicaciones Permanyer 2012. ISBN: 978-84-9926326-7.
AREA 3
M Chaparro, JP Gisbert. Dudas frecuentes sobre el
embarazo y la lactancia en pacientes con enfermedad de Crohn. 2012.
M Chaparro, JP Gisbert. Eficacia del adalimumab
en el mantenimiento de la remisión a largo plazo en
pacientes con enfermedad de Crohn con intolerancia a las tiopurinas. 2012.
JP Gisbert. Estómago: Helicobacter pylori. Curso
sobre trastornos digestivos. 2012. Gastroenterol
Hepatol; Eds: V Arrolyo, JP Piq. Págs.: 23-33.
JP Gisbert, X Calvet, A Lanas, JI Elizalde, L
Bujanda. Enfermedades del estómago y del duodeno (capítulo 15). Farreras-Rozman, Medicina
Interna Decimoséptima Edición. 2012. Págs.: 92123.
M Chaparro, JP Gisbert. Eficacia de adalimumab
en el mantenimiento de la remisión a largo plazo en
pacientes con enfermedad de Crohn con intolerancia a las tiopurinas.Eds: M Chaparro, E Torrella.
Evidencia vs experiencia. Paciente en tratamiento
continuado durante 2 años con adalimumab. 2012.
Publicaciones Permanyer. Págs.: 15-20.
M Chaparro, JP Gisbert. Desintensificación de la
dosis de adalimumab en pacientes con enfermedad
de Crohn. Casos clínicos en Enfermedad de Crohn.
2012. Publicaciones Permanyer. Pags.: 35-41.
B Hernández-Breijo, J Monserrat, D FernándezMoreno, ID Román, JP Gisbert, LG Guijarro. La
azatioprina produce autofagia en células HepG2.
2012.
M Chaparro, A Rodríguez-Nogueiras, JP Gisbert.
Nutrición y tabaco en pacientes con enfermedad
inflamatoria intestinal (Módulo Enfermería). 2012.
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: PEREZ GISBERT, FRANCISCO JAVIER
Estudio aleatorizado, doble ciego, controlado con
placebo, con grupos paralelos, multicéntrico para
investigar la seguridad y la eficacia de -CP-690,550
como tratamiento de mantenimiento en sujetos con
Enfermedad de Crohn de moderada a grave; (Versión
enmienda 2: 14-09-11). PFIZER INC. A3921084.
EudraCT: 2011-001754-28
Estudio abierto multicéntrico para evaluar el impacto
de adalimumab en la calidad de vida, la utilización de la
asistencia sanitaria y coste delos pacientes con Colitis
Ulcerosa en la práctica clínica habitual; (versión
amendment: 19-09-11). ABBOTT GMBH & CO. KG.
M13-045.
EudraCT: 2011-002411-29
Estudio de tratamiento aleatorizado, doble ciego, activo para inducir respuesta clínica y/o remisión con
GSK1605786A en pacientes con Enfermedad de
Crohn activa moderada o grave; (versión original: 2807-11). GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LIMITED. CCX114643.
EudraCT: 2011-002817-12
placebo y de 52 semanas de duración para evaluar la
eficacia y seguridad de GSK1605786A en el mantenimiento de la remisión en pacientes con Enfermedad
de Crohn; (versión 1: 03-08-11). GLAXOSMITHKLINE
RESEARCH & DEVELOPMENT LIMITED. CCX114157.
EudraCT: 2010-022383-12
Estudio abierto de extensión para evaluar la seguridad
de GSK1605786A en pacientes con Enfermedad de
– 121 –
AREA 3AREA 2 AREA 1
JP Gisbert, M Chaparro. Errores más frecuentes en
el manejo de pacientes con colitis ulcerosa y enfermedad de Crohn. Conductas de actuación en la
Enfermedad Inflamatoria Intestinal. Manual práctico, 5ª edición. 2012. Editores: J Hinojosa, P Nos.
Crohn; (versión 02:02-08-11). GLAXOSMITHKLINE
RESEARCH & DEVELOPMENT LIMITED. CCX114644.
EudraCT: 2010-022384-35
Ensayo clínico en fase II, aleatorizado y controlado con
placebo para estudiar la seguridad e inmunogenicidad
de V212 en pacientes adultos con enfermedades
autoinmunitarias; (Versión 00:11-11-11). MERCK
SHARP & DOHME CORP. V212-009.
EudraCT: 2011-002313-11
Estudio de fase III, de grupos paralelos, controlado con
placebo, doble ciego, aleatorizado, multicéntrico, internacional, para investigar la seguridad y eficacia de los
comprimidos de liberación modificada de propionil-Lcarnitina clorhidrato(ST 261) en pacientes afectados
por colitis ulcerosa leve bajo tratamiento oral estable;
(versión final:1.0:30-09-11). SIGMA-TAU INDUSTRIE
FARMACEUTICHE RIUNITE S.P.A. ST261 DM 11 006.
EudraCT: 2011-004770-28
Estudio fase III, multicéntrico, aleatorizado, doble
ciego, de grupos paralelos y controlado con placebo
para evaluar la eficacia y la seguridad de células madre
alogénicas expandidas derivadas del tejido adiposo
(eASC) para el tratamiento de la Enfermedad de Crohn
fistulizante perianal tras un periodo de 24 semanas.
Estudio ADMIRE-CD; (Versión 1.0: 13-12-11). CELLERIX S.A. CX601-0302.
EudraCT: 2011-006064-43
Evaluación de la respuesta a la vacunación de la
Hepatitis B en los pacientes con Enfermedad
Inflamatoria Intestinal;(version1:30-04-12). PRECOMVI-B
– 122 –
Efectividad del tratamiento Anti TNF-alfa en pacientes
con Enfermedad de Crohn que no han respondido a un
Anti TNF-alfa previo. JAVIER P. GISBERT. GIS-201202-NORES
Estudio para conocer la eficacia de dos pautas de la
vacuna frente al virus de la Hepatitis B en pacientes
con enfermedad inflamatoria; (versión 1: 30-04-12).
GIS-2012-VHB
placebo para investigar la eficacia y la seguridad de
GSK1605786A en el tratamiento de pacientes con
Enfermedad de Crohn activa de moderada a grave;
(versión
01:27-07-11).
GLAXOSMITHKLINE
RESEARCH
&
DEVELOPMENT
LIMITED.
CCX114151.
EudraCT: 2010-022382-10
Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo y de grupos paralelos de CP690,550 por vía oral como tratamiento de mantenimiento en pacientes con colitis ulcerosa; (Versión
final:30-09-11). PFIZER INC. A3921096.
EudraCT: 2011-004580-79
Estudio para evaluar las preferencias declaradas por
los pacientes respecto al tratamiento de la Enfermedad
de Crohn. -Estudio Implica-; (Versión: cambio administrativo nº1:09-02-12). ABBOTT LABORATORIES, S.A.
ABB-BIO-2011-01
Estudio multicéntrico abierto de CP-690,550 en
pacientes con colitis ulcerosa entre moderada e intensiva; (versión final: 30-09-11). PFIZER INC. A3921139.
EudraCT: 2011-004581-14
AREA 3
Estudio de extensión abierto de CP-690,550 como
tratamiento de mantenimiento en pacientes con
Enfermedad de Crohn; (versión final: 23-09-11). PFIZER INC. A3921086.
EudraCT: 2011-003622-27
UC-CARES- Colitis ulcerosa: Condición, actitud y
recursos; Estudio Educativo; (versión 3.00 final: 22-1211). MERCK&CO, INC. MER-TCU-2012-01
Tratamiento erradicado de H. pylori de rescate de 3Línea con una terapia cuádruple con bismuto. GIS2012-CUADRUPLE
Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo y de grupos paralelos de CP690,550 por vía oral como tratamiento de inducción en
pacientes con colitis ulcerosa entre moderada e intensa; (Versión final: 30-09-11). PFIZER INC. A3921094.
EudraCT: 2011-004578-27
Tratamiento triple con levofloxacino tras el fracaso de
las terapias cuádruples "secuencial" o "concomitante"
en la erradicación de Helicobacter Pylori; (versión 1:108-12). GIS-2012-LEVO-SECCON
Estudio clínico para evaluar el efecto de un complemento alimenticio en el alivio de síntomas de antibioterapia en pacientes tratados para la infección por
Helicobacter pylori; (versión 2: 25-06-12). LABORATORIOS CASEN FLEET, S.L.U. QTM/ABB009
Prevalencia, perfil clínico y manejo terapéutico del
paciente con Colitis Ulcerosa (CU) en servicios hospitalarios de gastroenterología de España. Estudio EPICURE; (versión2.0:10-05-12). ABBOTT LABORATORIES, S.A. ABB-TCU-2012-01
Registro europeo de manejo de la infección por
Helicobacter Pylori; (versión 1: 04-12-12). EUROPEAN
HELICOBACTER STUDY GROUP. HP-EUREG
Proteómica de la úlcera duodenal e infección por
Helicobacter Pylori; (versión 1: 12-09-12). NRGH-12231V1
Mejora de la seguridad en pacientes con Enfermedad
Inflamatoria Intestinal en tratamiento con biológicos
mediante el perfeccionamiento en la detección de
tuberculosis latente; (versión 2:28-10-11). GETECCU.
SEGURTB/GET-BIO-2011-01
Correlación entre los marcadores biológicos y la actividad clínica en pacientes con enfermedad inflamatoria
intestinal; (versión 1:15-06-12). GIS-MARCA-2012
– 123 –
AREA 3AREA 2 AREA 1
Fístulas enterourinarias en la Enfermedad de Crohn
prevalencia y características clínicas; (Versión 2). HOSPITAL CLINICO SAN CARLOS. CTS-FIS-2012-01
Line 3.3
Progenitors and
cell therapy
GRUPO 39
HEAD OF LABORATORY
Luis Madero López
GROUP MEMBERS
• Julián Sevilla Navarro
• Álvaro Lassaletta Atienza
• África González Murillo
• Evangelina Muñoz Mayoral
• Manuel Ramírez Orellana
• Isabel Colmenero Blanco
• Lucía Chamorro Casanova
• Ana María Gómez García
• Carolina Martínez Laperche
• Antonio Pérez Martínez
• Miguel Ángel Díaz Pérez
• Marta González Vicent
• Jaime Valentín Quiroga
RESEARCH INTEREST
The main results from the activity of the group led by Dr.
Luís Madero during 2012 were as follows:
• The Group published a total of 17 articles in scientific
journals, either as its own work or as collaborations
with other groups.
• The predoctoral candidate Ana María Gómez, supervised by Dr. Manuel Ramírez, obtained their doctoral
degree at School of Medicine, Universidad Autónoma
de Madrid, with the maximum grade.
• Dr. Manuel Ramírez and his group participate in the
consortium “Una nueva generación de medicamentos
celulares más eficaces y seguros. CellCAM
(S2010/BMD-2420)” funded by Comunidad de
Madrid.
– 124 –
(a) Reconstitution of T cells, (b) CD4+ cells, (c) CD8+ cells, (e) NK bright
CD56+ CD16- cells, (f) NK dim CD56+ CD16+, (g)DCs, (h) myeloid DCs,
(i) lymphoid DCs DC2+ and (j) lymphoid DC2 cells in MUD and HP
CD3/CD19-depleted grafts. Data are expressed as means +- s.e.m.
*is used to highlight statiscally significant differences.
The following work by several members of the group was
published in the journal Bone Marrow Transplantation in
November 2012 (Early evaluation of immune reconstitution following allogeneic CD3/CD19-depleted grafts from
alternative donors in childhood acute leukemia. PérezMartínez A, González-Vicent M, Valentín J, Aleo E,
Lassaletta A, Sevilla J, Vicario JL, Ramírez M, Díaz MA.
Bone Marrow Transplant. 2012 Nov;47(11):1419-27. doi:
10.1038/bmt.2012.43. Epub 2012 Mar 12.). This work
describes the kinetics of immune reconstitution in the first
3 months after transplanting a hematopoietic graft from
either an unrelated donor or a haploidentical donor, in children with high-risk leukemias.
MAJOR GRANTS
• Luis Madero López. Generación y diferenciación de
células madre pluripotentes inducidas (iPS) de
pacientes con enfermedades genéticas del sistema
inmuno-hematopoyético. MICINN. PLE2009-0100.
Duration: 2009 - 2012.
• Manuel Ramírez Orellana. Utilización de células madre
adultas como agentes terapéuticos antitumorales.
MICINN. PLE2009-0115. Duration: 2009 - 2012.
• Luis Madero López. Detección de infiltración leptomeníngea en niños con tumores del sistema nervioso
AREA 3
•
•
•
•
•
•
•
YEAR
Total IF
Publication No.
Q1
Q2
2010
30,791
10
3
5
2011
52,329
14
6
2
2012
38,06
16
2
4
Carrillo J, Martínez P, Solera J, Moratilla C, González A,
Manguán-García C, Aymerich M, Canal L, Del Campo M,
Dapena JL, Escoda L, García-Sagredo JM, Martín-Sala
S, Rives S, Sevilla J, Sastre L, Perona R. High resolution
melting analysis for the identification of novel mutations in
DKC1 and TERT genes in patients with dyskeratosis congenita. Blood Cells Mol Dis 49(3-4):140-146. 2012.
PMID: 22664374. IF: 2,351. DOI: 10.1016/j.bcmd.
2012.05.008
Pérez-Martínez A, González-Vicent M, Valentín J, Aleo E,
Lassaletta A, Sevilla J, Vicario JL, Ramírez M, Díaz MA.
Early evaluation of immune reconstitution following allogeneic CD3/CD19-depleted grafts from alternative
donors in childhood acute leukemia. Bone Marrow
Transplant. 47(11):1419-27. 2012. PMID: 22410752. IF:
3,746. DOI: 10.1038/bmt.2012.43
Navajas A, Lassaletta A, Morales A, López-Ibor B,
Sábado C, Moscardó C, Mateos E, Molina J, Sagaseta
M, Sastre A. Efficacy and safety of liposomal cytarabine
in children with primary CNS tumours with leptomeningeal involvement. Clin Transl Oncol. 14(4):280-6.
2012.
PMID:
22484635.
IF:
1,327.
DOI:
10.1007/s12094-012-0796-0
Pérez-Martínez A, de Prada Vicente I, Fernández L,
González-Vicent M, Valentín J, Martín R, Maxwell H,
Sevilla J, Vicario JL, Angel Díaz M. Natural killer cells can
exert a graft-vs-tumor effect in haploidentical stem cell
transplantation for pediatric solid tumors. Exp Hematol
40(11):882-891.e1. 2012. PMID: 22771496. IF: 2,905.
DOI: 10.1016/j.exphem.2012.07.004
Lehrnbecher T, Aplenc R, Rivas Pereira F, Lassaletta A,
Caselli D, Kowalczyk J, Chisholm J, Sung L; SIOP
Supportive Care Working. Variations in non-pharmacological anti-infective measures in childhood leukemia-results of an international survey. Haematologica.
97(10):1548-52. 2012. PMID: 22419572. IF: 6,424. DOI:
10.3324/haematol.2012.062885
Tolar J, Becker PS, Clapp DW, Hanenberg H, de Heredia
CD, Kiem HP, Navarro S, Qasba P, Rio P, Schmidt M,
Sevilla J, Verhoeyen E, Thrasher AJ, Bueren J. Gene therapy for fanconi anemia: one step closer to the clinic. Hum
– 125 –
AREA 3AREA 2 AREA 1
•
central. ISCIII. PI10/02811. Duration: 2011 - 2013.
Manuel Ramírez Orellana. Estudio de la regulación de la
vía de FAS por NIK en trasplante alogénico. ISCIII.
PI10/02802. Duration: 2011 - 2013.
Proyecto Coordinado. Ensayo clínico Fase I/II para evaluar la seguridad y eficacia de la movilización y colecta
de células CD34+ tras tratamiento con plerixafor y filgrastim en pacientes con anemia de Fanconi. MSPSI.
EC11-559. Duration: 2012 - 2013.
Proyecto Coordinado. Células Natural Killer autólogas
activadas y expandidas para el tratamiento del Mieloma
Múltiple. ISCIII. EC11/036. Duration: 2012 - 2013.
Proyecto Coordinado. Una nueva generación de
medicamentos celulares más eficaces y seguros.
CellCAM. CAM. S2010/BMD-2420. Duration: 2012 2015.
Julián Sevilla Navarro. Ensayo clínico Fase I/II para evaluar la seguridad y eficacia de la infusión de células
CD34+ autólogas transducidas con un vector lentiviral
portador del gen FANCA (medicamento huérfano) para
pacientes con Anemia de Fanconi del Subtipo A.
MSPSI. EC11-060. Duration: 2012 - 2013.
Manuel Ramírez Orellana. Ensayo clínico de seguridad
y eficacia de infusiones de infusiones repetidas de
Celyvir en niños y adultos con tumores sólidos
metastásicos y refractarios. MSPSI. EC11-061.
Duration: 2012 - 2013.
Antonio Pérez Martínez. Infusión de células natural killer
activadas y expandidas en combinación con quimioterapia en pacientes pediátricos con leucemia/linfoma T
refractaria. ISCIII. EC11/057. Duration: 2012 - 2013.
Miguel Ángel Díaz Pérez. Trasplante de progenitores
hematopoyéticos de donante familiar haploidentico con
infusion de linfocitos del donante tras alo-depleCción
selectiva “in vitro”, en pacientes pediatricos con
hemopatías malignas de alto riesgo. ISCIII. EC11/024.
Duration: 2012 - 2013.
Gene Ther 23(2):141-144. 2012. PMID: 22248350. IF:
4,218. DOI: 10.1089/hum.2011.237
Rodriguez-Milla MA, Mirones I, Mariñas-Pardo L, Melen
GJ, Cubillo I, Ramírez M, García-Castro J. Enrichment of
neural-related genes in human mesenchymal stem cells
from neuroblastoma patients. Int J Mol Med. 30(2):365373. 2012. PMID: 22641458. IF: 1,573. DOI:
10.3892/ijmm.2012.1008
Sevilla J, Schiavello E, Madero L, Pardeo M, Guggiari E,
Baragaño M, Luksch R, Massimino M. Priming of
Hematopoietic Progenitor Cells by Plerixafor and
Filgrastim in Children With Previous Failure of Mobilization
With Chemotherapy and/or Cytokine Treatment. J
Pediatr Hematol Oncol 34(2):146-50. 2012. PMID:
22009006. IF: 1,159. DOI: 10.1097/MPH.0b013e3182
1c2cb8
González-Vicent M, Molina B, Pérez A, Díaz MA. Oncedaily intravenous busulfan for 47 pediatric patients undergoing autologous hematopoietic stem cell transplantation: a single center study. J Pediatr Hematol Oncol
34(3):180-183. 2012. PMID: 22430583. IF: 1,159. DOI:
10.1097/MPH.0b013e3182431e1b
Herrero B, Ruiz de la Fuente J, Aleo E, Carceller F,
Lassaletta A, Orellana MR, Pérez-Martínez A.
Spontaneous Resolution of Hypereosinophilic Syndrome
in an Infant Without Treatment. J Pediatr Hematol Oncol
34(6):450-2. 2012. PMID: 22510769. IF: 1,159. DOI:
10.1097/MPH.0b013e318249579b
Cabeza B, Oñoro G, Salido AG, Lassaletta A, de Prada I,
Albi G, de Mingo L, Serrano A. Pleuropulmonary blastoma as characteristic cause of pneumothorax. J Pediatr
Hematol Oncol. 34(1):e42-4. 2012. PMID: 22134609. IF:
1,159. DOI: 10.1097/MPH.0b013e3182287d88
González-Vicent M, Díaz MA. Unrelated cord blood transplantation in adolescent and young adults with hematologic malignancies. Leuk Res 36(2):123-4. 2012. PMID:
22071140. IF: 2,923. DOI: 10.1016/j.leukres.2011.10.021
Cantarín-Extremera V, González-Gutiérrez-Solana L,
Ramírez-Orellana M, López-Marín L, Duat-Rodríguez A,
– 126 –
Ruíz-Falcó-Rojas ML. Immune-Mediated Mechanisms in
the Pathogenesis of Hopkins Syndrome. Pediatr Neurol.
47(5):373-4. 2012. PMID: 23044022. IF: 1,522. DOI:
10.1016/j.pediatrneurol.2012.08.006
Lassaletta A, Portugal R, Arce B, Gonzalez-Vicent M,
Andion M, Cormenzana M, Madero L. Intrathecal steroids
reduce the severity and frequency of adverse events
associated with intrathecal liposomal cytarabine administration in children with cancer. Pediatric Blood & Cancer.
59(6):1092-1092. 2012. IF: 1,891
López E, Madero L, López-Pascual J, Latterich M.
Clinical proteomics and OMICS clues useful in translational medicine research. Proteome Sci. 10(1):35. 2012.
PMID: 22642823. IF: 2,328. DOI: 10.1186/1477-595610-35
Molina B, Gonzalez-Vicent M, Albi G, Andión M, Herrero
B, Sevilla J, Díaz MA. Varicella zoster central nervous system vasculitis after allogeneic hematopoietic stem cell
transplant successfully treated with cyclophosphamide.
Transpl Infect Dis 14(5):107-110. 2012. PMID:
22967359. IF: 2,216. DOI: 10.1111/j.13993062.2012.00783.x
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: SEVILLA NAVARRO,
JULIÁN
Ensayo clínico fase I/II para evaluar la seguridad y eficacia de la infusión de células CD34+autólogas transducidas con un vector lentiviral portador del gen
FANCA (medicamento huérfano) para pacientes con
anemia de Fanconi del subtipo A. FANCOLEN-1.
EudraCT: 2011-006100-12
JULIÁN
Ensayo clínico fase I/II para evaluar la seguridad y eficacia de la movilización y colecta de células CD34+
tras tratamiento con plerixafor y filgrastim en pacientes
con anemia de Fanconi para su posterior transducción
con un vector lentiviral portador del gen FANCA y rein-
AREA 3
JULIÁN
Estudio abierto, de farmacocinética y farmacodinámica, y tolerabilidad de AVE5026 administrado en dosis
ajustadas al peso a pacientes menores de 18 años con
una vía venosa central (vvc). PKM11204.
EudraCT: 2011-005155-14
JULIÁN
Estudio de dos partes, doble ciego, aleatorizado, controlado con placebo y abierto para investigar la eficacia, seguridad y tolerabilidad de eltrombopag, un agonista del receptor de la trombopoyetina, en sujetos
pediátricos con púrpura trobocitopénica inmune
(idiopática) (PTI) crónica previamente tratados.
TRA115450.
EudraCT: 2011-002184-17
PRINCIPAL INVESTIGATOR: PÉREZ MARTÍNEZ,
ANTONIO
Infusión de células Natural Killer en combinación con
quimioterapia en pacientes pediátricos con
leucemia/linfoma Trefractaria. HNJ-NKAES-2012
EudraCT: 2012-000054-63
PRINCIPAL INVESTIGATOR: DÍAZ, PÉREZ, MIGUEL
ÁNGEL
Trasplante de progenitores hematopoyéticos de
donante familiar haploidéntico con infusión de linfocitos
del donante tras alo-deplección selectiva “in vitro” en
pacientes pediátricos con hemopatías malignas de alto
riesgo. HNJ-LINF-2012
EudraCT: 2012-000029-34
PRINCIPAL INVESTIGATOR: LASSALETTA ATIENZA,
ÁLVARO
Estudio en fase I/II de sunitinib en pacientes jóvenes con
tumor avanzado del estroma gastrointestinal. A6181196
EudraCT: 2011-002008-33
ÁLVARO
Estudio de fase Ib de farmacocinética y farmacodinamia, abierto, aleatorizado, adaptativo y multicéntrico de oseltamivir (Tamiflu®) en el tratamiento de
la gripe en menores inmunocomprometidos, entre 0
a 18 años, con infección de gripe confirmada.
NV25719
EudraCT: 2012-002633-11
ÁLVARO
Ensayo fase II multicéntrico y prospectivo con gemcitabina y rapamicina en segunda línea de osteosarcoma metastásico. EC11-4444 OSTEOSARC
EudraCT: 2012-001106-26
ÁLVARO
Estudio piloto multicéntrico, de brazo único, abierta
para explorar la seguridad, tolerabilidad, la farmacocinética y la eficacia de administraciones múltiples
intravenosas de NI-0501, un anticuerpo monoclonal
anti-interferón gamma (anti-ifny), en paciente
pediátricos con linfohistiocitosis hemofagocítica primaria que se ha reactivado. NI-0501-04
EudraCT: 2012-003632-23
PRINCIPAL INVESTIGATOR: MADERO LÓPEZ, LUIS
Estudio fase III, multicéntrico, abierto, aleatorizado,
controlado, que evalúa la seguridad y eficacia de
LDE225 oral frente a temozolomida en pacientes con
meduloblastoma en recidiva que tengan activación
de la vía Hh. CLDE225C2301
EudraCT: 2012-003066-40
GRUPO 43
HEAD OF LABORATORY
Guillermo Reyes Copa
GROUP MEMBERS
• Beatriz Aguado Bueno
– 127 –
AREA 3AREA 2 AREA 1
fusión en el paciente. FANCOSTEM-1.
EudraCT: 2011-006197-88
RESEARCH INTEREST
Our scientific investigation has been focused mainly in
two aspects: The clinical performance of aortic valve
prosthesis and the outcomes of a new treatment for
multiple myeloma.
Regarding the multiple myeloma we reported the efficacy,
safety and health-related quality-of-life (HRQoL) associated with long-term lenalidomide and dexamethasone (Len
+ Dex) treatment in patients with relapsed or refractory
multiple myeloma (RRMM) enrolled in the Spanish cohort
of the MM-018 study. In this open-label, multicenter, single-arm expanded access study, 63 patients received
Len + Dex until disease progression. The overall response
rate was 78%, with 21% of the patients achieving a complete response. The quality of response improved with
continuous treatment. Median time-to-progression and
progression-free survival was 13.3 months for both;
median overall survival was not reached. Len + Dex had
a manageable safety profile consistent with previously
reported phase III studies.
Considering heart diseases, we described a total of
168 patients (104 males, 64 females; mean age 62 ±
9.9 years) that underwent aortic valve replacement
with the Bicarbon Overline valve between September
2004 and June 2010. All patients were monitored by
means of clinical examination and serial echocardiography. At the 12-month follow up, peak and mean
transprosthetic gradients were 23.6 ± 8.1 mmHg and
12.9 ± 4.9 mmHg, respectively. Preoperatively, the
average effective orifice area (EOA) was 0.80 ± 0.41
cm2, while the postoperative average EOA was 2.01
– 128 –
Overall cumulative survival for up to four years after surgery.
± 0.26 cm2. No prosthesis-patient mismatch (PPM)
was observed. Freedom from any valve-related event
at three, 12 and 24 months was 98.6%, 97.8% and
93.3%, respectively.
YEAR
Total IF
Publication No.
Q1
Q2
2010
6,74
3
1
1
2011
3,373
2
2012
AREA 3
Line 3.4
Advanced therapies
in oncohematology
GRUPO 44
HEAD OF LABORATORY
Juan Luis Steegmann Olmedillas
In vitro dendrogram depicting the kinase targets of imatinib, nilotinib
and dasatinib. Illustration. Reproduced courtesy of Cell Signaling
Technology, Inc. (http://www.cellsignal.com). Steegmann, J.L., et al.,
LeukLymphoma, 2012. 53(12): p. 2351-61.
RESEARCH INTEREST
Our Group has produced, in the year 2012, twenty-four
papers, with an accumulated impact factor of 172. The
spectrum covers all hematologic neoplasms. The group
continues very active in its presence in Spanish and
International collaborative groups, and most of our production comes from this source, although this year has
shown more presence of our “home-made” production.
In this summary, we comment only the findings coming
from papers. Here follows a selection.
In Chronic Myeloid Leukemia (CML), Dr. Steegmann
has been the first author of a review of adverse events
(Fig 1) and coauthor of two papers on international
guidelines for management of CML, and on research
methodology and definitions (Fig 2).
In Multiple myeloma (MM), Dr Alegre was the first
author of a paper which summarized the Spanish
experience with lenalidomide plus dexamethasone in
relapsed MM, and coauthor of an important paper on
Outcomes and events in CML. Outcomes and events that may potentially occur during the course of CML disease are presented from diagnosis to death. Intercurrent events (IC) pertain to adverse events (ie,
toxicities resulting from treatment) or events unrelated with the disease or its treatment.Guilhot J, …, Steegmann JL, Zaritskey A, Hehlmann R: Blood 2012, 119:5963-5971
induction therapy of this disease. In Lymphoma, Dr.
Arranz has been coauthor in an study focused in prognosis of advanced Hodgkin`s Lymphoma, a field in
which she continues a long-term work.
Dr. Loscertales has been coauthor of a study which
shows the efficacy of Bendamustine in CLL. Dr. GarciaNoblejas continued to publish in CMV infections after
BMT, with a nice study of the kinetics of NK cells.
Finally, Dr. Figuera and Dr. Steegmann have been coauthors in a PLoS paper mastered by Dr. CuestaDominguez and Fernández Ruiz, describing the tumorigenic activity of a novel BCR-JAK2 kinase
– 129 –
AREA 3AREA 2 AREA 1
GROUP MEMBERS
• Adrián Alegre Amor
• Ángela Figuera Álvarez
• María Reyes Arranz Sáez
• Javier Loscertales Pueyo
• Valle Gómez García de Soria
• María Jimena Cannata Ortiz
• Ana María García-Noblejas Moya
• Jimena Jiménez Braña
MAJOR GRANTS
• Juan Luis Steegmann Olmedillas. European treatment and outcome study on CML, EUTOS.
European Leukemia Net. Proyecto EUTOS de la
European LeukemiaNet. Duration: 2009 - 2013.
• Juan Luis Steegmann Olmedillas. Aspectos de toxicidad, farmacocinética y farmacogenética que determinan la respuesta al tratamiento con inhibidores de
tirosina cinasa, en pacientes con leucemia mieloide
crónica. ISCIII. Red Europea de Leucemia.
PI07/91015 y Proyecto EUTOS de la European
LeukemiaNet. Duration: 2012 - 2014.
YEAR
Total IF
Publication No.
Q1
Q2
2010
99,48
15
8
7
2011
85,353
16
9
3
2012
164,1
22
15
4
Baccarani M, Pileri S, Steegmann JL, Muller M,
Soverini S, Dreyling M, Grp, ESMO Guidelines Working.
Chronic myeloid leukemia: ESMO Clinical Practice
Guidelines for diagnosis, treatment and follow-up.
Annals of Oncology 23(Suppl 7):vii72-77. 2012. PMID:
22997458. IF: 6,425. DOI: 10.1093/annonc/mds228
Robak T, Windyga J, Trelinski J, von Depka Prondzinski
M, Giagounidis A, Doyen C, Janssens A, AlvarezRomán MT, Jarque I, Loscertales J, Rus GP, Hellmann
A, Jedrzejczak WW, Kuliczkowski K, Golubovic LM,
Celeketic D, Cucuianu A, Gheorghita E, Lazaroiu M,
Shpilberg O, Attias D, Karyagina E, Svetlana K,
Vilchevska K, Cooper N, Talks K, Prabhu M, Sripada P,
Bharadwaj TP, Næsted H, Skartved NJ, Frandsen TP,
Flensburg MF, Andersen PS, Petersen J.
Rozrolimupab, a mixture of 25 recombinant human
monoclonal RhD antibodies, in the treatment of primary
immune thrombocytopenia. Blood 120(18):3670-6.
2012. PMID: 22915649. IF: 9,898. DOI:
10.1182/blood-2012-06-438804
Paiva B, Vídriales MB, Montalbán MA, Pérez JJ,
Gutiérrez NC, Rosiñol L, Martínez-López J, Mateos
MV, Cordón L, Oriol A, Terol MJ, Echeveste MA, De
Paz R, De Arriba F, Palomera L, la Rubia JD, DíazMediavilla J, Sureda A, Gorosquieta A, Alegre A,
Martin A, Lahuerta JJ, Bladé J, Orfao A, San Miguel
JF. Multiparameter Flow Cytometry Evaluation of
Plasma Cell DNA Content and Proliferation in 595
Transplant-Eligible Patients with Myeloma Included
in the Spanish GEM2000 and GEM2005. American
Journal Pathology 181(5):1870-8. 2012. PMID:
22974582. IF: 4,89. DOI: 10.1016/j.ajpath.2012.
07.020
Rosiñol L, Oriol A, Teruel AI, Hernández D, LópezJiménez J, de la Rubia J, Granell M, Besalduch J,
Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla
J, Hernández MT, de Arriba F, Gutiérrez NC, MartínRamos ML, Cibeira MT, Mateos MV, Martínez J, Alegre
A, Lahuerta JJ, San Miguel J, Bladé J; on behalf of the
Programa para el Estudio y la Terapéutica de las
Hemopatías Malignas/Grupo Español de Mieloma
(PETHEMA/GEM) group. Superiority of bortezomib,
thalidomide, and dexamethasone (VTD) as induction
pre- transplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood
120(8):1589-1596. 2012. PMID: 22791289. IF: 9,898.
DOI: 10.1182/blood-2012-02-408922
Font P, Loscertales J, Benavente C, Bermejo A,
Callejas M, Garcia-Alonso L, Garcia-Marcilla A, Gil
S, Lopez-Rubio M, Martin E, Muñoz C, Ricard P,
Soto C, Balsalobre P, Villegas A. Inter-observer
variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification. Ann Hematol. 92(1):19-24. 2012. PMID:
22948274. IF: 2,615. DOI: 10.1007/s00277-0121565-4
Paiva B, Gutiérrez NC, Rosiñol L, Vídriales MB,
Montalbán MÁ, Martínez-López J, Mateos MV, Cibeira
MT, Cordón L, Oriol A, Terol MJ, Echeveste MA, de
Paz R, de Arriba F, Palomera L, de la Rubia J, DíazMediavilla J, Sureda A, Gorosquieta A, Alegre A,
Martin A, Hernández MT, Lahuerta JJ, Bladé J, San
Miguel JF; PETHEMA/GEM (Programa para el Estudio
de la Terapéutica en Hemopatías Malignas/Grupo
Español de Mieloma) Cooperative Study Groups.
– 130 –
AREA 3
Guilhot J, Baccarani M, Clark RE, Cervantes F,
Guilhot F, Hochhaus A, Kulikov S, Mayer J, Petzer AL,
Rosti G, Rousselot P, Saglio G, Saussele S,
Simonsson B, Steegmann JL, Zaritskey A, Hehlmann
R. Definitions, methodological and statistical issues
for phase 3 clinical trials in chronic myeloid leukemia:
a proposal by the European LeukemiaNet. Blood.
Epub 2012 Apr 16 119(25):5963-5971. 2012. PMID:
22508936. IF: 9,898. DOI: 10.1182/blood-2011-10383711
Ljungman P, Locasciulli A, de Soria VG, Békássy AN,
Brinch L, Espigado I, Ferrant A, Franklin IM, O'Riordan
J, Rovira M, Shaw P, Einsele H. Long-term follow-up of
HCV-infected hematopoietic SCT patients and effects
of antiviral therapy. Bone Marrow Transplant.
47(9):1217-1221. Epub 2011 Dec 12. 2012. PMID:
22158388. IF: 3,746. DOI: 10.1038/bmt.2011.238
Delgado J, Espinet B, Oliveira AC, Abrisqueta P, de la
Serna J, Collado R,Loscertales J, Lopez M,
Hernandez-Rivas JA, Ferra C, Ramirez A, Roncero JM,
Lopez C, Aventin A, Puiggros A, Abella E, Carbonell F,
Costa D, Carrio A, Gonzalez M; on behalf of the Grupo
Español de Leucemia Linfatica Cronica (GELLC) y
Grupo Español de Citogenetica Hematologica
(GECGH). Chronic lymphocytic leukaemia with 17p
deletion: a retrospective analysis of prognostic factors
and therapy results. Br J Haematol 157(1):67-74.
2012. PMID: 22224845. IF: 4,941. DOI:
10.1111/j.1365-2141.2011.09000.x
Knauf WU, Lissitchkov T, Aldaoud A, Liberati AM,
Loscertales J, Herbrecht R, Juliusson G, Postner G,
Gercheva L, Goranov S, Becker M, Fricke HJ, Huguet
F, Del Giudice I, Klein P, Merkle K, Montillo M.
Bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic
leukaemia: updated results of a randomized phase III
trial. Br J Haematol 159(1):67-77. 2012. PMID:
22861163. IF: 4,941. DOI: 10.1111/bjh.12000
Dimopoulos MA, Terpos E, Goldschmidt H, Alegre A,
Mark T, Niesvizky R. Treatment with lenalidomide and
dexamethasone in patients with multiple myeloma and
renal impairment. Cancer Treatment Reviews.
38(8):1012-9. 2012. PMID: 22609463. IF: 6,054. DOI:
10.1016/j.ctrv.2012.02.009
Bustos A, Álvarez R, Aramburo PM, Carabantes F, Díaz
N, Florián J, Lázaro M, de Segovia JM, Gasquet JA,
Alegre A; RADAR Study Group. Evaluation of clinical
use and effectiveness of darbepoetin alfa in cancer
patients with chemotherapy-induced anemia. Curr
Med Res Opin. 28(1):57-67. Epub 2011 Nov 23. 2012.
PMID: 22070513. IF: 2,38. DOI: 10.1185/03007995.
2011.639352
Sureda A, Canals C, Arranz R, Caballero D, Ribera JM,
Brune M, Passweg J, Martino R, Valcarcel D,
Besalduch J, Duarte R, Leon A, Pascual MJ, GarciaNoblejas A, Lopez Corral L, Xicoy B, Sierra J, Schmitz
N. Allogeneic stem cell transplantation after reduced
intensity conditioning in patients with relapsed or
refractory Hodgkin'slymphoma. Results of the HDRALLO study - a prospectiveclinical tr ial by the Grupo
Espanol de Linfomas/ Trasplante deMedula Osea
(GEL/TAMO) and the Lymphoma Working Party ofthe
European
Group
for
Blood
and
Marrow
Transplantation. Haematologica 97(2):310-317. Epub
2011 Oct 11. 2012. PMID: 21993674. IF: 6,424. DOI:
10.3324/haematol.2011.045757
Rosiñol L, García-Sanz R, Lahuerta JJ, HernándezGarcía M, Granell M, de la Rubia J, Oriol A, HernándezRuiz B, Rayón C, Navarro I, García-Ruiz JC, Besalduch
J, Gardella S, Jiménez JL, Díaz-Mediavilla J, Alegre A,
Miguel JS, Bladé J; on behalf of the PETHEMA/Spanish Myeloma Group. Benefit from autologous
stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable
disease. Haematologica. 97(4):616-621. Epub 2011
Nov 4. 2012. PMID: 22058223. IF: 6,424. DOI:
10.3324/haematol.2011.051441
– 131 –
AREA 3AREA 2 AREA 1
High-risk cytogenetics and persistent minimal residual
disease by multiparameter flow cytometry predict
unsustained complete response after autologous
stem cell transplantation in multiple myeloma. Blood.
119(3):687-91. Epub 2011 Nov 29. 2012. PMID:
22128143. IF: 9,898. DOI: 10.1182/blood-2011-07370460
Llamas-Velasco M, Cannata J, Dominguez I, GarcíaNoblejas A, Maximiliano Aragües, Fraga J, Arranz R.
Coexistence of Langerhans cell histiocytosis, RosaiDorfman disease and splenic lymphoma with fatal outcome after rapid development of histiocytic sarcoma of
the liver. J Cutan Pathol. 39(12):1125-30. 2012. PMID:
23043641. IF: 1,561. DOI: 10.1111/cup.12013
Steegmann JL, Cervantes F, Le Coutre P, Porkka K,
Saglio G. Off-target effects of BCR-ABL1 inhibitors and
their potential long-term implications in patients with
chronic myeloid leukemia. Leuk Lymphoma
53(12):2351-61. 2012. PMID: 22616642. IF: 2,58. DOI:
10.3109/10428194.2012.695779
Guisado-Vasco P, Arranz-Saez R, Canales M, Cánovas
A, Garcia-Laraña J, García-Sanz R, Lopez A, López JL,
Llanos M, Moraleda JM, Rodriguez J, Rayón C, Sabin
P, Salar A, Marín-Niebla A, Morente M, Sánchez-Godoy
P, Tomás JF, Muriel A, Abraira V, Piris MA, Garcia JF,
Montalban C. Stage IV and age over 45 years are the
only prognostic factors of the International Prognostic
Score for the outcome of advanced Hodgkin lymphoma in the Spanish Hodgkin Lymphoma Study
Group series. Leuk Lymphoma. 53(5):812-9. 2012.
PMID: 22185637. IF: 2,58. DOI: 10.3109/10428194.
2011.635861
Leukemia & Lymphoma. 53(9):1714-1721. 2012.
PMID: 22292853. IF: 2,58. DOI: 10.3109/10428194.
2012.662643
Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci
MT, Catalano J, Gisslinger H, Wiktor-Jedrzejczak W,
Zodelava M, Weisel K, Cascavilla N, Iosava G, Cavo M,
Kloczko J, Bladé J, Beksac M, Spicka I, Plesner T,
Radke J, Langer C, Ben Yehuda D, Corso A, Herbein
L, Yu Z, Mei J, Jacques C, Dimopoulos MA; MM-015
Investigators (.., Alegre A, ..). Continuous lenalidomide
treatment for newly diagnosed multiple myeloma. N
Engl J Med. 366(19):1759-69. 2012. PMID: 22571200.
IF: 53,298. DOI: 10.1056/NEJMoa1112704
Cuesta-Domínguez Á, Ortega M, Ormazábal C,
Santos-Roncero M, Galán-Díez M, Steegmann JL,
Figuera Á, Arranz E, Vizmanos JL, Bueren JA, Río P,
Fernández-Ruiz E. Transforming and tumorigenic activity of JAK2 by fusion to BCR: molecular mechanisms of
action of a novel BCR-JAK2 tyrosine-kinase. PLoS
One. Epub 2012 Feb 27. 7(2):e32451. 2012. PMID:
22384256. IF: 4,092. DOI: 10.1371/journal.
pone.0032451
BOOKS
Sanchez-Gonzalez B, Peñalver FJ, Medina A, Guillén
H, Calleja M, Gironella M, Arranz R, Sebastian E, de
Oña R, Cánovas A, de la Fuente I, Grande C, Sancho
JM, Perez R, Domingo E, Lopez-Lorenzo JL, Prieto E,
Panizo C, Gorosquieta A, Perez I, Cervera JM, Marin
M, Mencha C, Ramila E, Salar A. Clinical experience of
bendamustine treatment for non-Hodgkin lymphoma
and chronic lymphocytic leukemia in Spain. Leuk Res.
Epub 2011 Dec 7. 36(6):709-14. 2012. PMID:
22154023. IF: 2,923. DOI: 10.1016/j.leukres.
2011.10.024
Alegre A, Oriol-Rocafiguera A, Garcia-Larana J,
Mateos MV, Sureda A, Martinez-Chamorro C, Cibeira
MT, Aguado B, Knight R, Rosettani B. Efficacy, safety
and quality-of-life associated with lenalidomide plus
dexamethasone for the treatment of relapsed or refractory multiple myeloma: the Spanish experience.
– 132 –
A Alegre, A Villegas. La formación de especialistas de
Hematología y Hemoterapia. Libro Blanco de
Hematología en España. Ed. SEEH. 2012. EDIMSA
Madrid.
María Reyes Arranz Sáez. Actualización del tratamiento
del LDCGB. Cuadernos de Hematología. Fundación
Leucemia y Linfoma Año 2012. 2012. You and Us. Reyes
Arranz, Coordinadora de la monografía: Actualización del
tratamiento en Linfomas. Online web F.L.L.
María Reyes Arranz Sáez. Actualización del
Tratamiento del Linfoma Folicular. Cuadernos de
Hematología. Fundación Leucemia y Linfoma. 2012.
You and Us. Reyes Arranz, Coordinadora de la monografía: Actualización del tratamiento en Linfomas.
Online web.
AREA 3
Gómez García de Soria, Valle. Guía Madrileña de
Síndromes Mielodisplásicos. 2012. Asociación
Madrileña de Hematología y Hemoterapia. ISBN: 97884-15351-41-2.
A Alegre, JM Fernández Rañada, N Cuenca y Pilar
Calvo-Sotelo. Las Fundaciones y Asociaciones de
Pacientes de Hematología. Libro Blanco de Heamtología
en España. Ed. SEEH. 2012. EDIMSA Madrid.
Editor asociado Adrián Alegre. Monografía
Bendamustina en Síndromes Linfoproliferativos
Crónicos. Casos Clínicos. 2012. You and Us.
Adrián Alegre. Actualización en el Tratamiento de los
Síndromes Linfoproliferativos. Módulo 2.- Cuadernos
de Hematología 2012. 2012. Editorial You and Us.
Editor asociado.
Adrián Alegre. Actualización en el Tratamiento de
Gammapatías Monoclonales Atípicas. Módulo 1.Cuadernos de Hematología 2012. 2012. Editorial You
and Us. Editor asociado.
Javier Loscertales. Bendamustina en monoterapia tras
FCR. Archivos Clínicos de Sindromes Linfoproliferativos
Crónicos. 2012.
Ana García Noblejas. Linfoma de células del manto.
Linfomas B y T: Biología, clínica y tratamiento. 2012.
ISBN: 978-84-7885-541-4.
Ana García Noblejas. Actualización del tratamiento del
linfoma folicular. Módulo 1.- Cuadernos de
Hematología 2012. 2012.
Ana García Noblejas. Actualización del tratamiento del
linfoma de células del manto. Módulo 1.- Cuadernos
de Hematología 2012. 2012.
A Alegre, EM Ocio. ¿Cuál es el futuro de los Nuevos
Agentes en el Mieloma Múltiple?. 100 Preguntas sobre
el Mieloma Múltiple. 2012. You and Us. JJ Lahuerta Ed.
María Reyes Arranz Sáez. Linfoma de células del
manto. 2012. Ediciones Aula Médica. ISBN: 978-847885-541.
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: ALEGRE AMOR, ADRIAN
Estudio multicéntrico, aleatorizado y doble ciego de
denosumab en comparación con ácido zoledrónico
(Zometa«) para el tratamiento de enfermedad ósea en
sujetos con mieloma múltiple de nuevo diagnóstico;
(versión amend1: 18-08-11). AMGEN INC. 20090482.
EudraCT: 2010-020454-34
Estudio de fase 2/3, multicéntrico, aleatorizado, doble
ciego, controlado con placebo, en el que se evalúa la
administración de tabalumab en combinación con
bortezomib y dexametasona en pacientes con mieloma múltiple previamente tratados; (versión a: 28-0212). LILLY, S.A. H9S-MC-JDCG.
EudraCT: 2011-005103-32
PRINCIPAL INVESTIGATOR: GOMEZ GARCIA-SORIA,
VALLE
Estudio fase Ib/IIb, abierto, multicéntrico, de panobinostat (LBH589) oral administrado con 5-azacitidina
(vidaza), en pacientes adultos con síndromes mielodisplásicos (SMD), leucemia mielomonocítica crónica
(LMMC) o leucemia mieloide aguda (LMA); (versión 02:
24-10-12). NOVARTIS FARMACEUTICA, S.A.
CLBH589H2101.
EudraCT: 2009-010548-32
PRINCIPAL INVESTIGATOR: LOSCERTALES PUEYO,
JAVIER
Estudio fase II, multicéntrico para investigar la seguridad y eficacia de la combinación de ofatumumab y
bendamustina en pacientes con leucemialinfocítica
crónica (LLC) no tratada o en recaída; (versión
2011N125324/00(España):17-11-11).
– 133 –
AREA 3AREA 2 AREA 1
María Reyes Arranz Sáez. Actualización del
Tratamiento de Linfoma de células del manto.
Cuadernos de Hematología. Fundación Leucemia y
Linfoma. 2012. You and Us. Reyes Arranz,
Coordinadora de la monografía: Actualización del
tratamiento en Linfomas. Online web F.L.L.
GLAXOSMITHKLINE, S.A. OMB115991.
EudraCT: 2011-005178-43
Estudio multicéntrico, abierto y de un solo brazo con
pomalidomida en combinación con dexametasona a
dosis bajas en sujetos con mieloma múltiple refractario
o mieloma múltiple en recaída y refractario; (versión
final: 23-05-12). CELGENE CORPORATION. CC4047-MM-010.
EudraCT: 2012-001888-78
PRINCIPAL INVESTIGATOR: ARRANZ SAEZ, MARIAREYES
Ensayo multicéntrico, internacional, de fase 3, de dos
grupos, aleatorizado y abierto de alisertib (MLN8237) o
la elección del investigador (agente único seleccionado) en pacientes con linfoma de células T periféricas
recidivante o resistentes al tratamiento; (Versión
enmienda 105-01-12). MILLENNIUM PHARMACEUTICALS, INC. C14012.
EudraCT: 2011-003545-18
Estudio fase 3, aleatorizado, controlado, abierto y multicéntrico del inhibidor de la Tirosina Quinasa de Bruton
(BTK), ibrutinib, frente a temsirolimus en sujetos con linfoma de células del manto en recaída o refractario que
han recibido al menos un tratamiento previo;(Versión
final: 26-06-12). JANSSEN-CILAG INTERNATIONAL
NV. PCI-32765MCL3001.
EudraCT: 2012-000601-74
Estudio de fase 3, aleatorizado, controlado, abierto,
multicéntrico para evaluar la seguridad y la eficacia de
dexametasona mas MLN9708 en comparación con el
tratamiento elegido por el médico administrado a
pacientes amiloidosis sistémica de cadenas ligeras
recidivante o refractaria;(versión Amend.1: 01-06-12).
MILLENNIUM PHARMACEUTICALS, INC. C16011.
EudraCT: 2011-005468-10
Registro observacional post autorización para evaluar
– 134 –
el impacto clínico del inicio de la terapia antitumoral de
rescate en pacientes con mieloma múltiple (MM) en
recaída biológica asintomática frente al inicio del
tratamiento en el momento de la recaída sintomática;
(Versión final: 17-09-12). (Estudio EPA-MMBR). CELGENE, S.L. CEL-MIE-2012-02
PRINCIPAL INVESTIGATOR: STEEGMANN OLMEDILLAS, JUAN-LUIS
Ensayo clínico fase II multicéntrico, abierto, no aleatorizado de dasatinib en pacientes con leucemia mieloide
crónica en fase crónica (LMC- -FC) con criterios de
respuesta subóptima tardía tras tratamiento con imatinib; (versión 2: 10-9-12). FUNDACION PETHEMA.
DASAPOST.
EudraCT: 2012-004259-36
Estudio retrospectivo del tratamiento con el esquema
R-COMP de pacientes mayores de 70 años con linfoma
no Hodgkin B de alto grado;(versión draftv03: diciembre
2011). MD ANDERSON IE. MDA-LNH-2011-01
PRINCIPAL INVESTIGATOR: FIGUERA ALVAREZ,
ANGELA
Estudio de fase III, aleatorizado y doble ciego de
Febuxostat para la prevención del síndrome de lisis
tumoral en las neoplasias malignas hematológicas en
comparación con alopurinol; (versión 1.1:2-04-12).
MENARINI RICERCHE S.P.A. FLO-01.
EudraCT: 2012-000776-42
Estudio de fase 2, aleatorizado, de bortezomib/dexametasona, con o sin elotuzumab, en sujetos con mieloma múltiple en recidiva o resistente al
tratamiento; (versión orig+amd1: 20-07-11). BRISTOL
MYERS SQUIBB INTERNATIONAL CORPORATION.
CA204009.
EudraCT: 2011-002695-16
PRINCIPAL INVESTIGATOR: GOMEZ GARCIA-SORIA,
VALLE
Estudio de fase III, multicéntrico, aleatorizado y controlado para evaluar la eficacia y la seguridad de ON
AREA 3
Estudio fase 2, multicéntrico, de un solo brazo de
tratamiento para evaluar la eficacia y seguridad del
inhibidor de la Tirosina Quinasa de Bruton (Btk), ibrutinib, en monoterapia, en sujetos con Linfoma de
Células del Manto que progresan después de la terapia con bortezomib; (versión final: 06-04-12).
JANSSEN-CILAG INTERNATIONAL NV. PCI-32765
MCL2001.
EudraCT: 2012-000711-88
Estudio de fase 3 aleatorizado y abierto de carfilzomib
y dexametasona en comparación con bortezomib y
dexametasona en pacientes con mieloma múltiple en
recidiva; (Versión 13-03-12). ONYX THERAPEUTICS,
INC. 2011-003.
EudraCT: 2012-000128-16
JAVIER
Estudio fase 3, aleatorizado, doble ciego, controlado
con placebo, de ibrutinib, un inhibidor de la Tirosina
Quinasa de Bruton (Btk), en combinación con bendamustina y rituximab (BR) en sujetos con Leucemia
Linfocítica Crónica/Linfoma Linfocítico de Células
Pequeñas en recaída o refractario;(Versión final:09-0512). JANSSEN-CILAG INTERNATIONAL NV. PCI32765CLL3001.
EudraCT: 2012-000600-15
JAVIER
Estudio de fase 3, aleatorizado, doble ciego, controlado con placebo para evaluar la eficacia y seguridad de
GS-1101 (CAL-101) en combinación con bendamustina y rituximab para la leucemia linfocítica crónica tratada previamente; (Versión 1:16-03-12). GILEAD SCIENCES, INC. GS-US-312-0115.
EudraCT: 2011-006292-20
– 135 –
AREA 3AREA 2 AREA 1
01910.Na al administrarse mediante infusión intravenosa continua de 72 horas en semanas alternas a
pacientes con síndrome mielodisplásico con exceso de
blastocitos que presentan recurrencia tras el tratamiento con azacitidina o decitabina, o resistencia o intolerancia a dichos fármacos, (versión 11-08-11).
ONCONOVA THERAPEUTICS INC. abr-21.
EudraCT: 2010-019755-21
Line 3.5
Biological, cellular and
molecular monitoring in
oncohematology
GRUPO 45
HEAD OF LABORATORY
Elena Fernández Ruiz
GROUP MEMBERS
• Álvaro Cuesta Domínguez
• Matilde Santos Roncero
• Irene Bodega Mayor
• Mónica Sala Valdés
RESEARCH INTEREST
JAK2 is a non-receptor tyrosine kinase, essential for signaling through a variety of cytokine receptors and required for
normal hematopoiesis. Activation of the JAK2-cytokine
receptor complex leads to STAT5 phosphorylation and
nuclear translocation triggering survival gene transcription.
We have described the transforming and tumorigenic activity of a new chimeric protein, BCR-JAK2, obtained from a
patient with acute lymphocytic leukemia (ALL) and nonfavorable cytogenetics. Patients with BCR-ABL negative
leukemia with JAK2 rearrangements are not responders to
small tyrosine-kinase inhibitors targeting ABL as Imatinib.
The finding that JAK2 inhibitors down regulate BCR-JAK2
in vitro indicates that patients with leukemia and JAK2
rearrangements may benefit from targeted therapies. That
could be extended to pediatric B-progenitor ALL with JAK2
mutations.
To prove that BCR-JAK2 could be a driving force in
leukemia, we have studied the functional behavior of this
tyrosine kinase in a mouse model of bone marrow transplantation. Lin- progenitors have been transduced with
retroviral vectors bearing BCR-JAK2 and transplanted into
– 136 –
TG101209, a JAK2 inhibitor, down-regulates JAK2, BCR-JAK2, and STAT5
tyrosine-phosphorylation, as well as target gene expression of Ba/F3BCR-JAK2 transduced cells. (A) Sigmoidal dose-response curve showing
viability of Ba/F3-mock growing with IL-3 (IC50= 3180 nM) and Ba/F3BCR-JAK2 and Ba/F3-TEL-JAK2 growing in absence of IL-3 (IC50= 246
and 369 nM, respectively). The percentage of growth, relative to that of
cells in the absence of drug, is plotted for increasing concentrations of
TG101209 (where X axis is the logarithm of concentration). (B) Western
blot analysis of transduced Ba/F3 cells treated for 12 h with 1 μM
TG101209 (TG) or the vehicle (DMSO). Cellular lysates were immunoprecipitated with anti-pTyr Ab and immunoblotted with anti-JAK2 (upper panel). Whole cell lysates were probed with anti-pSTAT5, anti-STAT5 and
anti-Bcl-xL Ab’s (bottom). The expression levels of tubulin were used as a
loading control. STAT5 levels were used as a loading control for pSTAT5.
(C) qPCR for Bcl-xL, Osm and Cis expression on Ba/F3-mock, Ba/F3-BCRJAK2 and Ba/F3-TEL-JAK2 cells treated for 12 h with 1 μM TG. For comparative purposes, mRNA levels in untreated cells were normalized to 1.
Bars represent fold changes of each gene after normalization with
GADPH levels. Samples from three independent experiments were measured. Results are given as mean ± SEM (n=3).
previously irradiated syngenic mice to assess its ability to
give rise to leukemia. These mice developed a myeloproliferative neoplasm. Therefore, BCR-JAK2 is a chimeric protein with oncogenic potential. We will use this model to
develop a preclinical study of the efficacy of new JAK2
inhibitors in disease reversion.
MAJOR GRANTS
Elena Fernández Ruiz. Implicación de JAK2 en el
reconocimiento de patógenos y en la respuesta inmune innata. ISCIII. PI11/00128. Duration: 2012 - 2014.
AREA 3
RESEARCH INTEREST
YEAR
Total IF
Publication No.
Q1
Q2
2010
7,013
2
1
1
4,092
1
1
2011
2012
Cuesta-Domínguez Á, Ortega M, Ormazábal C, SantosRoncero M, Galán-Díez M, Steegmann JL, Figuera Á,
Arranz E, Vizmanos JL, Bueren JA, Río P, Fernández-Ruiz
E. Transforming and tumorigenic activity of JAK2 by fusion
to BCR: molecular mechanisms of action of a novel BCRJAK2 tyrosine-kinase. PLoS One. Epub 2012 Feb 27.
7(2):e32451. 2012. PMID: 22384256. IF: 4,092. DOI:
10.1371/journal.pone.0032451
GRUPO 46
HEAD OF LABORATORY
Cecilia Muñoz Calleja
GROUP MEMBERS
• Amada Elia Beltrán Núñez
• Carlos Cuesta Mateos
• Fernando Gómez-Reino Carnota
• Beatriz Somovilla Crespo
CCR7 mediates the pathogenesis of graft-versus-host
disease (GVHD)
GVHD represents one of the major complications associated with allogeneic stem cell transplantation. Our results
imply that receiving a high number of CCR7+ T-cells, able
to migrate to the recipient´s secondary lymphoid organs,
increases the incidence of GVHD. Therefore, the absolute
numbers of CCR7+ T-cells in the allograft might provide a
predictive indicator of GVHD. In addition, our study indicates that alloreactive cells predominate within the
CCR7+CD62L+ subsets and supports the approaches
of selective T-cell depletion aiming to prevent GVHD.
The tyrosine kinase inhibitor dasatinib modifies NK cell
phenotype
It has been suggested that NK cells improve therapy
responses in dasatinib-treated chronic myeloid leukemia
(CML) patients, but the mechanism is unclear. We show
that the NK cells in dasatinib-treated patients have similar
phenotype to chronically activated NK cells, which might
be a sign of an anti-CML immune response, suggesting
a role of NK cells in the enhanced therapy response.
Predictive markers in rituximab treated rheumatoid arthritis patients
Rheumatoid arthritis (RA) is a chronic inflammatory disease, which has been successfully treated with Rituximab
(Rtx). We show that no B cell subset predict an early
relapse in RA patients treated with Rtx. Conversely, the
increase of effector-memory T cells and CXCR5+ T cells,
which are supposed to support antibody secretion, predicts an early relapse. Therefore, we propose that these
subsets may be used as biomarkers to predict poor
response to Rtx treatment.
– 137 –
AREA 3AREA 2 AREA 1
Lin- primary progenitor cells expressing BCR-JAK2 show increased
survival compared to wild-type (wt) and mock progenitor cells. Linprogenitor cells obtained from male Balb/c mice were transduced with
pLZR (mock cells) or pLZR-BCR-JAK2 retroviral particles and seeded
for proliferation assay during 30 days.
Cortactin controls CCR7-dependent motility and invasion
of breast cancer cells
This work uncovered important aspects of cortactin regulation induced by CCL19/CCL21 engagement of CCR7.
Our findings reveal that CCR7 and cortactin may contribute to breast cancer progression by promoting cellular
structures and processes like lamellipodia and invadopodia, which are essential for metastasis. These results
bring us closer to understanding the link between CCR7
and the pathogenesis of breast cancer.
YEAR
Total IF
Publication No.
Q1
Q2
2010
12,114
3
1
2
2011
2012
GRUPO 47
HEAD OF LABORATORY
Eva Arranz Muñoz
Serine phosphorylation of cortactin is required for CCR7-mediated migration and invasion of MCF-7 breast cancer cells.
A) Schematic cartoon of the cortactin protein constructs used in this
study. We show the relevant sites of serine (S) and tyrosine (Y) phosphorylation as well as the mutants used in this study (D, aspartic; A, alanine).
B) Assessment of MCF-7 cell invasion in transiently transfected cells with
an empty GFP-fusion vector (GFP), or the 2A or SD GFP-cortactin mutants.
Transfectants were first seeded on top of gelatin-coated inserts in transwell chambers. Then, cells were allowed to invade towards incomplete
medium (white columns) or incomplete medium supplemented with 1
µg/mL CCL19 (grey columns) or CCL21 (black columns) that were added
to the bottom wells. Cells were allowed to invade for 48 h, and they were
deattached of the bottom side of the insert and were counted. Columns
represent the average of four separate experiments, each with duplicate
determinations; bars, SE. **, P < 0.01.
C) MCF-7 cells transiently transfected with an empty GFP-fusion vector
(GFP), or the 2A or SD GFP-cortactin mutants were seeded on p60 plates
and allowed to achieve 100% confluence. Then the monolayer of MCF-7
cells was scratched with a pipette tip and cells were incubated in serumfree media with CCL19, CCL21 or without chemokines. The gaps were
measured after 48 h. Migration of MCF-7 cells in a representative
wound-healing experiment from three is shown. Pictures shown
were taken at 0 and 48 hours.
D) Percentage of open area relative to time 0. Quantification of
wound closure data at 48h and 72h. Change in wound area was calculated as described in Materials and Methods. Results represent
the average of three experiments at each time point. Columns represent the mean of experiments. Error bars indicate SEM. *, P < 0.05;
**, P<0.01; ***, P < 0.001; ns, not significant.
– 138 –
GROUP MEMBERS
• María Ángeles Sanz de Benito
• Francisco Sanz Garrido
YEAR
Total IF
Publication No.
Q1
Q2
2010
5,272
2
1
1
4,092
1
1
2011
2012
Cuesta-Domínguez Á, Ortega M, Ormazábal C, SantosRoncero M, Galán-Díez M, Steegmann JL, Figuera Á,
Arranz E, Vizmanos JL, Bueren JA, Río P, FernándezRuiz E. Transforming and tumorigenic activity of JAK2 by
fusion to BCR: molecular mechanisms of action of a
novel BCR-JAK2 tyrosine-kinase. PLoS One. Epub 2012
Feb 27. 7(2):e32451. 2012. PMID: 22384256. IF: 4,092.
BOOKS
Eva Arranz, Angeles Sanz. Citogenética de los síndromes
mielodisplásicos. Guía Madrileña de Síndromes
Mielodisplásicos. Documentos de consenso en SMD.
Asociación Madrileña de Hematología y Hemoterapia.
2012. Ergon.
AREA 3
Line 3.6
New diagnostic and
therapeutic advances in
cardiovascular diseases
GRUPO 48
arterial en pacientes mayores de 65 años con
hipertensión sistólica aislada refractaria. MSPSI.
EC11-111(SPI/2885/ 2011). Duration: 2012 2013.
• Iluminada García Polo. Efecto de los nitratos orales
sobre la presión de pulso y la elasticidad arterial en
pacientes mayores de 65 años con hipertensión
sistólica aislada refractaria. MCyT a través de la convocatoria de Ensayos no comerciales. EC11-111.
Duration: 2012 - 2014.
HEAD OF LABORATORY
Luis Jesús Jiménez Borreguero
MAJOR GRANTS
• Carmen del Arco Galán. Impacto de la implantación de
un registro electrónico compartido en la eliminación de
los errores de transcripción de la prescripción. MSPSI.
EC11-107(SPI/2885/2011). Duration: 2012 - 2013.
• Iluminada García Polo. Efectos de los nitratos
orales sobre la presión de pulso y la elasticidad
YEAR
Total IF
Publication No.
Q1
2010
43,518
8
3
Q2
4
2011
181,383
27
17
10
2012
149,991
20
12
6
Ibanez B, Fuster V, Macaya C, Sánchez-Brunete V,
Pizarro G, López-Romero P, Mateos A, JiménezBorreguero J, Fernández-Ortiz A, Sanz G, FernándezFriera L, Corral E, Barreiro MV, Ruiz-Mateos B,
Goicolea J, Hernández-Antolín R, Acebal C, GarcíaRubira JC, Albarrán A, Zamorano JL, Casado I,
Valenciano J, Fernández-Vázquez F, de la Torre JM,
Pérez de Prado A, Iglesias-Vázquez JA, MartínezTenorio P, Iñiguez A. Study design for the "effect of
METOprolol in CARDioproteCtioN during an acute
myocardial InfarCtion" (METOCARD-CNIC): a randomized, controlled parallel-group, observer-blinded clinical
trial of early pre-reperfusion metoprolol administration
in ST-segment elevation myocardial infarction. Am
Heart J. 164(4):473-480.e5. 2012. PMID: 23067904.
IF: 4,651. DOI: 10.1016/j.ahj.2012.07.020
Sarraj A, Zarra KV, Jiménez-Borreguero LJ, Caballero
P, Nuche JM. Isolated cardiac involvement of RosaiDorfman disease. Ann Thorac Surg. 94(6):2118-20.
2012. PMID: 23176929. IF: 3,741. DOI:
10.1016/j.athoracsur.2012.04.134
Caballero P, Alonso R, Rosado P, Mata N, FernándezFriera L, Jiménez-Borreguero LJ, Badimon L, Mata P.
Detection of subclinical atherosclerosis in familial
– 139 –
AREA 3AREA 2 AREA 1
GROUP MEMBERS
• Luis Martínez Elbal
• Carmen Suárez Fernández
• Nuria Ruiz-Giménez Arrieta
• Ramón Puchades Rincón de Arellano
• Carmen del Arco Galán
• Iluminada García Polo
• Paloma Gil Martínez
• Fernando Moldenhauer Díaz
• Javier Roldan Núñez
• Patricia Ibáñez Sanz
• Natividad Gómez Gómez
• Rosa María Moreno Carriles
• Antonio Reyes García
• Alfonsa Friera Reyes
• María José Olivera Serrano
• Amparo Benedicto Buendía
• Bernhard Seidelberger
• Fernando Rivero Crespo
• Paloma Caballero Sánchez-Robles
hypercholesterolemia using non-invasive imaging
modalities. Atherosclerosis. 222(2):468-72. 2012.
PMID:
22460051.
IF:
3,794.
DOI:
10.1016/j.atherosclerosis.2012.02.043
Real de Asúa D, Puchades R, García-Polo I, Suárez C.
Influence of multiple blood pressure measurements on
the estimation of the ankle-brachial index and the consequent diagnosis of peripheral artery disease. Blood
Press Monit. 17(2):73-5. 2012. PMID: 22343750. IF:
1,52. DOI: 10.1097/MBP.0b013e328351de79
Sánchez-Gómez LM, Fernández-Luque MJ, Ruiz-Díaz
L, Sánchez-Alcalde R, Sierra-García B, MayayoVicente S, Ruiz-López M, Loeches-Belinchón P,
López-Gónzález J, González-Gamarra A, GallegoArenas A, Cubillo-Serna A, Gil-Juberias G, PérezCayuela P, Cañedo-Arguelles CA, García-Pascual JN,
Ruiz-Chércoles E, Suarez-Fernández C, Garcia-Polo I,
Abad-Perez D, Ballesteros-Arribas JM, IzquierdoMartínez M, Salvador-Alcaide E, Arribas-Vela AB,
Alonso-Pérez JM, Veja-Piris L, Rodríguez-Salvanés F,
Novella-Arribas B. A cluster-randomised clinical trial
comparing two cardiovascular health education strategies in a child population: the Savinghearts project.
BMC Public Health. 12:1024. 2012. PMID: 23176593.
IF: 1,997. DOI: 10.1186/1471-2458-12-1024
Kozakova M, Palombo C, Eng MP, Dekker J, Flyvbjerg
A, Mitrakou A, Gastaldelli A, Ferrannini E; RISC
Investigators (.., Carraro R, Friera A, Novella B, ..). Fatty
liver index, gamma-glutamyltransferase, and early
carotid plaques. Hepatology. 55(5):1406-15. 2012.
PMID: 22334565. IF: 11,665. DOI: 10.1002/hep.25555
Di Micco P, Fontanella A, Falvo N, Bonithon-Kopp C,
Decousus H, Riera-Mestre A, Monreal M; RIETE
Investigators (.., Ruiz-Giménez N, ..). Natural history of
patients developing thrombocytopenia while receiving
anticoagulant therapy for venous thromboembolism.
Int Angiol. 31(1):92-5. 2012. PMID: 22330631. IF:
1,652
Merino P, Álvarez J, Cruz Martín M, Alonso Á, Gutiérrez
I; SYREC Study Investigators (Reyes García A).
Adverse events in Spanish intensive care units: the
– 140 –
SYREC study. Int J Qual Health Care. 24(2):105-13.
2012. PMID: 22190588. IF: 1,958. DOI:
10.1093/intqhc/mzr083
Handberg A, Højlund K, Gastaldelli A, Flyvbjerg A,
Dekker JM, Petrie J, Piatti P, Beck-Nielsen H; RISC
Investigators (.., Carraro R, Friera A, Novella B, ..).
Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population. J Intern Med. 271(3):294-304.
2012. PMID: 21883535. IF: 5,483. DOI:
10.1111/j.1365-2796.2011.02442.x
Tzoran I, Saharov G, Brenner B, Delsart D, Román P,
Visoná A, Jiménez D, Monreal M; RIETE Investigators
(.., Ruiz-Giménez N, ..). Silent pulmonary embolism in
patients with proximal deep vein thrombosis in the
lower limbs. J Thromb Haemost. 10(4):564-71. 2012.
PMID: 22288520. IF: 5,731. DOI: 10.1111/j.15387836.2012.04648.x
Nauffal D, Ballester M, Reyes RL, Jiménez D, Otero R,
Quintavalla R, Monreal M; RIETE Investigators (.., RuizGiménez N, ..). Influence of recent immobilization and
recent surgery on mortality in patients with pulmonary
embolism. J Thromb Haemost. 10(9):1752-60. 2012.
PMID: 22726525. IF: 5,731. DOI: 10.1111/j.15387836.2012.04829.x
Alfonso F, Pérez-Vizcayno MJ, Dutary J, Zueco J,
Cequier A, García-Touchard A, Martí V, Lozano I, Angel
J, Hernández JM, López-Mínguez JR, Melgares R,
Moreno R, Seidelberger B, Fernández C, Hernandez R;
RIBS-III Study Investigators (under the auspices of the
Working Group on Interventional Cardiology of the
Spanish Society of Cardiology)(.., Martinez Elbal L,..).
Implantation of a drug-eluting stent with a different drug
(switch strategy) in patients with drug-eluting stent
restenosis. Results from a prospective multicenter
study (RIBS III [Restenosis Intra-Stent: Balloon
Angioplasty Versus Drug-Eluting Stent]). JACC
Cardiovasc Interv. 5(7):728-37. 2012. PMID:
22814777. IF: 6,8. DOI: 10.1016/j.jcin.2012.03.017
Camenzind E, Wijns W, Mauri L, Kurowski V, Parikh K,
Gao R, Bode C, Greenwood JP, Boersma E, Vranckx P,
AREA 3
Dalton T, Cegielski P, Akksilp S, Asencios L, Campos
Caoili J, Cho SN, Erokhin VV, Ershova J, Gler MT,
Kazennyy BY, Kim HJ, Kliiman K, Kurbatova E,
Kvasnovsky C, Leimane V, van der Walt M, Via LE,
Volchenkov GV, Yagui MA, Kang H; Global PETTS
Investigators, Akksilp R, Sitti W, Wattanaamornkiet W,
Andreevskaya SN, Chernousova LN, Demikhova OV,
Larionova EE, Smirnova TG, Vasilieva IA, Vorobyeva AV,
Barry CE 3rd, Cai Y, Shamputa IC, Bayona J, Contreras
C, Bonilla C, Jave O, Brand J, Lancaster J, Odendaal
R, Chen MP, Diem L, Metchock B, Tan K, Taylor A,
Wolfgang M, Cho E, Eum SY, Kwak HK, Lee J, Lee J,
Min S, Degtyareva I, Nemtsova ES, Khorosheva T,
Kyryanova EV, Egos G, Perez MT, Tupasi T, Hwang SH,
Kim CK, Kim SY, Lee HJ, Kuksa L, Norvaisha I,
Skenders G, Sture I, Kummik T, Kuznetsova T, Somova
T, Levina K, Pariona G, Yale G, Suarez C, Valencia E,
Viiklepp P. Prevalence of and risk factors for resistance
to second-line drugs in people with multidrug-resistant
tuberculosis in eight countries: a prospective cohort
study. Lancet. 380(9851):1406-17. 2012. PMID:
22938757. IF: 38,278. DOI: 10.1016/S01406736(12)60734-X
20(10):2063-9. 2012. PMID: 22421925. IF: 4,284. DOI:
10.1038/oby.2012.69
Ruiz-Giménez Arrieta N. Scope of the latest RE-LY
substudies: clinical implications. Rev Clin Esp.
212(Supl 2):4-14. 2012. PMID: 23117716. IF: 2,008.
DOI: 10.1016/S0014-2565(12)70013-9
Marchena PJ, Nieto JA, Guil M, García-Bragado F,
Rabuñal R, Boccalon H, Trujillo-Santos J, Monreal M;
RIETE Investigators (.., Ruíz-Giménez N, ..). Long-term
therapy with low-molecular-weight heparin in cancer
patients with venous thromboembolism. Thromb
Haemost. 107(1):37-43. 2012. PMID: 22116496. IF:
5,044. DOI: 10.1160/TH11-06-0423
Soler S, Delgado C, Ballaz A, Cisneros E, Malý R,
Babalis D, Monréal M; RIETE Investigators (.., RuizGiménez N, ..). Unsuspected pulmonary embolism in
patients with cancer. Thromb Res. 129(Suppl 1):S1619. 2012. PMID: 22682127. IF: 2,44. DOI:
10.1016/S0049-3848(12)70010-5
Nuñez MJ, Villalba JC, Cebrián E, Visoná A, Lopez-Jimenez
L, Núñez M, Szwebel TA, Luque JM, Jaras MJ, Monreal M;
RIETE Investigators (.., Ruíz-Giménez N, ..). Venous thromboembolism in immobilized patients with dementia.
Findings from the RIETE registry. Thromb Res. 130(2):1737. 2012. PMID: 22374336. IF: 2,44. DOI:
10.1016/j.thromres.2012.02.006
Carcas AJ, Borobia AM, Velasco M, Abad-Santos F,
Díaz MQ, Fernández-Capitán C, Ruiz-Giménez N,
Madridano O, Sillero PL; PGX-ACE Spanish
Investigators Group (..., Ochoa D, Marrodan I, Moreno
I, Román M, Verge C,...). Efficiency and effectiveness of
the use of an acenocoumarol pharmacogenetic dosing
algorithm versus usual care in patients with venous
thromboembolic disease initiating oral anticoagulation:
study protocol for a randomized controlled trial. Trials
13:239. 2012. PMID: 23237631. IF: 2,496. DOI:
10.1186/1745-6215-13-239
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: ARCO GALAN, CARMEN
Estudio de registro prospectivo y observacional para
caracterizar las condiciones normales de uso, la dosis
y la seguridad tras la administración del concentrado
estéril de vernakalant i.v.;(Versión 5-05-11). MERCK
SHARP & DOHME CORP. MSD-VER-2011-01/6621049-00
– 141 –
AREA 3AREA 2 AREA 1
McFadden E, Serruys PW, O'Neil WW, Jorissen B, Van
Leeuwen F, Steg PG; PROTECT Steering Committee
and Investigators (.., Martinez Elbal L,..). Stent thrombosis and major clinical events at 3 years after
zotarolimus-eluting or sirolimus-eluting coronary stent
implantation: a randomised, multice ntre, open-label,
controlled trial. Lancet. 380(9851):1396-405. 2012.
PMID: 22951082. IF: 38,278. DOI: 10.1016/S01406736(12)61336-1
PRINCIPAL INVESTIGATOR: RIVERO CRESPO, FERNANDO
Ensayo internacional en fase IV de 30 días de
duración, aleatorizado, de grupos paralelos, doble
ciego, controlado con placebo, para evaluar eficacia y
seguridad del inicio del tratamiento con ticagrelor prehospitalización vs hospitalización, en pacientes con
síndrome coronario agudo con elevación del segmento ST, a los que se les realizará una ICP;(versión 1.0:
15-02-11). ASTRA ZENECA. D5130L00006.
EudraCT: 2011-000214-19
PRINCIPAL INVESTIGATOR: GARCIA POLO, ILUMINADA
Ensayo clínico aleatorizado, doble ciego controlado
con placebo, para comparar el efecto, a tres meses de
seguimiento, sobre la presión de pulso y la función
vascular de mononitrato de isosorbide de acción prolongada, asociado al tratamiento antihipertensivo en
pacientes mayores de 65 años con hipertensión
sistólica aislada refractaria; (versión 1: 11-07-12).
FUNDACION DE INVESTIGACION BIOMEDICA HUP.
1392-GJK-303.
EudraCT: 2012-002988-10
PRINCIPAL INVESTIGATOR: BENEDICTO BUENDIA,
AMPARO
Pronóstico a largo plazo de los pacientes diabéticos y
pre-diabéticos tratados con stent coronario liberador
de everolimus; (versión 3.0:15-02-12). FUNDACION
DE INVESTIGACION SANITARIA DE LEON. DISCO 8
PRINCIPAL INVESTIGATOR: SUAREZ FERNANDEZ,
CARMEN
XALIA - Xarelto« para la anticoagulación a largo plazo
e inicial en el Tromboembolismo Venoso (TEV);
(Versión 1.2: 09-02-12). BAYER HISPANIA S.L. BAYRIV-2012-01
PRINCIPAL INVESTIGATOR: JIMENEZ BORREGUERO, LUIS-JESUS
Fluctuaciones circadianas del tamaño del infarto en el
IAMCEST y el efecto del beta-bloqueo en
éstas;(versión 1.0: 27-11-11). CNIC (CENTRO
NACIONAL DE INVEST. CARDIOLOGICAS). ESTUDIO
METOCARD-CLOCK
– 142 –
PRINCIPAL INVESTIGATOR: ARCO GALAN, CARMEN
Estudio EMERG-AF (EMergency dEpartment stRoke
prophylaxis and Guidelinesimplementation in Atrial
Fibrilation): Implementación de las Guías de
Fibrilación Auricular y profilaxis de ictus de los
Servicios de Urgencias; (versión final: 20-07-12).
BAYER HISPANIA S.L. BAY-FIB-2012-01
PRINCIPAL INVESTIGATOR: SUAREZ FERNANDEZ,
CARMEN
GLORIA-AF: Registro global del tratamiento antitrombótico oral a largo plazo en pacientes con fibrilación
auricular; (versión 3.0: 23-03-12). BOEHRINGER
INGELHEIM ESPAÑA, S.A. 1160.136/BOE-DAB2012-01
GRUPO 49
HEAD OF LABORATORY
Blanca Novella Arribas
GROUP MEMBERS
• Amelia González Gamarra
• Ana Cubillo Serna
• Ángela Gallego Arenas
• Belén Sierra García
• Francisco José Rodríguez Salvanés
• María Lourdes Ruiz Díaz
• Luis María Sánchez Gómez
• María Jesús Fernández Luque
• María del Pilar Loeches Belinchón
• M. Soledad Mayayo Vicente
• Javier López González
• Rosa María Sánchez Alcalde
RESEARCH INTEREST
Research is essential to respond to specific questions
to help us manage uncertainty and help us in making
AREA 3
bide mononitrate prolonged action on pulse pressure
and vascular function associated with antihypertensive
treatment in elderly patients 65 with isolated refractory
systolic hypertension, a three-month follow-up., In this
project the group is part of a research collaboration
seeking an alternative to refractory hypertension in the
elderly, and is currently recruiting patients.
• María del Pilar Loeches Belinchón. Control de la presión arterial (PA) en pacientes diabéticos: estudio
comparativo entre el tratamiento basado en la PA
medida en la consulta médica y el basado en la
automedición de la PA en el domicilio del paciente
(AMPA en DM2). ISCIII. 10/01927. Duration: 2011 2013.
• Blanca Novella Arribas. A Clinical Trial Of Two
Educational Strategies In Cardiovascular Health In
Child Population (SAVINHEARTS). ISCIII. CAIBER:
expediente Nº 1668-BK-148. FIS: PI11/00798.
Duration: 2012 - 2014.
Study desing and participant plow through the trial. The Savinghearts project. BMC Public Health 2012, 12:1024
decisions. Our commitment to study cardiovascular
risk has led us this year to participate in two projects.
The first one, the hearts saving project, is a cluster-randomized clinical trial of cardiovascular health education
comparing two strategies in a child population., The
group members are IP and ICs. At this point we have
completed the field work. The assay combines education in prevention and promotion of healthy knowledge
in cardiovascular risk based on the WHO NAOS strategy to prevent childhood obesity and health education.
The study compares 2 strategies for changes: one
measure but not fully utilized, the healthy breakfasts
and another beginning to take hold in other fields of
education, but not in terms of health: healthy concerts.
Table 1 describes the study design.
The second project is a randomized, double-blind,
placebo-controlled trial to compare the effect of isosor-
YEAR
Total IF
Publication No.
Q1
Q2
2010
40,111
6
5
1
2011
37,684
8
4
3
2012
25,426
5
3
2
Sánchez-Gómez LM, Fernández-Luque MJ, Ruiz-Díaz
L, Sánchez-Alcalde R, Sierra-García B, MayayoVicente S, Ruiz-López M, Loeches-Belinchón P,
López-Gónzález J, González-Gamarra A, GallegoArenas A, Cubillo-Serna A, Gil-Juberias G, PérezCayuela P, Cañedo-Arguelles CA, García-Pascual JN,
Ruiz-Chércoles E, Suarez-Fernández C, Garcia-Polo I,
Abad-Perez D, Ballesteros-Arribas JM, IzquierdoMartínez M, Salvador-Alcaide E, Arribas-Vela AB,
Alonso-Pérez JM, Veja-Piris L, Rodríguez-Salvanés F,
Novella-Arribas B. A cluster-randomised clinical trial
comparing two cardiovascular health education strate-
– 143 –
AREA 3AREA 2 AREA 1
MAJOR GRANTS
gies in a child population: the Savinghearts project.
BMC Public Health. 12:1024. 2012. PMID: 23176593.
IF: 1,997. DOI: 10.1186/1471-2458-12-1024
Sanz-Cuesta T, González-Escobar P, Riesgo-Fuertes
R, Garrido-Elustondo S, del Cura-González I, MartínFernández J, Escortell-Mayor E, Rodríguez-Salvanés F,
García-Solano M, González-González R, Martín-de la
Sierra-San Agustín MÁ, Olmedo-Lucerón C, Sevillano
Palmero ML, Mateo-Ruiz C, Medina-Bustillo B,
Valdivia-Pérez A, García-de Blas-González F, MariñoSuárez JE, Rodríguez-Barrientos R, Ariza-Cardiel G,
Cabello-Ballesteros LM, Polenti nos-Castro E, RicoBlázquez M, Rodríguez-Monje MT, Soto-Díaz S,
Martín-Iglesias S, Rodríguez-González R, BretónLesmes I, Vicente-Herrero M, Sánchez-Díaz J, GómezGascón T, Drake-Canela M, Asúnsolo-del Barco Á;
OB12 Group. Oral versus intramuscular administration
of vitamin B12 for the treatment of patients with vitamin
B12 deficiency: a pragmatic, randomised, multicentre,
non-inferiority clinical trial undertaken in the primary
healthcare setting (Project OB12). BMC Public Health.
12:394. 2012. PMID: 22650964. IF: 1,997. DOI:
10.1186/1471-2458-12-394
– 144 –
Kozakova M, Palombo C, Eng MP, Dekker J, Flyvbjerg
A, Mitrakou A, Gastaldelli A, Ferrannini E; RISC
Fatty liver index, gamma-glutamyltransferase, and
early carotid plaques. Hepatology. 55(5):1406-15.
2012. PMID: 22334565. IF: 11,665. DOI:
10.1002/hep.25555
Handberg A, Højlund K, Gastaldelli A, Flyvbjerg A,
Dekker JM, Petrie J, Piatti P, Beck-Nielsen H; RISC
Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population. J Intern Med. 271(3):294-304.
2012. PMID: 21883535. IF: 5,483. DOI:
10.1111/j.1365-2796.2011.02442.x
20(10):2063-9. 2012. PMID: 22421925. IF: 4,284. DOI:
10.1038/oby.2012.69
AREA 3
Line 3.7
New therapies in
infectious pathologies
GRUPO 50
HEAD OF LABORATORY
Ignacio de los Santos Gil
RESEARCH INTEREST
Activity in Hematology
The use of prophylactic posaconazol in a population at high risk of invasive fungal infection (IFI)
(LAM patients treated with intensive chemotherapy)
is associated with a saving of 1800 euros per
patient compared with fluconazole or itraconazole
prophylaxis. This economic benefit is in addition to
the clinical benefits: lower incidence of IFI and
longer survival in those who received posaconazole. These facts have made posaconazole prophylaxis in these patients the first choice in the most
prestigious international guidelines.
Causes of death in the Spanish HIV Cohort (CoRIS) between 2004 and
2008
Activity in Infectious Diseases
We are involved in the study of treatment, epidemiology, evolution and mortality in HIV-infection. All of this
work is in the context of the CoRIS, the Spanish HIVcohort. Also, we are involved in the treatment of HIVHCV coinfected patients with the new protease
inhibitors of HCV. One of our publications refers to the
differences in the causes of death of HIV-positive
patients in a cohort study by data sources and coding
algorithms. In this study we concluded that there is
substantial variation in CoDs in HIV-infected persons
according to sources and algorithms. ICD-10 in
patients known to be HIV-positive overestimates
HIV/AIDS-related deaths at the expense of underestimating liver-related diseases, infections and ill defined
causes. CoDe seems to be the best option for cohort
studies.
MAJOR GRANTS
Results of the base case of posaconazole versus SAT in the prevention
of IFI among high-risk neutropenic patients
Ignacio de los Santos Gil. Prevalencia de infección por
VIH no diagnosticada en pacientes que acuden al
Servicio de Urgencias, cuyo objetivo principal es estimar la prevalencia de infección por VIH no diagnosticada en personas mayores de 15 años que acuden al
Servicio de Urgencias. GILEAD SCIENCIES, S.L.
Duration: 2011 - 2012.
– 145 –
AREA 3AREA 2 AREA 1
GROUP MEMBERS
• Jesús Sanz Sanz
• Cristina Sarriá Cepeda
• José Rafael De la Cámara de Llanza
• Ana Salas Aparicio
• María Teresa Sánchez Casasola
YEAR
Total IF
Publication No.
Q1
Q2
2010
121,683
26
9
11
2011
117,881
28
13
8
2012
104,505
22
12
4
Mira JA, Rivero A, de Los Santos-Gil I, López-Cortés
LF, Girón-González JA, Márquez M, Merino D, del Mar
Viloria M, Téllez F, Ríos-Villegas MJ, Omar M, RiveroJuárez A, Macías J, Pineda JA; Grupo HEPAVIR de la
Sociedad Andaluza de Enfermedades Infecciosas
(SAEI). Hepatitis C virus genotype 4 responds better to
pegylated interferon with ribavirin tan genotype 1 in
HIV-infected patients. AIDS 26(13):1721-1724. 2012.
PMID:
22695304.
IF:
6,245.
DOI:
10.1097/QAD.0b013e3283568884
Berenguer J, Alejos B, Hernando V, Viciana P, Salavert
M, Santos I, Gómez-Sirvent JL, Vidal F, Portilla J, Del
Amo J; CoRIS (AIDS Research Network Cohort) (colaboradores J Sanz, A Salas, C Sarriá). Trends in mortality according to hepatitis C virus serostatus in the era of
combination antiretroviral therapy. AIDS 26(17):22412246. 2012. PMID: 22781223. IF: 6,245. DOI:
10.1097/QAD.0b013e3283574e94
Blanco JR, Jarrín I, Vallejo M, Berenguer J, Solera C,
Rubio R, Pulido F, Asensi V, del Amo J, Moreno S;
CoRIS (.., de los Santos I, Sanz Sanz J, Salas Aparicio
A, Sarriá Cepeda C, ..). Definition of advanced age in
HIV infection: looking for an age cut-off. AIDS Res Hum
Retroviruses. 28(9):1000-6. 2012. PMID: 22607516.
IF: 2,246. DOI: 10.1089/AID.2011.0377
the causes of death of HIV-positive patients in a cohort
study by data sources and coding algorithms. AIDS.
26(14):1829-34. 2012. PMID: 22410685. IF: 6,245.
DOI: 10.1097/QAD.0b013e328352ada4
de la Cámara R, Jarque I, Grau S, Carreras E.
Inadequate references in recent article. Am J Health
Syst Pharm 69(11):917-922. 2012. PMID: 22610019.
IF: 1,962. DOI: 10.2146/ajhp120091
Sobrino-Vegas P, Rodríguez-Urrego J, Berenguer J,
Caro-Murillo AM, Blanco JR, Viciana P, Moreno S,
Bernardino I, del Amo J; CoRIS. Colaboradores: I. de
los Santos, J. Sanz. Educational gradient in HIV diagnosis delay, mortality, antiretroviral treatment initiation
and response in a country with universal health care.
Antiviral Therapy 17(1):1-8. 2012. PMID: 22267463. IF:
3,161. DOI: 10.3851/IMP1939
Grau S, de la Cámara R, Sabater FJ, Jarque I, Carreras
E, Casado MA, Sanz MA. Cost-effectiveness of
posaconazole versus fluconazole or itraconazole in the
prevention of invasive fungal infections among high-risk
neutropenic patients in Spain. BMC Infect Dis 12:83.
2012. PMID: 22471553. IF: 3,118. DOI:
10.1186/1471-2334-12-83
HIV-CAUSAL Collaboration (.., de los Santos I, Sanz
Sanz J, ..). Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in highincome countries. Clin Infect Dis. 54(9):1364-72. 2012.
PMID: 22460971. IF: 9,154. DOI: 10.1093/cid/cis203
HIV-CAUSAL Collaboration (.., de los Santos I, Sanz
Sanz J, ..). The effect of efavirenz versus nevirapinecontaining regimens on immunologic, virologic and
clinical outcomes in a prospective observational study.
AIDS. 26(13):1691-705. 2012. PMID: 22546987. IF:
6,245. DOI: 10.1097/QAD.0b013e328354f497
Mira JA, García-Rey S, Rivero A, de Los Santos-Gil I,
López-Cortés LF, Girón-González JA, Téllez F, Márquez
M, Merino D, Ríos-Villegas MJ, Macías J, Rivero-Juárez
A, Pineda JA. Response to pegylated interferon plus
ribavirin among HIV/Hepatitis C virus-coinfected
patients with compensated liver cirrhosis. Clin Infect
Dis. 55(12):1719-1726. 2012. PMID: 22955435. IF:
9,154. DOI: 10.1093/cid/cis779
Hernando V, Sobrino-Vegas P, Burriel MC, Berenguer
J, Navarro G, Santos I, Reparaz J, Martínez MA, Antela
A, Gutiérrez F, del Amo J; CoRIS cohort (.., Sanz Sanz
J, Salas Aparicio A, Sarriá Cepeda C, ..). Differences in
Berenguer J, Rodríguez E, Miralles P, Von Wichmann
MA, López-Aldeguer J, Mallolas J, Galindo MJ, Van
Den Eynde E, Téllez MJ, Quereda C, Jou A, Sanz J,
Barros C, Santos I, Pulido F, Guardiola JM, Ortega E,
– 146 –
AREA 3
Monge S, Guillot V, Alvarez M, Peña A, Viciana P,
García-Bujalance S, Pérez Elias MJ, Iribarren JA,
Gutiérrez F, Itziar Casado M, Garcia F; CoRIS (.., de los
Santos I, Sanz Sanz J, Salas Aparicio A, Sarriá Cepeda
C, ..). Analysis of transmitted drug resistance in Spain
in the years 2007-2010 documents a decline in mutations to the non-nucleoside drug class. Clin Microbiol
Infect. 18(11):E485-90. 2012. PMID: 23016666. IF:
4,54. DOI: 10.1111/1469-0691.12011
Podzamczer D, Tiraboschi JM, Mallolas J, Curto J,
Cárdenes MA, Casas E, Castro A, Echevarría S, Leal
M, Lopez Bernaldo de Quirós JC, Moreno S, Puig T,
Ribera E, Villalonga C, Gómez-Sirvent JL, GarcíaHenarejos JA, Lopez-Aldeguer J, Barrufet P, Force L,
Santos I, Sanz J. Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients,
followed-up a median of 9 years. Curr HIV Res.
10(6):513-520. 2012. PMID: 22716109. IF: 1,745. DOI:
10.2174/157016212802429820
Monge S, Del Romero J, Rodríguez C, de Mendoza C,
de Górgolas M, Cosín J, Dronda F, Pérez-Cecilia E,
Peña JM, Santos I, Rubio R, Del Amo J; Grupo de
Seroconvertores de la Comunidad de Madrid. Sociodemographic factors associated with the progression
of HIV infection and the impact of HAART in a seroconverter cohort in Madrid (1986-2009). Enferm Infecc
Microbiol Clin 30(3):117-123. 2012. PMID: 22014512.
IF: 1,491. DOI: 10.1016/j.eimc.2011.07.016
Macías J, Viloria MM, Rivero A, de los Santos I,
Márquez M, Portilla J, Di Lello F, Camacho A, SanzSanz J, Ojeda G, Mata R, Gómez-Mateos J, Pineda
JA; FIBROCEL study group. Lack of short-term
increase in serum mediators of fibrogenesis and in
non-invasive markers of liver fibrosis in HIV/hepatitis
C virus-coinfected patients starting maraviroc-based
antiretroviral therapy. Eur J Clin Microbiol Infec Dis
31(8):2083-2088. 2012. PMID: 22258426. IF: 2,859.
DOI: 10.1007/s10096-012-1546-5
Macías J, Neukam K, Mallolas J, López-Cortés LF,
Cartón JA, Domingo P, Moreno S, Iribarren JA, Clotet
B, Crespo M, de los Santos I, Ortega E, Knobel H,
Jiménez-Expósito MJ, Pineda JA; COINS Study Team.
Liver toxicity of initial antiretroviral drug regimen including two nucleoside analogs plus one non-nucleoside
analog or one ritonavir-boosted protease inhibitor in
HIV/HCV coinfected patients. HIV Clin Trials 13(2):6169. 2012. PMID: 22510353. IF: 1,638. DOI:
10.1310/hct1302-61
Labarga P, Barreiro P, da Silva A, Guardiola JM, Rubio
R, Aguirrebengoa K, Miralles P, Portu J, Téllez MJ,
Morano L, Castro A, Pineda JA, Terrón A, HernándezQuero J, Mariño A, Ríos MJ, Echeverría S, Asensi V,
Vispo E, Soriano V; PERICO Study Group (colaboradores de los Santos I). Comparison of high ribavirin
induction versus standard ribavirin dosing, plus peginterferon-alfa for the treatment of chronic hepatitis C in
HIV-infected patients: the PERICO trial. J Infect Dis.
206(6):961-968. 2012. PMID: 22807523. IF: 6,41. DOI:
10.1093/infdis/jis449
Muñoz-Cobo B, Solano C, Benet I, Costa E, Remigia
MJ, de la Cámara R, Nieto J, López J, Amat P, GarciaNoblejas A, Bravo D, Clari MÁ, Navarro D. Functional
profile of cytomegalovirus (CMV)-specific CD8+ T cells
and kinetics of NKG2C+ NK cells associated with the
resolution of CMV DNAemia in allogeneic stem cell
transplant recipients. J Med Virol 84(2):259-267. 2012.
PMID: 22170546. IF: 2,82. DOI: 10.1002/jmv.22254
Yebra G, de Mulder M, Martín L, Rodríguez C, Labarga
P, Viciana I, Berenguer J, Alemán MR, Pineda JA,
García F, Holguín A; Cohort of the Spanish AIDS
Research Network (CoRIS) (colaboradores I. de los
Santos, J. Sanz). Most HIV type 1 non-B infections in
the Spanish cohort of antiretroviral treatment-naïve
HIV-infected patients (CoRIS) are due to recombinant
viruses. Journal of Clinical Microbiology 50(2):407-413.
2012. PMID: 22162552. IF: 4,153. DOI:
10.1128/JCM.05798-11
– 147 –
AREA 3AREA 2 AREA 1
Rubio R, Jusdado JJ, Montes ML, Gaspar G, Esteban
H, Bellón JM, González-García J; GESIDA HIV/HCV
Cohort Study Group. Sustained virological response to
interferon plus ribavirin reduces non-liver-related mortality in patients coinfected with HIV and Hepatitis C
virus. Clin Infect Dis. 55(5):728-36. 2012. PMID:
22610932. IF: 9,154. DOI: 10.1093/cid/cis500
Hernando V, Perez-Cachafeiro S, Lewden C, Gonzalez
J, Segura F, Oteo JA, Rubio R, Dalmau D, Moreno S,
Amo JD (colsboradores I. de los Santos, J Sanz, C
Sarria, A Salas). All-cause and liver-related mortality in
HIV positive subjects compared to the general population: differences by HCV co-infection. Journal of
Hepatology 57(4):743-751. 2012. PMID: 22709620. IF:
9,264. DOI: 10.1016/j.jhep.2012.06.010
Pineda JA, Neukam K, Mallolas J, López-Cortés LF,
Cartón JA, Domingo P, Moreno S, Iribarren JA, Clotet
B, Crespo M, de Los Santos I, Ortega E, Knobel H,
Jiménez-Expósito MJ, Macías J. Hepatic safety of
efavirenz in HIV/hepatitis C virus-coinfected patients
with advanced liver fibrosis. Journal of Infection
64(2):204-211. 2012. PMID: 22138553. IF: 4,126. DOI:
10.1016/j.jinf.2011.10.016
Ferrera C, Vilacosta I, Fernández C, López J, Olmos C,
Sarriá C, Revilla A, Vivas D, Sáez C, Rodríguez E, San
Román JA. Reassessment of Blood Culture-Negative
Endocarditis: Its Profile Is Similar to That of Blood
Culture-Positive Endocarditis. Rev Esp Cardiol.
65(10):891-900. 2012. PMID: 22771081. IF: 2,53. DOI:
10.1016/j.recesp.2012.04.004
CLINICAL TRIALS
PRINCIPAL INVESTIGATOR: SANZ SANZ, JESUS
Estudio multicéntrico observacional retrospectivo de la
eficacia y tolerabilidad de tratamientos antiretrovirales
que contienen maraviroc (MVC) en la práctica clínica.
Estudio MVCohort; (versión 1:23-1-12). JOSEP M. LLIBRE, SANTIAGO MORENO Y ANTONIO RIVERO.
LMR-MAR-2012-01
PRINCIPAL INVESTIGATOR: SANTOS GIL, IGNACIO
DE LOS
Medidas de salud autopercibidas por los pacientes
infectados por VIH que cambian su targa previo a un
régimen de un comprimido una vez al día por intolerancia en la práctica clínica habitual (Estudio PRO-STR)
(Versión 2:10-11-11). DANIEL PODZAMCZER ENFERMEDAD.INFECC. H.U.BELLVITGE. POD-TAR-2011-01
– 148 –
PRINCIPAL INVESTIGATOR: SANTOS GIL, IGNACIO
DE LOS
Estudio en fase 3b abierto para determinar la eficacia y
la seguridad de telaprevir, interferon-alfa2a pegilado y
ribavirina en sujetos con coinfección por el virus de la
Hepatitis C Crónica de genotipo 1 y el virus de la
inmunodeficiencia humana de tipo 1 (VHC-1/VIH-1),
con y sin tratamiento previo para el virus de la Hepatitis
C; (Versión final:26-07-12). JANSSEN-CILAG INTERNATIONAL NV. VX-950HPC3008.
EudraCT: 2011-004928-35
PRINCIPAL INVESTIGATOR: CAMARA LLANZA,
JOSE-RAFAEL
Estudio observacional para determinar la tasa de incidencia de enfermedad invasiva por hongos filamentosos y los resultados de los tratamientos en pacientes
de riesgo: una auditoría prospectiva europea (PIMDA);
(Versión: 1.0: 22-07-11). EUROPEAN CONFEDERATION
OF
MEDICAL
MYCOLOGY
(ECMM).
PIMDA/ECM-ANT-2012-01
GRUPO 51
HEAD OF LABORATORY
Javier Aspa Marco
GROUP MEMBERS
• Olga Rajas Naranjo
• María del Mar Ortega Gómez
• Jose Andrés García Romero de Tejada
• Rosa Mar Gómez Punter
• Emma Vázquez Espinosa
RESEARCH INTEREST
During 2012, the group 51, has continued to work on
various aspects of genetic factors regulating
response to pulmonary infections, working with dif-
AREA 3
MAJOR GRANTS
Proyecto Coordinado. Variabilidad genética en la señalización mediada por los TLRs/IL-1R en enfermedades
respiratorias: neumonía comunitaria y alergia respiratoria. ISCIII. FIS PI10/01718. Duration: 2011 - 2013.
Martín-Loeches I, Solé-Violán J, Rodríguez de Castro F,
García-Laorden MI, Borderías L, Blanquer J, Rajas O,
Briones ML, Aspa J, Herrera-Ramos E, Marcos-Ramos
JA, Sologuren I, González-Quevedo N, Ferrer-Agüero
JM, Noda J, Rodríguez-Gallego C. Variants at the promoter of the interleukin-6 gene are associated with
severity and outcome of pneumococcal communityacquired pneumonia. Intensive Care Med 38(2):25662. 2012. PMID: 22113815. IF: 5,399. DOI:
10.1007/s00134-011-2406-y
Menéndez R, Torres A, Reyes S, Zalacain R,
Capelastegui A, Rajas O, Borderías L, MartínVillasclaras JJ, Bello S, Alfageme I, de Castro FR, Rello
J, Molinos L, Ruiz-Manzano J. Compliance with guidelines-recommended processes in pneumonia: impact
of health status and initial signs. PLoS One
7(5):e37570. 2012. PMID: 22629420. IF: 4,092. DOI:
10.1371/journal.pone.0037570
Cuesta-Domínguez Á, Ortega M, Ormazábal C,
Santos-Roncero M, Galán-Díez M, Steegmann JL,
Figuera Á, Arranz E, Vizmanos JL, Bueren JA, Río P,
Fernández-Ruiz E. Transforming and tumorigenic activity of JAK2 by fusion to BCR: molecular mechanisms of
action of a novel BCR-JAK2 tyrosine-kinase. PLoS
One. Epub 2012 Feb 27. 7(2):e32451. 2012. PMID:
22384256. IF: 4,092. DOI: 10.1371/journal.
pone.0032451
CLINICAL TRIALS
YEAR
Total IF
Publication No.
2010
4,691
2
Q1
2011
10,937
2
2
2012
19,478
4
4
Q2
1
Menéndez R, Torres A, Reyes S, Zalacain R,
Capelastegui A, Aspa J, Borderías L, MartínVillasclaras JJ, Bello S, Alfageme I, de Castro FR, Rello
J, Molinos L, Ruiz-Manzano J. Initial management of
pneumonia and sepsis: factors associated with
improved outcome. Eur Respir J 39(1):156-62. 2012.
PMID: 21828033. IF: 5,895. DOI: 10.1183/09031936.
00188710
PRINCIPAL INVESTIGATOR: GOMEZ PUNTER, ROSA
MAR
Estimación de utilidades en pacientes con enfermedad
pulmonar obstructiva crónica en España; (versión
1.0:28-06-12). GLAXOSMITHKLINE, S.A. HZC116842
PRINCIPAL INVESTIGATOR: GOMEZ PUNTER, ROSA
MAR
Caracterización fenotípica de la población EPOC en
España: Clasificación de fenotipos clínicos de la EPOC
y evaluación del diagnóstico y el tratamiento en práctica clínica habitual; Estudio FENEPOC;(versión
– 149 –
AREA 3AREA 2 AREA 1
ferent groups in Spain: Hospital Dr. Negrin, Las
Palmas de Gran Canaria; Corporació Sanitaria Parc
Tauli Sabadell; Hospital San Jorge, Huesca; Hospital
Clinic and University, Valencia; Hospital Jose Molina
Orosa, Lanzarote. The group has been involved in a
prospective epidemiological study of hospital-based
surveillance of invasive pneumococcal disease in
adults over 18 years of age in Spain. The project has
been active for two years and will continue enrolling
patients in the next year. Dra. Olga Rajas also participated in two research project studying different relevant aspects related to the management of community-acquired pneumonia in Spain. Furthermore, at
the end of this year, our group has obtained a grant
from FIS (Instituto de Salud Carlos III) for the next 3
years, to start a new line: Incidence of cardiovascular
events after hospitalization for community-acquired
pneumonia in adults and its association with different
inflammation markers.
final:enmienda1,5-10-12). NOVARTIS FARMACEUTICA, S.A. NOV-EPO-2012-01
PRINCIPAL INVESTIGATOR: RAJAS NARANJO, OLGA
Estudio observacional, de no intervención, de la viabilidad de la recogida prospectiva de datos demográficos
y clínicos en los pacientes con Cáncer de Pulmón en
un entorno Pan-Europeo; (versión 1.0:17-02-12).
EUROPEAN RESPIRATORY SOCIETY. EULUCA
PRINCIPAL INVESTIGATOR: RAJAS NARANJO, OLGA
Estudio NEUMO-NAC. Influencia de la vacunación antineumocócica en la epidemiología, serotipo y complicaciones de la NAC; (Versión. NEUMONAC
GRUPO 52
HEAD OF LABORATORY
Manuel López-Brea Calvo
GROUP MEMBERS
• Teresa Alarcón Cavero
• María Josefa Martínez Gómez
• Diego Domingo García
• Laura María Cardeñoso Domingo
• Buenaventura Buendía Moreno
• Justo Martiáñez Rodríguez
• Sandra Rodrigo Gil
• Elisea Lomas Lomas
• Carmen María Serrano Morago
• Ángela Somodevilla Solís
• María del Carmen Martínez Jiménez
• Marina Espínola Docio
• Ana Correa Ruiz
• Alba Guiu Martínez
RESEARCH INTEREST
1.- Helicobacter pylori infection
One H. pylori strain was completely sequenced and
– 150 –
IL-12 levels detected with different Helicobacter pylori clinical isolates
after coculture of strains with peripheral blood mononuclear cells.
it is 1,6 Mb. Prophage Finder was used to detect 4
possible prophage in its genome. CRISPRs and
CRISPRs associated proteins was found by using
CRISPR Finder: 2 confirmed and one possible. IL12 production was quantified in coculture of H.
pylori isolates and peripheral blood mononuclear
cells in order to detect association with its virulence
factors. High levels of IL-12 production was
detected (5.860-27.486pg/ml) indicating an important role of H. pylori as cytokine inductor. IL-12
level was not associated with presence of dupA
gene or other virulence factors.
2.- Resistance to antibiotic in several bacteria.
Distribution of Streptococcus pneumoniae
serotypes, its antimicrobial susceptibility profiles
and relationship with vaccines in pneumococcal
strains isolated from blood cultures of adult
patients were studied. A clinical case of an abdominal abscess due to NDM-1-producing Klebsiella
pneumoniae in a 35-year-old Spanish patient after
hospitalization in India due to perforated appendicitis and peritonitis was detected in our Department.
3.- in vitro activity of antifungal agents.
The epidemiology of fungaemia episodes in Spain
were
studied
in
a
multicentre
study.
Epidemiological cutoff values were proposed and
would be useful for monitoring the emergence of
isolates with reduced susceptibility by use of the
Sensititre YeastOne method.
AREA 3
4.- CMV infection
The COBAS AmpliPrep/COBAS TaqMan CMV Test
(CAP/CTM CMV test) was compared to local
assays used by 5 laboratories at transplant centers
in the United States and Europe and a high interlaboratory agreement and precision of the test was
found.
22563775. IF: 4,54. DOI: 10.1111/j.1469-0691.
2012.03883.x
Gavín P, Iglesias MJ, Jiménez MS, Rodríguez-Valín
E, Ibarz D, Lezcano MA, Revillo MJ, Martín C,
Samper S; Spanish Working Group on MDR-TB (..,
Cardeñoso L, ..). Long-term molecular surveillance
of multidrug-resistant tuberculosis in Spain. Infect
Genet Evol. 12(4):701-10. 2012. PMID: 21669301.
IF: 3,128. DOI: 10.1016/j.meegid.2011.05.016
MAJOR GRANTS
YEAR
Total IF
Publication No.
Q1
Q2
2010
14,705
4
2
1
2011
10,243
2
2
2012
23,741
6
4
2
Alcalá L, Martín A, Marín M, Sánchez-Somolinos
M, Catalán P, Peláez T, Bouza E; Spanish
Clostridium difficile Study Group (M. Lopez-Brea).
The undiagnosed cases of Clostridium difficile
infection in a whole nation: where is the problem?.
Clin Microbiol Infect. 18(7):204-213. 2012. PMID:
Pemán J, Cantón E, Quindós G, Eraso E, Alcoba J,
Guinea J, Merino P, Ruiz-Pérez-de-Pipaon MT,
Pérez-del-Molino L, Linares-Sicilia MJ, Marco F,
García J, Roselló EM, Gómez-G-de-la-Pedrosa E,
Borrell N, Porras A, Yagüe G; FUNGEMYCA Study
Group (B. Buendia). Epidemiology, species distribution and in vitro antifungal susceptibility of fungaemia in a Spanish multicentre prospective survey. J Antimicrob Chemother. 67(5):1181-1187.
2012. PMID: 22351683. IF: 5,068. DOI:
10.1093/jac/dks019
Cantón E, Pemán J, Hervás D, Iñiguez C, Navarro
D, Echeverría J, Martínez-Alarcón J, Fontanals D,
Gomila B, Buendía B, Torroba L, Ayats J, Bratos A,
Sánchez-Reus F, Fernández-Natal I; the FUNGEMYCA Study Group. Comparison of three statistical
methods to establish the tentative wild-type population and epidemiological cutoff values for
echinocandins, amphotericin B and flucytosine and
six Candida species determined bycolorimetric
Sensititre YeastOne(R). J Clin Microbiol.
50(12):3921-3926. 2012. PMID: 23015676. IF:
4,153. DOI: 10.1128/JCM.01730-12
Oteo J, Domingo-García D, Fernández-Romero S,
Saez D, Guiu A, Cuevas O, Lopez-Brea M, Campos
J. Abdominal abscess due to NDM-1-producing
Klebsiella pneumoniae in Spain. J Med Microbiol.
61(6):864-867. 2012. PMID: 22383442. IF: 2,502.
DOI: 10.1099/jmm.0.043190-0
Pintado V, Pazos R, Jiménez-Mejías ME,
Rodríguez-Guardado A, Gil A, García-Lechuz JM,
Cabellos C, Chaves F, Domingo P, Ramos A, Pérez-
– 151 –
AREA 3AREA 2 AREA 1
• Teresa Alarcón Cavero. Helicobacter pylori: aislamiento y estudio de fagovirus como mecanismo
de transferencia de resistencia a antimicrobianos
y fuente de nuevas estrategias terapéuticas.
ISCIII. PI08/1775 . Duration: 2009 - 2012.
• Teresa Alarcón Cavero. Estudio de aspectos moleculares e inmunológicos de la infección por helicobacter pylori en pacientes pediátricos y adultos. Impacto en salud pública. Argentina.
PROIPRO 0310. Duration: 2010 - 2012.
• Teresa Alarcón Cavero. Validación de la pirosecuenciación como técnica de genotipado exacto
en cuadros de ACV y otras patologías de base
infectocontagiosa. BlackBio. Duration: 2011 2012.
• Teresa Alarcón Cavero. Tigecycline European
Surveillance Trial (TEST). Pfizer. EPI 252.
Duration: 2012 - 2013.
Cecilia E, Domingo D. Methicillin-resistant
Staphylococcus aureus meningitis in adults: a multicenter study of 86 cases. Medicine (Baltimore).
91(1):10-7. 2012. PMID: 22198499. IF: 4,35. DOI:
10.1097/MD.0b013e 318243442b
– 152 –
BOOKS
A. Somodevilla, M. Espínola, T. Alarcón. Microbiología aplicada a la clínica. Manual de Infecciones Perioperatorias
"Casos Clínicos". 2012. Ergón. ISBN: 978-84-8473-991-3.
AREA 3
Line 3.8
Individualized medicine
in solid tumors
GRUPO 53
HEAD OF LABORATORY
Almudena Zapatero Laborda
RESEARCH INTEREST
During the last two years several projects in prostate
cancer have focused our current research work. The
main one is a multi-institutional, “Spanish Phase III Trial
comparing Long-Term Versus Short-Term Androgen
Deprivation Combined With High-Dose Radiotherapy
For Localized Prostate Cancer: GICOR Protocol
DART01/05. EudraCT 2005-000417-36”. The encouraging preliminary results have been presented in
national and international meetings along 2011and
2012. Our most immediate major project related to
DART01/05 trial is the participation in the “INTERMEDIATE CLINICAL ENDPOINTS IN CANCER OF THE
PROSTATE (ICECaP) INITIATIVE”, a meta-analysis that
will be carried out by the ICECaP Working Group, a
multidisciplinary team of academic cancer researchers
from the Dana-Farber Cancer Institute -Harvard
Medical School-. This meta-analysis will use individual
patient data of all prostate cancer adjuvant clinical trials
with the goal of identifying a validated intermediate clin-
(a) 3D reconstruction of the rectum and its internal filings, showing the
centerline of the rectum: (b) 3D reconstruction of the straightened rectum and its internal filings, showing the straightened centerline; (c)
Representation of the surface of the rectum wall using cylindrical coordinates theta in the X-axis, Z in the y-axis, and radius in the Z-axis.
Rodríguez-Vila, García-Vicente, and Gómez: Metodology for registration distended rectums pelvic CT Medical Physics, Vol. 39, No 10, October 2012
ical endpoint that will serve as an acceptable surrogate
endpoint for overall survival.
We have also finished the cooperative study with the
CNIO titled “Comparison Of Biological-Molecular
Markers Predictive Of Radiation Response In Localized
Prostate Cancer Ref.: CaPr-HLP-RT-01/ PI 197”. The
results are the subject of two presentations and will be
published in due course in specialized journals.
Our ongoing projects include the participation in a
cooperative project of organ deformation and adaptive
radiotherapy in collaboration with the Bio-Ingeniería y
– 153 –
AREA 3AREA 2 AREA 1
GROUP MEMBERS
• María del Carmen Martín de Vidales
• José Alfonso Cruz Conde
• Inmaculada Fernández González
• Mariano Rabadán Ruiz
• Ramón Cristóbal Arellano Gañán
• Feliciano García Vicente
• María Magdalena Adrados de Llano
• Leopoldo Pérez González
Telemedicina group from Universidad Politécnica de
Madrid that have led to a Doctoral Thesis and a paper
published in 2012 American Association of Physicists
in Medicine (Med. Phys), but also two studies in translational research:
1) A cooperative study, protocol-RTCTC-01/PI 197,
entitled: Prognostic value of tumor cell levels circulating (CTCS) in peripheral blood in patients with
prostate cancer high risk (stage IIB-III) undergoing
radical treatment with radiotherapy and hormone to
study the predictive value of CTCs (circulating
tumoral cells) in high-risk localized prostate cancer.
2) The participation in an EUROPEAN PROTOCOL
FOR ASSESSING MULTICENTER Heterogeneity
GENES BY TUMOR CELL CYCLE PROGRESSION
IN PROSTATE CANCER PATIENTS WITH STAGE
T1-3, N0-X, M0-X ACRONYM: EMPATHY-P
Zapatero A, Martin De Vidales C, Arellano R, Ibañez Y,
Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz
Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive
bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology 80(5):1056-1062.
2012.
PMID:
22999456.
IF:
2,428.
DOI:
10.1016/j.urology.2012.07.045
BOOKS
Almudena Zapatero, Guillermo Andrés, Javier Angulo,
Ignacio Durán, Helena Gimbernat, Fernando Lista, José
Ignacio López, Erika Mateo. Cáncer de próstata. Guías
Prácticas en Urología. 2012. Elsevier España, S.L. ISBN:
978-84-7592-757-2. Editor: Javier Angulo.
CLINICAL TRIALS
YEAR
Total IF
Publication No.
Q1
2010
21,259
7
5
2011
11,174
3
3
2012
10,295
4
1
Q2
2
García-Vicente F, Fernández V, Bermúdez R, Gómez
A, Pérez L, Zapatero A, Torres JJ. Sensitivity of a
helical diode array device to delivery errors in IMRT
treatment and establishment of tolerance level for
pretreatment QA. J Appl Clin Med Phys. 13(1):111123. 2012. PMID: 22231218. IF: 1,291
Rodriguez-Vila B, Garcia-Vicente F, Gomez EJ.
Methodology for registration of distended rectums
in pelvic CT studies. Med Phys. 39(10):6351-9.
2012. PMID: 23039671. IF: 2,83. DOI:
10.1118/1.4754798
Fernandez, I, Celada, G, Brime, R, Diego, V,
Bocardo, G, Romero, E, Olivier, C. Opportunity of
ureteroscopy in the management of complex lithiasis in a center without extracorporeal lithotripsy.
The Journal of Urology 187(4S):E693-E694. 2012.
IF: 3,746. DOI: 10.1016/j.juro.2012.02.1680
– 154 –
PRINCIPAL INVESTIGATOR: ZAPATERO LABORDA,
MARIA-ALMUDENA
Deprivación androgénica y radioterapia a altas dosis con
o sin radioterapia pélvica completa en cáncer de próstata de riesgo intermedio desfavorable o de alto riesgo
favorable: Ensayo aleatorizado fase III; (versión vo: 16-0611). GICOR. RTOG0924
MARIA-ALMUDENA
Estudio observacional sobre la prevalencia de síndrome
metabólico y osteoporosis en el cáncer de próstata tratado con deprivación androgénica y su repercusión en la
calidad de vida: SIMBOSPROST;(versión 16-8-11).
GICOR. SIMBOSPROST
MARIA-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; (versión 1: 23-07-12). CAPR-RTCTC-01/PI 197
AREA 3
GRUPO 54
HEAD OF LABORATORY
Laura Cerezo Padellano
GROUP MEMBERS
• Mario López Rodríguez
• Margarita Martín Martín
• Eduardo Raboso García-Baquero
• Luis Naval Gías
• Consuelo López Elzaurdia
• Alicia Marín Palomo
• Adolfo Hinojar Gutiérrez
• Mario Fernando Muñoz Guerra
Hematoxylin and eosin. prominent basaloid morphology, lobular
growth, infiltrating lymphocytes.
During the year 2012, the group has advanced in its
research lines on head and neck cancer. The multicentric study on the Incidence of Human
Papillomavirus related oropharyngeal cancers, sponsored by Fundación Mutua Madrileña, has been
accepted for publication in Head&Neck journal and in
Clinical & Translational Oncology, both included in
Medline. This work has also been commented on
general media this year, including El Mundo, El País
and ABC.
Another important line of investigation has been the
analysis of Polymorphisms in HIF-1alpha in carcinomas of the larynx, that has been carried out in the
Otorhinolaryngology Department and the Pathology
Department and has been published in Clinical &
Translational Oncology.
We continue to participate in clinical trials on the prevention and treatment of mucositis in head and neck
patients receiving radiotherapy or chemoradiotherapy.
One of these multicentric trials is testing the value of
Clonidine Lauriad, and is still recruiting patients. The
other observational study analyze the efficacy of
intranasal Fentanyl for the treatment of pain associat-
P16 immunostaining. p16 + staining: strong and diffuse nuclear and
cytoplasmatic staining
ed with oral mucositis. The results of these trials will
help to improve the quality of life of head and neck
cancer patients.
MAJOR GRANTS
• Consuelo López Elzaurdia. Identificación de factores
genéticos, ambientales y de expresión fenotípica
– 155 –
AREA 3AREA 2 AREA 1
RESEARCH INTEREST
asociados a la progresión de lesiones precursoras del cáncer gástrico: estudio coordinado
español de seguimiento. ISCIII. PI10/02654.
Duration: 2011 - 2013.
• Consuelo López Elzaurdia. Identificación de factores genéticos, ambientales y de expresión
fenotípica asociados a la progresión de lesiones
precursoras del cáncer gástrico: estudio coordinado español de seguimiento. Carlos A.
González Svatetz. PI-436. Duration: 2011 2014.
• Adolfo Hinojar Gutiérrez. Papel de las células
madre tumorales en la evolución clínica del carcinoma escamoso de laringe. Estudio de la expresión de Podoplanina, CD44 y ALDH-1.
Fundación Mutua Madrileña. Duration: 2011 2013..
PUBLICATIONS
YEAR
(3)
[IF: 4,607]
Total IF
Publication No.
Q1
Q2
2010
9,046
6
1
4
2011
25,234
5
2
2012
4,607
3
2
Mañas A, Cerezo L, de la Torre A, García M,
Alburquerque H, Ludeña B, Ruiz A, Pérez A,
Escribano A, Manso A, Glaria LA; Grupo de
Investigación Clínica en Oncología Radioterápica
(GICOR). Epidemiology and prevalence of oropharyngeal candidiasis in Spanish patients with head
and neck tumors undergoing radiotherapy treatment alone or in combination with chemotherapy.
Clin Transl Oncol. 14(10):740-746. Epub 2012 Sep
8. 2012. PMID: 22960994. IF: 1,327. DOI:
10.1007/s12094-012-0861-8
Muñoz-Guerra M, Rodríguez-Campo F, RosónGómez S, Naval-Gías L. A New Method to Improve
Defects of the Mandibular Angle Using an
Asymmetrical Bone Distraction Technique. J Oral
Maxillofac Surg. 70(4):925-30. Epub 2011 Jul 18.
2012. PMID: 21764495. IF: 1,64. DOI:
10.1016/j.joms.2011.02.080
– 156 –
Mancha de la Plata M, Gías LN, Díez PM, MuñozGuerra M, González-García R, Lee GY, CastrejónCastrejón
S,
Rodríguez-Campo
FJ.
Osseointegrated Implant Rehabilitation of Irradiated
Oral Cancer Patients. J Oral Maxillofac Surg.
70(5):1052-63. Epub 2011 Jul 22. 2012. PMID:
21778009.
IF:
1,64.
DOI:
10.1016/j.joms.2011.03.032
BOOKS
Luis
Naval
Gías,
Raúl
González-García.
Reconstrucción Maxilomandibular Compleja. 2012.
Panamericana. ISBN: 978-84-9835-607-6.
Cerezo L, Martín M, López M. Radioterapia sobre el
hueso maxilomandibular reconstruido mediante
microcirugía o distracción ósea. Reconstrucción
Maxilomandibular Compleja. 2012. Panamericana.
ISBN: 978-84-9835-607-6.
Naval Gías L. Rehabilitación implantológica sobre
colgajo libre microvascularizado de peroné.
Reconstrucción Maxilomandibular Compleja. 2012.
Panamericana. ISBN: 978-84-9835-607-6.
Naval Gías L. Distracción osteogénica en la reconstrucción de defectos complejos del tercio medio
facial y la calota craneal. Reconstrucción
ISBN: 978-84-9835-607-6.
Muñoz Guerra M. Distracción osteogénica en colgajos óseos microvascularizados. Reconstrucción
ISBN: 978-84-9835-607-6.
Naval Gías L, Rosón Gómez S. Rehabilitación
implantológica sobre hueso distraído en defectos
maxilomandibulares complejos. Reconstrucción
ISBN: 978-84-9835-607-6.
Martín M, Carrasco M. Radioterapia paliativa.
Enfermería en Cuidados Paliativos y al Final de la
Vida. 2012. Elsevier. ISBN: 978-84-8086-754-2.
AREA 3
PRINCIPAL INVESTIGATOR: CEREZO PADELLANO,
LAURA
Calidad de vida en dolor irruptivo (COP-Qol).
Comparación de su percepción por pacientes y médicos;(Versión final: 23-12-11). TEVA PHARMA S.L.U.
DIOQOL
PRINCIPAL INVESTIGATOR: CEREZO PADELLANO,
LAURA
Valoración de la capacidad del fentanilo intranasal en
pectina en la prevención de los episodios de dolor
irruptivo en pacientes con mucositis actínica orofaringea; (versión 1.0:6-06-12). GICOR. GIC-FEN2012-01
GRUPO 55
HEAD OF LABORATORY
Cecilio Santander Vaquero
GROUP MEMBERS
• Ana Isabel Ballesteros García
• José Cantero Perona
• José Andrés Moreno Monteagudo
• Jesús González Cajal
• María del Mar Pérez Pérez
• Olga Donnay Candil
• Elena Martín Pérez
• Francisco E. Viamontes Ugalde
• María Mercedes Guijarro Rojas
• Montserrat Alcañiz Rodríguez
• María José Galán Sánchez-Heredero
• Concepción Alonso Cerezo
• Yat Wah Pun Tam
• Ramón Moreno Balsalobre
• José Luis García Fernández
• Erich Alberto Vargas Díez
• Yolanda Delgado Jiménez
• Lourdes del Campo del Val
• Ramón Colomer Bosch
RESEARCH INTEREST
Our Group leads a team focused on the diagnosis and
management of cancer.
Main research Topics:
Diagnosis
• Colonoscopy versus Fecal Immunochemical Testing
in Colorectal- Cancer Screening
• Anaemia in patients with non-myeloid cancer
• The diagnostic importance of hemodynamics and liver
biopsy
• Abdominal Complications Following Hematopoietic
Stem Cell Transplantation
Therapies
• Extended-spectrum beta-lactamase producing bacteria
• Clinical experience with ertapenem in the treatment of
infections of the biliary tract
• Bladder-sparing trimodality approaches for invasive
bladder cancer: neoadjuvant chemotherapy and concurrent radiochemotherapy
Pancreas diseases
• Bronchial-pancreatic fistula
• Colloid carcinoma of the pancreas
• Association of thymidylate synthase and hypoxia
inducible factor-1alpha DNA polymorphisms with pancreatic cancer
Genetics
• Appropriate use of the Unit Family Cancer Genetic
Counseling from primary Care
• Sexual development disorder in a patient
45,X/46,X,DIC(Y)
Training
• Study on the activity of general and digestive surgery
residents based on the use of the computerised logbook
– 157 –
AREA 3AREA 2 AREA 1
CLINICAL TRIALS
YEAR
Total IF
Publication No.
Q1
Q2
2010
90,213
13
5
4
2011
70,961
21
10
9
2012
69,717
7
4
1
Santander C, Moreno-Otero R. Commentary:
ursodeoxycholic acid as chemoprevention in inflammatory bowel disease and primary sclerosing
cholangitis. Aliment Pharmacol Ther 35(7):846-846.
2012. PMID: 22404405. IF: 3,769. DOI:
10.1111/j.1365-2036.2012.05019.x
Pergolizzi J, Ahlbeck K, Aldington D, Alon E, Collett
B, Coluzzi F, Huygen F, Jaksch W, Kocot-Kepska M,
Mangas AC, Margarit C, Mavrocordatos P, Morlion
B, Müller-Schwefe G, Nicolaou A, Pérez Hernández
C, Sichere P, Varrassi G. The chronic pain conundrum: should we CHANGE from relying on past history to assessing prognostic factors?. Curr Med
Res Opin. 28(2):249-56. 2012. PMID: 22181344. IF:
2,38. DOI: 10.1185/03007995.2011.651525
A. Herreros de Tejada, J. L. Calleja, M. Jiménez, V.
Rojo, C. Santander, J. C. Rial, R. García, J.
Chennat, A. L. Picardo, L. Abreu. Gastric band cutter to remove a migrated gastric band. Endoscopy
44(Suppl 2 UCTN):E40-E41. 2012. PMID:
22396269. IF: 5,21. DOI: 10.1055/s-00311291520
Torres A, Llinares P, Turegano F, Martin-Perez E,
Lobo E, Martin-Antona E, Granizo JJ, Aguilar L;
Study Group. Clinical experience with ertapenem in
the treatment of infections of the biliary tract in daily
practice in five Spanish hospitals. J Chemother.
24(6):338-43. 2012. PMID: 23174098. IF: 1,084.
DOI: 10.1179/1973947812Y.0000000041
Quintero E, Castells A, Bujanda L, Cubiella J, Salas
D, Lanas Á, Andreu M, Carballo F, Morillas JD,
Hernández C, Jover R, Montalvo I, Arenas J,
Laredo E, Hernández V, Iglesias F, Cid E,
Zubizarreta R, Sala T, Ponce M, Andrés M, Teruel
G, Peris A, Roncales MP, Polo-Tomás M, Bessa X,
– 158 –
Ferrer-Armengou O, Grau J, Serradesanferm A,
Ono A, Cruzado J, Pérez-Riquelme F, AlonsoAbreu I, de la Vega-Prieto M, Reyes-Melian JM,
Cacho G, Díaz-Tasende J, Herreros-de-Tejada A,
Poves C, Santander C, González-Navarro A;
COLONPREV Study Investigators (...,Mª Chaparro,
Gisbert JP,...). Colonoscopy versus Fecal
Immunochemical Testing in Colorectal-Cancer
Screening. N Engl J Med 366(8):697-706. 2012.
PMID:
22356323.
IF:
53,298.
DOI:
10.1056/NEJMoa1108895
Miranda-García P, López-Martín MC, Alvarez-Malé
T, Casanova-González MJ, Santander C, Bañares
R, Moreno-Otero R, Trapero-Marugán M. Idiopathic
portal hypertension complicated by ischemic hepatitis: the diagnostic importance of hemodynamics
and liver biopsy. Rev Esp Enferm Dig 104(1):45-47.
2012. PMID: 22300122. IF: 1,548
Zapatero A, Martin De Vidales C, Arellano R, Ibañez
Y, Bocardo G, Perez M, Rabadan M, García Vicente
F, Cruz Conde JA, Olivier C. Long-term results of
two prospective bladder-sparing trimodality
approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radiochemotherapy. Urology 80(5):1056-1062. 2012.
PMID:
22999456.
IF:
2,428.
DOI:
10.1016/j.urology.2012.07.045
GROUP ASSOCIATED 2
HEAD OF LABORATORY
Carlos Manuel Olivier Gómez
GROUP MEMBERS
• Gloria Bocardo Fajardo
• Estefanía Romero Selas
• Ricardo Brime Menéndez
• Victoria Diego García
• Guillermo Celada Luis
AREA 3
Our group focused on three different research areas.
Prostate cancer(PC): We analyzed the relationship
between circulating tumor cells (CTC) levels and different parameters (PSA levels, Gleason score and
TNM staging) in patients with metastatic hormonesensitive PC and established the prognostic value in
the overall and progression-free survival. The risk of
mortality and progression with ≥ 4 CTC were 4.1 (IC
95 %: 1.1-14.6; P = 0.029) and 8.5 (IC 95 %: 2.626.9; P < 0.001) times higher. The immunomagnetic
test allows us to quantify the CTC in peripheral
blood and could provide a possibility for correctly
staging and estimate the prognostic value of the
metastatic hormone-sensitive PC. Bladder cancer
(BC): We establish a protein expression pattern of
high risk progression superficial BC. It may be an
instrument to discern the appropriate candidates for
more aggressive treatments. By using a
2DElectrophoresis, Mass Spectrometry and silver
staining for protein visualization we analyzed
cytoskeleton, apoptosis and cellular metabolism
related proteins. Cytoskeleton related proteins show
differences between invasive BC (IBC) and non invasive BC (NIBC) versus the control. Proteins related
with apoptosis are significantly increased in NIBC vs
IBC group. Erectile Dysfunction (ED): We determined changes in the plasma proteome of proteins
associated with inflammation and atherogenesis in
diabetic patients with ED after vardenafil administration. The treatment significantly reduced circulating
plasma levels of different biomarkers mainly associated with inflammation and atherogenesis. These
results may suggest that vardenafil plays an antiinflammatory and protective effect on atherogenesis
in diabetic patients with ED.
Resel Folkersma L, San José Manso L, Galante Romo
I, Moreno Sierra J, and Olivier Gómez C. Prognostic
significance of circulating tumor cell count in patients
with metastatic hormone-sensitive prostate cancer.
Urology 80(6):1328-1332. 2012. PMID: 23063057. IF:
2,428. DOI: 10.1016/j.urology.2012.09.001
MAJOR GRANTS
CLINICAL TRIALS
Carlos Manuel Olivier Gómez. Exosomas como marcadores de la progresión tumoral del carcinoma de
células transicionales (CCT) vesical. FIB-HUP. Proyecto
Intramural. Duration: 2012 - 2012.
PRINCIPAL INVESTIGATOR: OLIVIER GOMEZ, CARLOS
Estudio exploratorio de la actividad del extracto lípido
esterólico de Serenoa repens (Permixon« 160mg cápsulas duras) frente a tamsulosina LP sobre biomar-
YEAR
Total IF
Publication No.
Q1
Q2
2011
4,105
21
10
9
2012
10,429
7
4
1
2010
Galante Romo, I., San José Manso, L.A., Casado
Varela, J., López Farré, A., Blázquez Izquierdo, J.,
Hernando Arteche, A., Sanz Ortega, J., Carballido
Rodríguez, J., Olivier Gómez, C.M. Transitional cell
bladder cancer proteomic mapping and risk of progression. European Urology Suppl 11(1):E897-U887.
2012. IF: 1,827
Fernandez, I, Celada, G, Brime, R, Diego, V, Bocardo,
G, Romero, E, Olivier, C. Opportunity of ureteroscopy in
the management of complex lithiasis in a center without extracorporeal lithotripsy. The Journal of Urology
187(4S):E693-E694. 2012. IF: 3,746. DOI:
10.1016/j.juro.2012.02.1680
Zapatero A, Martin De Vidales C, Arellano R, Ibañez Y,
Bocardo G, Perez M, Rabadan M, García Vicente F,
Cruz Conde JA, Olivier C. Long-term results of two
prospective bladder-sparing trimodality approaches for
invasive bladder cancer: neoadjuvant chemotherapy
and concurrent radio-chemotherapy. Urology
80(5):1056-1062. 2012. PMID: 22999456. IF: 2,428.
DOI: 10.1016/j.urology.2012.07.045
– 159 –
AREA 3AREA 2 AREA 1
RESEARCH INTEREST
cadores inflamatorios en el tratamiento de los síntomas
urinarios relacionados con la HPB. Estudio prospectivo
multinacional, multicéntrico, aleatorizado, doble ciego y
de grupos paralelos;(Versión 0106-02-12). PIERRE
FABRE MEDICAMENT. P00048GP403.
EudraCT: 2011-005307-33
GROUP ASSOCIATED 3
HEAD OF LABORATORY
Concepción Pérez Hernández
Saldaña MT, Pérez C, Navarro A, Masramón X, Rejas
J. Pain alleviation and patient-reported health outcomes following switching to pregabalin in individuals
with gabapentin-refractory neuropathic pain in routine
medical practice. Clin Drug Investig. 32(6):401-12.
2012. PMID: 22480279. IF: 1,822. DOI:
10.2165/11599400-000000000-00000
Molina-Manso D, Del Prado G, Ortiz-Pérez A,
Manrubia-Cobo M, Gómez-Barrena E, CorderoAmpuero J, Esteban J. In vitro susceptibility of
Staphylococcus aureus and Staphylococcus epidermidis isolated from prosthetic joint infections. J
Antibiot (Tokyo). 65(10):505-8. 2012. PMID:
22854340. IF: 1,651. DOI: 10.1038/ja.2012.62
GROUP MEMBERS
• José Cordero Ampuero
• Emilio Marín Aráez
• Vicente Casa de Pantoja
• Antonio Gómez Pan
• Francisco Clement Fernández
• Enrique Alday Muñoz
• Fernando Teba del Pino
• Javier Izaguirre Anduaga
Gómez-Barrena E, Esteban J, Medel F, Molina-Manso
D, Ortiz-Pérez A, Cordero-Ampuero J, Puértolas JA.
Bacterial adherence to separated modular components in joint prosthesis: A clinical study. J Orthop
Res. 30(10):1634-1639. 2012. PMID: 22467526. IF:
2,811. DOI: 10.1002/jor.22114
YEAR
Total IF
Publication No.
Q1
Q2
2010
67,605
6
2
4
2011
3,205
1
2012
17,281
8
1
4
de Salas-Cansado M, Pérez C, Saldaña MT, Navarro
A, Rejas J. A cost-effectiveness analysis of the effect
of pregabalin versus usual care in the treatment of
refractory neuropathic pain in routine medical practice
in Spain. Pain Med. 13(5):699-710. 2012. PMID:
22594706. IF: 2,346. DOI: 10.1111/j.15264637.2012.01375.x
2
Esteban J, Alonso-Rodriguez N, del-Prado G, OrtizPérez A, Molina-Manso D, Cordero-Ampuero J,
Sandoval E, Fernández-Roblas R, Gómez-Barrena E.
PCR-hybridization after sonication improves diagnosis
of implant-related infection. Acta Orthop. 83(3):299304. 2012. PMID: 22616742. IF: 2,168. DOI:
10.3109/17453674.2012.693019
Muñoz-Mahamud E, Pons M, Matamala A, Tibau R,
Puig L, Cordero-Ampuero J, García S. Hematogenous
– 160 –
septic arthritis of the hip in adult patients. Am J Emerg
Med. 30(4):630-1. 2012. PMID: 22306386. IF: 1,976.
DOI: 10.1016/j.ajem.2011.12.042
Navarro A, Saldaña MT, Pérez C, Masramón X, Rejas
J. Costs and health resources utilization following
switching to pregabalin in individuals with gabapentinrefractory neuropathic pain: a post hoc analysis. Pain
Pract. 12(5):382-93. 2012. PMID: 22004531. IF:
2,207. DOI: 10.1111/j.1533-2500.2011.00515.x
Cordero-Ampuero J, Darder A, Santillana J, Caloto
MT, Nocea G. Evaluation of patients' and physicians'
expectations and attributes of osteoarthritis treatment
using Kano methodology. Qual Life Res. 21(8):1391-
404. Epub 2011 Dec 2. 2012. PMID: 22134806. IF:
2,3. DOI: 10.1007/s11136-011-0058-6
CLINICAL TRIALS
inmediato de los pacientes sometidos a cirugía de
resección pulmonar como profilaxis de las complicaciones respiratorias postoperatorias;(versión 2.0:
30-12-11). FUNDACION GREGORIO MARAÑON.
FIBHGM-ECNC010-2010.
EudraCT: 2010-022863-36
PRINCIPAL INVESTIGATOR: PEREZ HERNANDEZ,
CONCEPCION
Eficacia y seguridad del apósito adhesivo medicamentoso de lidocaína al 5% en el dolor neuropático posoperatorio localizado crónico; (Versión
2.0:26-04-12).
GRUNENTHAL
GMBH.
KF10004/10.
EudraCT: 2012-000347-28
CONCEPCION
Estudio epidemiológico para determinar las diferencias en el impacto sobre la calidad de vida en
pacientes con dolor crónico de moderado a intenso
de tipo nociceptivo, neuropático y mixto; (versión
final v7: 12-04-12). GRUNENTHAL PHARMA S.A.
GRU-DOL-2012-01
CONCEPCION
Estudio prospectivo observacional, para valorar la
eficacia de la capsaicina al 8% en los distintos signos y síntomas positivos en el dolor neuropático
periférico localizado; Título corto: ECASIDONEP;
(versión 1.00:23-07-12). PER-CAP-2012
PRINCIPAL
INVESTIGATOR:
CORDERO
AMPUERO, JOSE
Estudio prospectivo, internacional, doble ciego,
controlado para evaluar los efectos de ranelato de
estroncio frente a placebo en la reducción de pérdida ósea periprotésica en pacientes con artroplastia
total de cadera. Estudio de "pérdida ósea periprotésica"; (versión final: 5-1-11, enmienda 1:28-1011). LABORATORIOS SERVIER, S.L. CL3-12911037.
EudraCT: 2010-020215-36
CONCEPCION
Ensayo clínico exploratorio en fase II, aleatorizado,
doble ciego, controlado con placebo y con grupos
paralelos para evaluar la eficacia y seguridad de E52862 (400 mg) por vía oral en pacientes con neuralgia postherpética (NPH); (versión 1.0:13-04-12).
LABORATORIOS ESTEVE, S.A. ESTEVE-SIGM203.
EudraCT: 2012-000399-41
PRINCIPAL INVESTIGATOR: ALDAY MUÑOZ,
ENRIQUE
Estudio en fase 4, aleatorizado, controlado de eficacia y seguridad del uso de la presión continua de
la vía aérea CPAP en el periodo postoperatorio
CONCEPCION
Ensayo clínico en fase III, multicéntrico, aleatorizado, doble ciego, controlado con placebo, con diseño de grupos paralelos, de aumento de dosis
escalonada para investigar la eficacia, seguridad y
tolerabilidad de naloxona HCI LP en comprimidos
administrada en un intervalo de dosis de 3 mg a 24
mg dos veces al día en pacientes con estreñimiento inducido por opioides; (versión final 2.0: 30-0812). DEVELCO PHARMA SCHWEIZ AG. 0176/DEV.
EudraCT: 2012-003218-14
– 161 –
AREA 3AREA 2 AREA 1
AREA 3
ENSAYOS HUP
PRINCIPAL INVESTIGATOR: GONZALEZ GUIJARRO,
JUAN-JACOBO
Estudio aleatorizado, frente a placebo, doble enmascarado de eficacia y seguridad de gevokizumab en el
tratamiento de pacientes con uveítis no infecciosa
intermedia, posterior o panuveítis, actualmente controlada con tratamiento sistémico. Estudio EYEGUARD-C; (versión final: 31-08-12). XOMA (US) LLC.
X052131/CL3-78989-006.
EudraCT: 2012-001609-25
PRINCIPAL INVESTIGATOR: PLANAS ROCA, ANTONIO
Estudio multicéntrico, aleatorizado, doble ciego, de
grupos paralelos, controlado con placebo, para evaluar la eficacia y seguridad de una nueva formulación IV
de ibuprofeno 800mg cada 6 horas para el manejo del
dolor postoperatorio; (versión 1: 14-12-11). LABORATORIOS BIOMENDI S.A.U. BIBEC02.
EudraCT: 2011-005007-33
PRINCIPAL INVESTIGATOR: MARTINEZ NIETO,
MARIA-CONCEPCION
Estudio de persistencia en pacientes con psoriasis
que inicien tratamiento con fármacos biológicos, en la
práctica clínica habitual;(versión 1:09-10-12). CONCEPCION MARTINEZ NIETO. MAR-UST-2012-01
PRINCIPAL INVESTIGATOR: GONZALEZ DEL PINO
VILLANUEVA, JUAN
Condrosarcoma de la mano; Versión 1: 18-10-12.
JGP-1-2012
PRINCIPAL INVESTIGATOR: SPOTTORNO RUBIO,
MARIA-PIA
Estudio epidemiológico, observacional, prospectivo,
para evaluar la prevalencia de las distintas etiologías
de la artrosis en el ámbito sanitario español;(Versión
Final 27 de julio de 2012, Enmienda no relevante 1.0
de 02 de octubre de 2012). MUNDIPHARMA PHARMACEUTICALS, S. L. ESTUDIO STAR
PRINCIPAL INVESTIGATOR: GONZALEZ GUIJARRO,
JUAN-JACOBO
– 162 –
Estudio aleatorizado, frente a placebo, doble enmascarado de eficacia y seguridad de gevokizumab en el
tratamiento de la uveítis no infecciosa activa intermedia, posterior o panuveítis; (versión final: 05-09-12).
XOMA (US) LLC. X052130/CL3-78989-005.
EudraCT: 2012-001610-42
PRINCIPAL INVESTIGATOR: MONTES LOPEZ, CARMEN
Estudio clínico multicéntrico, aleatorizado, controlado
con placebo y de simple ciego para evaluar la eficacia
y la tolerabilidad de la asociación de crema de ubidecarenona, dexpantenol y clorhexidina y una pasta de
clorhidrato de diltiazem al 2% en el tratamiento de la
fisura anal crónica; (versión 7: 24-01-12). TECNIMEDE
SOCIEDADE TECNICO-MEDICINAL, S.A. DIL-UBIDEX-CLO II/2003/003/PT.
EudraCT: 2005-005675-15
PRINCIPAL INVESTIGATOR: RAMASCO RUEDA,
FERNANDO
Estudio para determinar si la utilización de la concentración sérica de procalcitonina puede condicionar
una menor duración del tratamiento antibiótico en la
infección intrabdominal complicada. Estudio multicéntrico, aleatorizado. Subtitulo PROCIA. EMILIO MASEDA GARRIDO (H.U. LA PAZ). PROCIA
FERNANDO
Estudio descriptivo SATURSEPSIS: Saturación cerebral como predictor de saturación venosa central de
oxígeno y de resultados clínicos en pacientes con sepsis de origen abdominal; (Versión 1: 14-05-12). STSEO 1
PRINCIPAL INVESTIGATOR: MUÑOZ DE NOVA, JOSE
LUIS
Influencia de las variantes anatómicas del tronco celíaco en las cirugías hepática y pancreática; (versión 1).
VATC
PRINCIPAL INVESTIGATOR: DUDLEY PORRAS,
FRANCISCO J.
Utilización de recursos sanitarios y costes asociados
al tratamiento de Dupuytren en España; (Versión 4:24-
AREA 3
PRINCIPAL INVESTIGATOR: GIL-DIEZ USANDIZAGA,
JOSE-LUIS
Ensayo clínico de fase II aleatorizado, doble ciego,
controlado con tratamiento activo (tramadol 100mg) y
placebo, de grupos paralelos, para establecer la dosis
eficaz de entre 4 concentraciones de E-58425 para
dolor dental de moderado a intenso; (versión 1.5:1811-11). LABORATORIOS ESTEVE, S.A. ESTEVESACO4-201.
EudraCT: 2011-002778-21
PRINCIPAL INVESTIGATOR: PEREZ FERNANDEZ,
MARIA CARMEN
Estudio para evaluar el efecto del tratamiento mediante hemoperfusión en sepsis grave y shock séptico
secundarios a peritonitis postquirúrgica; (versión 1:
19-6-12). CLS-EO1
PRINCIPAL INVESTIGATOR: CASADO ESCRIBANO,
PEDRO PABLO
Ensayo clínico aleatorizado para evaluar la efectividad de un programa de intervención multimodal en
pacientes diabéticos tipo 2 prefrágiles y frágiles
sobre la fragilidad y la calidad de vida: Estudio MIDFrail; (versión 2:21-06-12). FUNDACION INVESTIGACION BIOMEDICA HOSPITAL GETAFE. MIDFRAIL
PRINCIPAL INVESTIGATOR: PATIÑO RODRIGUEZ,
EVA
Estudio epidemiológico, observacional, prospectivo,
para evaluar la prevalencia de las distintas etiologías
del dolor lumbar en el ámbito sanitario
español;(versión final: 28-10-11). MUNDIPHARMA
PHARMACEUTICALS, S. L. SMILE
PRINCIPAL INVESTIGATOR: ROMAN GUERRERO,
JESUS-CARLOS
Estudio observacional retrospectivo y no intervencionista para registrar el uso, seguridad y eficacia de
anidulafungina en el paciente crítico; (versión 1.0: 2409-11). EMILIO MASEDA GARRIDO (H.U. LA PAZ).
GTI-ANI-2011-01
PRINCIPAL INVESTIGATOR: AGUILAR MULET, JUANMARIANO
Ensayo clínico en fase IV randomizado doble ciego y
multicéntrico para la evaluación del uso de una mezcla de oxígeno y óxido nitroso 50/50 en el tratamiento
del cólico renal en el servicio de urgencias; (Versión 1:
13-01-12). FUNDACION INVESTIGACION BIOMEDICA H. LA PRINCESA. PG-ON-09.
EudraCT: HUP
PRINCIPAL INVESTIGATOR: VEGA GONZALEZ,
GEMA
Ensayo clínico en fase IV aleatorizado, no ciego, controlado para comparar la oxigenoterapia de alto flujo
(grupo de intervención) frente a la oxigenoterapia convencional (grupo control) en pacientes con insuficiencia Respiratoria Aguda (IRA) severa;(versión 1: 04-0412). FUNDACION INVESTIGACION BIOMEDICA H. LA
PRINCESA. EC11-103.
EudraCT: HUP
PRINCIPAL INVESTIGATOR: RUBIO PEREZ, INES
Infección por microorganismos gram negativos multiresistentes en pacientes de cirugía general: epidemiología, factores de riesgo y perfil microbiológico; (versión 1: 17-07-12).Titulo abreviado: Infección multiresistente cirugía. IMRC
PRINCIPAL INVESTIGATOR: ORTS RODRIGUEZ,
MARIA DEL MAR
Ensayo clínico aleatorizado y doble ciego, controlado
con placebo, de esteroides perioperatorios en
pacientes adultos de alto riesgo sometidos a cirugía
cardiaca con circulación extracorpórea;(Versión 1: 2206-11). INSTITUT DE RECERCA H.SANTA CREU I
SANT PAU. IIBSP-EST-2011-35.
EudraCT: 2010-023093-39
FERNANDO
Relación entre las saturaciones cerebral y venosa central de oxígeno con las complicaciones perioperatorias
en cirugía torácica;(Versión 3). SATOR-DOS
PRINCIPAL INVESTIGATOR: CORTAZAR SAEZ, MILAGROS TERESA
– 163 –
AREA 3AREA 2 AREA 1
5-12). LABORATORIOS PFIZER ESPAÑA. PFI-COL2012-01
Estudio coste-efectividad de la atención especializada
en ostomia, (Versión 2:15-03-12.). HOLLISTER IBERICA S.A. HOL-OST-2012-01
PRINCIPAL INVESTIGATOR: MARTINEZ NIETO,
MARIA-CONCEPCION
Estudio de la influencia de las variaciones de dosis de
tratamiento con inhibidores de la proteasa en la eficacia y coste de pacientes en tratamiento de Hepatitis C
Crónica en la práctica clínica habitual;(versión 1:2-0712). ALBERTO MORELL (SERVICIO DE FARMACIA
HUP). MOR-TEL-2012-01
PRINCIPAL
INVESTIGATOR:
BUSTAMANTE
MUNGUIRA, JUAN
Registro europeo de reparación de la válvula mitral;
– 164 –
(versión rev 4: octubre 2011).Estudio MiCardia. TP 10046
PRINCIPAL INVESTIGATOR: TIENO DROVE, TANIA
Estudio multicéntrico de validez y fiabilidad de la
Escala de Conductas indicadoras de dolor ESCID
para medir el dolor en pacientes críticos, no comunicativos y sometidos a ventilación mecánica. FISESCID
PRINCIPAL INVESTIGATOR: CHOCANO HIGUERAS,
ALBERTO
Registro europeo multinacional sobre la prevención de
episodios tromboembólicos en fibrilación auricular;
(versión 1.0: 29-08-11). DAIICHI SANKYO EUROPE
GMBH. DSE-EAF-01-11
www.iis-princesa.org

AREA 1 - IIS LA PRINCESA

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