66 results on '"Ana Ortega"'
Search Results
2. Pembrolizumab plus platinum-based chemotherapy for squamous non-small cell lung cancer: the new kid on the block
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Raffaele Califano, Kimberley Hockenhull, and Ana Ortega-Franco
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Oncology ,medicine.medical_specialty ,education.field_of_study ,Chemotherapy ,Taxane ,Performance status ,business.industry ,medicine.medical_treatment ,Population ,Pembrolizumab ,medicine.disease ,Carboplatin ,chemistry.chemical_compound ,Docetaxel ,chemistry ,Internal medicine ,medicine ,Lung cancer ,education ,business ,medicine.drug - Abstract
Immune checkpoint inhibitors (ICIs) and targeted therapies have revolutionised the diagnostic and treatment paradigm of advanced non-small cell lung cancer (NSCLC). However, treatment advances in squamous cell subtype have been much slower than those occurring in adenocarcinoma, mainly due to the lack of targetable oncogenic aberrations in squamous tumours. The unprecedented durable response and favourable toxicity profile observed with ICIs in advanced squamous NSCLC, represents a true therapeutic milestone in a population previously limited to cytotoxic chemotherapy (Cht). The inhibition of programmed cell death ligand 1 (PD-1/PD-L1) pathway has been extensively investigated in NSCLC and currently dominates the treatment landscape of advanced NSCLC. The first approval of ICIs came from several randomized trials conducted in platinum-treated advanced NSCLC patients (any histology) (1-4) where overall survival (OS) and toxicity profile favoured PD-1/PD-L1 inhibitors over docetaxel. Subsequently, KEYNOTE-024 (5) showed that, in advanced NSCLC patients (all histologies) with a PD-L1 tumour proportion score (TPS) ≥50%, first-line pembrolizumab achieved higher objective response rates (ORR) and longer progression-free survival (PFS) and OS when compared to standard platinum-based Cht. However, high PD-L1 expression only occurs in a third of NSCLC patients and, until recently, platinum-based Cht remained the only approved option for fit patients with a PD-L1 TPS more...
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- 2021
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Catalog
3. Therapeutic Potential of Extracellular Vesicles in Hypertension-Associated Kidney Disease
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Olga Martinez-Arroyo, Raquel Cortés, Josep Redon, and Ana Ortega
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0301 basic medicine ,Cell type ,Hypertension, Renal ,Cell ,Inflammation ,030204 cardiovascular system & hematology ,Exosomes ,Extracellular Vesicles ,03 medical and health sciences ,Drug Delivery Systems ,0302 clinical medicine ,Fibrosis ,Internal Medicine ,medicine ,Humans ,Endothelial dysfunction ,Kidney ,Nephritis ,business.industry ,Mesenchymal Stem Cells ,medicine.disease ,Microvesicles ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Cancer research ,medicine.symptom ,business ,Biomarkers ,Kidney disease - Abstract
Hypertension-mediated organ damage frequently includes renal function decline in which several mechanisms are involved. The present review outlines the state of the art on extracellular vesicles in hypertension and hypertension-related renal damage. Emerging evidence indicates that extracellular vesicles, small vesicles secreted by most cell types and body fluids, are involved in cell-to-cell communication and are key players mediating biological processes such as inflammation, endothelial dysfunction or fibrosis, mechanisms present the onset and progression of hypertension-associated kidney disease. We address the potential use of extracellular vesicles as markers of hypertension-mediated kidney damage severity and their application as therapeutic agents in hypertension-associated renal damage. The capacity of exosomes to deliver a wide variety of cargos to the target cell efficiently makes them a potential drug delivery system for treatment of renal diseases. more...
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- 2021
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4. First-Line Immune Checkpoint Inhibition for Advanced Non-Small-Cell Lung Cancer: State of the Art and Future Directions
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Martin Reck, Christoph Jakob Ackermann, Adeel Khan, Raffaele Califano, Ana Ortega-Franco, and Helen Adderley
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Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Paclitaxel ,medicine.medical_treatment ,First line ,Programmed Cell Death 1 Receptor ,Pemetrexed ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,B7-H1 Antigen ,Carboplatin ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Quality of life ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,CTLA-4 Antigen ,Pharmacology (medical) ,Lung cancer ,Immune Checkpoint Inhibitors ,Lung ,Chemotherapy ,business.industry ,medicine.disease ,Ipilimumab ,Progression-Free Survival ,Immune checkpoint ,Review Literature as Topic ,Nivolumab ,Clinical Trials, Phase III as Topic ,030220 oncology & carcinogenesis ,Quality of Life ,Non small cell ,Neoplasm Recurrence, Local ,business ,030217 neurology & neurosurgery - Abstract
The advent of PD-(L)1 and CTLA-4 immune check point inhibitors (CPIs) has dramatically changed the treatment landscape of advanced non-small-cell lung cancer (NSCLC). For up to a quarter of patients with advanced NSCLC, CPIs have the potential to induce durable responses with long-term survival outcomes. Since the approval of first-line pembrolizumab for patients whose tumors express a PD-L1 ≥ 50%, several pivotal first-line CPI-based phase 3 studies have been conducted investigating combination treatments combining CPIs with chemotherapy (ChT) or combining different CPIs with or without ChT. As a result, there has been an increase in front-line treatment options for advanced NSCLC, and treatment algorithms are changing very quickly. In fit patients with advanced NSCLC, combination treatments including CPI and ChT are considered the new standard of care with improved clinical outcomes. CPI combination treatments are well tolerated and quality of life also seems to be better when CPIs are implemented in the first-line setting. The aim of this review is to provide a summary of the recently published first-line phase 3 studies investigating CPIs as monotherapy or in combination with other CPIs or ChT in advanced NSCLC, and to suggest possible treatment algorithms. more...
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- 2020
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5. XPO1 Gene Therapy Attenuates Cardiac Dysfunction in Rats with Chronic Induced Myocardial Infarction
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José Ramón González-Juanatey, María García-Manzanares, Miguel Rivera, Ana Ortega, Esther Roselló-Lletí, Luis Martínez-Dolz, Manuel Portolés, Estefanía Tarazón, Francisca Lago, Carolina Gil-Cayuela, Producción Científica UCH 2020, UCH. Departamento de Medicina y Cirugía Animal, and UCH. Departamento de Producción y Sanidad Animal, Salud Pública Veterinaria y Ciencia y Tecnología de los Alimentos more...
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Myocardial infarction - Treatment ,Male ,medicine.medical_specialty ,Genetic enhancement ,Fibrillar Collagens ,Corazón - Ventrículos - Enfermedades - Tratamiento ,Myocardial Infarction ,Pharmaceutical Science ,Receptors, Cytoplasmic and Nuclear ,Eukaryotic cells ,Karyopherins ,Placebo ,Ventricular Function, Left ,Cardiac dysfunction ,Rats, Sprague-Dawley ,Fibrosis ,Internal medicine ,Genetics ,Medicine ,Animals ,Myocardial infarction ,Left Ventricular Fractional Shortening ,RNA, Small Interfering ,Ventricular function ,Genetics (clinical) ,Heart - Ventricles - Diseases - Treatment ,Ischemic cardiomyopathy ,Ventricular Remodeling ,business.industry ,Myocardium ,Gene silencing ,medicine.disease ,Myocardial Contraction ,Células eucariotas ,Disease Models, Animal ,RNAi Therapeutics ,Cardiology ,cardiovascular system ,Molecular Medicine ,XPO1 ,Original Article ,RNA Interference ,Infarto de miocardio - Tratamiento ,Cardiology and Cardiovascular Medicine ,business - Abstract
Transcriptomic signature of XPO1 was highly expressed and inversely related to left ventricular function in ischemic cardiomyopathy patients. We hypothesized that treatment with AAV9-shXPO1 attenuates left ventricular dysfunction and remodeling in a myocardial infarction rat model. We induced myocardial infarction by coronary ligation in Sprague-Dawley rats (n = 10), which received AAV9-shXPO1 (n = 5) or placebo AAV9-scramble (n = 5) treatment. Serial echocardiographic assessment was performed throughout the study. After myocardial infarction, AAV9-shXPO1-treated rats showed partial recovery of left ventricular fractional shortening (16.8 ± 2.8 vs 24.6 ± 4.1%, P P P XPO1. more...
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- 2019
6. OA14.01 Family History of Cancer and Lung Cancer: Information from the Thoracic Tumors Registry (TTR Study)
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J.L. González Larriba, R. Bernabé, B. Massuti, D. Rodriguez Abreu, R. López-Castro, J. Mosquera, M. Cucurull, Manuel Domine, Ana Ortega, Oscar Juan, M. Provencio, M. Cobo, A. Collazo-Lorduy, V. Calvo, M. Guirado, Enric Carcereny, M. Martínez-Cutillas, E. Del Barco, Carlos Camps, J. Bosch Barrera, Gustavo Benítez, and C. Gonzalez Ojeda more...
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,biology ,business.industry ,Cancer ,medicine.disease ,Transthyretin ,Internal medicine ,biology.protein ,Medicine ,Family history ,business ,Lung cancer - Published
- 2021
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7. Urinary- and Plasma-Derived Exosomes Reveal a Distinct MicroRNA Signature Associated With Albuminuria in Hypertension
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Josep Redon, Angela L. Riffo-Campos, Ana Ortega, Fernando Martinez, Olga Martinez-Arroyo, Dolores Olivares, Sergio Martínez-Hervás, Raquel Cortés, Javier Perez-Hernandez, E. Solaz, Felipe J. Chaves, and Daniel Perez-Gil more...
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0301 basic medicine ,Male ,Down-Regulation ,030204 cardiovascular system & hematology ,Exosomes ,Transforming Growth Factor beta1 ,03 medical and health sciences ,Paracrine signalling ,0302 clinical medicine ,microRNA ,Internal Medicine ,medicine ,Albuminuria ,Humans ,Gene Regulatory Networks ,KEGG ,Cells, Cultured ,Aged ,Kidney ,business.industry ,Podocytes ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Middle Aged ,Microvesicles ,MicroRNAs ,030104 developmental biology ,Real-time polymerase chain reaction ,medicine.anatomical_structure ,Hypertension ,Cancer research ,Female ,medicine.symptom ,business ,Transforming growth factor - Abstract
Urinary albumin excretion (UAE) is a marker of cardiovascular risk and renal damage in hypertension. MicroRNAs (miRNAs) packaged into exosomes function as paracrine effectors in cell communication and the kidney is not exempt. This study aimed to state an exosomal miRNA profile/signature associated to hypertension with increased UAE and the impact of profibrotic TGF-β1 (transforming growth factor β1) on exosomes miRNA release. Therefore, exosomes samples from patients with hypertension with/without UAE were isolated and characterized. Three individual and unique small RNA libraries from each subject were prepared (total plasma, urinary, and plasma-derived exosomes) for next-generation sequencing profiling. Differentially expressed miRNAs were over-represented in Kyoto Encyclopedia of Genes and Genomes pathways, and selected miRNAs were validated by real-time quantitative polymerase chain reaction in a confirmation cohort. Thus, a signature of 29 dysregulated circulating miRNAs was identified in UAE hypertensive subjects, regulating 21 pathways. Moreover, changes in the levels of 4 exosomes-miRNAs were validated in a confirmation cohort and found associated with albuminuria. In particular miR-26a, major regulator of TGF-β signaling, was found downregulated in both type of exosomes when compared with healthy controls and to hypertension normoalbuminurics ( P more...
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- 2021
8. Integrating immune checkpoint inhibitors and targeted therapies in the treatment of early stage non-small cell lung cancer: a narrative review
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Raffaele Califano, Virginia Calvo, F. Franco, Mariano Provencio, and Ana Ortega-Franco
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Oncology ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Review Article on Looking for Chimeras in NSCLC: Widen Therapeutic Options Targeting Oncogenic Fusions ,non-small cell lung cancer (NSCLC) ,Context (language use) ,Immunotherapy ,medicine.disease ,respiratory tract diseases ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Targeted Molecular Therapy ,medicine ,Osimertinib ,030212 general & internal medicine ,Lung cancer ,business ,Adjuvant ,Neoadjuvant therapy - Abstract
Prognosis of early stage non-small cell lung cancer (eNSCLC) is poor even when treated radically with surgery and (neo)adjuvant chemotherapy (Cht). The discovery of tyrosine kinase inhibitors (TKIs) for oncogene addicted NSCLC and immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic paradigm and improved survival of advanced NSCLC. The unprecedented impact of these drugs has shifted the focus of investigation to early stage disease aiming at improving cure. In this context, several single arm phase II studies evaluating neoadjuvant ICI alone or in combination with platinum-based Cht have shown encouraging rates of pathological response which have spurred several ongoing randomized trials with (neo)adjuvant ICI. More recently, ADAURA study evaluating adjuvant osimertinib demonstrated a profound reduction of the risk of recurrence in patients with stage I (>4 cm)-IIIA eNSCLC harbouring EGFR sensitizing mutations. ICIs and TKIs represent a true revolution in the treatment of eNSCLC call to challenge the current standard of care. However, questions regarding drug resistance, recurrence patterns, biomarker identification, optimal treatment duration and sequencing need be answered to effectively integrate new drugs in the rapidly evolving therapeutic landscape of NSCLC. In this review we critically review new developments and future perspectives of TKIs and ICI as (neo)adjuvant strategies for eNSCLC. more...
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- 2021
9. Epidemiology, treatment, and survival in small cell lung cancer in Spain: Data from the Thoracic Tumor Registry
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Bartomeu Massuti, Paola García Coves, M. Guirado, Julia Calzas, Ana Ortega, R. López-Castro, Edel del Barco, Oscar Juan, Delvys Rodriguez-Abreu, Rosario García-Campelo, Jose Manuel Trigo, Francisco Aparisi, Enric Carcereny, Joaquim Bosch-Barrera, Mariano Provencio, Manuel Cobo, Fernando Faria Franco, José Luis González-Larriba, Manuel Domine, S. Cerezo, Marta Domenech, [Franco,F, Provencio,M] Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain. [Carcereny,E, Domènech,M] Catalan Institute of Oncology, Hospital Universitari Germans Trias i Pujol, B-ARGO, IGTP, Badalona, Spain. [Guirado,M, García Coves,P] Hospital General Universitario de Elche, Elche, Spain. [Ortega,AL] Hospital Universitario de Jaén, Jaén, Spain. [López-Castro,R] Hospital Clínico Universitario de Valladolid, Valladolid, Spain. [Rodríguez-Abreu,D] Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain. [García-Campelo,R] Complejo Hospitalario Universitario A Coruña, A Coruña, Spain. [Del Barco,E] Hospital Universitario de Salamanca, Salamanca, Spain. [Juan,O] Hospital Universitario y Politécnico La Fe, Valencia, Spain. [Aparisi,F] Hospital General de Valencia, Valencia, Spain. [González-Larriba,JL] Hospital Universitario Clínico San Carlos, Madrid, Spain. [Domine,M] Hospital Universitario Fundación Jiménez Díaz, IIS-FJD, Madrid, Spain. [Trigo,JM, Cobo,M] Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain. [Cerezo,S] Hospital General La Mancha Centro, Alcázar de San Juan, Spain. [Calzas,J] Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain. [Massutí,B] Hospital General Universitario de Alicante, Alicante, Spain. [Bosch-Barrera,J] Catalan Institute of Oncology, Girona, Spain., The TTR registry was supported by Fundación GECP, AstraZeneca, Novartis, Roche, the European Union’s Horizon 2020 research and innovation program (CLARIFY 875160)., and Servicio de Oncología. Hospital Universitario de Fuenlabrada more...
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Central Nervous System ,Male ,Lung Neoplasms ,Survival ,Epidemiology ,medicine.medical_treatment ,Terapéutica ,España ,Cancer Treatment ,Carcinoma pulmonar de células pequeñas ,Nervous System ,Lung and Intrathoracic Tumors ,Metastasis ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Small Cell Lung Cancer ,chemistry.chemical_compound ,STAGE ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Retrospective Studies [Medical Subject Headings] ,Basic Cancer Research ,Medicine and Health Sciences ,Registries ,Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Follow-Up Studies [Medical Subject Headings] ,Neurological Tumors ,Neoplasias torácicas ,Etoposide ,Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings] ,Multidisciplinary ,Supervivencia (salud pública) ,Middle Aged ,respiratory system ,Prognosis ,Combined Modality Therapy ,humanities ,Survival Rate ,PROPHYLACTIC CRANIAL IRRADIATION ,Oncology ,Neurology ,CISPLATIN-BASED CHEMOTHERAPY ,Medicine ,Female ,Anatomy ,Health Care::Population Characteristics::Demography::Vital Statistics::Mortality::Survival Rate [Medical Subject Headings] ,RADIOTHERAPY ,Research Article ,medicine.drug ,medicine.medical_specialty ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy [Medical Subject Headings] ,Science ,Check Tags::Male [Medical Subject Headings] ,Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings] ,Diagnostic Medicine ,Internal medicine ,Cancer Detection and Diagnosis ,medicine ,Humans ,Epidemiología ,Lung cancer ,neoplasms ,Aged ,Retrospective Studies ,Thoracic tumor ,Cisplatin ,Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings] ,Chemotherapy ,Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Small Cell Lung Carcinoma [Medical Subject Headings] ,Small cell lung cancer ,business.industry ,Cancers and Neoplasms ,Biology and Life Sciences ,Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,EFFICACY ,medicine.disease ,TRENDS ,Small Cell Lung Carcinoma ,Carboplatin ,Non-Small Cell Lung Cancer ,respiratory tract diseases ,Treatment ,chemistry ,Check Tags::Female [Medical Subject Headings] ,Spain ,Brain Metastasis ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings] ,Observational study ,1ST-LINE ,business ,Follow-Up Studies - Abstract
Background Small-cell lung cancer (SCLC) is an aggressive disease with high metastatic potential and poor prognosis. Due to its low prevalence, epidemiological and clinical information of SCLC patients retrieved from lung cancer registries is scarce. Patients and methods This was an observational multicenter study that enrolled patients with lung cancer and thoracic tumors, recruited from August 2016 to January 2020 at 50 Spanish hospitals. Demographic and clinical data, treatment patterns and survival of SCLC patients included in the Thoracic Tumor Registry (TTR) were analyzed. Results With a total of 956 cases, the age of 64.7 ± 9.1 years, 78.6% were men, 60.6% smokers, and ECOG PS 0, 1 or ≥ 2 in 23.1%, 53.0% and 23.8% of cases, respectively. Twenty percent of patients had brain metastases at the diagnosis. First-line chemotherapy (CT), mainly carboplatin or cisplatin plus etoposide was administered to >90% of patients. In total, 36.0% and 13.8% of patients received a second and third line of CT, respectively. Median overall survival was 9.5 months (95% CI 8.8–10.2 months), with an estimated rate of 70.3% (95% CI 67.2–73.4%), 38.9% (95% CI 35.4–42.4%), and 14.8% (95% CI 11.8–17.8%) at 6, 12 and 24 months respectively. Median progression-free survival was 6.3 months. Higher mortality and progression rates were significantly associated with male sex, older age, smoking habit, and ECOG PS 1–2. Long-term survival (> 2 years) was confirmed in 6.6% of patients, showing a positive correlation with better ECOG PS, poor smoking and absence of certain metastases at diagnosis. Conclusion This study provides an updated overview of the clinical situation and treatment landscape of ES-SCLC in Spain. Our results might assist oncologists to improve current clinical practice towards a better prognosis for these patients. more...
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- 2021
10. Decreased Urinary Levels of SIRT1 as Non-Invasive Biomarker of Early Renal Damage in Hypertension
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Josep Redon, E. Solaz, Raquel Cortés, Ana Ortega, Olga Martinez-Arroyo, Miriam Galera, and Sergio Martínez-Hervás
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Male ,0301 basic medicine ,podocyte ,Physiology ,030232 urology & nephrology ,Urine ,claudin 1 ,sirtuin 1 ,Podocyte ,lcsh:Chemistry ,0302 clinical medicine ,Claudin-1 ,lcsh:QH301-705.5 ,Spectroscopy ,medicine.diagnostic_test ,Podocytes ,General Medicine ,Middle Aged ,Computer Science Applications ,medicine.anatomical_structure ,diabetes mellitus ,urinary albumin excretion ,Female ,Kidney Diseases ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,hypertension ,Urinary system ,Urinalysis ,Article ,Catalysis ,Inorganic Chemistry ,Excretion ,03 medical and health sciences ,Western blot ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,miRNA ,business.industry ,Organic Chemistry ,medicine.disease ,Angiotensin II ,MicroRNAs ,030104 developmental biology ,Endocrinology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Albuminuria ,business ,Biomarkers - Abstract
Sirtuins have become important players in renal damage in hypertension and diabetes, but their value as biomarkers is poorly assessed. The aims of the study were to evaluate the levels of sirtuin1 (SIRT1), and two miRNAs that regulate SIRT1 expression in hypertensive patients with incipient renal damage with and without diabetes. We quantified urinary SIRT1 and claudin 1 (CLDN1) mRNA and miR34-a and miR-200a levels by quantitative real-time polymerase chain reaction (RT-qPCR) from patients and in cultured podocytes treated with high glucose and angiotensin II. Western blot and fluorescence analyses were also performed. We found decreased SIRT1 levels in patients with increased urinary albumin excretion (UAE), the lowest with diabetes presence, and a strong association with UAE, discriminating incipient renal damage. In vitro experiments also showed SIRT1 overall decreases in podocyte cultures under treatment conditions. In urine samples, miR-34a was reduced and miR-200a increased, both related to UAE levels. However, both miRNAs were generally increased in podocyte cultures under high glucose and angiotensin-II treatment. These results show a significant urinary SIRT1 decrease in albuminuric hypertensive patients, strongly associated with albuminuria, suggesting that SIRT1 could be a potential and non-invasive method to assess incipient renal damage in hypertensive patients. more...
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- 2020
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11. First-line immune checkpoint inhibitors for extensive stage small-cell lung cancer: clinical developments and future directions
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Ana Ortega-Franco, Luis Paz-Ares, Raffaele Califano, and Christoph Jakob Ackermann
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Oncology ,atezolizumab ,Cancer Research ,medicine.medical_specialty ,Durvalumab ,Lung Neoplasms ,durvalumab ,medicine.medical_treatment ,Disease ,Review ,immune checkpoint inhibitors ,Atezolizumab ,Internal medicine ,medicine ,small-cell lung cancer ,Humans ,Lung cancer ,Etoposide ,Platinum ,Chemotherapy ,business.industry ,medicine.disease ,Small Cell Lung Carcinoma ,Immune checkpoint ,Regimen ,lung cancer ,business ,medicine.drug - Abstract
Small-cell lung cancer (SCLC) is an aggressive and rapidly growing disease with poor prognosis. Despite intense efforts to improve clinical outcomes, platinum/etoposide chemotherapy has remained the most effective regimen for first-line extensive disease SCLC for decades. The addition of immune checkpoint inhibitors, and specifically programmed death-ligand 1 inhibitors, to standard platinum/etoposide, significantly improves survival and represents a promising advance in this field. However, identification of a predictive biomarker to refine patient selection is an area of unmet need. Further understanding of tumour immunity and mechanism of resistance is required to design novel strategies that improve survival. In this review, we describe recent developments and future directions on first-line immune checkpoint blockade for extensive disease-SCLC., Highlights • The addition of PD-L1 inhibitors but not CTLA-4 inhibitors to platinum/etoposide improves survival in first line SCLC. • A small proportion of patients derive long-term survival benefit which highlights the relevance of tumour heterogeneity. • At present, maintenance therapy with immune checkpoint inhibitors following platinum/etoposide can't be recommended. • Predictive biomarkers to aid patient selection for immune checkpoint inhibitors in SCLC remain an area of unmet need. • Upcoming trials will evaluate PD-L1 inhibitors plus chemotherapy in combination with drugs that promote tumour immunity. more...
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- 2020
12. The Rab-Rabphilin system in injured human podocytes stressed by glucose overload and angiotensin II
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Olga Martinez-Arroyo, Ana Ortega, Felipe J. Chaves, Josep Redon, Raquel Cortés, and Javier Perez-Hernandez
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0301 basic medicine ,medicine.medical_specialty ,podocyte ,Physiology ,Cellular differentiation ,030232 urology & nephrology ,Vesicular Transport Proteins ,Apoptosis ,Nerve Tissue Proteins ,Podocyte ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Albuminuria ,Humans ,Adaptor Proteins, Signal Transducing ,Chemistry ,Podocytes ,Angiotensin II ,Rab-Rabphilin system ,Vesicular transport protein ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Glucose ,rab GTP-Binding Proteins ,Glomerular Filtration Barrier ,kidney injury ,Rab ,medicine.symptom ,Research Article - Abstract
Kidney injury in hypertension and diabetes entails, among in other structures, damage in a key cell of the glomerular filtration barrier, the podocyte. Podocytes are polarized and highly differentiated cells in which vesicular transport, partly driven by Rab GTPases, is a relevant process. The aim of the present study was to analyze Rab GTPases of the Rab-Rabphilin system in human immortalized podocytes and the impact of high glucose and angiotensin II. Furthermore, alterations of the system in urine cell pellets from patients with hypertension and diabetes were studied. Apoptosis was analyzed in podocytes, and mRNA level quantification, Western blot analysis, and immunofluorescence were developed to quantify podocyte-specific molecules and Rab-Rabphilin components (Rab3A, Rab27A, and Rabphilin3A). Quantitative RT-PCR was performed on urinary cell pellet from patients. The results showed that differentiated cells had reduced protein levels of the Rab-rabphillin system compared with undifferentiated cells. After glucose overload and angiotensin II treatment, apoptosis was increased and podocyte-specific proteins were reduced. Rab3A and Rab27A protein levels were increased under glucose overload, and Rabphilin3A decreased. Furthermore, this system exhibited higher levels under stress conditions in a manner of angiotensin II dose and time treatment. Immunofluorescence imaging indicated different expression patterns of podocyte markers and Rab27A under treatments. Finally, Rab3A and Rab27A were increased in patient urine pellets and showed a direct relationship with albuminuria. Collectively, these results suggest that the Rab-Rabphilin system could be involved in the alterations observed in injured podocytes and that a mechanism may be activated to reduce damage through the vesicular transport enhancement directed by this system. more...
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- 2020
13. Urinary exosomal miR-146a as a marker of albuminuria, activity changes and disease flares in lupus nephritis
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Ana Ortega, Felipe J. Chaves, Josep Redon, María José Forner, Miriam Galera, Miguel A Solis-Salguero, Javier Perez-Hernandez, Raquel Cortés, and Olga Martinez-Arroyo
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Nephrology ,medicine.medical_specialty ,Urinary system ,030232 urology & nephrology ,Lupus nephritis ,030204 cardiovascular system & hematology ,Exosomes ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Renal fibrosis ,Albuminuria ,Humans ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,Proteinuria ,Systemic lupus erythematosus ,business.industry ,Intracellular Signaling Peptides and Proteins ,medicine.disease ,Symptom Flare Up ,Lupus Nephritis ,MicroRNAs ,Real-time polymerase chain reaction ,Interleukin-1 Receptor-Associated Kinases ,Immunology ,medicine.symptom ,business ,Biomarkers - Abstract
Urinary exosomes, especially microRNAs (miRNAs) packaged within, are ideal sources of renal damage markers. We investigated the association between exosomal miR-146a, (anti-inflammatory regulator) and disease activity, proteinuria and systemic lupus erythematosus (SLE) flares over a 36-month follow-up period. We isolated urinary exosomes from 41 SLE patients, 27 with lupus nephritis (LN) and 20 healthy controls, and exosomal miR-146a, quantified by the real-time quantitative polymerase chain reaction (RT-qPCR), was correlated with histological features in 13 renal biopsies. We also analysed the association between the exosomal miR-146a and TRAF6 axis. Exosomal miR-146a showed an inverse association with circulating C3 and C4 complement components, proteinuria, and with histological features such as chronicity index. This marker was able to identify LN with an AUC of 0.82 (p = 0.001). Basal exosomal miR-146a was associated with disease activity and proteinuria changes and was an independent marker of 36-month follow-up flares (OR 7.08, p = 0.02). Pathway analysis identified IRAK1 and TRAF6 as miR-146a target genes. Finally, in vitro experiments suggested that miR-146a exerts a protective effect through negative regulation of inflammation by suppressing IRAK1 and TRAF6. Urinary exosomal miR-146a levels are correlated with lupus activity, proteinuria and histological features, discriminating patients with LN and being a good baseline marker of SLE flares. We have identified a relevant biological miR-146a-TRAF6 axis association in LN renal fibrosis progression. more...
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- 2020
14. Effectiveness of Pharmacokinetic/Pharmacodynamic-Guided Meropenem Treatment in Critically Ill Patients: A Comparative Cohort Study
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Ana Ortega, Irene Aquerreta, Ana Isabel Idoate Grijalba, Azucena Aldaz, and Pablo Monedero
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medicine.medical_specialty ,Critical Illness ,030226 pharmacology & pharmacy ,Meropenem ,Procalcitonin ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Pharmacology (medical) ,Retrospective Studies ,Pharmacology ,medicine.diagnostic_test ,business.industry ,bacterial infections and mycoses ,Intensive care unit ,Confidence interval ,Anti-Bacterial Agents ,Intensive Care Units ,Therapeutic drug monitoring ,Relative risk ,business ,medicine.drug ,Cohort study - Abstract
BACKGROUND The proper dosage of antibiotics is a key element in the effective treatment of infection, especially in critically ill patients. This study aimed to evaluate the efficacy of optimized meropenem regimens based on pharmacokinetic/pharmacodynamic criteria in patients admitted to the intensive care unit. METHODS This observational, naturalistic, retrospective, unicentric cohort study was performed between May 2011 and December 2017. The clinical and bacteriologic responses of 77 control intensive care unit patients receiving meropenem were compared with those of 77 propensity score-balanced patients who received meropenem dose adjusted by therapeutic drug monitoring. The primary end point of clinical response was a reduction at the end of treatment of at least 80% of the maximum procalcitonin (PCT) value recorded during the meropenem treatment. RESULTS The primary end point was met by 55 patients (71.4%) in the adjusted group compared with 41 (53.3%) patients in the control group (mean difference 18.1%, P = 0.02). Fifty-one patients (66.2%) in the adjusted group required a meropenem dose adjustment, being necessary in 46 of them (90.2%) to decrease the dose. The reduction of PCT was the greatest in the adjusted group compared with the unadjusted group (93% versus 85%, P = 0.004); a greater percentage of patients reached a PCT level < 0.5 ng/mL (63.6% versus 41.6%, P = 0.006), and there was a trend toward an improved bacteriologic response (relative risk = 1.27; 95% confidence interval: 0.92-1.56). There were no differences in early mortality or safety between groups. CONCLUSIONS Adjustment of meropenem therapy by monitoring is a useful strategy for improving meropenem effectiveness in the treatment of infection in critically ill patients, with no impact on safety. more...
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- 2020
15. 4CPS-045 Cost effectiveness analysis of meropenem dose optimisation in critical patients
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Irene Aquerreta, A Idoate, Azucena Aldaz, and Ana Ortega
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medicine.medical_specialty ,business.industry ,Cost-effectiveness analysis ,Meropenem ,Procalcitonin ,Internal medicine ,Pharmacodynamics ,Cohort ,Propensity score matching ,medicine ,Dosing ,business ,Cohort study ,medicine.drug - Abstract
Background and importance Meropenem dose adjustment following pharmacokinetic/pharmacodynamic monitoring (TDM) in critical patients (CP) presents a clinical benefit. An economic analysis of this activity could facilitate its use in clinical practice. Aim and objectives To conduct a cost effectiveness analysis of meropenem TDM in CP versus standard dose (SD) according to the package insert recommendations. Material and methods We conducted a naturalistic, retrospective, observational cohort study of CP receiving meropenem between May 2011 and December 2017 in a university hospital. Two cohorts were analysed: patients with meropenem TDM (cohort A) and patients with SD meropenem (cohort B). The main effectiveness variable was the percentage of patients with a reduction of at least 80% in the procalcitonin value at the end of meropenem treatment compared with the maximum value during meropenem treatment. Costs included in the analysis were: meropenem, material for drug preparation, TDM, time for preparation, administration and infusion surveillance, meropenem adverse drug reactions (ADR), critical care hospitalisation days and re-entries. Propensity score (PS) matching was applied for patient selection. The χ2 was used to compare effectiveness and bootstrap to calculate the difference in costs between cohorts. A cost effectiveness analysis with deterministic and probabilistic sensitivity analyses was performed. Results A total of 154 patients were included (77 per cohort) after PS matching. Meropenem dose was changed in 51 (66.2%) patients with TDM, in most (90.2%) because they were overdosed. In cohort A, 71.4% of patients had reduced procalcitonin by at least 80% compared with 53.2% in cohort B (difference 18.2% (95% CI 3.1; 33.2; p=0.020)). No significant differences were found in ADR between the two cohorts. An average decrease in cost per patient of −1454€ (95% CI −4627;1720€) with TDM was observed, with lower cost per patient for meropenem −62€ (95% CI −116; −4), disposable material −12€ (95% CI −29; 4) and nursing time −38€ (95% CI −71; −4) in cohort A, that offset the TDM cost (47€). Mean hospitalisation cost in patients with TDM was 8912€ versus 10 325€ in cohort B. There was a 75% probability that TDM was more effective and cheaper (dominant) than SD according to the sensitivity analysis. Conclusion and relevance Meropenem dose adjustment following pharmacokinetic/pharmacodynamic criteria was more effective, with similar safety and lower costs, than dosing according to the package insert recommendations. References and/or acknowledgements 1. Schuetz P, et al. Procalcitonin-guided antibiotic stewardship. Clin Chem Lab Med 2019. No conflict of interest. more...
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- 2020
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16. Influence of Sex, Age, and Weight on Levetiracetam Pharmacokinetics
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Natalia Alzueta, Azucena Aldaz, and Ana Ortega
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Adult ,Male ,Aging ,medicine.medical_specialty ,Levetiracetam ,Adolescent ,Renal function ,Overweight ,030226 pharmacology & pharmacy ,Young Adult ,03 medical and health sciences ,Basal (phylogenetics) ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Young adult ,Aged ,Retrospective Studies ,Pharmacology ,Sex Characteristics ,medicine.diagnostic_test ,business.industry ,Body Weight ,Middle Aged ,Endocrinology ,Therapeutic drug monitoring ,Creatinine ,Anticonvulsants ,Female ,medicine.symptom ,business ,030217 neurology & neurosurgery ,medicine.drug ,Sex characteristics - Abstract
BACKGROUND Levetiracetam (LEV) is a second-generation antiepileptic drug extensively used in therapeutics. The aim of this study was to evaluate the influence that sex, age, and weight exert on LEV pharmacokinetics in clinical practice. METHODS We conducted a 6-year retrospective observational study. Patients were classified in subgroups according to sex, weight (normal range, overweight, and obese), and age (young adult: 16-30 years old, middle-aged adult: 31-50 years old, advanced adult: 51-64 years old, and elderly adult: ≥65 years old). We compared LEV apparent oral clearance (LEV CL/F) between the subgroups. RESULTS A total of 238 LEV basal serum concentrations (LEV C0) corresponding to 156 patients were identified. Significant differences were observed in LEV CL/F between males and females when LEV CL/F was expressed as L/h [mean (SD): 4.79 (1.84) L/h in males versus 4.13 (1.64) L/h in females; P < 0.001]. These differences were not significant when LEV CL/F was normalized by weight [mean (SD): 60.64 (24.90) mL/h/kg in males versus 64.10 (28.87) mL/h/kg in females; n.s.]. Weight in females was 17% lower compared with males. A progressive reduction in LEV CL/F was observed with increasing age, in a proportion that was similar to the decline in renal function. The elderly patients presented 30% lower LEV CL/F (mL/h/kg) and 43% lower creatinine clearance (CCr) in comparison with adults. No statistically significant differences were observed in LEV CL/F calculated in L/h between weight subgroups. However, when LEV CL/F was expressed in mL/h/kg, a progressive reduction was observed [normal weight: 72.21 (28.97); overweight: 57.84 (25.38); obese: 49.45 (14.50); P < 0.001]. A significant and positive correlation between CCr and LEV CL/F was observed, confirming the important role of the renal function in LEV CL/F. The CCr increased in each sex group when weight increased; however, LEV CL/F (L/h) remained constant. CONCLUSIONS Sex, age, and weight affect LEV pharmacokinetics, having an impact on the individual dosage regimen needed to achieve the therapeutic objective. Sex is a conditioning factor of LEV CL/F, although its influence is principally due to the weight. LEV CL/F decreases with advancing age, proportionally to the decline in renal function. It is confirmed that LEV dosage per body weight is not required, and prescribing higher doses of LEV in obese patients is not justified. These data suggest that routine LEV therapeutic drug monitoring in the elderly patients, patients with renal dysfunction, and obese patients is indicated. more...
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- 2018
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17. ASB1 differential methylation in ischaemic cardiomyopathy: relationship with left ventricular performance in end-stage heart failure patients
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Manuel Portolés, Juan Sandoval, Francisca Lago, Ana Ortega, José Ramón González-Juanatey, Esther Roselló-Lletí, Luis Martínez-Dolz, Estefanía Tarazón, Miguel Félix Mata Rivera, and Carolina Gil-Cayuela more...
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0301 basic medicine ,Heart transplantation ,medicine.medical_specialty ,Ejection fraction ,business.industry ,medicine.medical_treatment ,Diastole ,Stroke volume ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Heart failure ,DNA methylation ,medicine ,Cardiology ,Epigenetics ,Cardiology and Cardiovascular Medicine ,business ,Epigenomics - Abstract
Aims Ischaemic cardiomyopathy (ICM) leads to impaired contraction and ventricular dysfunction, causing high rates of morbidity and mortality. Epigenomics allows the identification of epigenetic signatures in human diseases. We analyse the differential epigenetic patterns of the ASB gene family in ICM patients and relate these alterations to their haemodynamic and functional status. Methods and results Epigenomic analysis was carried out using 16 left ventricular (LV) tissue samples, eight from ICM patients undergoing heart transplantation and eight from control (CNT) subjects without cardiac disease. We increased the sample size up to 13 ICM and 10 CNT for RNA sequencing and to 14 ICM for pyrosequencing analyses. We found a hypermethylated profile (cg11189868) in the ASB1 gene that showed a differential methylation of 0.26Δβ (P = 0.016). This result was validated by a pyrosequencing technique (0.23Δβ, P = 0.048). Notably, the methylation pattern was strongly related to LV ejection fraction (r = -0.849, P = 0.008), stroke volume (r = -0.929, P = 0.001), and end-systolic and diastolic LV diameters (r = -0.743, P = 0.035 for both). ASB1 showed a down-regulation in messenger RNA levels (-1.2-fold, P = 0.039). Conclusions Our findings link a specific ASB1 methylation pattern to LV structure and performance in end-stage ICM, opening new therapeutic opportunities and providing new insights regarding which is the functionally relevant genome in the ischaemic failing myocardium. more...
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- 2018
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18. A radiological score for the assessment of tuberculosis progression: Validation in mouse models
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Juan José Vaquero, Ana Ortega-Gil, Laura Guijarro-López, Jose Juan Roca, and Arrate Muñoz-Barrutia
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0301 basic medicine ,Microbiology (medical) ,Oncology ,medicine.medical_specialty ,Tuberculosis ,Time Factors ,030106 microbiology ,Immunology ,Disease ,Microbiology ,Correlation ,03 medical and health sciences ,In vivo ,Predictive Value of Tests ,Internal medicine ,Medicine ,Animals ,Lung volumes ,Adverse effect ,Lung ,Tuberculosis, Pulmonary ,Mice, Inbred C3H ,business.industry ,Reproducibility of Results ,Mycobacterium tuberculosis ,X-Ray Microtomography ,medicine.disease ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Radiological weapon ,Host-Pathogen Interactions ,Disease Progression ,Radiographic Image Interpretation, Computer-Assisted ,Female ,business - Abstract
The sensitivity of in vivo low-dose high-resolution micro-computed tomography imaging enables monitoring the lung damage caused by tuberculosis. Here, we propose a radiological score integrated in the experimental workflow that enables longitudinal monitoring for prospective efficacy studies in drug development programs. The score is based on an automatic measurement of total unaffected lung volume in vivo normalized for inter-subject comparison. It was validated on well-characterized progression of chronic tuberculosis in Erdman and H37Rv strains in C3HeB/FeJ-based models. We demonstrated that a decrease in the score value indicates increasing adverse effects and vice versa. The colony-forming units count confirmed the variability in the host response suggested by the score values. The correlation between changes in the mice's weight and the score is consistent with disease progression. The classification of disease extent by k-means clustering of the score values provided the definition of the lung damage severity according to the bacillus strain. The proposed score will reduce sources of bias and improve the statistical robustness of studies by the attrition of non-infected subjects or subjects with a weak immune response. Readily available quantifications allow for a fast assessment of the therapeutic potential in drug-resistant tuberculosis strains. more...
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- 2019
19. Effectiveness of adjunctive nebulized antibiotics in critically ill patients with respiratory tract infections
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A Idoate, Leire Leache, Ana Ortega, Irene Aquerreta, Azucena Aldaz, and Pablo Monedero
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0301 basic medicine ,Male ,Kidney ,Kidney Function Tests ,Procalcitonin ,0302 clinical medicine ,Respiratory infection ,Clinical endpoint ,030212 general & internal medicine ,Respiratory Tract Infections ,Antiinfective agent ,Aged, 80 and over ,Respiratory tract infections ,Drug Administration Routes ,General Medicine ,Middle Aged ,Anti-Bacterial Agents ,Infectious Diseases ,Treatment Outcome ,Inhalation ,Administration, Intravenous ,Female ,Original Article ,Cohort study ,Microbiology (medical) ,medicine.medical_specialty ,Calcitonin Gene-Related Peptide ,Critical Illness ,030106 microbiology ,Antimicrobial agent ,03 medical and health sciences ,Internal medicine ,Administration, Inhalation ,medicine ,Humans ,Critically ill ,Aged ,Retrospective Studies ,business.industry ,Nebulizers and Vaporizers ,Nebulizer ,Odds ratio ,Length of Stay ,medicine.disease ,Respiration, Artificial ,Pneumonia ,Critical care ,business - Abstract
The purpose of the study was to analyze the effectiveness of adding nebulized antibiotics to systemic antimicrobials in critically ill patients with respiratory tract infections (pneumonia or tracheobronchitis) and the effect on renal function. A retrospective observational cohort study including critically ill patients with respiratory tract infections during a 2-year period was conducted. Intervention group included patients that received nebulized and systemic antimicrobials. Patients in the control group received only systemic antimicrobials. Clinical resolution was the primary endpoint. Secondary outcomes included change in fever, inflammatory parameters, and creatinine clearance; length of hospital stay, systemic therapy, and mechanical ventilation; hospital readmission; and mortality. Regression models were performed to estimate the effect of nebulized antibiotics on outcome variables adjusted by potential confounders. A total of 136 patients were included (93 in control group and 43 in intervention group). The intervention group had higher odds of clinical resolution (adjusted odds ratio (OR): 7.1; 95% confidence interval (95% CI): 1.2, 43.3). Nebulized antibiotic therapy was independently associated with reduction in procalcitonin (adjusted OR: 12.4; 95% CI: 1.4, 109.7). There were no significant differences in the rest of the secondary outcomes or in creatinine clearance reduction. Adding nebulized antibiotics for the management of respiratory tract infections has a positive impact on clinical resolution without increasing the risk of renal toxicity. Electronic supplementary material The online version of this article (10.1007/s10096-019-03733-6) contains supplementary material, which is available to authorized users. more...
- Published
- 2019
20. EXOSOMAL MICRORNA-26A RESPONSE TO TGF-B1 STRESS IN HYPERTENSION
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Ana Ortega, Javier Perez-Hernandez, Olga Martinez-Arroyo, Raquel Cortés, Felipe J. Chaves, and Josep Redon
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Physiology ,business.industry ,Internal Medicine ,Cancer research ,Microrna 26a ,Medicine ,Cardiology and Cardiovascular Medicine ,business - Published
- 2021
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21. URINARY EXOSOME MIR-146A IS A POTENTIAL MARKER OF ALBUMINURIA IN ESSENTIAL HYPERTENSION
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Javier Perez-Hernandez, Ana Ortega, Olga Martinez-Arroyo, Felipe J. Chaves, Raquel Cortés, and Josep Redon
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medicine.medical_specialty ,Physiology ,business.industry ,Urinary system ,Urology ,Essential hypertension ,medicine.disease ,Exosome ,Internal Medicine ,Albuminuria ,medicine ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Published
- 2021
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22. TRPM7is down-regulated in both left atria and left ventricle of ischaemic cardiomyopathy patients and highly related to changes in ventricular function
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Manuel Portolés, Ana Ortega, Francisca Lago, Estefanía Tarazón, J.R. Gonzalez-Juanatey, Luis Martínez-Dolz, Miguel Rivera, Esther Roselló-Lletí, and Carolina Gil-Cayuela
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Ejection fraction ,business.industry ,Cardiac fibrosis ,Cardiomyopathy ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,Transient receptor potential channel ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Ventricle ,TRPM7 ,Heart failure ,Internal medicine ,Cardiac chamber ,cardiovascular system ,medicine ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Aims The kinase ion channel transient receptor potential melastatin 7 (TRPM7) is considered a modulator of cardiac fibrosis progression; nevertheless, we lack of studies analysing its role in human ischaemic cardiomyopathy (ICM). Our objective was to analyse the expression of genes encoding cardiac ion channels in human ICM, focusing on the alterations in mRNA levels of TRPM7 and its relationship with changes in the ventricular function. Methods and results RNA-sequencing was carried out in 13 left ventricular (LV) samples of patients with ICM compared with a control group (n = 10). The analysis revealed a total of 25 ion channel genes differentially expressed. We performed an RTqPCR analysis of the TRPM7 mRNA in LV and left atrial samples and found that it was down-regulated in both cavities (−1.43-fold and −1.52-fold, respectively). Atrial TRPM7 mRNA levels showed an excellent and inverse relationships with the depressed ejection fraction (r = −0.724, P = 0.042) and with the mitral A wave (r = −0.938, P = 0.006). Conclusions We report the down-regulation of TRPM7 in tissue samples from both left atria and left ventricle in patients with ICM. We found an inverse relationship between both cardiac chambers mRNA levels with LV dysfunction, suggesting an important role of TRPM7 in the left atrial and LV functional depression found in this cardiomyopathy. more...
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- 2016
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23. P2.10-02 Smoking Habit in Lung Cancer in Spain
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Carlos Camps, Ana Ortega, E. Del Barco, A. Padilla, Joaquim Bosch-Barrera, F. Franco, J. De Castro Carpeno, Manuel Domine, Jose-Luis Gonzalez-Larriba, R. Garcia Campelo, Juana Oramas, Gretel Benítez, M. Guirado, R. Lopez Castro, Montserrat Domenech, R. Blanco, Enric Carcereny, S. Cerezo, R. Bernabé, David Aguiar, Delvys Rodriguez-Abreu, G. Huidobro, M. Provencio, M.A. Sala, B. Massuti, E. Cuadrado Albite, and R. de las Peñas more...
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Oncology ,Smoking habit ,business.industry ,Internal medicine ,medicine ,Lung cancer ,medicine.disease ,business - Published
- 2019
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24. P2.03-16 Agreement Between Different Methodologies for Non-Invasive p.T790M and EGFR Sensitizing Mutation Testing
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Joaquim Bosch-Barrera, Ana Collazo, M. Provencio, Beatriz García-Peláez, Javier Perez Altozano, Santiago Viteri, E. Jantus, Pilar Diz, Oscar Juan, José Miguel Jurado, B. Massuti, E. S. Romero, M.A. Molina-Vila, Rosa Rosell, Jorge José García González, M. Cobo, F. Aparisi, Berta Hernandez, Ana Blasco, A. R. Festa, Ana Ortega, Margarita Majem, Avelino Martín, M. Guirado, Carlos Garcia Giron, Alejandro Romero, A. Insa, Gustavo Benítez, R. Bernabé, Patricia Cruz, Silvia Calabuig-Fariñas, Carlos Camps, and Sonia Argibay Vázquez more...
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,T790M ,business.industry ,Internal medicine ,Non invasive ,Mutation testing ,Medicine ,business - Published
- 2019
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25. Myocardium of patients with dilated cardiomyopathy presents altered expression of genes involved in thyroid hormone biosynthesis
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Miguel Rivera, Estefanía Tarazón, Ana Ortega, Esther Roselló-Lletí, Luis Martínez-Dolz, Manuel Portolés, José Ramón González-Juanatey, Francisca Lago, Carolina Gil-Cayuela, and Juan Cinca
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0301 basic medicine ,Male ,Molecular biology ,medicine.medical_treatment ,Cardiomyopathy ,lcsh:Medicine ,Gene Expression ,030204 cardiovascular system & hematology ,Biochemistry ,Autoantigens ,0302 clinical medicine ,Sequencing techniques ,Iron-Binding Proteins ,Medicine and Health Sciences ,lcsh:Science ,Heart transplantation ,Thyroid ,Dilated Cardiomyopathy ,Multidisciplinary ,Triiodothyronine ,biology ,Ventricular Remodeling ,High-Throughput Nucleotide Sequencing ,Dilated cardiomyopathy ,Heart ,RNA sequencing ,Receptors, Thyrotropin ,Middle Aged ,Dual Oxidases ,Chemistry ,medicine.anatomical_structure ,Physical Sciences ,Female ,Anatomy ,Cardiomyopathies ,Research Article ,Cardiomyopathy, Dilated ,medicine.medical_specialty ,Thyroid Hormones ,Cardiology ,Endocrine System ,Biosynthesis ,Iodide Peroxidase ,03 medical and health sciences ,Thyroid peroxidase ,Internal medicine ,medicine ,Genetics ,Humans ,Ventricular remodeling ,business.industry ,Gene Expression Profiling ,Myocardium ,lcsh:R ,Chemical Compounds ,Biology and Life Sciences ,Dual oxidase 2 ,Iodides ,medicine.disease ,Hormones ,Research and analysis methods ,030104 developmental biology ,Endocrinology ,Molecular biology techniques ,Gene Expression Regulation ,Case-Control Studies ,biology.protein ,Cardiovascular Anatomy ,lcsh:Q ,business ,Biomarkers - Abstract
Background The association between dilated cardiomyopathy (DCM) and low thyroid hormone (TH) levels has been previously described. In these patients abnormal thyroid function is significantly related to impaired left ventricular (LV) function and increased risk of death. Although TH was originally thought to be produced exclusively by the thyroid gland, we recently reported TH biosynthesis in the human ischemic heart. Objectives Based on these findings, we evaluated whether the genes required for TH production are also altered in patients with DCM. Methods Twenty-three LV tissue samples were obtained from patients with DCM (n = 13) undergoing heart transplantation and control donors (n = 10), and used for RNA sequencing analysis. The number of LV DCM samples was increased to 23 to determine total T4 and T3 tissue levels by ELISA. Results We found that all components of TH biosynthesis are expressed in human dilated heart tissue. Expression of genes encoding thyroperoxidase (-2.57-fold, P < 0.05) and dual oxidase 2 (2.64-fold, P < 0.01), the main enzymatic system of TH production, was significantlyaltered in patients with DCM and significantly associated with LV remodeling parameters. Thyroxine (T4) cardiac tissue levels were significantly increased (P < 0.01), whilst triiodothyronine (T3) levels were significantly diminished (P < 0.05) in the patients. Conclusions Expression of TH biosynthesis machinery in the heart and total tissue levels of T4 and T3, are altered in patients with DCM. Given the relevance of TH in cardiac pathology, our results provide a basis for new gene-based therapeutic strategies for treating DCM. more...
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- 2018
26. P2.05-12 Analysis of Biomarkers in Lung Cancer in Spain
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Anna Estival, Thomas M. Moran, R. Garcia Campelo, M. Guirado, M.A. Sala, J.L. González Larriba, M. Provencio, B. Massuti, Gretel Benítez, Ana Ortega, Juana Oramas, R. Blanco, M. Lázaro, R. Lopez Castro, Manuel Domine, Beatriz Nuñez, Carlos Camps, A. Padilla, Delvys Rodriguez-Abreu, E. Del Barco, R. Bernabé, and Joaquim Bosch-Barrera more...
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Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,business ,Lung cancer ,medicine.disease - Published
- 2019
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27. P2.05-10 Liquid Biopsy: Association Between the Burden of Disease in Patients with EGFR-Mutated NSCLC and the Frequency of Its Detection in Blood
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L.E. Chara, R. Blanco, X. Mielgo Rubio, Ana Ortega, Alejandro Romero, J. Coves, Manuel Domine, Juana Oramas, V. Calvo De Juan, E. Sánchez Romero, C. García Girón, J. Balsalobre, M.A. Sala, Berta Hernandez, Alfredo Sanchez-Hernandez, E. Jantus, Joaquim Bosch-Barrera, Jose Miguel Sanchez, M. Sotelo, A. Padilla, M. Provencio, María Sereno, Fábio Gazelato de Mello Franco, and M. Barquín Del Romo more...
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Pulmonary and Respiratory Medicine ,Oncology ,Burden of disease ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,In patient ,Liquid biopsy ,business - Published
- 2019
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28. Thyroid hormone biosynthesis machinery is altered in the ischemic myocardium: An epigenomic study
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Miguel Rivera, Manuel Portolés, Juan Sandoval, Francisca Lago, Estefanía Tarazón, José Ramón González-Juanatey, Luis Martínez-Dolz, Esther Jorge, Ana Ortega, Juan Cinca, Carolina Gil-Cayuela, and Esther Roselló-Lletí more...
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0301 basic medicine ,Epigenomics ,Male ,medicine.medical_specialty ,Thyroid Hormones ,medicine.medical_treatment ,Myocardial Ischemia ,Heart failure ,030204 cardiovascular system & hematology ,Methylation ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Thyroid peroxidase ,Internal medicine ,medicine ,Humans ,Ischemic cardiomyopathy ,Heart transplantation ,Triiodothyronine ,Ejection fraction ,biology ,business.industry ,Myocardium ,Thyroid ,Middle Aged ,medicine.disease ,Remodeling ,Thyroid hormone ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,biology.protein ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Abnormal thyroid hormone (TH) metabolism is significantly associated with impaired left ventricular (LV) function and death. Although THwas traditionally thought to be produced exclusively by the thyroid gland, an increasing number of studies report TH production in other tissues. Based on these findings, we evaluated whether the genes required for TH biosynthesis are expressed in the human heart, and whether their expression is altered in patients with ischemic cardiomyopathy (ICM) and is related to epigenetic variations. Methods: Twenty-three LV tissue sampleswere obtained fromICMpatients (n=13) undergoing heart transplantation and control donors (n=10) for RNA sequencing analysis. We increased the LV samples to 27 for the ELISA determination of total T4 and T3 tissue levels. For epigenomic studies, 850 K InfiniumMethylationEPIC BeadChip platform was performed. Results: Using RNA-sequencing, we displayed the expression levels of all components required for TH biosynthesis in human heart tissue. We observed significantly altered expression of genes encoding thyroperoxidase (TPO; -2.48-fold, P < 0.05) and dual oxidase 2 (2.83-fold, P < 0.05), themain enzymatic systemof TH production, and significant relationships between their altered expression and LV remodeling parameters. In addition, epigenetic analysis revealed a differential methylation pattern in TPO, and triiodothyronine tissue levels were significantly decreased (P < 0.01). Conclusions: These results showed that the human heart expresses the TH biosynthesismachinery, being altered its main enzymatic system in patients with ICM. Given the relevance of TH in cardiac pathology, our results provide a foundation for new therapeutic approaches based on TPO for treating ICM. (C) 2017 Published by Elsevier Ireland Ltd. more...
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- 2017
29. Changes in human Golgi apparatus reflect new left ventricular dimensions and function in dilated cardiomyopathy patients
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Ana Ortega, Miguel Rivera, Esther Roselló-Lletí, José Ramón González-Juanatey, Carolina Gil-Cayuela, Estefanía Tarazón, Manuel Portolés, Francisca Lago, and Luis Martínez-Dolz
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0301 basic medicine ,Cardiomyopathy, Dilated ,medicine.medical_specialty ,medicine.drug_class ,Cardiac Volume ,Heart Ventricles ,Cardiomyopathy ,Cardiac metabolism ,Golgi Apparatus ,heart failure ,030204 cardiovascular system & hematology ,left ventricular function ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Dogs ,Internal medicine ,Natriuretic peptide ,medicine ,Myocyte ,Animals ,Humans ,Myocytes, Cardiac ,Natriuretic Peptides ,natriuretic peptide ,business.industry ,Dilated Cardiomyopathy ,Dilated cardiomyopathy ,Golgi apparatus ,medicine.disease ,030104 developmental biology ,Heart failure ,symbols ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Published
- 2016
30. Human ischemic cardiomyopathy shows cardiac Nos1 translocation and its increased levels are related to left ventricular performance
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Manuel Portolés, Ana Ortega, Miguel Rivera, Francisca Lago, Ricardo Carnicer, Estefanía Tarazón, José Ramón González-Juanatey, Carolina Gil-Cayuela, and Esther Roselló-Lletí
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0301 basic medicine ,Cardiac function curve ,Male ,medicine.medical_specialty ,NOS1 ,Myocardial Ischemia ,Nitric Oxide Synthase Type I ,030204 cardiovascular system & hematology ,Biology ,Ventricular Function, Left ,Article ,03 medical and health sciences ,0302 clinical medicine ,Sarcolemma ,Downregulation and upregulation ,Internal medicine ,medicine ,Myocyte ,Humans ,Multidisciplinary ,Ischemic cardiomyopathy ,Sequence Analysis, RNA ,Middle Aged ,Pathophysiology ,Up-Regulation ,Protein Transport ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Homeostasis - Abstract
The role of nitric oxide synthase 1 (NOS1) as a major modulator of cardiac function has been extensively studied in experimental models; however, its role in human ischemic cardiomyopathy (ICM) has never been analysed. Thus, the objectives of this work are to study NOS1 and NOS-related counterparts involved in regulating physiological function of myocyte, to analyze NOS1 localisation, activity, dimerisation, and its relationship with systolic function in ICM. The study has been carried out on left ventricular tissue obtained from explanted human hearts. Here we demonstrate that the upregulation of cardiac NOS1 is not accompanied by an increase in NOS activity, due in part to the alterations found in molecules involved in the regulation of its activity. We observed partial translocation of NOS1 to the sarcolemma in ischemic hearts, and a direct relationship between its protein levels and systolic ventricular function. Our findings indicate that NOS1 may be significant in the pathophysiology of human ischemic heart disease with a preservative role in maintaining myocardial homeostasis. more...
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- 2016
31. Pten Positively Regulates Brown Adipose Function, Energy Expenditure, and Longevity
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Gonzalo Gómez-López, Ángela M. Valverde, Alejo Efeyan, M. Mar González-Barroso, Elena Lopez-Guadamillas, Eduardo Rial, Sonia Martinez, Joaquín Pastor, Marta Cañamero, Ana Ortega-Molina, James R. Bischoff, Maribel Muñoz-Martin, Manuel Serrano, Eduardo Romanos, Francisca Mulero, Comunidad de Madrid, Ministerio de Ciencia e Innovación (España), and Instituto de Salud Carlos III more...
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medicine.medical_specialty ,Physiology ,Longevity ,Adipose tissue ,Mice, Transgenic ,Biology ,Calorimetry ,Ion Channels ,Mitochondrial Proteins ,Mice ,Adipose Tissue, Brown ,Internal medicine ,Brown/metabolism ,Brown adipose tissue ,medicine ,Uncoupling protein ,PTEN ,Animals ,Energy Metabolism/genetics/physiology ,Protein kinase B ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Uncoupling Protein 1 ,PRDM16 ,Imidazoles ,PTEN Phosphohydrolase ,Cell Biology ,Thermogenin ,DNA-Binding Proteins ,medicine.anatomical_structure ,Endocrinology ,DNA-Binding Proteins/genetics/metabolism ,Pyrazines ,biology.protein ,Energy Metabolism ,Ion Channels/genetics/metabolism ,Transcription Factors - Abstract
13 páginas, 7 figuras, 7 figuras suplementarias, 7 tablas suplementarias.-- et al., Aging in worms and flies is regulated by the PI3K/Akt/Foxo pathway. Here we extend this paradigm to mammals. Ptentg mice carrying additional genomic copies of Pten are protected from cancer and present a significant extension of life span that is independent of their lower cancer incidence. Interestingly, Ptentg mice have an increased energy expenditure and protection from metabolic pathologies. The brown adipose tissue (BAT) of Ptentg mice is hyperactive and presents high levels of the uncoupling protein Ucp1, which we show is a target of Foxo1. Importantly, a synthetic PI3K inhibitor also increases energy expenditure and hyperactivates the BAT in mice. These effects can be recapitulated in isolated brown adipocytes and, moreover, implants of Ptentg fibroblasts programmed with Prdm16 and Cebpβ form subcutaneous brown adipose pads more efficiently than wild-type fibroblasts. These observations uncover a role of Pten in promoting energy expenditure, thus decreasing nutrient storage and its associated damage, Work in the laboratory of A.M.V. was funded by grant SAF2009-08114 and by the CIBERDEM (ISCIII), and work in the laboratory of E. Rial was funded by grants SAF2010-20256 and Consolider-Ingenio CSD2007-00020. A.O.-M. was recipient of a predoctoral contract of the Regional Government of Madrid. E.L.-G. was recipient of a predoctoral contract from the Spanish Ministry of Education. M.M.G.-B. was supported by the “Ramon y Cajal” program of the Spanish Ministry of Science and Innovation. more...
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- 2012
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32. Differential gene expression of C-type natriuretic peptide and its related molecules in dilated and ischemic cardiomyopathy. A new option for the management of heart failure
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Miguel Rivera, Ana Ortega, José Ramón González-Juanatey, Maria Micaela Molina-Navarro, Manuel Portolés, Francisca Lago, Esther Roselló-Lletí, Estefanía Tarazón, and Ignacio Sánchez-Lázaro
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Adult ,Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Management of heart failure ,Myocardial Ischemia ,Internal medicine ,Gene expression ,Humans ,Medicine ,RNA, Messenger ,Receptor ,Heart Failure ,chemistry.chemical_classification ,Ischemic cardiomyopathy ,business.industry ,Disease Management ,Natriuretic Peptide, C-Type ,Genetic Therapy ,Middle Aged ,medicine.disease ,Endocrinology ,Enzyme ,Gene Expression Regulation ,C-type natriuretic peptide ,chemistry ,Heart failure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Published
- 2014
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33. KRAS mutations as a prognostic factor after metastasectomy in colorectal cancer patients
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G. Soler, M. Martinez Villacampa, Carlos Ferreira dos Santos, Alexandre Teule, N. Mulet Margalef, J. M. Perez, Ana Ortega, J. Torras, Xavier Sanjuan, M. Bergamino, J.C. Ruffinelli Rodriguez, R. Salazar, Emilio Ramos, M. Domenech Viñolas, and María Rosario Varela more...
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Oncology ,Prognostic factor ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,Hematology ,medicine.disease_cause ,medicine.disease ,Internal medicine ,medicine ,KRAS ,Metastasectomy ,business - Published
- 2018
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34. PCN150 - COST-EFFECTIVENESS ANALYSIS OF PHARMACOKINETIC-GUIDED (PK) 5-FLUOROURACIL (5-FU) DOSING WHEN COMBINED WITH LEUCOVORIN, IRINOTECAN AND OXALIPLATIN (FOLFIRINOX) CHEMOTHERAPY FOR ADVANCED PANCREAS CANCER
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A. Egues, L. Delgado, A. Aldaz, J. Rodriguez, and Ana Ortega
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Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,FOLFIRINOX ,Health Policy ,medicine.medical_treatment ,Public Health, Environmental and Occupational Health ,Cancer ,medicine.disease ,030226 pharmacology & pharmacy ,Oxaliplatin ,Irinotecan ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Fluorouracil ,Internal medicine ,medicine ,030212 general & internal medicine ,Dosing ,business ,medicine.drug - Published
- 2018
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35. New Cell Adhesion Molecules in Human Ischemic Cardiomyopathy. PCDHGA3 Implications in Decreased Stroke Volume and Ventricular Dysfunction
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Manuel Portolés, Estefanía Tarazón, José Anastasio Montero, Esther Roselló-Lletí, Ana Ortega, Miguel Rivera, María García-Manzanares, Carolina Gil-Cayuela, and Juan Cinca
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0301 basic medicine ,Male ,Pathology ,Molecular biology ,Physiology ,Myocardial Ischemia ,Gene Expression ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Nervous System ,0302 clinical medicine ,Sequencing techniques ,Ventricular Dysfunction ,Medicine and Health Sciences ,lcsh:Science ,Multidisciplinary ,Ejection fraction ,Cell adhesion molecule ,Gap Junctions ,Heart ,RNA sequencing ,Stroke volume ,Hematology ,Middle Aged ,Cadherins ,Electrophysiology ,Cardiology ,Female ,Anatomy ,Junctional Complexes ,Cardiomyopathies ,Research Article ,medicine.medical_specialty ,Cell Physiology ,Blotting, Western ,Diastole ,Cadherin Related Proteins ,Neurophysiology ,Biology ,Adherens junction ,03 medical and health sciences ,Internal medicine ,medicine ,Genetics ,Cell Adhesion ,Humans ,Cell adhesion ,Ischemic cardiomyopathy ,Cadherin ,Sequence Analysis, RNA ,lcsh:R ,Hemodynamics ,Biology and Life Sciences ,Stroke Volume ,Cell Biology ,Research and analysis methods ,030104 developmental biology ,Molecular biology techniques ,Synapses ,Cardiovascular Anatomy ,lcsh:Q ,Transcriptome ,Cell Adhesion Molecules ,Neuroscience - Abstract
Background Intercalated disks are unique structures in cardiac tissue, in which adherens junctions, desmosomes, and GAP junctions co-localize, thereby facilitating cardiac muscle contraction and function. Protocadherins are involved in these junctions; however, their role in heart physiology is poorly understood. We aimed to analyze the transcriptomic profile of adhesion molecules in patients with ischemic cardiomyopathy (ICM) and relate the changes uncovered with the hemodynamic alterations and functional depression observed in these patients. Methods and Results Twenty-three left ventricular tissue samples from patients diagnosed with ICM (n = 13) undergoing heart transplantation and control donors (CNT, n = 10) were analyzed using RNA sequencing. Forty-two cell adhesion genes involved in cellular junctions were differentially expressed in ICM myocardium. Notably, the levels of protocadherin PCDHGA3 were related with the stroke volume (r = -0.826, P = 0.003), ejection fraction (r = -0.793, P = 0.004) and left ventricular end systolic and diastolic diameters (r = 0.867, P = 0.001; r = 0.781, P = 0.005, respectively). Conclusions Our results support the importance of intercalated disks molecular alterations, closely involved in the contractile function, highlighting its crucial significance and showing gene expression changes not previously described. Specifically, altered PCDHGA3 gene expression was strongly associated with reduced stroke volume and ventricular dysfunction in ICM, suggesting a relevant role in hemodynamic perturbations and cardiac performance for this unexplored protocadherin. more...
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- 2016
36. New Altered Non-Fibrillar Collagens in Human Dilated Cardiomyopathy: Role in the Remodeling Process
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Ana Ortega, Esther Roselló-Lletí, Carolina Gil-Cayuela, Manuel Portolés, Francisca Lago, Juan Carlos Triviño, Luis Martínez-Dolz, Estefanía Tarazón, José Ramón González-Juanatey, and Miguel Rivera
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0301 basic medicine ,Male ,Molecular biology ,Cardiomyopathy ,lcsh:Medicine ,Gene Expression ,Apoptosis ,030204 cardiovascular system & hematology ,Molecular biology assays and analysis techniques ,Biochemistry ,Polymerase Chain Reaction ,Extracellular matrix ,0302 clinical medicine ,Fibrosis ,Gene expression ,Medicine and Health Sciences ,lcsh:Science ,Dilated Cardiomyopathy ,Multidisciplinary ,Cell Death ,Nucleic acid analysis ,Ventricular Remodeling ,Dilated cardiomyopathy ,Heart ,RNA analysis ,Middle Aged ,medicine.anatomical_structure ,Cell Processes ,cardiovascular system ,Female ,Collagen ,Anatomy ,Cardiomyopathies ,Research Article ,Adult ,Cardiomyopathy, Dilated ,medicine.medical_specialty ,Cardiac Ventricles ,Cardiology ,03 medical and health sciences ,Internal medicine ,medicine ,Genetics ,Humans ,Ventricular remodeling ,Ischemic cardiomyopathy ,business.industry ,lcsh:R ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,Research and analysis methods ,030104 developmental biology ,Endocrinology ,Molecular biology techniques ,Ventricle ,Cardiovascular Anatomy ,lcsh:Q ,business ,Collagens ,Developmental Biology - Abstract
Background In dilated cardiomyopathy (DCM), cardiac failure is accompanied by profound alterations of extracellular matrix associated with the progression of cardiac dilation and left ventricular (LV) dysfunction. Recently, we reported alterations of non-fibrillar collagen expression in ischemic cardiomyopathy linked to fibrosis and cardiac remodeling. We suspect that expression changes in genes coding for non-fibrillar collagens may have a potential role in DCM development. Objectives This study sought to analyze changes in the expression profile of non-fibrillar collagen genes in patients with DCM and to examine relationships between cardiac remodeling parameters and the expression levels of these genes. Methods and Results Twenty-three human left ventricle tissue samples were obtained from DCM patients (n = 13) undergoing heart transplantation and control donors (n = 10) for RNA sequencing analysis. We found increased mRNA levels of six non-fibrillar collagen genes, such as COL4A5, COL9A1, COL21A1, and COL23A1 (P < 0.05 for all), not previously described in DCM. Protein levels of COL8A1 and COL16A1 (P < 0.05 for both), were correspondingly increased. We also identified TGF-beta 1 significantly upregulated and related to both COL8A1 and COL16A1. Interestingly, we found a significant relationship between LV mass index and the gene expression level of COL8A1 (r = 0.653, P < 0.05). Conclusions In our research, we identified new non-fibrillar collagens with altered expression in DCM, being COL8A1 overexpression directly related to LV mass index, suggesting that they may be involved in the progression of cardiac dilation and remodeling. more...
- Published
- 2016
37. A simple validated method for predicting the risk of hospitalization for worsening of heart failure in ambulatory patients : the Redin-SCORE
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Manuel Gómez-Bueno, Andreu Ferrero-Gregori, Manuel Portoles, Juan Francisco Delgado Jiménez, Ana Fernández-Palacín, Rafael Vazquez-Garcia, Julián Pérez-Villacastín, Montserrat Batlle, Esther Sanz-Girgas, Pamela Lear, Miquel Vives-Borrás, Rafael Salguero Bodes, Pere Pericas, Pere Torán-Monserrat, Leif Hove-Madsen, Domingo A. Pascual Figal, Luis Martinez-Dolz, Felix Perez-Villa, Esther Roselló-Lletí, Violeta Sanchez, Jaume Aguero, Isabel Hernández-Martín, José Ramón González Juanatey, Jesus Alvarez-Garcia, Dulcenombre Gomez-Garre, María Eugenia Vázquez Mosquera, Alfredo Bardaji, Jorge G. Quintanilla, Ana Ortega, Fernando Arribas, María Amparo Pérez Navarro, and Estefanía Tarazón more...
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Male ,medicine.medical_specialty ,Prognostic variable ,Renal function ,Heart failure ,Competing risks ,Patient Readmission ,Internal medicine ,Outpatients ,Heart rate ,medicine ,Humans ,Intensive care medicine ,Aged ,Models, Statistical ,Framingham Risk Score ,business.industry ,Score ,Competing risk ,Prognosis ,medicine.disease ,Death ,Acute Disease ,Chronic Disease ,Ambulatory ,Cohort ,Cardiology ,Female ,Original Article ,Cardiology and Cardiovascular Medicine ,business ,Readmission - Abstract
AimsPrevention of hospital readmissions is one of the main objectives in the management of patients with heart failure (HF). Most of the models predicting readmissions are based on data extracted from hospitalized patients rather than from outpatients. Our objective was to develop a validated score predicting 1-month and 1-year risk of readmission for worsening of HF in ambulatory patients. Methods and resultsA cohort of 2507 ambulatory patients with chronic HF was prospectively followed for a median of 3.3years. Clinical, echocardiographic, ECG, and biochemical variables were used in a competing risk regression analysis to construct a risk score for readmissions due to worsening of HF. Thereafter, the score was externally validated using a different cohort of 992 patients with chronic HF (MUSIC registry). Predictors of 1-month readmission were the presence of elevated natriuretic peptides, left ventricular (LV) HF signs, and estimated glomerular filtration rate (eGFR) 26mm/m(2), heart rate >70 b.p.m., LV HF signs, and eGFR 5% event rate) for 1-month HF readmission. Likewise, low-risk (7.8%), intermediate-risk (15.6%) and high-risk groups (26.1%) were identified for 1-year HF readmission risk. The C-statistics remained consistent after the external validation ( more...
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- 2015
38. Patients with Dilated Cardiomyopathy and Sustained Monomorphic Ventricular Tachycardia Show Up-Regulation of KCNN3 and KCNJ2 Genes and CACNG8-Linked Left Ventricular Dysfunction
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Manuel Portolés, Francisca Lago, Carolina Gil-Cayuela, Juan Cinca, Luis Martínez-Dolz, Ana Ortega, Estefanía Tarazón, Miguel Rivera, Esther Jorge, J.R. Gonzalez-Juanatey, and Esther Roselló-Lletí
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Tachycardia ,Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Small-Conductance Calcium-Activated Potassium Channels ,Cardiomyopathy ,lcsh:Medicine ,Ventricular Dysfunction, Left ,Internal medicine ,medicine ,Humans ,Potassium Channels, Inwardly Rectifying ,lcsh:Science ,Multidisciplinary ,Ejection fraction ,Voltage-dependent calcium channel ,Cardiac cycle ,Voltage-gated ion channel ,business.industry ,Gene Expression Profiling ,lcsh:R ,Dilated cardiomyopathy ,Middle Aged ,medicine.disease ,Up-Regulation ,Endocrinology ,Heart failure ,Cardiology ,Tachycardia, Ventricular ,cardiovascular system ,Female ,lcsh:Q ,Calcium Channels ,medicine.symptom ,business ,Research Article - Abstract
Aims Disruptions in cardiac ion channels have shown to influence the impaired cardiac contraction in heart failure. We sought to determine the altered gene expression profile of this category in dilated cardiomyopathy (DCM) patients and relate the altered gene expression with the clinical signs present in our patients, such as ventricular dysfunction and sustained monomorphic ventricular tachycardia (SMVT). Methods and Results Left ventricular (LV) tissue samples were used in RNA-sequencing technique to elucidate the transcriptomic changes of 13 DCM patients compared to controls (n = 10). We analyzed the differential gene expression of cardiac ion channels, and we found a total of 34 altered genes. We found that the calcium channel CACNG8 mRNA and protein levels were down-regulated and highly and inversely related with LV ejection fraction (LVEF) (r = -0.78, P more...
- Published
- 2015
39. Radical chemoradiotherapy for patients with locally advanced esophageal cancer. Long-term follow up of an ambispective study
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Olbia Serra, Marta Domenech Viñolas, Maica Galán, Mariona Calvo, Manglio Rizzo, L. Aliste, Kevin Molina, Isabel Padrol, Maria Borràs Josep, Nuria Virgili, Milana Bergamino Sirven, Gloria Creus, Ana Ortega Franco, L. Farran, Maria Boladeras Ana, and Gloria Hormigo more...
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Oncology ,medicine.medical_specialty ,business.industry ,Long term follow up ,Internal medicine ,medicine ,Locally advanced ,Hematology ,Esophageal cancer ,medicine.disease ,business ,Chemoradiotherapy - Published
- 2017
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40. Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys
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Ismael González-García, Joaquín Pastor, Kelli L. Vaughan, Sarah J. Mitchell, Julie A. Mattison, Elena Lopez-Guadamillas, Ana Ortega-Molina, Sonia Sánchez Martínez, Maribel Muñoz-Martin, Manuel Serrano, David Cebrián, Rafael de Cabo, Miguel López, Gema Iglesias, Mark D. Szarowicz, and Vincent M. Gutierrez more...
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medicine.medical_specialty ,Indazoles ,Physiology ,Immunoblotting ,Mice, Obese ,Biology ,Mass Spectrometry ,Insulin resistance ,Internal medicine ,medicine ,Animals ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Obese Mice ,Adiposity ,Phosphoinositide-3 Kinase Inhibitors ,Metabolic Syndrome ,Sulfonamides ,Histological Techniques ,Imidazoles ,Cell Biology ,medicine.disease ,Obesity ,Macaca mulatta ,Endocrinology ,Liver ,Pyrazines ,Lean body mass ,Metabolic syndrome ,Thermogenesis ,Homeostasis - Abstract
SummaryGenetic inhibition of PI3K signaling increases energy expenditure, protects from obesity and metabolic syndrome, and extends longevity. Here, we show that two pharmacological inhibitors of PI3K, CNIO-PI3Ki and GDC-0941, decrease the adiposity of obese mice without affecting their lean mass. Long-term treatment of obese mice with low doses of CNIO-PI3Ki reduces body weight until reaching a balance that is stable for months as long as the treatment continues. CNIO-PI3Ki treatment also ameliorates liver steatosis and decreases glucose serum levels. The above observations have been recapitulated in independent laboratories and using different oral formulations of CNIO-PI3Ki. Finally, daily oral treatment of obese rhesus monkeys for 3 months with low doses of CNIO-PI3Ki decreased their adiposity and lowered their serum glucose levels, in the absence of detectable toxicities. Therefore, pharmacological inhibition of PI3K is an effective and safe anti-obesity intervention that could reverse the negative effects of metabolic syndrome in humans. more...
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- 2014
41. Effect of high extracellular Ca2+ levels in spontaneously hypertensive rat aorta
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Ana Ortega Mateo and María Amaya Aleixandre de Artiñano
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Male ,Dihydropyridines ,medicine.medical_specialty ,Endothelium ,Indomethacin ,chemistry.chemical_element ,Aorta, Thoracic ,In Vitro Techniques ,Calcium ,Rats, Inbred WKY ,Methoxamine ,Potassium Chloride ,Phenylephrine ,chemistry.chemical_compound ,Spontaneously hypertensive rat ,Rats, Inbred SHR ,Internal medicine ,medicine ,Extracellular ,Animals ,Vasoconstrictor Agents ,Pharmacology ,Dose-Response Relationship, Drug ,business.industry ,Endothelium-derived relaxing factor ,Rats ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Vasoconstriction ,Hypertension ,cardiovascular system ,Endothelium, Vascular ,medicine.symptom ,business ,medicine.drug - Abstract
The release of endothelial relaxing factors has been suggested to be important in modulating the inhibition of the contractile activity caused by the increase in extracellular Ca 2+ concentration in arterial tissue. Since the hypertensive process in spontaneously hypertensive rats (SHR) could be associated with the release of endothelial vasoconstrictor factors (mainly cyclooxygenase-dependent endoperoxides and endothelin-1), we studied the contractile responses to KCl, methoxamine and phenylephrine in different aorta ring preparations (intact, de-endothelized, 10 −5 M indomethacin-treated, 10 −6 M CGS-27830 [meso-1,4-dihydro-5-methoxycarbonyl-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridine carboxylic acid anhydride]-treated, and treated simultaneously with 10 −5 M indomethacin and 10 −6 M CGS-27830) from SHR and normotensive Wistar Kyoto rats (WKY), at various Ca 2+ concentrations (1.25, 2.5, 5 and 10 mM) in the organ bath. In endothelium-intact preparations from WKY rats we observed a decrease in KCl, methoxamine and phenylephrine contractions with high Ca 2+ concentrations (5 and 10 mM), but in the endothelium-intact preparations from SHR, the increase in extracellular Ca 2+ concentration potentiated methoxamine contractions and caused no change in KCl and phenylephrine contractions. When the endothelium was disrupted in preparations from both WKY rats and SHR, we observed a decrease in KCl and methoxamine contractions with high Ca 2+ concentrations. The decrease in phenylephrine contractions caused by high Ca 2+ concentrations was clear in de-endothelized preparations from WKY rats but slight in de-endothelized preparations from SHR. In all indomethacin- and CGS-27830-treated preparations, and also in the preparations from WKY rats and SHR treated with both drugs, we observed a decrease in all the contractile responses with increased Ca 2+ concentration. Besides, there was a clear reduction in the responses of the α 1 -adrenoceptor agonists in the WKY and SHR preparations treated with both drugs. The results indicate that, in the hypertensive arteries, endothelium-derived contractile factors can counteract the relaxing effect of high extracellular Ca 2+ concentrations. more...
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- 2001
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42. A Multinational Study to Measure the Value that Patients with Cancer Place on Improved Emesis Control Following Cisplatin Chemotherapy
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Maria Spinthouri, Renoto Ciotti, Antonello Quadri, Roberto Labianca, Lycurgus Liaropoulos, Ana Ortega, George Dranitsaris, and Pauline Leung
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Male ,Oncology ,Canada ,medicine.medical_specialty ,Vomiting ,medicine.drug_class ,Nausea ,medicine.medical_treatment ,jel:D ,Antineoplastic Agents ,jel:C ,jel:I ,jel:I1 ,Neoplasms ,Internal medicine ,medicine ,Humans ,Antiemetic ,Dolasetron ,Pharmacology ,Cisplatin ,Chemotherapy ,jel:Z ,business.industry ,Antiemetics, Nausea, Neurokinin 1 antagonists, Pharmacoeconomics, Quality of life, Vomiting ,Health Policy ,Public Health, Environmental and Occupational Health ,Middle Aged ,jel:I11 ,Europe ,jel:I18 ,jel:I19 ,Anesthesia ,Income ,Quality of Life ,Antiemetics ,Female ,Tropisetron ,NK1 receptor antagonist ,medicine.symptom ,business ,Attitude to Health ,medicine.drug - Abstract
The neurokinin-1 (NK1) receptor antagonists are a new class of agents designed to reduce the risk of emesis following chemotherapy, particularly with cisplatin. Early data from double-blind randomised trials suggest that an orally administered NK1 antagonist can reduce the absolute risk of acute and delayed emesis following cisplatin by 20 and 30%, respectively.To measure the value that patients with cancer place on improved emesis control and quality of life.Willingness-to-pay analysis.Five study sites in Canada, Italy, Spain and Greece.245 patients with cancer either receiving chemotherapy with cisplatin or who had received cisplatin-based chemotherapy within the previous 6 months.After background information had been presented, patients were asked to define the maximum that they would pay per day for a drug that reduced their risk of acute and delayed (days 2 to 5) emesis by 20 and 30%, respectively. Costs were converted to US dollars ($US) using year 2000 exchange rates.For a 20% improvement in acute emesis, Canadian, Italian and Spanish patients with cancer were willing to pay $US46, $US34 and $US63 per day, respectively, compared with $US8 for patients from Greece (p0.001). For a 30% improvement in delayed emesis, Canadian, Italian and Spanish patients with cancer were also willing to pay more than their Greek counterparts (SUS41, $US31, $US50 and $US9 daily for 4 days, respectively; p0.001). These significant differences in patient value between countries remained, even after adjusting for socioeconomic variables and previous history of emesis.There are substantial cultural differences in how patients with cancer value benefit and improved quality of life. Since the majority of the world's population resides outside North America and Western Europe, there may be a need to re-evaluate perceived levels of patient benefit and measures of quality of life. more...
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- 2001
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43. Effects of Hepatic Function on Vancomycin Pharmacokinetics in Patients With Cancer
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Antonio Brugarolas, A Idoate, Joaquín Giráldez, Ana Ortega, and Azucena Aldaz
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Population ,Pharmacology ,Models, Biological ,Gastroenterology ,Pharmacokinetics ,Vancomycin ,Neoplasms ,Internal medicine ,Ascites ,medicine ,Humans ,Pharmacology (medical) ,In patient ,Dosing ,education ,Aged ,education.field_of_study ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Anti-Bacterial Agents ,Liver ,Linear Models ,Female ,Liver function ,medicine.symptom ,business ,Liver Failure ,medicine.drug - Abstract
Vancomycin is widely used in the prophylaxis and treatment of infections in neutropenic patients with cancer. The objective of this study was to analyze liver damage effects on vancomycin pharmacokinetics and determine the necessity for liver function evaluation when selecting vancomycin dosing schedules in these patients. A population pharmacokinetic analysis was performed using the global two-stage method. To this purpose serum vancomycin concentrations from 154 cancer patients were measured and individual vancomycin pharmacokinetic parameters were estimated by the Sawchuk and Zaske method. Mean and standard deviation of the vancomycin pharmacokinetic parameters were estimated for various subgroups of patients classified according to the degree of liver damage. Then a multiple linear regression analysis was performed to select the best predictive models for vancomycin clearance (Clvan) and steady state distribution volume (V). Results revealed that Clvan is not influenced by liver failure. Differences in V between patients with and without hepatic failure were initially observed, but these disappeared when patients with ascites were excluded. In conclusion, vancomycin dosing schedule does not need to be modified for patients with liver failure, with the exception of patients with ascites. more...
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- 2000
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44. What are cancer patients willing to pay for prophylactic epoetin alfa?
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Ana Ortega, Anitasha L. V. Puodziunas, and George Dranitsaris
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Male ,Cancer Research ,medicine.medical_specialty ,Anemia ,Cost-Benefit Analysis ,medicine.medical_treatment ,Antineoplastic Agents ,Sensitivity and Specificity ,Life Expectancy ,Willingness to pay ,Neoplasms ,Internal medicine ,medicine ,Humans ,Erythropoietin ,Health Services Needs and Demand ,Chemotherapy ,Myelosuppressive Chemotherapy ,Cost–benefit analysis ,business.industry ,Prescription Fees ,Epoetin alfa ,Cancer ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Surgery ,Epoetin Alfa ,Socioeconomic Factors ,Oncology ,Multivariate Analysis ,Cohort ,Hematinics ,Income ,Female ,Cisplatin ,Erythrocyte Transfusion ,business ,medicine.drug - Abstract
BACKGROUND Anemia, one of the most common complications of cancer chemotherapy, has been managed with red blood cell (RBC) transfusions. As an alternative, the agent epoetin alfa has the potential to reduce the transfusion requirements of patients receiving cancer chemotherapy. To estimate the value that cancer patients place on the drug, an economic analysis using the concept of willingness to pay (WTP) was conducted. METHODS The method of WTP was used within the framework of a classical cost-benefit analysis to estimate the net cost or benefit of administering prophylactic epoetin alfa to cancer patients. This estimate included the direct cost of epoetin alfa administration and savings secondary to reduced RBC transfusions. A cohort of 100 cancer patients who received or were scheduled to receive cisplatin or noncisplatin chemotherapy (50 per group) were then interviewed to measure the maximum WTP (net benefit) that they experienced with epoetin alfa. RESULTS Regarding the benefits they would experience after 3 months of epoetin alfa administration, patients receiving cisplatin and noncisplatin therapy stated that they would be willing to pay an average of 587 U.S. dollars (U.S.$587) (95%CI: $300-$875) and U.S.$613 (95%CI: $324-$902), respectively. These benefits were then subtracted from the total cost of the drug when administered to patients receiving cisplatin (U.S.$3530) and noncisplatin (U.S.$3653) therapy. This produced a net incremental treatment cost of U.S.$2943 (95%CI: $2655-$3230) and U.S.$3039 (95%CI: $2750-$3328) for the respective treatment groups. CONCLUSIONS The results of the current study suggest that the routine administration of epoetin alfa to cancer patients receiving myelosuppressive chemotherapy is a highly resource-intensive treatment policy with modest benefit to patients. Additional research is required to identify high risk patient subgroups who would benefit most from the drug. [See editorial on pages 2427-9, this issue.] Cancer 1998;83:2588-2596. © 1998 American Cancer Society. more...
- Published
- 1998
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45. Predictors of multivessel disease in cases of acute chest pain
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Ana Ortega, Juan-Luis Delcán, José-Luis Cantalapiedra, Juan-Ramón Rey, Esteban López de Sá, Jaime Fernández-Bobadilla, Javier Fernández-Portales, and Raúl Moreno
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Ischemia ,Disease ,Coronary artery disease ,Predictive Value of Tests ,Internal medicine ,Heart rate ,medicine ,Humans ,Angina, Unstable ,cardiovascular diseases ,Myocardial infarction ,Risk factor ,Aged ,Retrospective Studies ,Cardiac catheterization ,business.industry ,Unstable angina ,Middle Aged ,Prognosis ,medicine.disease ,Heart Function Tests ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Patients with unstable angina not showing ischemia at the exercise treadmill test after medical stabilization usually have a low-risk coronary anatomy. However, some of them have multivessel disease, and it is not known what characteristics are associated with the extension of the coronary artery disease in this subset of patients. Objective: To determine clinical and exertional characteristics associated with multivessel disease in patients with unstable angina and a negative exercise test. Methods: 312 hospitalised patients with unstable angina and a negative exercise test who had undergone cardiac catheterization were reviewed. The relationship between coronariographic findings (presence of multivessel disease) and clinical characteristics, exercise parameters and left ventricular function was studied. Results: Multivessel disease was present in 97 patients (31%). The following variables were associated with the presence of multivessel disease: age more than 65 years old, previous myocardial infarction, previous admissions because of unstable angina, peripheral artery disease, presence of more than two coronary risk factors, left ventricular dysfunction, functional capacity less than 6 METS, duration of exercise less than 8 min and less than 85% of the maximum heart rate. Multivariate analysis showed, as independent predictors of multivessel disease: previous myocardial infarction, previous admissions because of unstable angina, presence of more than two coronary risk factors and peripheral artery disease. Conclusions: In patients with medically stabilized unstable angina and a negative exercise test, previous myocardial infarction, previous admissions because of unstable angina, presence of more than two coronary risk factors and peripheral artery disease, but not exercise parameters, are independent predictors of multivessel disease. more...
- Published
- 1998
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46. HIGHLIGHTS ON ENDOTHELINS: A REVIEW
- Author
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Ana Ortega Mateo and Amaya Aleixandre De Artiñano
- Subjects
Endothelin Receptor Antagonists ,medicine.hormone ,medicine.medical_specialty ,Vascular smooth muscle ,Endothelium ,Molecular Sequence Data ,Vasodilation ,Prostacyclin ,Muscle, Smooth, Vascular ,Endothelins ,Internal medicine ,Animals ,Humans ,Medicine ,Amino Acid Sequence ,Receptor ,Pharmacology ,Endothelin-1 ,Receptors, Endothelin ,business.industry ,Endothelin 1 ,medicine.anatomical_structure ,Endocrinology ,Cardiovascular Diseases ,Endothelium, Vascular ,business ,Endothelin receptor ,medicine.drug - Abstract
The endothelins (ET) are a family of contractile peptides made up of 21 amino acids. They are synthesised from larger precursors and they are expressed in different tissues. ET-1 is synthesised in endothelial cells by means of a specific endothelin converting enzyme and it is assumed that most of it is secreted into the basolateral compartment. It acts in a paracrine manner on the ETA and ETB2 receptors located on the surface of the vascular smooth muscle to elicit an increase in intracellular calcium and vasoconstriction. The circulating ET-1 can also activate endothelial ETC and ETB1 receptors releasing vascular smooth muscle relaxing factors, such as nitric oxide and prostacyclin. At present, it is generally accepted that ET-1 is a vasodilator in physiological conditions acting on endothelium ETB1 receptors. Nevertheless, in pathological situations such as hypertension, heart failure, acute myocardial infarction, acute renal failure and vasospastic conditions (Raynaud's disease and subarachnoid haemorrhage), ET-1 levels increase and it binds to the receptors present in vascular smooth muscle in such a way that its vasoconstrictor effect is manifested. Currently, experimental and clinical evidence exists to support the importance of the development of drugs that block the production or actions of ET for use in cardiovascular medicine, particularly in conditions in which these peptides are clearly implicated. more...
- Published
- 1997
- Full Text
- View/download PDF
47. Cost–Utility Analysis of Paclitaxel in Combination with Cisplatin for Patients with Advanced Ovarian Cancer
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Ana Ortega, Amit M. Oza, Jeremy Sturgeon, H. J. Sutherland, and George Dranitsaris
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Adult ,Oncology ,Canada ,medicine.medical_specialty ,Paclitaxel ,Cyclophosphamide ,Cost-Benefit Analysis ,Health Status ,medicine.medical_treatment ,Disease-Free Survival ,Drug Costs ,Decision Support Techniques ,chemistry.chemical_compound ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Ovarian Neoplasms ,Cisplatin ,Cost–utility analysis ,Chemotherapy ,business.industry ,Standard treatment ,Decision Trees ,Obstetrics and Gynecology ,Middle Aged ,Antineoplastic Agents, Phytogenic ,Chemotherapy regimen ,Surgery ,Treatment Outcome ,chemistry ,Cohort ,Female ,business ,medicine.drug - Abstract
The standard treatment for patients with advanced ovarian cancer (AOC) has been cyclophosphamide and cisplatin (CP). Recently, the results of a large randomized comparative trial demonstrated that the combination of paclitaxel and cisplatin (TP) provided a progression-free survival benefit of 5 months. In this study, a cost–utility analysis was performed from a Canadian health care system perspective to estimate the incremental cost-effectiveness of the TP combination. Twelve AOC patients who received treatment with TP were matched for age and disease stage on a 1-to-2 basis with a CP control. Total hospital resource consumption was then collected for all patients. Treatment preferences were estimated from a cohort of 20 patients and 40 healthy female volunteers using the time trade-off technique. The outcomes were then generated through a decision-analytic model. First-line treatment costs with TP were approximately fourfold greater on a per-cycle basis than the CP alternative (Can$1911 vs Can$459). When progression-free survival benefit and patient treatment preferences were incorporated into the analysis, the results of the decision model revealed an incremental cost between Can$12,000 and Can$24,000 per quality-adjusted progression-free year with the TP protocol. Even though the TP combination has a considerably higher drug acquisition cost, the results of the current analysis suggest that this new chemotherapy regimen does provide patients with substantial quality-adjusted progression-free survival benefit at a reasonable cost to the Canadian health care system. more...
- Published
- 1997
- Full Text
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48. MA06.07 Impact of Type 2 Diabetes Mellitus and Its Metabolic Control on Prognosis of Unresectable Non-Small Cell Lung Cancer Patients
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Marta Domenech Viñolas, I. Brao, Ernest Nadal, Eduard Montanya, Aj Rullan, Ramon Palmero, Felipe Cardenal, Ana Ortega Franco, Susana Padrones, Jose Carlos Ruffinelli, I. Peiró, Samantha Aso, Maria Saigi, Milana Bergamino Sirven, and Arturo Navarro-Martin more...
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Metabolic control analysis ,medicine ,Type 2 Diabetes Mellitus ,Non small cell ,business ,Lung cancer ,medicine.disease - Published
- 2017
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- View/download PDF
49. Heart failure entails significant changes in human nucleocytoplasmic transport gene expression
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Estefanía Tarazón, Pablo García-Pavía, Manuel Portolés, Miguel Rivera, José Anastasio Montero, Francisca Lago, Ana Ortega, Antonio Salvador, Esther Roselló-Lletí, Dolors Sánchez-Izquierdo, José Ramón González-Juanatey, and Maria Micaela Molina-Navarro more...
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Male ,medicine.medical_specialty ,Microarray ,Heart disease ,medicine.medical_treatment ,Active Transport, Cell Nucleus ,In Vitro Techniques ,Transcriptome ,Internal medicine ,Medicine ,Humans ,Heart transplantation ,Heart Failure ,Ischemic cardiomyopathy ,business.industry ,Dilated cardiomyopathy ,Middle Aged ,medicine.disease ,Cell biology ,Endocrinology ,Gene Expression Regulation ,Nucleocytoplasmic Transport ,Heart failure ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Heart failure (HF) induces alterations in nucleocytoplasmic transport, which is essential to the cardiomyocyte biology. The objective of this study was to analyze the changes in gene expression in human HF, particularly focusing on nucleocytoplasmic transport-related genes.29 RNA heart samples from dilated cardiomyopathy (DCM, n = 12) and ischemic cardiomyopathy (ICM, n = 12) patients undergoing heart transplantation and control donors (CNT, n = 5) were extracted to perform a microarray profiling using Affymetrix Human Gene® 1.0 ST arrays. We focused on the study of 5 nucleocytoplasmic transport-related genes, since this functional category has not previously been studied in HF. XPO1, GABPB2, and RANBP17 were upregulated, while KALRN was downregulated in both DCM and ICM, and XPO5 only in DCM. Validation of the results by RT-qPCR increasing the total heart samples up to 41 showed a high degree of consistency with microarray results. Moreover, we observed a strong relationship between the XPO1 mRNA and robust left ventricular function parameters in ICM: left ventricular end-systolic (r = 0.81, p0.0001) and end-diastolic diameters (r = 0.80, p0.0001), and ejection fraction (r = -0.57, p0.05).We show that the expression of nucleocytoplasmic transport-related genes is altered in HF. Furthermore, XPO1 mRNA level is closely related with robust left ventricular function parameters in ICM patients. These changes may help to distinguish DCM and ICM in HF at the level of the transcriptome and provide a base for novel therapeutic approaches. more...
- Published
- 2013
50. Breast-GPA and type of treatment predictors of survival in brain metastasis patients
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Miguel Gil, Roser Velasco, Sabela Recalde, Idoia Morilla, Miquel Macia Garau, Sonia Pernas Simon, Noemi Vidal Sarro, Jenniffer Linares Aceituno, Valentín Navarro-Perez, Manuel Galdeano, Ana Lucas Calduch, Ana Ortega Franco, Catalina Falo Zamora, Agostina Stradella, and Adela Fernandez more...
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Oncology ,Cancer Research ,Pathology ,medicine.medical_specialty ,business.industry ,Internal medicine ,Medicine ,skin and connective tissue diseases ,business ,medicine.disease ,Metastatic breast cancer ,Brain metastasis - Abstract
e13530Background: brain metastases (BM) occur in 15-30% of patients with metastatic breast cancer (MBC). In spite of improvements in the treatment, the development of BM is still being a major limi... more...
- Published
- 2016
- Full Text
- View/download PDF
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