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Bellmunt J.,University of the Sea | Bellmunt J.,Municipal Institute for Medical Research | Maroto-Rey P.,Sant Pau Hospital | Trigo J.M.,University of Barcelona | And 5 more authors.
Clinical and Translational Oncology | Year: 2010

Aims: Our aim was to evaluate first-line treatment of metastatic renal cell carcinoma (mRCC) with sorafenib in patients unwilling to receive immunotherapy or with early intolerance to immunotherapy. Patients and methods: Patients had clear-cell mRCC with good or intermediate risk status, were unsuited to cytokine therapy due to preference or intolerance (based on <4 weeks prior immunotherapy) and had not received antiangiogenic agents. Patients received sorafenib 400 mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Results: Twenty-six evaluable patients were enrolled at six centres between March and July 2006. The most common metastatic sites were lung and bone; nine patients had one or two metastatic lesions. Median PFS was 7.5 months (95% confidence interval [CI] 5.1-17.5) and overall survival (OS) 15.4 months (95% CI 12.9-17.4). Among 21 patients evaluable for response, 19 (90.5%) experienced disease control (including one complete response; four partial responses; 14 stable disease). The majority of adverse events were grade 1-2 (87.3%). The most common were asthenia (53.0%) and diarrhoea (50.0%). Conclusion: In patients with mRCC who were unwilling to receive or intolerant to immunotherapy, treatment with sorafenib led to a high rate of disease control with toxicities that were generally mild and manageable. The PFS achieved in this essentially treatment-naïve population compares favourably with that obtained in the randomised first-line phase II study. © 2010 Feseo. Source


Cerutti A.,Catalan Institution for Research and Advanced Studies | Cerutti A.,Municipal Institute for Medical Research | Cerutti A.,Mount Sinai School of Medicine | Chen K.,Mount Sinai School of Medicine | Chorny A.,Mount Sinai School of Medicine
Annual Review of Immunology | Year: 2011

Mucosal surfaces are colonized by large communities of commensal bacteria and represent the primary site of entry for pathogenic agents. To prevent microbial intrusion, mucosal B cells release large amounts of immunoglobulin (Ig) molecules through multiple follicular and extrafollicular pathways. IgA is the most abundant antibody isotype in mucosal secretions and owes its success in frontline immunity to its ability to undergo transcytosis across epithelial cells. In addition to translocating IgA onto the mucosal surface, epithelial cells educate the mucosal immune system as to the composition of the local microbiota and instruct B cells to initiate IgA responses that generate immune protection while preserving immune homeostasis. Here we review recent advances in our understanding of the cellular interactions and signaling pathways governing IgA production at mucosal surfaces and discuss new findings on the regulation and function of mucosal IgD, the most enigmatic isotype of our mucosal antibody repertoire. © 2011 by Annual Reviews. All rights reserved. Source


Corella D.,University of Valencia | Corella D.,CIBER ISCIII | Carrasco P.,University of Valencia | Carrasco P.,CIBER ISCIII | And 23 more authors.
Journal of Lipid Research | Year: 2010

Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D = 0.88; P < 0.001). They were independently associated with higher HDL-C ( P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically signifi cant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc. Source


Mayneris-Perxachs J.,CIBER ISCIII | Guerendiain M.,University of Barcelona | Castellote A.I.,CIBER ISCIII | Castellote A.I.,University of Barcelona | And 16 more authors.
Clinical Nutrition | Year: 2014

Background & aims: The metabolic syndrome (MetS) is a clustering of various metabolic abnormalities which is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus. Due to its increasing prevalence, it has become an important public health concern. Altered fatty acid (FA) composition and desaturase activities have been associated with several metabolic diseases, including MetS. The aim of the present study was to evaluate the relationship of the plasma FA profile and desaturase activities with the MetS in a Mediterranean population at high risk of CVD. Methods: Baseline data from 427 participants aged 55-80 years who took part in the interventional PREDIMED study were obtained. Individual FA was determined in plasma and desaturase activities were estimated from product/precursor ratios. Odds ratios (OR) and partial correlation coefficients were used to examine these relations with MetS and its components, respectively. Results: We found higher levels of C14:0, C16:0, C16:1n-7, estimated δ9- or stearoyl-CoA desaturase (SCD), and estimated δ6 desaturase (D6D), and lower levels of C18:2n-6 in people with MetS compared to those without it. After adjustment for several confounders, only higher quartiles of C14:0, C16:0, C16:1n-7, and D6D were found to be associated with an increasing prevalence of MetS, while higher quartiles of C18:2n-6 were inversely associated with MetS. High proportions of C14:0, C16:0, C16:1n-7, C20:3n-6, SCD, and D6D, and decreased proportions of C18:2n-6 and estimated δ5-desaturase (D5D) were associated with adverse profiles of several metabolic risk factors. Women showed more unhealthy FA pattern and lipid profiles than men, but only among those with MetS. Conclusion: A FA composition and estimated desaturase activities consisting in high levels of SFA, SCD and D6D, and low levels of PUFA and D5D are associated with increased MetS probability and are characteristic of people presenting MetS, especially women. These findings support those observed in non-Mediterranean populations in which an altered FA profile and estimated desaturase activities are associated with MetS. © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. Source


Tresserra-Rimbau A.,University of Barcelona | Tresserra-Rimbau A.,CIBER ISCIII | Tresserra-Rimbau A.,Institute Salud Carlos III | Medina-Remon A.,University of Barcelona | And 37 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2013

Background and aims: Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. Methods and results: The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55-80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820±323mg day-1 (443±218mg day-1 of flavonoids and 304±156mg day-1 of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. Conclusion: In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil. Clinical trial registry: International Standard Randomised Controlled Trial Number (ISRCTN of London, England) 35739639. © 2012 Elsevier B.V. Source

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