Institute Investigacion Sanitaria Of Santiago Idis

Santiago de Compostela, Spain

Institute Investigacion Sanitaria Of Santiago Idis

Santiago de Compostela, Spain
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Roca-Rivada A.,Institute Investigacion Sanitaria Of Santiago Idis | Roca-Rivada A.,CIBER ISCIII | Bravo S.B.,Institute Investigacion Sanitaria Of Santiago Of Compostela Idis | Perez-Sotelo D.,Institute Investigacion Sanitaria Of Santiago Idis | And 9 more authors.
Scientific Reports | Year: 2015

In the context of obesity, strong evidences support a distinctive pathological contribution of adipose tissue depending on its anatomical site of accumulation. Therefore, subcutaneous adipose tissue (SAT) has been lately considered metabolically benign compared to visceral fat (VAT), whose location is associated to the risk of developing cardiovascular disease, insulin resistance, and other associated comorbidities. Under the above situation, the chronic local inflammation that characterizes obese adipose tissue, has acquired a major role on the pathogenesis of obesity. In this work, we have analyzed for the first time human obese VAT and SAT secretomes using an improved quantitative proteomic approach for the study of tissue secretomes, Comparison of Isotope-Labeled Amino acid Incorporation Rates (CILAIR). The use of double isotope-labeling-CILAIR approach to analyze VAT and SAT secretomes allowed the identification of location-specific secreted proteins and its differential secretion. Additionally to the very high percentage of identified proteins previously implicated in obesity or in its comorbidities, this approach was revealed as a useful tool for the study of the obese adipose tissue microenvironment including extracellular matrix (ECM) remodeling and inflammatory status. The results herein presented reinforce the fact that VAT and SAT depots have distinct features and contribute differentially to metabolic disease. © 2015, Nature Publishing Group. All rights reserved.


Gayoso-Diz P.,Hospital Clinico Universitario | Gayoso-Diz P.,Institute Investigacion Sanitaria Of Santiago Idis | Rodriguez-Alvarez M.X.,Hospital Clinico Universitario | Rodriguez-Alvarez M.X.,Institute Investigacion Sanitaria Of Santiago Idis | And 6 more authors.
BMC Endocrine Disorders | Year: 2013

Background: Insulin resistance has been associated with metabolic and hemodynamic alterations and higher cardio metabolic risk. There is great variability in the threshold homeostasis model assessment of insulin resistance (HOMA-IR) levels to define insulin resistance. The purpose of this study was to describe the influence of age and gender in the estimation of HOMA-IR optimal cut-off values to identify subjects with higher cardio metabolic risk in a general adult population. Methods: It included 2459 adults (range 20-92 years, 58.4% women) in a random Spanish population sample. As an accurate indicator of cardio metabolic risk, Metabolic Syndrome (MetS), both by International Diabetes Federation criteria and by Adult Treatment Panel III criteria, were used. The effect of age was analyzed in individuals with and without diabetes mellitus separately. ROC regression methodology was used to evaluate the effect of age on HOMA-IR performance in classifying cardio metabolic risk. Results: In Spanish population the threshold value of HOMA-IR drops from 3.46 using 90th percentile criteria to 2.05 taking into account of MetS components. In non-diabetic women, but no in men, we found a significant non-linear effect of age on the accuracy of HOMA-IR. In non-diabetic men, the cut-off values were 1.85. All values are between 70th-75th percentiles of HOMA-IR levels in adult Spanish population.Conclusions: The consideration of the cardio metabolic risk to establish the cut-off points of HOMA-IR, to define insulin resistance instead of using a percentile of the population distribution, would increase its clinical utility in identifying those patients in whom the presence of multiple metabolic risk factors imparts an increased metabolic and cardiovascular risk. The threshold levels must be modified by age in non-diabetic women. © 2013 Gayoso-Diz et al.; licensee BioMed Central Ltd.


Perez-Sayans M.,Institute Investigacion Sanitaria Of Santiago Idis | Garcia-Garcia A.,Institute Investigacion Sanitaria Of Santiago Idis | Scozzafava A.,University of Florence | Supuran C.T.,University of Florence
Current Pharmaceutical Design | Year: 2012

Two of the key proteins involved in tumor acidification are the V-ATPase and the tumor-associated carbonic anhydrases (CAs), such as CA IX and XII. Although there are many chemical classes of V-ATPase inhibitors, most of them are toxic for mammals and their potential use as antitumor drugs is limited. The proton pump inhibitors (PPIs), a class of antiulcer agents in clinical use for more than 30 years, have been proven to be useful in modulating tumor acidification, presumably by inactivating V-ATPase, through modification of Cys residues essential for the catalytic activity of the ATPase. This mechanism of action has yet to be demonstrated, but several recent clinical trials showed the efficacity of this approach for inhibiting the growth of tumors and their re-sensitivization to anticancer drugs such as cisplatin, or doxorubicin. Further studies are anyhow warranted to better understand the role of PPIs in the management of cancer. The monoclonal antibodies (mAbs) girentuximab, and its 124I -radiolabelled variant targeting CA IX are in advanced clinical trials both for the treatment and imaging of hypoxic tumors overexpressing CA IX. Small molecule CA IX inhibitors, of sulfonamide and cou-marin type are in advanced preclinical evaluation, both for imaging and treatment of solid tumors and metastases in which CA IX/XII are present. As cancer is still a big clinical problem and most of the hypoxic tumors do not respond to classical anticancer drugs or to radiotherapy, the development of alternative anticancer approaches, such as interference with tumor acidification through inhibition of V-ATPase and CAs, represents an interesting avenue for future research. © 2012 Bentham Science Publishers.


Inacio V.,University of Lisbon | Gonzalez-Manteiga W.,University of Santiago de Compostela | Febrero-Bande M.,University of Santiago de Compostela | Gude F.,Hospital Clinico Universitario Of Santiago | And 2 more authors.
Biostatistics | Year: 2012

The receiver operating characteristic (ROC) curve is the most widely used measure for evaluating the discriminatory performance of a continuous marker. Often, covariate information is also available and several regression methods have been proposed to incorporate covariate information in the ROC framework. Until now, these methods are only developed for the case where the covariate is univariate or multivariate. We extend ROC regression methodology for the case where the covariate is functional rather than univariate or multivariate. To this end, semiparametric-and nonparametric-induced ROC regression estimators are proposed. A simulation study is performed to assess the performance of the proposed estimators. The methods are applied to and motivated by a metabolic syndrome study in Galicia (NW Spain). © 2012 The Author.


Perez-Sayans M.,Institute Investigacion Sanitaria Of Santiago Idis | Suarez-Penaranda J.M.,University of Santiago de Compostela | Pilar G.-D.,Hospital Clinico Universitario Of Santiago Of Compostela | Supuran C.T.,University of Florence | And 4 more authors.
Journal of Oral Pathology and Medicine | Year: 2012

Introduction: Carbonic anhydrases (CAs), a group of ubiquitously expressed metalloenzymes, are involved in numerous physiological and pathological processes, including tumorigenicity. Specifically, CA-IX has been primarily found in hypoxic tumor tissues. Material and methods: This is a retrospective study of tumors from the Tissue Bank of the Pathology Department of the University Hospital of Santiago de Compostela. We selected 50 oral squamous cell carcinomas (OSCCs) using Tissue Microarray (TMA) technology. The immunohistochemical study was performed to determine CA-IX expression. The resulting data were subject to statistical analysis and survival curves. Results: Of the 50 cases, 23 were detected in early stages (I and II) and 27 in advanced stages (III and IV). In the first year, almost 50% of patients in stages III-IV died, which contrasted with those patients in initial stages who registered a survival rate of 80% (P=0.019). Regarding the expression of CA-IX, nine cases (18%) were negative, 18 cases (36%) were moderate, while 23 cases (46%) were intense. Tumors in stages I-II showed a positivity of 52.6%; however, in advanced stages, the percentage reached 95.5% (P=0.002). Regarding CA-IX expression and survival, patients with tumors with strong staining had a lower average survival time (13.8months) than patients with negative or weak-moderate staining (33.4 and 32.8months, respectively), log-rank=6.1, P value=0.0484. Conclusions: Early diagnosis of these tumors is essential to improve patient survival. CA-IX expression augments with increasing tumor stage, probably related with the degree of hypoxia; thus, its measurement can be used as a prognostic factor. © 2012 John Wiley & Sons A/S.


Spugnini E.P.,Instituto Superiore Of Sanita | Sonveaux P.,Catholic University of Louvain | Stock C.,Hannover Medical School | Perez-Sayans M.,Institute Investigacion Sanitaria Of Santiago Idis | And 5 more authors.
Biochimica et Biophysica Acta - Biomembranes | Year: 2015

Although cancer is characterized by an intratumoral genetic heterogeneity, a totally deranged pH control is a common feature of most cancer histotypes. Major determinants of aberrant pH gradient in cancer are proton exchangers and transporters, including V-ATPase, Na+/H+ exchanger (NHE), monocarboxylate transporters (MCTs) and carbonic anhydrases (CAs). Thanks to the activity of these proton transporters and exchangers, cancer becomes isolated and/or protected not only from the body reaction against the growing tumor, but also from the vast majority of drugs that when protonated into the acidic tumor microenvironment do not enter into cancer cells. Proton transporters and exchangers represent a key feature tumor cells use to survive in the very hostile microenvironmental conditions that they create and maintain. Detoxifying mechanisms may thus represent both a key survival option and a selection outcome for cells that behave as unicellular microorganisms rather than belonging to an organ, compartment or body. It is, in fact, typical of malignant tumors that, after a clinically measurable yet transient initial response to a therapy, resistant tumor clones emerge and proliferate, thus bursting a more malignant behavior and rapid tumor progression. This review critically presents the background of a novel and efficient approach that aims to fight cancer through blocking or inhibiting well characterized proton exchangers and transporters active in human cancer cells. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. © 2014 Elsevier B.V.


Perez-Sayans M.,Institute Investigacion Sanitaria Of Santiago Idis | Suarez-Penaranda J.M.,Hospital Clinico Universitario Of Santiago | Pilar G.-D.,Hospital Clinico Universitario Of Santiago Of Compostela | Pilar G.-D.,Institute Investigacion Sanitaria Of Santiago Idis | And 3 more authors.
Oral Oncology | Year: 2011

The influence of c-myc in the carcinogenic process has been previously described although in the specific case of oral tumors it has been poorly tested. Myc proteins are a family of proto-oncogenes involved in the cell proliferation regulation, differentiation and apoptosis. The goal of this paper is to describe the functions of c-myc and its role as oncogene, assessing its expression by immunohistochemistry and genetic amplification studies, and studying its relationship with tumoral clinical and pathological variables, and describing genetic and molecular interactions in OSCC. © 2011 Elsevier Ltd. All rights reserved.


Rodriguez-Alvarez M.X.,University of Santiago de Compostela | Rodriguez-Alvarez M.X.,Institute Investigacion Sanitaria Of Santiago Idis | Roca-Pardinas J.,University of Vigo | Cadarso-Suarez C.,University of Santiago de Compostela | Cadarso-Suarez C.,Institute Investigacion Sanitaria Of Santiago Idis
Statistics and Computing | Year: 2011

Continuous diagnostic tests are often used to discriminate between diseased and healthy populations. The receiver operating characteristic (ROC) curve is a widely used tool that provides a graphical visualisation of the effectiveness of such tests. The potential performance of the tests in terms of distinguishing diseased from healthy people may be strongly influenced by covariates, and a variety of regression methods for adjusting ROC curves has been developed. Until now, these methodologies have assumed that covariate effects have parametric forms, but in this paper we extend the induced methodology by allowing for arbitrary non-parametric effects of a continuous covariate. To this end, local polynomial kernel smoothers are used in the estimation procedure. Our method allows for covariate effect not only on the mean, but also on the variance of the diagnostic test. We also present a bootstrap-based method for testing for a significant covariate effect on the ROC curve. To illustrate the method, endocrine data were analysed with the aim of assessing the performance of anthropometry for predicting clusters of cardiovascular risk factors in an adult population in Galicia (NW Spain), duly adjusted for age. The proposed methodology has proved useful for providing age-specific thresholds for anthropometric measures in the Galician community. © 2010 Springer Science+Business Media, LLC.


De Castro M.J.,Hospital Clinico Universitario Of Santiago Of Compostela | Pardo-Seco J.,Institute Investigacion Sanitaria Of Santiago Idis | Pardo-Seco J.,University of Santiago de Compostela | Martinon-Torres F.,Hospital Clinico Universitario Of Santiago Of Compostela | Martinon-Torres F.,Institute Investigacion Sanitaria Of Santiago Idis
Clinical Infectious Diseases | Year: 2015

Background: Bacille Calmette-Guerin (BCG) vaccination has been suggested to have nonspecific beneficial effects in children from developing countries, reducing morbidity and mortality caused by unrelated pathogens. Objective: We aimed to assess the heterologous protective effects of BCG vaccination against respiratory infection (RI) and sepsis not attributable to tuberculosis in children born in Spain. Methods: We conducted a retrospective epidemiological study using data from the Official Spanish Registry of Hospitalizations (CMBD-HA) to identify differences in hospitalization rates (HR) in BCG-vaccinated children (Basque Country, where neonatal BCG is part of the immunization schedule and has a 100% coverage) as compared to non-BCG-vaccinated children (from the rest of Spain, where BCG is not used). Results: A total of 464 611 hospitalization episodes from 1992 to 2011 were analyzed. The HR due to RI not attributable to tuberculosis in BCG-vaccinated children was significant lower compared to non-BCG-vaccinated children for all age groups, with a total preventive fraction (PF) of 41.4% (95% confidence interval: 40.3-42.5; Pvalue <.001). According to age group, PF was 32.4% (30.9-33.9; P-value <.001) for children under 1 year old, 60.1% (58.5-61.7; P-value <.001) for children between 1 and 4 years old, 66.6% (62.8-70.2; P-value <.001) for children between 5 and 9 years old, and 69.6% (63.3-75.0; P-value <.001) for children between 10 and 14 years old. The HR due to sepsis not attributable to tuberculosis in BCG-vaccinated children under 1 year of age was also significantly lower, with a PF of 52.8% (43.8-60.7; P-value <.001). Conclusions. BCG vaccination at birth may decrease hospitalization due to RI and sepsis not related to tuberculosis through heterologous protection. © 2015 The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.


Parguina A.F.,University of Santiago de Compostela | Parguina A.F.,Institute Investigacion Sanitaria Of Santiago Idis | Alonso J.,Hospital Clinico Universitario Of Santiago | Rosa I.,University of Santiago de Compostela | And 11 more authors.
Blood | Year: 2012

C-type lectin-like receptor 2 (CLEC-2) is an essential platelet-activating receptor in hemostasis and thrombosis that is activated by the snake venom rhodocytin. We present here a differential proteomic analysis of basal and rhodocytin-activated platelets with the aim of providing novel clues on CLEC-2 signaling regulation. Proteome analysis was based on 2D-DIGE, phosphotyrosine immunoprecipitations followed by 1D SDS-PAGE and mass spectrometry. Protein-protein interactions were studied by coimmunoprecipitations and a systems biology approach. Overall, we identified 132 proteins differentially regulated after CLEC-2 platelet activation, including most of the major players reported so far in the signaling cascade. In addition, we identified various proteins not previously known to participate in CLEC-2 signaling, such as the adapters Dok-2 and ADAP, tyrosine kinase Fer, and tyrosine phosphatase SHIP-1. We also report an increased association between Dok-2 and SHIP-1 in rhodocytin-stimulated platelets, which might negatively regulate CLEC-2 signaling. Moreover, we also present a comparative analysis of proteomic data for CLEC-2 and glycoprotein VI signaling. We think that our data provide thrombosis-relevant information on CLEC-2 signaling regulation, contributing to a better understanding of this important signaling cascade. © 2012 by The American Society of Hematology.

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