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5,056 results on '"Fundación Jiménez Díaz"'

1. Trophic Nutrition in Patients Submitted to High Flow Oxygen Therapy and / or Non Invasive Mechanical Ventilation

Author

Hospital Universitario de Gran Canaria Doctor Negrín, Hospital Universitario Fundación Jiménez Díaz, Hospital Barbastro, Hospital del Rio Hortega, Hospital Universitario Infanta Cristina, Hospital Universitario Ramon y Cajal, Hospital Universitari Dr Josep Trueta, Hospital Universitario Infanta Leonor, Hospital Regional Universitario Carlos Haya, Hospital Universitario Cruces, Hospital Universitario 12 de Octubre, Hospital Universitario Virgen de la Arrixaca, Hospital Virgen de la Concha, Hospital Universitario de Torrevieja, Complejo Hospitalario Universitario de Santiago, Hospital Universitario Puerto Real, Hospital Miguel Servet, Hospital Universitario Severo Ochoa, Hospital Universitario La Fe, and Antonio Luis Blesa Malpica, Principal Investigator

Published
2024

3. INOCA Spanish National Registry (ESP-INOCA)

Author

Hospital San Carlos, Madrid, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa, Hospital Universitario Virgen de la Arrixaca, University Hospital Gregorio Marañón, Hospital Clínico Universitario de Valladolid, Hospital Universitario Puerta del Mar, Hospital Universitari de Bellvitge, Hospital Universitario La Fe, Hospital Clínico Universitario de Valencia, Hospital Universitario La Paz, Hospital General Universitario de Alicante, Complejo Hospitalario Universitario de Huelva, Hospital General Universitario de Castellón, Hospital de Manises, Hospital Clinic of Barcelona, Hospital Miguel Servet, Hospital Clínico Universitario Lozano Blesa, Hospital Universitario Donostia, Hospital General Universitario Elche, Hospital Universitario Virgen del Rocio, Hospital de la Ribera, Hospital de la Santa creu i Sant Pau - Barcelona, Hospital Virgen de la Salud, Hospital Universitario San Juan de Alicante, Hospital Universitario de Torrevieja, University Hospital of the Nuestra Señora de Candelaria, Hospital de Basurto, Hospital Universitario Ramon y Cajal, Hospital Universitario Fundación Jiménez Díaz, Puerta de Hierro University Hospital, Hospital Universitario 12 de Octubre, University of Salamanca, Hospital Universitario Marqués de Valdecilla, Hospital Clinico Universitario de Santiago, Complexo Hospitalario Universitario de A Coruña, and Eva Rumiz González, Principal Investigator

Published
2024

5. Lentiviral-mediated Gene Therapy of Fanconi Anemia Patients Subtype A (FANCOLEN-1)

Author

Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación en Red de Enfermedades Raras (CIBERER), Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, and Julian Sevilla, M.D.PhD Specialist in Hematology Hemotherapy, Responsible for the Transfusion Service and Unit for the Obtention and Processing of Hematopoietic Progenitors and other cellular therapies at the Hospital Infantil Universitario Niño Jesús de Madrid.

Published
2024

12. Study and Follow-up of the Clinical Effectiveness and Comparative Safety of Biosimilar Teriparatide in the Management of Postmenopausal or Senile. (ESECTO)

Author

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa, Instituto Palacios, Complexo Hospitalario de Ourense, Hospital Universitario Central de Asturias, Parc Taulí Hospital Universitari, Hospital Universitario Fundación Jiménez Díaz, Hospital Universitario Infanta Leonor, Hospital Universitario Virgen Macarena, Hospital d´Igualada, and Alpha Bioresearch S.L.

Published
2022

13. Pilot Study to Evaluate the Effectiveness of Online Familiar Metacognitive Training (MCTf) (MCTf)

Author

Parc Sanitari Sant Joan de Déu, Hospital de Sant Pau, Institut Pere Mata, Parc Taulí Hospital Universitari, Hospital de Mataró, Centre d'Higiene Mental Les Corts, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Hospital del Mar, Hospital Universitario Marqués de Valdecilla, Hospitales Universitarios Virgen del Rocío, Fundació Vidal i Barraquer, and Hospital Sant Joan de Deu

Published
2022

14. A New Clinic-Genetic Risk Score for Predicting Venous Thromboembolic Events in Cancer Patient (ONCOTHROMB)

Author

Servicio de Oncología Médica. HGU Gregorio Marañón. Madrid, Unitat de Genòmica de Malalties Complexes. Institut d'Investigació Sant Pau, Hospital Universitario La Paz, Hospital Universitario Ramon y Cajal, Hospital Clinic of Barcelona, Hospital Universitario de Fuenlabrada, Hospital Universitario Marqués de Valdecilla, Complexo Hospitalario de Ourense, Complejo Universitario Torrecárdenas, Almería, Gendiag, Ferrer inCode, S.L., Unitat d'Hemostasia i Trombosi. Hospital de la Santa Creu i Sant Pau, LEO Pharma, Sociedad Española de Trombosis y Hemostasia (SETH), Sociedad Española de Oncología Médica (SEOM), University Hospital Virgen de las Nieves, Hospital Obispo Polanco, Teruel, Complejo Hospitalario Universitario de Vigo, Hospital General Universitario Elche, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Hospital General de Ciudad Real, and Andres muñoz, MD PhD

Published
2022

15. Peri-Implant and Peri-Prosthetic Fractures: Epidemiology, Morbidity, Mortality, Treatment and Outcome Analysis (PIPPAS)

Author

Hospital Mutua de Terrassa, Althaia Xarxa Assistencial Universitària de Manresa, Hospital Clinic of Barcelona, Hospital Universitario 12 de Octubre, Hospital Vall d'Hebron, Hospital de Jove, Gijón, Spain, Hospital de Basurto, Hospital Álvaro Cunqueiro, Hospital Galdakao-Usansolo, Hospital Universitario de Canarias, Hospital Infanta Elena de Valdemoro, Madrid, Hospital Universitario Doctor Peset, Hospital Royo Villanova - Ntra. Sra. de Gracia, Zaragoza, Hospital Universitario de Cabueñes, Asturias, Hospital Universitario Fundación Alcorcón, Madrid, Hospital Nuestra Señora de Sonsoles, Ávila, Hospital Clínico Universitario San Carlos, Madrid, Complejo Hospitalario Universitario, A Coruña, Hospital Gregorio Marañón, Madrid, Hospital Universitario de Álava - Txagorritxu, Alava, Hospital Universitario General de Elche, Elche, Hospital Gral. Univ. Los Arcos del Mar Menor de Murcia, Hospital Vega Baja de Orihuela, Alicante, Hospital Gral. Univ. Morales Meseguer, Murcia, Hospital Can Misses, Ibiza, Hospital Son Llàtzer, Palma de Mallorca, Hospital Marqués de Valdecilla, Santander, Hospital Virgen de la Salud, Hospital Puerta de Hierro, Madrid, Hospital General de Segovia, Hospital Moisés Broggi de Sant Joan Despí, Barcelona, Hospital Universitari Sagrat Cor, Barcelona, Complejo Hospitalario Llerena-Zafra, Badajoz, Hospital Universitario Lucus Augusti, Hospital Universitario La Paz, Hospital Universitario Ramón y Cajal de Madrid, Hospital Universitario Pcpe. de Asturias de Alcalá de Henares, Madrid, Hospital General Universitario Reina Sofía, Murcia, Hospital General Obispo Polanco, Teruel, Hospital Universitario de Guadalajara, Hospital Josep Trueta, Girona, Complejo Hospitalario Universitario de Albacete, Hospital Sierrallana de Torrelavega, Cantabria, Complejo Hospitalario de Palencia, Hospital Universitario Fundación Jiménez Díaz, Madrid, Complexo Hospitalario Universitario de Pontevedra, Hospital Parc Taulí de Sabadell, Barcelona, Hospital Universitario Miguel Servet, Zaragoza, Hospital Universitari Arnau de Vilanova, Lleida, Hospital Universitario de León, Hospital Universitario de Burgos, Hospital Santa Bárbara, Soria, Hospital San Pedro de Logroño, Hospital Costa del Sol de Marbella, Málaga, Hospital Parc De Salut Mar, Barcelona, Hospital Italiano de Buenos Aires, Argentina, Complejo Hospitalario de Navarra, Hospital Santos Reyes de Aranda de Duero, Burgos, Hospitales Universitarios Virgen del Rocío, Hospital de la Santa creu i Sant Pau - Barcelona, Hospital Universitario Dr. Negrín, Gran Canaria, Hospital Universitario Infanta Leonor, Madrid, Hospital Comarcal Alto Guadalquivir de Andújar, Jaén, Hospital Universitario de Donostia, Guipúzcoa, Hospital Carmen y Severo Ochoa de Cangas de Narcea, Asturias, Hospital Reina Sofía de Tudela, Navarra, Hospital Universitario San Agustín de Avilés, Asturias, Hospital Universitario Virgen de la Macarena, Sevilla, Hospital Universitario El Escorial, Madrid, and Héctor J Aguado, MD PhD Associate Professor Trauma/Orthogeriatric unit

Published
2022

16. Assessing Health-related Quality of Life in Sarcoma Patients

Author

Radboud University Medical Center, Leiden University Medical Center, Centre Leon Berard, University Hospital Carl Gustav Carus, Heidelberg University, Johannes Gutenberg University Mainz, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, National Cancer Institute, Naples, Maria Sklodowska-Curie National Research Institute of Oncology, Hospital San Carlos, Madrid, Royal Marsden NHS Foundation Trust, Beatson West of Scotland Cancer Centre, University Hospital Southampton NHS Foundation Trust, Royal National Orthopaedic Hospital NHS Trust, Bank of Cyprus Oncology Centre, Institut Català d'Oncologia, University of Adelaide, King Hussein Cancer Center, Oslo University Hospital, Erasmus Medical Center, University Medical Center Groningen, Centre Oscar Lambret, Aretaieio Hospital, Hospital Universitario Fundación Jiménez Díaz, The Christie NHS Foundation Trust, Ain Shams University, Prince of Wales Hospital, Shatin, Hong Kong, and Sheba Medical Center

Published
2021

18. Antiseptic Mouth Rinses to Reduce Salivary Viral Load in COVID-19 Patients (BUCOSARS)

Author

Hospital Universitario Fundación Jiménez Díaz, Hospital Universitario General de Villalba, Hospital Universitario Infanta Elena, Hospital Universitario Virgen de la Arrixaca, Hospital Clínico Universitario de Valencia, Dentaid SL, and Alejandro Mira Obrador, BSc in Biological Sciences (Alicante University), MSc PhD (Oxford University), Senior Researcher (FISABIO Foundation)

Published
2021

21. Interval Between Neoadjuvant Therapy and Surgery in the Treatment of Locally Advanced Rectal Cancer (CRONOS) (CRONOS)

Author

Complejo Hospitalario Universitario de Santiago, Hospital Universitario Marqués de Valdecilla, Hospital de Sant Joan Despí Moisès Broggi, Hospital del Mar, Hospital Son Espases, Hospital Universitario La Fe, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, and Fundacion del Hospital Nacional de Paraplejicos para la Investigacion y la Integracion

Published
2021

22. Clinical, Immunological, Genomic, Virological and Bioethical Actors of COVID-19

Author

Hospital Universitario 12 de Octubre, Fundacion Investigacion Biomedica Hospital 12 de Octubre, Hospital Universitario Fundación Jiménez Díaz, Hospital Universitario Infanta Elena, Hospital Universitario Virgen de la Arrixaca, and Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca

Published
2020

23. Effectiveness of the Individualized Metacognitive Training (EMC+) in People With Psychosis of Brief Evolution

Author

Parc Sanitari Sant Joan de Déu, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Servicio Andaluz Jaén y Málaga, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Parc de Salut Mar, Centre d'Higiene Mental Les Corts, Institut Pere Mata, Institut Assistència Sanitària Girona, and Hospital Clínico Universitario de Valencia

Published
2020

24. Sequential Therapy With Tacrolimus and Rituximab in Primary Membranous Nephropathy (STARMEN)

Author

Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Hospital Universitario Fundación Alcorcón, Fundación para la Investigación Biomédica Hospital Universitario 12 de Octubre, Biobanco REDinREN, ERA-EDTA, REDinREN, Spanish Society of Nephrology, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa, University Hospital, Aachen, and Manel Praga, MD, MD, PhD

Published
2020

25. High Blood Pressure in Paediatric Patients With Sleep Disorder Breathing.

Author

Hospital General Universitario de Guadalajara, Instituto de Investigación Hospital Universitario La Paz, Instituto de Investigaciones del Sueño, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Hospital General Universitario Santa Lucía, Hospital Universitario de Burgos, and OlgaMediano, Principal Investigator

Published
2020

26. Proteomic Prediction and Renin Angiotensin Aldosterone System Inhibition Prevention Of Early Diabetic nephRopathy In TYpe 2 Diabetic Patients With Normoalbuminuria (PRIORITY)

Author

Mosaiques Diagnostics GmbH, University Medical Center Groningen, University of Glasgow, Istituto Di Ricerche Farmacologiche Mario Negri, Univerzita Karlova v Praze, Geniko Nosokomeio Athinas Ippokrateio, Institut Klinické a Experimentální Mediciny Praze, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Klinikum St. Georg Leipzig, Cyril and Methodius University in Skopje, Hannover Clinical Trial Center, European Commission, Diabetes Vascular Research Foundation Hoogeveen, Universitair Ziekenhuis Gent, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Stichting VUMC, Diabetologen Hessen, and Peter Rossing, Professor, Chief Physician, MD, DMSc

Published
2018

27. Determinants of Onset and Progression of COPD in Young Adults (EARLY COPD)

Author

Spanish Research Center for Respiratory Diseases, Hospital Son Espases, Hospital Clinic of Barcelona, Hospital del Mar, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Hospital Universitario 12 de Octubre, Parc Taulí Hospital Universitari, Hospitales Universitarios Virgen del Rocío, Hospital Universitari de Bellvitge, Hospital Arnau de Vilanova, Hospital Universitario Central de Asturias, University Hospital of the Nuestra Señora de Candelaria, University Hospital A Coruña, Barcelona Institute for Global Health, Boehringer Ingelheim, and Borja Cosio, Dr Fco. de Borja García-Cosío Piqueras

Published
2018

28. Prediction of Recurrent Pregnancy Loss by a New Thrombophilia Based Genetic Risk Score (TiC-RPL)

Author

Clinica Universidad de Navarra, Universidad de Navarra, Instituto de Salud Carlos III, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Instituto Valenciano de Infertilidad, IVI VALENCIA, IVI-RMA London, Instituto de Investigacion Sanitaria La Fe, Gendiag.exe, S.L., and Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Published
2017

30. Synbiotics in Advanced HIV Infection (PROMALTIA)

Author

Hospital San Carlos, Madrid, Hospital Universitario 12 de Octubre, Hospital Universitario La Paz, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Hospital San Pedro de Logroño, Hospital del Mar, and Sergio Serrano-Villar, MD, PhD

Published
2017

31. Harnessing homeostatically active RhoC at cell junctions preserves human endothelial barrier function during inflammation

Author

Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, European Commission, Consejo Superior de Investigaciones Científicas (España), Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Colás-Algora, Natalia, Muñoz-Pinillos, Pablo, Barroso, Susana, Cacho-Navas, Cristina, Caballero, Álvaro, Cerro-Tello, Gema, Rivas, Gema de, González-Fernández, Martin, Jimenez-Alfaro, Ignacio, Fresno, Manuel, Ribas, Catalina, Paradela, Alberto, López-Collazo, Eduardo, Fernández, José-Jesús, Millán, Jaime, Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, European Commission, Consejo Superior de Investigaciones Científicas (España), Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Colás-Algora, Natalia, Muñoz-Pinillos, Pablo, Barroso, Susana, Cacho-Navas, Cristina, Caballero, Álvaro, Cerro-Tello, Gema, Rivas, Gema de, González-Fernández, Martin, Jimenez-Alfaro, Ignacio, Fresno, Manuel, Ribas, Catalina, Paradela, Alberto, López-Collazo, Eduardo, Fernández, José-Jesús, and Millán, Jaime

Abstract

The GTPase RhoA plays a critical role in generating actomyosin-mediated contractile forces that cause endothelial hyperpermeability during systemic inflammatory diseases. RhoA is almost identical to RhoB and RhoC, all of which are molecular targets of specific bacterial toxins. Searching for new treatments to modulate Rho-dependent endothelial integrity, we demonstrate that the selective and simultaneous activation of these three Rho GTPases with a chimeric recombinant toxin does not induce cell contraction but enhances microvascular endothelial barrier function in response to pathological inflammatory challenges in vitro and in vivo. This pro-barrier effect is specifically mediated by RhoC, whose activity is increased by cell confluence. The uniqueness of RhoC relies on an arginine residue (R188) within its hypervariable region that determines its junctional localization, high homeostatic activity, and barrier-protective function, in contrast to the permeability-inducing, low homeostatic activity of RhoA and RhoB. Quantitative proteomics and high-resolution confocal microscopy revealed that RhoC regulates perijunctional actomyosin and the expression of myosin light chain proteins. Thus, harnessing the activity of RhoC represents a potential therapy for strengthening endothelial barriers during pathological inflammation.

Published
2024

32. SOCS3 deregulation contributes to aberrant activation of the JAK/STAT pathway in precursor T-cell neoplasms

Author

Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Fundación Ramón Areces, Comunidad de Madrid, Asociación Española Contra el Cáncer, Banco Santander, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Lahera, Antonio, López-Nieva, Pilar, Alarcón, Hernán, Marín-Rubio, José L., Cobos-Fernández, M. A., Fernández-Navarro, Pablo, Fernández, Agustín F., Vela-Martín, Laura, Sastre, Isabel, Ruiz-García, Sara, Llamas, Pilar, López-Lorenzo, José L., Cornago, Javier, Santos, Javier, Fernández-Piqueras, José, Villa-Morales, María, Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Fundación Ramón Areces, Comunidad de Madrid, Asociación Española Contra el Cáncer, Banco Santander, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Lahera, Antonio, López-Nieva, Pilar, Alarcón, Hernán, Marín-Rubio, José L., Cobos-Fernández, M. A., Fernández-Navarro, Pablo, Fernández, Agustín F., Vela-Martín, Laura, Sastre, Isabel, Ruiz-García, Sara, Llamas, Pilar, López-Lorenzo, José L., Cornago, Javier, Santos, Javier, Fernández-Piqueras, José, and Villa-Morales, María

Abstract

Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBL.

Published
2023

33. Comprehensive characterization of a novel, oncogenic and targetable SEPTIN6::ABL2 fusion in T-ALL

Author

Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Fundación Ramón Areces, European Commission, Comunidad de Madrid, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Banco Santander, Lahera, Antonio, Vela-Martín, Laura, López-Nieva, P., Salgado, Rocío N., Rodríguez-Perales, Sandra, Torres-Ruiz, Raúl, López-Lorenzo, Jose L, Cornago, Javier, Llamas, Pilar, Fernández-Navarro, Pablo, Sánchez-Domínguez, Rebeca, Segovia, Jose C., Sastre, Isabel, Cobos-Fernández, María, Menéndez, Pablo, Santos, Javier, Fernández-Piqueras, José, Villa-Morales, María, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Fundación Ramón Areces, European Commission, Comunidad de Madrid, Asociación Española Contra el Cáncer, Instituto de Salud Carlos III, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Banco Santander, Lahera, Antonio, Vela-Martín, Laura, López-Nieva, P., Salgado, Rocío N., Rodríguez-Perales, Sandra, Torres-Ruiz, Raúl, López-Lorenzo, Jose L, Cornago, Javier, Llamas, Pilar, Fernández-Navarro, Pablo, Sánchez-Domínguez, Rebeca, Segovia, Jose C., Sastre, Isabel, Cobos-Fernández, María, Menéndez, Pablo, Santos, Javier, Fernández-Piqueras, José, and Villa-Morales, María

Abstract

descripción no proporcionada por scopus

Published
2023

35. Madrid at the center of the Spanish COVID-19 pandemic: the result of ill-advised political decision-making

Author

IIS-Fundación Jiménez Díaz Uam and Alberto Ortiz

Subjects
Politics, Coronavirus disease 2019 (COVID-19), business.industry, Pandemic, Medicine, Center (algebra and category theory), Public administration, business
Abstract

In this issue of the Portuguese Journal of Nephrology and Hypertension, Deira et al report on the epidemiology of coronavirus disease 2019 (COVID-19) in Spanish dialysis units outside the largest cities. This unique viewpoint allows to further trace the spread of the pandemic from Madrid, which became the epicenter of COVID-19 in Spain as a consequence of successive ill-advised political decisions. Deira et al further observed a disconnect between general population infection rates and dialysis unit infection rates in several provinces, pointing to local factors that should be identified and corrected prior to the next pandemic. Although they did not provide specific data on the topic, prior studies from Spain characterized shared healthcare transport to and for dialysis units as a key contributor to infection rates among hemodialysis patients.

Published
2021
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37. Preclinical and clinical characterization of fibroblast-derived neuregulin-1 on trastuzumab and pertuzumab activity in HER2-positive breast cancer

Author

Instituto de Salud Carlos III, Generalitat de Catalunya, European Commission, Hospital Universitario Fundación Jiménez Díaz, Ministerio de Economía y Competitividad (España), Fundación CRIS contra el Cáncer, Breast Cancer Research Foundation, Asociación Española Contra el Cáncer, Guardia, Cristina, Bianchini, Giampaolo, Arpí, Oriol, Menendez, Silvia, Casadevall, David, Galbardi, Barbara, Dugo, Matteo, Servitja, Sonia, Montero, Juan Carlos, Soria-Jiménez, Luis, Sabbaghi, Mohammad A., Peña, Raúl, Madoz-Gúrpide, Juan, Lloveras, Belén, Lluch, Ana, Eroles, Pilar, Arribas, Joaquín, Pandiella, Atanasio, Gianni, Luca, Rojo, Federico, Rovira, Ana, Albanell, Joan, Instituto de Salud Carlos III, Generalitat de Catalunya, European Commission, Hospital Universitario Fundación Jiménez Díaz, Ministerio de Economía y Competitividad (España), Fundación CRIS contra el Cáncer, Breast Cancer Research Foundation, Asociación Española Contra el Cáncer, Guardia, Cristina, Bianchini, Giampaolo, Arpí, Oriol, Menendez, Silvia, Casadevall, David, Galbardi, Barbara, Dugo, Matteo, Servitja, Sonia, Montero, Juan Carlos, Soria-Jiménez, Luis, Sabbaghi, Mohammad A., Peña, Raúl, Madoz-Gúrpide, Juan, Lloveras, Belén, Lluch, Ana, Eroles, Pilar, Arribas, Joaquín, Pandiella, Atanasio, Gianni, Luca, Rojo, Federico, Rovira, Ana, and Albanell, Joan

Abstract

[Purpose]: To characterize expression of neuregulin-1 (NRG1), an HER3 ligand, in HER2-positive breast cancer and its relation with the efficacy of trastuzumab with or without pertuzumab., [Experimental Design]: Characterization of NRG1 expression in tumor cell lines, in tumor specimens, and in cancer-associated fibroblasts (CAFs). Patient-derived CAFs were used to investigate NRG1 impact on the activity of trastuzumab with or without pertuzumab in HER2-positive breast cancer cells. The relationship between NRG1 expression and pathologic response to anti-HER2–based neoadjuvant therapy was assessed in a retrospective patient cohort and in the NeoSphere trial., [Results]: NRG1 was expressed in HER2-positive breast cancer–derived fibroblasts at significantly higher levels than in cancer cells. NRG1 and the conditioned media (CM) from CAFs phosphorylated HER3 and AKT in cancer cells and mediated trastuzumab resistance. Stable genetic depletion of NRG1 from CAFs overcame trastuzumab resistance. Pertuzumab effectively suppressed trastuzumab resistance mediated by either NRG1 or CAF's CM. NRG1 engaged an epithelial-to-mesenchymal transition that was prevented by trastuzumab and pertuzumab. In clinical samples, stromal and/or tumor cell expression of NRG1 determined by immunohistochemistry was uncommon (13.2%) yet significantly linked with residual disease following trastuzumab-based neoadjuvant therapy. In the NeoSphere trial, the magnitude of the difference of pathologic complete response rates favoring the pertuzumab arm was higher in the NRG1-high group., [Conclusions]: CAF-derived NRG1 mediates trastuzumab resistance through HER3/AKT, which might be reverted by pertuzumab. In patients with HER2-positive breast cancer, high expression of NRG1 was associated to poor response to trastuzumab, but not in combination with pertuzumab.

Published
2021

38. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Author

Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Fundación Banco Santander, Agencia Estatal de Investigación (España), Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Cortón, Marta [0000-0003-0087-1626], Martínez-González, Brenda [0000-0002-4482-5181], Lobo-Vega, Rebeca [0000-0002-4882-6763], Vázquez-Sirvent, Lucía [0000-0002-0396-7781], Mínguez, Pablo [0000-0003-4099-9421], Macías-Valcayo, Alicia [0000-0003-3879-0493], Esteban, Jaime [0000-0002-8971-3167], Gadea, Ignacio [0000-0003-4684-7816], Ayuso, Carmen [0000-0002-9242-7065], Perales, Celia [000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, Perales, Celia, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Fundación Banco Santander, Agencia Estatal de Investigación (España), Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Cortón, Marta [0000-0003-0087-1626], Martínez-González, Brenda [0000-0002-4482-5181], Lobo-Vega, Rebeca [0000-0002-4882-6763], Vázquez-Sirvent, Lucía [0000-0002-0396-7781], Mínguez, Pablo [0000-0003-4099-9421], Macías-Valcayo, Alicia [0000-0003-3879-0493], Esteban, Jaime [0000-0002-8971-3167], Gadea, Ignacio [0000-0003-4684-7816], Ayuso, Carmen [0000-0002-9242-7065], Perales, Celia [000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, and Perales, Celia

Abstract

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work was to determine a possible association between viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or death. Also, Ct values were determined using SARS-CoV-2-specific oligonucleotides directed to ORF1ab. Here we report a statistically significant association between viral load and disease severity, a high viral load being associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

Published
2021

39. Presence of rare potential pathogenic variants in subjects under 65 years old with very severe or fatal COVID-19.

Author

López-Rodríguez, Rosario, Del Pozo-Valero, Marta, Corton, Marta, Minguez, Pablo, Ruiz-Hornillos, Javier, Pérez-Tomás, María Elena, Barreda-Sánchez, María, Mancebo, Esther, Villaverde, Cristina, Núñez-Moreno, Gonzalo, Romero, Raquel, The STOP_Coronavirus Study Group, Associated Clinical and Researchgroup of Fundación Jiménez Díaz University Hospital, Fernández-Caballero, Lidia, Fernández Sanchez, Ruth, García Vara, Inés, Marzal Gordo, Laura, Martinez-Ramas, Andrea, Ondo, Lorena, and Górgolas, Miguel

Subjects
COVID-19, GENETIC variation, BLOOD coagulation, CARBOHYDRATE metabolism, DNA repair
Abstract

Rare variants affecting host defense against pathogens could be involved in COVID-19 severity and may help explain fatal outcomes in young and middle-aged patients. Our aim was to report the presence of rare genetic variants in certain genes, by using whole exome sequencing, in a selected group of COVID-19 patients under 65 years who required intubation or resulting in death (n = 44). To this end, different etiopathogenic mechanisms were explored using gene prioritization-based analysis in which genes involved in immune response, immunodeficiencies or blood coagulation were studied. We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic and were located in genes mainly involved in immune response. A network analysis, including the 42 genes with candidate variants, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks composed by genes enriched in carbohydrate metabolism and in DNA metabolism and repair processes. In conclusion, we have detected candidate variants that may potentially influence COVID-19 outcome in our cohort of patients. Further studies are needed to confirm the ultimate role of the genetic variants described in the present study on COVID-19 severity. [ABSTRACT FROM AUTHOR]

Published
2022
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40. Author Correction: Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer (Scientific Reports, (2019), 9, 1, (2589), 10.1038/s41598-019-39291-2)

Author

Borrero-Palacios, A., Cebrián, A., Gómez del Pulgar, M. T., García-Carbonero, R., Garcia-Alfonso, P., Aranda, E., Elez, E., López-López, R., Cervantes, A., Valladares, M., Nadal, C., Viéitez, J. M., Guillén-Ponce, C., Rodríguez, J., Hernández, I., García, J. L., Vega-Bravo, R., Puime-Otin, A., Martínez-Useros, J., Del Puerto-Nevado, L., Rincón, R., Rodríguez-Remírez, M., Rojo, F., García-Foncillas, J., Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD), and UAM. Departamento de Medicina

Subjects
Metastatic colorectal cancer, Medicina, Combination, Cetuximab, Polymorphism FcγRIIIa V158F, KIR2DS4
Abstract

The original version of this Article contained an error in the spelling of the author P. Garcia-Alfonso, which was incorrectly given as P. Garcia. This error has now been corrected in the PDF and HTML versions of this Article.

Published
2019

41. Interleukin-17A blockade reduces albuminuria and kidney injury in an accelerated model of diabetic nephropathy

Author

Lavoz, Carolina, Sánchez Matus, Yenniffer, Orejudo, Macarena, Carpio, J. Daniel, Droguett, Alejandra, Egido, Jesús, Mezzano, Sergio, Ruiz-Ortega, Marta, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD), and UAM. Departamento de Medicina

Subjects
Inflammation, Medicina, IL-17A, BTBR ob/ob, Diabetic nephropathy
Abstract

Diabetic nephropathy (DN) is one of the most common complications of diabetes, and currently the first end-stage renal disease worldwide. New strategies to treat DN using agents that target inflammatory pathways have attracted special interest. Recent pieces of evidences suggest a promising effect of IL-17A, the Th17 effector cytokine. Among experimental DN models, mouse strain BTBR ob/ob (leptin deficiency mutation) develops histological features similar to human DN, which means an opportunity to study mechanisms and novel therapies aimed at DN regression. We found that BTBR ob/ob mice presented renal activation of the factors controlling Th17 differentiation. The presence of IL-17A-expressing cells, mainly CD4D and gd lymphocytes, was associated with upregulation of proinflammatory factors, macrophage infiltration and the beginning of renal damage. To study IL-17A involvement in experimental DN pathogenesis, treatment with an IL-17A neutralizing antibody was carried out starting when the renal damage had already appeared. IL-17A blockade ameliorated renal dysfunction and disease progression in BTBR ob/ob mice. These beneficial effects correlated to podocyte number restoration and inhibition of NF-kB/ proinflammatory factors linked to a decrease in renal inflammatory-cell infiltration. These data demonstrate that IL-17A takes part in diabetes-mediated renal damage and could be a promising therapeutic target to improve DN., This work was supported by grants PAI 82140017 to CL; Fondecyt 1160465 to SM; Division of Nephrology, Universidad Austral de Chile, the Instituto de Salud Carlos III and FEDER European Union funds (PI14/00041, PI17/00119 to MR-O, and PI14/00386 and PI17/01495 to JE); Red de Investigación Renal (REDinREN; RD16/009) and Comunidad de Madrid (B2017/BMD-3751 NOVELREN-CM) to MR-O, and Sociedad Española de Nefrología

Published
2019

42. High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease

Author

Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Lobo-Vega, Rebeca [0000-0002-4882-6763], Perales, Celia [0000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, Perales, Celia, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), European Commission, Consejo Superior de Investigaciones Científicas (España), Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), Fundación Ramón Areces, Banco Santander, Comunidad de Madrid, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Soria, María Eugenia [0000-0002-4719-3351], Lobo-Vega, Rebeca [0000-0002-4882-6763], Perales, Celia [0000-0003-1618-1937], Soria, María Eugenia, Cortón, Marta, Martínez-González, Brenda, Lobo-Vega, Rebeca, Vázquez-Sirvent, Lucía, López-Rodríguez, Rosario, Almoguera, Berta, Mahillo-Fernández, Ignacio, Mínguez, Pablo, Herrero, Antonio, Taracido, Juan Carlos, Macías-Valcayo, Alicia, Esteban, Jaime, Fernández-Roblas, Ricardo, Gadea, Ignacio, Ruíz-Hornillos, Javier, Ayuso, Carmen, and Perales, Celia

Abstract

COVID-19 severity and progression are determined by several host and virological factors that may influence the final outcome of SARS-CoV-2-infected patients. The objective of this work is to determine a possible association between the viral load, obtained from nasopharyngeal swabs, and the severity of the infection in a cohort of 448 SARS-CoV-2-infected patients from a hospital in Madrid during the first outbreak of the pandemic in Spain. To perform this, we have clinically classified patients as mild, moderate and severe COVID-19 according to a number of clinical parameters such as hospitalization requirement, need of oxygen therapy, admission to intensive care units and/or exitus. Here we report a statistically significant correlation between viral load and disease severity, being high viral load associated with worse clinical prognosis, independently of several previously identified risk factors such as age, sex, hypertension, cardiovascular disease, diabetes, obesity, and lung disease (asthma and chronic obstructive pulmonary disease). The data presented here reinforce the viral load as a potential biomarker for predicting disease severity in SARS-CoV-2-infected patients. It is also an important parameter in viral evolution since it relates to the numbers and types of variant genomes present in a viral population, a potential determinant of disease progression.

Published
2020

43. FADD phosphorylation is altered in human T-cell lymphoblastic lymphoma

Author

J. Fernández Piqueras, Centro de Biología Molecular Severo Ochoa , Madrid, Spain., Isabel Sastre, M. Villa Morales, IIS-Fundación Jiménez Díaz, Madrid, Spain., C. Barrios Donoso, J. L. Marín Rubio, and M. A. Cobos Fernández

Subjects
medicine.anatomical_structure, biology, Chemistry, T cell, Lymphoblastic lymphoma, biology.protein, Cancer research, medicine, Phosphorylation, FADD, medicine.disease
Published
2018
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44. Study of the role of microRNAs in T-cell lymphoblastic lymphoma development through the regulation of expression of FBXW7 gene

Author

Marcos Malumbres, Isabel Sastre, Iis Puerta de Hierro, Majadahonda, Spain., María Ángeles Cobos Fernández, Iis Fundación Jiménez Díaz, Madrid, Spain., Pilar López Nieva, José Fernández Piqueras, María Villa Morales, Irene Vázquez Domínguez, Agustín F. Fernández, Centro de Biología Molecular Severo Ochoa , Madrid, Spain., Laura González Sánchez, Pablo Fernández Navarro, and Javier Santos

Subjects
medicine.anatomical_structure, FBXW7 Gene, T cell, microRNA, Lymphoblastic lymphoma, Cancer research, medicine, Biology, medicine.disease
Published
2018
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45. Postoperative analgesia requirements after propofol anaesthesia with intercostal nerve block versus sevofluorane and opioids for breast cancer surgery

Author

López, V., Cassinello, F., Fundación Jiménez Díaz, Madrid, and Ntra Sra de la Candelaria, Tenerife

Abstract

Comparation of pectoral block/propofol anaesthesia versus sevofluorane/fentanyl anaesthesia for breast cancer surgeryBackground: Breast cancer surgery is one of the most frequently performed surgeries. This include tumorectomies and mastectomies with axillary clearance when needed. Even relatively minor breast surgery can be associated with significant postoperative pain. Thoracic epidural analgesia, paravertebral blocks and other regional techniques are commonly associated to general anaesthesia.Intercostal nerve block (PIB) is another alternative described as particularly useful for ambulatory patients Goal of study: We aim to demostrate that PIB provides better postoperative analgesia than general anaesthesia with sevofluorane and opioids (SAO) with less nausea and vomiting (PONV) and better patient comfort.Material & Methods: 20 women with diagnosis of breast cancer were randomized to recieve either PIB, with 20 ml chirocane 0.25% , performed under ultrasound guidance , or SAO anesthesia. Intraoperative fentanyl consumption, postoperative Visual analogic scale (VAS) pain scores at 1 and 24 h postoperative, postoperative fentanyle consumption, PONV scores and postsurgical hospital stay were recorded.Resultados: Patient demographics and duration of surgery were comparable for both groups(Fig I). PIB group had no need of opioids in the recovery room and presented significantly lower VAS pain scores and less PONV scores.There was no difference in hospital stay or intraoperative fentanyl(Fig 2).Discursion:Intercostal nerve block is easy to perform and is associated to less adverse events then epidural o paravertebral block

Published
2017

46. Calcineurin inhibitors cyclosporine A and tacrolimus induce vascular inflammation and endothelial activation through TLR4 signaling

Author

Rodrigues Díez, Raquel, González-Guerrero, Cristian, Ocaña-Salceda, Carlos, Rodrigues Díez, Raúl, Egido, Jesús, Ortiz, Alberto, Ruiz-Ortega, Marta, Ramos, Adrián M., Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD), and UAM. Departamento de Medicina

Subjects
0301 basic medicine, Vascular smooth muscle, Medicina, medicine.medical_treatment, Calcineurin Inhibitors, Vascular Cell Adhesion Molecule-1, Inflammation, 030204 cardiovascular system & hematology, Biology, Pharmacology, Muscle, Smooth, Vascular, Tacrolimus, Article, Cell Line, Proinflammatory cytokine, Endothelial activation, Mice, 03 medical and health sciences, 0302 clinical medicine, Calcineurin inhibitors, medicine, Animals, Aorta, Mice, Knockout, Multidisciplinary, Calcineurin, Endothelial Cells, Intercellular Adhesion Molecule-1, Mice, Inbred C57BL, Toll-Like Receptor 4, Vascular endothelial growth factor B, 030104 developmental biology, Cytokine, Myeloid Differentiation Factor 88, Immunology, Cyclosporine, Vascular toxicity, medicine.symptom, Reactive Oxygen Species, Signal Transduction
Abstract

The introduction of the calcineurin inhibitors (CNIs) cyclosporine and tacrolimus greatly reduced the rate of allograft rejection, although their chronic use is marred by a range of side effects, among them vascular toxicity. In transplant patients, it is proved that innate immunity promotes vascular injury triggered by ischemia-reperfusion damage, atherosclerosis and hypertension. We hypothesized that activation of the innate immunity and inflammation may contribute to CNI toxicity, therefore we investigated whether TLR4 mediates toxic responses of CNIs in the vasculature. Cyclosporine and tacrolimus increased the production of proinflammatory cytokines and endothelial activation markers in cultured murine endothelial and vascular smooth muscle cells as well as in ex vivo cultures of murine aortas. CNI-induced proinflammatory events were prevented by pharmacological inhibition of TLR4. Moreover, CNIs were unable to induce inflammation and endothelial activation in aortas from TLR4−/− mice. CNI-induced cytokine and adhesion molecules synthesis in endothelial cells occurred even in the absence of calcineurin, although its expression was required for maximal effect through upregulation of TLR4 signaling. CNI-induced TLR4 activity increased O2 −/ROS production and NF-κB-regulated synthesis of proinflammatory factors in cultured as well as aortic endothelial and VSMCs. These data provide new insight into the mechanisms associated with CNI vascular inflammation, This work was supported by grants from the Instituto de Salud Carlos III (Ministerio de Economía Competitividad, Gobierno de España): FEDER funds ISCIII RETIC REDINREN RD12/0021, PI11/02242, PI13/00047, PI14/0041, PI14/00386, PI15/01460; Comunidad de Madrid (CIFRA S2010/BMD-2378); Sociedad Española de Nefrología. Salary support: RR-D: CIFRA; CO-S: Fundación Conchita Rábago de Jiménez Díaz; CG-G and RRR-D: REDINREN; AO: Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM); JE and MRO: Universidad Autónoma de Madrid; AMR: Contrato Miguel Serve (ISCIII)

Published
2016
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47. C-Jun N-terminal kinase inactivation by mitogen-activated protein kinase phosphatase 1 determines resistance to taxanes and anthracyclines in breast cancer

Author

Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Generalitat de Catalunya, Instituto de Salud Carlos III, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, European Commission, Fundación Conchita Rábago de Jiménez Díaz, Red Temática de Investigación Cooperativa en Cáncer (España), Rincón, Raúl, Zazo, Sandra, Manso, Rebeca, Perona Abellón, Rosario, Albanell, Joan, Madoz-Gúrpide, Juan, Rojo, Federico, Ministerio de Economía y Competitividad (España), Comunidad de Madrid, Generalitat de Catalunya, Instituto de Salud Carlos III, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, European Commission, Fundación Conchita Rábago de Jiménez Díaz, Red Temática de Investigación Cooperativa en Cáncer (España), Rincón, Raúl, Zazo, Sandra, Manso, Rebeca, Perona Abellón, Rosario, Albanell, Joan, Madoz-Gúrpide, Juan, and Rojo, Federico

Abstract

MAPK phosphatase-1 (MKP-1) is overexpressed during malignant transformation of the breast in many patients, and it is usually associated with chemoresistance through interference with JNK-driven apoptotic pathways. Although the molecular settings of the mechanism have been documented, details about the contribution of MKP-1 to the failure of chemotherapeutic interventions are unclear. Transient overexpression of MKP-1 and treatment with JNK-modulating agents in breast carcinoma cells confirmed the mediation of MKP-1 in the resistance to taxanes and anthracyclines in breast cancer, through the inactivation of JNK1/2. We next assessed MKP-1 expression and JNK1/2 phosphorylation status in a large cohort of samples from 350 early breast cancer patients treated with adjuvant anthracycline-based chemotherapy. We detected that MKP-1 overexpression is a recurrent event predominantly linked to dephosphorylation of JNK1/2 with an adverse impact on relapse of the tumor and overall and disease-free survival. Moreover, MKP-1 and p-JNK1/2 determinations in 64 locally advanced breast cancer patients treated with neoadjuvant taxane-based chemotherapy showed an inverse correlation between MKP-1 overexpression (together with JNK1/2 inhibition) and the pathologic response of the tumors. Our results emphasize the importance of MKP-1 as a potential predictive biomarker for a subset of breast cancer patients with worse outcome and less susceptibility to treatment.

Published
2016

48. Cellular Barriers after Extravasation: Leukocyte Interactions with Polarized Epithelia in the Inflamed Tissue

Author

Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Ministerio de Economía y Competitividad (España), Reglero-Real, Natalia, García-Weber, Diego, Millán, Jaime, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Ministerio de Economía y Competitividad (España), Reglero-Real, Natalia, García-Weber, Diego, and Millán, Jaime

Abstract

During the inflammatory response, immune cells egress from the circulation and follow a chemotactic and haptotactic gradient within the tissue, interacting with matrix components in the stroma and with parenchymal cells, which guide them towards the sites of inflammation. Polarized epithelial cells compartmentalize tissue cavities and are often exposed to inflammatory challenges such as toxics or infections in non-lymphoid tissues. Apicobasal polarity is critical to the specialized functions of these epithelia. Indeed, a common feature of epithelial dysfunction is the loss of polarity. Here we review evidence showing that apicobasal polarity regulates the inflammatory response: various polarized epithelia asymmetrically secrete chemotactic mediators and polarize adhesion receptors that dictate the route of leukocyte migration within the parenchyma. We also discuss recent findings showing that the loss of apicobasal polarity increases leukocyte adhesion to epithelial cells and the consequences that this could have for the inflammatory response towards damaged, infected or transformed epithelial cells.

Published
2016

49. Activation of Rac1 and Rhoa preserve corneal endothelial barrier function

Author

Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Ministerio de Economía y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), Ortega, María C., Santander-García, Diana, Marcos Ramiro, Beatriz, Barroso, Susana, Cox, Susan, Jiménez-Alfaro, Ignacio, Millán, Jaime, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Ministerio de Economía y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), Ortega, María C., Santander-García, Diana, Marcos Ramiro, Beatriz, Barroso, Susana, Cox, Susan, Jiménez-Alfaro, Ignacio, and Millán, Jaime

Abstract

PURPOSE. The corneal endothelium is responsible for the correct hydration of the corneal stroma. Corneal endothelial cells have a low proliferative capacity, so preserving their barrier function under suboptimal conditions that cause osmotic imbalance, such as those arising from corneal pathologies, age, cryopreservation, and transplantation, is essential for maintaining corneal transparency. We have investigated the signaling induced by hyperosmotic shock that reversibly disrupts corneal endothelial barriers in human endothelial cells and in murine corneas. METHODS. Endothelial barrier properties were analyzed in vitro by electric cell substrate impedance sensing (ECIS) and confocal microscopy of the human endothelial cell line B4G12-HCEC, and, ex vivo, by confocal microscopy and stimulated emission-depletion (STED) superresolution microscopy of murine corneas. Cell signaling in response to hyperosmotic stress, induced with an excess of sodium chloride, was investigated in B4G12-HCECs. Rho GTPase activity was detected by pulldown assays with recombinant GST proteins fused to the Rho binding domains of Rho effectors. RESULTS. Hyperosmotic stress increased actin polymerization and activated the Rho GTPases Rac1 and RhoA, but not Cdc42. Rac1-and RhoA-mediated pathway inhibition had a minor effect on barrier disruption but partially delayed barrier reformation after stress withdrawal. In contrast, Rac1 and RhoA activation enhanced constitutive endothelial barrier function and accelerated barrier repair. CONCLUSIONS. Our results indicate that Rac1 and RhoA activation do not mediate stress-induced cell contraction but are endothelial responses that act to restore and maintain barrier homeostasis. Therefore, pharmacological activation of these two GTPases could be a therapeutic strategy for preserving corneal endothelial barrier function.

Published
2016

50. Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids

Author

Gil-Martínez, Marta, Lorente-Sorolla, Clara, Rodrigo-Muñoz, José M., Lendínez, Miguel Ángel, Núñez-Moreno, Gonzalo, de la Fuente, Lorena, Mínguez, Pablo, Mahíllo-Fernández, Ignacio, Sastre, Joaquin, Valverde-Monge, Marcela, Quirce, Santiago, Caballero, María L., González-Barcala, Francisco J., Arismendi, Ebymar, Bobolea, Irina, Valero, Antonio, Muñoz Gall, Xavier, Cruz, María Jesús, Martínez Rivera, Carlos, Plaza, Vicente, Olaguibel, José M., del Pozo, Victoria, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Gil-Martínez M, Rodrigo-Muñoz JM] Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Lorente-Sorolla C, Lendínez MÁ] Immunoallergy Laboratory, Immunology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. [Núñez-Moreno G] Department of Genetics, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. Center for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Bioinformatics Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. [de la Fuente L] Department of Genetics, Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD, UAM), Madrid, Spain. [Muñoz X, Cruz MJ] CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [CHEMICALS AND DRUGS], Asma - Tractament, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Mirnas, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Catalysis, acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::hormonas, sustitutos de hormonas y antagonistas de hormonas::hormonas::glucocorticoides [COMPUESTOS QUÍMICOS Y DROGAS], Inorganic Chemistry, biomarker, oral corticosteroids, miRNAs, individuals with severe asthma, Oral corticosteroids, Other subheadings::/therapeutic use [Other subheadings], Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, MicroARN, Individuals with severe asthma, Otros calificadores::/uso terapéutico [Otros calificadores], Organic Chemistry, General Medicine, Biomarker, Respiratory Tract Diseases::Bronchial Diseases::Asthma [DISEASES], Computer Science Applications, enfermedades respiratorias::enfermedades bronquiales::asma [ENFERMEDADES], Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Glucocorticoids [CHEMICALS AND DRUGS], nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN [COMPUESTOS QUÍMICOS Y DROGAS], Glucocorticoides - Ús terapèutic
Abstract

Biomarker; Individuals with severe asthma; Oral corticosteroids Biomarcador; Persones amb asma greu; Corticosteroides orals Biomarcador; Personas con asma grave; Corticosteroides orales Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV1/FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes (FOXO3, PTEN, and MAPK3) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment. This work was supported by ISCIII—Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria—Spanish Health Research Fund) grants PI18/00167, PI21/00896, and FI19/00067; Ciber de Enfermedades Respiratorias (CIBERES); RTC-2017-6501-1 (Ministerio de Ciencia, Innovación y Universidades), a Carlos III Institute of Health Initiative; and FEDER funds (Fondo Europeo de Desarrollo Regional).

Published
2023

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