AREA 1 - IIS LA PRINCESA

Transcripción

2013
ANNUAL REPORT OF
SCIENTIFIC ACTIVITY
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2013
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
AREA 2 AREA 3
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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
2013 ANNUAL REPORT OF
SCIENTIFIC ACTIVITY
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© INSTITUTO DE
INVESTIGACIÓN SANITARIA
Hospital Universitario de La Princesa
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AREA 2 · Neurotransmission, pharmacological neuroprotection and
neurodegenerative and neuropsychiatric diseases . . . . . . . . . . . . . 73
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AREA 2
Editing: Ibáñez&Plaza Asociados S.L.
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AREA 3 · Advanced therapies and individualized medicine . . . . . . . . . . . . . . . 97
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AREA 3
Diego de León, 62
28006 Madrid
Phone 91 520 25 08
e-mail: [email protected]
Web: www.iis-princesa.org
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–3–
PRÓLOGO FOREWORD
Prólogo IP
Foreword IP
IIS-Princesa 2013
–5–
Carta del Director Científico
Letter from the Scientific Director
Francisco Sánchez Madrid
Director Científico / Scientific Director
2013 ha supuesto
un año de consolidación para nuestro IP. Los investigadores han publicado un total de
362 artículos en
revistas indexadas
en Journal Citation Report (JCR),
con factor de
impacto superior
a1
–6–
E
s un grato placer presentaros de
nuevo otro año más un pequeño resumen de la actividad llevada a
cabo durante el año 2013 en nuestro Instituto de Investigación sanitaria IP.
Diariamente los investigadores del IP
trabajan para avanzar en el conocimiento
de las enfermedades y sus aplicaciones. Ya
sea desde los laboratorios o desde las consultas médicas, los profesionales del IP llevan a cabo su tarea teniendo como objetivo
la mejora de la salud.
En cuanto a la producción científica, el
2013 ha supuesto un año de consolidación
para nuestro IP. Los investigadores han publicado un total de 362 artículos en revistas
indexadas en Journal Citation Report
(JCR), con factor de impacto superior a 1.
El factor de impacto acumulado (FIA) de
2135,248 ha supuesto un incremento en
más de 300 puntos, respecto al año 2012.
Este incremento ha hecho que el FIM pasara de 5,2 en 2012 a 5,9 en el año 2013.
Este dato ha posicionado a nuestro IP entre
los mejores en cuanto a calidad de su producción científica.
Esta actividad es el resultado del gran
trabajo llevado a cabo por el personal del IP,
cuya tarea se traduce no sólo en la publicación de artículos en revistas científicas, sino
en su divulgación a través de libros y aplicación reflejada en las numerosas guías clínicas editadas en 2013.
No hay que olvidar los difíciles momentos económicos por los que el entorno
científico está pasando. A pesar de ellos,
durante el año 2013 se ha mantenido la tra-
t is a great pleasure to present again
another year a brief summary of the
activities carried out during 2013 in
our Institute for Health Research, IP.
Day after day IP researchers work
to advance the understanding of diseases and its applications. Whether
from their laboratories or their doctor´s
office, IP professionals perform their
task aiming at improving health.
In terms of scientific output, 2013
has been a year of consolidation for our
IP. Researchers have published a total
of 362 articles in journals indexed in
Journal Citation Report (JCR), with an
impact factor higher than 1. The cumulative impact factor of 2135,248 has
represented an increase of over 300
points, compared to the year 2013.
This increase has resulted in a shift of
mean impact factor (MIF) from 5.2 in
2012 to 5.9 in 2013. This figure has positioned our IP among the best in terms
of quality of scientific output.
This activity is the result of the
hard work done by the staff of IP, whose
activity is reflected not only in the publication of articles in scientific journals,
but in its dissemination through books
and its application in the numerous clinical guidelines published in 2013.
It is worth reminding here that the
scientific environment is currently going
through a tough economic situation.
Despite that, during the year 2013 IP
has maintained an upward trend in
terms of fundraising from public and
I
yectoria ascendente en cuanto a captación
de fondos de entidades públicas y privadas. La ayuda proporcionada por la Fundación de Investigación (FIB) ha supuesto un
importante apoyo en la captación de parte
de estos fondos.
Me gustaría terminar dando las gracias
a todas y cada una de las personas que forman parte de esta institución. Todos ellos
contribuyen con su trabajo, creatividad y dinamismo, a mantener la tendencia creciente en cuanto a la calidad de nuestra investigación. Gracias a todos.
private sources. The Biomedical Research Foundation (FIB) has provided
important assistance to support the
raising of part of these funds.
I would like to end by thanking
each and every one of the people who
are part of this Institution. They all contribute with their work, creativity and dynamism to keep the growing trend in
the quality of our research. Thank you
all.
2013 has been a
year of consolidation for our IP. Researchers have
published a total
of 362 articles in
journals indexed
in Journal Citation Report
(JCR), with an
impact factor
higher than 1
–7–
PRÓLOGO IP / FOREWORD IP
ESTRUCTURA ORGANIZATIVA
ORGANISATIONAL CHART
CONSEJO RECTOR
GOVERNING COUNCIL
PRESIDENTE / CHAIRMAN
Javier Maldonado González
Viceconsejero de Asistencia Sanitaria de la Comunidad de Madrid.
Deputy Minister of Health Care, Comunidad de Madrid
VICEPRESIDENTE / VICE-CHAIRMAN
José Mª Sanz Martínez
Rector de la UAM
Chancelor of UAM
MIEMBROS / MEMBERS
Miguel Ángel Andrés Molinero
Director Gerente, Hospital U. La Princesa
Managing Director, Hospital U. La Princesa
Paloma Martín Martín
Directora General de Investigación Formación e Infraestructura
(Comunidad de Madrid)
Julio Ancochea Bermúdez
Servicio de Neumología, Hospital U. La Princesa
Respiratory Department, Hospital U. La Princesa
Alfonso Garrigós Garnica
Director de Gestión y SS.GG., Hospital U. La Princesa
Margarita González Grande
Directora Gerente, Hospital U. Niño Jesús
Managing Director Hospital U. Niño Jesús
José Antonio Gutierrez Fuentes
Fundación Lilly
Lilly Foundation
Federico Mayor Menéndez
Centro Biología Molecular Severo Ochoa, Madrid
Severo Ochoa Molecular Biology Centre, Madrid
Ana Miquel Gómez
Gerente adjunto de Planificación y Calidad de Atención Primaria
Deputy Manager of Planning and Care Quality, Atención Primaria
Rosar Mª Ramos Pérez
Directora Gerente, Hospital U. Santa Cristina
Managing Director Hospital U. Santa Cristina
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
Managing Director, Hospital U. La Princesa
VICEPRESIDENTE / VICE-CHAIRMAN
Antonio García García
Instituto Teófilo Hernando, UAM
Servicio de Farmacología Clínica, Hospital U. La Princesa.
Instituto Teófilo Hernando, UAM
Clinical Farmacology Department, Hospital U. La Princesa
MIEMBROS / MEMBERS
Javier Aspa Marco
Director Médico, Hospital U. La Princesa
Medical Director, Hospital U. La Princesa
Gustavo Casero Balboa
Subdirector de Gestión/RR.HH, Hospital U. La Princesa
Manuel Fresno Escudero
–9–
Alfonso Garrigós Garnica
Director de Gestión Y SS.GG., Hospital U. La Princesa
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
Deputy Manager of Planning and Care Quality, Atención Primaria
Emilio Úcar Corral
Subdirector Médico, Hospital U. Santa Cristina
Medical Sub-director, Hospital U. Santa Cristina
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
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 –
José López Barneo
Director del Instituto de Investigación Biomédica, Sevilla
Director of Biomedical Research Institute, Sevilla
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
Felipe Rodríguez 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
COMISIÓN DE INVESTIGACIÓN
RESEARCH COMMITTEE
MIEMBROS / MEMBERS
Francisco Abad Santos
Servicio de Farmacología Clínica, Hospital U. La Princesa
Adrián Alegre Amor
Servicio de Hematología, Hospital U. La Princesa
Hematology Department, Hospital U. La Princesa
Servicio de Neumología, Hospital U. de La Princesa
Respiratory Department, Hospital U. La Princesa
Jesús Argente Oliver
Servicio de Endocrinología, Hospital U. Niño Jesús
Endocrinology Department, Hospital U. Niño Jesús
Javier Aspa Marco
Director Médico, Hospital U. La Princesa
Medical Director, Hospital U. La Princesa
Ramón Colomer Bosch
Servicio de Oncología Médica, Hospital U. La Princesa
Medical Oncolgy Department, Hospital U. La Princesa
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
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
Francisco Javier Pérez Gisbert
Servicio de Digestivo, Hospital U. La Princesa
Gastroenterology Department, Hospital U. La Princesa
María Yañez Mó
Unidad de Investigación, Hospital U. Santa Cristina
Research Unit, Hospital U. Santa Cristina
Andrés López Romero
Elena Martín Pérez
Concepción Martínez Nieto
Licinio Medina Moreno
Dolores Ochoa Mazarro
Igor Pinedo García
Carolina Pozuelo González
Eduardo Sánchez Sánchez
Alberto Sebastián Palomino
Alba Serrano Ruiz
Tania Tineo Drove
Mª Ángeles Vallejo
DIRECTOR / DIRECTOR
COMITÉ ÉTICO DE INVESTIGACIÓN CLÍNICA
CLINICAL RESEARCH ETHICS COMMITTEE
VICEPRESIDENTE/ DEPUTY CHAIRMAN
Mara Ortega Gómez
VOCAL / CHAIR
Enrique Alday Muñoz
Carmen del Arco Galán
Mª José Galán Sánchez Heredero
Carmelo García-Monzón
SECRETARIA TÉCNICA / TECHNICAL SECRETARY
Cecilia López García
Julio Rodríguez de Castro
FUNDACIÓN INVESTIGACIÓN BIOMÉDICA (FIB)
FOUNDATION FOR BIOMEDICAL RESEARCH (FBR)
RECURSOS HUMANOS Y CONTRATOS / HUMAN RESOURCES
DEPARTMENT
Gema Jiménez Jiménez
GESTIÓN DE PROYECTOS / PROJECTS MANAGEMENT DEPARTMENT
Jesús Santamaría Pérez
German Fernández Carracedo
GESTIÓN DE ENSAYOS CLÍNICOS / CLINICAL TRIALS MANAGEMENT DEPARTMENT
Alba Serrano Ruiz
CONTABILIDAD / ACCOUNTING DEPARTMENT
Jorge Gómez Juan
Ana Aroca Martínez
ORDENANZA / ADMINISTRATIVE ASSITANT
José Corrochano de la Cruz
– 11 –
PRODUCCIÓN CIENTÍFICA
SCIENTIFIC OUTPUT
SCIENTIFIC OUTPUT
La evaluación de los resultados científicos surge ante la necesidad
de evaluar el rendimiento de la actividad científica y su impacto en
la sociedad. Para llevar a cabo este análisis se utilizan los indicadores bibliométricos que tienen como objetivo el análisis cuantitativo de las publicaciones científicas. Aunque no es posible conocer
de forma absoluta la calidad y el impacto de las publicaciones
científicas, existen indicadores cuantitativos que permiten evaluar
de una forma relativa dichos parámetros. El Factor de Impacto o
índice de impacto (IF), mide la frecuencia con la que una revista ha
sido citada en un año concreto. Es un indicador que permite comparar revistas y evaluar la importancia relativa de una revista dentro de un mismo campo científico. Consideraremos como Factor de
Impacto el publicado por Thomson Reuters en el Journal Citation
Report (JCR) 2013.
Sólo se computaron aquellos artículos que estaban ya publicados (no se tuvieron en cuenta los artículos “Epub ahead of print”)
en revistas incluidas en el JCR cuyo factor de impacto sea superior
a 1. Dichas publicaciones sólo se contabilizarán una vez, para realizar el análisis global. Sin embargo aquellas en las que participen
diferentes grupos se computarán individualmente para cada uno
de ellos y se mostrarán en el resumen detallado de cada grupo.
De acuerdo a lo expresado previamente, en el 2013 se publicaron 362 artículos, con un factor de impacto acumulado (FIA) de
2135,248 y un factor de impacto medio (FIM) de 5.9. Estos datos
implican un incremento del 18% respecto al año 2012.
The evaluation of scientific results arises from the need to
determine the performance of scientific activity and its impact on
society. To carry out this analysis, bibliometric indicators are used
for quantitative analysis of scientific publications. Although it is not
possible to know absolutely the quality and impact of scientific
publications, they can be assessed to a certain extent by quantitative indicators. The impact factor (IF), measures the frequency with
which a journal has been cited in a particular year. It is an indicator that allows to compare journals and to assess the relative
importance of a journal within a scientific field. The impact factor
was considered as published by Thomson Reuters in the Journal
Citation Report (JCR) 2013. Only the articles that were already published in journals included in the JCR (with impact factor exceeding 1) were scored. The articles “Epub ahead of print" were not
taken into account. These publications were only considered once
for global analysis. However, those involving different groups were
– 12 –
scored for each of them and are shown in the detailed summary of
each group.
According to the stated above, in 2013 362 articles were published with a cumulative impact factor (CIF) of 2135,248 and a
mean impact factor (MIF) of 5.9. These data represent an increase
of 18% over 2012.
Aunque en el año 2013, el número de artículos en revistas de
Q1 es el mismo que el año anterior, se puede observar un incremento del 25% de artículos en revistas en primer decil (D1) de su
categoría.
Although in 2013 the number of articles in journals of fist quartile (Q1) is the same as the previous year, we can see an increase
of 25% of articles in first decile journals (D1).
LISTADO REVISTAS
JOURNAL INDEX
Las tablas que se muestran a continuación muestran el listado de
las 50 revistas con mayor factor de impacto y el número de artículos publicados en cada una de ellas.
The tables below show the list of the 50 journals with the highest impact factor and the number of articles published in each.
JOURNAL
IF
Articles
JOURNAL
IF
Articles
J CLIN INVEST
13.765
2
AM J PSYCHIAT
13.559
1
GUT
13.319
2
IMMUNOL REV
12.909
1
WORLD PSYCHIATRY
12.846
1
HEPATOLOGY
11.190
1
NAT REV GASTRO HEPAT
10.807
2
NAT COMMUN
10.742
1
J HEPATOL
10.401
2
NEUROSCI BIOBEHAV R
10.284
1
TRENDS MOL MED
10.110
1
CURR BIOL
9.916
1
BLOOD
9.775
1
CLIN INFECT DIS
9.416
3
LEUKEMIA
9.379
2
ANN RHEUM DIS
9.270
2
DIABETES CARE
8.570
1
CEREB CORTEX
8.305
1
MED RES REV
8.131
1
ANTIOXID REDOX SIGN
7.667
2
HYPERTENSION
7.632
1
JACC-CARDIOVASC INTE
7.440
1
J PATHOL
7.330
1
EUR RESPIR J
7.125
2
JACC-CARDIOVASC IMAG
6.986
1
AIDS
6.557
1
NEW ENGL J MED
54.42
4
J CLIN ENDOCR METAB
6.310
3
LANCET
39.207
7
RADIOLOGY
6.214
1
NAT MED
28.054
1
HEART
6.023
2
STROKE
6.018
3
LANCET ONCOL
24.725
1
COCHRANE DB SYST REV
5.939
2
LANCET INFECT DIS
19.446
1
HAEMATOL-HEMATOL J
5.868
2
J AM COLL CARDIOL
15.343
5
CELL MOL LIFE SCI
5.856
2
JNCI-J NATL CANCER I
15.161
1
THROMB HAEMOSTASIS
5.760
1
CIRCULATION
14.948
2
AM J KIDNEY DIS
5.756
2
EUR HEART J
14.723
3
FREE RADICAL BIO MED
5.710
1
PSYCHONEUROENDOCRINO
5.591
1
GASTROENTEROLOGY
13.926
2
ACTA PSYCHIAT SCAND
5.545
1
J EXP MED
13.912
1
ARTERIOSCL THROM VAS
5.533
1
– 13 –
GUÍAS CLÍNICAS
CLINICAL GUIDELINES
La relación entre la investigación básica y clínica supone siempre
un importante reto. Los investigadores trabajan con gran dedicación y esfuerzo para potenciar esta investigación traslacional. El
resultado es el gran número de guías editadas en 2013.
TITLE
The relationship between basic and clinical research is always
a major challenge. Researchers are working with great dedication
and effort to promote this translational research. The result is the
large number of guides published in 2013.
AUTHORS
JOURNAL
AREA GROUP
Guidelines for the Study of Nonspecific
Bronchial Hyperresponsiveness in Asthma
Perpiñá Tordera M, García Río F, Alvarez Gutierrez FJ, Cisneros
Serrano C, Compte Torrero L, Entrenas Costa LM, Melero Moreno C,
Rodríguez Nieto MJ, Torrego Fernández A
Arch
Bronconeumol.
(49) 10:432446.
1
22
Guidelines for the diagnosis and treatment of
idiopathic pulmonary fibrosis. Sociedad Española
de Neumología y Cirugía Torácica (SEPAR)
Research Group on Diffuse Pulmonary Diseases
Xaubet A, Ancochea J, Bollo E, Fernández-Fabrellas E, Franquet T,
Molina-Molina M, Montero MA, Serrano-Mollar A
Arch
Bronconeumol.
49(8):343-53.
1
22
A new approach to grading and treating COPD
based on clinical phenotypes: summary of the
Spanish COPD guidelines (GesEPOC)
Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J, Almagro P,
Quintano JA, Trigueros JA, Piñera P, Simón A, Riesco JA, Ancochea J,
Soriano JB
Prim Care
Respir J.
22(1):117-21.
1
22
Clinical practice guidelines in intracerebral
haemorrhage
Rodríguez-Yáñez M, Castellanos M, Freijo MM, López Fernández JC,
Martí-Fàbregas J, Nombela F, Simal P, Castillo J; por el Comitéad hoc
del Grupo de Estudio de Enfermedades Cerebrovasculares de la
SEN:, Díez-Tejedor E, Fuentes B, Alonso de Leciñana M, AlvarezSabin J, Arenillas J, Calleja S, Casado I, Dávalos A, Díaz-Otero F, Egido
JA, Gállego J, García Pastor A, Gil-Núñez A, Gilo F, Irimia P, Lago A,
Maestre J, Masjuan J, Martínez-Sánchez P, Martínez-Vila E, Molina C,
Morales A, Purroy F, Ribó M, Roquer J, Rubio F, Segura T, Serena J,
Tejada J, Vivancos J
Neurología
28(4):236-49
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
Neurología 28
(7): 435-42
2
35
Endovascular treatment in acute ischaemic
stroke. A Stroke Care Plan for the Region of
Madrid
Alonso de Leciñana M, Díaz-Guzmán J, Egido JA, García Pastor A,
Martínez-Sánchez P, Vivancos J, Díez-Tejedor E; Comité ad hoc del
Foro de Ictus de la Asociación Madrileña de Neurología
Neurología
28(7):425-434.
2
35
Endovascular treatment in acute ischaemic
stroke. A Stroke Care Plan for the Region of
Madrid
Alonso de Leciñana M, Díaz-Guzmán J, Egido JA, García Pastor A,
Martínez-Sánchez P, Vivancos J, Díez-Tejedor E; Comité ad hoc del
Foro de Ictus de la Asociación Madrileña de Neurología
Neurología
28(7):425-434.
2
35
– 14 –
TITLE
AUTHORS
JOURNAL
AREA
GROUP
Abatacept use in rheumatoid arthritis: evidence review
and recommendations
Martín Mola E, Balsa A, Martínez Taboada V, Sanmartí R,
Marenco JL, Navarro Sarabia F, Gómez-Reino J, AlvaroGracia JM, Román Ivorra JA, Lojo L, Plasencia C, Carmona L
Reumatol Clin (9)
1:5-17
3
36
Rheumatology in the community of Madrid: current
availability of rheumatologists and future needs using a
predictive model
Lázaro y De Mercado P, Blasco Bravo AJ, Lázaro y De
Mercado I, Castañeda S, López Robledillo JC
Reumatol Clin.
9(6):353-8.
3
36
Gestión de Comorbilidad en artritis reumatoide. Proyecto
GECOARr
Santos Castañeda Sanz
SERCOM
3
36
Clinical practice guideline for an integrated approach to
comorbidity in patients with psoriasis
Daudén E, Castañeda S, Suárez C, García-Campayo J,
Blasco AJ, Aguilar MD, Ferrándiz C, Puig L, SánchezCarazo JL; on behalf of the Working Group on Comorbidity in Psoriasis
J Eur Acad Dermatol
Venereol.
27(11):1387-404.
3
37
Therapeutic guidelines on ulcerative colitis: a GRADE
methodology based effort of GETECCU
Gomollón F, García-López S, Sicilia B, Gisbert JP,
Hinojosa J
Gastroenterol Hepatol.
36(2):104-14
3
38
Current Management of Iron Deficiency Anemia in
Inflammatory Bowel Diseases: A Practical Guide
Gomollón F, Gisbert JP
Drugs. 73(16):176170
3
38
III Spanish Consensus Conference on Helicobacter pylori
infection
Gisbert JP, Calvet X, Bermejo F, Boixeda D, Bory F,
Bujanda L, Castro-Fernández M, Dominguez-Muñoz E,
Elizalde JI, Forné M, Gené E, Gomollón F, Lanas Á, Martín
de Argila C, McNicholl AG, Mearin F, Molina-Infante J,
Montoro M, Pajares JM, Pérez-Aisa A, Pérez Gibsert J
Gastroenterol
Hepatol. 36(5):34074
3
38
Recommendations of the Spanish Working Group on
Crohn's Disease and Ulcerative Colitis on the use of antitumor necrosis factor drugs in inflammatory bowel disease
Cabriada JL, Vera I, Domènech E, Barreiro-de Acosta M,
Esteve M, Gisbert JP, Panés J, Gomollón F; Grupo
Español de Trabajo en Enfermedad de Crohn y Colitis
Ulcerosa (GETECCU)
Gastroenterol
Hepatol. 36(3):12746
3
38
Criterios de utilización de fármacos hipolipemiantes para
el tratamiento y control de la dislipemia como factor de
riesgo cardiovascular
Blanca Novella, Marta Alcaráz, Ignacio Morón Merchante
3
49
European guidelines for prevention and management of
influenza in hematopoietic stem cell transplantation and
leukemia patients: summary of ECIL-4 (2011), on behalf
of ECIL, a joint venture of EBMT, EORTC, ICHS, and ELN
Engelhard D, Mohty B, de la Camara R, Cordonnier C,
Ljungman P
Transpl Infect Dis
15(3):219-232.
3
50
Consenso sobre la vacunación anti-neumocócica en el
adulto con patología de base
Picazo JJ, González-Romo F, García Rojas A, PérezTrallero E, Gil Gregorio P, De La Camara R, Morató ML,
Rodríguez a, Barberán J, Hernández D, Linares Rufo M,
Jimeno Sanz I, Portolés JM, Sanz Herrero F, Espinosa
Arranz J, García-Sánchez V, Galindo Izquierdo M
Rev Esp Quimioter.
26(3):232-252
3
50
Consensus statement of the national AIDS plan secretariat, spanish society of emergency medicine and AIDS
study group of the spanish society of infectious diseases
and clinical microbiology on emergency and human immunodeficiency virus infection
Grupo de expertos de la Secretaría del Plan Nacional
sobre el sida
Enferm Infecc
Microbiol Clin
31(7):455
3
50
Guía de Delimitación de volúmenes de Irradiación de
Tumores Digestivos
Laura Cerezo (editora)
SEOR-G
3
54
– 15 –
SCIENTIFIC OUTPUT
INNOVACIÓN Y TRANSFERENCIA
DE RESULTADOS
INNOVATION AND TRANSFERENCE
La Unidad de Innovación del Instituto de Investigación Sanitaria H.U. de
La Princesa, aunque nace con la creación de éste, se ha consolidado al
incorporarse, en el 2013, a la nueva Plataforma de Innovación
Tecnologías Médica y Sanitarias (ITEMAS). Se ha obtenido financiación
en la convocatoria 2013 de concesión de subvenciones de la Acción
Estratégica en Salud 2013-2016, del Instituto de Salud Carlos III.
Esta Plataforma Unidad de Innovación tiene como objetivo principal el fomento de la innovación en el seno del hospital y facilitar
la transferencia del conocimiento al sector productivo.
Entre sus tareas están la generación del mapa de innovación y
del conocimiento en el seno del Hospital La Princesa, manteniendo contactos activos y continuos con sus investigadores; el fortalecimiento de las relaciones con las empresas tecnológicas del
sector de la salud, generando y potenciando las colaboraciones
para proyectos de investigación.
También se encarga de la gestión y mantenimiento de los
derechos de propiedad industrial generados con los resultados de
investigación del instituto.
The Innovation Unit of the Health Research Institute HU La
Princesa, though born with the creation of this, has been consolidated to join in 2013, to the new Innovation Platform Medical
Technologies and Health (ITEMAS). Funding has been obtained in
the call 2013 grant from the Strategic Action for Health 2013-2016
Health Institute Carlos III.
This Platform Innovation Unit's main objective is the promotion
of innovation within the hospital and facilitates the transfer of
knowledge to the productive sector.
Its tasks include the generation of the map of innovation and
knowledge within the Hospital La Princesa, keeping active and continuous contacts with researchers; strengthening relationships with
technology companies in the health sector, creating and strengthening partnerships for research projects.
It is also responsible for the management and maintenance of
intellectual property rights generated with the research results of
the institute.
PATENTES NACIONALES CONCEDIDAS
NUMBER
TITLE
OWNER
P201031782
Uso de PSGL-1 para el
tratamiento de enfermedades
inflamatorias y autoinmunes
UAM (100%)
P201131754
Fármacos inhibidores de p38 y
aplicaciones
INVENTORS
DATE OF APPLICATION
GRANT DATE
GROUP
Norman Núñez, F SánchezMadrid, A Urzainqui
01/12/2010
04/07/2013
56, 1
UAM (100%)
F. Mayor, Jr., C. Murga, P. Campos,
J. Heijnen, A. Kavelaars, A.
Morreale, R. Gil Redondo
02/11/2011
19/12/2013
11, 17
12/11/2010
06/05/2013
11,17
21/07/2011
16/07/2013
Associated
1, 35
P201031673
Péptido Inhibidor de P38 y
aplicaciones
UAM (100%)
Mayor Menéndez Federico, Murga
Montesinos Cristina, Campos
Muelas Pedro Manuel, Johanna
Heijnen Jacoba , Antonius
Kavelaars Anna Maria Agnes,
Morreale De León Antonio
P201100829
Uso de una composición en la
elaboración de una solución de
diálisis para el tratamiento de
las enfermedades cerebrovasculares mediante diálisis
peritoneal
UCM (50%)
/SERMAS "HOSPITAL DE LA
PRINCESA"
(50%)
Moro MA, Lizasoain I, SánchezPrieto J, Torres M, Godino MC,
Sobrado M, González VM, Vivancos
J
– 16 –
NUMBER
TITLE
P201131315
Uso de una combinación de
azatioprina y l-butionina-[s,r]sulfoximina en la preparación
de un medicamento útil para el
tratamiento de un tumor
refractario
OWNER
Universidad Alcalá (95%) /
UAM (5%)
INVENTORS
Gonzalez Guijarro, Luis;
Hernandez-Breijo, Borja; Roman
Curto, Irene De Los Dolores;
Fernandez Moreno, María De Los
Dolores; Perez Gisbert, Javier
DATE OF APPLICATION
GRANT DATE
GROUP
29/07/2011
25/06/2013
38
PATENTES INTERNACIONALES SOLICITADAS
NUMBER
TITLE
PCT/ES2013/
070576
Therapeutic use of CD44 inhibitor
agents against human acute
lymphoblastic leukamia (ALL)
PCT/EP2013/
070204
Nucleotide sequence motifs directing nucleic acid location to
extracellular vesicles
OWNER
INVENTORS
DATE OF APPLICATION
GRANT DATE
GROUP
CSIC (80%) /
UAM (20%)
Toribio García , María Luisa, García
Peydro, Marina, Sánchez Madrid,
Francisco
02/08/2013
1
CNIC / UAM
Villarroya-Beltri, C., Mittelbrunn,
M., Gutierrez-Vazquez, C.,
Sánchez-Cabo, F. and SánchezMadrid, F
27/09/2013
1
– 17 –
SCIENTIFIC OUTPUT
TESIS DOCTORALES
DOCTORAL THESES
La gran dedicación de formación del IP se ve reflejada en el gran
número de tesis doctorales que son dirigidas por miembros del IP.
A continuación se proporciona una lista de las 17 tesis dirigidas
por investigadores del IP durante el año 2013.
DOCTORATE
THESIS READER
The dedication of IP to training is reflected in the large number of
doctoral theses directed by members of the IP. A list of the 17 theses supervised by IP researchers in 2013 is shown.
TITLE
DIRECTOR/S
AREA
GROUP
Giulia Morlino
Miro-1 controls mitochondrial dynamics and regulates lymphocyte adhesion
and migration
1
1
Raquel Bienes
Martínez
Regulación de la proteína de matriz extracelular trombospondina-1 por el gen
supresor de tumores VHL y por la hipoxia. Aspectos funcionales de su regulación en células de carcinoma renal de célula clara
María Josefa Calzada García
1
8
Ainara Elorza Peregrina
Papel fisiopatológico del factor de respuesta a hipoxia HIF2a mediante el
control del transportador de aminoácidos SLC7A5 y el regulador de síntesis
proteica mTORC1
Julián Aragonés López
1
9
Guzmán Sánchez
Fernández
Characterization of Gaq-coupled receptor signalling via the novel effector
PKCz
Federico Mayor Menéndez,
Catalina Ribas Núñez
1
11
Néstor A. Guerrero
Gutiérrez
Role or arachidonic acid metabolites in Trypanosoma cruzi infection
Manuel Fresno Escudero,
Nuria Gironés Pujol
1
12
Gema Marín Alberca
Regulación de la expresión de ciclooxigenasa- 2 PO
Manuel Fresno Escudero,
Miguel Ángel Íñiguez Peña
1
12
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
Silvia Sánchez Cuéllar
El papel de la familia de las Galectinas como moléculas Inmunorreguladoras
en el Asma
Julio Ancochea Bermúdez,
1
22
Gonzalo Segrelles
Calvo
Telemonitorización domiciliaria en pacientes con EPOC grave (Programa
PROMETE)
1
22
José Carlos
Fernández Morales
Estudio comparativo de señales de calcio y de exocitosis en las células
cromafines de embriones de rata y en las de sus madres
Antonio García García, Antonio
Miguel García de Diego
2
28
María Isabel Cuartero
Desviat
Implicación del receptor AhR en neuroprotección y neurorreparación en ictus
isquémico experimental
María Ángeles Moro
Sánchez, Ignacio Lizasoain
Hernández
2
Associated 1
Pablo Miranda García
Utilidad de los marcadores biológicos en la enfermedad inflamatoria intestinal
Javier Pérez Gisbert, María
Chaparro Sánchez
3
38
María José Casanova
González
Seguridad del tratamiento con tiopurinas y anti-TNFα durante el embarazo
en pacientes con enfermedad inflamatoria intestinal
Javier Pérez Gisbert
3
38
– 18 –
DOCTORATE
THESIS READER
TITLE
DIRECTOR/S
AREA
GROUP
Francisco Borja Hernández Breijo
Evaluación preclínica de la eficacia de la azatioprina en el tratamiento de
tumores sólidos
3
38
Javier Loscertales
Pueyo
Evaluación de la estrategias terapéuticas actuales con nuevos fármacos en la
leucemia linfocítica crónica: impacto en la eficacia antitumoral y en la
supervivencia
Adrián Alegre Amor
3
44
Álvaro Cuesta Domínguez
Caracterización de la capacidad oncogénica de la proteína quimérica BCRJAK2
Elena Fernández Ruiz
3
45
Borja Rodríguez Villa
Mejoras en el procesamiento de imágenes de TC para el tratamiento con
radioterapia adaptativa del cáncer de próstata
Feliciano García Vicente
3
53
TESIS EUROPEAS
DOCTORATE
THESIS READER
TITLE
DIRECTOR/S
AREA
GROUP
Guzmán Sánchez Fernández
Characterization of Gaq-coupled receptor signalling via the novel effector
PKCz
Catalina Ribas
1
11
Olga Pérez Nyssen
Systematic review of sequential therapy versus standard triple therapy for
Helicobacter pylori eradication
3
38
– 19 –
SCIENTIFIC OUTPUT
COMUNICACIÓN Y DIFUSIÓN
COMMUNICATION AND DIFUSSION
La difusión de la información científica se ha convertido en un pilar
fundamental dentro de nuestro IP no sólo para el personal del instituto, sino para todo el ámbito científico y la población general. El
alcance de dicha difusión no es sólo nacional sino internacional, lo
que supone una importante vía para dar a conocer nuestra actividad. Nuestra página Web (www.iis-princesa.org) es una parte
importante para la comunicación de los eventos científicos, cursos
y congresos, ofertas de empleo y noticias destacables que tienen
lugar en nuestro entorno. Durante el pasado año, recibió 90.763
visitas, lo que supone un incremento del 15% respecto al año
2012.
The dissemination of scientific information has become a mainstay
in our IP not only for the staff of the institute, but also for the entire
scientific community and the general public. The scope is not only
national but international, which is an important way to raise
awareness of our activities. Our website (www.iis-princesa.org) is
crucial for the communication of scientific events, conferences and
courses, job offers and outstanding news happening in our environment. Over the past year, our web received 90,763 visits, representing an increase of 15% over 2012.
Las noticias publicadas han recibido un 21% más de visitas
que en 2012, indicador de la importante herramienta de difusión
que supone nuestra Web.
The news published have received 21% more visits than in
2012, an indicator of the importance of our website as a dissemination tool.
COUNTRY
2012
2011
25875
24295
UK
748
321
+133%
COLOMBIA
357
390
-8%
US
277
225
+23%
MÉXICO
271
202
+34%
SPAIN
– 20 –
IMPROVEMENT
+7%
PLATAFORMAS CIENTÍFICAS
SCIENTIFIC PLATFORMS
BIOBANCO
BIOBANK
UNIDAD INNOVACIÓN
INNOVATION UNIT
DIRECTORA / DIRECTOR
Dra. Mara Ortega Gómez
DIRECTORA / DIRECTOR
Dra. Carmen Suárez Fernández
COMITÉ COLABORADOR / SENIOR COMMITTEE
Dr. Ramón Colomer Bosch (Oncología Médica)
Dr. Isidoro González Álvaro (Reumatología)
Dr. José A. Jiménez Heffernan (Anatomía Patológica)
Dr. Carlos Manuel Olivier Gómez (Urología)
COMITÉ DE INNOVACIÓN / INNOVATION COMMITTEE
Dr. Julio Ancochea Bermúdez (Neumología)
Dra. Carmen del Arco Galán (Medicina Interna- Urgencias)
Dr. Francisco Javier Aspa Marco (Dirección Médica)
Dª Marian Centellas (Dirección de Enfermería)
Dr. Guillermo Fernández Jiménez (Admisión y Documentación
Clínica)
Dr. Jesús Jiménez Borreguero (Cardiología)
Dr. Alberto Morell Baladrón (Farmacia Hospitalaria)
Dr. Ramón Moreno Balsalobre (Cirugía Torácica)
D. Francisco Redondo Montserrat (Enfermería)
Dr. Luis Sánchez-Urdazpal González (Cirugía General y Aparato
Digestivo)
Dr. Alberto Sebastián Palomino (Dirección de Continuidad
Asistencial)
Dra. Gema Vega González (Medicina Intensiva)
Dr. José Aurelio Vivancos Mora (Neurología)
Dña. Mº José Peláez García (Secretaria)
PERSONAL TÉCNICO / TECHNICAL STAFF
D. Sergio Luquero Bueno
UNIDAD ENSAYOS CLÍNICOS (UCICEC)
CLINICAL RESEARCH AND CLINICAL TRIALS UNIT
DIRECTOR / DIRECTOR
Dr. Francisco Abad Santos
EQUIPO / TEAM
Dra. Mª Dolores Ochoa Mazarro
D. Manuel Román Martínez
Dña. Alba Serrano Ruiz
PERSONAL CONTRATADO / HIRED STAFF
D.Juan Diego López de la Reina Maroto
Monitor Ensayos Clínicos
Clinical Trials Monitor
Dña. Gloria Elizabeth Barreto Quiñones
Farmacólogo Clínico-Gestor de Proyectos
Clinical Farmacologist Projetct Manager
UNIDAD METODOLOGÍA
METHODOLOGICAL UNIT
DIRECTOR / DIRECTOR
Dr. Francisco Rodríguez Salvanés
PERSONAL TÉCNICO / TECHNICAL STAFF
Dña. Lorena Vega Piris
– 21 –
SCIENTIFIC OUTPUT
UNIDAD DE APOYO ADMINISTRATIVO
AMINISTRATIVE SUPPORT UNIT
COORDINADOR / COORDINATOR
Dr. Javier Aspa Marco
PERSONAL ADMINISTRATIVO / ADMINISTRATIVE STAFF
D. José Palao Albendea
PLATAFORMAS TÉCNICAS DE APOYO
SCIENTIFIC PLATFORMS
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
Directora Técnica
Technical Director
Dra María Teresa Rejas Marco
COORDINADORA / COORDINATOR
Dra. María Yañez Mó
Servicio de Proteómica CBMSO IP
Proteomic Unit CBMSO IP
Coordinadora
Coordinator
Ana Isabel Marina Ramirez
Sala Blanca IP (Hospital U. Niño Jesús)
Clean Room IP (Hospital U. Niño Jesús)
Directora Técnica
Technical Director
Dra. Maria Antonia Varela-Portas San Juan
Servicio de Videomicroscopía Confocal
Confocal Microscopy Service
Coordinadora
Coordinator
Dra. María Yáñez Mó
Servicio de Citometría
Cytometry Service
Coordinadora
Coordinator
Dra. Cecilia Muñoz Calleja
Gabinete Veterinario UAM
Animal Facility UAM
Directora
Director
Carmen Fernández Criado
– 22 –
ÁREAS DE INVESTIGACIÓN
RESEARCH AREAS
A continuación se muestra un resumen de las tres áreas de
investigación en las que está estructurado el Instituto y las líneas
que forman parte de ellas. La actividad científica de cada área
muestra el número de publicaciones, su factor de impacto medio
y acumulado, de los 3 últimos años. Se muestra un resumen de
las líneas de investigación actualizadas del año 2014. También se
presenta la línea 1.4 desaparecida en diciembre de 2013.
A summary of the three research areas in which the Institute is
structured and lines that are part of them is shown. The scientific
activity of each area shows the number of publications, their
mean impact factor and accumulated for the last 3 years. Below
is shown a summary of current research lines (2014). Line 1.4 is
also shown dissapeared in December 2013.
AREA 1: Cellular and Molecular Etiopathogenic Mechanisms
in Inflammatory and Autoimmune Diseases. Coordinator:
LINE
NAME
DIRECTOR
1.1
Intercellular Communication in the Inflammatory
Response
Francisco
Sánchez Madrid
1.2
Animal Models of Inflammatory Diseases and Intercellular Signalling
Julián Aragonés
López
1.3
Animal models of inflammatory diseases and intercellular signalling
Federico Mayor
Menéndez
1.4
Etiopathogenic and Immunological Mechanisms of
Dermatological Diseases
Amaro García
Diez
1.5
Cellular Mechanisms and Molecular Determinants of
Allergy-Based Diseases
Carlos Blanco
Guerra
1.6
Inflammatory Processes in Nephrological Diseases
José Antonio
Sánchez Tomero
1.7
Inflammatory Mechanisms in Pulmonary Diseases
Julio Ancochea
Bermúdez
1.8
Inflammatory Response in Hepatic Diseases
Pedro L. Majano
Rodríguez
1.9
Mechanisms and Mediators of Endocrine Diseases
Mónica Marzuela
Azpiroz
1.10
Children´s Development (Obesity and Growth)
Jesús Argente
Oliver
1.11
Metabolic Syndrome and Vascular Risk
Raffaelle Carraro
– 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
Manuela García
López
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
3.3
Progenitors and Cell Therapy
Luis Madero López
3.4
Advanced Therapies in Oncohematology
Juan Luis Steegmann
Olmedillas
3.5
Biological, Cellular and Molecular
Monitoring in Oncohematology
3.6
New Diagnostic and Therapeutic Advances in Cardiovascular Diseases
Fernando Alfonso
Manterola
3.7
New Therapies in Infectious Pathologies
Ignacio de los Santos
Gil
3.8
Individualized Medicine in Solid Tumors
Ramón Colomer
Bosch
– 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
GROUP 1
HEAD OF LABORATORY
Francisco Sánchez-Madrid.
Scientific Director, Inmmunology.
RESEARCH INTEREST
Cell-cell communication is the basis of the organization of the Immune System. T lymphocytes and
Antigen-Presenting Cezlls (APCs) establish a specific
intercellular structure through the Immune Synapse
(IS) formation to secure the interchange of information. The presence of specific receptors at the cell
membrane is essential for the correct transfer of
information between T lymphocytes and APCs. The
tetraspanin CD81 localizes at the IS and marks the
degree of maturation of the IS, controlling the dynamics and fate of the T cell receptor complex at the IS.
The molecular architecture of the IS is organized and
maintained through the dynamics of the cytoskeleton
AREA 3 AREA 2 AREA 1
GROUP MEMBERS
• Francesc Baixauli Celda
• Olga Barreiro del Río
• Noelia Blas Rus
• Eugenio Bustos Moran
• Danay Cibrián Vera
• Hortensia de la Fuente Flores
• Marta Esther Ramírez Huesca
• Manuel Gómez Gutiérrez
• Cristina Gutiérrez Vázquez
• María José López Campos
• Noa Beatriz Martín Cófreces
• Gloria Martínez del Hoyo Cañizares
• Adela Matesanz Marín
• María Mittelbrunn Herrero
• Olga Moreno Gonzalo
• Vera Rocha Perugini
• María Laura Saiz Álvarez
• Mª Ángeles Ursa Pecharromán
• María Ángeles Vallejo Rodríguez
• Alicia Vara Vega
• Carolina Villarroya Beltri
Fig.1
– 29 –
Cellular and molecular etiopathogenic mechanisms
in inflammatory and autoimmune diseases
components, such as the centrosome or MTOC
(microtubule-organizing centre), a cell-polarity keeping organelle. The MTOC allows the organization of an
intense vesicular trafficking that helps to the T Cell
Receptor downstream signaling at the IS. Indeed, the
Multivesicular Bodies (MVB) concentrate at the IS to
favor the exocytosis of small membrane vesicles (exosomes) in a new way of cell-cell communication with
the APC, that involves a role for the miRNA loaded in
the exosomes. Specific repertoires of miRNAs are
sorted to the exosomes upon binding to ROA2
(hnRNPA2B1), which localization in exosomes is regulated by sumoylation.
The study of intercellular communication in the
establishment and development of different diseases is a promising field in biomedicine. Psoriasis
is a chronic inflammatory disease characterized by
well-defined erythematous scares that are well
delineated from apparently healthy adjacent skin.
The analysis of these affected areas (lesional skin)
unveiled an important immune cell infiltrate, mainly
T lymphocytes and dendritic cells. These cells
showed a state of activation that corresponds to
Th1 and Th17 responses, and produce cytokines,
such as TNF-a, IFN-g, IL-17, IL-22, IL-23, IL-12
and IL-1b, that induce the keratinocytes and other
resident skin cells to secrete mediators. Our studies of immunoregulatory molecules and specific
miRNAs in subpopulations of immune cells in psoriatic skin support their critical role in the control of
the inflammatory cytokines in the cutaneous
immune response.
INDISNET S2011/BMD-2332. Duration: 2012 2015.
• Francisco Sánchez Madrid. Mechanisms of MTOC
guidance and genetic transfer at the immune
synapse: novel modes of Immunomodulation.
European Research Council. ERCEA-AdG-2011294340_GENTRIS. Duration: 2012 - 2017.
• Francisco Sánchez Madrid. Redes Temáticas 2012
- RECAVA/CARDIO. FIB. RD12/0042/0056.
Duration: 2013 – 2016.
2013 Awarded Projects:
• Francisco Sánchez Madrid. Immunoregulatory molecules as biomarkers predicting response to biological therapies and disease severity in immune-mediated inflamatory disorders. BIOIMID PROJECT.
ISCIII. PIE13/00041. Duration: 2014 – 2016.
PUBLICATIONS (12) [IF: 76,543]
YEAR
Total IF
Publication No.
Q1
2011
74,667
12
11
2012
122,628
13
10
2013
76,543
12
10
Carolina Villaroya-Beltri,Cristina Gutiérrez-Vázquez,
Fátima Sánchez- Cabo,Dienl Pérez Hernández,Jesús
Vázquez,Noa Martín-Cofreces,Dannys Jorge MartínHerrera, Alberto Pascual-Montano,María Mittelbrunn,
Francisco Sánchez Madrid. Sumoylated hnRNPA2B1
controls the sorting of miRNAs into exosomes
through binding TO specific motifs. Nature
Communication. 4:2980. 2013. PMID: 24356509. IF:
10,742 DOI: 10.1038/ncomms3980
MAJOR GRANTS
• Francisco Sánchez Madrid. Nuevos mecanismos
de inmunomodulación: moléculas reguladoras,
polaridad celular y transferenciade información
genética en la comunicación intercelular. MICINN.
SAF-2011-25834. Duration: 2012 - 2014.
• Francisco Sánchez-Madrid. Proyecto Coordinado.
Redes moleculares y celulares en enfermedades
inflamatorias. Programa Biomedicina. CAM.
– 30 –
Domínguez-Luis M, Herrera-García A, Arce-Franco
M, Armas-González E, Rodríguez-Pardo M,
Lorenzo-Díaz F, Feria M, Cadenas S, SánchezMadrid F, Díaz-González F. Superoxide anion mediates the L-selectin down-regulation induced by
non-steroidal anti-inflammatory drugs in human
neutrophils. Biochem Pharmacol. 85(2):245-256.
2013. PMID: 23142710. IF: 4,650. DOI: 10.1016/
j.bcp.2012.10.024
AREA 1
Herrera-García A, Domínguez-Luis M, Arce-Franco M,
López-Fernández J, Feria M, Barreiro O, SánchezMadrid F, Díaz-González F. In vivo modulation of the
inflammatory response by non-steroidal anti-inflammatory drug-related compounds that TRIGGER Lselectin shedding. Eur J Immunol. 43(1):55-64. 2013.
PMID: 22975861. IF: 4,518. DOI: 10.1002/
eji.201242805
Gutiérrez-Vázquez C, Villarroya-Beltri C, Mittelbrunn M,
Sánchez-Madrid F. Transfer of extracellular vesicles
during immune cell-cell interactions. Immunol Rev.
251(1):125-142. 2013. PMID: 23278745. IF: 12,909.
DOI: 10.1111/imr.12013
Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I,
López-Martín S, Ursa A, Sánchez-Madrid F, Vázquez J,
Yáñez-Mó M. The intracellular interactome of
tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. J Biol
Chem. 288(17):11649-61. 2013. PMID: 23463506. IF:
4,600. DOI: 10.1074/ jbc.M112.445304
Gordón-Alonso M, Rocha-Perugini V, Álvarez S, Ursa Á,
Izquierdo-Useros N, Martinez-Picado J, MuñozFernández MA, Sánchez-Madrid F. Actin-binding protein drebrin regulates HIV-1-triggered actin polymerization and viral infection. J Biol Chem. 288(39):28382-97.
2013. PMID: 23926103. IF: 4,600. DOI: 10.1074/
jbc.M113.494906
Leskela S, Rodríguez-Muñoz A, de la Fuente H,
Figueroa-Vega N, Bonay P, Martín P, Serrano A,
Sánchez-Madrid F, González-Amaro R, Marazuela M.
Plasmacytoid dendritic cells in patients with autoimmune thyroid disease. J Clin Endocrinol Metab.
98(7):2822-2833. 2013. PMID: 23666960. IF: 6,310.
DOI: 10.1210/jc.2013-1273
Perugini V, López-Martín S, Pérez-Hernández D, Bachir
AI, Horwitz AR, Vázquez J, Sánchez-Madrid F, YáñezMo M. CD81 regulates cell migration through its association with Rac GTPase. Mol Biol Cell. 24(3):261-273.
2013. PMID: 23264468. IF: 4,548. DOI:
10.1091/mbc.E12-09-0642
Rocha-Perugini V, Zamai M, González-Granado JM,
Barreiro O, Tejera E, Yañez-Mó M, Caiolfa VR, SanchezMadrid F. CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate
immunological synapses. Mol Cell Biol. 33(18):3644-58.
2013. PMID: 23858057. IF: 5,036. DOI:
10.1128/MCB.00302-13
González-Amaro R, Cortés JR, Sánchez-Madrid F,
Martín P. Is CD69 an effective brake to control inflammatory diseases?. Trends Mol Med. 19(10):625-632.
2013. PMID: 23954168. IF: 10,110. DOI: 10.1016
/j.molmed.2013.07.006
Lizbeth Estrada-Capetillo, Berenice Hernández-Castro,
Adriana Monsiváis-Urenda, Crisol Alvarez-Quiroga,
Esther Layseca-Espinosa, C. Abud-Mendoza, L.
Baranda, Ana Urzainqui, F. Sánchez-Madrid and R.
González-Amaro. Induction of Th17 lymphocytes and
Treg cells by monocyte-derived dendritic cells in
patients with rheumatoid arthritis and systemic lupus
erythematosus. Clin. Dev. Immunol. 2013:584303.
2013. PMID: 24288552. IF: 2,934. DOI:
101155/2013/584303
GROUP 2
HEAD OF LABORATORY
Esteban Veiga Chacón
GROUP MEMBERS
• Aranzazu Cruz Adalia
• Guillermo Ramírez Santiago
• Mónica Torres Torresano
– 31 –
Medraño-Fernandez I, Reyes R, Olazabal I, Rodriguez
E, Sanchez-Madrid F, Boussiotis VA, Reche PA,
Cabañas C, Lafuente EM. RIAM (Rap1-interacting
adaptor molecule) regulates complement-dependent
phagocytosis. Cell Mol Life Sci. 70(13):2395-410.
2013. PMID: 23420480. IF: 5,856. DOI:
10.1007/s00018-013-1268-6
MAJOR GRANTS
Esteban Veiga Chacón. Sinapsis inmunológica y control
bacteriano del sistema inmune. MICINN. BFU201129450. Duration: 2012 – 2014.
PUBLICATIONS (0) [IF: 0]
YEAR
Total IF
Publication No.
Q1
2011
20,235
3
2
2012
10,994
2
1
2013
-
-
-
GROUP 3
HEAD OF LABORATORY
María Yáñez Mó
GROUP MEMBERS
• Soraya López Martín
• Henar Suárez Montero
RESEARCH INTEREST
During the year 2013 our group completed and
published the characterization of the intracellular
interactome of tetraspanin-enriched microdomains.
These analyses allowed us to decipher the role of
these specialized adhesion platforms in the recruitment of adhesion receptors and, surprisingly, RNA
binding proteins to exosomes. Thus, the 45% of
the proteome of these extracellular vesicles was
connected to tetraspanin-enriched microdomains.
Deletion of a single tetraspanin was able to selec-
– 32 –
Fig.1. Protein interaction networks for tetraspanin-enriched microdomainsin human primary lymphoblast-derived exosomes. A, intracellular ligands of CD81 and EWI-2 were manually clustered into groups according to their function. Symbol size is proportional to the number of
peptides identified for each protein in the pull-down assays. B, proportions of proteins in exosomes that were identified as ligands of EWI-2
and CD81 in exosomes.
tively reduce the incorporation of associated molecules to exosomes.
In addition, among the tetraspanin CD81 cytosolic
associated proteins we found the small GTPase
Rac. This GTPase is a master regulation of actin
assembly, playing a fundamental role in cell motility
and invasion. We demonstrated that the association of Rac with CD81 was important to modulate
the cycling time of activation-deactivation of the
GTPase at the plasma membrane. We observed
that deletion or truncation of the C-term domain of
CD81 slowed down Rac deactivation resulting in an
enhanced focal adhesion formation and reduced
cell motility. Moreover, cytopermeable peptides
with the sequence of the C-terminal domain of
CD81 also reduced cell motility, suggesting their
potential in anti-tumoral therapy.
AREA 1
Images displayed are the average projections, in pseudocolor intensity scale, of more than 20 cells acquired in a wide-field fluorescence microscope. Scale bar: 10 µm. (D) Primary HUVECs
were transfected with negative oligonucleotide or CD81 siRNA,
together with GFP, GFP-CD81, or the GFP- tagged truncated Cterminal deletion form of CD81, and seeded on 2 µg/ml of fibronectin. Cells were stained for paxillin, and the area of focal adhesions (µm2) was quantified. Data are means ± SEM of measurements from three independent experiments. *, p< 0.05 in oneway ANOVA. (E) Cells were transfected with mOrange-paxillin together with negative oligonucleotide or CD81 siRNA and GFP,
GFP-CD81, or the GFP-tagged truncated C-terminal deletion form
of CD81, then allowed to spread on 10 µg/ml fibronectin, and adhesion assembly and disassembly (depicted by paxillin) were
analyzed in TIRFM time-lapse sequences. Data are means ± SEM
of measurements from three independent experiments. **, p<
0.01 in one-way ANOVA.
• María Yáñez 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.
Fig.2. CD81 down-regulation increases protrusion rate and focal
adhesion formation. (A) SUM159 cells were transfected with
negative oligonucleotide or CD81 siRNA, together with GFP, GFPCD81, or the GFP-tagged truncated C-terminal deletion form of
CD81. In parallel experiments, cells were transfected with GFP
or GFP-CD81. Protrusion rate (µm/s) was analyzed in TIRF timelapse sequences of cells spreading on 10 µg/ml fibronectin.
Data represent kymographs from three independent experiments (mean ± SEM). *, p< 0.05; **, p < 0.01; and ***, p < 0.001
in one-way ANOVA (silencing and rescue experiments); *, p <
0.05 in Student’s t test for overexpression experiments. (B)
Examples of cell spreading measured in (A). Binary images
show the total area of spreading at 5 min, while the linear outline corresponds to the cell perimeter at time 0. Scale bar: 10 µm.
(C) SUM159 cells were transfected with negative oligonucleotide or CD81 siRNA and seeded onto micropatterned slides. After
3 h of adhesion, samples were fixed, permeabilized, and stained
for paxillin or F-actin.
• María Yañez Mó. Immunoregulatory molecules as biomarkers predicting response to biological therapies and
disease severity in immune-mediated inflamatory disorders. BIOIMID PROJECT. ISCIII. PIE13/00041. Duration:
2014 – 2016.
YEAR
Total IF
Publication No.
Q1
2011
19,372
4
2
2012
28,890
4
3
2013
18,784
4
3
Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I, LópezMartín S, Ursa A, Sánchez-Madrid F, Vázquez J, Yáñez-Mó
M. The intracellular interactome of tetraspanin-enriched
– 33 –
MAJOR GRANTS
microdomains reveals their function as sorting machineries
toward exosomes. J Biol Chem. 288(17):11649-61. 2013.
PMID: 23463506. IF: 4,600. DOI: 10.1074/
jbc.M112.445304
Gordón-Alonso M, Rocha-Perugini V, Álvarez S, Ursa
Á, Izquierdo-Useros N, Martinez-Picado J, MuñozFernández MA, Sánchez-Madrid F. Actin-binding protein drebrin regulates HIV-1-triggered actin polymerization and viral infection. J Biol Chem.
288(39):28382-97. 2013. PMID: 23926103. IF: 4,600.
DOI: 10.1074/jbc.M113.494906
GROUP MEMBERS
• Rocío Aguilar Cuenca
• Cristina Delgado Arévalo
• Lidia Feo Lucas
• Alba Juanes García
• Álvaro Ortega Carrión
• Irene Ríos Guillén
MAJOR GRANTS
BOOKS
• Miguel Vicente Manzanares. Myosin II orchestrates
chemical and mechanical signals in inflammation.
European Union. Marie Curie-Career Integration
Grant (CIG293719). Duration: 2011 - 2015.
• Miguel Vicente Manzanares. La miosina no muscular
de clase II coordina la señalización adhesiva y de
citocinas con la respuestacelular a las propiedades
mecánicas del microentorno inflamatorio. MICINN.
SAF2011-24953. Duration: 2012 - 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 Ramón Areces. CIVP16A1831.
Duration: 2012 – 2015.
• Miguel Vicente Manzanares. Análisis multiparamétrico de la morfología y migración celular para la asistencia al diagnóstico de enfermedades inflamatorias
y cáncer. CTO.WIMASIS.2012. Duration: 20122013.
Tejera E; Sala-Valdés M; Rocha-Perugini V; Yáñez Mó M.
Role of tetraspanins in cell migration and intercellular adhesion. Tetraspanins. Series Proteins and Cell Regulation.
2013. Springer. ISBN: 978-94-007-6070-7.
Tejera E, Rocha-Perugini V, López-Martín S, PérezHernández D, Bachir AI, Horwitz AR, Vázquez J, SánchezMadrid F, Yáñez-Mo M. CD81 regulates cell migration
through its association with Rac GTPase. Mol Biol. Cell
24(3):261-273. 2013. PMID: 23264468. IF: 4,548. DOI:
10.1091/mbc.E12-09-0642
Rocha-Perugini V, Zamai M, González-Granado JM,
Barreiro O, Tejera E, Yañez-Mó M, Caiolfa VR, SanchezMadrid F. CD81 controls sustained T cell activation signaling and defines the maturation stages of cognate
immunological synapses. Mol Cell Biol. 33(18):3644-58.
2013.
PMID:
23858057.
IF:
5,036.
DOI:
10.1128/MCB.00302-13
GROUP 4
HEAD OF LABORATORY
Miguel Vicente Manzanares
– 34 –
YEAR
Total IF
Publication No.
2011
-
-
Q1
-
2012
7,398
2
2
2013
9,916
1
1
Vicente-Manzanares M. Cell migration: cooperation
between myosin II isoforms in durotaxis. Curr Biol.
23(1):R28-9. 2013. PMID: 23305668. IF: 9,916.
DOI: 10.1016/j.cub.2012.11.024
AREA 1
GROUP 56
HEAD OF LABORATORY
Ana Carmen Urzainqui Mayayo
GROUP MEMBERS
• Rafael González Tajuelo
P-Selectin Glycoprotein Ligand-1 (PSGL-1) is a leucocyte receptor that interacts with P-, E- and LSelectins and is responsible for the leukocyte
extravasation to inflammation sites. Our lab has
described that PSGL-1 participates in the generation
of regulatory T cells (Treg) and contributes to the
maintenance of peripheral tolerance. We have
recently described that PSGL-1 KO mice develop an
autoimmune disease similar to systemic sclerosis
(SSc). During the last year we have obtained preliminary data indicating that P-Selectin KO mice develop an autoimmune syndrome different to that of
PSGL-1 KO and that both P-Selectin and PSGL-1
KO aged mice have thickened the muscular layer of
the pulmonary small vessels, suggesting that they
could develop pulmonary arterial hypertension (PAH)
(Fig. 1). We have also observed that aged P-Selectin
deficient mice have giant seminal vesicles and that
both PSGL-1 and the P-Sel deficient mice have
Fig.1. Microphotographs of anti-αSMA stained lung sections of 3month-old WT and PSGL-1 KO mice. Right panel: vessel wall area with
respect to the total vessel area in <50 μm-diameter lung vessels of 3month-old WT and PSGL-1 KO mice. Bars represent mean±SD. Statistical significance was determined by two-tailed Student’s t test.
lower number of offspring per litter (Fig. 2). Very
importantly, we have initiated a study with patients
and healthy controls to evaluate whether the serum
levels of PSGL-1, P-Selectin, E-Selectin and LSelectin, together with the expression of PSGL-1 in
the surface of leukocyte subpopulations, could constitute an early diagnostic signature to differentiate
between SSc, systemic lupus erythematosus and
mixed connective tissue diseases.
MAJOR GRANTS
• Ana Carmen Urzainqui Mayayo. Estudio del papel de
PSGL-1 en el control del desarrollo de enfermedades
autoinmunes. Fundación Ramón Areces. Duration:
2012 – 2014.
• 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. Immunoregulatory molecules as biomarkers predicting response
to biological therapies and disease severity in
immune-mediated inflamatory disorders. BIOIMID
PROJECT. ISCIII. PIE13/00041. Duration: 2014 –
2016.
– 35 –
RESEARCH INTEREST
Fig.2. Pups per litter of WT (PW) and PSGL-1 KO (PO) females that have
been crossing along 6 months with either WT or PSGL-1 KO males.
YEAR
Total IF
Publication No.
Q1
2011
17,735
3
3
2012
-
-
-
2013
16,846
2
1
Lizbeth Estrada-Capetillo, Berenice Hernández-Castro,
Adriana Monsiváis-Urenda, Crisol Alvarez-Quiroga,
Esther Layseca-Espinosa, C. Abud-Mendoza, L.
Baranda, Ana Urzainqui, F. Sánchez-Madrid and R.
González-Amaro. Induction of Th17 lymphocytes and
– 36 –
Treg cells by monocyte-derived dendritic cells in
patients with rheumatoid arthritis and systemic lupus
erythematosus. Clin. Dev. Immunol. 2013:584303.
2013. PMID: 24288552. IF: 2,934. DOI:
101155/2013/584303
Stadtmann A, Germena G, Block H, Boras M, Rossaint J,
Sundd P, Lefort C, Fisher CI, Buscher K, Gelschefarth B,
Urzainqui A, Gerke V, Ley K, Zarbock A. The PSGL-1-Lselectin signaling complex regulates neutrophil adhesion
under flow. J Exp Med. 210(11):2171-2180. 2013. PMID:
24127491. IF: 13,912. DOI: 10.1084/jem.20130664
AREA 1
Line 1.2
Cellular and molecular
responses to Hypoxia
GROUP 9
GROUP MEMBERS
• Ainara Elorza Peregrina
• Glenn Marsboom
• Florinda Meléndez Rodríguez
• Noelia Sánchez Bolívar
• Inés Soro Arnaíz
• Qilong Oscar Yang Li
RESEARCH INTEREST
An insufficient oxygen supply (hypoxia) is a hallmark
of numerous life-threatening pathologies with unmet
medical needs. Pulmonary diseases such as chronic
obstructive pulmonary disease (COPD) and sleepapnea hypoapnea syndrome (SAHS) are the most
common respiratory diseases causing illness and
death, and are being projected to be the third leading
cause of death worldwide by 2020. They are characterized by an insufficient level of oxygen in the blood
(hypoxemia), continuous in the COPD and intermittent in the SAHS and they are associated to pulmonary oxidative damage, an exaggerated inflammatory response in the lung and systemically. The compensatory oxygen-sensing pathway, executed by the
hypoxia-inducible factors (HIFs), is central in the cellular/tissular response to pathological oxygen fluctuations, but surprisingly, despite of the fact that lung
tissue - bronchial epithelium - is a first barrier
Fig.1. Hypoxia-induced bronchial epithelial cell RELM-a expression.
Immunostaining detecting RELM-A positive cells localized in bronchial epithelium of mice exposed to hypoxia. RELM-A has been shown
to be a bronchial epithelial cell mitogen.
encountered by oxygen, it remains largely unknown
the role of the HIF oxygen-sensing responses in lung
pathophysiology. Furthermore it remains unexplored
the potential of HIF pathways for novel therapeutical
approaches. Based on (i) our recent studies about
the HIF pathways as activators of proliferative markers in bronchial epithelium including mTORC1 (Elorza
et al. Molecular Cell 2012) or resistin-alpha (RELM.A),
we are currently studying together in collaboration
with other researchers including pneumologists in
Hospital de la Princesa IIS-IP (Dr. Julio Ancochea) the
role of HIF oxygen sensing pathways in (i) lung protection and repair (ii) ventilation and (iii) of novel HIFdependent non-invasive airway and plasma biomarkers for diagnosis and prognosis of these fatal respiratory diseases.
MAJOR GRANTS
• 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.
– 37 –
HEAD OF LABORATORY
Julián Aragonés López
2012 - RECAVA/CARDIO. UCM. RD12/0042/0065.
Duration: 2013 –2016.
• Julián Aragonés López. Inflamación e hipoxia:
mecanismos en desarrollo y progresión en EPOC y
SAHS. CAM. P2010 / BMD-2542. Duration: 2012
– 2015.
I
YEAR
Total IF
Publication No.
Q1
2011
21,077
3
2
2012
33,260
3
3
2013
-
-
-
GROUP 6
YEAR
Total IF
Publication No.
Q1
2011
21,077
3
2
2012
55,018
6
5
2013
5,710
1
1
Anedda A, López-Bernardo E, Acosta-Iborra B, Saadeh
Suleiman M, Landázuri MO, Cadenas S. The transcription factor Nrf2 promotes survival by enhancing the
expression of uncoupling protein 3 under conditions of
oxidative stress. Free Radic Biol Med. 16(61C):395-407.
2013.
PMID:
23597505.
IF:
5,710.
DOI:
10.1016/j.freeradbiomed.2013.04.007
HEAD OF LABORATORY
Manuel Ortiz de Landázuri Busca
GROUP 7
GROUP MEMBERS
• Bárbara Acosta Iborra
• Eduardo Balsa Martínez
• Esther Fuertes Yebra
• Gemma Muruáis Martínez
• Ángel Ordóñez Navadijo
• Silvia Noemí Vázquez Cuesta
HEAD OF LABORATORY
Antonio Martínez Ruiz
GROUP MEMBERS
• Alicia Izquierdo Álvarez
• Pablo Hernansanz Agustín
• Elena Ramos Serrano
MAJOR GRANTS
• Manuel Ortiz de Landázuri Busca. Metastatic tumours
facilitated by hypoxic tumour microenvironments. (7º
programa
MARCO).CEE.
FP7-HEALTH-2007.
Duration: 2007 - 2014.
• Manuel Ortiz de Landázuri Busca. Inflamación e hipoxia: Mecanismos de desarrollo y progresión en EPOC y
SAHS. Programa Biomedicina. CAM. S2011/BMD2542. Duration: 2012 - 2015.
• Manuel Ortiz de Landázuri Busca. Redes Temáticas
– 38 –
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,
Fig.1. Hypothetical S-nitrosylation/denitrosylation mechanisms in T
cell development. A) Local high extracellular levels of NO produced by
iNOS from dendritic cells (DC) promote S-nitrosylation in thymocytes,
fostering negative selection of CD4+CD8+ double positive thymocytes
by promoting apoptosis. B) Through denitrosylation, up-regulated
GSNOR expression or activity in thymocytes ongoing CD4+ maturation
may counteract the proapoptotic actions of protein S-nitrosylation
mediated by iNOS-derived NO from DCs. C) Low levels of NO generated
in thymocytes by constitutive NOS (cNOS) during their cognate interactions with iNOS non-expressing DCs and macrophages (APC) may
protect thymocytes from cell death by S-nitrosylation of caspase-1.
From Hernansanz-Agustín et al., 2013
especially cysteine reversible oxidative modifications.
We also study their relevance in cell function and
pathophysiology, mainly in the molecular and cellular
responses to hypoxia.
We have previously identified several proteins that are
differentially oxidised in the acute response of endothelial cells subjected to hypoxia. Currently, we are investigating the origin of such response, and we have identified an acute superoxide production when different
cells are subjected to acute hypoxia (published in
2014).
We are also collaborating with different groups in
the study of the role of oxidative post-translational
modifications in different pathophysiological scenarios. In an animal model of acute pancreatitis we
have described a novel type of oxidative stress that
takes part in this inflammatory disease, disulfide
Fig.2. Postsynaptic localization of nNOS and S-nitrosylation signaling in
a glutamatergic synapse. Production of NO by nNOS following glutamate
release is coupled to activation of Ca2+-permeable NMDA receptors
(NMDAr), which are anchored at the postsynaptic density by scaffolding
proteins, including PSD-95. NO produced in close proximity to NMDA receptors triggers the S-nitrosylation of NR2A subunits (SNO-NR2A), which
then allow less Ca2+ in. S-nitrosylation of stargazin (SNO-stargazin) and
NSF (SNO-NSF) contributes to increase the surface expression of AMPAr
during events of synaptic plasticity following the activation of NMDAr. On
the other hand, S-nitrosylation of PICK1 facilitates its release from AMPAr
after membrane insertion and also facilitates surface expression of AMPAr. When these proteins are out of range of NO and are not S-nitrosylated, PICK1 interacts more strongly with the receptor while NSF interacts
more weakly; allowing the binding of proteins that facilitate endocytosis
of AMPAr.
stress (published in 2014). We are also studying the
role of S-nitrosylation in the neurogenesis induced
by nitric oxide (NO).
We have also made some contributions in the study of
S-nitrosylation, a paradigmatic oxidative post-translational modification related with NO signalling. 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.
– 39 –
AREA 1
MAJOR GRANTS
GROUP MEMBERS
• David Labrousse Arias
• Antonio Martínez Ruiz. Identificación de dianas de Snitrosilación en la estimulación de la neurogénesis
endógena.
MICINN.
PRI-AIBPT-2011-1015.
Duration: 2011 - 2013.
• Antonio Martínez Ruiz. Identificación proteómica de
proteínas vegetales S-nitrosiladas en la respuesta a
auxina. MICINN. PRI-AIBAR-2011-0782. Duration:
2011 - 2013.
• Antonio Martínez Ruiz. Modificaciones postraduccionales oxidativas en fisiopatología molecular.
Instituto de Salud Carlos III, Ministerio de Economía.
PI12/00875. Duration: 2013 – 2015.
RESEARCH INTEREST
Hypoxia and Pulmonary Aortic Hypertension:
Deciphering Molecular Mechanisms
Pulmonary arterial hypertension (PAH) is a progressive lung disease characterized by pulmonary
vasoconstriction and vascular remodeling leading
to increased pulmonary vascular resistance and
YEAR
Total IF
Publication No.
Q1
2011
44,908
5
5
2012
11,339
2
2
2013
15,334
2
2
Hernansanz-Agustín P, Izquierdo-Álvarez A, GarcíaOrtiz A, Ibiza S, Serrador JM, Martínez-Ruiz A.
Nitrosothiols in the immune system: signalling and protection. Antioxid Redox Signal. 18(3):288-308. 2013.
PMID:
22746191.
IF:
7,667.
DOI:
10.1089/ars.2012.4765
Martínez-Ruiz A., Araújo IM, Izquierdo-Álvarez A,
Hernansanz-Agustín P, Lamas S, Serrador JM.
Specificity in S-nitrosylation: a short-range mechanism
for NO signaling? Antioxid Redox Signal. 19(11):122035. 2013. PMID: 23157283. IF: 7,667. DOI:
10.1089/ars.2012.5066
GROUP 8
HEAD OF LABORATORY
María Josefa Calzada García
– 40 –
Fig. 1. Immunofluorescent analysis showing TSP-1, HIF-2a and SMA or
CNN1 staining in lung. Paraffin-embedded lung tissue sections were
prepared from mice lungs subjected to normoxia (Nx) or three days
hypoxia at 10% O2 (Hp). A) Double immunofluorescence labeling was
performed with antibodies against HIF-2a (red) and smooth muscle
actin, SMA (green), a known marker of smooth muscle cells. B) Double
immunofluorescence labeling with antibodies against TSP1 and CNN1
(a known marker of smooth muscle cells). The merged images indicate the colocalization of HIF-2a and TSP1 in bronchus (white arrows)
and vessels (red arrows). Dapi labeling for nuclei was used. Images
were taken with confocal microscopy in Leica SP5 system at a magnification of 63x.
AREA 1
We are investigating the role of Hypoxia Inducible
Factors in the regulation of TSP1 in the lungs and
how this regulation translates into functional
effects. TSP-1 production in lungs might not be
limited to endothelial cells, and pulmonary smooth
muscle cells and fibroblasts might also stimulate
TSP1 levels under hypoxia (Figure 1). Therefore
TSP1 effects on PAH might include paracrine
effects stimulated from endothelial cells in the intima, inflammatory cells or platelets, but also
autocrine effects in pulmonary smooth muscle cells
and fibroblasts. All this will contribute to functional
aspects of pulmonary physiology.
MAJOR GRANTS
• María Josefa Calzada García. TSP1-CD47 in promotion of PAH-associated aasoconstriction and
vascular overgrowth. NIH. FOA:PA10-067, period
2011-2015. Duration: 2011 – 2015.
• María Josefa Calzada García. Estudio de nuevas
dianas terapeúticas en la hipertensión pulmonar.
Contirubción del nexo TSP1/CD47 en las
propiedades estructurales y funcionales de la arteria pulmonar en modelos de ratón. ISCIII.
PI13/01866. Duration: 2014 – 2016.
Palazon
A, Aragones
Lopez J, Morales-Kastresana
YEAR
Total IF
Publication No.
Q1
A, Ortiz
Del
Landazuri
M, Melero IJ. 2Molecular P1
2011
16,603
2012
16,667
4
3
2013
-
-
-
GROUP 10
HEAD OF LABORATORY
Susana Cadenas Álvarez
GROUP MEMBERS
• Andrea Anedda
• Elia López Bernardo
• Cristina Vaca Sanz
RESEARCH INTEREST
Uncoupling proteins (UCPs) have been involved in the
control of mitochondrial reactive oxygen species
(ROS) production and the protection against oxidative
stress. Since oxidative stress underlies a wide variety
of pathophysiological processes, UCPs are potentially important drug targets. The elucidation of the
molecular pathways that control their expression and
activity is essential to develop strategies for modulating their function. In addition, reduced oxygen availability modulates mitochondrial function although the
mechanism is unclear. Hypoxia induces metabolic
responses that have adaptive significance for the protection against excessive ROS production. During
2013, we have followed several lines of research.
1) We have studied the regulation of UCP3 expression
and function by oxidative stress. Hydrogen peroxide
(H2O2) increases UCP3 expression in mouse skeletal
muscle and cardiac cells, an effect mediated by the
antioxidant transcription factor Nrf2. UCP3 up-regulation increases proton leak and promotes survival, sug– 41 –
right heart failure. Loss of nitric oxide (NO) signaling and endothelial nitric oxide synthase (eNOS)derived oxidative stress are key events in the
pathogenesis of PAH yet the mechanisms involved
remain incompletely known. Our previous results
proved that TSP1-mediated activation of CD47 is
increased in experimental and human PAH, and
promotes disease by limiting Cav-1 inhibition of
dysregulated eNOS (Bauer P.M. et al. Cardiovas.
Res. 2012). It is accepted that hypoxia is a cause
of pulmonary vascular cell proliferation and vascular remodeling, but the mechanisms are not completely clear. Our group is interested in deciphering
the mechanisms by which hypoxia affects PAH
onset and development.
nism by which a reduced oxygen supply limits mitochondrial oxygen consumption. In particular, we are
analyzing the regulation of NDUFA4 and other complex IV subunits in response to fluctuating oxygen
availability by hypoxia-inducible factor (HIF)-dependent and -independent pathways.
MAJOR GRANTS
Perfused mouse heart and perfusion protocols used for measuring
the effect of cardiac ischemia (I) and ischemia-reperfusion (IR) on
Nrf2 nuclear accumulation and UCP3 expression.
gesting a role for this protein in attenuating ROSinduced damage (Anedda et al. Free Radic. Biol. Med.
2013). We are also investigating the effects of the lipid
peroxidation product 4-hydroxy-2-nonenal (4-HNE)
on UCP3 expression, and the potential involvement of
Nrf2 in this pathway.
2) Reperfusion of ischemic tissues results in an excessive production of ROS that may cause tissue injury.
Ischemia-reperfusion (IR) increases Nrf2 nuclear
accumulation and UCP3 expression in the mouse
heart (Anedda et al. Free Radic. Biol. Med. 2013). We
are currently studying the potential protective role of
UCP3 against IR injury in the isolated perfused mouse
heart.
3) In collaboration with Dr. F. Díaz-González (Hospital
Universitario de Canarias, La Laguna) and Dr. F.
Sánchez-Madrid (Hospital de La Princesa, Madrid),
we analyzed the involvement of ROS in the down-regulation of L-selectin induced by non-steroidal antiinflammatory drugs in human neutrophils. We reported the implication of superoxide anion generated by
plasma membrane NADPH-oxidase in this effect
(Dominguez-Luis et al. Biochem. Pharmacol. 2013).
4) In collaboration with Dr. M.O. Landázuri (Hospital
de La Princesa, Madrid), we are studying the mecha-
– 42 –
• 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.
• Susana Cadenas Álvarez. Papel cardioprotector del
desacoplamiento mitocondrial en condiciones de
isquemia. ISCIII. PI12/00933. Duration: 2013 –
2015
YEAR
Total IF
Publication No.
Q1
2011
19,091
2
2
2012
4,025
1
-
2013
10,36
2
2
Domínguez-Luis M, Herrera-García A, Arce-Franco M,
Armas-González E, Rodríguez-Pardo M, Lorenzo-Díaz
F, Feria M, Cadenas S, Sánchez-Madrid F, DíazGonzález F. Superoxide anion mediates the L-selectin
down-regulation induced by non-steroidal anti-inflammatory drugs in human neutrophils. Biochem
Pharmacol. 85(2):245-256. 2013. PMID: 23142710. IF:
4,650. DOI: 10.1016/j.bcp.2012.10.024
Anedda A, López-Bernardo E, Acosta-Iborra B,
Saadeh Suleiman M, Landázuri MO, Cadenas S. The
transcription factor Nrf2 promotes survival by enhancing the expression of uncoupling protein 3 under conditions of oxidative stress. Free Radic Biol Med.
16(61C):395-407. 2013. PMID: 23597505. IF: 5,710.
DOI: 10.1016/j.freeradbiomed.2013.04.007
AREA 1
Line 1.3
Animal models of
inflammatory diseases
and intercellular signalling
GROUP 11
GROUP MEMBERS
• Sofía Cabezudo Violero
• Laura Nogués Vera
• Adolfo Molejón García
• Julia Palacios García
• Petronila Penela Márquez
• Catalina Ribas Núñez
• Paula Ramos Barbeito
• Clara Reglero Gómez
• Verónica Rivas Guerrero
• Susana Rojo Berciano
• Guzmán Sánchez Fernández
• Almudena Inés Santos Bajo
Fig. 1. GRK2 downregulation is a relevant event in the tumoral angiogenic
switch. Decreased GRK2 levels in endothelial cells (in genetically engineered animals or promoted by factors secreted from cancer cells) led to biased TGFbeta signaling, and altered PDGF gradients, critical for a balanced
angiogenic process. Mouse embryos with systemic or endothelium-selective Grk2 ablation had marked vascular malformations and an altered pattern of vessel growth and maturation in postnatal retinas, involving impaired recruitment of mural cells. On the other hand, decreased endothelial
Grk2 dosage accelerated tumor growth in mice, along with reduced pericyte vessel coverage and enhanced macrophage infiltration, and this transformed environment promoted decreased GRK2 in endothelial cells and
human breast cancer vessels (Rivas et al., J Clin Invest 2013).
sion in relevant clinical situations such as tumor progression, inflammation or cardiovascular diseases, and to
evaluate the pathological impact of such changes. This is
critical to assess the feasibility of GRK2 as a useful diagnostic biomarker and/or therapeutic target.
RESEARCH INTEREST
G protein-coupled receptor kinases (GRKs) were initially
identified as negative regulators of G protein-coupled
receptors (GPCR). However, novel roles for these proteins
are being unveiled, in particular for the ubiquitous and
essential GRK2 isoform, which is emerging as a key node
in signal transduction pathways. Thus, GRK2 is able to
dynamically interact with other important signal transduction partners and to phosphorylate a variety of nonGPCR substrates. Our group is interested in unveiling the
cell type-specific networks of GRK2 interactions that
underlie its participation in basic cellular processes such
as cell cycle, cell migration or insulin resistance, to understand the mechanisms leading to altered GRK2 expres-
To this end we are using both cellular and animal models with altered GRK2 dosage or functionality (either systemic hemizygous mice, conditional or tissue-specific
knock-outs) and samples from patients or animal models of disease. Our group is also involved in sorting out
new signaling routes downstream of Gq-coupled GPCR
and in developing a new family of p38MAPK inhibitors
patented by our laboratory.
In 2013 we highlight our contribution showing that
GRK2 is a key regulator of angiogenesis during development and in tumor progression, and that GRK2
downregulation is a relevant event in the tumoral
angiogenic switch.
– 43 –
HEAD OF LABORATORY
MAJOR GRANTS
• Federico Mayor Menéndez. Red RECAVA (Red
Temática de Investigación en enfermedades
Cardiovascula-res).ISCIII. RD06/0014/0037. Duration:
2007 - 2013.
• Federico Mayor Menéndez. La quinasa GRK2 (G protein-coupled receptor kinase 2) como un nodo central
en las redes de señalización celular. Papel en fisiopatología. MICINN. SAF2011-23800. Duration: 2012 2014.
• Petronila Penela Márquez. Repercusiones de la regulación de Mdm2 y p53 por la quinasa GRK2 en cáncer
de mama: estabilidad genómica y quimioresistencia.
ISCIII. PI11/00859. Duration: 2012 - 2014.
• Federico Mayor Menéndez. Redes Moleculares y
Celulares en Enfermedades Inflamatorias. CAM. S2010/BMD-2332 - Programade 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.
• Federico Mayor Menéndez. Red RECAVA (Red
Temática de Investigación en Enfermedades
Cardiovasculares).
ISCIII.
RD12/0042/0012.
Duration: 2013 – 2016.
YEAR
Total IF
Publication No.
Q1
2011
36.765
7
5
2012
27,937
6
4
2013
17,495
2
2
Verónica Rivas, Rita Carmona, Ramón Muñoz-Chápuli,
Marta Mendiola, Laura Nogués, Clara Reglero, María
Miguel-Martín, Ramón García-Escudero, Gerald W Dorn II,
David Hardisson, Federico Mayor, Jr. and Petronila Penela.
Developmental and tumoral vascularization is regulated by
G protein-coupled receptor kinase 2. Journal of Clinical
Investigation. 123(11):4714-30. 2013. PMID: 24135140. IF:
13,765. DOI: 10.1172/JCI67333
– 44 –
Sánchez-Fernández G, Cabezudo S, García-Hoz C, Tobin
AB, Mayor F Jr, Ribas C. ERK5 activation by Gq-coupled
muscarinic receptors is independent of receptor internalization and -arrestin recruitment. PLoS One. 8(12):e84174.
2013. PMID: 24358341. IF:3,73. DOI: 10.1371/journal.pone.0084174
GROUP 12
HEAD OF LABORATORY
Manuel Fresno Escudero
GROUP MEMBERS
• Ruth Álvarez Díaz
• Beatriz Barrocal López
• Isabel M. Chico-Calero
• Carlos Chillón Marinas
• Natalia Cuesta Rubio
• Mª de los Ángeles de Chorro y de Villa-Ceballos
• Nuria Gironés Pujol
• Néstor Adrián Guerrero Gutiérrez
• Marta Jiménez Martínez
• Alba Jiménez Segovia
• Alberto Jiménez Buiza
• María Gema Marín Alberca
• Inés Claire Osma García
• Carmen Punzón Gálvez
• Carmen Mº Sánchez-Valdepeñas Villegas
• Konstantinos Stamatakis Andriani
RESEARCH INTEREST
We are analysing the involvement of Toll-like receptors
(TLR)/NFAT/Cyclooxygenase
(Cox)2/prostaglandins (PGs) in novel functions of the
immune system and in inflammatory pathologies as
Obesity and Cancer. PGs trigger activation and
migration of T lymphocytes, including the duration
AREA 1
of their interaction with antigen presenting cells.
Macrophage migration is also induced by PGs due
to activation of p110g PI3K by PG receptors. We
have also found that PGF2alfa negatively regulates
adipocyte differentiation and this activity is mediated by the transcription factor NFAT. Through specific silencing of the 4 NFAT members (NFATc1-4)
we were able to identify the member responsible
for this activity. Moreover, we found that NFATc4
deficiency induces obesity in mice indicating a key
role to this factor in controlling obesity and fatty
acid metabolism.
Increased growth of HT-29 colon cancer cells overexpressing COX-2 or
MPGES1 compared to control, (EV) injected subcutaneously in athymic
nude mice detected by bioluminescence monitoring 5 weeks post injection.
gamma and play a negative role in the infection
through repression of the NADPH oxidase. All
intended for improved understanding and prevention of Chagas’ disease.
MAJOR GRANTS
On the other hand, we are analysing Chagas’ disease. Different genetic lineages have been defined
in Trypanosoma cruzi, the causative agent of this
disease. However, understanding of their comparative biology and pathogenesis is fragmentary. We
were able to develop genetic tools to identify
infecting strains in patients. We have identified different T dependent immune responses both in
patients and mouse model that differ depending of
the infecting strain. Besides, we are studying how
the parasite enters, infects and escapes destruction by myeloid cells, defining Slamf1 (CD150) as a
new T. cruzi receptor. In contrast, we found that
Slamf8 (CD353) is a cell surface receptor that is
expressed upon activation of macrophages by IFN-
• Manuel Fresno Escudero. Receptores toll-like,
prostanoides y redes de señalización en enfermedades inflamatorias. MICINN. SAF201018733. Duration: 2011 - 2013.
• Manuel Fresno Escudero. Redes Moleculares y
Celulares en Enfermedades Inflamatorias. CAM.
S-2010/BMD-2332 - Programa de Actividades
I+D en BIOMEDICINA. Duration: 2012 – 2015
• Manuel Fresno Escudero. Identificación de biomarcadores para el seguimiento de pacientes
infectados con distintos linajes de Trypanosoma
cruzi y sometidos a tratamiento. UAM-BANCO
DE SANTANDER. Cooperación con América
Latina. Duration: 2013 -2014.
– 45 –
Through microarray analysis of gene expression we
have identified downstream genes involved in Cox2 inflammatory and pro-tumorogenic activities in
colon Cancer. Among those genes, we identified,
mPGES1, PMEPA1 and DUSP10 as Cox-2 induced
molecules in ovarian or colon cancer. mPGES1 is
involved in increased growth in vivo and in vitro and
is always co-expressed with Cox-2 in colon tumors
and is induced through a PGF2alfa/Egr-1 mechanism. DUSP10 controls stress response to serum
deprivation and confluence arrest whereas
PMEP1A induce Epithelial Mesenchymal Transition
(EMT), key in promoting tumorogenicity on colon or
ovarian carcinoma. At the molecular level, DUSP10
inhibits p38 mitogen activated protein kinase
(MAPK) activation, whereas PMEPA1 is able to
inhibit phosphorylation of SMAD1,5,8 by TGF .
• Manuel Fresno Escudero. Mediatori dell’infiammazione e angiogenesi: nuovi target per lo
sviluppo di farmaci e per terapie personalizzate MIA. Universidad de Siena, Italia - UE. Programa
de Acción en "Desarrollo de Estudio de la
Educación Superior presentada por la Universidad
de Siena en colaboración con centros de investigación y empresas". Duration: 2013 - 2014.
• Manuel Fresno Escudero. Red de Investigación
Colaborativa en Enfermedades Tropicales
(RICET). ISCIII. RD/12/0018/0004. Duration:
2013 - 2016.
• Manuel Fresno Escudero. Host-microbe interactions in Health and disease. Interface with the
immune system. UE - Marie Curie Actions - Initial
Training Networks (ITN). HOMIN - 317057 - FP7PEOPLE-2012-ITN. Duration: 2013 – 2017.
2013 Awarded Projects
• Manuel Fresno Escudero. Immunoregulatory molecules as biomarkers predicting response to biological therapies and disease severity in immunemediated inflamatory disorders. BIOIMID PROJECT. ISCIII. PIE13/00041. Duration: 2014 – 2016.
PUBLICATIONS
(6)
[IF: 28,438]
YEAR
Total IF
Publication No.
Q1
2011
23,852
7
4
2012
45,476
8
7
2012
28,438
6
5
Tamargo B, Márquez Y, Ramírez W, Cedré B,
Fresno M, Sierra G. New proteoliposome vaccine
formulation from N. meningitidis serogroup B, without aluminum hydroxide, retains its antimeningococcal protectogenic potential as well as Th-1
adjuvant capacity. BMC Immunol. 14(Supp1):S12.
2013. PMID: 23458443. IF: 2,246. DOI:
10.1186/1471-2172-14-S1-S12.
Díaz-Muñoz MD, Osma-García IC, Iñiguez MA,
Fresno M. Cyclooxygenase-2 deficiency in
– 46 –
macrophages leads to defective p110y PI3K signaling and impairs cell adhesion and migration. J
Immunol. 191(1):395-406. 2013. PMID: 23733875.
IF: 5,362. DOI: 10.4049/jimmunol.1202002
Sandoval P, Jiménez-Heffernan JA, Rynne-Vidal A,
Pérez-Lozano ML, Gilsanz A, Ruiz-Carpio V, Reyes
R, García-Bordas J, Stamatakis K, Dotor J, Majano
PL, Fresno M, Cabañas C, López-Cabrera M.
Carcinoma-associated fibroblasts derive from
mesothelial cells via mesothelial to mesenchymal
transition in peritoneal metastasis. Journal of
Pathology. 231(4) 517-531. 2013. PMID:
24114721. IF: 7,330. DOI: 10.1002/path.4281
Gutierrez-Erlandsson
S,
Herrero-Vidal
P,
Fernandez-Alfara
M,
Hernandez-Garcia
S,
Gonzalo-Flores S, Mudarra-Rubio A, Fresno M,
Cubelos B. R-RAS2 overexpression in tumors of
the human central nervous system. Mol Cancer.
12(1):127. 2013. PMID: 24148564. IF: 5,397. DOI:
10.1186/1476-4598-12-127
Corral RS, Guerrero NA, Cuervo H, Gironès N,
Fresno M. Trypanosoma cruzi infection and
endothelin-1 cooperatively activate pathogenic
inflammatory pathways in cardiomyocytes. PLoS
Negl Trop Dis. 7(2):e2034. 2013. PMID: 23409199.
IF: 4,569. DOI: 10.1371/journal.pntd.0002034
Sanoja C, Carbajosa S, Fresno M, Gironès N.
Analysis of the dynamics of infiltrating CD4(+) T cell
subsets in the heart during experimental
Trypanosoma
cruzi
infection.
PLoS
One
8(6):e65820. 2013. PMID: 23776551. IF: 3,534.
DOI: 10.1371/journal.pone.0065820
GROUP 17
HEAD OF LABORATORY
Cristina Murga Montesinos
AREA 1
GROUP MEMBERS
• Marta Cruces Sande
• Elisa Lucas Fernández
• Rocío Vila Bedmar
RESEARCH INTEREST
1.- Characterization of a mouse model resistant to
hypertension induced by angiotensin II infusion and the
biomechanical and vascular responses in mice hemizygous for the GRK2 protein (in collaboration with the
group of Dr. Mercedes Salaíces/Dr. Ana Briones).
2.- Identification of GRK2 as a novel therapeutic target
in the development of obesity and/or insulin resistance
(IR). Using a tamoxifen-inducible mice model that
allows for the deletion of this protein once the pathology has been established, we have been able to proof
that GRK2 deletion not only prevents but also reverts
weight gain and IR (manuscript in preparation 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).
3.- Analysis of the cardiac effect of lowering GRK2 levels in adult (9 months-old) mice fed with high fat diet,
as well as characterization of the status of key cardioprotective signaling routes in hemizygous GRK2 mice
(Lucas E et al, manuscript submitted in collaboration
with the groups of Dr. W.J.Koch- Temple University-and
Dr. Javier Díez-CIMA-).
Fig.1. Role of GRK2 in hypertension and vascular responses. GRK2
participates in the regulation of vasoconstrictor and vasodilator G
protein-coupled receptors (GPCR). However, GRK2 is also involved
in non GPCR-dependent pathways such as the interaction with Akt
that inhibits Akt-dependent activation of nitric oxide synthase
(NOS) thus impairing nitric oxide (NO) production. Upon Angiotensin II (AngII) challenge, adult GRK2+/- mice show improved vascular remodeling, decreased vascular stiffness, increased Akt activation, less reduced eNOS expression and increased NO production. This provokes decreased vasoconstrictor and increased vasodilator responses what, together with improved vascular structure and mechanics, leads to resistance to severe AngII-induced
hypertension.
• ES2382289B1 (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 aplicaciones"International publication number:WO 2013/
064714
MAJOR GRANTS
4.- Identification of a family of small molecule inhibitors
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. Derived from this line of research are the following
registered patents:
• Cristina Murga Montesinos. Joint collaborative effort in
the identification of novel therapeutic targets for the
treatment of diabetes and obesity.UAM. Proyectos de
Cooperación Interuniversitaria UAM – Banco
Santander con Estados Unidos. Duration: 2013 –
2014.
– 47 –
During the past year, the group has developed the following lines of research:
YEAR
Total IF
Publication No.
Q1
2011
12,714
2
2
2012
13,352
2
2
2013
-
-
-
GROUP 18
HEAD OF LABORATORY
Miguel Ángel Iñiguez Peña
GROUP MEMBERS
• Paloma Guillem Llobat
• Elena Hernández Subirá
• Raquel Nieto Pintado
• Ana Renshaw Calderón
RESEARCH INTEREST
Ongoing studies of our group comprise different lines
of research about the regulation of the expression of
COX and PG synthases and the influence of
prostanoids on the immune response. The main
objectives within this project during 2013 have been
aimed to the analysis of the effects of prostanoids
and LXR ligands in leukocyte (T cells and
macrophages) function and activation. Regarding to
this, we have shown the influence of COX-2 derivatives on macrophage migration by the use of COX-2
KO mice. We are also working on the differential
effect of prostanoids as PGF2 or cyclopentenones
on macrophage and T cell activation. In particular, we
have some interesting data about their effects on the
regulation of gene expression in these cells.
In addition, we have started a new line of research
focused in the analysis of the role of other bioactive
– 48 –
Fig.1. Cyclooxygenase-2 deficiency in macrophages impairs
macrophage migration. A) Cell recruitment to the peritoneal cavity is diminished in cox-2-/- mice. Quantification of the total
number of cells migrated to the peritoneal cavity of cox-2+/+
or cox-2-/- mice four days after i.p. injection of sodium thioglycolate. B) Flow cytometry analysis of cell populations in the peritoneal cavity of cox-2+/+ and cox-2-/- mice shows that the
decrease in the total number of migrated cells in cox-2-/- mice
was almost exclusively due to a reduction in the migration of
F4/80+ CD11c+ CD11b+ macrophages The number of CD3+
cells (T lymphocytes), CD45R/B220+ cells (mainly B lymphocytes), NK1.1+ cells (NK cells) and Gr1+ cells (granulocytes) recruited to the peritoneal cavity was similar in cox-2+/+ or cox2-/- mice.
lipids in inflammation, including oxidized derivatives
of cholesterol as oxysterols and LXR (liver receptor X)
ligands. LXR ligands play a central regulatory role in
lipid uptake, metabolism and efflux through their
properties as transcriptional regulators of gene
expression. In addition to their function in lipid
metabolism, LXRs have also been found to modulate
immune and inflammatory responses. In this regard,
our data show the influence of these agents in the
modulation of T cell and macrophage activation, with
a key role as negative regulators of gene expression
in these cells.
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.
AREA 1
YEAR
Total IF
Publication No.
Q1
2011
3,536
1
1
2012
12,011
2
2
2013
5,362
1
1
Díaz-Muñoz MD, Osma-García IC, Iñiguez MA, Fresno
M. Cyclooxygenase-2 deficiency in macrophages leads
to defective p110y PI3K signaling and impairs cell
adhesion and migration. J Immunol. 191(1):395-406.
2013. PMID: 23733875. IF: 5,362. DOI: 10.4049/jimmunol.1202002
– 49 –
Line 1.4
Etiopathogenic
and immunological
mechanisms of
dermatological diseases
Gallo E, Cabaleiro T, Román M, Solano-López G,
Abad-Santos F, García-Díez A, Daudén E. The relationship between tumour necrosis factor (TNF)-a promoter
and IL12B/IL-23R genes polymorphisms and the efficacy of anti-TNF-a therapy in psoriasis: a case-control
study. Br J Dermatol. 169(4):819-29. 2013. PMID:
23662788. IF: 4,100. DOI: 10.1111/bjd.12425
Gallo E, Pérez-Gala S, Navarro R, Fraga J, Adrados M,
Arranz R, García-Diez A, Aragüés M. Coexistence of
marginal zone cutaneous B-cell lymphoma and classic
Hodgkin disease: does a biological relationship exist?.
Clin Exp Dermatol. 38(4):383-5. 2013. PMID:
23551363. IF: 1,234. DOI: 10.1111/j.13652230.2012.04478.x
GROUP 19
HEAD OF LABORATORY
Amaro García Díez
Fraga J, Montalvo AM, Maes L, Dujardin JC, Van der
Auwera G. HindII and SduI digests of heat-shock protein 70 PCR for Leishmania typing. Diagn Microbiol
Infect Dis. 77(3):245-247. 2013. PMID: 24050933. IF:
2,568. DOI: 10.1016/j.diagmicrobio.2013.07.023
GROUP MEMBERS
• Maximiliano Aragüés Montañés
• Javier Fraga Fernández
YEAR
Total IF
Publication No.
Q1
2011
5,846
4
1
2012
25,329
9
5
2013
28,179
13
3
Llamas-Velasco M, Godoy A, Sánchez-Pérez J,
García-Diez A, Fraga J. Acute generalized exanthematous pustulosis with histopathologic findings of lymphomatoid drug reaction. Am J Dermatopathol.
35(6):690-691. 2013. PMID: 23291582. IF: 1,426. DOI:
10.1097/DAD.0b013e31827a0c46
Navarro R, Vilarrasa E, Herranz P, Puig L, Bordas X,
Carrascosa JM, Taberner R, Ferrán M, GarcíaBustinduy M, Romero-Maté A, Pedragosa R, GarcíaDiez A, Daudén E. Safety and effectiveness of ustekinumab and anti-tumor necrosis factor therapy in
patients with psoriasis and chronic viral hepatitis b or c.
A retrospective, multicentre study in a clinical setting.
Br J Dermatol. 168(3):609-616. 2013. PMID:
22985451. IF: 4,100. DOI: 10.1111/ bjd.12045
– 50 –
Cabaleiro T, Román M, Gallo E, Ochoa D, Tudelilla F,
Talegón M, Prieto-Pérez R, García-Díez A, Daudén E,
Abad-Santos F. Association between psoriasis and
polymorphisms in the TNF, IL12B, and IL23R genes in
Spanish patients. Eur J Dermatol. 23(5):640-5. 2013.
PMID: 24135300. IF: 1,953. DOI: 10.1684/
ejd.2013.2144
Delgado-Jiménez Y, Fraga J, Requena C, Requena L,
Aragües M, Fernandez Herrera J, Garcia Diez A.
Acute bacterial septic vasculopathy. Int J Dermatol.
52(9):1071-80. 2013. PMID: 23231414. IF: 1,227.
DOI: 10.1111/j.1365-4632.2012.05468.x
Gallo E, Llamas-Velasco M, Daudén E, García-Diez
A. Refractory generalized pustular psoriasis responsive to a combination of adalimumab and acitretin. Int
J Dermatol. 52(12):1610-1. 2013. PMID: 22834488.
IF: 1,227. DOI: 10.1111/j.1365-4632.2012.05472.x
Llamas-Velasco M, García-Martín P, Sánchez-Pérez J,
Fraga J, García-Diez A. Sweet's syndrome with subcutaneous involvement associated with pegfilgrastim
treatment: first reported case. J Cutan Pathol.
AREA 1
Gallo E, Llamas-Velasco M, Navarro R, Fraga J, GarcíaDiez A. Eccrine squamous syringometaplasia secondary to cutaneous extravasation of docetaxel: report of
three cases. J Cutan Pathol. 40(3):326-9.. 2013. PMID:
23170995. IF: 1,560. DOI: 10.1111/ cup.12041
Sotomayor E, Fraga J, García-Diez A. Macular lymphocytic arteritis: first clinical presentation with ulcers. J
Cutan Pathol. 40(4):424-7. 2013. PMID: 23384039. IF:
1,560. DOI: 10.1111/cup.12094
Sampaio F, Pimenta J, Bettencourt N, FontesCarvalho R, Silva AP, Valente J,Bettencourt P,
Fraga J, Gama V. Systolic and diastolic dysfunction
in cirrhosis:a tissue-Doppler and speckle tracking
echocardiography study. Liver Int. 33(8):1158-65.
2013. PMID: 23617332. IF: 4,412. DOI: 10.1111/
liv.12187
Grillo E, Pérez-Gala S, Vano-Galván S, Jaén-Olasolo P.
Multiple sebaceous hyperplasia secondary to
ciclosporin in a heart transplant patient. Med Clin
(Barc). 141(2):e3. 2013. PMID: 23664109. IF: 1,252.
DOI: 10.1016/j.medcli.2013.02.023
40(1):46-9. 2013. PMID: 23131080. IF: 1,560. DOI:
10.1111/cup.12042
– 51 –
Line 1.5
Cellular mechanisms and
molecular determinants of
allergy-based diseases
GROUP 20
HEAD OF LABORATORY
Carlos Blanco Guerra
GROUP MEMBERS
• Álvaro Daschner
• María Teresa Belver González
• Consolación de Frutos Moreno
• M. Paloma Las Heras Almazán
• María Victoria Múgica García
• Tania María Ramos García
• Ana Valls Sánchez
• Francisco Félix Vega de la Osada
Fig. 1. Fish eating habits in different phenotypes of chronic urticaria. Results afte logistic regression analysis including all possible fish-eating variables. Median wookly (total, oily fish, canned
fish) and monthly (anchovies in vinegar sauce) portions of fish in
chronic utricaria without (CU-) and with (CU+) previous parasitism by Anisakis simplex
RESEARCH INTEREST
Our group has focused on three different research
areas throughout 2013:
- Anisakis simplex allergy: Within the project on
characterizing Anisakis simplex sensitization associated allergic diseases, led by Dr. Daschner, we
have shown that IgE immunoglobulin avidities are
dependent on fish-eating habits and the time
elapsed to the last parasitic episode. We have
demonstrated differential avidity behaviour when
comparing gastro-allergic Anisakiasis and Anisakis
associated chronic urticaria (AACU).
With respect to the characterization of AACU, we
have concluded a clinical trial, confirming a complex relationship between fish-eating habits,
cytokine production and prognosis. Improvement
– 52 –
Fig. 2. Avidity index of specific IgE and specific IgG against
Anisakis simplex in gastroallergic Anisakiasis depending on the
amount of detectable specific IgE
was clinically associated with higher oily fish intake
and immunologically with higher Concanavalin A
AREA 1
- Food allergy: we continue to work with Centre for
Plant Biotechnology and Genomics (UPM-INIA),
now studying the role of N-glycosylation in kiwi
allergy. At the same time, we have collaborated in a
couple of FISS research projects, focused on nut
allergy and on sensitization to the pollen-food panallergen profilin.
- Respiratory allergy: in the context of the MEICA
research project formerly funded by Fundación
Genoma España, a 2 yr study prolongation of a
phase IV study, checking immunological changes
induced by grass-pollen immunotherapy, is currently running. Moreover, a new placebo controlled clinical trial has been started, in collaboration with ALK
laboratory and the CNB (National Biotechnology
Centre).
series. J Investig Allergol Clin Immunol. 23(6):383391. 2013. IF: 2,642
Boyano-Martínez T, Pedrosa M, Belver T, Quirce S,
García-Ara C. Peach allergy in Spanish children:
tolerance to the pulp and molecular sensitization
profile. Pediatr Allergy Immunol. 24(2):168-172.
2013. PMID: 23506291. IF: 3,859. DOI:
10.1111/pai.12037
BOOKS
Tejera E; Sala-Valdés M; Rocha-Perugini V; Yáñez Mó M.
Role of tetraspanins in cell migration and intercellular
adhesion. Tetraspanins. Series Proteins and Cell
Regulation. 2013. Springer. ISBN: 978-94-007-6070-7.
CLINICAL TRIALS
PUBLICATIONS
(3)
[IF: 9,247]
YEAR
Total IF
Publication No.
2011
4,87
2
Q1
-
2012
17,568
5
4
2013
9,247
3
1
García-Ara C, Pedrosa M, Belver MT, Martín-Muñoz
MF, Quirce S, Boyano-Martínez T. Efficacy and
safety of oral desensitization in children with cow's
milk allergy according to their serum specific IgE
level. Ann Allergy. Asthma Immunol. 110(4):290294. 2013. PMID: 23535095. IF: 2,746. DOI:
10.1016/j.anai.2013.01.013
Tejedor-Alonso MA, Múgica-Garcia MV, EstenaHernández J, Moro-Moro M, Rojas-Pérez-Ezquerra
PE, Rosado-Ingelmo A, Vila-Albelda C. A study of
recurrence of Anaphylaxis in a Spanish Anaphylaxis
PRINCIPAL RESEARCHER: BLANCO GUERRA,
CARLOS
Mecanismos moleculares y celulares implicados en
la inmunoterapia con un liofilizado oral de Phleum
pratense; (versión final: 05-11-12). ALK-ABELLO,
S.A. GT-24. EudraCT: 2012-005092-14.
CARLOS
Análisis de la respuestas de células T en sujetos
alérgicos sensibilizados a profilina (Phl p 12);
(Versión borrador 1: 31-07-13). OBS-ESP-P01.
CARLOS
Identificación y prevalencia de nuevos alérgenos en
España. Proyecto Prometeo; (versión 1.0:29-1013). MERCK S.L. MER-ALG-2013-01/PROYECTO
PROMETEO
– 53 –
induced IL-10/IFN- and IL-10/IL-6 ratios. The
results have important consequences in dietary
advice.
Line 1.6
Inflammatory processes in
nephrological diseases
3.- Virology and CKD: Participation in the SHECTS study to
establish the prevalence of HCV infection in the Spanish
haemodialysis population and the prevalence of the hidden
HCV infection in CKD.
GROUP 21
4.- Bone alterations and mineral metabolism in CKD.
Definition and treatment of this alterations in different situations: pre-dialysis, dialysis and in transplant patients.
HEAD OF LABORATORY
José Antonio Sánchez Tomero
GROUP MEMBERS
• Abelardo Isaac Aguilera Peralta
• Vicente Álvarez Chiva
• Guillermina Barril Cuadrado
• Carmen Bernis Carro
• Antonio Carlos Fernández Perpén
• Martín Giorgi González
• Isabel Herráez Jiménez
• Pablo Ruano Suárez
• Laura Salanova Villanueva
• Carmen Sánchez González
RESEARCH INTEREST
Most important contributions during 2013:
1.- Peritoneal Dialysis (PD): We have developed studies
about Mesothelial to Mesenchymal Transition in PD: to
define the mechanisms of the Switch of VEGF
Receptors/Co-Receptors during PD, and the role of
Tamoxifen in ameliorating Peritoneal Membrane Damage.
Expanding the use of PD we have studied the role of this
technique in ameliorating the ischemic brain damage in a rat
model.
2.- Renal Nutrition: We have defined several tables showing
dietary phosphorus/protein ratio for the Spanish population
and the usefulness of this parameter in chronic kidney disease (CKD). Moreover, we have studied the endogenous
testosterone, muscle strength, and fat-free mass in men
with chronic kidney disease.
– 54 –
5.- Mechanisms and treatment of glomerular diseases:
Effect of Dual Blockade of the Renin-Angiotensin System on
the Progression of Type 2 Diabetic Nephropathy: A
Randomized Trial. And the role of oral paricalcitol as antiproteinuric agent in chronic kidney disease.
6.- Ethical aspects and Nephrology: Thoughts on the start
and withdrawal of dialysis
MAJOR GRANTS
• Carmen Bernis Carro. Utilizacion de modelos animales y
celulares para caracterizar el fracaso renal agudo y multiorgánico. CIFRA-CM. S2010/BMD-2378. Duration: 2012
- 2015.
• Abelardo Isaac Aguilera Peralta. La cavidad abdominal
como fuente de factores de riesgo cardiovascular y de
ateroesclerosis durante la dialisis peritoneal:alternativasa
terapeuticas. ISCIII. PI12/01175. Duration: 2012 - 2015.
• José Antonio Sánchez Tomero. Protective effect of icodextrin on mesothelial-to-mesenchymal transition of mesothelial cells induced by peritoneal dialysis fluids. Baxter SA. PI
468. Duration: 2013 - 2014.
• José Antonio Sánchez Tomero. Desarrollo de un programa
para el abordaje integral del tratamiento de la Enfermedad
Renal Crónica Avanzada. United Surgical Partners Madrid,
SL. Hospital Quiron San Camilo. Duration: 2013 - 2015.
• José Antonio Sánchez Tomero. Estudio de los marcadores
de riesgo cardiovascular en la enfermedad renal y proyección pronóstica. Nipro Europe SA. Duration: 2013 - 2015.
• Guillermina Barril Cuadrado. Balance de miocitoquinas en
hemodialisis. variaciones segun el esquema de hemodialisis. Fund- Médica de Nefrología. SOMANE.2013.
Duration: 2013 – 2015.
AREA 1
• Carmen Bernis Carro. European Multicenter and OpenLabel. Controlled Randomized Trial to evaluate the Efficacy
of Sequential Treatment with Tacrolimus-Rituximab versus
Steroids plus Cyclophosphamide in patientes with Primary
Membranous Nephropathy. STARMEN01-2013. Duration:
2014 – 2016.
YEAR
Total IF
Publication No.
Q1
2011
33,655
12
5
2012
28,282
11
3
2013
42,669
14
4
Fernandez Juarez G, Luño J, Barrio V, de Vinuesa SG,
Praga M, Goicoechea M, Cachofeiro V, Nieto J, Fernández
Vega F, Tato A, Bernis C, Gutierrez E; PRONEDI
StudyGroup. Effect of Dual Blockade of the ReninAngiotensin System on the Progressionof Type 2 Diabetic
Nephropathy: A Randomized Trial. Am J Kidney. Dis
61(2):211-8. 2013. PMID: 22939518. IF: 5,756. DOI:
10.1053/j.ajkd.2012.07.011
Godino MD, Romera VG, Sánchez-Tomero JA, Pacheco J,
Canals S, Lerma J, Vivancos J, Moro MA, Torres M,
Lizasoain I, Sánchez-Prieto J. Amelioration of ischemic
brain damage by peritoneal dialysis. J Clin Invest.
123(10):4359-4363. 2013. PMID: 23999426. IF: 13,765.
DOI: 10.1172/JCI67284
Martin-Malo A, Papadimitriou M, Cruz J, Bustamante J,
Verbeelen D, Nony A, Vanholder R, Jacobson SH,
Montenegro J, Hannedouche T, Wizemann V, Locatelli
F; Membrane Permeability Outcome (MPO) Study
Group. Geographical variability of patient characteristics and treatment patterns affect outcomes for incident hemodialysis patients. J Nephrol. 26(1):119-128.
2013. PMID: 22476964. IF: 1,996. DOI: 10.5301/
jn.5000116
Cigarrán S, Pousa M, Castro MJ, González B, Martínez A,
Barril G, Aguilera A, Coronel F, Stenvinkel P, Carrero JJ.
Endogenous testosterone, muscle strength, and fat-free
Fig.1. Peritoneal dialysis attenuates ischemia-induced increases in
plasma glutamate concentration and cerebral infarct size. (A) The glutamate concentration was determined in plasma samples taken prior
to (basal) and at different times (hours) after pMCAO (samples were taken at 2.5 hours [S2.5], 4.5 hours [S4.5], 5.5 hours [S5.5], and 24 hours
[S24]), with peritoneal dialysis initiated 2.5 hours after pMCAO induction. Cerebral infarct size was measured 24 hours after pMCAO. Plasma
glutamate (normalized to basal levels) and cerebral infarct size were
determined in the following conditions: (B, D, and E) pMCAO as well as
pMCAO plus peritoneal dialysis at 2.5 hours [+dialysis (2.5h)]; (C and D)
pMCAO plus peritoneal dialysis at 2.5 hours with 400 ⎧M glutamate in
the dialysate [+dialysis (2.5h) 400 ⎧M GLU] as well as sham-operated
rats (SHAM); and (D) pMCAO plus peritoneal dialysis at 5 hours [+dialysis (5h)]. (E) Correlation between plasma glutamate (measured 4.5
hours after pMCAO) and infarct size. The average basal glutamate values were 51.8 ± 2.6 ⎧M (n = 21). Data represent the mean ± SEM, and
n = 5–9 for each condition. *P < 0.05 versus basal values (ANOVA); #P <
0.05, ##P < 0.01, ###P < 0.001 versus corresponding values in pMCAO
(ANOVA); &&&P < 0.001 versus corresponding values in [+dialysis
(2.5h)] (ANOVA). Amelioration of ischemic brain damage by peritoneal
dialysis. J Clin Invest. 2013;123(10):4359–4363.
mass in men with chronic kidney disease. J Ren Nutr.
23(5):e89-95. 2013. PMID: 23046736. IF: 2,548. DOI:
10.1053/j.jrn.2012.08.007
José A. Sánchez Tomero. Thoughts on the start and withdrawal of dialysis. Nefrologia. 33(6):758-63. 2013. PMID:
24241362. IF: 1,442. DOI: 10.3265/Nefrologia.pre2013.
Jul.12053
– 55 –
Górriz JL, Molina P, Bover J, Barril G, Martín-de Francisco
AL, Caravaca F, Hervás J, Piñera C, Escudero V, Molinero
LM; en nombre de los investigadores del estudio OSERCE.
Characteristics of bone mineral metabolism in patients with
stage 3-5 chronic kidney disease not on dialysis: results of
the OSERCE study. Nefrología. 33(1):46-90. 2013. PMID:
23364626. IF: 1,442. DOI: 10.3265/Nefrologia.
pre2012.Nov.11703
García-Agudo R, Aoufi-Rabih S, Barril-Cuadrado G; Grupo
de Virus en Diálisis de la Sociedad Española de Nefrología.
SHECTS multi-centre Spanish study: liver situation of
patients with chronic hepatitis from HCV on renal replacement therapy with haemodialysis. Nefrología. 33(2):188195. 2013. PMID: 23511755. IF: 1,442. DOI:
10.3265/Nefrologia.pre2012.Nov.11668
Portolés J, Janeiro D, Lou-Arnal LM, López-Sánchez P,
Ortega M, del Peso G, Felipe C, Tato AM, Velo M,
Castellano I, Pérez-Díaz V; Grupo Centro de Diálisis
Peritoneal (GCDP). First episodes of peritoneal infection:
description and prognostic factors. Nefrología. 33(3):316324. 2013. PMID: 23712221. IF: 1,442. DOI:
10.3265/Nefrologia.pre2013.Feb.11733
Guillermina Barril-Cuadrado, M. Bernardita Puchulu, José
A. Sánchez-Tomero. Table showing dietary phosphorus/protein ratio for the Spanish population. Usefulness in
chronic kidney disease. Nefrología. 33(3):362-371. 2013.
PMID:
23640120.
IF:
1,442.
DOI:
10.3265/Nefrologia.pre2013.Feb.11918
Alberto de Lorenzo, Laura Salanova, Andrew S. Bomback,
María Moya, Francisco Coronel, Carmen Bernis, José A.
Sánchez-Tomero, Vicente Álvarez. Oral paricalcitol as
antiproteinuric agent in chronic kidney disease. Nefrología.
33(5):709-715. 2013. PMID: 24089163. IF: 1,442. DOI:
10.3265/Nefrologia.pre2013.Jun.11928
Josep F. Crespo, Juan J. Amenábar, Isabel Beneyto,
Carmen Bernis, Natividad Calvo, Patricia Delgado, Roberto
Gallego, Ernesto Gómez, Rita Guerra, Manel Perelló, Ana
– 56 –
Ramos, Manuel Á. Rodríguez, Eugenia Solá. Tratamiento
de las alteraciones óseas y del metabolismo mineral postrasplante. Nefrología Sup Ext. 4(1):43-51. 2013. IF: 1,442.
DOI:10.3265/NefrologiaSuplementoExtraordinario.
pre2013.Jan.11952
Guillermina Barril-Cuadrado. Virus oculto de la hepatitis C en pacientes en hemodiálisis. Nefrología Sup
Ext.
4(3):22-26.
2013.
IF:
1,442.
DOI:
10.3265/NefrologiaSuplementoExtraordinario.pre201
3.Apr.12076
Pérez-Lozano ML, Sandoval P, Rynne-Vidal A, Aguilera
A, Jiménez-Heffernan JA, Albar-Vizcaíno P, Majano PL,
Sánchez-Tomero JA, Selgas R, López-Cabrera M.
Functional Relevance of the Switch of VEGF
Receptors/Co-Receptors during Peritoneal DialysisInduced Mesothelial to Mesenchymal Transition. Plos
One. 8(4):e60776. 2013. PMID: 23585849. IF: 3,534.
Loureiro J, Sandoval P, del Peso G, Gonzalez-Mateo L,
Fernandez- Millara V, Santamaria B, Bajo MA,
Sanchez-Tomero JA, Guerra-Azcona G, Selgas R,
López-Cabrera M, Aguilera A. Tamoxifen Ameliorates
Peritoneal Membrane Damage by Blocking Mesothelial
to Mesenchymal Transition in Peritoneal Dialysis. Plos
One. 8(4):e61165. 2013. PMID: 23637793. IF: 3,534.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: BERNIS CARRO, CARMEN
Ensayo multicéntrico, aleatorizado, controlado y abierto para evaluar la eficacia del tratamiento secuencial
con tacrolimus-rituximab versus esteroides más ciclofosfamida en pacientes con nefropatía membranosa
primario; (Versión 3: 17-01-14). FUNDACIÓN RENAL
IÑIGO ALVÁREZ DE TOLEDO. STARMEN01-2013.
EudraCT: 2013-000226-55.
AREA 1
Line 1.7
Inflammatory mechanisms
in pulmonary diseases
GROUP 22
HEAD OF LABORATORY
RESEARCH INTEREST
The Pneumology service of of La Princesa Hospital is
part of the R+D Biomedicine Programme. HUP CONSEPOC-CM: Inflammation and hypoxia: mechanisms
of development and progression of COPD and SAHS
(S1010/BMD-2542). Julio Ancochea is responsible for
the group (EPOC- HLPR) which includes other members of La Princesa Institute (IP). The role of this group
in this project has focused on the selection, characterization, monitoring and sampling of peripheral venous
blood of patients with COPD and SAHS.
Several active clinical trials have been developed during 2013 on different respiratory disease (COPD, asthma, idiopathic pulmonary fibrosis, bronchiectasis and
cystic fibrosis).
Two different projects received grants from the Spanish
Society of Respiratory pathology (SEPAR): “Correlation
between nocturnal desaturation and walk test in adult
patients with cystic fibrosis” for two years (IP: RM
Gómez) and “Epidemiology and clinical and microbiological characterization of acute exacerbation of
Fig. 2. Serum biomarkers of patients with and without the overlap
COPD-asthma phenotype
patients with bronchiectasis not caused by cystic fibrosis” (IP: RM. Girón).
Dr. Girón works as a collaborating researcher at the
FISS Project (reference PI12/00734): “Multicenter study
of the population structure of P.Aeruginosa in chronic
bronchopulmonary primo colonization and pathogenic
colonization and dynamics of the microbiome in cystic
fibrosis”.
PhD theses published in 2013:
- "Home Telemonitoring in patients with severe
– 57 –
GROUP MEMBERS
• Carolina Cisneros Serrano
• Rosa María Girón Moreno
• Ana Martínez Meca
• Silvia Sánchez Cuéllar
• Enrique Domingo Zamora García
Fig. 1. Prevalence of respiratory syntoms in patients with or without the overlap COPD-asthma phenotype. *p<0.001
chronic obstructive pulmonary disease." July 2013:
Gonzalo Calvo Segrelles. Excellent Cum Laude.
- "The role of the family of galectins as immunoregulatory molecules in asthma". May 2013: Silvia
Sánchez Cuéllar. Excellent Cum Laude.
Most relevant publication in 2013:
- “Characterisation of the overlap COPD-asthma
phenotype. Focus on physical activity and health
status”. Miravitlles M, Soriano JB, Ancochea J,
Muñoz L, Duran-Tauleria E, Sánchez G, Sobradillo
V, García-Río F. Respir Med. 2013 Jul;107(7):105360.
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.
• Rosa María Girón Moreno. Epidemiologia y caracterización clínico-microbiológica de las exacerbaciones agudas de los pacientes con Bronquiectasias no debidas a
fibrosis quistica. SEPAR. Duration: 2013 - 2015.
• Carolina Cisneros Serrano. Eficacia de una estrategia
simple para promover el cumplimiento terapéutico.
SEPAR. Duration: 2013 – 2015.
– 58 –
YEAR
Total IF
Publication No.
Q1
2011
2012
54,608
7
3
28,228
14
2013
3
26,617
12
1
Girón Moreno RM, Fernandes Vasconcelos G,
Cisneros C, Gómez-Punter RM, Segrelles Calvo G,
Ancochea J. Presence of Anxiety and Depression
in Patients With Bronchiectasis Unrelated to Cystic
Fibrosis. Arch Bronconeumol. 49(10):415-420.
2013. PMID: 24008154. IF: 1,816. DOI:
10.1016/j.arbres.2013.01.012
Perpiñá Tordera M, García Río F, Alvarez Gutierrez
FJ, Cisneros Serrano C, Compte Torrero L,
Entrenas Costa LM, Melero Moreno C, Rodríguez
Nieto MJ, Torrego Fernández A. Guidelines for the
Study
of
Nonspecific
Bronchial
Hyperresponsiveness
in
Asthma.
Arch
Bronconeumol. 49(10):432-446. 2013. PMID:
23896599. IF: 1,816. DOI: 10.1016/j.arbres.2013.
05.001
Ancochea J, Miravitlles M, García-Río F, Muñoz L,
Sánchez G, Sobradillo V, Duran-Tauleria E, Soriano
JB. Underdiagnosis of chronic obstructive pulmonary disease in women: quantification of the
problem, determinants and proposed actions. Arch
Bronconeumol.
49(6):223-9.
2013.
PMID:
23317767. IF: 1,816. DOI: 10.1016/j.arbres.2012.
11.010
Xaubet A, Ancochea J, Bollo E, FernándezFabrellas E, Franquet T, Molina-Molina M, Montero
MA, Serrano-Mollar A. Guidelines for the diagnosis
and treatment of idiopathic pulmonary fibrosis.
Sociedad Española de Neumología y Cirugía
Torácica (SEPAR) Research Group on Diffuse
Pulmonary
Diseases.
Arch
Bronconeumol.
49(8):343-53. 2013. PMID: 23742884. IF: 1,816.
DOI: 10.1016/j.arbres.2013.03.011
García-Rio F, Soriano JB, Miravitlles M, Muñoz L,
Duran-Tauleria E, Sánchez G, Sobradillo V,
AREA 1
Correa-Ruiz A, Girón R, Buendía B, MedinaPascual MJ, Valenzuela C, López-Brea M, SáezNieto JA. Burkholderia cepacia complex infection in
an Adult Cystic Fibrosis unit in Madrid. Enferm
Infecc Microbiol Clin. 31(10):649-54. 2013. PMID:
23528342.
IF:
1,881.
DOI:
10.1016/j.eimc.2012.12.001
Máiz L, Girón RM, Olveira C, Quintana E, Lamas A,
Pastor D, Cantón R, Mensa J. Inhaled antibiotics
for the treatment of chronic bronchopulmonary
Pseudomonas aeruginosa infection in cystic fibrosis: systematic review of randomised controlled trials. Expert Opin Pharmacother. 14(9):1135-49.
2013. PMID: 23586963. IF: 3,085. DOI:
10.1517/14656566.2013.790366
Urrutia I, Plaza V, Pascual S, Cisneros C, Entrenas
LM, Luengo MT, Caballero F. Asthma control and
concordance of opinions between patients and pulmonologists. J Asthma. 50(8):877-83. 2013. PMID:
23808796.
IF:
1,848.
DOI:
10.3109/02770903.2013.819886
Cisneros C, Segrelles G, Herráez L, Gonzalez A,
Girón R. Churg-Strauss syndrome in a patient
treated with Omalizumab. J Investig Allergol Clin
Immunol. 23(7):515-6. 2013. PMID: 24654320. IF:
2,642
Dang MT, Gu C, Klavanian JI, Jernigan KA, Friderici
KH, Cui Y, Molina-Molina M, Ancochea J, Xaubet A,
Uhal BD. Angiotensinogen promoter polymorphisms predict low diffusing capacity in U.S. and
Spanish IPF cohorts. Lung. 191(4):353-60. 2013.
PMID: 23715995. IF: 2,171. DOI: 10.1007/s00408013-9476-2
Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J,
Almagro P, Quintano JA, Trigueros JA, Piñera P,
Simón A, Riesco JA, Ancochea J, Soriano JB. A
new approach to grading and treating COPD based
on clinical phenotypes: summary of the Spanish
COPD guidelines (GesEPOC). Prim Care Respir J.
22(1):117-21. 2013. PMID: 23443227. IF: 2,209.
DOI: 10.4104/pcrj.2013.00016
Miravitlles M, Soriano JB, Ancochea J, Muñoz L,
Duran-Tauleria E, Sánchez G, Sobradillo V, GarcíaRío F. Characterisation of the overlap COPD-asthma phenotype. Focus on physical activity and
health status. Respir Med. 107(7):1053-60. 2013.
PMID:
23597591.
IF:
2,917.
DOI:
10.1016/j.rmed.2013.03.007
BOOKS
Carolina Cisneros Serrano, Celia Pinedo Sierra. Monografía
de Neumomadrid: “Actualización en asma”. 2013. Ergon.
ISBN: 978-84-15950-06-6.
Mª Ángeles Ruiz Cobos, Silvia Sánchez-Cuéllar, Julio
Ancochea Bermúdez. Tratamiento de la crisis asmática.
Avances en el Manejo del Asma. 2013. Neumomadrid.
Curso/Libro on line.
Silvia Sánchez-Cuéllar, María del Valle Somiedo Gutiérrez,
Cristina López Riolobos. Patogenia y Bases moleculares
del Asma. Monografía de la Sociedad Madrileña de
Neumología y Cirugía Torácica de Asma. Neumomadrid.
2013. Ergon. ISBN: 978-84-15950-06-6.
Carolina Cisneros Serrano, Rosa Mar Gómez Punter, Gilda
Fernandes. Epidemiología e impacto socio-sanitario del
asma. Monografía de Neumomadrid: “Actualización en
asma”. 2013. Ergon. ISBN: 978-84-15950-06-6.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ANCOCHEA BERMÚDEZ,
JULIO
Estudio internacional aleatorizado de fase IV para la
evaluación médica y médico-económica de un pro-
– 59 –
Ancochea J. Frequency of multi-dimensional COPD
indices and relation with disease activity markers.
COPD. 10(4):436-43. 2013. PMID: 23537163. IF:
2,600. DOI: 10.3109/15412555.2012.761959
grama de tratamiento domiciliario de pacientes con
Enfermedad Pulmonar Obstructiva crónica de estadio
gold III/IV (Versión4.0: 23-05-12, enmienda 3). AIR
LIQUIDE SANTE INTERNATIONAL. ALMED-07-C4008
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
Pulmonar Obstructiva Crónica en comparación con
pacientes controlados según práctica clínica habitual;
(Versión enmienda v01:17-10-12). NOVARTIS FARMACEUTICA, S.A. CIDD001D2401
JULIO
Estudio de fase II, multicéntrico, aleatorizado, doble ciego,
controlado con placebo, para evaluar la eficacia y la seguridad de GS-6624 en pacientes con fibrosis pulmonar
idiopática (RAINIER);(versión enmienda 2:20-03-13).
GILEAD SCIENCES INTERNATIONAL LTD. GS-US-3220207. EudraCT: 2012-001571-36.
JULIO
Estudio comparativo con placebo, doble ciego y aleatorizado de fase II para valorar la eficacia y seguridad de lebrikizumab en pacientes con fibrosis pulmonar idiopática;
– 60 –
(Versión 2: 06-06-13). F. HOFFMANN-LA ROCHE LTD.
GB28547. EudraCT: 2013-001163-24
JULIO
Estudio aleatorizado, multicéntrico, de 52 semanas de
seguimiento para evaluar la mejora de la calidad de vida
mediante un programa de apoyo a pacientes con enfermedad pulmonar obstructiva crónica (EPOC), en comparación con los pacientes atendidos de forma habitual. Estudio
On-health 1 (versión final 3.0: 04-06-13). NOVARTIS FARMACEUTICA, S.A. NOV-EPO-2012-002
JULIO
Proyecto madrileño sobre el manejo de la Enfermedad
Pulmonar Obstructiva Crónica con telemonitorización a
domicilio; (Versión 1: 02-10-13). FUNDACION TEOFILO
HERNANDO. PROMETE
PRINCIPAL RESEARCHER: GIRÓN MORENO, ROSAMARÍA
Estudio aleatorizado, en doble ciego, controlado con placebo y multicéntrico, de ciprofloxacino 32,5mg en polvo seco
para inhalación dos veces al día en administración intermitente, durante 28 días con otros 28 de descanso o durante
14 días con otros 14 de descanso, en comparación con
placebo, en la evaluación del tiempo hasta la primera exacerbación pulmonar y la frecuencia de las exacerbaciones en
sujetos con bronquiectasias no debidas a fibrosis quística;
(versión 1.0: 24-08-12). BAYER HEALTHCARE, A. G. BAY
Q 3939/15625. EudraCT: 2011-004208-39
AREA 1
Line 1.8
Inflammatory response
in hepatic diseases
GROUP 24
HEAD OF LABORATORY
Pedro Lorenzo Majano Rodríguez
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 ribavi-
Fig.2. Effects of apo B and apoE knockdown in HCV cell-to-cell
spread
rina, is frequently not effective depending on both viral
and host factors.
We are interested in understanding how HCV interacts
with target cells, with particular emphasis on the role of the
cellular factors implicated in different steps of the viral life
cycle including entry, assembly, egress and spread. Our
unpublished studies have determined that HCV egress is
a clathrin-dependent process. We have also analyzed the
role of apolipoproteins E and B in HCV cell to cell spread.
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
Fig.1. Effects of clathrin and AP-1 silencing in Huh cells permanently infected with HCVcc
• 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
– 61 –
GROUP MEMBERS
• Ignacio Benedicto Español
• Virgínia Manuela Gondar de Sousa e Silva
• Francisca Molina Jiménez
Hepatitis C. Fundación Mutua Madrileña. Duration:
2011 – 2013.
• Pedro Lorenzo Majano Rodríguez. Estudio de la interacción entre virus de la hepatitis C y sus células diana: papel
del "micorambiente hepático", la asociación con liproteínas y el modo de diseminación en distintas fases del ciclo
viral. ISCIII. PI13/00159. Duration: 2014 – 2016.
GROUP MEMBERS
• María Jesús Alonso Martín
• María Jesús Borque Iñurrita
• Luisa Consuelo García Buey
• Asunción García Sánchez
• Leticia González Moreno
• Ángel Hernández Bartolomé
• Jorge Mendoza Jiménez-Ridruejo
• Rosario López Rodríguez
• Yolanda Real Martínez
• Yolanda Rodríguez Muñoz
• María Paloma Sanz Cameno
YEAR
Total IF
Publication No.
Q1
2011
12,134
2
1
2012
16,440
5
3
2013
11,119
2
2
Sandoval P, Jiménez-Heffernan JA, Rynne-Vidal A,
Pérez-Lozano ML, Gilsanz A, Ruiz-Carpio V, Reyes R,
García-Bordas J, Stamatakis K, Dotor J, Majano PL,
Fresno M, Cabañas C, López-Cabrera M. Carcinomaassociated fibroblasts derive from mesothelial cells via
mesothelial to mesenchymal transition in peritoneal
metastasis. Journal of Pathology. 231(4) 517-531.
2013. PMID: 24114721. IF: 7,585. DOI:
10.1002/path.4281
Pérez-Lozano ML, Sandoval P, Rynne-Vidal A, Aguilera
A, Jiménez-Heffernan JA, Albar-Vizcaíno P, Majano PL,
Sánchez-Tomero JA, Selgas R, López-Cabrera M.
Functional Relevance of the Switch of VEGF
Receptors/Co-Receptors during Peritoneal DialysisInduced Mesothelial to Mesenchymal Transition. PLOS
ONE. 8(4):e60776. 2013. PMID: 23585849. IF: 3,534.
GROUP 23
HEAD OF LABORATORY
Ricardo Moreno Otero
– 62 –
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 altered expression of multiple angiogenic and fibrogenic-related factors during the course of CHC provides a valuable tool for the non-invasive assessment of
liver fibrosis, clue for clinical decision-making. Among
other clinical and demographic variables, peripheral
levels of angiopoietins correlated significantly with
hepatic fibrosis (Figure 1). Such finding allowed us to
develop a novel index for non invasive evaluation of liver
fibrosis, AngioScore, which was further validated in an
independent series of patients with CHC (PMID:
23823085).
Monocytes, essential precursors of antigen-presenting
cells, notably contribute to the pathogenesis of chronic inflammatory diseases and cancer. Interestingly, we
detected in the peripheral blood of CHC patients a significant increment of a subtype of monocytes, with
marked proangiogenic properties but notable immunosuppressive nature, able to express the angiopoietin
receptor Tie2 (TEMs), highlighting the relevant role of
Angiopoietin/Tie-2 axis on the regulation of inflammatory response during the progression of chronic liver diseases (PMID:23419030).
Fig.2. Decision tree model of response to CHC treatment, calculated
by the CHAID algorithm. The hierarchy model included IL-28B,
HDAC2, age and HDAC5 as significant factors for treatment decision. Pie charts indicate the rate (%) of response (black) and nonresponse (gray) in each group of patients after splitting for each
factor. The number of patients and the percentage that is represented in the overall population are indicated under each pie chart. Pc:
corrected P-value.
In addition, we have characterized the significance of
certain genetic variants of ISGs and HDACs for the
optimization of IL28B predictive value of therapeutic
response of CHC patients (Figure 2, PMID:23615070);
interestingly, some of them were markedly related to
fibrosis progression (Patents: ES-2422874_A1 and ES2423154_A1).
MAJOR GRANTS
Fig.1. Serum levels of Ang1 and Ang2 in the training set of 108 CHC
patients. Distribution of Angiopoietin-1 (A), Angiopoietin-2 (B), and
Ang2/Ang1 (C) serum concentrations against METAVIR fibrosis stage. Medians are represented by horizontal lines. Two-sided p-values were calculated by non-parametric Mann-Whitney U Test.
• 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.
– 63 –
AREA 1
• 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. Proyecto Coordinado.
Quasispecies study of hepatitis virus b and c (HBV and
HCV) by pyrosequencing during acute infection and
chronic antiviral treatment. MICINN-CDTI, Roche, ABL
y CIBERehd. Duration: 2010 - 2013.
• María Paloma Sanz Cameno. Implicación de polimorfismos genéticos de factores angiogénicos en la
etiopatogenia de la Hepatitis crónica C y su evolución
a carcinoma hepatocelular. AECC. Duration: 2010 2015.
• María Paloma Sanz Cameno. Influencia de las histonas
desacetilasas en la progresión de la hepatitis crónica C
a carcinoma hepatocelular: polimorfimos genéticos,
niveles de expresión y funcionalidad. Fundación Mutua
Madrileña. Duration: 2011 – 2014.
• María Paloma Sanz Cameno. Modulación epigenética
de la progresión de la Hepatitis crónica C a carcinoma
hepatocelular: papel de las variantes genéticas de las
histonas deacetilasas. Fundación Mutua Madrileña.
Duration: 2012 – 2015.
YEAR
Total IF
Publication No.
Q1
2011
66,493
19
8
2012
25,304
9
2
2013
50,027
15
6
Trapero-Marugán M, Moreno-Otero R. Letter: impact of
mild alcohol consumption in chronic hepatitis C treatment. Aliment Pharmacol Ther. 37(11):1118-1119. 2013.
PMID: 23656425. IF: 5,478. DOI: 10.1111/apt.12321
Moreno-Otero R. May oxidative stress contribute to
autoimmune hepatitis pathogenesis, and can antioxidants be of value as adjuvant therapy for refractory
patients?. Dig Dis Sci. 58(5):1440-1441. 2013. PMID:
23504353. IF: 2,550. DOI: 10.1007/s10620-013-2622-0
– 64 –
Moreno-Otero R. Liver biopsy in the management of
autoimmune hepatitis acute severe onset. Dig Dis Sci.
58(6):1808-1809. 2013. PMID: 23589142. IF: 2,550.
DOI: 10.1007/s10620-013-2662-5
Cabaleiro T, Roman M, Ochoa D, Talegon M, PrietoPerez R, Wojnicz A, Lopez-Rodriguez R, Novalbos J,
Abad-Santos F. Evaluation of the relationship between
sex, polymorphisms in CYP2C8 and CYP2C9, and pharmacokinetics of angiotensin receptor blockers. Drug
Metab Dispos. 41(1):224-9. 2013. PMID: 23118328. IF:
3,334. DOI: 10.1124/ dmd.112.046292
López-Rodríguez R, Hernández-Bartolomé Á, Borque
MJ, Rodríguez-Muñoz Y, Martín-Vílchez S, TraperoMarugán M, García-Buey L, Muñoz de Rueda P, Rodrigo
L, Vidal-Castiñeira JR, Salmerón J, Moreno-Otero R,
Sanz-Cameno P. Polymorphisms in histone deacetylases
improve the predictive value of IL-28B for chronic hepatitis C therapy. Genes Immun. 14(5):317-324. 2013.
PMID: 23615070. IF: 3,789. DOI: 10.1038/gene.2013.24
Cabaleiro T, López-Rodríguez R, Ochoa D, Román M,
Novalbos J, Abad-Santos F. Polymorphisms influencing
olanzapine metabolism and adverse effects in healthy
subjects. Hum Psychoparmacol Clin Exp. 28(3):205-14.
2013.
PMID:
23559402.
IF:
1,854.
DOI:
10.1002/hup.2308
Chaparro M, Trapero-Marugán M, Guijarro M, López C,
Moreno-Otero R, Gisbert JP. Dysplasia and colorectal cancer in a patient with ulcerative colitis and primary sclerosing
cholangitis: a case report and a short review of the literature.
J Crohns Colitis. 7(2):e61-5. 2013. PMID: 22552273. IF:
3,562. DOI: 10.1016/j.crohns.2012.04.005
Poynard T, Bruix J, Schiff ER, Diago M, Berg T, MorenoOtero R, Lyra AC, Carrilho F, Griffel LH, Boparai N, Jiang
R, Burroughs M, Brass CA, Albrecht JK. Improved
inflammatory activity with peginterferon alfa-2b maintenance therapy in non-cirrhotic prior non-responders: a
randomized study. J Hepatol. 58(3):452-9. 2013. PMID:
23159770. IF: 10,401. DOI: 10.1016/j.jhep.2012.11.001
Rodríguez-Muñoz Y, Martín-Vílchez S, López-Rodríguez
R, Hernández-Bartolomé Á, García-Buey L, Borque MJ,
AREA 1
Solano-Iturri G, García-Buey ML, BlancoSampascual S, Moreno-Otero R. Hepatitis B vaccine-induced liver injury. Med Clin (Barc).
141(11):510-1. 2013. PMID: 23611823. IF: 1,252.
DOI: 10.1016/j.medcli.2013.02.033
Moreno-Otero R. Pathogenesis, diagnosis and
treatment of non-alcoholic fatty liver disease. Rev
Esp Enferm Dig, 105(7):409-420. 2013. PMID:
24206551. IF: 1,317
Casals-Seoane F, Arberas-Díez B, García-Buey L.
Tenofovir treatment of the severe acute hepatitis B.
Rev Esp Enferm Dig. 105(1):57-59. 2013. PMID:
23548017. IF: 1,317
Martín-Vílchez S, Moreno-Otero R, Sanz-Cameno P,
Grupo CIBERehd de Hepatología del Hospital
Universitario de La Princesa. Effects of hepatitis B
virus X protein on chronic hepatitis B pathophysiology. Med Clin (Barc). 140(11):508-13. 2013. PMID:
23245531.
IF:
1,252.
DOI:
10.1016/j.medcli.2012.09.012
BOOKS
López-Rodríguez R, Cabaleiro T, Ochoa D, Román
M, Borobia AM, Carcas AJ, Ayuso C, Novalbos J,
Abad-Santos F. Pharmacodynamic genetic variants
related to ntipsychotic adverse reactions in healthy
volunteers. Pharmacogenomics. 14(10):1203-1214.
2013. PMID: 23859574. IF: 3,425. DOI:
10.2217/pgs.13.106
CLINICAL TRIALS
Hernández-Bartolomé A, López-Rodríguez R,
Rodríguez-Muñoz Y, Martín-Vílchez S, Borque MJ,
García-Buey L, González-Moreno L, Real Y, MorenoOtero R, Sanz-Cameno P. Angiopoietin-2 Serum Levels
Improve Noninvasive Fibrosis Staging in Chronic
Hepatitis C: A Fibrogenic-Angiogenic Link. PLoS One
8(6):e66143. 2013. PMID: 23823085. IF: 3,534
Martín-Domínguez
V,
González-Casas
R,
Mendoza-Jiménez-Ridruejo J, García-Buey L,
Luisa Consuelo García Buey. “Libro blanco de hepatología en España”. 2013. Asociación Española para
el Estudio del Hígado (AEEH).
PRINCIPAL RESEARCHER: GARCÍA BUEY, LUISACONSUELO
VICTRELIS LEAD-IN: Estudio observacional retrospectivo para describir la respuesta al lead-in con
peginterfereon/ribavirina como herramienta de
decisión clínica en pacientes tratados con Victrelis
(boceprevir); (Versión1: 20-11-12). MERCK SHARP &
DOHME DE ESPAÑA, S.A. MSD-BOC-2012-01
PRINCIPAL RESEARCHER: GARCÍA BUEY, LUISACONSUELO
Registro de telaprevir y boceprevir en la práctica clínica habitual; Versión 1.0 de 5 de Julio de 2013;
Enmienda 1 Versión 2.0 de 10-10-13). FUNDACIÓN
PÚBLICA ANDALUZA PROGRESO Y SALUD. FPSTEL-2013-01.
– 65 –
Moreno-Otero R, Sanz-Cameno P. Preliminary evidence of sustained expression of angiopoietin-2
during monocyte differentiation in chronic hepatitis
C. Liver Int. 33(6):864-870. 2013. PMID: 23419030.
IF: 4,412. DOI: 10.1111/liv.12125
Line 1.9
Mechanisms and
mediators of endocrine
diseases
GROUP 25
HEAD OF LABORATORY
Mónica Marazuela Azpíroz
GROUP MEMBERS
• Manuel Luque Ramírez
• Susanna Leskelä
• Andrés Pérez Casas
• Ana María Ramos Leví
• Javier Riveiro Villanueva
• Ana Rodríguez Muñoz
• Miguel Antonio Sampedro Núñez
• Ana Serrano Somavilla
MAJOR GRANTS
• Mónica Marazuela Azpíroz. Estudio del potencial
tolerogénico de células dendríticas y su interacción con células T reguladoras y linfocitos Th17
en pacientes con enfermedad tiroidea autoinmune. ISCIII. PI10/2521. Duration: 2011 - 2013.
• Mónica Marazuela Azpíroz. Study of “escape” to
pegvisomant (PEG) therapy in acromegalic
patients: its definition, prevalence and determinants. Pfizer. Duration: 2013 – 2014.
• Mónica Marazuela Azpíroz (Coordinator, Proyecto
Integrado Excelencia, PIE). Immunoregulatory
molecules as biomarkers predicting response to
biological therapies and disease severity in
immune-mediated inflamatory disorders. BIOIMID
– 66 –
PROJECT. ISCIII. PIE13/00041. Duration: 2014 –
2016.
• Mónica Marazuela Azpíroz. Identificación y caracterización de microRNAs implicados en la
etiopatogenia de las enfermedades tiroideas
autoinmunes. ISCIII. PI13/01299. Duration:
2014-2016.
.
PUBLICATIONS
(12)
[IF: 32,73]
YEAR
Total IF
Publication No.
Q1
2011
14,934
5
1
2012
12,200
4
1
2013
32,73
12
4
Ramos-Levi AM, Cabrerizo L, Matía P, SánchezPernaute A, Torres AJ, Rubio MA. Which criteria
should be used to define type 2 diabetes remission
after bariatric surgery? BMC Surg. 28;13:8. 2013.
PMID: 23537494. IF: 1,240. DOI: 10.1186/14712482-13-8
Cascón A, Inglada-Pérez L, Comino-Méndez I, de
Cubas AA, Letón R, Mora J, Marazuela M, Galofré
JC, Quesada-Charneco M, Robledo M. Genetics of
pheochromocytoma and paraganglioma in Spanish
pediatric patients. Endocr Relat. Cancer. 20(3):L16. 2013. PMID: 23404858. IF: 4.933. DOI:
10.1530/ERC-12-0339
Leskela S, Rodríguez-Muñoz A, de la Fuente H,
Figueroa-Vega N, Bonay P, Martín P, Serrano A,
Sánchez-Madrid F, González-Amaro R, Marazuela
M. Plasmacytoid dendritic cells in patients with
autoimmune thyroid disease. J Clin Endocrinol
Metab. 98(7):2822-2833. 2013. PMID: 23666960.
IF: 6,310. DOI: 10.1210/jc.2013-1273
Martin-Perez E, Capdevila J, Castellano D,
Jimenez-Fonseca P, Salazar R, Beguiristain-Gomez
A, Alonso-Orduña V, Martinez Del Prado P,
Villabona-Artero C, Diaz-Perez JA, Monleon A,
Marazuela M, Pachon V, Sastre-Valera J, Sevilla I,
AREA 1
Castaño A, Garcia-Carbonero R. Prognostic Factors
and
Long-Term
Outcome
of
Pancreatic
Neuroendocrine Neoplasms: Ki-67 Index Shows a
Greater Impact on Survival than Disease Stage. The
Large Experience of the Spanish National Tumor
Registry RGETNE. Neuroendocrinology. 98(2):156168. 2013. PMID: 23988576. IF: 4,934.
DOI: 10.1159/000355152
Ramos-Levi A, Sanchez-Pernaute A, Matia P,
Cabrerizo L, Barabash A, Hernandez C, Calle-Pascual
A, Torres A, Rubio M. Diagnosis of Diabetes Remission
After Bariatic Surgery May be Jeopardized by
Remission Criteria and Previous Hypoglycemic
Treatment. Obes Surg. 23(10):1520-1526. 2013.
PMID: 23702908. IF: 3,102. DOI: 10.1007/s11695013-0995-y
Ramos-Levi AM, Matia P, Cabrerizo L, Barabash A,
Torrejón MJ, Sánchez-Pernaute A, Torres AJ, Rubio
MA. C-peptide levels predict type 2 diabetes remission
after bariatric surgery. Nutr Hosp. 25(5):1599-1603.
2013. PMID: 24160222. IF: 1,250. DOI:
10.3305/nh.2013.28.5.6554
Ramos-Levi AM, Sanchez-Pernaute A, Cabrerizo L,
Matia P, Barabash A, Hernandez C, Calle-Pascual AL,
Torres AJ, Rubio MA. Remission of Type 2 Diabetes
Mellitus Should Not Be the Foremost Goal after
Bariatric Surgery. Obes Surg. 23(12):2020-5. 2013.
PMID: 23893315. IF: 3,739. DOI: 10.1007/s11695013-1032-x
Ramos-Leví AM, Pérez-Ferre N, Sánchez-Pernaute A,
Torres García AJ, Rubio Herrera MA. Severe vitamin A
deficiency after malabsortive bariatric surgery. Nutr
Hosp. 28(4):1337-1340. 2013. PMID: 23889662. IF:
1,250. DOI: 10.3305/nh.2013.28.4.6610
Cabrerizo García L, Ramos-Leví A, Moreno Lopera C,
Rubio Herrera MA. Update on pharmacology of obesity: benefits and risks. Nutr Hosp Suppl. 5:121-7. 2013.
PMID:
24010752.
IF:
1,250.
DOI:
10.3305/nh.2013.28.sup5.6927
Ramos-Leví AM, Sánchez-Pernaute A, Rubio Herrera
MA. Dermatitis and optic neuropathy due to zinc deficiency after malabsortive bariatric surgery. Nutr Hosp.
28(4):1345-7. 2013. PMID: 23889664. IF: 1,250. DOI:
10.3305/nh.2013.28.4. 6606
Bernabeu I, Alvarez-Escolá C, Paniagua AE, Lucas T,
Pavón I, Cabezas-Agrícola JM, Casanueva FF,
Marazuela M. Pegvisomant and cabergoline combination therapy in acromegaly. Pituitary. 16(1):101-8.
2013. PMID: 22396133. IF: 2,222. DOI:
10.1007/s11102-012-0382-z
CLINICAL TRIALS
PRINCIPAL RESEARCHER: MARAZUELA AZPIROZ,
MÓNICA
Estudio ACROSTART: Estudio español, retrospectivo y
observacional para determinar el tiempo transcurrido
hasta alcanzar la normalización hormonal según las
dosis de inicio e intervalos de administración de
Somatulina Autogel comúnmente utilizados en la práctica clínica habitual de tratamientos de pacientes
acromegálicos; (Versión final: 19-11-12). IPSEN PHARMA, S. A. PS-SOM-2012-01
– 67 –
Ramos-Leví AM, Matías-Guiu JA, Guerrero A,
Sánchez-Pernaute A, Rubio MA. Peroneal palsy after
bariatric surgery; is nerve decompresion always necessary?. Nutr Hosp. 28(4):1330-1332. 2013. PMID:
23889660.
IF:
1,250.
DOI:
10.3305/nh.2013.28.4.6495
Line 1.10
Children´s development
(obesity and growth)
GROUP 26
HEAD OF LABORATORY
Jesús Argente Oliver
• Julie Ann Chowen King. Regulación de los astrocitos
hipotalámicos por la leptina: implicaciones en el control metabólico sistémico. MICINN. BFU2011-27492.
Duration: 2012 – 2014.
• Jesús Argente Oliver. Obesidad infantil grave de
comienzo precoz: Fundamentos metabólicos, hormonales, genéticos, genómicos y metabolómicos.
ISCIII. PI13/02195. Duration: 2014 – 2016.
GROUP MEMBERS
• Pilar Argente Arizón
• Eva Baquedano Caballero
• Vicente Barrios Sabador
• Emma Burgos Ramos
• Sandra Canelles Ortiz
• David Castro González
• Julie Ann Chowen King
• Esther de la Fuente Martín
• Francisca Díaz González
• Laura María Frago Fernández
• Cristina García Cáceres
• Gabriel Ángel Martos Moreno
• María Teresa Muñoz Calvo
• Jesús Pozo Román
• Oscar Rubio Cabezas
• Silvia Tapia González
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 • Jesús Argente Oliver. Fisiopatología de la Obesidad.
ISCIII. CIBER: CB06/03/0022. Duration: 2006 • Jesús Argente Oliver. Obesidad infantil grave de
comienzo precoz: fundamentos metabólicos, genéticos y proteomicos. ISCIII. PI10/00747. Duration: 2011
- 2013.
– 68 –
YEAR
Total IF
Publication No.
Q1
2011
61,045
21
7
2012
96,523
31
12
2013
41,756
10
6
Fuente-Martín E, García-Cáceres C, Díaz F, ArgenteArizón P, Granado M, Barrios V, Argente J, Chowen
JA. Hypothalamic inflammation without astrogliosis in
response to high sucrose intake is modulated by
neonatal nutrition in male rats. Endocrinology
154(7):2318-2330. 2013. PMID: 23671260. IF: 4,664.
DOI: 10.1210/en.2012-2196
Chowen JA, Argente J, Horvath TL. Uncovering novel
roles of nonneuronal cells in body weight homeostasis and obesity. Endocrinology. 154(9):3001-3007.
2013. PMID: 23798599. IF: 4,664. DOI:
10.1210/en.2013-1303
Donoso MÁ, Muñoz-Calvo MT, Barrios V, Martínez G,
Hawkins F, Argente J. Increased leptin/adiponectin
ratio and free leptin index are markers of insulin resistance in obese girls during pubertal development.
Horm Res Paediatr. 80(5):363-70. 2013. PMID:
24217338. IF: 1,713. DOI: 10.1159/000356046
Fernández-Rebollo E, Lecumberri B, Gaztambide S,
Martinez-Indart L, Perez de Nanclares G, Castaño L;
Spanish PHP Group. Endocrine profile and phenotype-(epi)genotype correlation in Spanish patients
with pseudohypoparathyroidism. J Clin Endocrinol
AREA 1
Clayton P, Bonnemaire M, Dutailly P, Maisonobe P,
Naudin L, Pham E, Zhang Z, Grupe A, Thiagalingam
A, Denèfle P; EPIGROW Study Group. Characterizing
short stature by insulin-like growth factor axis status
and genetic associations: results from the prospective, cross-sectional, epidemiogenetic EPIGROW
study. J Clin Endocrinol Metab. 98(6):E1122-E1130.
2013. PMID: 23596138. IF: 6,310. DOI:
10.1210/jc.2012-4283.
Baquedano E, Chowen JA,
Differential effects of GH and
on astrocytes. J Endocrinol.
PMID: 23792323. IF: 3,586.
0053
Argente J, Frago LM.
GH-releasing peptide-6
218(3):263-274. 2013.
DOI: 10.1530/JOE-13-
Perianes-Cachero A, Burgos-Ramos E, PueblaJiménez L, Canelles S, Frago LM, Hervás-Aguilar A,
de Frutos S, Toledo-Lobo MV, Mela V, Viveros MP,
Argente J, Chowen JA, Arilla-Ferreiro E, Barrios V.
Acute up-regulation of the rat brain somatostatin
receptor-effector system by leptin is related to activation of insulin signaling and may counteract central
leptin actions. Neuroscience. 252:289-301. 2013.
PMID:
23973620.
IF:
3,327.
DOI:
10.1016/j.neuroscience.2013.08.019
Diz-Chaves Y, Baquedano E, Frago LM, Chowen
JA, Garcia-Segura LM, Arevalo MA. Maternal stress
alters the developmental program of embryonic hippocampal neurons growing in vitro. Psychoneuroendocrinology.
38(3):455-9.
2013.
PMID:
22832184. IF: 5,591. DOI: 10.1016/j.psyneuen.
2012.07.001
Fuente-Martin E, Garcia-Caceres C, Morselli E, Clegg
DJ, Chowen JA, Finan B, Brinton RD, Tschöp MH.
Estrogen, astrocytes and the neuroendocrine control
of metabolism. Rev Endocr Metab Disord. 14(4):3318. 2013. PMID: 24009071. IF: 3,807. DOI:
10.1007/s11154-013-9263-7
Martos-Moreno GÁ, Barrios V, Chowen JA, Argente J.
Adipokines in childhood obesity. Vitam Horm.
91:107-142. 2013. PMID: 23374715. IF: 1,784. DOI:
10.1016/B978-0-12-407766-9.00006-7
BOOKS
Barrios V, Burgos-Ramos E, Argente J. Insulin-leptin signaling in the brain. Metabolic Syndrome and
Neurological Disorders. 2013. Wiley-Blackwell.
ISBN: 978-1-118-39527.
Barrios V, Burgos-Ramos E. Valores de referencia.
Bioquímica. Manual de Endocrinología Pediátrica.
2013. Editorial Médica Panamericana. ISBN: 9788-498-356762.
– 69 –
Metab. 98(5):E996-1006. 2013. PMID: 23533243. IF:
6,310. DOI: 10.1210/jc.2012-4164
Line 1.11
Metabolic syndrome
and vascular risk
insulin sensitivity: a cross-sectional analysis of the RISC
Study. Diabetes Care. 36(12):4125-31. 2013. PMID:
24130363. IF: 8,570. DOI: 10.2337/dc13-0682
GROUP 27
Romacho T, Villalobos LA, Cercas E, Carraro R, SánchezFerrer CF, Peiró C. Visfatin as a novel mediator released by
inflamed human endothelial cells. PLoS One. 8(10):e78283. 2013. PMID: 24130902. IF: 3,534. DOI: 10.1371/journal.
pone.0078283
HEAD OF LABORATORY
Raffaele Carraro Casieri
GROUP MEMBERS
• Andrea Azcárate Villalón
• Elena Cercas Alonso
• Lourdes Martínez-Piñeiro Muñoz
• Erika Palacios Rosas
• María Concepción Peiró Vallejo
• Tania del Mar Romacho Romero
• Carlos Félix Sánchez Ferrer
• Isabelle Sharmiashvili
• Iñigo Tejado Elviro
• Marta Vázquez Bella
• Laura Alicia Villalobos Rodríguez
GROUP 5
HEAD OF LABORATORY
Carmelo García Monzón
GROUP MEMBERS
• Faustino Manuel La Banda Brusi
• Enrique Chávez Jiménez
• María Eugenia Miquilena Colina
• Javier Rodríguez de Cía
• Alicia Sáez Sáez
• Rodolfo Javier Vargas Castrillón
YEAR
Total IF
Publication No.
Q1
2011
39,347
9
5
2012
31,512
6
5
2013
17,637
3
3
Kozakova M, Natali A, Dekker J, Beck-Nielsen H, Laakso
M, Nilsson P, Balkau B, Ferrannini E; RISC Investigators.
Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk
study. Arterioscler Thromb Vasc Biol. 33(6):1409-1417.
2013. PMID: 23599442. IF: 5,533. DOI: 10.1161/ATVBAHA.112.300948
Baldi S, Bonnet F, Laville M, Morgantini C, Monti L, Hojlund
K, Ferrannini E, Natali A; RISC Investigators. Influence of
apolipoproteins on the association between lipids and
– 70 –
RESEARCH INTEREST
During the last decade, genetic association studies
have proved to be useful for identifying biomarkers
for susceptibility to complex multifactorial diseases,
including non-alcoholic fatty liver disease (NAFLD),
but, in most of the cases, there is a lack of functional testing of the identified genes. Therefore, we aimed
to identify genetic variants that are associated with,
and directly influence the development of, NAFLD.
For this purpose, a candidate gene-association study
was performed, followed by functional analyses of
the associated gene. Allele frequencies of 3,072 single-nucleotide polymorphisms (SNPs) in 92 genes
AREA 1
Fig.1. Differential expression of SLC2A1 in liver biopsies. Y-axis
indicates the FC of SLC2A1 mRNA expression detected in control and NAFLD liver biopsies relative to the characterized housekeeping genes (GAPDH and ARP). Values of relative FC and
their standard deviation (SD) are detailed in the table, where
“n” is the number of biopsies considered in each group and a t
test was performed
Fig.2. OA treatment induces steatosis in siSLC2A1-THLE2 cells.
(A) fluorescent images of double staining THLE2-silenced cells.
Lipid droplets were stained with BODIPY 493/503 (green), and
nucleus was stained with DAPI (blue). Note that after 1 mM OA
treatment, siSLC2A1-silenced cells present higher lipid droplets levels, also shown. (B) By scanning microscope (Nomaski). (C) Graphic representation of TG quantification using the
Menarine (Pomezia, Italy) commercial kit. Eight independent
experiments were performed in triplicates. Diferences between
siControl and siSLC2A1-transfected cells were statistically significant (*P<0.05).
were characterized in 69 NAFLD patients and 217
healthy individuals. Several SNPs of SLC2A1 (solute
carrier family 2 member 1) showed association with
NAFLD, but not with T2DM, with the haplotype con-
A cell-free form of the fatty acid translocase CD36
has recently been identified in human plasma and
was termed soluble CD36 (sCD36). A recent large
cross-sectional study on non-diabetic healthy subjects found that sCD36 is associated with fatty liver,
suggesting that sCD36 might be a biomarker of liver
fat. Therefore, we aimed to determine serum sCD36
levels in a population of 399 individuals including
patients with biopsy-proven NAFLD, with chronic
hepatitis C and with histologically normal liver,
searching for potential correlations between circulating sCD36 and hepatic CD36 expression as well as
clinical, metabolic and histological features of each
liver disease. The main conclusion of this study is
that serum level of sCD36 correlates with the histological grade of steatosis and is an independent factor associated with advanced steatosis in NAFLD but
not in chronic hepatitis C patients. This easily accessible biomarker, if appropriately validated by independent researchers as a potential marker of steatosis severity, may represent a promising tool for future
studies on the epidemiology, non-invasive diagnosis,
treatment outcome and prognosis of NAFLD (2).
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. Duration: 2011 - 2013.
– 71 –
taining the minor allele of SLC2A1 sequence being
related to the susceptibility to develop NAFLD. Geneexpression analysis demonstrated a significant
down-regulation of SLC2A1 in NAFLD livers. In vitro
silencing of SLC2A1 induces an increased oxidative
stress activity and a higher lipid accumulation under
oleic acid treatment. Based on these findings, we
conclude that genetic variants of SLC2A1 are associated with NAFLD and in vitro down-regulation of
this gene promotes lipid accumulation (1).
• 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
• Carmelo García Monzón. Papel de la hipoxia intermitente del síndorme de apnea-hipopnea obstructiva del sueño en la patogenia del hígado graso no
alchólico. ISCIII. PI13/01299. Duration: 2014 –
2016.
– 72 –
YEAR
Total IF
Publication No.
Q1
2011
23,692
3
3
2012
26,121
4
4
2013
14,024
2
1
García-Monzón C, Lo Iacono O, Crespo J, RomeroGómez M, García-Samaniego J, Fernández-Bermejo
M, Domínguez-Díez A, Rodríguez de Cía J, Sáez A,
Porrero JL, Vargas-Castrillón J, Chávez-Jiménez E,
Soto-Fernández S, Díaz A, Gallego-Durán R,
Madejón A, Miquilena-Colina ME. Increased soluble
CD36 is linked to advanced steatosis in non-alcoholic fatty liver disease. Eur J Clin Invest. 44(1):6573. 2013. PMID: 24134687. IF: 2,834. DOI:
10.1111/eci.12192
Vazquez-Chantada
M,
Gonzalez-Lahera
A,
Martinez-Arranz I, Garcia-Monzon C, Regueiro MM,
Garcia-Rodriguez JL, Schlangen KA, Mendibil I,
Rodriguez-Ezpeleta N, Lozano JJ, Banasik K,
Justesen JM, Joergensen T, Witte DR, Lauritzen T,
Hansen T, Pedersen O, Veyrie N, Clement K,
Tordjman J, Tran A, Marchand-Brustel YL, Buque X,
Aspichueta P, Echevarria-Uraga JJ, Martin-Duce A,
Caballería J, Gual P, Castro A, Mato JM, MartinezChantar ML, Aransay AM. Solute carrier family 2
member 1 is involved in the development of nonalcoholic fatty liver disease. Hepatology. 57(2):505-14.
2013. PMID: 22961556. IF: 11,190. DOI:
10.1002/hep.26052
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.
– 73 –
AREA 2
NEUROTRANSMISSION,
PHARMACOLOGICAL NEUROPROTECTION
AND NEURODEGENERATIVE AND
NEUROPSYCHIATRIC DISEASES
– 74 –
AREA 2
NEUROTRANSMISSION, PHARMACOLOGICAL
NEUROPROTECTION AND NEURODEGENERATIVE
AND NEUROPSYCHIATRIC DISEASES
GROUP 28
HEAD OF LABORATORY
GROUP MEMBERS
• Juan Alberto Arranz Tagarro
• Enrique Calvo Gallardo
• Cristóbal de los Ríos Salgado
• Francisco Javier Egea Máiquez
• Manuela García López
• Marcos Maroto Pérez
• Juan Fernando Padín Nogueira
• Esther Parada Pérez
• Mercedes Villarroya Sánchez
• Aneta Wojnicz
MAJOR GRANTS
• Antonio García García. RENEVAS (Red
Neurovascular).
FIS-RETICS-RENEVAS.
RD06/0026/0009. Duration: 2006 - 2013.
• 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.
• Cristóbal de los Ríos Salgado. Fármacos moduladores del balance del Ca2+ celular regulado
por la mitocondria para el tratamiento de la
isquemia cerebral y la enfermedad de alzheimer.
MICINN. SAF2012-36093. Duration: 2013 –
• Cristóbal de los Ríos Salgado. La proteína fosfatasa 2A como diana terapeútica para el desarrollo de nuevos fármacos para el tratamiento de
enfermedades
neurodegenerativas.
ISCIII.
PI13/00789. Duration: 2014 – 2016.
PUBLICATIONS
(10)
[IF: 36,433]
YEAR
Total IF
Publication No.
Q1
2011
45,763
14
5
2012
37,253
11
2
2013
36,433
10
3
Padín J.F, Fernández-Morales J.C, Olivares R, Vestring
S, Arranz-Tagarro J.A, Calvo-Gallardo E, De Pascual
R, Gandía L. and García A.G. Plasmalemmal sodiumcalcium exchanger shapes the calcium and exocytotic signals of chromaffin cells at physiological temperature. Am J Physiol Cell Physiol. 305(2):C160-72. 2013.
PMID: 23596174. IF: 3,674. DOI: 10.1152/ajpcell.00016.2013
García-Parra P, Maroto M, Cavaliere F, NaldaizGastesi N, Alava J.I, García A.G, López De Muniaín
– 75 –
AREA 3AREA 2 AREA 1
Line 2.1
Neuropharmacology
and neuroprotection
Neurotransmission, pharmacological neuroprotection and
neurodegenerative and neuropsychiatric diseases
A and Izeta A. A neural extracellular matrix-based
method for in vitro hippocampal neuron culture and
dopaminergic differentiation of neural stem cells.
BMC Neuroscience. 14:48. 2013. PMID: 23594371.
IF: 2,845. DOI: 10.1186/1471-2202-14-48
Cañas F, Alptekin J, Azorín J.M, Emsley R, García
A.G, Gorwood P, Haddad P.M, Naber D, Olivares
J.M, Papagergiou G. and Roca M. Improving treatment adherence in your patents with Schizophrenia:
the STAY initiative. Clin. Drug. Invest. 33(2):97-107.
2013. PMID: 23288695. IF: 1,704. DOI:
10.1007/s40261-012-0047-8
Musial D.C, Da Silva E.D, Da Silva R.M, MirandaFerreira R, De Lima-Landman T.R, Jurkiewicz A,
García A.G. and Jurkiewicz N.H. Increase of
angiotensin-converting enzyme activity and peripheral sympathetic dysfunction could contribute to
hypertension development in streptozotocininduced diabetic rats. Diabetes & Vasc. Dis. Res.
10(6):498-504. 2013. PMID: 23975725. IF: 3,043.
DOI: 10.1177/1479164113496441
De Pascual R, Miranda-Ferreira R, Galvão K.M,
Lameu C, Ulrich H, Smaili S.S, Jurkiewicz A, García
A.G. and Gandía L. Lower density of L-type and
higher density of P/Q-type of calcium channels in
chromaffin cells of hypertensive, compared with
normotensive rats. Eur. J. Pharmacol. 706(1-3):2535. 2013. PMID: 23499685. IF: 2,684. DOI:
10.1016/j.ejphar.2013.02.046
Maroto M , Fernández-Morales J.C, Padín J.F,
González J.C, Hernández-Guijo J.M, Montell E,
Vergés J, De Diego A.M.G. and García A.G.
Chondroitin sulfate, a major component of the perineuronal net, elicits inward currents, cell depolarization and calcium transients by acting on AMPA
and kainate receptors of hippocampal neuros. J.
Neurochem. 125 (2) 205-213. 2013. PMID:
23350646. IF: 4,244. DOI: 10.1111/jnc.12159
León R, Garcia AG, Marco-Contelles J. Recent
advances in the multitarget-directed ligands
approach for the treatment of Alzheimer's disease.
– 76 –
Med Res Rev. 33(1):139-89. 2013. PMID:
21793014. IF: 8,131. DOI: 10.1002/med.20248
Alonso E, Cano-Abad M.F, Moreno-Ortega A.J,
Novalbos J, Milla J, García A.G. and Ruiz-Nuño A.
Nanomolar ouabain elicits apoptosis through a
direct action on HeLa cell mitocondria. Steroids.
78(11):1110-1118. 2013. PMID: 23933121. IF:
2,716. DOI: 10.1016/j.steroids.2013.07.010
García-Parra P, Naldaiz-Gastesi N, Maroto M, Padín
J.F, Goicoechea M, Aiastui A, Fernández-Morales
J.C, García-Belda P, Lacalle J, Álava J.I, GarcíaVerdugo J.M, García A.G, Izeta A. and López De
Munain A. Murine muscle engineered from dermal
precursors: an in vitro model for skeletal muscle
generation, degeneration and fatty infiltration.
Tissue Engineering. 20(1):28-41. 2013. PMID:
23631552. IF: 4,065. DOI: 10.1089/ten.TEC.
2013.0146
Cunha MP, Martín-de-Saavedra MD, Romero A,
Parada E, Egea J, Del Barrio L, Rodrigues AL,
López MG. Protective effect of creatine against 6hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells: Involvement of intracellular signaling pathways. Neuroscience. 238:18594. 2013. PMID: 23485810. IF: 3,327. DOI:
10.1016/j.neuroscience.2013.02.030
GROUP 29
HEAD OF LABORATORY
María Francisca Cano Abad
GROUP MEMBERS
• Rafael León Martínez
• Ana José Moreno Ortega
• Ana Ruiz Nuño
AREA 2
• Rafael León Martínez. Nrf2-ARE pathway up-regulation
combined with GSK3-beta inhibition as key targets for
a novel disease modifying multitarget drug development program for neurodegenerative diseases. ISCIII.
CP11/00165. Duration: 2012- 2016.
• 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. PI10/01426. Duration: 2011 - 2013.
• Rafael León Martínez. Desarrollo de fármacos contra
enfermedades neurodegenerativas basados en dianas
no-convencionales. MICINN. SAF2012-37182.
Duration: 2013 –
• Rafael León Martínez. Non-conventional target
approach for drug discovery against neurodegenerative diseases: Nrf2 upregulation. EU/PRG. MARCO.
Marie Curie Career Integration Grant (CIG) 2012. FP7People-2012. CIG-322156. Duration: 2012 – 2016.
PUBLICATIONS
(3)
[IF: 12,557]
YEAR
Total IF
Publication No.
Q1
2011
13,011
4
1
2012
8,461
2
2
2013
12,557
3
2
Moreno JM, Wojnicz A, Steegman JL, Cano-Abad MF,
Ruiz-Nuño A. Imatinib assay by high-performance liquid
chromatography in tandem mass spectrometry with
solid-phase extraction in human plasma. Biomed.
Chromatogr. 27(4):502-8. 2013. PMID: 23034891. IF:
1,662. DOI: 10.1002/bmc.2819
Wojnicz A, Cabaleiro-Ocampo T, Román-Martínez M,
Ochoa-Mazarro D, Abad-Santos F, Ruiz-Nuño A. A simple assay for the simultaneous determination of human
plasma albendazole and albendazole sulfoxide levels by
high performance liquid chromatography in tandem
mass spectrometry with solid-phase extraction. Clin
Chim Acta. 15;426:58-63. 2013. PMID: 24008168. IF:
2,764. DOI: 10.1016/j.cca.2013.08.019
León R, Garcia AG, Marco-Contelles J. Recent
advances in the multitarget-directed ligands approach
for the treatment of Alzheimer's disease. Med Res Rev.
33(1):139-89. 2013. PMID: 21793014. IF: 8,131. DOI:
10.1002/med.20248
– 77 –
AREA 3AREA 2 AREA 1
MAJOR GRANTS
Line 2.2
Neurotransmission
in the hippocampus
chromaffin cells at physiological temperature. Am J Physiol
Cell Physiol. 305(2):C160-72. 2013. PMID: 23596174. IF:
3,674. DOI: 10.1152/ajpcell.00016.2013
De Pascual R, Miranda-Ferreira R, Galvão K.M, Lameu
C, Ulrich H, Smaili S.S, Jurkiewicz A, García A.G. and
Gandía L. Lower density of L-type and higher density of
P/Q-type of calcium channels in chromaffin cells of
hypertensive, compared with normotensive rats. Eur. J.
Pharmacol. 706(1-3):25-35. 2013. PMID: 23499685.
IF: 2,684. DOI: 10.1016/j.ejphar.2013.02.046
GROUP 30
HEAD OF LABORATORY
Luis Gandía Juan
GROUP MEMBERS
• Inés Colmena Crespo
• Ángela Orozco Alarcón
• Ricardo de Pascual y del Castillo
• Carmen Pérez de Nanclares Fernández
GROUP 31
HEAD OF LABORATORY
Jesús Miguel Hernández Guijo
MAJOR GRANTS
• 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
2011
12,287
4
2
2012
3,567
2
-
2013
6,358
2
1
Padín J.F, Fernández-Morales J.C, Olivares R, Vestring S,
Arranz-Tagarro J.A, Calvo-Gallardo E, De Pascual R,
Gandía L. and García A.G. Plasmalemmal sodium-calcium
exchanger shapes the calcium and exocytotic signals of
– 78 –
GROUP MEMBERS
• Elisa Albiñana Durá
• José Carlos González San Frutos
YEAR
Total IF
Publication No.
Q1
2011
10,933
3
1
2012
7,847
2
1
2013
7,317
2
1
Maroto, M. , Fernández-Morales, J.C., Padín, J.F.,
González, J.C., Hernández-Guijo, J.M., Montell, E.,
Vergés, J., De Diego, A.M.G. and García, A.G.
Chondroitin sulfate, a major component of the perineuronal net, elicits inward currents, cell depolarization and
calcium transients by acting on AMPA and kainate
receptors of hippocampal neuros. J. Neurochem. 125
(2) 205-213. 2013. PMID: 23350646. IF: 4,244. DOI:
10.1111/jnc.12159
AREA 2
nels in bovine chromaffin cells: an integrative study.
Pflugers Arch. 465(12):1727-40. 2013. PMID:
23821297. IF:3,073. DOI: 10.1007/s00424-0131311-3
AREA 3AREA 2 AREA 1
Fuentes-Antrás J, Osorio-Martínez E, Ramírez-Torres
M, Colmena I,Fernández-Morales JC, HernándezGuijo JM. Methylmercury decreases cellular excitability by a direct blockade of sodium and calcium chan-
– 79 –
Line 2.3
Clinical pharmacology
and pharmacogenetics
GROUP 32
HEAD OF LABORATORY
GROUP MEMBERS
• María Teresa Cabaleiro Ocampo
• María Fagoaga Torija
• Igone Marrodán Remírez
• María Isabel Moreno Arza
• Dolores Ochoa Mazarro
• Rocío María Prieto Pérez
• Angela Rivas Acosta
• Manuel Román Martínez
• Sergio Daniel Sánchez Rojas
• Javier Soriano Ventura
• María Talegón García
• Ana María Tello Miller
• Sarahi Elizabeth Valdez Acosta
• Carmen Verge González
RESEARCH INTEREST
The aim of the investigation performed in this group is to
evaluate pharmacokinetics, pharmacodynamics and
pharmacogenetics in order to predict the response of the
patients to drugs, in terms of efficacy and safety.
Our group has wide experience 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 stud-
– 80 –
Fig.1.
Time-concentration profiles of celecoxib (200 mg) after administration to healthy volunteers depending on polymorphism. (A) CYP2C9:
*l/*l (n=13), *l/*2 (n=7), *l*3 (n=3), and *3/*3 (n=1). (B) CYP2C8: *l/*l
(n=10), 2 carriers (n=1), 3 carriers (n=7), and 4 carriers (n=2).
ies in healthy volunteers, and studies in patients to probe
the efficacy of new drugs in collaboration with several specialists in the hospital and primary care. Our group has
performed more than 30 clinical trials during 2013.
Pharmacogenetic research is related with various clinical
diseases, trying to look for new pharmacogenetic markers
to predict drug responses, both therapeutic and toxic, that
could help physicians to decide the best treatment for
every patient. In 2013, 240 patients benefited from pharmacogenetic testing.
During 2013, our group had published 15 articles related
to pharmacogenetics of several drugs (antipsychotics,
anti-inflammatory drugs, antidepressants, biological
drugs, angiotensin receptor blockers) and clinical trials. In
addition, we participated in 2 projects, one about biomarkers predicting response to biological drugs in psoriasis, and other about generic drugs.
MAJOR GRANTS
• Francisco Abad Santos. Consorcio de apoyo a la
investigación Biomédicas en red. CAIBER.
CAI08/01/0018. Duration: 2009 -2013.
AREA 2
• Francisco Abad Santos. Plataforma de Ensayos
Clínicos: Plataforma de unidades de investigación
clínica y ensayos clínicos. ISCIII. PT13/0002/0027.
Duration: 2014 – 2016.
• Francisco Abad Santos. Estudios de marcadores
epigenéticos asociados a la respuesta a fármacos
biológicos en el tratamiento de la psoriasis. ISCIII.
PI13/01598. Duration: 2014 – 2016.
YEAR
Total IF
Publication No.
Q1
2011
15,862
5
2
2012
8,841
5
1
2013
46,685
14
8
Abad-Santos F, García-Díez A, Daudén E. The relationship between tumour necrosis factor (TNF)-a
promoter and IL12B/IL-23R genes polymorphisms
and the efficacy of anti-TNF-a therapy in psoriasis: a
case-control study. Br J Dermatol. 169(4):819-29..
2013. PMID: 23662788. IF: 4,100. DOI:
10.1111/bjd.12425
Wojnicz A, Cabaleiro-Ocampo T, Román-Martínez M,
Ochoa-Mazarro D, Abad-Santos F, Ruiz-Nuño A. A
simple assay for the simultaneous determination of
human plasma albendazole and albendazole sulfoxide
levels by high performance liquid chromatography in
tandem mass spectrometry with solid-phase extraction. Clin Chim Acta. 15;426:58-63. 2013. PMID:
24008168. IF: 2,764. DOI: 10.1016/j.cca.2013.08.019
Cabaleiro T, Roman M, Ochoa D, Talegon M, Prieto-
Perez R, Wojnicz A, Lopez-Rodriguez R, Novalbos J, AbadSantos F. Evaluation of the relationship between sex, polymorphisms in CYP2C8 and CYP2C9, and pharmacokinetics of angiotensin receptor blockers. Drug Metab Dispos.
41(1):224-9. 2013. PMID: 23118328. IF: 3,334. DOI:
10.1124/dmd.112.046292
Talegón M, Prieto-Pérez R, García-Díez A, Daudén E, AbadSantos F. Association between psoriasis and polymorphisms in the TNF, IL12B, and IL23R genes in Spanish
patients. Eur J Dermatol. 23(5):640-5. 2013. PMID:
24135300. IF: 1,953. DOI: 10.1684/ejd.2013.2144
Cabaleiro T, López-Rodríguez R, Ochoa D, Román M,
Novalbos J, Abad-Santos F. Polymorphisms influencing olanzapine metabolism and adverse effects in
healthy subjects. Hum Psychoparmacol Clin Exp.
28(3):205-14. 2013. PMID: 23559402. IF: 1,854. DOI:
10.1002/hup.2308
Prieto-Pérez R, Ochoa D, Cabaleiro T, Román M,
Sánchez-Rojas SD, Talegón M, Abad-Santos F.
Evaluation of the relationship between polymorphisms
in CYP2C8 and CYP2C9 and the pharmacokinetics of
celecoxib. J Clin Pharmacol. 53(12):1261-7. 2013.
PMID: 23996211. IF: 2,472. DOI: 10.1002/jcph.169
Cabaleiro T, Prieto-Pérez R, Ochoa D, Abad-Santos F.
Application of pharmacogenomics and other new technologies to drug development. Med Clin (Barc).
140(12):558-63. 2013. PMID: 23582104. IF: 1,252.
DOI: 10.1016/j.medcli.2013.02.010
Almoguera B, Riveiro-Alvarez R, Lopez-Castroman J,
Dorado P, Vaquero-Lorenzo C, Fernandez-Piqueras J,
Llerena A, Abad-Santos F, Baca-García E, Dal-Ré R,
Ayuso C; Spanish Consortium of Pharmacogenetics
Research in Schizophrenia. CYP2D6 poor metabolizer
status might be associated with better response to
risperidone treatment. Pharmacogenet Genomics.
23(11):627-630.2013. PMID: 24026091. IF: 3,450.
DOI: 10.1097/FPC.0b013e3283659a94
Prieto-Pérez R, Cabaleiro T, Daudén E, Ochoa D,
Román M, Abad-Santos F. Pharmacogenetics of topi-
– 81 –
AREA 3AREA 2 AREA 1
• Francisco Abad Santos. Búsqueda de marcadores
genéticos predictores de respuesta a fármacos
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.
cal and systemic treatment of psoriasis.
Pharmacogenomics 14(13):1623-1634. 2013. PMID:
24088133. IF: 3,425. DOI: 10.2217/pgs.13.163
Almoguera B, Riveiro-Alvarez R, Lopez-Castroman J,
Dorado P, Vaquero-Lorenzo C, Fernandez-Piqueras
J, Llerena A, Abad-Santos F, Baca-García E, Dal-Ré
R, Ayuso C. Association of common genetic variants
with risperidone adverse events in a Spanish schizophrenic
population.
Pharmacogenomics
J.
13(2):197-204. 2013. PMID: 22212732. IF: 5,513.
DOI: 10.1038/tpj.2011.57
Prieto-Pérez R, Cabaleiro T, Dauden E, Abad-Santos
F. Gene polymorphisms that can predict response to
anti-TNF therapy in patients with psoriasis and related autoimmune diseases. Pharmacogenomics J.
13(4):297-305. 2013. PMID: 23337970. IF: 5,513.
DOI: 10.1038/tpj.2012.53
González-Vacarezza N, Abad-Santos F, CarcasSansuan A, Dorado P, Peñas-Lledó E, EstévezCarrizo F, Llerena A. Use of pharmacogenetics in
bioequivalence studies to reduce sample size: an
example
with
mirtazapine
and
CYP2D6.
Pharmacogenomics J. 13(5):452-5. 2013. PMID:
22733239. IF: 5,513. DOI: 10.1038/tpj.2012.29
López-Rodríguez R, Cabaleiro T, Ochoa D, Román
M, Borobia AM, Carcas AJ, Ayuso C, Novalbos J,
Abad-Santos F. Pharmacodynamic genetic variants
related to antipsychotic adverse reactions in healthy
volunteers. Pharmacogenomics. 14(10):1203-1214.
2013. PMID: 23859574. IF: 3,425. DOI:
10.2217/pgs.13.106
Abad-Pérez D, Novella-Arribas B, RodríguezSalvanés FJ, Sánchez-Gómez LM, García-Polo I,
Verge-González C and Suárez-Fernández C on
behalf of the NISH group. Effect of oral nitrates on
pulse pressure and arterial elasticity in patients
aged over 65 years with refractory isolated systolic
hypertension: study protocol for a randomized controlled trial. Trials. 14;14:388. 2013. PMID:
24228894. IF: 2,117. DOI: 10.1186/1745-621514-388
– 82 –
CLINICAL TRIALS
PRINCIPAL RESEARCHER: OCHOA MAZARRO,
DOLORES
Ensayo clínico cruzado aleatorizado de bioequivalencia de
dos formulaciones de olmesartán comprimidos recubiertos
de 40mg, tras su administración en dosis única a voluntarios sanos en ayunas; (versión 1:11-12-12) LABORATORIOS ALTER, S.A. ITHUEC-OLM/12-7. EudraCT: 2012005323-32
DOLORES
Ensayo clínico aleatorizado para evaluar la biodisponibilidad
de ibuprofeno (arginina)/tramadol hidrocloruro 400/37,5 mg
gránulos para solución oral y 400mg de Espidifen (ibuprofeno arginina) gránulos para so--lución oral más 37,5mg de
Adolonta gotas orales en solución tras su administración
oral en dosis única a voluntarios sanos en ayunas; (versión
1.0: 15-01-13). LABORATORIOS FARMALIDER, S.A.
FMLD-IOTRA-20_FI. EudraCT: 2013-000196-32
DOLORES
Ensayo clínico cruzado y aleatorizado de bioequivalencia de
dos formulaciones de bosentán comprimidos recubiertos
con película de 125mg, tras su administración oral en dosis
única a voluntarios sanos en ayunas, con diseño replicado;
(Versión 1: 05-03-13). LABORATORIOS NORMON, S.A. NBOS-13-187. EudraCT: 2013-000813-20
DOLORES
Ensayo clínico aleatorizado, abierto, cruzado, para estudiar
la bioequivalencia de dos formulaciones de ibuprofeno
600mg comprimidos recubiertos con película frente a
Neobrufen 600mg comprimidos recubiertos con película
tras su administración oral en dosis a voluntarios sanos en
ayunas; (versión 1: 01-04-13). LABORATORIOS FARMALIDER, S.A. FMLD-IBUPROFENO600-21. EudraCT:
2013-001518-13
DOLORES
dos formulaciones de rosuvastina 20mg comprimidos
AREA 2
DOLORES
dos formulaciones de rosuvastina 20mg comprimidos
recubiertos con película, tras su administración oral en
dosis única a voluntarios sanos en ayunas; (versión 1: 0705-13). LABORATORIOS ALTER, S.A. ITHUEC-RSV/13-1.
EudraCT: 2013-002047-28
DOLORES
dos formulaciones de rasagilina comprimidos de 1mg, tras
su administración oral en dosis única a voluntarios sanos en
ayunas; (Versión 1.0: 14-05-13). LABORATORIOS FARMALIDER, S.A. FMLD-RABAT-22. EudraCT: 2013-00215914
DOLORES
dos formulaciones de olmesartán comprimidos recubiertos
de 40mg, tras su administración en dosis única a voluntarios sanos en ayunas; (Versión 1: 04- -06-13). LABORATORIOS ALTER, S.A. ITHUEC-OLM/13-2. EudraCT: 2013002443-28
DOLORES
Ensayo clínico aleatorizado para evaluar la biodisponibilidad
de paracetamol/ibuprofeno 500/200 mg suspensión oral y
500 mg de Apiretal 100mg/ml solución oral (paracetamol)
más 200 mg de Junifen suspensión« (ibuprofeno) tras su
administración oral en dosis única a voluntarios sanos en
ayunas; (versión 1: 20-06-13). LABORATORIOS FARMALIDER, S.A. FMLD-UMBRIEL-23. EudraCT: 2013002762-40
DOLORES
dos formulaciones de olmesartán/hidroclorotiazida comprimidos recubiertos de 40/25mg, tras su administración en
dosis única a voluntarios sanos en ayunas;(Versión 1: 0409-13). LABORATORIOS ALTER, S.A. ITHUEC-OLMHTZ/13-3. EudraCT: 2013-002661-19
DOLORES
dos formulaciones de comprimidos bucodispersables de
aripiprazol de 10mg, tras su administración oral en dosis
única a voluntarios sanos en ayunas; (Versión 1: 17-10-13).
LABORATORIOS NORMON, S.A. N-ARI-13-195.
EudraCT: 2013-004146-42
DOLORES
dos formulaciones de diclofenaco 50mg comprimidos gastrorresistentes, tras su administración oral en dosis única a
voluntarios sanos en ayunas; (Versión 1: 21-10-13). LABORATORIOS NORMON, S.A. N-DIC-13-194. EudraCT:
2013-003992-36
DOLORES
Ensayo clínico aleatorizado de bioequivalencia de dos formulaciones de comprimidos recubiertos con película de
tadalafilo 20mg, tras su administración oran en dosis única
a voluntarios sanos en ayunas en un diseño cruzado de dos
etapas; (Versión 1: 30-10-13). LABORATORIOS KERN
PHARMA S.L. KP-TDF-59. EudraCT: 2013-001079-20
DOLORES
Ensayo clínico cruzado, aleatorizado de bioequivalencia de
dos formulaciones de efavirenz comprimidos recubiertos de
600mg, tras su administración oral en dosis única a voluntarios sanos; (Versión 1: 28-11-13). LABORATORIOS KERN
PHARMA S.L. KP-EFA-64. EudraCT: 2013-004289-32
PRINCIPAL RESEARCHER: TELLO MILLER, ANA
MARÍA
Estudio de la personalidad de los voluntarios que participan en ensayos clínicos de fase I; (Versión 1: 08-0113). ATM-TP-2013/01
– 83 –
AREA 3AREA 2 AREA 1
recubiertos con película, tras su administración oral en
dosis única a voluntarios sanos en ayunas; (Versión 1: 1405-13). LABORATORIOS KERN PHARMA S.L. KP-RSV58. EudraCT: 2013-001078-15
Line 2.4
Diagnostic and
therapeutic advances
in affective disorders
GROUP 33
HEAD OF LABORATORY
José Luis Ayuso Mateos
GROUP MEMBERS
• José David Albillo Labarra
• Montserrat Alcañiz Rodríguez
• Celia Anaya Suárez
• Francisco Félix Caballero Díaz
• María Cabello Salmerón
• Elena Ezquiaga Terrazas
• Luis Miguel García Olmos
• Eduardo García-Camba de la Muela
• Miguel Ángel Gorriti Irigai
• Matilde Hernández Álvarez
• Itziar Leal Leturia
• Pilar López García
• Herminio Martínez Cano
• Blanca Mellor Marsá
• Marta Miret García
• Roberto Nuevo Benítez
• María del Mar Rivas Rodríguez
• Jesús Valle Fernández
RESEARCH INTEREST
The team’s research topics are the following:
• Nosology of mental disorders: Our research team
keeps on collaborating with the World health organization in the revision of the International Classification
of Diseases 10th edition (ICD-10).
• Study of efficacy and efficiency of clinical interven-
– 84 –
Fig.1. Diurnal variation of experienced well-being (positive and negative affect) in population samples of 6 different countries (Ayuso Mateos, 2013)
Fig.2. Cumulative distribution functions of Quality of Life (WHO-QOL)
scores by group of age in three different European countries and total.
tions in affective disorders: Our team is working on a
randomized clinical trial to verify the efficacy of
methylphenidate in patients with acute bipolar mania
(MEMAP study). In addition we are conducting a multiapproach study for the identification of the available
interventions for targeting psychosocial difficulties in
major depression (meta-analyses and expert consultation) (MARATONE project). Finally our team has
demonstrated the usefulness of a novel psychological
coadjutant intervention (functional remediation) specifically aimed to improve neurocognitive deficits and
global functioning of bipolar disorders.
• Assessment of the health status, quality of life, and
well-being in large population studies: Our research
staff has been publishing numerous scientific works
from a health survey comprising representative sample
of adults from Poland, Finland, and Spain (COURAGE
in Europe project). Our team has also compared these
data to make other cross-national comparisons with
other available datasets from other countries (e.g. India,
Mexico) and validating new tools to measure the wellbeing at population level. In addition, the team has
received funding from Carlos III National health institute
to conduct the second wave of this health survey
including the Spanish population.
• Identification of the priorities for mental health research
in Europe: Our team is also participating in an important European project aimed to identify the main gaps
of knowledge in mental health research and to set the
priorities for mental health and well-being research in
Europe (ROAMER project)
• Prevention and promotion of mental health in low and
middle income countries (LAMICs): We are participating in an international project (EMERALD project) aimed
to enhance mental health in LAMICs by means of
improvement of all the systems related to health care.
The project is willing to identify the main barriers that
health systems have to overcome to apply treatments
of mental disorders and to subsequently foster and
improve the quality of mental health care in LAMICs.
• Study of the environmental and genetic risk factors for
the development of psychotic episodes: Our group is
working in collaboration with Niño Jesús hospital to
identify some of the risk factors for first psychotic
episodes. This is part of a multi-center longitudinal
study (AGES-CM project) in which we are interviewing
patients and their families to collect social, psychological and genetic factors that may be responsible for the
onset of this symptomatology. In addition, it is expected to conduct a psycho-educational intervention within this program to improve the autonomy and selfawareness of the younger participants.
•
•
•
•
•
•
•
•
•
MAJOR GRANTS
• José Luis Ayuso Mateos. Proyecto Coordinado. An
age-friendly city for successful ageing. Caixa
Recerca. Duration: 2011 - 2013.
• José Luis Ayuso Mateos. Use of antidepressants in
the last decade and its relation to mortality and sui-
•
cide-related events, with special focus on children
and adolescents. CIBERSAM Convocatoria
Intramural. 11INT1. Duration: 2011 - 2013.
José Luis Ayuso Mateos. Proyecto Coordinado.
Metilfenidato de liberación inmediata en la mejoría
sintomática de la manía aguda: un estudio frente a
placebo. CAIBER. 1392-D-079-EudraCT 2010023992-24. Duration: 2011 - 2013.
José Luis Ayuso Mateos. Metilfenidato de liberación
inmediata en la mejoría sintomática de la manía
aguda: un estudio frente a placebo. CIBERSAM,
Convocatoria Intramural. 11INT2. 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. Una hoja de ruta para la
investigación en salud mental y bienestar en Europa:
ROAMER. MICINN. ACI Promociona. ACI-PRO2011-1080. 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 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.
Roberto Nuevo Benítez. Bienestar y salud mental y
física en población general: un análisis longitudinal.
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.
José Luis Ayuso Mateos. Mental health training
through research network in Europe. MARATONE. VII
Programa Marco de la UE. FP7-31795. Duration:
2013 - 2017.
– 85 –
AREA 3AREA 2 AREA 1
AREA 2
• Marta Miret García. Desarrollo y validación de un
instrumento para evaluar calidad de vida en personas de edad avanzada. Convocatoria intramural
CIBERSAM. 13INT. Duration: 2013 – 2014.
• José Luis Ayuso Mateos. Depresión, bienestar subjetivo, salud y mortalidad: Un estudio longitudinal en
población general. ISCIII. PI13/00059. Duration:
2014 – 2016.
2,491.
DOI:
Caballero FF, Miret M, Power M, Chatterji S, TobiaszAdamczyk B, Koskinen S, Leonardi M, Olaya B, Haro JM,
Ayuso-Mateos JL. Validation of an instrument to evaluate
quality of life in the aging population: WHOQOL-AGE.
Health and quality of life outcomes. 11(1):177. 2013. PMID:
24152691. IF: 2,099. DOI: 10.1186/1477-7525-11-177
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(1-2):65-71. 2013. PMID:
22862890. IF: 3,705. DOI: 10.1016/j.jad.2012.06.005
YEAR
Total IF
Publication No.
Q1
2011
61,137
16
8
2012
59,692
20
4
2012
117,703
18
7
Duarte J, García Olmos LM, Mendoza A, Clavería LE. The
natural history of Parkinson's disease in the province of
Segovia: mortality in a longitudinal study (20-year follow-up).
Acta Neurol Scand. 127(5):295-300. 2013. PMID:
22957805. IF: 2,437. DOI: 10.1111 /ane.12003
Nuevo R, Van Os J, Arango C, Chatterji S, Ayuso-Mateos
JL. Evidence for the early clinical relevance of hallucinatorydelusional states in the general population. Acta Psychiatr
Scand. 127(6):482-93. 2013. PMID: 22943634. IF: 5,545.
DOI: 10.1111/acps.12010
Kluge M, Hegerl U, Sander C, Dietzel J, Mergl R, Bitter I,
Demyttenaere K, Gusmão R, Gonzalez-Pinto A, Sola VP,
Vieta E, Juckel G, Zimmermann US, Bauer M, Sienaert P,
Quintão S, Edel MA, Bolyos C, Ayuso-Mateos JL, LópezGarcía P. Methylphenidate in mania project (MEMAP): study
protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania
with methylphenidate. BMC psychiatry. 13:71. 2013. PMID:
23446109. IF: 2,237. DOI: 10.1186/1471-244X-13-71
Mendez-Bustos P, de Leon-Martinez V, Miret M, BacaGarcia E, Lopez-Castroman J. Suicide reattempters: a systematic review. Harv Rev Psychiatry. 21(6):281-95. 2013.
– 86 –
PMID:
24201820.
IF:
10.1097/HRP.0000000000000001
Reed GM, Roberts MC, Keeley J, Hooppell C, Matsumoto
C, Sharan P, Robles R, Carvalho H, Wu C, Gureje O, LealLeturia I, Flanagan EH, Correia JM, Maruta T, AyusoMateos JL, de Jesus Mari J, Xiao Z, Evans SC, Saxena S,
Medina-Mora ME. Mental health professionals' natural taxonomies of mental disorders: implications for the clinical utility of the ICD-11 and the DSM-5. J Clin Psychol.
69(12):1191-212. 2013. PMID: 24122386. IF: 2,111 DOI:
10.1002/jclp.22031.
Torres CV. Sola RG. Pastor J. Pedrosa M. Navas M. GarcíaNavarrete E. Ezquiaga E. García-Camba E. Long-term
results of posteromedial hypothalamic deep brain stimulation for patients with resistant aggressiveness. J Neurosurg.
119(2):277-287. 2013. PMID: 23746102. IF: 3,227. DOI:
10.3171/2013.4.JNS121639
Huerta-Ramírez R, Bertsch J, Cabello M, Roca M, Haro JM,
Ayuso-Mateos JL. Diagnosis delay in first episodes of major
depression: A study of primary care patients in Spain.
Journal of affective disorders. 150(3):1247-50. 2013. PMID:
23827532. IF: 3,705. DOI: 10.1016/j.jad.2013.06.009
Caballero FF, Miret M, Olaya B, Perales J, Lopez Riadura R,
Haro JM, Chatterji S, Ayuso Mateos JL. Evaluation of Affect
in Mexico and Spain: Psychometric Properties and
Usefulness of an Abbreviated Version of the Day
Reconstruction Method. Journal of Happiness studies. 14.
2013. IF: 1,772. DOI: 10.1007/s10902-013-9456-5
AREA 2
Miret M, Ayuso-Mateos JL, Sanchez-Moreno J, Vieta E.
Depressive disorders and suicide: Epidemiology, risk factors, and burden. Neurosci Biobehav Rev. 37(10 Pt
1):2372-4. 2013. PMID: 23313644. IF: 10,284. DOI:
10.1016/j.neubiorev.2013.01.008
Ayuso-Mateos JL, Miret M, Caballero FF, Olaya B, Haro JM,
Kowal P, Chatterji S. Multi-country evaluation of affective
experience: validation of an abbreviated version of the day
reconstruction method in seven countries. PloS
one.8(4):e61534. 2013. PMID: 23626697. IF: 3,534. DOI:
10.1371/journal.pone.0061534
Ayesa-Arriola R, Pérez-Iglesias R, Rodríguez-Sánchez JM,
Pardo-García G, Tabares-Seisdedos R, Ayuso-Mateos JL,
Vázquez-Barquero JL, Crespo-Facorro B. Predictors of
neurocognitive impairment at 3years after a first episode
non-affective psychosis. Prog Neuropsychopharmacol Biol
Psychiatry. 43:23-8. 2013. PMID: 23228461. IF: 4,025.
DOI: 10.1016/j.pnpbp.2012.11.012
Lopez-Garcia P, Young Espinoza L, Molero Santos P, Marin
J, Ortuño Sanchez-Pedreño F. Impact of COMT genotype
on cognition in schizophrenia spectrum patients and their
relatives. Psychiatry Res. 208(2):118-24. 2013. PMID:
23102922.
IF:
2,682.
DOI:
10.1016/j.psychres.2012.09.043
Torrent C, Bonnin C del M, Martínez-Arán A, Valle J, Amann
BL, González-Pinto A, Crespo JM, Ibáñez Á, Garcia-Portilla
MP, Tabarés-Seisdedos R, Arango C, Colom F, Solé B,
Pacchiarotti I, Rosa AR, Ayuso-Mateos JL, Anaya C,
Fernández P, Landín-Romero R, Alonso-Lana S, Ortiz-Gil J,
Segura B, Barbeito S, Vega P, Fernández M, Ugarte A,
Subirà M, Cerrillo E, Custal N, Menchón JM, Saiz-Ruiz J,
Rodao JM, Isella S, Alegría A, Al-Halabi S, Bobes J, Galván
G, Saiz PA, Balanzá-Martínez V, Selva G, Fuentes-Durá I,
Correa P, Mayoral M, Chiclana G, Merchan-Naranjo J,
Rapado-Castro M, Salamero M, Vieta E. Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study. The American journal of psychiatry.
170(8):852-9. 2013. PMID: 23511717. IF: 13,559. DOI:
10.1176/appi.ajp.2012.12070971
Moreno C, Nuevo R, Chatterji S, Verdes E, Arango C,
Ayuso-Mateos JL. Psychotic symptoms are associated
with physical health problems independently of a mental
disorder diagnosis: results from the WHO World Health
Survey. World Psychiatry.12(3):251-7. 2013. PMID:
24096791. IF: 12,846. DOI: 10.1002/wps.20070
Cieza A, Bostan C, Ayuso-Mateos JL, Oberhauser C,
Bickenbach J, Raggi A, Leonardi M, Vieta E, Chatterji S.
The psychosocial difficulties in brain disorders that explain
short term changes in health outcomes. BMC psychiatry.
11; 13(1):78. 2013. PMID: 23497332. IF: 2,237. DOI:
10.1186/1471-244X-13-78
CLINICAL TRIALS
PRINCIPAL RESEARCHER: AYUSO MATEOS, JOSÉLUIS
Estudio transversal y revisión retrospectiva de los
pacientes con síntomas persistentes de esquizofrenia
para estimar la utilización de recursos médicos y la carga
de la enfermedad; (versión 1.1: 18-12-12). F. HOFFMANN-LA ROCHE LTD. ROC-ESQ-2013-01 (MN28222)
Ambiente y genes en Esquizofrenia-grupos de investigación de la Comunidad de Madrid AGES-S2010/BMD2422 (AGES); (Versión AGES-CM)
Estudio de fase 3, multicéntrico, aleatorizado, doble
ciego, controlado con placebo y con comparador activo
de la administración de brexpiprazol(OPC-34712) en
dosis flexible como tratamiento adyuvante de adultos
con trastorno depresivo mayor: Estudio Delphius;
(Versión 11-10-12). OTSUKA PHARMACEUTICAL
DEVELOP. & COMMERC. INC. 331-12-282. EudraCT:
2012-003948-67
– 87 –
AREA 3AREA 2 AREA 1
Ayuso-Mateos JL, Barros PP, Gusmão R. Financial crisis,
austerity, and health in Europe. Lancet. 382(9890):391-2.
2013. PMID: 23911370. IF: 39,207. DOI: 10.1016/S01406736(13)61663-3
Line 2.5
Neurosurgery of epilepsy
GROUP 34
HEAD OF LABORATORY
Rafael García de Sola
GROUP MEMBERS
• Angela Adgyan de Abreu Arvelo
• Eva de Dios Tomás
• Luís Domínguez Gadea
• Eduardo García Navarrete
• Oscar Garnés-Camarena Estruch
• José Luis Martínez-Chacón Crespo
• María Luisa Meilán Paz
• Marta Navas García
• Guillermo Ortega Rabbione
• Desislava Panova Tzonova
• Jesús Pastor Gómez
• Paloma Pulido Rivas
• Cristina Virginia Torres Díaz
• Lorena Vega Zelaya
• Rybel Wix Ramos
RESEARCH INTEREST
The presence of spikes and sharp waves in recordings of epileptic patients contaminates background
signal synchronization. When estimating functional
connectivity between extended cortical areas, the
influence of epileptic spikes in specific areas should
be considered; however, this step is sometimes
overlooked. We present a simple method for quantifying the influence of epileptic activity on background signal synchronization.
Standard synchronization measures were calculated
for both pure correlated Gaussian signals and correlat-
– 88 –
Fig.1. Analysis of subdural electrodes (electrocorticography) showing
normal and abnormal cortical activity in the epileptogenic network
(patient with focal epilepsy).
Fig.2. Analysis of scalp and foramen ovale electrodes showing abnormal desynchronization (electrodes Rf5 and Rf6) in the right mesial
area, in a patient with right temporal lobe epilepsy.
ed Gaussian signals with different levels of epileptic
spikes in order to determine the influence of epileptic
activity on synchronization estimates. Synchronization
from invasive epileptic recordings (e.g., depth electrodes) displays a much higher bias due to epileptic
activity than superficial electrodes. Moreover, statistical
methods such as mutual information are more affected
by spike presence than phase synchronization methods. The influence of spikes is far greater at low values
of background synchronization. The information provided by this procedure makes it possible to differentiate
true background synchronization from spike synchronization. Thus, our procedure serves as a guide for
analyzing synchronization and functional connectivity
calculations in epileptic recordings.
AREA 2
• 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:
2011 - 2013.
• Jesús Pastor Gómez. Tratamiento radioquirúrgico de
alta precisión en epilepsia temporal mesial. ISCIII.
PI12/02839. Duration: 2013 – 2015.
YEAR
Total IF
Publication No.
Q1
2011
8,242
8
-
2012
8,446
6
1
2013
28,96
8
3
Pastor J, Vega-Zelaya L, Pulido P, Garnés-Camarena
O, Abreu A, Sola RG. Role of intraoperative neurophysiological monitoring during fluorescence-guided resection surgery. Acta Neurochir (Wien). 155(12):2201-13.
2013. PMID: 24072425. IF: 1,546. DOI:
10.1007/s00701-013-1864-0
Medina-Rodríguez EM, Arenzana FJ, Pastor J,
Redondo M, Palomo V, Sola RG, Gil C, Martínez A,
Bribián A, de Castro F. Inhibition of endogenous phosphodiesterase 7 promotes oligodendrocyte precursor
differentiation and survival. Cell Mol Life Sci.
70(18):3449-3462. 2013. PMID: 23661015. IF: 5,856.
DOI: 10.1007/s00018-013-1340-2
Navarrete M, Perea G, Maglio L, Pastor J, García de
Sola R, Araque A. Astrocyte calcium signal and gliotransmission in human brain tissue. Cereb Cortex.
23(5):1240-6. 2013. PMID: 22581850. IF: 8,305. DOI:
10.1093/cercor/bhs122
Valentín A, García Navarrete E, Chelvarajah R, Torres
C, Navas M, Vico L, Torres N, Pastor J, Selway R,
Sola RG, Alarcon G. Deep brain stimulation of the
centromedian thalamic nucleus for the treatment of
generalised and frontal epilepsies. Epilepsia.
54(10):1823-33. 2013. PMID: 24032641. IF: 4,584.
DOI: 10.1111/epi.12352
Pastor J, Sola RG, Vega-Zelaya L, Garnés O, Ortega
G. New network and synchronization approaches in
focal research epilepsy and treatment. Health.
5(6A1):1-8. 2013. IF: 1,324. DOI: 10.4236/health.
2013.56A1001
Torres CV, Sola RG, Pastor J, Pedrosa M, Navas M,
García-Navarrete E, Ezquiaga E, García-Camba E.
Long-term results of posteromedial hypothalamic deep
brain stimulation for patients with resistant aggressiveness. J Neurosurg. 119(2):277-287. 2013. PMID:
23746102.
IF:
3,227.
DOI:
10.3171/2013.4.JNS121639
García-Navarrete E, Torres CV, Gallego I, Navas M,
Pastor J, Sola RG. Response to "Vagus nerve stimulation: urgent need for the critical reappraisal of clinical
effectiveness". Seizure. 66(6):490-491. 2013. PMID:
23587867.
IF:
2,059.
DOI:
10.1016/j.seizure.2013.03.009
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. 2013. PMID: 23041031. IF: 2,059. DOI:
10.1016/j.seizure.2012.09.008
BOOKS
Pastor J. Diagnóstico funcional: Neurofisiología.
Cirugía raquimedular. 2013. Viguera Editores.
Pastor J. Quirófano: Neurofisiología intraoperatoria.
– 89 –
AREA 3AREA 2 AREA 1
MAJOR GRANTS
Pastor J. Cirugía medular. Cirugía raquimedular.
2013. Viguera Editores.
Pastor J. Instrumentación en patología cervical.
– 90 –
BOOKS
PRINCIPAL RESEARCHER: PASTOR GÓMEZ,
JESÚS
Tratamiento radioquirúrgico de alta precisión en
epilepsia temporal mesial; (Versión 1: 29-05-13).
FUNDACION DE INVESTIGACION BIOMEDICA
HUP.
AREA 2
GROUP 35
HEAD OF LABORATORY
José Aurelio Vivancos Mora
GROUP MEMBERS
• Teresa Carreras Rodríguez
• Ana Beatriz Gago Veiga
• Lydia López Manzanares
• Virginia Meca Lallana
• Noemí Mora Pérez
• Florentino Nombela Merchán
• Gemma Reig Roselló
• Mónica Sobrado Sanz
• Álvaro Ximenez-Carrillo Rico
GROUP ASSOCIATED 1
HEAD OF LABORATORY
Ignacio Lizasoain Hernández
GROUP MEMBERS
• Tamara Atanes Pérez
• Iván Ballesteros Martín
• Roberto Cañadas Martín
• María Isabel Cuartero Desviat
• Isaac García de Yébenes y Castro
• Víctor Manuel González Romera
• Macarena Hernández Jiménez
• Olivia Hurtado Moreno
• Ana Moraga Yébenes
• María Ángeles Moro Sánchez
RESEARCH INTEREST (G.35 & G.ASSOC 1)
The Neurological Service and Stroke Unit of Hospital
Universitario de la Princesa (2013) is a medical service
of the Spanish public health system specialized in neurological diseases. It is a public provider of comprehensive neurological care for the metropolitan population of
Madrid, integrated in the reference area #2 with
312,743 inhabitants who live in the Chamartín and
Salamanca districts. It is also a reference centre for specific processes and special procedures (Stroke Unit,
Stroke Code and Thrombolysis, Neurointerventional
Procedures, etc.) for the population attached to area #2,
which currently includes Hospital del Henares (164,810
inhabitants) and all area #3 (Alcalá de Henares and
Torrejón de Ardoz with 380,757 inhabitants). Currently,
the outpatient activity includes more than 19.000 office
visits. The Neurology Service of La Princesa University
Hospital has also a neurology certified program for
under and postgraduate students belonging to the
Autonoma University of Madrid and a well-known clinical research tradition of almost 50 years.
The main research lines of The Neurology Service of La
Princesa University Hospital 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
– 91 –
AREA 3AREA 2 AREA 1
Line 2.6
Cerebrovascular
diseases
Fig.2. Peritoneal dialysis decreases serum glutamate levels in patients
with severe chronic kidney disease. (A) Serum glutamate concentration in patients prior to and after one 4-hour session of peritoneal
dialysis. Glutamate levels were determined fluorimetrically using glutamate dehydrogenase. (B) Time-dependent accumulation of glutamate in the dialysate. Godino et al., JCI. 2013.
Fig.1. Peritoneal dialysis attenuates ischemia-induced increases in
plasma glutamate concentration (A) and cerebral infarct size (B). Godino et al., JCI. 2013.
• Cephaleas.
- Botulinum toxin in chronic migraine
- Occipital nerve block for the treatment of cephaleas.
The results obtained by our group during 2013 include:
Eight papers published in international and national
journals belonging to the Neurosciences field (N Engl J
Med., J Clin Invest, Stroke, Radiology, Rev Neurol,
Neurología); One publicly funded project in Stroke
(phase IIa clinical trial; translational study); Award at
project Cephaleas by Sociedad Española de
Neurología; About 9 ongoing clinical trials (in Stroke,
Multiple Sclerosis, Epilepsy and Alzheimer´s and
Parkinson´s disease -private companies) and 7 observational studies; Participation in numerous international
and national projects (29th ECTRIMS, European Stroke
Conference, LXV Sociedad Española de Neurología).
– 92 –
The Neurovascular Research Unit (UIN), located at the
Department of Pharmacology of the School of
Medicine at the Universidad Complutense is an associated group of the “Instituto de Investigación Sanitaria
La Princesa (IIS IP)”. It was formed in 1996 and since
then our team has been studying the pathophysiology
and pharmacology of stroke. Our unit is devoted to the
study of the cerebrovascular disease (stroke) from a
basic point of view but also with a strong translational
projection, a vocation due to our location in a School of
Medicine and developed through a tight partnership
with IIS IP.
The results obtained by our group during 2013, include
15 papers published in international journals belonging
to the Neurosciences field and directly related to cerebral ischemia (J Clin Invest, Stroke, Radiology,
Hypertension, J Biol Chem, FEBS J, J. Neurochem), 8
research projects and 1 PhD Thesis, and participation
in numerous meetings and conferences.
MAJOR GRANTS GR.35
• José Aurelio Vivancos Mora. Open, randomized and controlled study of safety and viability, to evaluate the neuroprotective effect of plasma glutamate dialysis in acute
AREA 2
MAJOR GRANTS GR.AS.1
• 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.
• Ignacio Lizasoain Hernández. CITI-SIRCTUS. Ferrer
Internacional SA. Duration: 2012 – 2014
• 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/BMD2336, 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.
• Ignacio Lizasoain Hernández. Proyecto ApTLR:
Desarrollo de aptámeros moduladores de la actividad de receptores TLR-4, enfermedad cerebrovascular (ictus). Aptus-Biotech. Duration: 2013 2014.
• Ignacio Lizasoain Hernández. RETICS. Enfermedad
vascular cerebral (ICTUS). MSC. INVICTUS
RD12/0014/0003. Duration: 2013 - 2016.
• María Ángeles Moro Sánchez. BrainFate (El Destino
del Cerebro): Modulacion de la respuesta neuroinflamatoria en el ictus. MINECO. SAF2012-33216.
Duration: 2013 – 2015.
PUBLICATIONS GR.35 (11) [IF GR35: 97,96]
YEAR
Total IF
Publication No.
Q1
2011
2012
25,809
7
4
36,416
15
2013
4
97,96
11
6
Bustamante J, Leal O, Soto de Prado D, Domínguez
L, Nombela F, Guijarro M, Gamallo C. Hamartomatous
malformation of the left atrium: a rare cause of recurrent transient ischemic attack. Ann Thorac Surg.
96(3):1068-70. 2013. PMID: 23992702. IF: 3,631.
DOI: 10.1016/j.athoracsur.2013.01.036
Segura T, Ayo-Martín O, Gómez-Fernandez I, Andrés
C, Barba MA, Vivancos J. Cerebral hemodynamics
and endothelial function in patients with Fabry disease. BMC Neurol. 11;13:170. 2013. PMID:
24207059. IF: 2,486. DOI: 10.1186/1471-2377-13170
Godino MD, Romera VG, Sánchez-Tomero JA,
Pacheco J, Canals S, Lerma J, Vivancos J, Moro MA,
Torres M, Lizasoain I, Sánchez-Prieto J. Amelioration
of ischemic brain damage by peritoneal dialysis. J Clin
Invest. 123(10):4359-4363. 2013. PMID: 23999426.
IF: 13,765. DOI: 10.1172/JCI67284
Zapata-Wainberg G, Vivancos J. Images in clinical
medicine: Bilateral earlobe creases. N Engl J Med.
368(24):e32. 2013. PMID: 23758258. IF: 54,420.
DOI: 10.1056/NEJMicm1213006
Rodríguez-Yáñez M, Castellanos M, Freijo MM,
López Fernández JC, Martí-Fàbregas J, Nombela F,
Simal P, Castillo J; por el Comitéad hoc del Grupo de
Estudio de Enfermedades Cerebrovasculares de la
SEN:, Díez-Tejedor E, Fuentes B, Alonso de Leciñana
M, Alvarez-Sabin J, Arenillas J, Calleja S, Casado I,
Dávalos A, Díaz-Otero F, Egido JA, Gállego J, García
Pastor A, Gil-Núñez A, Gilo F, Irimia P, Lago A,
Maestre J, Masjuan J, Martínez-Sánchez P, MartínezVila E, Molina C, Morales A, Purroy F, Ribó M, Roquer
J, Rubio F, Segura T, Serena J, Tejada J, Vivancos J.
Clinical practice guidelines in intracerebral haemorrhage. Neurologia. 28(4):236-49. 2013. PMID:
– 93 –
AREA 3AREA 2 AREA 1
ischemic stroke. MSPSI. EC11-109 (SAS/2885/2011).
Duration: 2012 - 2013.
• José Aurelio Vivancos Mora. Imagen molecular multimodal de la inflamación. Consejeria de Educación de la
Comunidad de Madrid. S2010/BMD-23494. Duration:
2012 – 2015.
21570742. IF: 1,352. DOI: 10.1016/j.nrl.2011.
03.010
Hernández MA, Mora S; grupo de trabajo del Estudio
SLIMS. Use of the PRIMUS scale to assess quality of
life in a Spanish population of multiple sclerosis
patients. Neurologia. 28(6):340-7. 2013. PMID:
23067780. IF: 1,352. DOI: 10.1016/j.nrl.2012.06.003
Serena J, Irimia P, Calleja S, Blanco M, Vivancos J,
Ayo-Martín O. Ultrasound measurement of carotid
stenosis: recommendations from the Spanish Society
of Neurosonology. Neurologia. 28(7):435-442. 2013.
PMID:
23040716.
IF:
1,352.
DOI:
10.1016/j.nrl.2012.07.011
Alonso de Leciñana M, Díaz-Guzmán J, Egido JA,
García Pastor A, Martínez-Sánchez P, Vivancos J,
Díez-Tejedor E; Comité ad hoc del Foro de Ictus de la
Asociación Madrileña de Neurología. Endovascular
treatment in acute ischaemic stroke. A Stroke Care
Plan for the Region of Madrid. Neurologia. 28(7):425434. 2013. PMID: 23664054. IF: 1,352. DOI:
10.1016/j.nrl.2012.12.009
Nombela F, Blanco M, Perez de la Ossa N, Caniego
JL, Sobrino T, Escudero D, Campos F, Moro MA,
Lizasoain I, Dávalos A, Castillo J, Vivancos J.
Neurotoxicity alter carotid angioplasty and stenting
procedures. Radiology. 268(2):515-20. 2013. PMID:
23525205. IF: 6,214. DOI: 10.1148/radiol.13112104
Lees KR, Bornstein N, Diener HC, Gorelick PB,
Rosenberg G, Shuaib A; MACSI Investigators. Results
of Membrane-Activated Chelator Stroke Intervention
randomized trial of DP-b99 in acute ischemic stroke.
Stroke. 44(3):580-584. 2013. PMID: 23391764. IF:
6,018. DOI: 10.1161/STROKEAHA.111.000013
Cuartero MI, Ballesteros I, Moraga A, Nombela F,
Vivancos J, Hamilton JA, Corbí A, Lizasoain I, Moro
MA. N2 neutrophils, novel players in brain inflammation after stroke: modulatieon by the PPAR agonist
rosiglitazone. Stroke. 44(12):3498-508. 2013. PMID:
24135932. IF: 6,018. DOI: 10.1161/STROKEAHA.113.002470
– 94 –
PUBLICATIONS GR.AS.1 (7) [IF GRAS1: 47,877]
YEAR
Total IF
Publication No.
Q1
2011
33,486
6
5
2012
37,632
9
4
2013
47,877
7
5
Gubern C, Camos S, Romera VG, Rodriguez R,
Ballesteros I, Lizasoain I, Moro MA, Serena J, Mallolas
J, Castellanos M. miRNA expression is modulated over
time after focal ischaemia: Up-regulation of miR-347
promotes neuronal apoptosis. FEBS J. 280(23):623346. 2013. PMID: 24112606. IF: 3,986. DOI:
10.1111/febs.12546
Faraco G, Moraga A, Moore J, Anrather J, Pickel VM,
Iadecola C. Circulating endothelin-1 alters critical
mechanisms regulating cerebral microcirculation.
Hypertension. 62(4):759-66. 2013. PMID: 23959559.
IF:
7,632.
DOI:
10.1161/HYPERTENSIONAHA.113.01761
Godino MD, Romera VG, Sánchez-Tomero JA,
Pacheco J, Canals S, Lerma J, Vivancos J, Moro MA,
Torres M, Lizasoain I, Sánchez-Prieto J. Amelioration of
ischemic brain damage by peritoneal dialysis. J Clin
Invest. 123(10):4359-4363. 2013. PMID: 23999426. IF:
13,765. DOI: 10.1172/JCI67284
Hurtado O, Hernández-Jiménez M, Zarruk JG,
Cuartero MI, Ballesteros MI, Camarero G, Moraga A,
Pradillo JM, Moro MA, Lizasoain I. Citicoline (CDPcholine) increases Sirtuin1 expression concomitant to
neuroprotection in experimental stroke. J Neurochem
(126):819-826. 2013. PMID: 23600725. IF: 4,244. DOI:
10.1111/jnc.12269
Nombela F, Blanco M, Perez de la Ossa N, Caniego JL,
Sobrino T, Escudero D, Campos F, Moro MA, Lizasoain
I, Dávalos A, Castillo J, Vivancos J. Neurotoxicity alter
carotid angioplasty and stenting procedures.
Radiology. 268(2):515-20. 2013. PMID: 23525205. IF:
6,214. DOI: 10.1148/radiol.13112104
Cuartero MI, Ballesteros I, Moraga A, Nombela F,
Vivancos J, Hamilton JA, Corbí A, Lizasoain I, Moro
AREA 2
Hernández-Jiménez M, Hurtado O, Cuartero MI,
Ballesteros I, Moraga A, Pradillo JM, McBurney MW,
Lizasoain I, Moro MA. Silent information regulator 1
(Sirt1) protects the brain from ischemia. Stroke.
44(8):2333-7. 2013. PMID: 23723308. IF: 6,018.
DOI: 10.1161/STROKEAHA.113.001715
CLINICAL TRIALS GR.35
PRINCIPAL RESEARCHER: LÓPEZ MANZANARES,
LYDIA
Estudio multicéntrico, multinacional, doble ciego,
controlado con placebo, de tres grupos, de fase 4,
para evaluar la eficacia de la rotigotina en la apatía,
los síntomas motores y el estado de ánimo asociados con la Enfermedad de Parkinson; (versión final:
17-07-12).
UCB
BIOSCIENCES
GMBH.
PD0005.EudraCT: 2012-002840-26
PRINCIPAL RESEARCHER: LÓPEZ MANZANARES,
LYDIA
Estudio multicéntrico, multinacional, doble ciego,
controlado con placebo, de tres grupos, de fase 4,
para evaluar la eficacia de la rotigotina en la apatía,
los síntomas motores y el estado de ánimo asociados con la Enfermedad de Parkinson; (versión final:
17-07-12).
UCB
BIOSCIENCES
GMBH.
PD0005.EudraCT: 2012-002840-26
PRINCIPAL RESEARCHER: MECA LALLANA, VIRGINIA
Estudio fase 2/3, multicéntrico, aleatorizado, doble
ciego, controlado con placebo(Parte A) y doble
ciego, con doble simulación y con control activo
(Parte B), de grupos paralelos para evaluar la eficacia
y la seguridad de RPC1063 administrado por vía oral
a pacientes con esclerosis múltiple recidivante;
(Versión 2.0: 14-09-12). RECEPTOS INC. RPC01201 EudraCT: 2012-002714-40
Estudio multicéntrico retrospectivo para evaluar el
cumplimiento a largo plazo con el tratamiento con
IFN beta-1a mediante el dispositivo RebiSmart en
pacientes con esclerosis múltiple remitente-recurrente; (versión final: 11-03-13). MERCK S.L. MERINT-2013-02
Estudio ADRES: Estudio observacional, retrospectivo
y transversal para evaluar el cumplimiento subóptimo
en pacientes con esclerosis múltiple remitente-recurrente que presentan un brote tras un mínimo de 6
meses de tratamiento con IFN beta-1a; (Versión final:
11-03-13). MERCK S.L. MER-INT-2013-01
Ensayo multicéntrico, aleatorizado, doble ciego y
controlado con placebo para evaluar la seguridad y
la eficacia de eculizumab en pacientes con neuromielitis óptica (NMO) recidivante; (Versión 3.0: 1505-13). ALEXION PHARMACEUTICALS INC. ECUNMO-301. EudraCT: 2013-001150-10.
Ensayo de extensión abierto de fase III sobre ECUNMO-301 para evaluar la seguridad y la eficacia de
eculizumab en pacientes con neuromielitis óptica
(NMO) recidivante; (Versión 1.1: 24-05-13). ALEXION
PHARMACEUTICALS
INC.
ECU-NMO-302.
EudraCT: 2013-001151-12
Estudio de fase II, multicéntrico, aleatorizado, doble
ciego, de grupos paralelos, controlado con placebo,
con diseño adaptativo de determinación de dosis,
para evaluar la eficacia y seguridad de AIN457
(secukinumab) en pacientes con esclerosis múltiple
– 95 –
AREA 3AREA 2 AREA 1
MA. N2 neutrophils, novel players in brain inflammation after stroke: modulation by the PPAR agonist
rosiglitazone. Stroke. 44(12):3498-508. 2013. PMID:
24135932. IF: 6,018. DOI: 10.1161/STROKEAHA.113.002470
que cursa con brotes;(Versionv01: 13-02-13).
NOVARTIS FARMACEUTICA, S.A. CAIN457B2203.
EudraCT: 2012-004019-29
Estudio multinacional, multicéntrico, aleatorizado,
doble ciego, con grupos paralelos y controlado con
– 96 –
placebo, seguido de un periodo de tratamiento activo, para evaluar la eficacia, la seguridad y la tolerabilidad de dos dosis de laquinimod administradas por
vía oral (0,6mg/día o 1,2 mg/día) en sujetos con
esclerosis múltiple remitente-recurrente (EMRR);
(Versión Enmienda Global/ 1/2013-07-22). TEVA
PHARMACEUTICAL INDUSTRIES, LTD. LAQ-MS305 (CONCERTO). EudraCT: 2012-003647-30
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.
– 97 –
AREA 3
– 98 –
AREA 3
GROUP 36
HEAD OF LABORATORY
Isidoro González Álvaro
deepen in personalized medicine in the field of biological therapies for immune mediated inflammatory diseases. BioIMID involves 8 groups of our
Institute coordinated by Dr Monica Marazuela and
the Biological Therapies Unit, directed by Dr
Alvaro-Gracia, plays a key role in this project.
On the other hand, once again 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). Our research is mainly focused
on the detection of prognostic and cardiovascular
GROUP MEMBERS
• José María Álvaro-Gracia Álvaro
• Santos Castañeda Sanz
• Belén Díaz Sánchez
• Carlos Gamallo Amat
• Jesús Alberto García Vadillo
• Rosario García de Vicuña Pinedo
• María de las Nieves Gómez León
• Amalia Lamana Domínguez
• Ana María Ortiz García
• Esther Patiño Ruiz
• Eva Gloria Tomero Muriel
• Teresa Velasco Ripoll
• Esther Francisca Vicente Rabaneda
RESEARCH INTEREST
The main goal for our group during year 2013 was
to be involved in the development of BioIMID project that was granted by the PIE program
(Integrated Projects for Excellence at Health
Research Institutes) from the Instituto de Salud
Carlos III (ISCIII). This is a project that intends to
Fig.1. Distribution of the values for the Hospital Universitario de la
Princesa Index, version 10 (HUPl10), the Disease Activity Score in 28
joints (DAS28) with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level, and the Simplified Disease Activity Index
(SDAI) in the entire cohort (n=303). The W value refers to the score obtained by each index in the Shapiro-Wilk normality test; higher values
represent a better fit to the normal distribution.
Castrejón I, Carmona L, Ortiz AM, Belmonte MA, Martínez-López JA,
González-Álvaro I. Development and validation of a new disease activity index as a numerical sum of four variables in patients with early
arthritis. Arthritis Care Res (Hoboken). 2013 Apr;65(4):518-25.
PMID:23002022.
– 99 –
AREA 3AREA 2 AREA 1
Line 3.1
Prognostic and
predictor markers in
autoimmune diseases
Advanced therapies and individualized medicine
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 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.
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.
•
•
•
•
•
MAJOR GRANTS
• Rosario García de Vicuña Pinedo. Proyecto CARMA:
Estudio sobre el riesgo cardiovascular (CV) en los
pacientes con enfermedades reumáticas inflamatorias crónicas. Fundación Española de Reumatología
con el patrocinio de Abbott Laboratories. Duration:
2010 - 2021.
• Santos Castañeda Sanz. Predictive value of cortical
bone mineral density variation determined by radiogrammetry at metacarpal bones as a prognostic
marker in early arthritis. Pfizer España. Duration:
2011 - 2013.
• 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
– 100 –
•
•
•
•
de pacientes con artritis reumatoide. Papel modulador de CD69 en la gravedad de esta enfermedad.
ISCIII. INTRASALUD PROGRAM. 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.
Rosario García de Vicuña Pinedo. Análisis prospectivo de los factores predictivos de evolución clínica
desfavorable en una corte multicéntrica española de
pacientes con Lupus eritematoso sistémico. ISCIII.
PI11/02857. Duration: 2012 - 2014.
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.
María de las Nieves Gómez León. Evaluación de la
técnica TC multidetector 64 frente a la PET/CT en el
Estudio clínico de pacientes con linfoma y su estudio
de coste efectividad: Estudio Multicéntrico. ISCIII.
PI11/01800. Duration: 2012 - 2014.
Isidoro González Álvaro. RIER: Red de Inflamación y
Enfermedades Reumáticas. ISCIII. RD12/0009/
0017. Duration: 2013 - 2016.
Jesús
Alberto
García
Vadillo.
Proyecto
SJÖNGRESER: Registro de pacientes con Síndrome
de Sjörgren primario. SER y FER. Duration: 2013 2014.
Santos Castañeda Sanz. Estudio de marcadores de
respuesta en artritis psosiásica. Proyecto
INNPACTO. Duration: 2013 - 2014.
Santos Castañeda Sanz. Valor predictivo de la
variación mineral ósea cortical en manos determinada mediante densitometría dual de rayos X
como marcador pronóstico en pacientes con artritis de inicio. ISCIII. PI12/01578. Duration: 2013 –
2015.
AREA 3
• Isidoro González Álvaro. Immunoregulatory molecules as biomarkers predicting response to biological
therapies and disease severity in immune-mediated
inflamatory disorders. BIOIMID PROJECT. ISCIII.
PIE13/00041. Duration: 2014 – 2016.
YEAR
Total IF
Publication No.
Q1
2011
152,428
46
15
2012
135,080
43
15
2013
130,346
26
15
Serrano A, Márquez A, Mackie SL, Carmona FD,
Solans R, Miranda-Filloy JA, Hernández-Rodríguez J,
Cid MC, Castañeda S, Morado IC, Narváez J, Blanco
R, Sopeña B, García-Villanueva MJ, Monfort J, OrtegoCenteno N, Unzurrunzaga A, Marí-Alfonso B, SánchezMartín J, de Miguel E, Magro C, Raya E, Braun N,
Latus J, Molberg O, Lie BA, Moosig F, Witte T, Morgan
AW, González-Gay MA, Martín J; UK GCA Consortium
Spanish GCA Consortium. Identification of the PTPN22
functional variant R620W as susceptibility genetic fac-
tor for giant cell arteritis. Ann Rheum Dis. 72(11):18826. 2013. PMID: 23946333. IF: 9,270. DOI:
10.1136/annrheumdis-2013-203641.
Serrano A, Carmona FD, Castañeda S, Solans R,
Hernández-Rodríguez J, Cid MC, Prieto-González
S, Miranda-Filloy JA, Rodríguez-Rodríguez L,
Morado IC, Gomez-Vaquero C, Blanco R, Sopeña
B, Ortego-Centeno N, Unzurrunzaga A, MaríAlfonso B, Sánchez-Martín J, García-Villanueva MJ,
Hidalgo-Conde A, Pazzola G, Boiardi L, Salvarani C,
González-Gay MA, Martín J. Evidence of association of the NLRP1 gene with giant cell arteritis. Ann
Rheum Dis. 72(4):628-30. 2013. PMID: 23253924.
IF: 9,270. DOI: 10.1136/annrheumdis-2012202609
Bustamante J, Leal O, Soto de Prado D, Domínguez L,
Nombela F, Guijarro M, Gamallo C. Hamartomatous
96(3):1068-70. 2013. PMID: 23992702. IF: 3,631. DOI:
10.1016/j.athoracsur.2013.01.036
Hernández MV, Sanmartí R, Cañete JD, Descalzo MA,
Alsina M, Carmona L, Gomez-Reino JJ; BIOBADASER
2.0 Study Group. Cutaneous adverse events during
treatment of chronic inflammatory rheumatic conditions
with tumor necrosis factor antagonists: study using the
Spanish registry of adverse events of biological therapies in rheumatic diseases. Arthritis Care Res
(Hoboken). 65(12):2024-31. 2013. PMID: 23926075.
IF: 4,039. DOI: 10.1002/acr.22096
Castrejón I, Carmona L, Ortiz AM, Belmonte MA,
Martínez-López JA, González-Álvaro I. Development
and validation of a new disease activity index as a
numerical sum of 4 variables in patients with early
arthritis. Arthritis Care Res (Hoboken). 65(4):518-25.
2013. PMID: 23002022. IF: 4,039. DOI:
10.1002/acr.21854
Serrano A, Carmona FD, Castañeda S, Miranda-Filloy
JA, Morado IC, Gomez-Vaquero C, Solans R, Sopeña
B, Blanco R, Unzurrunzaga A, Ortego-Centeno N,
– 101 –
AREA 3AREA 2 AREA 1
• Rosario García de Vicuña Pinedo. Registro Digital
Ulcer Outcome (DUO) (post-marketing commitment
for Tracleer, marketed by Actelion Pharmaceuticals
Ltd to the European Medicine Agency (EMA).
• Rosario García de Vicuña Pinedo. Proyecto SCORE:
Seguimiento y Control en Reumatología-Enfermería.
Sociedad Española de Reumatología-ABBOTT.
• Eva Gloria Tomero Muriel. RELESSER-PRO. Registro
prospectivo español de pacientes con lupus eritematoso
sistémico.
Sociedad
Española
de
Reumatología (SER).
• Eva Gloria Tomero Muriel. ESTUDIO REMICAM:
Comorbilidad y supervivencia de las miopatías
inflamatorias de origen autoinmune en la Comunidad
Autónoma de Madrid. Sociedad Española de
Reumatología de la Comunidad de Madrid (SORCOM).
Marí-Alfonso B, Hidalgo-Conde A, HernándezRodríguez J, Cid MC, Martín J, González-Gay MA. A
case-control study suggests that the CCR6 locus is not
involved in the susceptibility to giant cell arteritis. Clin
Exp Rheumatol. 31(1 Supp):S5-8. 2013. PMID:
23306142. IF: 2,973
Guillevin L, Hunsche E, Denton CP, Krieg T, Schwierin
B, Rosenberg D, Matucci-Cerinic M; DUO Registry
Group. Functional impairment of systemic scleroderma
patients with digital ulcerations:results from the DUO
Registry. Clin Exp Rheumatol. 31(2 Supp):71-80. 2013.
PMID: 23910613. IF: 2,973
Almagro MI, Roman-Blas JA, Bellido M, Castañeda S,
Cortez R, Herrero-Beaumont G. PTH [1-34] enhances
bone response around titanium implants in a rabbit
model of osteoporosis. Clin OralImplants Res.
24(9):1027-34. 2013. PMID: 22626278. IF: 3,433. DOI:
10.1111/j.1600-0501.2012.02495.x
Mera-Menéndez F, Hinojar-Gutiérrez A, Guijarro Rojas
M, de Gregorio JG, Mera-Menéndez E, Sánchez JJ,
Quintanilla M, Cerezo L, Gamallo C. Polymorphisms in
HIF-1alpha affect presence of lymph node metastasis
and can influence tumor size in squamous-cell carcinoma of the glottic larynx. Clin Transl Oncol. 15(5):35863. 2013. PMID: 22914908. IF:1,600. DOI:
10.1007/s12094-012-0930-z
García-Bermúdez M, López-Mejías R, GonzálezJuanatey C, Corrales A, Castañeda S, Ortiz AM,
Miranda-Filloy JA, Gómez-Vaquero C, FernándezGutiérrez B, Balsa A, Pascual-Salcedo D, Blanco R,
Llorca J, Martín J, González-Gay MA. CARD8
rs2043211 (p.C10X) polymorphism is not associated
with disease susceptibility or cardiovascular events in
Spanish rheumatoid arthritis patients.DNA Cell Biol.
32(1):28-33. 2013. PMID: 23088220. IF: 2,344. DOI:
10.1089/dna.2012.1836
Vicente Rabaneda EF, Herrero-Beaumont G,
Castañeda S. Update on the use of abatacept for the
treatment of rheumatoid arthritis. Expert Rev Clin
Immunol. 9(7):599-621. 2013. PMID: 23899231. IF:
3,342. DOI: 10.1586/1744666X.2013.811192
– 102 –
Cénit MC, Ortego-Centeno N, Raya E, Callejas JL,
García-Hernandez FJ, Castillo-Palma MJ, FernandezSueiro JL, Magro C, Solans R, Castañeda S, Camps
M, Hidalgo A, Espinosa G, González-Gay MA,
González-Escribano MF, Martín J. Influence of the
STAT3 genetic variants in the susceptibility to psoriatic
arthritis and Behcet's disease. Hum Immunol.
74(2):230-3. 2013. PMID: 23127549. IF: 2,282. DOI:
10.1016/j.humimm.2012.10.019
Blasco AJ, Aguilar MD, Ferrándiz C, Puig L, SánchezCarazo JL; on behalf of the Working Group on
Comorbidity in Psoriasis. Clinical practice guideline for
an integrated approach to comorbidity in patients with
psoriasis. J Eur Acad Dermatol Venereol. 27(11):1387404. 2013. PMID: 23134338. IF: 3,105. DOI:
10.1111/jdv.12024
Somovilla-Crespo B, Alfonso-Pérez M, Cuesta-Mateos
C, Carballo-de Dios C, Beltrán AE, Terrón F, Pérez-Villar
JJ, Gamallo-Amat C, Pérez-Chacón G, FernándezRuiz E, Zapata JM, Muñoz-Calleja C. Anti-CCR7 therapy exerts a potent anti-tumor activity in a xenograft
model of human mantle cell lymphoma. J Hematol
Oncol. (4):6-89. 2013. PMID: 24305507. IF: 4,933.
DOI: 10.1186/1756-8722-6-89
Martín-Millán M, Castañeda S. Estrogens, osteoarthritis and inflammation. Joint Bone Spine. 80(4):368-73.
2013. PMID: 23352515. IF: 3,218. DOI:
10.1016/j.jbspin.2012.11.008
Gabay C, Emery P, van Vollenhoven R, Dikranian A,
Alten R, Pavelka K, Klearman M, Musselman D,
Agarwal S, Green J, Kavanaugh A; ADACTA Study
Investigators. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid
arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. . 381(9877):1541-50.
2013. PMID: 23515142. IF: 39,207. DOI:
10.1016/S0140-6736(13)60250-0
Carrión M, Pérez-García S, Jimeno R, Juarranz Y,
González-Álvaro I, Pablos JL, Gutiérrez-Cañas I,
Gomariz RP. Inflammatory mediators alter interleukin-
AREA 3
Acosta-Colman I, Palau N, Tornero J, FernándezNebro A, Blanco F, González-Alvaro I, Cañete JD,
Maymó J, Ballina J, Fernández-Gutiérrez B, Olivé A,
Corominas H, Erra A, Canela-Xandri O, Alonso A,
López Lasanta M, Tortosa R, Julià A, Marsal S. GWAS
replication study confirms the association of PDE3ASLCO1C1 with anti-TNF therapy response in rheumatoid arthritis. Pharmacogenomics. 14(7):727-734.
2013. PMID: 23651021. IF: 3,425. DOI:
10.2217/pgs.13.60
García-Bermúdez M, López-Mejías R, Genre F,
Castañeda S, González-Juanatey C, Llorca J, Corrales
A, Miranda-Filloy JA, Rueda-Gotor J, Gómez-Vaquero
C, Rodríguez-Rodríguez L, Fernández-Gutiérrez B,
Pascual-Salcedo D, Balsa A, López-Longo FJ, Carreira
P, Blanco R, González-Álvaro I, Martín J, González-Gay
MA. SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular accidents
and subclinical atherosclerosis in anti-CCP negative
Spanish rheumatoid arthritis patients. PLoS One.
8(10):e77695. 2013. PMID: 24204921. IF: 3,534. DOI:
10.1371/journal.pone.0077695
Teruel M, McKinney C, Balsa A, Pascual-Salcedo D,
Rodriguez-Rodriguez L, Ortiz AM, Gómez-Vaquero C,
González-Gay MA, Smith M, Witte T, Merriman T, Lie
BA, Martin J. Association of CD247 polymorphisms
with rheumatoid arthritis: a replication study and a
meta-analysis. PLoS One. 8(7):e68295. 2013. PMID:
23861880. IF: 3,534. DOI:10.1371/journal.pone.
0068295
Carrión M, Juarranz Y, Martínez C, González-Álvaro I,
Pablos JL, Gutiérrez-Cañas I, Gomariz RP. IL-22/IL-22R1
axis and S100A8/A9 alarmins in human osteoarthritic and
rheumatoid arthritis synovial fibroblasts. Rheumatology
(Oxford). 52(12):2177-86. 2013. PMID: 24056519. IF:
4,435. DOI: 10.1093/rheumatology/ket315
Descalzo MA, Villaverde Garcia V, González-Alvaro I,
Carbonell J, Balsa A, Sanmartí R, Lisbona P,
Hernandez-Barrera V, Jiménez-Garcia R, Carmona L;
on behalf of SERAP Study Group (.., Ortiz AM, GarciaVicuña R,..). Tackling missing radiographic progression
data: multiple imputation technique compared with
inverse probability weights and complete case analysis.
Rheumatology (Oxford). 52(2):331-6. 2013. PMID:
23024115. IF: 4,435. DOI: 10.1093/rheumatology/
kes245
Vega B, Calle A, Sánchez A, Lechuga LM, Ortiz AM,
Armelles G, Rodríguez-Frade JM, Mellado M. Real-time
detection of the chemokine CXCL12 in urine samples
by surface plasmon resonance. Talanta. 15(109):20915. 2013. PMID: 23618162. IF: 3,511. DOI:
10.1016/j.talanta.2013.02.018
López-Mejías R, Genre F, García-Bermúdez M,
A, Miranda-Filloy JA, Rueda-Gotor J, Gómez-Vaquero
C, Rodríguez-Rodríguez L, Fernández-Gutiérrez B,
Balsa A, Pascual-Salcedo D, López-Longo FJ, Carreira
MA. The 11q23.3 genomic region-rs964184-is associated with cardiovascular disease in patients with
rheumatoid arthritis. Tissue Antigens. 82(5):344-7.
2013. PMID: 24131021. IF: 2,350. DOI:
10.1111/tan.12217
García-Bermúdez M, López-Mejías R, Genre F,
A, Miranda-Filloy JA, Pina T, Gómez-Vaquero C,
Rodríguez-Rodríguez L, Fernández-Gutiérrez B,
Pascual-Salcedo D, Balsa A, López-Longo FJ, Carreira
MA. Single-nucleotide polymorphisms at the 9p21.3
genomic region not associated with the risk of cardiovascular disease in patients with rheumatoid arthritis.
Tissue Antigens. 82(6):405-9. 2013. PMID: 24498997.
IF: 2,350. DOI: 10.1111/tan.12227
Pérez-Esteban S, González-Gay MA, Castañeda S.
Therapeutic update in large vessel vasculitides. Rev
Clin Esp. 8 213(7):338-346. 2013. PMID: 23683962.
IF: 1,334 DOI: 10.1016/j.rce.2013.03.00
– 103 –
AREA 3AREA 2 AREA 1
17 receptor, interleukin-12 and -23 expression in
human osteoarthritic and rheumatoid arthritis synovial
fibroblasts: immunomodulation by vasoactive intestinal
Peptide. Neuroimmunomodulation. 20(5):274-84.
2013. PMID: 23880957. IF: 1,779. DOI:
10.1159/000350892
BOOKS
M Martín-Millán and S Castañeda. Sex hormones and related compounds, including hormonal contraceptives. Side
Effects of Drugs, Annual 35 (chapter 40). 2013. J. Aronson,
Elsevier. ISBN: 978-04-446-2635-6.
Santos Castañeda, Gabriel Herrero-Beaumont. Futuro en la
atención y abordaje de la artrosis. Curso online para
Ginecólogos y Atención Primaria sobre “Artrosis posmenopáusica”. 2013. Curso/Libro Online.
García Vadillo, A. Monografía nº 1 Clasificación y diagnóstico de la Artritis Reumatoide. Monografías de Artritis
Reumatoide. 2013. Pfizer. Madrid.
Esther F. Vicente y Santos Castañeda. Diagnóstico diferencial de la artrosis tipo ii de la mujer menopáusica. Módulo 2
del Curso online para Ginecólogos y Atención Primaria
sobre Artrosis Tipo II – La artrosis de la mujer menopáusica. 2013. Curso/Libro OnLine.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ÁLVARO-GRACIA ÁLVARO,
JOSÉ M.
Estudio de fase IIIB para evaluar la eficacia, seguridad y tolerabilidad de tocilizumab (TCZ) subcutáneo (SC) administrado como monoterapia o en combinación con metotrexato
(MTX) u otros FAMES no biológicos en pacientes con artritis
reumatoide; (Versión 1: 30-05-13). ROCHE FARMA, S.A.
ML28709. EudraCT: 2013-002429-52
PRINCIPAL RESEARCHER: GARCÍA DE VICUÑA PINEDO, ROSARIO
Preferencias de reumatólogos y pacientes por los atributos
de los agentes biológicos empleados en el tratamiento de
enfermedades reumáticas en España; (versión 0.4 septiembre 2012). MERCK SHARP & DOHME DE ESPAÑA, S.A.
MSD-BIO-2012-01
PRINCIPAL RESEARCHER: TOMERO MURIEL, EVA
Comorbilidad y supervivencia de las miopatías inflamatorias
– 104 –
de origen autoinmune en la Comunidad Autónoma de
Madrid. Estudio Remicam; (versión5: 02-02-13). REMICAM
PRINCIPAL RESEARCHER: VICENTE RABANEDA,
ESTHER
Estudio observacional transversal sobre la limitación funcional y de las actividades laborales y de la vida diaria en
pacientes con esclerosis sistémica que presentan o no
úlceras digitales: Estudio Laudes; (Versión 21-11-12).
ACTELION PHARMACEUTICALS LTD. ACT-NUL-201201.
GRUPO 37
HEAD OF LABORATORY
Esteban Daudén Tello
GROUP MEMBERS
• Diego de Argila Fernández-Durán
• María José Concha Garzón
• María Carmen García García
• María Jesús Gómez Gago
• Javier Sánchez Pérez
• Fátima Tudelilla Fernández
RESEARCH INTEREST
The activity of the Group is focused on:
- Immune-mediated inflammatory diseases, particularly
psoriasis and other desquamative dermatoses
• Gene Expression Profile as a marker of response in
patients with psoriasis treated with biologic therapy
• Immunoregulatory molecules as biomarkers predicting response to Biological Therapies and disease
severity in Immune-Mediated Inflammatory Disorders
• Epigenetics in psoriasis
• Psoriasiform paradoxical reactions in patients treated
with biologics
• Survival analysis in psoriasis systemic therapies
AREA 3
ical therapies and disease severity in immunemediated inflamatory disorders. BIOIMID PROJECT. ISCIII. PIE13/00041. Duration: 2014 – 2016.
• Patient-relevant needs and treatment goals in nail
psoriasis
• Role of GADD45-alpha, GADD45-beta and TSP-1 in
the immunopathogenesis of psoriasis
- Eczematous dermatitis
- Photobiology
- Lymphomas
- Connective Tissue Diseases
- Oncology
MAJOR GRANTS
• Esteban Daudén Tello. Biobadaderm: Registro
Español de Acontecimientos Adversos de terapias
biológicas en Dermatología. Duration: 2008.
• Esteban Daudén Tello. INNPACTO. Estudio de biomarcadores en Psoriasis. Duration: 2013 - 2015.
• Diego de Argila Fernández-Durán. EPIDERMOLISIS AMPOLLOSA. CIBERERu714. Duration: 2013
• Diego de Argila Fernández-Durán. Proyecto de
investigación de GEF: Medición de las MED en
población española sana. Duration: 2011.
• Esteban Daudén Tello. Desarrollo y validación de
un Índice Combinado de las uñas para evaluar el
impacto de la afectación ungueal en la calidad de
vida de los pacientes con psoriasis vulgar. SCIDERM. Duration: 2011.
• Esteban Daudén Tello. Immunoregulatory molecules as biomarkers predicting response to biolog-
YEAR
Total IF
Publication No.
Q1
2011
31,284
23
6
2012
44,043
15
8
2013
29,379
10
6
Navarro R, Vilarrasa E, Herranz P, Puig L, Bordas X,
Carrascosa JM, Taberner R, Ferrán M, GarcíaBustinduy M, Romero-Maté A, Pedragosa R, GarcíaDiez A, Daudén E. Safety and effectiveness of ustekinumab and anti-tumor necrosis factor therapy in
patients with psoriasis and chronic viral hepatitis b or c.
A retrospective, multicentre study in a clinical setting.
Br J Dermatol. 168(3):609-616. 2013. PMID:
22985451. IF: 4,100. DOI: 10.1111/bjd.12045
Abad-Santos F, García-Díez A, Daudén E. The relationship between tumour necrosis factor (TNF)-a
promoter and IL12B/IL-23R genes polymorphisms
and the efficacy of anti-TNF-a therapy in psoriasis: a
case-control study. Br J Dermatol. 169(4):819-29..
2013. PMID: 23662788. IF: 3,759. DOI: 10.1111/
bjd.12425
Talegón M, Prieto-Pérez R, García-Díez A, Daudén E,
Abad-Santos F. Association between psoriasis and
polymorphisms in the TNF, IL12B, and IL23R genes in
Spanish patients. Eur J Dermatol. 23(5):640-5. 2013.
PMID:
24135300.
IF:
1,953.
DOI:
10.1684/ejd.2013.2144
Gallo E, Llamas-Velasco M, Daudén E, García-Diez A.
Refractory generalized pustular psoriasis responsive to
a combination of adalimumab and acitretin. Int J
Dermatol. 52(12):1610-1. 2013. PMID: 22834488. IF:
1,227. DOI: 10.1111/j.1365-4632.2012.05472.x
– 105 –
AREA 3AREA 2 AREA 1
Fig.1. Recommended screening tests for latent tuberculosis infection
(AEDV Spanish Psoriasis Group)
Fraga J, García-Diez A. Sweet's syndrome with subcutaneous involvement associated with pegfilgrastim
treatment: first reported case. J Cutan Pathol.
40(1):46-9. 2013. PMID: 23131080. IF: 1,560. DOI:
10.1111/cup.12042
Sotomayor E, Fraga J, García-Diez A. Macular lymphocytic arteritis: first clinical presentation with ulcers. J
Cutan Pathol. 40(4):424-7. 2013. PMID: 23384039. IF:
1,560. DOI: 10.1111/cup.12094
Pharmacogenomics 14 (13):1623-1634. 2013. PMID:
24088133. IF: 3,857. DOI: 10.2217/pgs.13.163
Prieto-Pérez R, Cabaleiro T, Dauden E, Abad-Santos F.
Gene polymorphisms that can predict response to antiTNF therapy in patients with psoriasis and related
autoimmune diseases. Pharmacogenomics J.
13(4):297-305. 2013. PMID: 23337970. IF: 5,513. DOI:
10.1038/tpj.2012.53
CLINICAL TRIALS
Sánchez-Moya AI, García-Doval I, Carretero G,
Sánchez-Carazo J, Ferrandiz C, Herrera Ceballos E,
Alsina M, Ferrán M, López-Estebaranz JL, GómezGarcía F, De la Cueva Dobao P, Carrascosa M,
Vanaclocha F, Belinchón I, Peral F, Dauden E; the
BIOBADADERM StudyGroup. Latent tuberculosis
infection and active tuberculosis in patients with psoriasis: a study on the incidence of tuberculosis and the
prevalence of latent tuberculosis disease in patients
with
moderate-severe
psoriasis
in
Spain.BIOBADADERM registry. J Eur Acad Dermatol
Venereol. 27(11):1366-74. 2013. PMID: 23134268. IF:
3,105. DOI: 10.1111/jdv.12011
10.1111/jdv.12024
Prieto-Pérez R, Cabaleiro T, Daudén E, Ochoa D,
Román M, Abad-Santos F. Pharmacogenetics of topical and systemic treatment of psoriasis.
– 106 –
PRINCIPAL RESEARCHER: DE ARGILA FERNÁNDEZDURÁN, DIEGO
Carga de la enfermedad y calidad de vida del paciente con
urticaria crónica en España. Prevalencia de urticaria crónica
refractaria a la terapia estándar en práctica clínica habitual.
Estudio UCREX; (Versión final01-02-13). NOVARTIS FARMACEUTICA, S.A. NOV-URT-2012-01/CIGE025 EES02.
PRINCIPAL RESEARCHER: DAUDÉN TELLO, ESTEBAN
Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo para demostrar la eficacia a las 16
semanas de secukinumab 150 y 300mg s.c. y para
evaluar la seguridad, tolerabilidad y la eficacia a largo
plazo hasta 80 semanas en pacientes con psoriasis
ungueal moderada a severa; (Versión 01:19-12-13).
NOVARTIS FARMACEUTICA, S.A. CAIN457A2313.
EudraCT: 2012-005413-40
PRINCIPAL RESEARCHER: SÁNCHEZ PÉREZ, ABILIO
JAVIER
Lesiones cutáneas graves asociadas a medicamentos:
registro de casos para la vigilancia epidemiológica, evaluación del manejo clínico y estudio de los determinantes y
mecanismos biológicos. CONSORCIO PIELENRED .PERMED-2010-01
AREA 3
Line 3.2
Esophagogastrointestinal
inflammatory diseases
GRUPO 38
HEAD OF LABORATORY
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
Fig.1. Bactericidal testing of the novel singlet oxygen photosensitising
material. a) H. Pylori control exposed to light; b) H. pylori incubated
with sensitiser in darkness; c) H. Pylori incubated with glass beads without sensitiser exposed to light; s) H. Pylori incubated with photosensitiser exposed to light. “The curves cannot be distinguished, CFU mL1 count after 30 min are: a) 4.6 x 108 ; b) 4.7 x 108 ; c) 4.0 x 108
department of the Complutense University of Madrid,
the Spanish National Cancer Research Centre, 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 2013 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 led the organization of the International
Workshop on Helicobacter held 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 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.
– 107 –
AREA 3AREA 2 AREA 1
GROUP MEMBERS
• María José Beceiro Pedreño
• María José Casanova González
• Carlos Castaño Milla
• María Chaparro Sánchez
• Almudena Durán Vegue
• María Encarnación Fernández Contreras
• Adrián Gerald Mcnicholl
• Alicia Marín Gómez
• José Maté Jiménez
• Pablo Muñoz Linares
• Mercedes Ramas López
• Cecilio Santander Vaquerizo
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, mainly anti-TNF treatments
• 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, mainly for those treated
with anti-TNF regimens
- 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 and IBD
- 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 (PSGL1, MT1-MMP, IFG-1, ER , AIF-1, CB1 and CB2)
•
•
•
•
•
•
•
•
•
MAJOR GRANTS
• Adrián Gerald Mcnicholl. Detección de H. pylori
mediante RT-PCR e inmunohistoquímica en el
– 108 –
•
paciente con linfoma MALT gástrico H. pylori negativo por métodos convencionales (estudio multicéntrico nacional). Asociación Española de
Gastroenterología. Duration: 2009 - 2014.
Javier Pérez Gisbert. Efecto del adalimumab
sobre la expresión de factores angiogénicos y
linfagiogénicos en la enfermedad inflamatoria
intestinal. ABBOTT Laboratories. Duration: 2011 2013.
Javier Pérez Gisbert. Biobanco IMIDs diferencial
permite identificar biomarcadores y nuevas terapias. Subprograma INNPACTO. MICINN. IPT010000-2010-036. Duration: 2011 - 2013.
María Chaparro Sánchez. Impacto de la vacuna
frente al virus de la hepatitis B en el sistema inmune.
GETTECCU-Otsuka. Duration: 2012 - 2013.
María
Encarnación
Fernández
Contreras.
Involvement of estrogen receptor beta (ER ) and
thymidylate syntase polymorphisms in inflammatory
bowel disease. GETECCU. Duration: 2012 - 2013.
Javier Pérez Gisbert. Asesoramiento en la realización de protocolos y procedimientos de investigación del área de enfermedades inflamatorias
esófago-gastro-intestinales y análisis de resultados. CTO.CASEN. FLEET. 2013. Duration: 2013 Javier Pérez Gisbert. Optimal H. pylori
Management in Primary Care. United European
Gastroenterology (UEG) (Long-term Projects).
Duration: 2013 - 2015.
Javier Pérez Gisbert. European Registry on the
management of Helicobacter pylori infection.
European Helicobacter Study Group. Duration:
2013 - 2015.
María Chaparro Sánchez. Predicción de respuesta a corto y largo plazo al tratamiento con fármacos anti-TNF en pacientes con Enfermedad de
Crohn. Estudio PREDICROHN. Instituto de Salud
Carlos III Evaluación de Tecnologías Sanitarias.
María Chaparro Sánchez. Desarrollo de un método basado en ELISA para la medición de los niveles séricos de anti-TNF y anticuerpos contra el
fármaco. PRE-PREDICROHN. MSD. Duration:
2013 – 2015
Javier Pérez Gisbert. Búsqueda de factores
genéticos asociados a la eficacia y toxicidad del
AREA 3
• Javier Pérez Gisbert. Immunoregulatory molecules as biomarkers predicting response to biological therapies and disease severity in immunemediated inflamatory disorders. BIOIMID PROJECT. ISCIII. PIE13/00041. Duration: 2014 – 2016.
YEAR
Total IF
Publication No.
Q1
2011
177,979
45
22
2012
336,480
63
35
2013
449,884
56
41
E Domenech, JP Gisbert. Letter: should colectomy be
the end-point to evaluate the effectiveness of drug therapies in severe ulcerative colitis?. Aliment Pharmacol
Ther. 37(1): 160-1. 2013. PMID: 23205480. IF: 5,478.
DOI: 10.1111/apt.12095
M Chaparro, JP Gisbert. Letter: measurement of antiTNF- levels and antibodies against the drug. Aliment
Pharmacol Ther. 37(1):163-164. 2013. PMID:
23205484. IF: 5,478. DOI: 10.1111/apt.12106
C Taxonera, JP Gisbert. Letter: Recommendations for
the management of latent tuberculosis infection in IBD
patients may not be applicable in all settings. Aliment
Pharmacol Ther. 37(3):365-6. 2013. PMID: 23281725.
IF: 5,478. DOI: 10.1111/apt.12154
Pedersen N, Bortoli A, Duricova D, D Inca R, Panelli MR,
Gisbert JP, Zoli G, López-Sanromán A, Castiglione F,
Riegler G, Annese V, Gionchetti P, Prada A, Pont ED,
Timmer A, Felley C, Shuhaibar M, Tsianos EV, Dejaco C,
Baert FJ, Jess T, Lebech M, Hommes DW, Munkholm P;
European Crohn-Colitis Organisation (ECCO) study
group of Epidemiology Committee (EpiCom). The course
of inflammatory bowel disease during pregnancy and
postpartum: A prospective European ECCO-EpiCom
Study of 209 pregnant women. Aliment Pharmacol Ther.
38(5):501-512. 2013. PMID: 23855425. IF: 5,478. DOI:
10.1111/apt.12412
Kahrilas PJ, Howden CW, Wernersson B, Denison H,
Nuevo J, Gisbert JP. Impact of persistent, frequent
regurgitation on quality of life in heartburn responders
treated with acid suppression: a multinational primary
care study. Aliment Pharmacol Ther. 37(10):1005-1010.
2013.
PMID:
23557078.
IF:
5,478.
DOI:
10.1111/apt.12298
Chaparro M, Gisbert JP. Letter: dry blood spots for antiTNF treatment monitoring in IBD--authors' reply. Aliment
23590543. IF: 5,478. DOI: 10.1111/apt.12311
Molina-Infante J, Gisbert JP. Letter: seeking
oesophageal eosinophilia among unselected patients-looking for a needle in a haystack?. Aliment Pharmacol
Ther. 37(10):1029-1030. 2013. PMID: 23590547. IF:
5,478. DOI: 10.1111/apt.12315
F Fernández-Bañares, M Esteve, JP Gisbert. Letter:
mucosal healing and mortality in coeliac disease. Aliment
23458540. IF: 5,478. DOI: 10.1111/apt.12229
Barreiro-de Acosta M, Gisbert JP. Letter: infliximab in
severe ulcerative colitis - is it useful for all patients?.
Aliment Pharmacol Ther. 38(11-12):1413. 2013. PMID:
24206379. IF: 5,478. DOI: 10.1111/apt.12509
Barreiro-de Acosta M, Gisbert JP. Letter: mucosal healing in ulcerative colitis--higher relevance than in Crohn's
disease?. Aliment Pharmacol Ther. 38(2):207-207. 2013.
PMID: 23772904. IF: 5,478. DOI: 10.1111/apt.12333
Nunes T, Etchevers MJ, Domènech E, García-Sánchez
V, Ber Y, Peñalva M, Merino O, Nos P, Garcia-Planella E,
– 109 –
AREA 3AREA 2 AREA 1
tratamiento con tiopurínicos en pacientes con
enfermedad inflamatoria intestinal (estudio
GENTÍO) (ENEIDA) (estudio multicéntrico
nacional). GETECCU. Duration: 2010• Javier Pérez Gisbert. ENEIDA: Estudio Nacional
en Enfermedad Inflamatoria Intestinal sobre
Determinanates dependientes de ADN. GETECCU. PR. GENTÍO. Duration: 2006-
Casbas AG, Esteve M, Taxonera Samsó C, Montoro
Huguet M, Gisbert JP, Martín Arranz MD, GarcíaSepulcre MF, Barreiro-de Acosta M, Beltrán B, Alcaide
Suárez N, Saro Gismera C, Cabriada JL, Cañas-Ventura
A, Gomollón F, Panés J; Tobacco-Eneida Study Group of
GETECCU. Smoking does influence disease behaviour
and impacts the need for therapy in Crohn's disease in
the biologic era. Aliment Pharmacol Ther. 38(7):752-760.
2013.
PMID:
23980933.
IF:
5,478.
DOI:
10.1111/apt.12440
Lopez-Sanroman A, Gisbert JP. Letter: ciclosporin
of infliximab in acute ulcerative colitis: still undecided. Aliment Pharmacol Ther. 38(8):992. 2013. PMID:
24074311. IF: 5,478. DOI: 10.1111/apt.12422
Molina-Infante J, Katzka DA, Gisbert JP. Review article: proton pump inhibitor therapy for suspected
eosinophilic oesophagitis. Aliment Pharmacol Ther.
37(12):1157-64. 2013. PMID: 23656497. IF: 5,478.
DOI: 10.1111/apt.12332
Molina-Infante J, Gisbert JP. Commentary: overcoming antibiotic resistance with Helicobacter pylori
therapy--optimisation is the way forward. Aliment
Pharmacol
Ther.38(2):204-5..
2013.
PMID:
23772902. IF: 5,478. DOI: 10.1111/apt.12357
MJ Casanova, M Chaparro, E Domènech, M
Mañosa, M Barreiro-de Acosta, F Bermejo, E
Iglesias, F Gomollón, L Rodrigo, X Calvet , M Esteve,
E García-Planella, S García, C Taxonera, M Calvo, JL
Cabriada, D Ginard, M Gómez, E Garrido, JL PérezCalle, B Beltrán, M Piqueras, C Saro, B Botella, C
Dueñas, A Ponferrada, V García, J Maté, JP Gisbert.
Safety of thiopurines and anti-TNF drugs during
pregnancy in patients with inflammatory bowel disease. Am J Gastroenterol. 108(3):433-40. 2013.
PMID:
23318480.
IF:
9,213.
DOI:
10.1038/ajg.2012.430
Gisbert JP, Chaparro M. Safety of anti-TNF agents during pregnancy and breastfeeding in women with inflammatory bowel disease. Am J Gastroenterol.
108(9):1426-1438. 2013. PMID: 23752881. IF: 9,213.
DOI: 10.1038/ajg.2013.171
– 110 –
María Chaparro and Javier P Gisbert. Response to
Tung et al. Am J Gastroenterology. 108, 621-622.
2013.
PMID: 23552315 IF: 9,213. DOI:
10.1038/ajg.2013.34
J. Molina-infante, SD Georgopoulos, JP Gisbert. Re:
Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy. BMJ. 347. 2013. IF: 2,063
Yuan Y, Ford AC, Khan KJ, Gisbert JP, Forman D,
Leontiadis GI, Tse F, Calvet X, Fallone C, Fischbach L,
Oderda G, Bazzoli F, Moayyedi P. Optimum duration of
regimens for Helicobacter pylori eradication. Cochrane
Database Syst Rev. 11;12:CD008337. 2013. PMID:
24338763. IF: 5,939. DOI: 10.1002/14651858.
CD008337.pub2
Gomollón F, Gisbert JP. Intravenous iron in inflammatory bowel diseases. Curr Opinion Gastroenterol.
29(2):201-7. 2013. PMID: 23274316. IF: 3,664. DOI:
10.1097/MOG.0b013e32835bdc2e
Chaparro M, Zanotti C, Burgueño P, Vera I, Bermejo F,
Marín-Jiménez I, Yela C, López P, Martín MD, Taxonera
C, Botella B, Pajares R, Ponferrada A, Calvo M,
Algaba A, Pérez L, Casis B, Maté J, Orofino J, Lara N,
García-Losa M, Badia X, Gisbert JP. Health care cost
of complex perianal fistula in Crohn’s disease. Dig Dis
Sci. 58(12):3400-6. 2013. PMID: 24026400. IF: 2,889.
DOI: 10.1007/s10620-013-2830-7
Bermejo F, Algaba A, Chaparro M, Taxonera C,
Garrido E, García-Arata I, Guerra I, Gisbert JP,
Olivares D, de-la-Poza G, López-Sanromán A. How
frequently do tuberculosis screening tests convert in
inflammatory bowel disease patients on anti-tumour
necrosis factor-alpha? A pilot study. Dig Liver Dis.
45(9):733-7. 2013. PMID: 23587496. IF: 2,889. DOI:
10.1016/j.dld.2013.03.005
Juliao F, Marquez J, Aristizabal N, Yepes C, Zuleta J,
Gisbert JP. Clinical efficacy of infliximab in moderate to
severe ulcerative colitis in a latin american referral population. Digestion. 88(4):222-8. 2013. PMID:
24281150. IF: 2,032. DOI: 10.1159/000355529
AREA 3
Calvino-Fernández M, García-Fresnadillo D, BenitoMartínez S, McNicholl AG, Calvet X, Gisbert JP, ParraCid T. Helicobacter pylori inactivation and virulence gene
damage using a supported sensitiser for photodynamic
therapy. Eur J Med Chem. 68C:284-290. 2013. PMID:
23988411. IF: 3,499. DOI: 10.1016/j.ejmech.2013.
07.023
Marin AC, McNicholl AG, Gisbert JP. A review of rescue regimens after clarithromycin-containing triple
therapy failure (for Helicobacter pylori eradication).
Expert Opin Pharmacother. 14(7):843-861. 2013.
PMID: 23537368. IF: 3,085. DOI: 10.1517/
14656566.2013.782286
Guerra I, Gisbert JP. Onset of psoriasis in patients with
inflammatory bowel disease treated with anti-TNF
agents. Expert Rev Gastroenterol Hepatol. 7(1):41-48.
2013.
PMID:
23265148.
IF:
2,546.
DOI:
10.1586/egh.12.6
Molina-Infante J, Romano M, Fernandez-Bermejo M,
Federico A, Gravina AG, Pozzati L, Garcia-Abadia E,
Vinagre-Rodriguez G, Martinez-Alcala C, HernandezAlonso M, Miranda A, Iovene MR, Pazos-Pacheco C,
Gisbert JP. Optimized nonbismuth quadruple therapies
cure most patients with Helicobacter pylori infection in
populations with high rates of antibiotic resistance.
Gastroenterology. 145(1):121-128. 2013. PMID:
23562754. IF: 13,926. DOI: 10.1053/j.gastro.2013.
03.050
Panés J, López-Sanromán A, Bermejo F, GarcíaSánchez V, Esteve M, Torres Y, Domènech E, Piqueras
M, Gomez-García M, Gutiérrez A, Taxonera C, Sans M;
AZTEC Study Group. Early Azathioprine Therapy is no
More Effective Than Placebo for Newly Diagnosed
Crohn's Disease. Gastroenterology. 145(4):766-774.
2013. PMID: 23770132. IF: 13,926. DOI:
10.1053/j.gastro.2013.06.009
R Jover, P Zapater, E Polanía, L Bujanda, ALanas,
JA Hermo, J Cubiella, A Ono, Y González-Méndez,
A Peris, M Pellisé, A Seoane, A Herreros, M Ponce,
JC Marín-Gabriel, M Chaparro, G Cacho, S
Fernández-Díez, J Arenas, F Sopeña, L de-Castro, P
Vega-Villaamil, M Rodríguez-Soler, F Carballo, D
Salas, JD Morillas, M Andreu, E Quintero, A Castells
and COLONPREV study investigators. Modifiable
endoscopic factors that influence the adenoma
detection rate in colorectal cancer screening colonoscopies. Gastrointest Endosc. 77(3):381-389.e1.
2013. PMID: 23218945. IF: 4,900. DOI:
10.1016/j.gie.2012.09.027
Álvarez C, Andreu M, Castells A, Quintero E,
Bujanda L, Cubiella J, Salas D, Lanas Á, Carballo F,
Morillas JD, Hernández C, Jover R, Sarasqueta C,
Enriquéz-Navascués JM, Hernández V, Estévez
P,Macenlle R, Sala T, Balaguer F, Pellisé M, Moreira
L, Gil I, Peris A, González-Rubio F, Ferrández A,
Poves C, Ponce M, Grau J, Serradesanferm A, Ono
A, Cruzado J, Pérez-Riquelme F, Alonso-Abreu I,
Carrillo-Palau M, Santander C, Díaz Tasende J,
Herreros A, Cacho G, Barranco LE, Bessa X;
ColonPrev study investigators. Relationship of
colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals. Gastrointest Endosc. 78(2):333-341. 2013.
PMID:
23623039.
IF:
4,900.
DOI:
10.1016/j.gie.2013.03.003
F Megraud, S Coenen, A Versporten, M Kist, M
Lopez-Brea, A Hirschl, L Andersen, H Goossens, Y
Glupczynski, on behalf of the Study Group participants (.., T Alarcón, J Gisbert,) Helicobacter pylori
resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 62(1):34-42.
2013. PMID: 22580412. IF: 13,319. DOI:
10.1136/gutjnl-2012-302254
A Julià, E Domènech, E Ricart, R Tortosa, V García,
JP Gisbert, P Nos, A Gutiérrez, F Gomollón, JL
Mendoza, E García-Planella, M Barreiro, F Muñoz, M
Vera, C Saro, M Esteve, M Andreu, A Alonso, M
López-Lasanta, L Codó, JL Gelpí, AC GarcíaMontero, J Bertanpetit, D Absher, J Panés, S
– 111 –
AREA 3AREA 2 AREA 1
Gomollón F, Gisbert JP. Current Management of Iron
Deficiency Anemia in Inflammatory Bowel Diseases: A
Practical Guide. Drugs. 73(16):1761-70. 2013. PMID:
24114623. IF: 4,133. DOI: 10.1007/s40265-013-01312
Marsal. A genome-wide association study on a
southern European population identifies a new
Crohn's disease susceptibility locus at RBX1EP300. Gut. 62(10):1440-5. 2013. PMID:
22936669. IF: 13,319. DOI: 10.1136/gutjnl-2012302865
RECOMINA Project, GETECCU (Grupo Español de
Enfermedades de Crohn y Colitis Ulcerosa). Impact
of current smoking on the clinical course of microscopic colitis. Inflamm Bowel Dis. 19(7):1470-6.
2013. PMID: 23552765. IF: 5,475. DOI:
10.1097/MIB.0b013e318281f3cc
O'Connor A, Molina-Infante J, Gisbert JP, O'Morain
C. Treatment of Helicobacter pylori Infection 2013.
Helicobacter. 18(Suppl):58-65. 2013. PMID:
24011247. IF: 2,993. DOI: 10.1111/hel.12075
CA González, JM Sanz-Anquela, JP Gisbert, P
Correa. Utility of subtyping intestinal metaplasia as
marker of gastric cancer risk. A review of the evidence. Int J Cancer. 133(5):1023-32. 2013. PMID:
23280711. IF: 5,007. DOI: 10.1002/ijc.28003
F Fernández-Bañares, MR de Sousa, A Salas, B
Beltrán, M Piqueras, E Iglesias, JP Gisbert, B Lobo,
V Puig-Diví, E García-Planella, I Ordás, M Andreu, M
Calvo, M Montoro, M Esteve, JM Viver, for the
RECOMINA Project, GETECCU (Grupo Español de
Enfermedades de Crohn y Colitis Ulcerosa).
Epidemiological risk factors in microscopic colitis: a
prospective case-control study. Inflamm Bowel Dis.
19(2):411-417. 2013. PMID: 23344243. IF: 5,475.
DOI: 10.1002/ibd.23009
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. 2013. PMID: 23380936. IF: 5,475. DOI:
10.1097/MIB.0b013e31827febe9
Chaparro M, Ordás I, Cabré E, Garcia-Sanchez V,
Bastida G, Peñalva M, Gomollón F, García-Planella
E, Merino O, Gutiérrez A, Esteve M, Márquez L,
Garcia-Sepulcre M, Hinojosa J, Vera I, Muñoz F,
Mendoza JL, Cabriada JL, Montoro MA, Barreiro-de
Acosta M, Ceña G, Saro C, Aldeguer X, Barrio J,
Maté J, Gisbert JP. Safety of thiopurine therapy in
inflammatory bowel disease: long-term follow-up
study of 3931 patients. Inflamm Bowel Dis.
19(7):1404-10. 2013. PMID: 23665964. IF: 5,475.
DOI: 10.1097/MIB.0b013 e318281f28f
F Fernández-Bañares, MR de Sousa, A Salas, B
Beltrán, M Piqueras, EI glesias, JP Gisbert, B Lobo,
V Puig-Diví, E García-Planella, I Ordás, M Andreu, M
Calvo, M Montoro, M Esteve, JM Viver for the
– 112 –
Gisbert JP, Pérez-Aisa A, Bermejo F, CastroFernández M, Almela P, Barrio J, Cosme A, Modolell
I, Bory F, Fernández-Bermejo M, Rodrigo L, Ortuño
J, Sánchez-Pobre P, Khorrami S, Franco A, Tomas
A, Guerra I, Lamas E, Ponce J, Calvet X. Secondline rescue therapy with levofloxacin after failure of
treatment to eradicate Helicobacter pylori infection:
time trends in a Spanish multicenter study of 1,000
patients. J Clin Gastroenterol. 47(2):130-5. 2013.
PMID:
22647827.
IF:3,186.
DOI:
10.1097/MCG.0b013e318254ebdd
P Marticorena-Álvarez, M Chaparro, A Pérez-Casas,
JP Gisbert. Reply to Dr. Katsanos et al's letter. J
Crohn Colitis. 7(1):e23-4. 2013. PMID: 22921467.
IF: 3,562. DOI: 10.1016/j.crohns.2012.07.008
Chaparro M, Trapero-Marugán M, Guijarro M, López
C, Moreno-Otero R, Gisbert JP. Dysplasia and colorectal cancer in a patient with ulcerative colitis and
primary sclerosing cholangitis: a case report and a
short review of the literature. J Crohns Colitis.
7(2):e61-5. 2013. PMID: 22552273. IF: 3,562. DOI:
10.1016/j.crohns.2012.04.005
García-Bosch O, Gisbert JP, Cañas-Ventura A,
Merino O, Cabriada JL, García-Sánchez V, Gutiérrez
A, Nos P, Peñalva M, Hinojosa J, García-Planella E,
Muñoz F, Calvet X, Panés J. Observational study on
the efficacy of adalimumab for the treatment of
ulcerative colitis and predictors of outcome. J
Crohns Colitis. 7(9):717-22. 2013. PMID: 23142005.
IF: 3,562. DOI: 10.1016/j.crohns.2012.10.004
AREA 3
Molina-Infante J, Gisbert JP. Quadruple therapy for
Helicobacter
pylori
infection.
Lancet.
381(9876):1459-1459. 2013. PMID: 23622281. IF:
39,207. DOI: 10.1016/S0140-6736(13)60925-3
Feagan BG, Rutgeerts P, Sands BE, Hanauer S,
Colombel JF, Sandborn WJ, Van Assche G, Axler J,
Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant
T, Xu J, Parikh A; GEMINI 1 Study Group.
Collaborators (225). Vedolizumab as induction and
maintenance therapy for ulcerative colitis. N Engl J
Med. 369(8):699-710. 2013. PMID: 23964932. IF:
54,420. DOI: 10.1056/NEJMoa1215734
Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S,
Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee
S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J,
Stephens K, Milch C, Parikh A; GEMINI 2 Study
Group. Vedolizumab as induction and maintenance
therapy for Crohn's disease. N Engl J Med.
369(8):711-721. 2013. PMID: 23964933. IF: 54,420.
DOI: 10.1056/NEJMoa1215739
DY Graham, JP Gisbert. Helicobacter pylori: tailored
therapy with novel sequential quadruple therapies.
Nature Reviews Gastroenterol & Hepatol. 10(1):6-8.
2013.
PMID:
23183788.
IF:
10,807.DOI:
10.1038/nrgastro.2012.232
JP Gisbert, M Chaparro. Vaccination strategies in
patients with inflammatory bowel disease. Nature
Reviews Gastroenterol & Hepatol. 10(5):277-85.
2013. PMID: 23419290. IF: 10,807. DOI:
10.1038/nrgastro.2013.28
W Zabala, R Cruz, M Barreiro-de Acosta , M
Chaparro, J Panes, A Echarri, M Esteve, D Carpio, M
Andreu, E García-Planella, E Domenech, A
Carracedo, JP Gisbert, F Barros. New genetic associations in thiopurines related bone marrow toxicity
among inflammatory bowel disease patients.
Pharmacogenomics. 14(6):631-40. 2013. PMID:
23570467. IF: 5,513. DOI: 10.2217/pgs.13.38
JP Gisbert. Gastric MALT lymphoma. Rev Esp
Enferm Dig. 105(5):303. 2013. PMID: 23971664. IF:
1,317. DOI: 10.2217/pgs.13.38
J Molina-Infante, JP Gisbert. Probiotics for
Helicobacter pylori eradication therapy: not ready for
prime time. Rev Esp Enferm Dig. 105(8):441-444.
2013. PMID: 24274440. IF: 1,317
Bermejo F, Algaba A, Guerra I, Chaparro M, De-LaPoza G, Valer P, Piqueras B, Bermejo A, GarcíaAlonso J, Pérez MJ, Gisbert JP. Should be monitor
vitamin B12 and folate levels in Crohn's disease
patients?. Scand J Gastroenterol. 48(11):12721277. 2013. PMID: 24063425. IF: 2,329. DOI:
10.3109/00365521.2013.836752
Gisbert JP, Molina-Infante J, Marin AC, Vinagre G,
Barrio J, McNicholl AG. Second-line rescue triple
therapy with levofloxacin after failure of non-bismuth
quadruple "sequential" or "concomitant" treatment
to eradicate H. pylori infection. Scand J
– 113 –
AREA 3AREA 2 AREA 1
Algaba A, Linares PM, Fernández-Contreras ME,
Ordoñez A, Trápaga J, Guerra I, Chaparro M, de la
Poza G, Gisbert JP, Bermejo F. Relationship
between levels of angiogenic and lymphangiogenic
factors and the endoscopic, histological and clinical
activity, and acute-phase reactants in patients with
inflammatory
bowel
disease.
J
Crohns
Colitis.7(11):e569-79. 2013. PMID: 23642997. IF:
3,562. DOI: 10.1016/ j.crohns.2013.04.005
Castells A, Bessa X, Quintero E, Bujanda L, Cubiella
J, Salas D, Lanas A, Carballo F, Morillas JD,
Hernández C, Jover R, Montalvo I, Arenas J, Cosme
A, Hernández V, Iglesias B, Castro I, Cid L, Sala T,
Ponce M, Andrés M, Teruel G, Peris A, Roncales MP,
González-Rubio F, Seoane-Urgorri A, Grau J,
Serradesanferm A, Pellisé M, Ono A, Cruzado J,
Pérez-Riquelme F, Alonso-Abreu I, Carrillo-Palau M,
de la Vega-Prieto M, Iglesias R, Amador J, Blanco
JM, Sastre R, Ferrándiz J, González-Hernández MJ,
Andreu M; COLONPREV study investigators.. Risk
of advanced proximal neoplasms according to distal
colorectal findings: comparison of sigmoidoscopybased strategies. J Natl Cancer Inst. 105(12):878886. 2013. PMID: 23708054. IF: 15,161. DOI:
10.1093/jnci/djt117
Gastroenterol. 48(6):652-656. 2013. PMID:
23556551. IF: 2,329. DOI: 10.3109/00365521.
2013.786132
Hernández-Breijo B, Monserrat J, Román ID,
González-Rodríguez A, Fernández-Moreno MD,
Lobo MV, Valverde AM, Gisbert JP, Guijarro LG.
Azathioprine desensitizes liver cancer cells to
insulin-like growth factor 1 and causes apoptosis
when it is combined with bafilomycin A1. Toxicol
Appl Pharmacol. 272(3):568-578. 2013. PMID:
23958494. IF: 3,630. DOI: 10.1016/j.taap.2013.
07.024
BOOKS
JP Gisbert. Errores frecuentes en el manejo de las
formas graves de enfermedad inflamatoria intestinal.
Manual de Emergencias en Gastroenterología y
Hepatología. 2ª edición. 2013. Editores: M Montoro,
JC García-Pagán. Jarpyo. Edit. Pag. 271-284.
T Parra Cid, M Calvino Fernández, S Benito, JP
Gisbert. Role of reactive oxygen species (ROS) and
apoptosis in Helicobacter pylori infection. I. Laher
(ed.), Systems Biology of Free Radicals and AntiOxidants. 2013. Springer-Verlag Berlín Heidelberg.
ISBN: 978-3-642-300-17-2. págs. 1-22.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: PÉREZ GISBERT,
FRANCISCO JAVIER
Crónica-UC: Evaluación de la capacidad diagnóstica del
cuestionario de Walmsley utilizado en una aplicación
online(cumplimentado por el propio paciente "vía web")
en comparación con el mismo cuestionario aplicado por
el médico en su consulta en pacientes con colitis
ulcerosa; (versión1: 20-11-12). MERCK SHARP &
DOHME DE ESPAÑA, S.A. MSD-COL-2012-01
– 114 –
PRINCIPAL RESEARCHER: PÉREZ GISBERT, FRANCISCO JAVIER
Estudio de la maduración de los linfocitos B "naïve" y la
capacidad de secreción de anticuerpos contra los fármacos anti-TNF; (versión diciembre 2012). Estudio SECRECION. GIS-CB-2013
Estudio aleatorizado, controlado con producto activo, con
doble enmascaramiento y periodo de extensión abierto
para evaluar la eficacia, seguridad y tolerabilidad a largo
plazo de 3,2g/día de TP05 para el tratamiento de la colitis ulcerosa (CU) activa; (Versión 1.2: 10-04-13). TILLOTS
PHARMA AG. TP0503. EudraCT: 2013-000366-11
Atención telemática por enfermería en una unidad monográfica de enfermedad inflamatoria intestinal; (versión 1 de
julio 2013). GIS-2013-TELEMATICA
Rifaximina asociado a la triple terapia clásica (inhibidor de
la bomba de protones, amoxicilina y claritromicina) para la
erradicación de la infección por Helicobacter pylori;
(Versión 1: 09-04-13). JAVIER P. GISBERT (DIGESTIVO).
R+OCA. EudraCT: 2013-001080-23
Estudio en fase II, multicéntrico, aleatorizado, doble ciego,
con dosis múltiples, controlado con placebo, con grupos
paralelos para evaluar la eficacia, farmacocinética y
seguridad de BI 655066, un anticuerpo monoclonal
antagonista de IL-23 p 19, en pacientes con Enfermedad
de Crohn activa de moderada a grave sin tratamiento previo anti-TNF o en pacientes que hayan recibido previamente tratamiento anti-TNF, versión 1.0: 08-08-13).
BOEHRINGER INGELHEIM ESPAÑA, S.A. 1311.6.
EudraCT: 2013-002902-29
FRANCISCO JAVIER
Estudio retrospectivo sobre práctica clínica en
AREA 3
FRANCISCO JAVIER
Terapia erradicadora de H. pylori de rescate con moxifloxacino tras el fracaso de un primer tratamiento erradicador; (Versión 1: 13-11-13). GIS-MOXI-2013
AREA 3AREA 2 AREA 1
pacientes con Enfermedad de Crohn y cirugía
ileocólica en España; (Versión 1: 20-09-13). Estudio
PRACTICROHN. MERCK SHARP AND DOHME DE
ESPAÑA, S.A. MSD-CRO-2013-01
– 115 –
Line 3.3
Progenitors and
cell therapy
GRUPO 39
HEAD OF LABORATORY
Luis Madero López
GROUP MEMBERS
• Isabel Colmenero Blanco
• Miguel Ángel Díaz Pérez
• Lucía Fernández Casanova
• Ana María Gómez García
• África González Murillo
• Marta González Vicent
• Álvaro Lassaletta Atienza
• Evangelina Muñoz Mayoral
• Antonio Pérez Martínez
• Manuel Ramírez Orellana
• Julián Sevilla Navarro
• Jaime Valentín Quiroga
RESEARCH INTEREST
The main results from the activity of the group led
by Dr. Luís Madero during 2013 were as follows:
• The Group published a total of 18 articles in scientific journals, 2 chapters in books, and 8
abstracts in scientific meetings, either as its own
work or as collaborations with other groups.
• Two proposals were funded by Ministerio de
Sanidad at the 2013 call. Dr. Luís Madero
(Identifying and validating biomarkers of relapse in
childhood
acute
lymphoblastic
leukemia,
PI13/02475) and Dr. Manuel Ramírez (Study of
mechanisms of action of CELYVIR in pediatric
tumors: optimizing clinical outcomes, PI13/02487)
are principal investigators in each of these projects.
– 116 –
Fig.1.
We published a multicentric study (MartínezLaperche C, Gómez-García AM, Lassaletta A,
Moscardó C, Vivanco JL, Molina J, Fuster JL,
Couselo JM, Sánchez de Toledo J, Bureo E,
Madero L, Ramírez M. Detection of occult cerebrospinal fluid involvement during maintenance
therapy identifies a group of children with acute
lymphoblastic leukemia at high risk for relapse. Am.
J.
Hematol.
2013;
88:359-64.
DOI:
10.1002/ajh.23407.) on the role of flow cytometry
(FCM) for detecting subclinical leukemic involvement of the central nervous system (CNS).
While no differences in relapse free survival (RFS)
and overall survival (OS) were observed between
patients with (FCM+) or without (FCM-) CNS
leukemia at diagnosis, the detection of subclinical
CNS disease by FCM during maintenance was
associated with significantly lower 3-years RFS and
OS. A sensitive methodology like FCM can be
applied for a close follow-up of the levels of ALL in
AREA 3
MAJOR GRANTS
• Luis Madero López. Detección de infiltración leptomeníngea en niños con tumores del sistema
nervioso 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. EC11559. Duration: 2012 - 2013.
• Antonio Pérez Martínez. 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.
• Miguel Ángel Díaz Pérez. Trasplante de progenitores hematopoyéticos de donante familiar haploidéntico con infusión de linfocitos del donante
tras alodeplección selectiva “in vitro”, en
pacientes pediátricos con hemopatías malignas
de alto riesgo. ISCIII. EC11/024. 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.
• Luis Madero López. Estudio de los mecanismos
de acción de la terapia con CELVIR en tumores
infantiles: hacia la optimización de los resultados
clínicos. ISCIII. PI13/02487. Duration: 2014 –
2016.
• Luis Madero López. Identificación y validación de
biomarcadores de recaída infantil LLA leucemia.
PUBLICATIONS
(10)
[IF: 31,15]
YEAR
Total IF
Publication No.
Q1
2011
56,421
20
6
2012
37,913
21
2
2013
31,15
10
3
Martínez-Laperche
C,
Gómez-García
AM,
Lassaletta Á, Moscardó C, Vivanco JL, Molina J,
Fuster JL, Couselo JM, de Toledo JS, Bureo E,
Madero L, Ramírez M. Detection of occult cerebrospinal fluid involvement during maintenance
therapy identifies a group of children with acute
lymphoblastic leukemia at high risk for relapse. Am
J Hematol. 88(5):359-364. 2013. PMID: 23468276.
IF: 3,477. DOI: 10.1002/ajh.23407
Rabusin M, Snowden JA, Veys P, Quartier P, Dalle
JH, Dhooge C, Di Bartolomeo P, Gonzalez-Vicent
M, Gibson B, Iriondo A, Juergens H, Lisukov I,
Messina C, Mialou V, Steward CG, Urban C,
Renard M, Giurici N, Peters C, Badoglio M, Ronfani
L, Dini G, Farge D, Saccardi R; European Group for
– 117 –
AREA 3AREA 2 AREA 1
CFS samples, and may identify a group of patients
at high risk for relapse.
Blood and Marrow Transplantation Autoimmune
Diseases and Paediatric Disease Working Parties.
Long-term outcomes of hematopoietic stem cell
transplantation for severe treatment-resistant
autoimmune cytopenia in children. Biol Blood
Marrow Transplant. 19(4):666-669. 2013. PMID:
23253561.
IF:
3,348.
DOI:
10.1016/j.bbmt.2012.12.008
Sanz J, Picardi A, Hernández Boluda JC, Martín C,
Ferrá C, Nozzoli C, Gonzalez-Vicent M, Rambaldi
A, Valcarcel D, Verdeguer A, Serrano D, de Heredia
CD, Pascual MJ, de Paz R, Montesinos P,
Bartolozzi B, Algarotti A, Sanz MA, Arcese W, Sanz
GF; GETH and GITMO. Impact of graft-versus-host
disease prophylaxis on outcomes after myeloablative single-unit umbilical cord blood transplantation. Biol Blood Marrow Transplant. 19(9):13871392. 2013. PMID: 23850652. IF: 3,348. DOI:
10.1016/j.bbmt.2013.07.004
Fiuza-Luces C, González-Murillo A, SoaresMiranda L, Palacio JM, Colmenero I, Casco F,
Melén G, Morán M, Lucía A, Ramírez M. Effects of
exercise interventions in graft versus host disease
models. Cell Transplant. 22(12):2409-20. 2013.
PMID:
23127525.
IF:
3,570.
DOI:
10.3727/096368912X658746
Soares-Miranda L, Fiuza-Luces C, Lassaletta A,
Santana-Sosa E, Padilla JR, Fernández-Casanova
L, Lorenzo-González R, López-Mojares LM, Pérez
M, Pérez-Martínez A, Lucia A. Physical Activity in
Pediatric Cancer patients with solid tumors
(PAPEC): trial rationale and design. Contemp Clin
Trials. 36(1):106-15. 2013. PMID: 23747802. IF:
1,986. DOI: 10.1016/j.cct.2013.05.012
Sevilla J, Guillén M, Castillo A, Prudencio M,
González-Vicent M, Lassaletta Á, Cormenzana M,
Ramírez M, Pérez-Martínez A, Madero L, DíazPérez MÁ. Defining "poor mobilizer" in pediatric
patients who need an autologous peripheral blood
progenitor cell transplantation. Cytotherapy.
15(1):132-137. 2013. PMID: 23260093. IF: 3,100.
DOI: 10.1016/j.jcyt.2012.10.004
– 118 –
Fiuza-Luces C, Soares-Miranda L, GonzálezMurillo A, Palacio JM, Colmenero I, Casco F, Melén
GJ, Delmiro A, Morán M, Ramírez M, Lucia A.
Exercise benefits in chronic graft versus host disease: a murine model study. Med Sci Sports Exerc
45(9):1703-1711. 2013. PMID: 23954992. IF:
4,459. DOI: 10.1249/MSS.0b013e31828fa004
Baskin JL, Lezcano E, Kim BS, Figueredo D,
Lassaletta A, Perez-Martinez A, Madero L, Caniza
MA, Howard SC, Samudio A, Finlay JL.
Management of children with brain tumors in
Paraguay. Neuro Oncol. 15(2):235-41. 2013. PMID:
23197688.
IF:
5,286.
DOI:
10.1093/neuonc/nos291
Mirones I, de Prada I, Gómez AM, Luque A, Matín
T R, Pérez-Jiménez MA, Madero L, García-Castro
J, Ramírez M. A Role for the CXCR3/CXCL10 Axis
in Rasmussen Encephalitis. Pediatr Neurol.
49(6):451-457. 2013. PMID: 24080276. IF: 1,504.
DOI: 10.1016/j.pediatrneurol.2013.07.019
González-Vicent M, Herrero B, Guillén M, Sevilla J,
Díaz MA. Using Rheopheresis for stem cell
Transplantation-Associated
Thrombotic
Microangiopathy (TA-TMA). Transfus Apher Sci.
49(2):234-7. 2013. PMID: 23768689. IF: 1,072.
DOI: 10.1016/j.transci.2013.05.004
BOOKS
J Sevilla, L Madero. Linfomas Infantiles. Manual de
Pediatría 3ª edición. 2013. Ergón ed. ISBN: 97884-15351-57-3.
Ramírez M, García-Castro J. Treatment of
Metastatic Neuroblastoma with Mesenchymal Stem
Cell–Based Oncolytic Virotherapy. “Stem cell therapeutics for cancer”. 2013. John Wiley & Sons.
ISBN: 978-1-118282427.
AREA 3
PRINCIPAL RESEARCHER: LASSALETTA ATIENZA, ÁLVARO
Estudio de fase 2, multicéntrico y de un solo brazo
de moxetumomab pasudotox en pacientes
pediátricos con leucemia linfoblástica aguda infantil o linfoma linfoblástico b refractarios o en recidiva. MedImmune, LLC. CD-ON-CAT8015-1036.
EudraCT: 2012-003101-10
PRINCIPAL RESEARCHER: LASSALETTA ATIENZA, ÁLVARO
Estudio multicéntrico de seguimiento a largo plazo
de pacientes con LNH que han recibido tratamiento con NI-0501, un anticuerpo monoclonal antiinterferón gamma. Novlmmune S.A. NI-0501-05.
EudraCT: 2012-005753-23
PRINCIPAL RESEARCHER: SEVILLA NAVARRO,
JULIÁN
Estudio abierto, aleatorizado, de grupos paralelos,
controlado con fármaco activo, multicéntrico, de
no-inferioridad de dabigatrán etexilato frente al
cuidado estándar para el tratamiento del tromboembolismo venoso en niños desde recién nacidos hasta menos de 18 años. Boehringer Ingelheim
España, S.A. 1160.106. EudraCT: 2013-00211412
PRINCIPAL RESEARCHER: SEVILLA NAVARRO,
JULIÁN
Estudio combinado de fase 1/2 de búsqueda de
dosis y comparativo, abierto, aleatorizado, para
evaluar la eficacia y seguridad de plerixafor junto
con regímenes estándar para la movilización de
células madre hematopoyéticas a sangre periférica, y posterior recolección por aféresis, frente a
solo regímenes estándar para la movilización en
pacientes pediátricos, de 2 a <18 años, con
tumores sólidos que reúnen los requisitos para
trasplantes autólogos. Genzyme Europe BV.
MOZ15609/DFI12860. EudraCT: 2010-019340-40
AREA 3AREA 2 AREA 1
CLINICAL TRIALS
– 119 –
Line 3.4
Advanced therapies
in oncohematology
Guillem V, Hernández-Boluda JC, Gallardo D, Buño I,
Bosch A, Martínez-Laperche C, de la Cámara R,
Brunet S, Martin C, Nieto JB, Martínez C, Pérez A,
Montoro J, Garcia-Noblejas A, Solano C. A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell
transplantation. Am J Hematol. 88(10):883-889. 2013.
PMID: 23813863. IF: 3,477. DOI: 10.1002/ajh.23523
GRUPO 44
HEAD OF LABORATORY
Juan Luis Steegmann Olmedillas
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. 2013. PMID: 22948274. IF: 2,396. DOI:
10.1007/s00277-012-1565-4
GROUP MEMBERS
• Adrián Alegre Amor
• María Reyes Arranz Sáez
• María Jimena Cannata Ortiz
• Ángela Figuera Álvarez
• Ana María García-Noblejas Moya
• Valle Gómez García de Soria
• Jimena Jiménez Braña
• Javier Loscertales Pueyo
Blanes M, Lahuerta JJ, González JD, Ribas P, Solano
C, Alegre A, Bladé J, San Miguel JF, Sanz MA, de la
Rubia J. Intravenous Busulfan and Melphalan as a
Conditioning Regimen for Autologous Stem Cell
Transplantation in Patients with Newly Diagnosed
Multiple Myeloma: A Matched Comparison to a
Melphalan-only Approach. Biology Blood Marrow
Transplantation. 19(1):69-74. 2013. PMID: 22897964.
IF: 3,348. DOI: 10.1016/j.bbmt.2012.08.009
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
– 120 –
YEAR
Total IF
Publication No.
2011
86,163
17
Q1
9
2012
148,549
21
14
2013
92,258
15
9
Moreno JM, Wojnicz A, Steegman JL, Cano-Abad MF,
Ruiz-Nuño A. Imatinib assay by high-performance liquid chromatography in tandem mass spectrometry
with solid-phase extraction in human plasma. Biomed.
Chromatogr. 27(4):502-8. 2013. PMID: 23034891. IF:
1,945. DOI: 10.1002/bmc.2819
Baccarani M, Deininger MW, Rosti G, Hochhaus A,
Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes
JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian
HM, Kim DW, Larson RA, Lipton JH, Mahon FX,
Martinelli G, Mayer J, Müller MC, Niederwieser D, Pane
F, Radich JP, Rousselot P, Saglio G, Saußele S, Schiffer
C, Silver R, Simonsson B, Steegmann JL, Goldman JM,
Hehlmann R. European Leukemianet recommendations
for the management of chronic myeloid leukemia. Blood
122(6):872-884. 2013. PMID: 23803709. IF: 9,975.
DOI: 10.1182/blood-2013-05-501569
AREA 3
Steegmann JL, Sánchez Torres JM, Colomer R, Vaz A,
López J, Jalón I, Provencio M, González-Martín A,
Pérez M. Prevalence and management of anaemia in
patients with non-myeloid cancer undergoing systemic
therapy: a Spanish survey. Clin Transl Oncol.
15(6):477-83. 2013. PMID: 23263906. IF: 1,600. DOI:
10.1007/s12094-012-0953-5
Costa D, Muñoz C, Carrió A, Nomdedeu M, Calvo X,
Solé F, Luño E, Cervera J, Vallespí T, Berneaga D,
Gómez C, Arias A, Such E, Sanz G, Grau J, Insunza A,
Calasanz MJ, Ardañaz MT, Hernández JM, Azaceta G,
Álvarez S, Sánchez J, Martín ML, Bargay J, Gómez V,
Cervero CJ, Allegue MJ, Collado R, Campo E,
Nomdedeu B; Spanish Group of Myelodysplastic
Syndromes (GESMD). Reciprocal translocations in
myelodysplastic syndromes and chronic myelomonocytic leukemias: review of 5,654 patients with an evaluable karyotype. Genes Chromosomes Cancer
52(8):753-763. 2013. PMID: 23686965. IF: 3,836. DOI:
10.1002/gcc.22071
Ribrag V, Caballero D, Fermé C, Zucca E, Arranz R,
Briones J, Gisselbrecht C, Salles G, Gianni AM, Gomez
H, Kahatt C, Corrado C, Szyldergemajn S, Extremera
S, de Miguel B, Cullell-Young M, Cavalli F. Multicenter
phase II study of plitidepsin in patients with
relapsed/refractory
non-Hodgkin's
lymphoma.
Haematologica. 98(3):357-63. 2013. PMID: 23065525.
IF: 5,868. DOI: 10.3324/haematol.2012.069757
Arranz R, García-Noblejas A, Grande C, Cannata-Ortiz
J, Sánchez JJ, García-Marco JA, Aláez C, Pérez-Calvo
J, Martínez-Sánchez P, Sánchez-González B, Canales
MA, Conde E, Martín A, Arranz E,Terol MJ, Salar A,
Caballero D. First-line treatment with rituximabhyperCVAD alternating with rituximab-methotrexatecytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from
the GELTAMO group. Haematologica. 98(10):15631570. 2013. PMID: 23753021. IF: 5,868. DOI:
10.3324/haematol.2013.088377
Almeida C, Stepkowska A, Alegre A, Nogueira JM.
Determination of trace levels of benzophenone-type
ultra-violet filters in real matrices by bar adsorptive
micro-extraction using selective sorbent phases. J
Chromatogr A. 1311:1-10. 2013. PMID: 24011723. IF:
4,258. DOI: 10.1016/j.chroma.2013.08.007
Miguel JS, Weisel K, Moreau P, Lacy M, Song K,
Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A,
Alegre A, Chen C, Cavo M, Garderet L, Ivanova V,
Martinez-Lopez J, Belch A, Palumbo A, Schey S,
Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M,
Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for
patients with relapsed and refractory multiple myeloma
(MM-003): a randomised, open-label, phase 3 trial.
Lancet Oncol. 14(11):1055-1066. 2013. PMID:
24007748. IF: 24,725. DOI: 10.1016/S14702045(13)70380-2
Hoffmann VS, Baccarani M, Lindoerfer D, Castagnetti
F, Turkina A, Zaritsky A, Hellmann A, Prejzner W,
Steegmann JL, Mayer J, Indrak K, Colita A, Rosti G,
Pfirrmann M. The EUTOS prognostic score-review and
validation in 1288 patients with CML treated frontline
with imatinib. Leukemia. 27(10):2016-2022. 2013.
PMID:
23752173.
IF:
9,379.
DOI:
10.1038/leu.2013.171
Paiva B, Vídriales MB, Rosiñol L, Martínez-López J,
Mateos MV, Ocio EM, Montalbán MÁ, Cordón L,
Gutiérrez NC, Corchete L, Oriol A, Terol MJ, Echeveste
MA, De Paz R, De Arriba F, Palomera L, de la Rubia J,
– 121 –
AREA 3AREA 2 AREA 1
Martinez-Lopez J, Fernández-Redondo E, García-Sánz
R, Montalbán MA, Martínez-Sánchez P, Pavia B,
Mateos MV, Rosiñol L, Martín M, Ayala R, Martínez R,
Blanchard MJ, Alegre A, Besalduch J, Bargay J,
Hernandez MT, Sarasquete ME, Sanchez-Godoy P,
Fernández M, Blade J, San Miguel JF, Lahuerta JJ;
GEM
(Grupo
Español
Multidisciplinar
de
Melanoma)/PETHEMA (Programa para el Estudio de la
Terapéutica en Hemopatías Malignas) cooperative
study group. Clinical applicability and prognostic significance of molecular response assessed by fluorescentPCR of immunoglobulin genes in multiple myeloma.
Results from a GEM/PETHEMA study. Br J Haematol.
163(5):581-9. 2013. PMID: 24117042. IF: 4,952. DOI:
10.1111/bjh.12576
Díaz-Mediavilla J, Granell M, Gorosquieta A, Alegre A,
Orfao A, Lahuerta JJ, Bladé J, Miguel JF. A multiparameter flow cytometry immunophenotypic algorithm for
the identification of newly diagnosed symptomatic
myeloma with an MGUS-like signature and long-term
disease control. Leukemia. 27(10):2056-2061. 2013.
PMID: 23743858. IF: 9,379. DOI: 10.1038/leu.2013
García-Noblejas A, Velasco A, Cannata-Ortiz J, Arranz
R. Spontaneous regression of immunodeficiency associated plasmablastic lymphoma related to methotrexate after decrease of dosage. Med Clin (Barc).
140(12):569-70. 2013. PMID: 23177304. IF: 1,252.
DOI: 10.1016/j.medcli.2012.10.001
BOOKS
A Alegre. Mapa Docente y Elección Preferente de
Plazas MIR de Hematología. Libro de Ponencias del III
Curso de Tutores MIR de Hematología. 2013. FEHH.
Madrid.
M Santamaría, A Marbini, N Cuenca, A Alegre et al.
Guía de Recursos Sociales para Pacientes
Hematológicos. 2013. Fundación Leucemia y Linfoma.
Madrid.
M Santamaría, A Marbini, N Cuenca, A Alegre et al.
Guía de Recursos Sociales para Pacientes
Hematológicos. 2013. Fundación Leucemia y Linfoma.
Madrid.
A Alegre, M Canales y J Delgado. Monografía de
Bendamustina en Síndromes Linfoproliferativos
Crónicos. 2013. Editorial You and Us. Madrid.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ALEGRE AMOR, ADRIÁN
Estudio en fase II, multicéntrico y sin enmascaramiento
– 122 –
para determinar la eficacia y la seguridad de pomalidomida (CC-4047) en combinación con dosis bajas de
dexametasona en sujetos con mieloma múltiple recurrente o resistente al tratamiento y con insuficiencia
renal moderada o grave, incluidos los sujetos sometidos a hemodiálisis; (Versión 01-05-13). CELGENE
CORPORATION. CC-4047-MM-013. EudraCT: 2013001903-36
PRINCIPAL RESEARCHER: ALEGRE AMOR, ADRIÁN
Estudio prospectivo, longitudinal y observacional en
pacientes con diagnóstico reciente de mieloma múltiple (MM), para evaluar la relación entre los resultados
alcanzados en los pacientes, sus pautas de tratamiento y sus perfiles moleculares; (versión 2.0: 09-09-11).
MULTIPLE MYELOMA RESEARCH FOUNDATION
(MMRF). MMR-INM-2013-01
PRINCIPAL RESEARCHER: ARRANZ SÁEZ, MARÍAREYES
Estudio fase 3, aleatorizado, doble ciego, controlado
con placebo del inhibidor de la Tirosina Quinasa de
Bruton (BTK), PCI-32765 (Ibrutinib) en combinación
con bendamustina y rituximab (BR) en sujetos con
Linfoma de Células del Manto de nuevo diagnóstico;
(Versión original: 20-12-12). JANSSEN-CILAG INTERNATIONAL NV. PCI-32765MCL3002. EudraCT: 2012004056-11
Estudio de fase III, aleatorizado, doble ciego, controlado con placebo, para evaluar la eficacia y seguridad de
idelalisib (GS-1101) en combinación con bendamustina
y rituximab en linfomas no Hodgkin previamente tratados;(Versión Amend 2.1: 19-03-13). GILEAD SCIENCES, INC GS-US-313-0125. EudraCT: 2012004034-42
Estudio fase 3, aleatorizado, doble ciego y controlado con placebo del inhibidor de la tirosina quinasa de
Bruton (BTK), PCI-327665 (ibrutinib) en comparación
con rituximab, ciclofosfamida, doxorubicina, vincristina y prednisona (R-CHOP) en sujetos con nuevo
AREA 3
Estudio fase IIIB, multicéntrico, randomizado, abierto, comparativo, con dos brazos sobre la eficacia y la
seguridad de lipegfilgrastim (Lonquex,TEVA) en comparación con pegfilgrastim (Neulasta«, Amgen) en
pacientes de edad avanzada con linfomas no
Hodgkin agresivos de células B con alto riesgo de
neutropenia inducida por R-CHOP-21 Avoid
Neutropenia; (Versión 23-05-13). MERCKLE
GMBH/LACER S.A. XM22-ONC-305. EudraCT:
2013-001284-23
Registro de PNH (hemoglobinuria paroxística nocturna); (Versión 4.0.1 ESP: 27-01-11). Aplicable solo
para España. LEXION PHARMACEUTICALS INC.
ALE-ECU-2009-01/M07-001
PRINCIPAL RESEARCHER: FIGUERA ÁLVAREZ,
ÁNGELA
Estudio fase 3, aleatorizado, doble ciego y controlado con placebo para comparar la eficacia y la seguridad de azacitidina oral más el mejor tratamiento de
apoyo frente al mejor tratamiento de apoyo como
terapia de mantenimiento en pacientes con leucemia
mieloide aguda en remisión completa ;(versión: final:
15-08-12). CELGENE CORPORATION. CC-486AML-001. EudraCT: 2012-003457-28
ÁNGELA
Estudio en fase IB/II para evaluar la seguridad y la eficacia de PF-004449913, inhibidor oral de la Vía
Hedgehog, en combinación con quimioterapia intensiva, dosis bajas de Ara-C o decitabina, administrado a pacientes con leucemia mieloide aguda o síndrome mielodisplásico de alto riesgo; (versión
enmienda 2: 01-11-12). PFIZER INC. B1371003.
EudraCT: 2012-000684-24
ÁNGELA
Estudio multicéntrico, observacional, retrospectivo,
según práctica clínica, de la profilaxis de la infección
fúngica invasiva con posaconazolen pacientes diagnosticados de Leucemia Mieloide Aguda y Síndrome
Mielodisplásico sometidos a tratamiento de quimioterapia intensiva; (versión Mayo 2013). ASOCIACION
MADRILEÑA DE HEMATOLOGIA. FMH-POS-01
PRINCIPAL RESEARCHER: GARCÍA NOBLEJAS
MOYA, ANA MARÍA
Análisis de la experiencia nacional con Trasplante
Autólogo de Progenitores Hematopoyéticos (TASPE)
en pacientes diagnosticados de Linfoma de Células del
Manto (LCM); (Versión final: julio de 2013). GELTAMO.
AUTO-LCM
PRINCIPAL RESEARCHER: GÓMEZ GARCÍA-SORIA,
VALLE
Estudio piloto abierto, fase II, randomizado, para evaluar el efecto de deferasirox combinado con
eritropoyetina comparado con eritropoyetina sola, en
términos de mejoría eritroide, en pacientes con síndrome mielodisplásico de riesgo bajo e int-1. (Versión
00: 17-04-13). NOVARTIS FARMACEUTICA, S.A.
CICL670A2421. EudraCT: 2013-000981-12
PRINCIPAL RESEARCHER: LOSCERTALES PUEYO,
JAVIER
Estudio de fase 3, aleatorizado, controlado para evaluar la eficacia y seguridad de GS-1101 (CAL-101) en
combinación con ofatumumab para el tratamiento de
la leucemia linfocítica crónica previamente tratada;
(versión: 1.1: 16-10-12). NUEVO TITULO: Estudio de
fase 3, aleatorizado, controlado para evaluar la eficacia
y seguridad de idelalisib (GS-1101) en combinación
con ofatumumab para el tratamiento de la leucemia linfocítica crónica previamente tratada; (Versión 3.0: 1710-13). GILEAD SCIENCES, INC. GS-US-312-0119.
EudraCT: 2012-001236-65
PRINCIPAL RESEARCHER: LOSCERTALES PUEYO,
JAVIER
Estudio multicéntrico, aleatorizado, doble ciego, de
grupos paralelos, controlado con placebo, de fase 3
– 123 –
AREA 3AREA 2 AREA 1
diagnóstico de linfoma difuso de células grandes B
del subtipo no centro germinal; (Versión final: 01-0513). JANSSEN-CILAG INTERNATIONAL NV. PCI32765DBL3001. EudraCT: 2013-000959-40
sobre la eficacia y seguridad de lenalidomida (Revlimid)
como tratamiento de mantenimiento en pacientes con
leucemia linfocítica crónica de alto riesgo tras el
tratamiento de primera línea (versión 2.1: 04-06-12).
UNIVERSIDAD DE COLONIA. RV-CLL-GCLLSG-0725.
EudraCT: 2011-004698-98
remisión libre de tratamiento (RLT)en pacientes con
LMC cromosoma Filadelfia positivo, después de dos
duraciones distintas de tratamiento de consolidación
con nilotinib 300mg BID; (versión 00: 20-11-12).
NOVARTIS FARMACEUTICA, S.A. CAMN107AIC05.
EudraCT: 2012-005124-15
PRINCIPAL RESEARCHER: STEEGMANN OLMEDILLAS, JUAN-LUIS
Estudio Fase II, abierto, de un único brazo, de remisión
libre de tratamiento en pacientes con leucemia
mieloide crónica (LMC) en fase crónica (FC)1 después
de conseguir una RM4.5 sostenida con nilotinib; versión 01: 07-07-13). NOVARTIS FARMACEUTICA, S.A.
CAMN107A2408. EudraCT: 2012-003186-18
Estudio fase III, aleatorizado, abierto de ponatinib
frente a imatinib en pacientes adultos con Leucemia
Mieloide Crónica de nuevo diagnóstico en fase crónica;
(Versión 2.0 enmienda 1: 05-07-12). ARIAD PHARMACEUTICALS, INC. AP24534-12-301. EudraCT: 2012001355-38
Estudio multicéntrico, de un único brazo, de remisión
libre de tratamiento de nilotinib en pacientes con
leucemia mieloide crónica en fase crónica con BCRABL1 positivo, que han alcanzado un estado de enfermedad residual mínima (ERM) duradera con tratamiento de primera línea con nilotinib; (versión 00: 31-10-12).
NOVARTIS FARMACEUTICA, S.A. CAMN107I2201.
EudraCT: 2012-004092-40
Estudio de extensión abierto del tratamiento de bosutinib para pacientes con Leucemia Mieloide Crónica
(LMC) que han participado previamente en los estudios
de bosutinib B1871006 o B1871008; (Versión final: 2502-13). PFIZER INC. B1871040. EudraCT: 2013000691-15
Estudio fase III, prospectivo, aleatorizado, abierto, con
dos brazos de tratamiento, para evaluar la tasa de
– 124 –
Registro de pacientes con leucemia mieloide crónica
con alta probabilidad de alcanzar respuesta molecular
completa; (Versión 5: julio de 2013). FUNDACIÓN
MIGUEL SERVET. FMS-LMC-2012-01/CM-REGISTRY
AREA 3
Line 3.5
Biological, cellular and
molecular monitoring in
oncohematology
this model as a relevant preclinical tool to validate new
therapeutic approaches with JAK2 inhibitors. This therapy warrant further investigation for use alone or in combination with standard chemotherapy in treating human
cancers with elevated JAK2 activity.
GRUPO 45
MAJOR GRANTS
GROUP MEMBERS
• Irene Bodega Mayor
• Álvaro Cuesta Domínguez
• Mónica Sala Valdés
• Matilde Santos Roncero
• Elena Fernández Ruiz . Implicación de JAK2 en el
reconocimiento de patógenos y en la respuesta inmune
innata. ISCIII. PI11/00128. Duration: 2012 - 2014.
• Elena Fernández Ruiz . Preclinical study of the efficacy of TG101348 inhibitor on ex-vivo cells from
high-risk BCR-ABL negative adult and childhood
acute lymphoblastic leukaemia with JAK2 mutations
and CRLF2 overexpression: assessment of disease
reversion in vivo in immunodeficient mice. SanofiAventis. Duration: 2013 – 2014.
RESEARCH INTEREST
Chromosomal translocations that give rise to fusion proteins are frequently associated with the etiology of hematologic neoplasm. The search for small tyrosine-kinase
inhibitors specific for fusion protein leading to leukemia is
an active area of research after the success of imatinibbased therapy. We have described the transforming and
tumorigenic activity of a new fusion protein, BCR-JAK2,
obtained from a patient with acute lymphoblastic
leukemia. This chimeric protein involves the BCR
oligomerization domain fused to the JAK2 tyrosinekinase domain. JAK2 is a non-receptor tyrosine-kinase
that mediates signaling of different cytokine receptors
and is crucial to normal hematopoiesis through the
recruitment of downstream effectors of cell proliferation
and survival. Our group successfully proved that cells
expressing BCR-JAK2 developed tumors when injected
subcutaneously into immunodeficient mice. In addition,
using a retrovirally-transduced bone marrow progenitor
transplantation model in mice, we demonstrated BCRJAK2 as the driving force of myeloproliferative disorder
with a fatal outcome. These findings support the use of
YEAR
Total IF
Publication No.
2011
-
-
Q1
-
2012
3,730
1
1
2013
7,587
2
1
Salazar-Aldrete C, Galán-Díez M, Fernández-Ruiz E,
Niño-Moreno P, Estrada-Capetillo L, Abud-Mendoza
C, Layseca-Espinosa E, Baranda L, GonzálezAmaro R. Expression and Function of Dectin-1 is
Defective in Monocytes from Patients with Systemic
Lupus Erythematosus and Rheumatoid Arthritis. J
Clin Immunol. 33(2):368-377. 2013. PMID:
23097038. IF: 2,654. DOI: 10.1007/s10875-0129821-x
– 125 –
AREA 3AREA 2 AREA 1
HEAD OF LABORATORY
Oncol. (4):6-89. 2013. PMID: 24305507. IF: 4,933.
DOI: 10.1186/1756-8722-6-89
• Cecilia Muñoz Calleja . Estudio de Dianas terapeúticas
novedosas en modelos preclínicos de linfoma y de
transplante de progenitores hematopoyéticos. ISCIII.
PI12/00494. Duration: 2013 – 2015.
GRUPO 46
HEAD OF LABORATORY
Cecilia Muñoz Calleja
GROUP MEMBERS
• Amada Elia Beltrán Núñez
• Carlos Cuesta Mateos
• Fernando Gómez-Reino Carnota
• Beatriz Somovilla Crespo
MAJOR GRANTS
• Cecilia Muñoz Calleja . Red de Investigación en
Inflamación y Enfermedades Reumáticas “RIER”. ISCIII. RD08/0075/0001. Duration: 2009 - 2013.
– 126 –
YEAR
Total IF
Publication No.
Q1
Q2
2011
-
-
-
2
2012
-
-
-
2013
4,933
1
1
Oncol. (4):6-89. 2013. PMID: 24305507. IF: 4,933.
DOI: 10.1186/1756-8722-6-89
AREA 3
GRUPO 48
HEAD OF LABORATORY
Luis Jesús Jiménez Borreguero
GROUP MEMBERS
• Río Jorge Aguilar Torres
• Fernando Alfonso Manterola
• Amparo Benedicto Buendía
• Paloma Caballero Sánchez-Robles
• Carmen del Arco Galán
• Alfonsa Friera Reyes
• Iluminada García Polo
• Paloma Gil Martínez
• Natividad Gómez Gómez
• Patricia Ibáñez Sanz
• Luis Martínez Elbal
• Fernando Moldenhauer Díaz
• Rosa María Moreno Carriles
• María José Olivera Serrano
• Ramón Puchades Rincón de Arellano
• Diego Real de Asúa Cruzat
• Antonio Reyes García
• Fernando Rivero Crespo
• Javier Roldan Núñez
• Nuria Ruiz-Giménez Arrieta
• Bernhard Seidelberger
• Carmen Suárez Fernández
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 arterial en
pacientes mayores de 65 años con hipertensión sistólica
aislada refractaria. MSPSI. EC11-111 (SPI/2885/2011).
Duration: 2012 - 2013.
• Fernando Moldenhauer Díaz. Estudio clínico, neuroanatómico y funcional mediante técnicas de neuroimagen en adultos con sd y sin demencia: patrones predictivos para el desarrollo de demencia. ISCIII. PI12/01695.
Duration: 2013 – 2015.
• Carmen Suárez Fernández. Plataforma Innovación: Red
de innovación en tecnologías médicas y sanitarias. ISCIII. PT13/0006/0016. Duration: 2014 - 2016.
• Fernando Alfonso Manterola. PREvention of late Stent
Thrombosis by an Interdisciplinary Global European
effort. EU/PRG.MARCO. PRESTIGE. Duration: 2014 -
YEAR
Total IF
Publication No.
Q1
2011
181,383
27
17
2012
154,580
22
11
2013
342,188
36
22
Fernández-Ortiz A, Jiménez-Borreguero LJ, Peñalvo
JL, Ordovás JM, Mocoroa A, Fernández-Friera L,
Laclaustra M, García L, Molina J, Mendiguren JM,
López-Melgar B, de Vega VM, Alonso-Farto JC, Guallar
E, Sillesen H, Rudd JH, Fayad ZA, Ibañez B, Sanz G,
Fuster V. The Progression and Early detection of
Subclinical Atherosclerosis (PESA) study: rationale and
design. Am Heart J. 166(6):990-8. 2013. PMID:
24268213. IF: 4,555. DOI: 10.1016/j.ahj.2013.08.024
Trujillo-Santos J, Schellong S, Falga C, Zorrilla V,
Gallego P, Barrón M, Monreal M; RIETE Investigators.
Low-molecular-weight or unfractionated heparin in
venous thromboembolism: the influence of renal function. Am J Med. 126(5):425-434. 2013. PMID:
– 127 –
AREA 3AREA 2 AREA 1
Line 3.6
New diagnostic and
therapeutic advances in
cardiovascular diseases
23499331. IF: 5.302. DOI: 10.1016/j.amjmed.2012.
09.021
Ibanez B, Macaya C, Sánchez-Brunete V, Pizarro G,
Fernández-Friera L, Mateos A, Fernández-Ortiz A,
García-Ruiz JM, García-Álvarez A, Iñiguez A, JiménezBorreguero J, López-Romero P, Fernández-Jiménez R,
Goicolea J, Ruiz-Mateos B, Bastante T, Arias M,
Iglesias-Vázquez JA, Rodriguez MD, Escalera N,
Acebal C, Cabrera JA, Valenciano J, Pérez de Prado A,
Fernández-Campos MJ, Casado I, García-Rubira JC,
García-Prieto J, Sanz-Rosa D, Cuellas C, HernándezAntolín R, Albarrán A, Fernández-Vázquez F, de la
Torre-Hernández JM, Pocock S, Sanz G, Fuster V.
Effect of early metoprolol on infarct size in ST-segmentelevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of
Metoprolol in Cardioprotection During an Acute
Myocardial Infarction (METOCARD-CNIC). Circulation.
128(14):1495-503. 2013. PMID: 24002794. IF: 14,948.
DOI: 10.1161/CIRCULATIONAHA.113.003653
García-Álvarez A, Fernández-Friera L, García-Ruiz JM,
Nuño-Ayala M, Pereda D, Fernández-Jiménez R,
Guzmán G, Sanchez-Quintana D, Alberich-Bayarri A,
Pastor-Escuredo D, Sanz-Rosa D,García-Prieto J,
Gonzalez-Mirelis JG, Pizarro G, Jimenez-Borreguero
LJ, Fuster V, Sanz J, Ibáñez B. Noninvasive monitoring
of serial changes in pulmonary vascular resistance and
acute vasodilator testing using cardiac magnetic resonance. J Am Coll Cardiol. 62(17):1621-31. 2013.
PMID:
23954344.
IF:
15,343.
DOI:
10.1016/j.jacc.2013.07.037
10.1111/jdv.12024
Oliveras A, García-Ortiz L, Segura J, Banegas JR,
Martell-Claros N, Vigil L, Suarez C, Gomez-Marcos MA,
Abad-Cardiel M, Vazquez S, de la Cruz JJ, Franklin SS,
– 128 –
Ruilope LM, de la Sierra A; on behalf of the PRESCEN
Study, Spain. Association between urinary albumin
excretion and both central and peripheral blood pressure in subjects with insulin resistance. J Hypertens.
31(1):103-8. 2013. PMID: 23137953. IF: 4,022. DOI:
10.1097/HJH.0b013e32835ac7b5
Casado Cerrada J, Parra Caballero P, Vega Piris L,
Suárez Fernández C. Relation between parathyroid
hormone and cardiovascular risk in patients with vitamin D deficiency. Med Clin (Barc). 141(7):292-4. 2013.
PMID:
23790578.
IF:
1,252
DOI:
10.1016/j.medcli.2013.02.039
Luxán G, Casanova JC, Martínez-Poveda B, Prados B,
D'Amato G, MacGrogan D, Gonzalez-Rajal A, Dobarro
D, Torroja C, Martinez F, Izquierdo-García JL,
Fernández-Friera L, Sabater-Molina M,Kong YY,
Pizarro G, Ibañez B, Medrano C, García-Pavía P,
Gimeno JR, Monserrat L, Jiménez-Borreguero LJ, de la
Pompa JL. Mutations in the NOTCH pathway regulator
MIB1 cause left ventricular noncompaction cardiomyopathy. Nat Med. 19(2):193-201. 2013. PMID:
23314057. IF: 28,054. DOI: 10.1038/nm.3046
Bertoletti L, Quenet S, Laporte S, Sahuquillo JC,
Conget F, Pedrajas JM, Martin M, Casado I, RieraMestre A, Monreal M; RIETE Investigators. Pulmonary
embolism and 3-month outcomes in 4036 patients
with venous thromboembolism and chronic obstructive
pulmonary disease: data from the RIETE registry.
Respir Res. 18(14):75. 2013. PMID: 23865769. IF:
3,382. DOI: 10.1186/1465-9921-14-75
i Micco P, Ruiz-Giménez N, Nieto JA, Aujesky D, del
Molino F, Valle R, Barrón M, Maestre A, Monreal M;
RIETE investigators. Platelet count and outcome in
patients with acute venous thromboembolism. Thromb
Haemost. Thromb Haemost. 110(5):1025-34. 2013.
PMID: 23925476. IF: 5,760. DOI: 10.1160/TH13-040352
Otero R, Elías T, Jara L, Trujillo-Santos J, Bertoletti L,
Nauffal D, Ruiz-Ruiz J, Blanco-Molina Á, Monreal M;
RIETE investigators. Factors associated with elevated
pulmonary arterial pressure levels on the echocardio-
AREA 3
Nieto JA, Solano R, Trapero Iglesias N, Ruiz-Giménez
N, Fernández-Capitán C, Valero B, Tiberio G, BuraRiviere A, Monreal M; RIETE Investigators. Validation of
a score for predicting fatal bleeding in patients receiving anticoagulation for venous thromboembolism.
Thromb Res. 132(2):175-9. 2013. PMID: 23849097. IF:
2,247. DOI: 10.1016/j.thromres.2013.06.019
Abad-Pérez D, Novella-Arribas B, Rodríguez-Salvanés
FJ, Sánchez-Gómez LM, García-Polo I, VergeGonzález C and Suárez-Fernández C on behalf of the
NISH group. Effect of oral nitrates on pulse pressure
and arterial elasticity in patients aged over 65 years
with refractory isolated systolic hypertension: study
protocol for a randomized controlled trial. Trials.
14;14:388. 2013. PMID: 24228894. IF: 2,117. DOI:
10.1186/1745-6215-14-388
Sambola A, Montoro JB, Del Blanco BG, Llavero N,
Barrabés JA, Alfonso F, Bueno H, Cequier A, Serra A,
Zueco J, Sabaté M, Rodríguez-Leor O, García-Dorado
D. Dual antiplatelet therapy versus oral anticoagulation
plus dual antiplatelet therapy in patients with atrial fibrillation and low-to-moderate thromboembolic risk
undergoing coronary stenting: design of the MUSICA2 randomized trial. Am Heart J. 166(4):669-75. 2013.
PMID:
24093846.
IF:
4,555.
DOI:
10.1016/j.ahj.2013.07.028
Echavarría-Pinto M, Lopes R, Gorgadze T, Gonzalo N,
Hernández R, Jiménez-Quevedo P, Alfonso F,
Bañuelos C, Nuñez-Gil IJ, Ibañez B, Fernández C,
Fernandez-Ortiz A, García E, Macaya C, Escaned J.
Safety and efficacy of intense antithrombotic treatment
and percutaneous coronary intervention deferral in
patients with large intracoronary thrombus. Am J
Cardiol. 111(12):1745.. 2013. PMID: 23528026. IF:
3,425. DOI: 10.1016/j.amjcard.2013.02.027.
De la Torre Hernandez JM, Alfonso F, Sanchez
Recalde A, Jimenez Navarro MF, Perez de Prado A,
Hernandez F, Abdul-Jawad Altisent O, Roura G,
Garcia Camarero T, Elizaga J, Rivero F, Gimeno F,
Calviño R, Moreu J, Bosa F, Rumoroso JR, Bullones
JA, Gallardo A, Fernandez Diaz JA, Ruiz Arroyo JR,
Aragon V, Masotti M; ESTROFA-LM Study Group.
Comparison of paclitaxel-eluting stents (Taxus) and
everolimus-eluting stents (Xience) in left main coronary
artery disease with 3 years follow-up (from the
ESTROFA-LM registry). Am J Cardiol. 111(5):676-83..
2013. PMID: 23273715. IF: 3,425. DOI:
10.1016/j.amjcard.2012.11.019
Martín P, Cárdenas A, Bañuelos C, Alfonso F. Peri-stent
abluminal hematoma and pin-hole balloon rupture during treatment of calcified drug-eluting stent in-stent
restenosis. Circ J. 77(6):1587-9.. 2013. PMID:
23519899. IF: 3,685
Echavarria-Pinto M, Escaned J, Macías E, Medina M,
Gonzalo N, Petraco R, Sen S, Jimenez-Quevedo P,
Hernandez R, Mila R, Ibañez B, Nuñez-Gil IJ,
Fernández C, Alfonso F, Bañuelos C, García E, Davies
J, Fernández-Ortiz A, Macaya C. Disturbed coronary
hemodynamics in vessels with intermediate stenoses
evaluated with fractional flow reserve: a combined
analysis of epicardial and microcirculatory involvement
in ischemic heart disease. Circulation. 128(24):255766.. 2013. PMID: 24141255. IF: 14,948. DOI:
10.1161/CIRCULATIONAHA.112.001345
Alfonso F, Ambrosio G, Ector H, Gonçalves L, Pinto F,
Timmis A, Vardas P; Editors’ Network European
Society of Cardiology Task Force. National Society
Cardiovascular Journals and the New European
Society of Cardiology search engine. Eur Heart J.
34(41):3161-3. 2013. PMID: 24344396. IF: 14,723
Escaned J, Echavarría-Pinto M, Gorgadze T, Gonzalo
N, Armengol F, Hernández R, Jiménez-Quevedo P,
Nuñez-Gil IJ, Pérez-Vizcayno MJ, Alfonso F, Bañuelos
C, Ibañez B, García E, Fernández-Ortiz A, Macaya C.
Safety of lone thrombus aspiration without concomitant
coronary stenting in selected patients with acute
myocardial infarction. EuroIntervention. 8(10):1149-56.
2013. PMID: 23425541. IF: 3,758. DOI:
10.4244/EIJV8I10A178
– 129 –
AREA 3AREA 2 AREA 1
graphic assessment in patients with prior pulmonary
embolism. Thromb Res. 131(5):e191-5. 2013. PMID:
23466216.
IF:
2,247.
DOI:
10.1016/j.thromres.2013.01.034
Jiménez-Quevedo P, Hernando L, Gómez-Hospital JA,
Iñiguez A, SanRoman A, Alfonso F, Hernández-Antolín
R, Angiolillo DJ, Bañuelos C, Escaned J, Gonzalo N,
Fernández C, Macaya C, Sabaté M; DIABETES
Investigators. Sirolimus-eluting stent versus bare metal
stent in diabetic patients: the final five-year follow-up of
the DIABETES trial. EuroIntervention. 9(3):328-35..
2013. PMID: 23518240. IF: 3,758. DOI:
10.4244/EIJV9I3A54
ficial calcified coronary plaques. J Am Coll Cardiol.
10;62(23):2254. 2013. PMID: 24080108. IF: 15,343.
DOI: 10.1016/j.jacc.2013.04.106
Alfonso F, Scheller B. Management of recurrent in-stent
restenosis: onion skin full metal jacket?.
EuroIntervention. 9(7):781-5.. 2013. PMID: 24280153.
IF: 3,758. DOI: 10.4244/EIJV9I7A129
Alfonso F, Cárdenas A, Cuevas C, Pérez-Vizcayno MJ.
Paclitaxel-eluting balloons for small-vessel disease. J
Am Coll Cardiol. 61(17):1831-2. 2013. PMID:
23500288. IF: 15,343. DOI: 10.1016/j.jacc.2012.
11.067
Roura G, Gomez-Lara J, Ferreiro JL, Gomez-Hospital
JA, Romaguera R, Teruel LM, Carreño E, Esplugas E,
Alfonso F, Cequier A. Multislice CT for assessing instent dimensions after left main coronary artery stenting: a comparison with three dimensional intravascular
ultrasound. Heart. 99(15):1106-12. 2013. PMID:
23723447. IF: 6,023. DOI: 10.1136/heartjnl-2013303679
Núñez-Gil IJ, Estrada I, Pérez de Isla L, Feltes G, De
Agustín JA, Vivas D, Viana-Tejedor A, Escaned J,
Alfonso F, Jiménez-Quevedo P, García-Fernández MA,
Macaya C, Fernández-Ortiz A. Functional mitral regurgitation after a first non-ST segment elevation acute
coronary syndrome: very-long-term follow-up, prognosis and contribution to left ventricular enlargement and
atrial fibrillation development. Heart. 99(20):1502-8..
2013. PMID: 23958756. IF: 6,023. DOI:
10.1136/heartjnl-2013-304298
Hernando L, Corros C, Gonzalo N, Hernández-Antolin
R, Bañuelos C, Jiménez-Quevedo P, Bernardo E,
Fernández-Ortiz A, Escaned J, Macaya C, Alfonso F.
Morphological characteristics of culprit coronary
lesions according to clinical presentation: insights from
a multimodality imaging approach. Int J Cardiovasc
Imaging. 29(1):13-21. 2013. PMID: 22527256. IF:
2,322. DOI: 10.1007/s10554-012-0043-3
Alfonso F, Gonzalo N, Nuñez-Gil I, Bañuelos C.
Coronary thrombosis from large, nonprotruding, super-
– 130 –
Alfonso F, Fernandez-Viña F, Medina M, Hernandez R.
Neoatherosclerosis: the missing link between very late
stent thrombosis and very late in-stent restenosis. J
Am Coll Cardiol. 61(12): e155. 2013. PMID: 23500332.
IF: 15,343. DOI: -
Alfonso F, Angiolillo DJ. Targeting p-selectin during
coronary interventions: the elusive link between inflammation and platelets to prevent myocardial damage. J
Am Coll Cardiol. 61(20):2056-9. 2013. PMID:
23500231. IF: 15,343. DOI: 10.1016/j.jacc.2013.
03.004
Paulo M, Sandoval J, Lennie V, Dutary J, Medina M,
Gonzalo N, Jimenez-Quevedo P, Escaned J,
Bañuelos C, Hernandez R, Macaya C, Alfonso F.
Combined use of OCT and IVUS in spontaneous
coronary artery dissection. JACC Cardiovasc
Imaging. 6(7):830-2. 2013. PMID: 23747066. IF:
6,986
Alfonso F, Paulo M, Lennie V, Das-Neves B, EchavarríaPinto M. Fibromuscular dysplasia and spontaneous
coronary artery dissection: coincidental association or
causality?. JACC Cardiovasc Interv. 6(6):638.. 2013.
PMID: 23787240. IF: 7,440. DOI: Alfonso F, Pérez-Vizcayno MJ. Drug-eluting balloons
for restenosis after stent implantation. Lancet.
381(9865):431-3. 2013. PMID: 23206833. IF: 39,207.
DOI: 10.1016/S0140-6736(12)62120-5
Alfonso F, Hernandez R. Revascularization strategies in
patients with diabetes. N Engl J Med. 368(15):1453..
2013. PMID: 23574127. IF: 54,420. DOI:
10.1056/NEJMc1301244#SA1
AREA 3
Bertomeu V, Cequier Á, Bernal JL, Alfonso F, Anguita
MP, Muñiz J, Barrabés JA, García-Dorado D, Goicolea
J, Elola FJ. In-hospital mortality due to acute myocardial infarction. relevance of type of hospital and care
provided. RECALCAR study. Rev Esp Cardiol (Engl
Ed). 66(12):935-42. 2013. PMID: 24774106. IF: 3,342.
DOI: 10.1016/j.rec.2013.06.006
Alfonso F. New drug-eluting stents: polymer-free,
biodegradable polymers or bioabsorbable scaffolds?.
Rev Esp Cardiol (Engl Ed). 66(6):423-6. 2013. PMID:
24776042. IF: 3,342. DOI: 10.1016/j.rec.2013.02.005
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ALFONSO MANTEROLA,
FERNANDO
Ensayo de eficacia y seguridad de la doble antiagregación comparada con la combinación de anticoagulación oral + doble antiagregación en pacientes con
fibrilación auricular de bajo-moderado riesgo sometidos a la implantación de un Stent coronario; (Versión
2.3:
30-03-12).
DAVID
GARCIA
DORADO
(S.CARDIOLOGIA H.VALL D`HEBRON). MUSICA-2.
EudraCT: EudraCT: 2009-017256-27
PRINCIPAL RESEARCHER: ALFONSO MANTEROLA,
FERNANDO
Prevention of late stent thrombosis by an interdisciplinary global european effort; (Versión 5.0: enero 2011).
UNIVERSITAIRE ZIEKENHUIZEN LEUVEN. ESTUDIO
PRESTIGE.
PRINCIPAL RESEARCHER: BENEDICTO BUENDIA,
AMPARO
Registro de pacientes con dispositivo biorreabsorbible
en la práctica clínica habitual; (Versión 1.0:31-07-13).
SOCIEDAD ESPAÑOLA DE CARDIOLOGIA (S.E.C.).
COR-BVS-2013-01/ESTUDIO REPARA
PRINCIPAL RESEARCHER: MORENO CARRILES,
ROSA MARÍA
Ensayo fase IIIb aleatorizado, doble ciego, de grupos
paralelos, multicéntrico, para comparar el riesgo de
muerte cardiovascular, infarto de miocardio e ictus
isquémico en pacientes con enfermedad arterial periférica establecida, tratados con ticagrelor vs clopidogrel (EUCLID- Examinando el uso de tiCagreLor en
EAP); (versión 1: 29-10-12). ASTRAZENECA AB
D5135C00001. EudraCT: 2011-004616-36
PRINCIPAL RESEARCHER: MORENO CARRILES,
ROSA MARÍA
Registro logic; (versión 1.0: 09-05-11). CID SPA.
P21102/REGISTRO LOGIC
PRINCIPAL RESEARCHER: SUÁREZ FERNÁNDEZ,
CARMEN
PREFER en TEV: Prevención de episodios de tromboembolia. Registro europeo sobre tromboembolia
venosa. DAIICHI SANKYO EUROPE GMBH. DSEVTE-01-12/DAI-VTE-2013-01
GRUPO 49
HEAD OF LABORATORY
Blanca Novella Arribas
GROUP MEMBERS
• Ana Cubillo Serna
• María Jesús Fernández Luque
• Ángela Gallego Arenas
• Amelia González Gamarra
• María del Pilar Loeches Belinchón
– 131 –
AREA 3AREA 2 AREA 1
Pascual I, Avanzas P, Muñoz-García AJ, López-Otero
D, Jimenez-Navarro MF, Cid-Alvarez B, del Valle R,
Alonso-Briales JH, Ocaranza-Sanchez R, Alfonso F,
Hernández JM, Trillo-Nouche R, Morís C.
Percutaneous implantation of the CoreValve® selfexpanding valve prosthesis in patients with severe aortic stenosis and porcelain aorta: medium-term followup. Rev Esp Cardiol (Engl Ed). 66(10):775-81. 2013.
PMID:
24773857.
IF:
3,342.
DOI:
10.1016/j.rec.2013.03.001
•
•
•
•
•
•
•
Javier López González
M. Soledad Mayayo Vicente
Francisco José Rodríguez Salvanés
María Lourdes Ruiz Díaz
Luis María Sánchez Gómez
Rosa María Sánchez Alcalde
Belén Sierra García
Gorostidi M, Sarafidis PA, de la Sierra A, Segura J, de
la Cruz JJ, Banegas JR, Ruilope LM; Spanish ABPM
Registry Investigators. (B Novella Arribas). Differences
between office and 24-hour blood pressure control in
hypertensive patients with CKD: A 5,693-patient crosssectional analysis from Spain. Am J Kidney. Dis.62
(2):285-294. 2013. PMID: 23689071. IF: 5,756. DOI:
10.1053/j.ajkd.2013.03.025
MAJOR GRANTS
• 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.
PI10/01927. 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
– 132 –
YEAR
Total IF
Publication No.
Q1
2011
37,684
9
4
2012
26,532
6
3
2013
19,345
4
3
Kozakova M, Natali A, Dekker J, Beck-Nielsen H,
Laakso M, Nilsson P, Balkau B, Ferrannini E; RISC
Investigators.. Insulin sensitivity and carotid intimamedia thickness: relationship between insulin sensitivity and cardiovascular risk study. Arterioscler Thromb
Vasc Biol 33(6):1409-1417. 2013. PMID: 23599442. IF:
5,533. DOI: 10.1161/ATVBAHA.112.300948
Main C, Knight B, Moxham T, Gabriel Sanchez R,
Sanchez Gomez LM, Roqué i Figuls M, Bonfill Cosp
X. Hormone therapy for preventing cardiovascular
disease in post-menopausal women. Cochrane
Database Syst Rev. 30;4:CD002229. 2013. PMID:
23633307. IF: 5,939. DOI: 10.1002/14651858.
CD002229.pub3
Abad-Pérez D, Novella-Arribas B, Rodríguez-Salvanés
FJ, Sánchez-Gómez LM, García-Polo I, VergeGonzález C and Suárez-Fernández C on behalf of the
NISH group. Effect of oral nitrates on pulse pressure
and arterial elasticity in patients aged over 65 years
with refractory isolated systolic hypertension: study
protocol for a randomized controlled trial. Trials.
14;14:388. 2013. PMID: 24228894. IF: 2,117. DOI:
10.1186/1745-6215-14-388
AREA 3
Line 3.7
New therapies in
infectious pathologies
GRUPO 50
HEAD OF LABORATORY
Ignacio de los Santos Gil
GROUP MEMBERS
• José Rafael de la Cámara de Llanza
• Ana Salas Aparicio
• María Teresa Sánchez Casasola
• Jesús Sanz Sanz
• Cristina Sarriá Cepeda
Our group remains part of the AIDS Research Network
(Coris) within the thematic network funded by the
Ministry of Health. In this network, we collaborate providing patients to the cohort, and sending blood samples to the Biobank created for this purpose. We have
incorporated a new collaborator to the group,
employed with funding for staff recently received.
We continue working in the study of HIV infection,
treatment, adverse effects, evolution, and we have a
wide range of patients treated especially with
monotherapy with protease inhibitors to avoid toxicities
with nucleoside analogues.
Also, we have an open line of research for patients with
HIV and hepatitis C virus co-infection, making treatment with triple therapy, clinical trials with new drugs
like Simeprevir and new therapeutic strategies with
Telaprevir.
We have presented several conference papers on the
early diagnosis of HIV infection, carried out in collabo-
Fig. 1.Proportion of patients free from events. (A) Overall mortality, (B)
liverrelatedevents (liver-related mortality, liver decompensation, hepatocellularcarcinoma, liver transplantation) according to treatment
response, (C) liverdecompensation, and (D) hepatocellular carcinoma.
⁄p <0.05 with the NR group (Log-Rank test); _p <0.05 with the REL
group (Log-Rank test). SVR, Sustainedvirologic response; REL, end-oftreatment response with subsequent relapse; NR,no response.
From the paper “Clinical effects of viral relapse after interferon plus ribavirinin patients co-infected with human immunodeficiency virus
and hepatitis C virus”. Journal of Hepatology 2013; 58: 1104–1112.
– 133 –
AREA 3AREA 2 AREA 1
RESEARCH INTEREST
ration with the Emergency Department to avoid late
presentation of the disease.
MAJOR GRANTS
Ignacio de los Santos Gil. Redes Temáticas 2012 - Red
de SIDA (RIS). FIB. RD12/0017/0011. Duration: 2013 –
2016
Jarrín I, Hernández-Novoa B, Alejos B et al.
(Colaborador I. de los Santos). Persistence of novel
first-line antiretroviral regimen in a cohort of HIV-positive subjetcs, CoRIS 2008-2010. Antiviral Therapy.
18(2):161-170. 2013. PMID: 22997147. IF: 3,143. DOI:
10.3851/IMP2287
YEAR
Total IF
2011
2012
2013
Publication No.
Q1
117,881
28
13
108,214
24
12
211,823
26
12
Grupo de expertos de la Secretaría del Plan Nacional
sobre el sida. Consensus statement of the national
AIDS plan secretariat, spanish society of emergency
medicine and AIDS study group ofthe spanish society
of infectious diseases and clinical microbiology on
emergency and human immunodeficiency virus infection. Enferm Infecc Microbiol Clin. 31(7):455.e1455.e16. 2013. PMID: 23601916. IF: 1,881. DOI:
10.1016/j.eimc.2012.11.020
Masiá M, Padilla S, Álvarez D, López JC, Santos I,
Soriano V, Hernández-Quero J, Santos J, Tural C, del
Amo J, Gutiérrez F; CoRIS (Colaborador I. de los
Santos). Risk, predictors and mortality associated with
non-AIDS events in newly diagnosed HIV-infected
patients: role of antiretroviral therapy. AIDS. 27(2):181189. 2013. PMID: 23018442. IF: 6,557. DOI:
10.1097/QAD.0b013e32835a1156
Rivero-Juárez A, Mira JA, Santos Gil I, et al. Atazanavirbased therapy is associated with higher hepatitis C viral
load in HIV type 1-infected subjects with untreated
hepatitis C. AIDS Research and Human Retroviruses.
29(2):223-225. 2013. PMID: 22966845. IF: 2,457. DOI:
10.1089/AID.2012.0126
– 134 –
Guillem V, Hernández-Boluda JC, Gallardo D, Buño I,
Bosch A, Martínez-Laperche C, de la Cámara R,
Brunet S, Martin C, Nieto JB, Martínez C, Pérez A,
Montoro J, Garcia-Noblejas A, Solano C. A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell
transplantation. Am J Hematol. 88(10):883-889.
2013. PMID: 23813863. IF: 3,477. DOI: 10.1002/
ajh.23523
Hernando V, Alejos B, Monge S et al. (Colaborador I. de
los Santos). All-cause mortality in the cohorts of the
Spanish AIDS Research Network (RIS) compared with
the general population: 1997-2010. BMC Infect Dis.
2013 Aug 20;13:382. 2013. PMID: 23961924. IF:
2,561. DOI: 10.1186/1471-2334-13-382
Martin-Antonio B, Suarez-Lledo M, Arroyes M,
Fernandez-Aviles F, Martinez C, Rovira M, Espigado I,
Gallardo D, Bosch A, Buno I, Martinez-Laperche C,
Jimenez-Velasco A, de la Camara R, Brunet S, Nieto
JB, Urbano-Ispizua A. A variant in IRF3 impacts on the
clinical outcome of AML patients submitted to AlloSCT. Bone Marrow Transplant 48(9):1205-12011.
2013. PMID: 23542224. IF: 3,466. DOI:
10.1038/bmt.2013.43
Babiker AG, Emery S, Fätkenheuer G et al.
(Colaborador I. de los Santos). Considerations in the
rationale, design and methods of the Strategic Timing
of Antiretroviral Treatment (START) study. Clin
Trials.10(1 Suppl):S5-S36. 2013. PMID: 22547421. IF:
1,944. DOI: 10.1177/1740774512440342
Mira JA, Rivero-Juárez A, López-Cortés LF et al.
(Colaborador I. de los Santos). Benefits from sustained
virological response to pegylated interferon plus ribavirin in HIV/hepatitis C virus-coinfected patients with
compensated cirrhosis. Clinical Infectious Diseases.
AREA 3
Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly
JP, van der Velden W, Omar H, Martino R, Halkes C,
Faraci M, Theunissen K, Kalwak K, Hubacek P, Sica
S, Nozzoli C, Fagioli F, Matthes S, Diaz MA,
Migliavacca M, Balduzzi A, Tomaszewska A, De La
Camara R, van Biezen A, Hoek J, Iacobelli S,
Einsele H, Cesaro S. Response to rituximab-based
therapy and risk factor analysis in epstein barr virusrelated
lymphoproliferative
disorder
after
hematopoietic stem cell transplant in children and
adults: a study from the infectious diseases working
party of the European group for blood and marrow
transplantation. Clinical infectious diseases.
57(6):794-802. 2013. PMID: 23771985. IF: 9,416.
DOI: 10.1093/cid/cit391
Suárez-García I, Jarrín I, Iribarren JA et al. (Colaborador
I. de los Santos). Incidence and risk factors of AIDSdefining cancers in a cohort of HIV-positive adults:
important of the definition of incident cases. Enferm
22608566. IF: 1,881. DOI: 10.1016/j.eimc.2012.
03.009
Arazo Garcés P, de los Santos Gil I. Interacciones farmacocinéticas de Rilpivirina. Enferm Infecc Microbiol
Clin. 31(Supl 2):12-19. 2013. IF: 1,881. DOI:
10.1016/S0213-005X(13)70138-1
López J, Sevilla T, Vilacosta I, Sarriá C, Revilla A, Ortiz
C, Ferrera C, Olmos C, Gómez I, San Román JA.
Prognostic role of persistent positive blood cultures
after initiation of antibiotic therapy inleft-sided infective
endocarditis. Eur Heart J. 34(23):1749-54. 2013.
PMID: 23144047. IF: 14,723. DOI: 10.1093/eurheartj/ehs379
Olmos C, Vilacosta I, Fernández C, López J, Sarriá C,
Ferrera C, Revilla A, Silva J, Vivas D, González I, San
Román JA. Contemporary epidemiology and prognosis
of septic shock in infective endocarditis. Eur Heart J.
34(26):1999-2006. 2013. PMID: 23060453. IF: 14,723.
DOI: 10.1093/eurheartj/ehs336
Casado JL, de los Santos I, del Palacio M et al. Lipidlowering effect and efficacy after switching to etravirine
in HIV-infected patients with intolerance to suppressive
HAART. HIV Clin Trials 14(1):1-9. 2013. PMID:
23372109. IF: 2,141. DOI: 10.1410/hct1401-1
I de los Santos, A Gómez-Berrocal, E Valencia et al.
Efficacy and tolerability of Darunavir/Ritonavir in combination with Abacavir/Lamivudine: an option in selected
HIV-infected patients. HIV Clin Trials. 14(5):254-259.
2013. PMID: 24144901. IF: 2,141. DOI:
10.1310/hct1405-254
Ribera E, Larrousse M, Curran A, Negredo E, Clotet B,
Estrada V, Sanz J, Berenguer J, Rubio R, Pulido F,
Ferrer P, Alvarez ML, Arterburn S, Martínez E. Impact of
switching from zidovudine/lamivudine to tenofovir/emtricitabine on lipoatrophy: the RECOMB study.
HIV Med. 14(6):327-336. 2013. PMID: 23298339. IF:
3,454. DOI: 10.1111/hiv.12011
Monge S, Alejos B, Dronda S et al. (Colaborador I. de
los Santos) Inequalities in HIV disease management
and progression in migrants from Latin America and
sub-Saharan Africa living in Spain. HIV Medicine.
14(5):273-283. 2013. PMID: 23171059. IF: 3,454. DOI:
10.1111/hiv.12001
Guzmán-Fulgencio M, Jiménez JL, García-Álvarez M
et al. (Colaborador I. de los Santos). Mitochondrial
haplogroups are associated with clinical pattern of
AIDS progression in HIV-infected patients. J Acquir
Immune Defic Syndr. 63(2):178-183. 2013. PMID:
23666137. IF: 4,394. DOI: 10.1097/QAI.0b013
e3182893f74
Saira K, Lin X, DePasse JV, Halpin R, Twaddle A,
Stockwell T, Angus B, Cozzi-Lepri A, Delfino M, Dugan
V, Dwyer DE, Freiberg M, Horban A, Losso M, Lynfield
R, Wentworth DN, Holmes EC, Davey R, Wentworth
DE, Ghedin E; INSIGHT FLU002 Study Group;
INSIGHT FLU003 Study Group. (Collaborators: Sanz J
et al). Sequence analysis of in vivo defective interferinglike RNA of influenza A H1N1 pandemic virus. J Virol.
87(14):8064-8074. 2013. PMID: 23678180. IF: 4,648.
DOI: 10.1128/JVI.00240-13
– 135 –
AREA 3AREA 2 AREA 1
56(11):1646-1653. 2013. PMID: 23429381. IF: 9,416.
DOI: 10.1093/cid/cit103
Berenguer J, Álvarez-Pellicer J, Carrero A et al.
(Colaborador I de los Santos). Clinical effects of viral
relapse after interferon plus ribavirin in patients coinfected with human immunodeficiency virus and hepatitis C virus. Journal of Hepatology. 58(6):1104-1112.
2013. PMID: 23395690. IF: 10,401. DOI:
10.1016/j.jhep.2013.01.042
François Raffi , Hans Jaeger, Eugenia Quiros-Roldan,
Helmut Albrecht, Elena Belonosova, Jose M Gatell,
Jean-Guy Baril, Pere Domingo, Clare Brennan, Steve
Almond, Sherene Min, on behalf ofthe extended
SPRING-2 Study Group (Collaborators: J Sanz et al).
Once-daily dolutegravir versus twice-daily raltegravir in
antiretroviral-naive adults with HIV-1 infection: 96-week
results from the randomized, double-blind, non-inferiority SPRING-2 study. Lancet Infectious Diseases.
13(11):927-935. 2013. PMID: 24074642. IF: 19,466.
DOI: 10.1016/S1473-3099(13)70257-3
Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C,
Orkin C, Bloch M, Podzamczer D, Pokrovsky V, Pulido
F, Almond S, Margolis D, Brennan C, Min S; SPRING2 Study Group. (Collaborators: Sanz J et al). Once-daily
dolutegravir versus raltegravir in antiretroviral-naive
adults with HIV-1 infection: 48 week results from the
randomised, double-blind, non-inferiority SPRING-2
study. Lancet. 381(9868):735-743. 2013. PMID:
23306000. IF: 39,207. DOI: 10.1016/S01406736(12)61853-4
Bjerk SM, Baker JV, Emery S, Neuhaus J, Angus B,
Gordin FM, Pett SL, Stephan C, Kunisaki KM; INSIGHT
SMART Study Group. (Collaborators: Sanz J et al).
Biomarkers and bacterial pneumonia risk in patients
with treated HIV infection: a case-control study. PLoS
One. 8(2):e56249. 2013. PMID: 23457535. IF: 3,534.
Cahn P, Pozniak AL, Mingrone H et al. (Colaborador I.
de los Santos) Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults
with HIV: 48 weeks results from the randomized, double-blind, non-inferiority SAILING study. The Lancet.
382(9893):700-708. 2013. PMID: 23830355. IF:
39,207. DOI: 10.1016/S0140-6736(13)61221-0
– 136 –
Engelhard D, Mohty B, de la Camara R, Cordonnier C,
Ljungman P. European guidelines for prevention and
management of influenza in hematopoietic stem cell
transplantation and leukemia patients: summary of
ECIL-4 (2011), on behalf of ECIL, a joint venture of
EBMT, EORTC, ICHS, and ELN. Transpl Infect Dis.
15(3):219-232. 2013. PMID: 23363310. IF: 2,250.
DOI: 10.1111/tid.12054
CLINICAL TRIALS
PRINCIPAL RESEARCHER: CÁMARA LLANZA,
JOSÉ-RAFAEL
Estudio de fase 3 aleatorizado, doble ciego y controlado con placebo para evaluar la eficacia protectora y
la seguridad de una vacuna, ASP0113en receptores
seropositivos para el citomegalovirus (CMV) sometidos a alotrasplante de células hematopoyéticas
(ATCH); (Versión 1.0:27-03-13). ASTELLAS PHARMA
GLOBAL DEVELOPMENT, INC. (APGD). 0113-CL1004. EudraCT: 2013-000903-18
PRINCIPAL RESEARCHER: CÁMARA LLANZA,
JOSÉ-RAFAEL
Estudio de fase 2, aleatorizado, de búsqueda de
dosis para evaluar la seguridad y la actividad anti-citomegalovirus (CMV) de maribavir frente a valganciclovir para el tratamiento de infecciones por CMV en
receptores de trasplantes sin enfermedad orgánica
por CMV;(versión final: 09- 11-11). VIROPHARMA
INCORPORATED. 1263-203. EudraCT: 2010024247-32
PRINCIPAL RESEARCHER: DE LOS SANTOS GIL,
IGNACIO
Eficacia de la biterapia con maraviroc y darunavir
potenciado con ritonavir para el tratamiento de
rescate precoz en pacientes infectados porVIH-1:
ensayo clínico piloto en fase II, multicéntrico aleatorizado, controlado y abierto. Estudio BIMARTHE;
(Versión 1.1: 17-12-12). FUNDACIO HOSPITAL UNIVERSITARI VALL D'HEBRON (VHIR). 3883. EudraCT:
2012-003501-10
AREA 3
GRUPO 51
HEAD OF LABORATORY
Javier Aspa Marco
RESEARCH INTEREST
Our group maintains an open line of collaboration
with several groups, mainly with the Immunology
Service, Hospital Dr Negrin (Gran Canaria, Spain).
We collaborate in several topics, principally
Mannose-binding lectin and surfactant protein,
related to different aspects of host defense in pneumonia.
A great deal of articles has been published recently,
focused on three key issues: Late pneumonia mortality, Cardiovascular events and community-acquired
pneumonia (CAP), and Biomarkers and CAP. New
scores for the prognosis of CAP that take into
account the appearance of cardiovascular events
have been proposed, Various articles dealing with the
handling of CAP with the help of several biomarkers
have also been published, in order to try to differentiate the degree of severity of CAP, or help to improve
patient stratification in accordance with their levels of
inflammatory cytokines. We have initiated a research
project (funded by FISS): Incidence of cardiovascular
Fig.1. Meta-analysis of association between MBL2 and pneumococcal
pneumonia. RE: random effects. *: additional group of patients
events following hospitalization for communityacquired pneumonia in adults and its association
with different markers of inflammation. In this project
we intend to quantify the incidence of cardiovascular
disease, in adult patients, in the year after hospital
admittance due to CAP, and to establish its possible
relationship with mortality. Moreover, we will try to
describe the distribution in CAP patients of a wide
spectrum of immune response mediators upon the
admittance to and release from hospital. In this study
some already well-known mediators, and some others that are being analyzed for the first time, have
been included. This will permit to characterize an
inflammatory profile for these patients and determine
its possible relationship with the incidence of cardiovascular disease.
MAJOR GRANTS
• Javier Aspa Marco. Incidencia de episodios cardiovasculares tras un ingreso hospitalario por Neumonía
Adquirida en la Comunidad en pacientes adultos y
su asociación con diferentes marcadores de inflamación. ISCIII. PI12/01142. Duration: 2013 - 2016.
• Olga Rajas Naranjo. Determinación del papel de los
proteoglicanos en la interacción entre microorganismos y el tejido respiratorio. Sociedad Española de
Patología de Aparato Respiratorio (SEPAR).
125/2012. Duration: 2013 – 2015.
– 137 –
AREA 3AREA 2 AREA 1
GROUP MEMBERS
• Gilda Fernandes Vasconcelo
• Guillermo Fernández Jímenez
• José María Galván Román
• Jose Andrés García Romero de Tejada
• Rosa Mar Gómez Punter
• Sergio Luquero Bueno
• Olga Rajas Naranjo
• María del Mar Ortega Gómez
• María del Valle Somiedo Gutiérrez
• Emma Vázquez Espinosa
• Lorena Vega Piris
• María del Mar Ortega Gómez. Plataforma Biobanco:
Red
nacional
de
Biobancos.
ISCIII.
PT13/0010/0058. Duration: 2014 – 2016.
1:04-10-12). CEMPRA PHARMACEUTICALS INC.
CE01-300. EudraCT: 2012-003971-20
GRUPO 52
HEAD OF LABORATORY
Manuel López-Brea Calvo
YEAR
Total IF
Publication No.
Q1
2011
10,937
3
2
2012
20,445
6
4
2013
7,125
1
1
Rajas Naranjo O, Aspa Marco J, Usetti Gil P, GarcíaGallo C. Infecciones respiratorias en el paciente
inmunosuprimido. Manual de Neumología Clínica. II
Edición. 2013. Ergon. 213-231. ISBN: 978-84-8473754-4. Páginas: 213-231.
GROUP MEMBERS
• Teresa Alarcón Cavero
• María Luz Balsalobre Arenas
• Ana Blanco Suárez
• Buenaventura Buendía Moreno
• Laura María Cardeñoso Domingo
• Ana Correa Ruiz
• Carmen de las Cuevas Torresano
• Diego Domingo García
• Marina Espínola Docio
• María Dolores Guerrero Torres
• Alba Guiu Martínez
• Laura Llorca Otero
• Elisea Lomas Lomas
• Justo Martiáñez Rodríguez
• María Josefa Martínez Gómez
• María del Carmen Martínez Jiménez
• Sandra Rodrigo Gil
• Cristina Santa Olalla Peralta
• Carmen María Serrano Morago
• Ángela Somodevilla Solís
CLINICAL TRIALS
RESEARCH INTEREST
PRINCIPAL RESEARCHER: ASPA MARCO, F. JAVIER
Estudio multicéntrico, aleatorizado, doble ciego para
evaluar la eficacia y seguridad de solitromicina oral
(CEM-101) en comparación con moxifloxacino oral
para el tratamiento de pacientes adultos con neumonía
bacteriana adquirida en la comunidad; (Versión 2 amd
1.- Antibiotic resistance in Helicobacter pylori
Resistance to antibiotics is the major cause of treatment failure of H. pylori infection. A study was conducted to assess prospectively the antibacterial resistance
rates of H pylori in Europe (April 2008-June 2009 in 18
European countries) and to study the link between out-
García-Laorden MI, de Castro FR, Solé-Violán J,
Payeras A, Luisa Briones M, Borderías L, Aspa J,
Blanquer J, Rajas O, Marcos-Ramos JA, HerreraRamos E, García-Bello MA, Noda J, Ferrer JM, Rello J,
Rodríguez-Gallego C. The role of mannose-binding
lectin on pneumococcal infection. Eur Respir J.
41(1):131-9. 2013. PMID: 22523362. IF: 7,125. DOI:
10.1183/09031936.00174111
BOOKS
– 138 –
AREA 3
Fig.1. Correlation between outpatient antibiotic use in 2005 in DID (Defined Daily Dose per 1000 inhabitants) and proportion of resistant H.
pylori strains isolated from adults and children in 17 European countries. (A) macrolide use and clarithromycin resistance (B) quinolone
use and levofloxacin resistance.
patient antibiotic use and resistance levels in different
countries. Data on yearly and cumulative use of systemic antibacterial agents in ambulatory care for the
period 2001-8 were expressed in Defined Daily Doses
(DDD) per 1000 inhabitants per day. Of 2204 patients
included, H pylori resistance rates for adults were
17.5% for clarithromycin, 14.1% for levofloxacin and
34.9% for metronidazole, and were significantly higher
for clarithromycin and levofloxacin in Western/Central
and Southern Europe (>20%) than in Northern
European countries (<10%). Model fit improved for
each additional year of antibiotic use accumulated, but
the best fit was obtained for 2005. A significant association was found between outpatient quinolone use and
the proportion of levofloxacin resistance (p=0.0013)
and between the use of long-acting macrolides only
and clarithromycin resistance (p=0.036) (figure 1).
2.- Geographic differences in bacterial distribution
Helicobacter pylori and Non tuberculosis mycobacteria
were analyzed in 2 different studies for geographic differences. Recent evidence suggests that in the current human
mixing in Latin America, European H. pylori (hpEurope) are
increasingly dominant at the expense of Amerindian haplotypes (hspAmerind). This phenomenon might occur via
DNA recombination, modulated by restriction-modification
systems (RMS), in which differences in cognate recognition
sites (CRS) and in active methylases will determine direction
and frequency of gene flow. The observed and expected
frequencies of CRS for RMS in DNA from 7 H. pylori whole
genomes and 110 multilocus sequences were determined.
The number of active methylases by resistance to in vitro
digestion by 16 restriction enzymes of genomic DNA from
9 hpEurope and 9 hspAmerind strains, and determined the
direction of DNA uptake in co-culture experiments of
hspAmerind and hpEurope strains were also measured.
Most of the CRS were underrepresented with consistency
between whole genomes and multilocus sequences.
Although neither the frequency of CRS nor the number of
active methylases differ among the bacterial populations
(average 8.6 ± 2.6), hspAmerind strains had a restriction
profile distinct from that in hpEurope strains, with 15 recognition sites accounting for the differences. Amerindians
strains also exhibited higher transformation rates than
European strains, and were more susceptible to be subverted by larger DNA hpEurope-fragments than vice versa. In
conclusion, the geographical variation in the pattern of CRS
– 139 –
AREA 3AREA 2 AREA 1
Fig.2. Model of H. pylori strain dynamics in Latin America hosts.
provides evidence for ancestral differences in RMS representation and function, and the transformation findings support the hypothesis of Europeanization of the Amerindian
strains in Latin America via DNA recombination (Figure 2).
A significant knowledge gap exists concerning the geographical distribution of nontuberculous mycobacteria
(NTM) isolation worldwide. To provide a snapshot of NTM
species distribution, global partners in the NTM-Network
European Trials Group (NET) framework, provided identification results of the total number of patients in 2008 in
whom NTM were isolated from pulmonary samples (identification data for 20.182 patients, 62 laboratories in 30 countries across six continents). 91 different NTM species were
isolated. Mycobacterium avium complex (MAC) bacteria
predominated in most countries, followed by M. gordonae
and M. xenopi with important differences in geographical
distribution. These differences in species distribution may
partly determine the frequency and manifestations of pulmonary NTM disease in each geographical location.
3.- Helicobacter pylori: Study of Phages
The presence of phages was detected by studying the
genetic sequences related with phages in H. pylori clinical
isolates and a high percentage of strains with phage integrase was found. One H. pylori strains, HP146128, was
sequenced and aligned with J99 whole sequence founding
2 unpaired regions. One present in J99 correspond to Cag
Pathogenicity Ireland. The second is an inversion (position
1.475.137 to 1.563.951 in J99 genome) also described in
H. pylori HPAG1. Genes were detected and translate to
proteins and selected those similar to known phages: 3
integrases, a gene Fic/Doc (Fic, Filamentous Induced by
cAMP, related to cellular division) and Doc, Death On Cure,
both of them involved in killing daughter bacteria without
prophage after lysogenie. Some proteins found in the 4
possible prophage in HP146128 genome (Prophage
Finder) were: gp250, an adenylsuccinate sintetase homologous present in Micobacteriaceae and other bacteria
phages, the citosine-methylase of Sulfolobus STSV1,
homologous of restriction-modification systems, a ribonucleotide-reductase, a methylase, a subunit of DNA polymerase, and a unknown function protein of phage origin.
4.- In vitro activity of different antifungal agents.
A population-based survey was conducted to investigate
the epidemiology of antifungal resistance in Spanish clinical
– 140 –
strains of filamentous fungi isolated from deep tissue samples, blood cultures, and respiratory samples. The study
was conducted in two different periods (October 2010 and
May 2011) to analyze seasonal variations. A total of 325
strains were isolated in 29 different hospitals. The average
prevalence was 0.0016/1,000 inhabitants. Strains were
identified by sequencing of DNA targets and susceptibility
testing by the European Committee for Antimicrobial
Susceptibility Testing reference procedure. The most frequently isolated genus was Aspergillus, accounting for
86.3% of the isolates (A. fumigates, 48.5%, A. flavus, 8.4%,
A. terreus, 8.1%, A. tubingensis, 6.8%, and A. niger, 6.5%),
followed by Scedosporium at 4.7%; the order Mucorales at
2.5%; Penicillium at 2.2%, and Fusarium at 1.2%..
Cryptic/sibling Aspergillus species accounted for 12% of
the cases. Resistance to amphotericin B was found in
10.8% of the isolates tested, while extended-spectrum triazole resistance ranged from 10 to 12.7%, depending on the
azole tested. Antifungal resistance was more common
among emerging species such as those of Scedosporium
and Mucorales and also among cryptic species of
Aspergillus, with 40% of these isolates showing resistance
to all of the antifungal compounds tested. Cryptic
Aspergillus species seem to be underestimated, and their
correct classification could be clinically relevant.
5.- Quantitative PCR for Cytomegalovirus (CMV) infection
Using 380 samples from 135 hematopoietic stem cell transplantation (HSCT) recipients, the new FDA approved quantitative PCR assay, COBAS(®) AmpliPrep/COBAS(®)
TaqMan(®) CMV test (CAP/CTM CMV test) developed and
standardized using the 1st WHO International Standard for
CMV with pp65 antigenemia and COBAS(®) AMPLICOR
MONITOR CMV tests were compared. The median time
between transplantation and testing samples was 57 days
(range, 0-207 days). The median CMV load (log(10)) was
3.17 IU/mL (3.21 copies/mL). Among samples with
detectable CMV load, 52% were negative by pp65 antigenemia. CMV loads were higher in pp65 antigenemia-positive
than in negative samples. One pp65-antigenemia-positive
cell per 100,000 leukocytes corresponded to a median
CMV load of 1200 IU/mL. CMV loads determined by the
CAP/CTM CMV test were slightly lower than the ones by
the AMPLICOR MONITOR CMV test (-0.15 [95% CI, -0.18
to -0.13] copies/mL), but slope differences indicated only
limited co-linearity. The CAP/CTM CMV test is more sensi-
AREA 3
PhD Thesis
STUDY OF HELICOBACTER PYLORI PHAGES BY PHENOTYPIC AND GENOTYPIC METHODS Esteban Aznar
Cano. Directors: Manuel López-Brea and Teresa Alarcón.
Medical School, Complutense University of Madrid. January
2014.
MAJOR GRANTS
• Teresa Alarcón Cavero. Study of molecular and
immunologic aspects pf Helicobacter pylori infection
in children and adults. Impact in Public Health.
PROIPRO, Argentina. PROIPRO 0310. Duration:
2012 – 2013.
• Teresa Alarcón Cavero. Tigecycline European
Surveillance Trial (TEST). Pfizer. EPI/252. Duration:
2012 – 2013.
YEAR
Total IF
Publication No.
Q1
2011
11,053
3
2
2012
24,954
10
4
2013
49,859
9
5
Alastruey-Izquierdo A, Mellado E, Peláez T, Pemán
J, Zapico S, Alvarez M, Rodríguez-Tudela JL,
Cuenca-Estrella M; FILPOP Study Group.
Population-Based survey of Filamentous Fungi and
Antifungal Resistance in Spain (FILPOP Study).
Antimicrob Agents Chemother. 57(7):3380-3387.
2013. PMID: 23669377. IF: 4,451. DOI:
10.1128/AAC.00383-13
Maldonado-Contreras A, Mane SP, Zhang XS,
Pericchi L, Alarcón T, Contreras M, Linz B, Blaser
MJ, Domínguez-Bello MG. Phylogeographic evidence of cognate recognition site patterns and
transformation efficiency differences in H. pylori:
theory of strain dominance. BMC Microbiol.
13(1):211-224. 2013. PMID: 24050390. IF: 2,976.
DOI: 10.1186/1471-2180-13-211
Hirsch HH, Lautenschlager I, Pinsky BA,
Cardeñoso L, Aslam S, Cobb B, Vilchez RA,
Valsamakis A. An international multicenter performance analysis of cytomegalovirus load tests.
Clin Infect Dis. 56(3):367-73. 2013. PMID:
23097587. IF: 9,416. DOI: 10.1093/cid/cis900
Correa-Ruiz A, Girón R, Buendía B, MedinaPascual MJ, Valenzuela C, López-Brea M, SáezNieto JA. Burkholderia cepacia complex infection
in an Adult Cystic Fibrosis unit in Madrid. Enferm
23528342.
IF:
1,881.
DOI:
10.1016/j.eimc.2012.12.001
Hoefsloot W, Van Ingen J, AndrejaK C, Angeby K,
Bauriaud R, Bemer P, Beylis N, Boeree MJ, Cacho
J, Chihota V, Chimara E, Churchyard G, Cias R,
Dasa R, Daley CL, Dekhuijzen PN, Domingo D,
Drobniewski F, Esteban J, Fauville-Dufaux M,
Folkvardsen DB, Gibbons N, Gómez-Mampaso E,
Gonzalez R, Hoffmann H, Hsueh PR, Indra A,
Jagielski T, Jamieson F, Jankovic m, Jong E,
Keane J, Koh WJ, Lange B, Leao S, Macedo R,
Mannsåker T, Marras TK, Maugein J, Milburn HJ,
Mlinkó t, Morcillo N, Morimoto K, Papaventsis D,
Palenque E, paez-Peña M, PIersimoni C, Polanová
M, Rastogi N, Richter E, Ruiz-Serrano MJ, Silva A,
Da Silva MP, Simsek H, Van Soolingen D, Szabó N,
Thomson R, Fernández MT, Tortoli E, Totten SE,
Tyrrell G, Vasankari T, Villar M, Walkiewicz R,
Winthrop K, Wagner D; FOR NTM-NET. The geographic diversity of nontuberculous mycobacteria
isolated from pulmonary samples: A NTM-NET collaborative study. Eur Respir J. 42(6):1604-13.
2013. PMID: 23598956. IF: 7,125. DOI:
10.1183/09031936.00149212
– 141 –
AREA 3AREA 2 AREA 1
tive than pp65 antigenemia and the AMPLICOR MONITOR
CMV test in HSCT recipients. The lower limit of quantification and co-linearity with the international WHO standard
renders the CAP/CTM CMV test suitable for future clinical
trials defining viral load thresholds of CMV therapy.
F Megraud, S Coenen, A Versporten, M Kist, M
Lopez-Brea, A Hirschl, L Andersen, H Goossens, Y
Glupczynski, on behalf of the Study Group participants (T Alarcón, J Gisbert, ). Helicobacter pylori
resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut. 62(1):34-42.
2013. PMID: 22580412. IF: 13,319. DOI:
10.1136/gutjnl-2012-302254
Alarcón T, Martínez MJ, Urruzuno P. Helicobacter
pylori in Pediatrics. Helicobacter. 18(SUPL 1):5257. 2013. PMID: 24011246. IF: 2,993. DOI:
10.1111/hel.12070
Cantón E, Pemán J, Iñiguez C, Hervás D, LopezHontangas JL, Pina-Vaz C, Camarena JJ, Campos-
– 142 –
Herrero I, García-García I, García-Tapia AM, Guna R,
Merino P, Pérez del Molino L, Rubio C, Suárez A;
FUNGEMYCA
Study
Group
(BUENDIA
B).
Epidemiological cutoff values for fluconazole, itraconazole, posaconazole, and voriconazole for six Candida
species as determined by the colorimetric Sensititre
YeastOne method. J Clin Microbiol. 51(8):2691-2695.
2013. PMID: 23761155. IF: 4,232. DOI:
10.1128/JCM.01230-13
Cardeñoso L, Pinsky BA, Lautenschlager I, Aslam
S, Cobb B, Vilchez RA, Hirsch HH. CMV antigenemia and quantitative viral load assessments in
hematopoietic stem cell transplant recipients. J
Clin Virol. 56(2):108-12. 2013. PMID: 23146665.
IF: 3,466. DOI: 10.1016/j.jcv.2012.10.001
AREA 3
GRUPO 55
HEAD OF LABORATORY
GROUP MEMBERS
• Concepción Alonso Cerezo
• Ana Isabel Ballesteros García
• José Cantero Perona
• Lourdes del Campo del Val
• Yolanda Delgado Jiménez
• Olga Donnay Candil
• Iñigo García Sanz
• José Luis García Fernández
• Jesús González Cajal
• María Mercedes Guijarro Rojas
• Elena Martín Pérez
• Santiago Martínez San Martín
• José Andrés Moreno Monteagudo
• Ramón Moreno Balsalobre
• Erich Alberto Vargas Díez
• Francisco E. Viamontes Ugalde
• Yat Wah Wah Tam
MAJOR GRANTS
• Cecilio Santander Vaquero. Proyecto coordinado.
Cribado del cáncer colorrectal en población de riesgo intermedio: estudio multicéntrico en el que se
compara la prueba de detección de sangre oculta en
heces con método inmunológico y la colonoscopia.
• Ramón Colomer Bosch. Desestabilización estructural de la adicción a oncogenes en cáncer de mama
mediante el bloqueo de la sintasa de ácidos grasos.ISCIII. PI11/00832. Duration: 2012 – 2014.
YEAR
Total IF
Publication No.
Q1
2011
2012
74,154
30
10
97,843
17
2013
5
69,258
10
5
Lucendo AJ, Arias Á, Molina-Infante J, RodríguezSánchez J, Rodrigo L, Nantes Ó, Pérez-Arellano E, de
la Riva S, Pérez-Aisa Á, Barrio J; ACAD Group of
Researchers. Collaborators, Ávila CM,RodríguezTéllez M, San Juan AM, Santander VC, Balbuena GT,
Delgado PM, Eizaguirre AF, Rodrigo SL, Pérez MI,
Hernández AT, Vila J, Sancho del VL, Barrio J, Alcaide
SN, Alcalá EM, Lucendo AJ, Legido GJ, Doménech
WJ, Simó JR, Soto FS, Nantes O, Valer López-Fando
P, Rodríguez Sánchez-Migallón J, Molina-Infante J,
Pérez-Aisa A, Rodríguez TA, Mearin MF, Balboa RA,
Benito VL, Fernández SL, Pérez AE, De la Riva OS,
Gastaminza LG, Guilarte M. Diagnostic and therapeutic management of eosinophilic oesophagitis in children and adults: results from a Spanish registry of
clinical practice. Dig Liver Dis. 45(7):562-8. 2013.
PMID: 23461842. IF: 2,889. DOI: 10.1016/j.dld.
2013.01.013
Gómez-Ramírez J, Tagarro D, Bravo JM, Martín-Pérez
E, Larrañaga E. Preoperative parathyroid harpoon
localisation: a new technique helpful in reoperative
patients with persistent hyperparathyroidism. Ann R
Coll Surg Engl. 95(2):e25-6. 2013. PMID: 23484975.
IF: 1,223. DOI: 10.1308/003588413X1351160995
5896
Bustamante J, Leal O, Soto de Prado D, Domínguez L,
Nombela F, Guijarro M, Gamallo C. Hamartomatous
96(3):1068-70. 2013. PMID: 23992702. IF: 3,631. DOI:
10.1016/j.athoracsur.2013.01.036
– 143 –
AREA 3AREA 2 AREA 1
Line 3.8
Individualized medicine
in solid tumors
Quintela-Fandino M, Krzyzanowska M, Duncan G,
Young A, Moore MJ, Chen EX, Stathis A, Colomer
R, Petronis J, Grewal M, Webster S, Wang L, Siu
LL. In vivo RAF signal transduction as a potential
biomarker for sorafenib efficacy in patients with
neuroendocrine
tumours.
Br
J
Cancer.
108(6):1298-305. 2013. PMID: 23412107. IF:
4,817. DOI: 10.1038/bjc.2013.64 108
Sánchez-Ferrero E, Coto E, Beetz C, Gámez J,
Corao AI, Díaz M, Esteban J, del Castillo E, Moris
G, Infante J, Menéndez M, Pascual-Pascual SI,
López de Munaín A, Garcia-Barcina MJ, Alvarez V;
Genetics of Spastic Paraplegia study group. SPG7
mutational screening in spastic paraplegia patients
supports a dominant effect for some mutations and
a pathogenic role for p.A510V. Clin Genet.
83(3):257-262. 2013. PMID: 22571692. IF: 3,562.
DOI: 10.1111/j.1399-0004.2012.01896.x
Steegmann JL, Sánchez Torres JM, Colomer R,
Vaz A, López J, Jalón I, Provencio M, GonzálezMartín A, Pérez M. Prevalence and management of
anaemia in patients with non-myeloid cancer
undergoing systemic therapy: a Spanish survey.
Clin Transl Oncol. 15(6):477-83. 2013. PMID:
23263906. IF: 1,600. DOI: 10.1007/s12094-0120953-5
R Jover, P Zapater, E Polanía, L Bujanda, ALanas,
JA Hermo, J Cubiella, A Ono, Y González-Méndez,
A Peris, M Pellisé, A Seoane, A Herreros, M Ponce,
JC Marín-Gabriel, M Chaparro, G Cacho, S
Fernández-Díez, J Arenas, F Sopeña, L de-Castro,
P Vega-Villaamil, M Rodríguez-Soler, F Carballo, D
Salas, JD Morillas, M Andreu, E Quintero, A
Castells and COLONPREV study investigators.
Modifiable endoscopic factors that influence the
adenoma detection rate in colorectal cancer
screening colonoscopies. Gastrointest Endosc
77(3):381-389.e1. 2013. PMID: 23218945. IF:
4,900. DOI: 10.1016/j.gie.2012.09.027
Davies C, Pan H, Godwin J, Gray R, Arriagada R,
Raina V, Abraham M, Medeiros Alencar VH, Badran
A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis
– 144 –
SR, Delmestri A, Forbes JF, Haddad P, Hou MF,
Inbar M, Khaled H, Kielanowska J, Kwan WH,
Mathew BS, Mittra I, Müller B, Nicolucci A, Peralta
O, Pernas F, Petruzelka L, Pienkowski T, Radhika
R, Rajan B, Rubach MT, Tort S, Urrútia G, Valentini
M, Wang Y, Peto R; Adjuvant Tamoxifen: Longer
Against Shorter (ATLAS) Collaborative Group.
Long-term effects of continuing adjuvant tamoxifen
to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer:
ATLAS, a randomised trial. Lancet. 381(9869):80516. 2013. PMID: 23219286. IF: 39,207
Martin-Perez E, Capdevila J, Castellano D,
Jimenez-Fonseca P, Salazar R, Beguiristain-Gomez
A, Alonso-Orduña V, Martinez Del Prado P,
Villabona-Artero C, Diaz-Perez JA, Monleon A,
Marazuela M, Pachon V, Sastre-Valera J, Sevilla I,
Castaño A, Garcia-Carbonero R. Prognostic
Factors and Long-Term Outcome of Pancreatic
Neuroendocrine Neoplasms: Ki-67 Index Shows a
Greater Impact on Survival than Disease Stage.
The Large Experience of the Spanish National
Tumor Registry RGETNE. Neuroendocrinology.
98(2):156-168. 2013. PMID: 23988576. IF: 4,934.
DOI: 10.1159/000355152
Gascón P, Rodríguez CA, Valentín V, Mata JG,
Carulla J, Cassinello J, Colomer R, Baró E.
Usefulness of the PERFORM questionnaire to
measure fatigue in cancer patients with anemia: a
prospective, observational study. Support Care
Cancer. 21(11):3039-49. 2013. PMID: 23793142.
IF: 2,495. DOI: 10.1007/s00520-013-1862-z
BOOKS
Collazo Lorduy, G. Viñas Villaró, R. Colomer Bosch.
Los agentes antimicrotúbulo: taxanos, alcaloides de
la vinca, epotilonas y halicondrinas. Oncomecum.
2013. Publicidad Permanyer. ISBN: 978-84-9926544-5.
AREA 3
CLINICAL TRIALS
Disfagia como origen de malnutrición en pacientes hospitalizados; (versión DISF-HULP)
PRINCIPAL RESEARCHER: BALLESTEROS GARCIA,
ANA-ISABEL
Patrones de práctica y cumplimiento del tratamiento adyuvante con dosis altas de interferón y resultados clínicos con
melanoma completamente extirpado con riesgo alto de
recidiva: un análisis retrospectivo realizado en centros
españoles; (Versión 1: 16-11-12). MERCK SHARP &
DOHME DE ESPAÑA, S.A. MSD-MEL-2012-01
ANA-ISABEL
Estudio multicéntrico de un sólo brazo para evaluar la
seguridad de eribulina en 3línea de quimioterapia para
pacientes con cáncer de mama HER2 negativo metastásico o locamente avanzado tratado previamente con taxanos
y antraciclina: Estudio OnSITE; (Versión 3.0:18-03-13).
ONCOSUR. ONCOSUR-2012-02. EudraCT: 2013001416-30
PRINCIPAL RESEARCHER: COLOMER BOSCH, RAMON
Estudio piloto, abierto, de fase II y con un solo brazo de
tratamiento para evaluar la asociación de los biomarcadores de resistencia hormonal y la vía mTOR con la eficacia clínica de everolimus más letrozol en el tratamiento de
primera línea de mujeres posmenopáusicas con cáncer de
mama metastásico o localmente avanzado con receptores
hormonales positivos; (Versión 1: 15-07-13). NOVARTIS
FARMACEUTICA, S.A. CRAD001JES13. EudraCT: 2013004139-62
PRINCIPAL RESEARCHER: DELGADO JIMENEZ,
YOLANDA
Protocolo de registro español de cirugía de Mohs; (Versión
1: 12-03-13).FAE-MOH-2013-01
PRINCIPAL RESEARCHER:
HEREDERO, M. JOSE
GALAN
PRINCIPAL RESEARCHER: SANCHEZ TORRES, JOSE
MIGUEL
Estudio de fase II de dabrafenib, un inhibidor selectivo de
BRAF, en monoterapia y en combinación con trametinib,
un inhibidor de MEK, en pacientes con cáncer de pulmón
no microcítico, metastásico (esta-dio IV) y positivo para la
mutación BRAF V600E. GLAXOSMITHKLINE, S.A.
BRF113928. EudraCT: 2011-001161-41
PRINCIPAL RESEARCHER: SANCHEZ TORRES, JOSÉ
MIGUEL
Estudio observacional retrospectivo para describir el manejo de los pacientes con cáncer de pulmón no microcítico
avanzado o metastásico con mutaciones del EGFR en
España (versión 1.0: 31-10-12). ASTRAZENECA FARMACEUTICA SPAIN, S.A. NIS-OES-XXX-2012/1
PRINCIPAL RESEARCHER: SANCHEZ TORRES, JOSE
MIGUEL
Estudio abierto de afatinib en pacientes no tratados
(primera línea) o tratados previamente con quimioterapia
con cáncer de pulmón no microcítico (CPNM) localmente
avanzado o metastásico portadores de mutación(es) de
EGFR; (Versión1: 13-03-13). BOEHRINGER INGELHEIM
ESPAÑA, S.A. 1200.55. EudraCT: 2009-017661-34
PRINCIPAL RESEARCHER: VARGAS DIEZ, ERICHALBERTO
Prevalencia de Queratosis Actínica en servicios generales
de dermatología hospitalarios españoles. Estudio epidemiológico. (Estudio EPIQA); (Versión 8.0: 24-05-13). ALMIRALL S.A. ALM-QA-2013-1
GRUPO 53
HEAD OF LABORATORY
Almudena Zapatero Laborda
SANCHEZ-
– 145 –
AREA 3AREA 2 AREA 1
ANA-ISABEL
Estudio ABSOLUT-BRAF. Estudio epidemiológico sobre la
mutación BRAF v600en población española diagnosticada
de melanoma metastásico; (versión final: 20-06-12).
ROCHE FARMA, S.A. ROC-BRA-2012-01.
GROUP MEMBERS
• María Magdalena Adrados de Llano
• Ramón Cristóbal Arellano Gañán
• José Alfonso Cruz Conde
• María del Carmen Martín de Vidales Cervantes
• Feliciano García Vicente
• Leopoldo Pérez González
• Mariano Rabadán Ruiz
RESEARCH INTEREST
Our investigation team is focused on the global and
multidisciplinary approach of prostate cancer: molecular markers, treatment of localized and advanced
cancer, and predictive models. We also participate in
the National Register of Prostate Cancer Treated with
Radiotherapy (RECAP).
The main activities of our team along 2013 are represented by the presentation of 13 communications in
international and national meetings and are summarized in the following projects and results:
Prostate Cancer
1. Prostate Cancer treatment
• Presentation in the American Society for Radiation
Oncology (ASTRO) and European Society for
Radiotherapy and Oncology (ESTRO) of the results
on early and late toxicity of the phase III national trial
entitled:“ 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”. This is a pioneer trial in its class
that tests the optimal hormonal treatment length
when combined with high dose radiotherapy in the
treatment of high-risk patients. At the end of the year
2013 we completed the five years analysis report on
disease free survival and overall survival with excellent results. This study has been accepted, as one of
the top five trials, to be presented in the Plenary
Session of the 56th ASTRO international meeting,
and will be published along 2014.
– 146 –
• Presentation of the International project objectives
and preliminary data in the American Society of
Clinical Oncology (ASCO) of the “INTERMEDIATE
CLINICAL ENDPOINTS IN CANCER OF THE
PROSTATE (ICECaP) INITIATIVE”, a meta-analysis
carried out by the ICECaP Working Group, a multidisciplinary team of academic cancer researchers
from the Dana-Farber Cancer Institute -Harvard
Medical School.
2. High Technology and Innovation
• Intensity Modulated Radiation Treatment – Image
Guided Radiotherapy (IMRT-IGRT) versus ·dimensional conformal radiotherapy (3DCRT): comparative results on 671 patients treated in a single institution, that demonstrate the significant reduction in
acute and late genitourinary and rectal toxicity in
patients with prostate cancer treated with IMRTIGRT .
• Implementation of the new technology of VMAT
(Volumetric Modulated Arc Therapy) that improves
the accuracy and safety of prostate cancer treatments and the efficiency in the delivery.
• Our radiation oncology group in colaboration with
the urology team has been selected to participate
in a international phase III trial in Patients Non
Metastatic Castration Resistant Prostate Cancer
(PROSPER) titled: PROSPER: A Multinational,
Phase 3, Randomized, Double-Blind, PlaceboControlled, Efficacy and Safety Study of
Enzalutamide inPatients With Nonmetastatic
Castration-ResistantProstate
CancerCódigo:
MDV3100-14Nº EudraCT: 2012-005665-12that
will initiate the enrolment along 2014.
3. Biological Markers
• Presentation of the results of the study performedin
collaboration with the team of Dr Morente of the
CNIO: The Prognostic Value of Expression of
HIF1a, PAK-6, and PSMB4 in intermediate- and
High-Risk Localized Prostate Cancer Patients
Treated With Androgen Deprivation and Dose
Escalation Radiation Therapy Ref.: CaPr-HLP-RT01/ PI 197”. This is the first description of PAK6
and PSMB4 expression in the diagnostic specimens of men with prostate cancer treated with RT.
AREA 3
4. National Register Of Prostate Cancer Treated with
Radiotherapy (RECAP)
• We participate in the design of this ambitious project whose most relevant work is the construction
of nomograms for predicting the development of
metastases and biochemical failure in cancer of
prostate treated with radiation therapy.
Bladder Cancer - Bladder Sparing Program
The optimal management of muscle-invasive bladder
cancer remains a continuous subject of controversy.
Although
trimodality
treatment,
including
transurethral resection of bladder tumour (TURBT)
and radio-chemotherapy (RCT), has proven to be an
alternative to primary cystectomy, the optimal regimen and combination of RT and chemotherapy
remains to be established.
Our team is one of the most active and successfully
experienced groups in the conservative treatment of
invasive bladder cancer. We continue to study the
optimal sequence of treatment concerning tumor
control, bladder preservation quality of life and efficient delivery.
MAJOR GRANTS
• Almudena Zapatero Laborda. Assessment of intermediate clinical endpoints from studies of clinically localized prostate cancer to identify a reliable surrogate of
overall survival benefit. DF/HCC Investigator. DFCI
Protocol No.: 12-473. Duration: 2013 –
YEAR
Total IF
Publication No.
Q1
2011
11,174
4
3
2012
9,990
5
2
2013
2,834
2
-
Gallo E, Pérez-Gala S, Navarro R, Fraga J, Adrados
M, Arranz R, García-Diez A,Aragüés M. Coexistence
of marginal zone cutaneous B-cell lymphoma and
classic Hodgkin disease: does a biological relationship exist?. Clin Exp Dermatol. 38(4):383-5. 2013.
PMID: 23551363. IF: 1,234. DOI: 10.1111/j.13652230.2012.04478.x
Zapatero A, López-Torrecilla J, Herruzo I, Calvo FA;
SEOR
URONCOR
GICOR
participating
Investigators. Practice patterns in the management
of prostate cancer in Spain: results from a national
survey among radiation oncologists in 2009. Clinical
& Translational Oncology. 15(3):226-32. 2013.
PMID: 22855195. IF: 1,600. DOI: 10.1007/s12094012-0913-0
BOOKS
José Miguel Delgado Rodríguez, Feliciano García
Vicente, Alejandro García Romero, Esther Millán Cebrián.
Editor Antonio Brosed Serreta. Radioterapia externa II:
dosimetría clínica, algoritmos de cálculo, sistemas de
planificación y control de calidad. Fundamentos de Física
Médica. Volumen 4. 2013. Aula documental de investigación. ISBN: 978-84-940849-7-3.
Almudena Zapatero. Guillermo Andrés. Javier Angulo.
Ignacio Durán. Helena Gimbernat. Fernando Lista. José
Ignacio López. Erika Mateo. Cáncer de próstata. 2013.
Elsevier España, S.L. ISBN: 978-84-7592-757-2.
Almudena Zapatero, Carmen Martin de Vidales, Pilar
Samper, Yamilé Ibáñez. Toxicidad Urológica. Soporte
Médico en oncología radioterápica. 2013. Editorial Arán.
ISBN: 978-8492977-60-4. Capítulo 6 Páginas 271-306.
– 147 –
AREA 3AREA 2 AREA 1
The results of this study has been accepted for
publication in UrolOncol.
• We have initiated the recruitment of patients of the
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.
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ZAPATERO LABORDA,
MARÍA-ALMUDENA
Tratamiento radioterápico en pacientes con cáncer de
próstata en función del nivel de riesgo conforme a la
práctica clínica habitual en los servicios de oncología
radioterápica españoles; (Versión final 1.0:30-01-13).
GICOR. GIC-RAD-2013-01
GRUPO 54
HEAD OF LABORATORY
Laura Cerezo Padellano
GROUP MEMBERS
• Consuelo López Elzaurdia
• Mario López Rodríguez
• Adolfo Hinojar Gutiérrez
• Rafael Manzanares Soler
• Alicia Marín Palomo
• Margarita Martín Martín
• Mario Fernando Muñoz Guerra
• Eduardo Raboso García-Baquero
• Francisco José Rodríguez Campo
RESEARCH INTEREST
During the year 2013, the group progressed in its multidisciplinary treatment of head and neck cancer. The multicentric study on oropharyngeal cancer related to Human
Papilloma Virus, sponsored by Fundación Mutua Madrileña,
has been published in Head & Neck journal and in Clinical
& Translational Oncology, both included in the citation index
and Medline. Several conference talks have been given on
this subject, the most recent one on the HPH Infection
Conference held in the Hospital Universitario Infanta Leonor,
Madrid, on May 28, 2014.
– 148 –
Fig.1. Proportion of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas in different countries. The incidence in
Spain has been taken from our study: Incidence of human papillomavirus-related oropharyngeal cancer and outcomes after chemoradiation. Head Neck 2014; 36:782-786.
We are planning to expand this research, analyzing all
patients with oropharyngeal cancer treated from 2011 to
2014 from six large hospitals in Madrid and studying the
percentage of HPV positive. Thus, we will have a clear picture of the incidence of oropharyngeal cancer related to
HPV infection in our region.
A review on neck dissection after chemoradiation for head
and neck cancer has been done, in collaboration with the
E.N.T. department, and the Radiology department to establish which patients undergoing a conservative treatment
need to be operated.
Our multicentric phase III study on the benefit of Clonidine
for the prevention of oral mucositis in head and neck cancer patients has completed accrual now and statistical
analysis is planned for this year. Also, the study on
intranasal Fentanyl for the treatment of pain associated with
oral mucositis, has completed its accrual now. 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
AREA 3
asociados a la progresión de lesiones precursoras
del cáncer gástrico: estudio coordinado español de
seguimiento. ISCIII. PI10/02654. Duration: 2011 2013.
• 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
Laura Cerezo, Alicia Marín, Ángel Montero. Piel y tejido
subcutáneo. Práctica clínica en Oncología
Radioterápica. 2013. Arán. ISBN: 978-84-92977-60-4.
L.A. Pérez-Romasanta, Laura Cerezo, F.A. Calvo.
Práctica clínica en el área de cabeza y cuello.
Práctica clínica en Oncología Radioterápica. 2013.
Arán. ISBN: 978-84-92977-60-4.
CLINICAL TRIALS
[IF: 2,88]
YEAR
Total IF
Publication No.
Q1
2011
25,234
8
2
2012
4,509
6
-
2013
2,88
2
-
Mera-Menéndez F, Hinojar-Gutiérrez A, Guijarro Rojas
M, de Gregorio JG, Mera-Menéndez E, Sánchez JJ,
Quintanilla M, Cerezo L, Gamallo C. Polymorphisms in
HIF-1alpha affect presence of lymph node metastasis
and can influence tumor size in squamous-cell carcinoma of the glottic larynx. Clin Transl Oncol. 15(5):35863. 2013. PMID: 22914908. IF: 1,600. DOI:
10.1007/s12094-012-0930-z
Capote-Moreno AL, Naval-Gías L, Muñoz-Guerra
MF,Rodriguez-Campo FJ. Zygomatic distraction
osteogenesis for correction of midfacial support
after hemimaxillectomy: Experience and technical
considerations. J Oral Maxillofac Surg. 71(4):189197. 2013. PMID: 23507326. IF: 1,280. DOI:
10.1016/j.joms.2012.11.019
PRINCIPAL RESEARCHER: CEREZO PADELLANO,
LAURA
Estudio de fase III, abierto, aleatorizado, multicéntrico
sobre los efectos de la inyección de interleucina
[Multikine]
más
tratamiento
de
referencia
(cirugía+radioterapia o cirugía+quimirradioterapia concurrente) en pacientes con carcinoma epidermoide primario avanzado de la cavidad oral/paladar blando
frente al tratamiento de referencia únicamente; (versión
2.0: 19-12-11). CEL-SCI CORPORATION
CS001P3. EudraCT: 2010-019952-35
PRINCIPAL RESEARCHER: MUÑOZ GUERRA, MARIO
FERNANDO
Evaluación del ácido hialurónico como coadyuvante a
la artroscopia de ATM en estadios III y IV de Wilke.
DUROLANE
GROUP ASSOCIATED 2
HEAD OF LABORATORY
Carlos Manuel Olivier Gómez
BOOKS
Laura Cerezo, Margarita Martín, Mario López.
Actualización de radioterapia más terapias biológicas. Radioterapia en Cáncer de Cabeza y Cuello.
2013. You & Us. ISBN: 978-84-695-7133-0.
GROUP MEMBERS
• Gloria Bocardo Fajardo
• Ricardo Brime Menéndez
– 149 –
AREA 3AREA 2 AREA 1
PUBLICATIONS
(2)
•
•
•
•
•
Guillermo Celada Luis
Victoria Diego García
Inmaculada Fernández González
María José Galán Sánchez-Heredero
Estefanía Romero Selas
RESEARCH INTEREST
Our group focused on different research areas:
• Erectile dysfunction: Endothelial dysfunction is one
of the first symptoms of erectile dysfunction (ED)
and is closely related to atherosclerosis and risk
factors such as diabetes mellitus (DM), both of
them characterized by inflammatory and oxidative
advanced state. Vardenafil is one of the more
effective 5-phosphodiesterase inhibitors in
patients with ED and DM. We have determined
plasma proteome of patients with DM and the
effect of vardenafil administration in the expression
of proteins related to inflammatory oxidative stress
and cellular homeostasis. We have observed a
significant negative correlation between plasma
levels of beta-tropomyosin and IIEF-EF score.
Elevated levels of beta-tropomyosin in plasma
indicate cell damage and loss of cellular regenerative capacity.
• Urothelial cancer: Exosomes extracellular vesicles
are potent intercellular mediators containing membrane and cytosolic proteins, mRNA and specific
miRNA, which in turn can be obtained from fluids
such as urine. We have analyzed urinary exosomas, miRNA and protein content in order to find
diagnostic markers for bladder urothelial cancer.
Some of the miRNAs that are involved in tumor cell
proliferation, inhibition of tumor suppressor genes,
activation of EMT and metastatic state, are significantly reduced in urinary exosomes from patients
with bladder urothelial carcinoma and may be useful as non-invasive diagnostic biomarkers in bladder cancer.
With regard to surgical techniques, we have optimized the diagnosis and therapeutic endourologic
approach to the upper urothelial tract cancer.
YEAR
Total IF
Publication No.
Q1
2011
4,105
1
1
2012
10,706
4
1
2013
4,948
2
1
Otta R, Gordillo C, Olivier C. Early penile metastasis as
the first sign of urothelial carcinoma spread. Int J Urol.
20(7):740. 2013. PMID: 23231547. IF: 1,798. DOI:
10.1111/iju.12046
Fig.1. a) Elevated levels of plasma beta-tropomyosin indicate cell damage and induce loss of cell regenerative capacity. b)Significant negative correlation between plasma levels of beta-tropomyosin and
IIEF-EF
– 150 –
Zamorano-León JJ, Olivier C, de Las Heras N, MateosCáceres PJ, Brime Menéndez R, Rodríguez-Sierra P,
Martín Palacios N, Manso LS, Modrego J, Segura A,
Macaya C, López-Farré AJ. Vardenafil Improves Penile
Erection in Type 2 Diabetes Mellitus Patients with
Erectile Dysfunction: Role of Tropomyosin. J Sex Med.
10(12):3110-20.. 2013. PMID: 24112450. IF: 3,150.
DOI: 10.1111/jsm.12324
AREA 3
PRINCIPAL RESEARCHER: OLIVIER GOMEZ, CARLOS
Estudio postautorización, observacional, prospectivo, longitudinal, multicéntrico para evaluar el porcentaje de pacientes con cáncer de próstata en
tratamiento con análogos de la LHRH que muestran resistencia a la castración (CPRC) tras un periodo de seguimiento de 3 años (Estudio ANARESISTANCE); (Versión 1: 28-06-12). IPSEN PHARMA, S.
A. IPS-PRO-2012-02
Pérez C, Navarro A, Saldaña MT, Figueras-Balsells M,
Muñoz-Tudurí M, Rejas J. Cost savings associated with
early initiation of pregabalin in the management of
peripheral neuropathic pain. Clin J Pain. 29(6):471-7.
2013. PMID: 23328322. IF: 2,703. DOI:
10.1097/AJP.0b013e3182652c2b
Cordero-Ampuero J, González-Fernández E,
Martínez-Vélez D, Esteban J. Are antibiotics necessary in hip arthroplasty with asymptomatic bacteriuria? Seeding risk with/without treatment. Clin
Orthop Relat Res. 471(12):3822-9. 2013. PMID:
23430723. IF: 2,882. DOI: 10.1007/s11999-0132868-z
Pergolizzi J, Ahlbeck K, Aldington D, Alon E, Coluzzi F,
Dahan A, Huygen F, Kocot-Kepska M, Mangas AC,
Mavrocordatos P, Morlion B, Müller-Schwefe G,
Nicolaou A, Pérez Hernández C, Sichère P, Schäfer M,
Varrassi G. The development of chronic pain: physiological CHANGE necessitates a multidisciplinary
approach to treatment. Curr Med Res Opin.
29(9):1127-35. 2013. PMID: 23786498. IF: 2,372. DOI:
10.1185/03007995.2013.810615
GROUP ASSOCIATED 3
HEAD OF LABORATORY
Concepción Pérez Hernández
GROUP MEMBERS
• Enrique Alday Muñoz
• Vicente Casa de Pantoja
• Francisco Clement Fernández
• José Cordero Ampuero
• Antonio Gómez Pan
• Jacobo González Guijarro
• Javier Izaguirre Anduaga
• Emilio Marín Aráez
• Mar Orts Rodríguez
• Antonio Planas Roca
• Fernando Ramasco Rueda
• Fernando Teba del Pino
Pérez C, Margarit C, Serrano M; Spanish group of
CHANGE PAIN patient survey. Survey of European
patients assessing their own noncancer chronic pain:
results from Spain. Curr Med Res Opin. 29(6):643-51.
2013. PMID: 23514116. IF: 2,372. DOI:
10.1185/03007995.2013.787978
Pérez C, Ribera MV, Gálvez R, Micó JA, Barutell C,
Failde I, Sánchez-Magro I, Stern A. High prevalence of
confirmed, but also of potential and believed, neuropathic pain in pain clinics. Eur J Pain. 17(3):347-56.
2013. PMID: 22927200. IF: 3,218. DOI:
10.1002/j.1532-2149.2012.00204.x
YEAR
Total IF
Publication No.
Q1
2011
10,687
8
1
2012
114,018
16
7
2013
20,049
7
5
Molina-Manso D, del Prado G, Ortiz-Pérez A,
Manrubia-Cobo M, Gómez-Barrena E, CorderoAmpuero J, Esteban J. In vitro susceptibility to antibiotics of staphylococci in biofilms isolated from
orthopaedic infections. Int J Antimicrob Agents.
41(6):521-3. 2013. PMID: 23611308. IF: 4,259. DOI:
10.1016/j.ijantimicag.2013.02.018
– 151 –
AREA 3AREA 2 AREA 1
CLINICAL TRIALS
Pérez C, Navarro A, Saldaña MT, Masramón X, Pérez
M, Rejas J. Clinical and resource utilization patterns in
patients with refractory neuropathic pain prescribed
pregabalin for the first time in routine medical practice
in primary care settings in Spain. Pain Med.
14(12):1954-63. 2013. PMID: 24330229. IF: 2,243.
DOI: 10.1111/pme.12276
CLINICAL TRIALS
PRINCIPAL RESEARCHER: ALDAY MUÑOZ,
ENRIQUE
Efecto de sevoflurano vs desflurano en la vía aérea
tras sedación en ventilación espontánea con mascarilla laríngea; EAM-SEV-2013-01.
PRINCIPAL RESEARCHER: CLEMENT FERNANDEZ, FRANCISCO
Estudio POLARIS: Estudio prospectivo no intervencionista para valorar la efectividad de los
regímenes de tratamiento actuales con anti-factor
de crecimiento endotelial vascular (Anti-VEGF) en
pacientes con edema macular diabético (EMD) con
afectación central; (Versión 1.0:15-10-12). BAYER
HISPANIA S.L. BAY-RAN-2012-02
PRINCIPAL RESEARCHER: CLEMENT FERNANDEZ, FRANCISCO
Ensayo clínico en fase IV para evaluar las variantes
genéticas de la vía VEGF como biomarcadores de
– 152 –
eficacia del tratamiento con aflibercept en
pacientes con degeneración macular asociada a la
edad (DMAE) neovascular. Estudio BIOIMAGE;
(Versión final: 10-05-13). FUNDACIO DE RECERCA
DE IMO. IMO-AFLI-2013-01. EudraCT: 2013002124-17
PRINCIPAL RESEARCHER: PEREZ HERNANDEZ,
CONCEPCION
Estudio piloto de fase 4, multicéntrico y abierto, de
pregabalina y predicción de la respuesta al
tratamiento en pacientes con neuralgia posherpética; (versión amendment 1: 19-10-12). PFIZER INC.
A9001464. EudraCT: 2011-005972-41
CONCEPCIÓN
Estudio de fase IIa, controlado con placebo, de
retirada aleatorizada y con doble enmascaramiento, para evaluar la seguridad y la eficacia de
CNV1014802 en pacientes con neuralgia del
trigémino;(versión 1.0: 29- -11-12). CONVERGENCE PHARMACEUTICALS LTD 1014802/202.
EudraCT: 2010-023963-16
CONCEPCIÓN
Estudio epidemiológico, observacional, prospectivo, para evaluar la relación entre la empatía
médico-pac iente y el alivio del dolor y de la calidad
de vida, en unidades de dolor; (Versión final: 2606-13). MUNDIPHARMA PHARMACEUTICALS, S.
L. ESTUDIO EMPATIA
www.iis-princesa.org

AREA 1 - IIS LA PRINCESA

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