Institute Of Recerca Hospital Del Mar Imim

Barcelona, Spain

Institute Of Recerca Hospital Del Mar Imim

Barcelona, Spain
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Jose A.,Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Jose A.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | Sobrevals L.,Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Sobrevals L.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | And 7 more authors.
Oncotarget | Year: 2013

Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p<0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors. © Jose et al.

PubMed | Institute Of Recerca Hospital Del Mar Imim, Hospital Universitario Virgen Of Las Nieves, University of Granada, Hospital Universitario Of Gran Canaria Dr Negrin and 7 more.
Type: Journal Article | Journal: Prostate cancer and prostatic diseases | Year: 2016

Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients.A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator.(XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and DAmico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing DAmico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002).We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.

Funtikova A.N.,Institute Of Recerca Hospital Del Mar Imim | Funtikova A.N.,CIBER ISCIII | Benitez-Arciniega A.A.,Autonomous University of Mexico State | Gomez S.F.,Institute Of Recerca Hospital Del Mar Imim | And 5 more authors.
British Journal of Nutrition | Year: 2014

Abdominal obesity is a strong predictor of metabolic disorders. Prospective data on the association between the Mediterranean diet and surrogate markers of abdominal adiposity are scarce. The present study evaluated the relationship between adherence to the Mediterranean diet and (1) changes in waist circumference (WC) and (2) 10-year incidence of abdominal obesity. We conducted a prospective, population-based study in 3058 male and female Spaniards aged 25-74 years, followed from 2000 to 2009. Dietary intake and leisure-time physical activity levels were recorded using validated questionnaires. Weight, height and WC were measured. Adherence to the Mediterranean diet, determined using the previously validated REGICOR-Mediterranean diet score (R-MDS), based on the distribution of population food intake and on the dietary recommendations (MDS-rec), was negatively associated with WC gain (P= 0.007 and 0.024, respectively) in fully adjusted models. In the multivariate logistic analysis, the odds of abdominal obesity incidence decreased across the tertiles of the R-MDS, but the association was not significant. In conclusion, adherence to the Mediterranean diet was associated with lower abdominal fat gain, but not with 10-year incidence of abdominal obesity. © The Authors 2013.

Flores-Mateo G.,Institute dInvestigacio en Atencio Primria Jordi Gol | Flores-Mateo G.,CIBER ISCIII | Grau M.,Institute Of Recerca Hospital Del Mar Imim | O'Flaherty M.,University of Liverpool | And 9 more authors.
Revista Espanola de Cardiologia | Year: 2011

Introduction and objectives: To examine the extent to which the decrease in coronary heart disease mortality rates in Spain between 1988 and 2005 could be explained by changes in cardiovascular risk factors and by the use of medical and surgical treatments. Methods: We used the previously validated IMPACT model to examine the contributions of exposure factors (risk factors and treatments) to the main outcome, changes in the mortality rates of death from coronary heart disease, among adults 35 to 74 years of age. Main data sources included official mortality statistics, results of longitudinal studies, national surveys, randomized controlled trials, and meta-analyses. The difference between observed and expected coronary heart disease deaths in 2005 was then partitioned between treatments and risk factors. Results: From 1988 to 2005, the age-adjusted coronary heart disease mortality rates fell by almost 40%, resulting in 8530 fewer coronary heart disease deaths in 2005. Approximately 47% of the fall in deaths was attributed to treatments. The major treatment contributions came from initial therapy for acute coronary syndromes (11%), secondary prevention (10%), and heart failure (9%). About 50% of the fall in mortality was attributed to changes in risk factors. The largest mortality benefit came from changes in total cholesterol (about 31% of the mortality fall) and in systolic blood pressure (about 15%). However, some substantial gender differences were observed in risk factor trends with an increase in diabetes and obesity in men and an increase in smoking in young women. These generated additional deaths. Conclusions: Approximately half of the coronary heart disease mortality fall in Spain was attributable to reductions in major risk factors, and half to evidence-based therapies. These results increase understanding of past trends and will help to inform planning for future prevention and treatment strategies in low-risk populations. © 2011 Sociedad Española de Cardiología. Published by Elsevier España, S.L. All rights reserved.

Navarro E.,Bellvitge Biomedical Research Institute IDIBELL | Funtikova A.N.,Institute Of Recerca Hospital Del Mar Imim | Funtikova A.N.,CIBER ISCIII | Funtikova A.N.,University of Barcelona | And 4 more authors.
Molecular Nutrition and Food Research | Year: 2015

A substantial proportion of obese individuals do not present cardiometabolic complications such as diabetes, hypertension, or dyslipidemia. Some, but not all, prospective studies observe similar risk of cardiovascular events and all-cause mortality among individuals with this so-called "metabolically healthy obese" (MHO) phenotype, compared to the metabolically healthy normal weight or metabolically healthy non-obese phenotypes. Compared to the metabolically unhealthy obese (MUO) phenotype, MHO is often characterized by a more favorable inflammatory profile, less visceral fat, less infiltration of macrophages into adipose tissue, and smaller adipocyte cell size. Tipping the inflammation balance in adipose tissue might be particularly important for metabolic health in the obese. While the potential role of genetic predisposition or lifestyle factors such as diet in the MHO phenotype is yet to be clarified, it is well known that diet affects inflammation profile and contributes to the functionality of adipose tissue. This review will discuss genetic predisposition and the molecular mechanisms underlying the potential effect of food on the development of the metabolic phenotype characteristic of obesity © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fiz J.,Institute Of Recerca Hospital Del Mar Imim | Fiz J.,Autonomous University of Barcelona | Duran M.,Fundacio Institute Catala Of Farmacologia | Capella D.,Autonomous University of Barcelona | And 4 more authors.
PLoS ONE | Year: 2011

Background: The aim of this study was to describe the patterns of cannabis use and the associated benefits reported by patients with fibromyalgia (FM) who were consumers of this drug. In addition, the quality of life of FM patients who consumed cannabis was compared with FM subjects who were not cannabis users. Methods: Information on medicinal cannabis use was recorded on a specific questionnaire as well as perceived benefits of cannabis on a range of symptoms using standard 100-mm visual analogue scales (VAS). Cannabis users and non-users completed the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI) and the Short Form 36 Health Survey (SF-36). Results: Twenty-eight FM patients who were cannabis users and 28 non-users were included in the study. Demographics and clinical variables were similar in both groups. Cannabis users referred different duration of drug consumption; the route of administration was smoking (54%), oral (46%) and combined (43%). The amount and frequency of cannabis use were also different among patients. After 2 hours of cannabis use, VAS scores showed a statistically significant (p<0.001) reduction of pain and stiffness, enhancement of relaxation, and an increase in somnolence and feeling of well being. The mental health component summary score of the SF-36 was significantly higher (p<0.05) in cannabis users than in non-users. No significant differences were found in the other SF-36 domains, in the FIQ and the PSQI. Conclusions: The use of cannabis was associated with beneficial effects on some FM symptoms. Further studies on the usefulness of cannabinoids in FM patients as well as cannabinoid system involvement in the pathophysiology of this condition are warranted. © 2011 Fiz et al.

Rajmil L.,Catalan Agency for Health Information | Rajmil L.,CIBER ISCIII | Rajmil L.,Institute Of Recerca Hospital Del Mar Imim | Herdman M.,Insight Consulting and Research | And 4 more authors.
International Journal of Public Health | Year: 2014

Objectives: To assess the presence and magnitude of social inequalities in mental health and health-related quality of life (HRQOL) in the population aged 8-18 years in 11 European countries. Methods: Cross-sectional surveys were carried out in representative samples of children/adolescents (8-18 years) from the participating countries of the KIDSCREEN project. Mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ), and HRQOL by means of the KIDSCREEN-10. Socioeconomic status (SES) was assessed using the Family Affluence Scale and parental level of education. The association between health outcomes and SES was analyzed with the regression-based relative index of inequalities (RII) and population attributable risk. Results: A total of 16,210 parent-child pairs were included. The SDQ showed inequalities in mental health according to family level of education in all countries (RII = 1.45; 1.37-1.53). The RII for HRQOL was 2.15 (1.79-2.59) in the whole sample, with less consistent results by age and country. Conclusions: Socioeconomic inequalities in mental health were consistently found across Europe. Future research should clarify the causes of these inequalities and define initiatives which prevent them continuing into adulthood. © 2013 Swiss School of Public Health.

Torrens M.,Institute Of Recerca Hospital Del Mar Imim | Torrens M.,Institute Of Neuropsiquiatria I Addiccions Inad | Torrens M.,Autonomous University of Barcelona | Gilchrist G.,Institute Of Recerca Hospital Del Mar Imim | And 2 more authors.
Drug and Alcohol Dependence | Year: 2011

Background: Few studies have differentiated between independent and substance-induced psychiatric disorders. In this study we determine the risks associated with independent and substance-induced psychiatric disorders among a sample of 629 illicit drug users recruited from treatment and out of treatment settings. Methods: Secondary analysis of five cross-sectional studies conducted during 2000-2006. Independent and substance-induced DSM-IV psychiatric diagnoses were assessed using the Psychiatric Research Interview for Substance and Mental Disorders. Results: Lifetime prevalence of Axis I disorders other than substance use disorder (SUD) was 41.8%, with independent major depression being the most prevalent (17%). Lifetime prevalence of antisocial or borderline personality disorders was 22.9%. In multinominal logistic regression analysis (SUD only as the reference group), being female (OR 2.45; 95% CI 1.59, 3.77) and having lifetime borderline personality disorder (OR 2.45; 95% CI 1.31, 4.59) remained significant variables in the group with independent disorders. In the group with substance-induced disorders, being recruited from an out of treatment setting (OR 3.50; 95% CI 1.54, 7.97), being female (OR 2.38; 95% CI 1.24, 4.59) and the number of SUD (OR 1.31; 95% CI 1.10, 1.57) remained significant in the model. These variables were also significant in the group with both substance-induced and independent disorders, together with borderline personality disorder (OR 2.53; 95% CI 1.03, 6.27). Conclusions: Illicit drug users show high prevalence of co-occurrence of mainly independent mood and anxiety psychiatric disorders. Being female, recruited from an out of treatment setting and the number of SUD, are risk factors for substance-induced disorders. © 2010 Elsevier Ireland Ltd.

Pichini S.,National Health Research Institute | Gottardi M.,Company for Provincial Health Services | Marchei E.,National Health Research Institute | Svaizer F.,Company for Provincial Health Services | And 4 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2014

Background: Drug testing in hair is a unique analysis in pharmacotoxicology for establishing a past repeated history of consumption or passive exposure to psychotropic substances. A rather lengthy sample treatment is usually required before parent drugs and eventual metabolites are amenable to quali-quantitative analysis. Methods: We evaluated a high throughput screening and confirmation analysis of drugs of abuse in hair by immunoassay and a validated ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) after applying a rapid digestion of the keratin matrix with VMA-T reagent before screening assay and M3 reagent before confirmatory analysis. Results: Samples digestion with VMA-T reagent and immunometric screening analysis of hair calibrators, controls and clinical samples for a total of 150 samples was completed in 4 h. No false-positive and-negative results were found for the control material. UPLC-MS/MS analysis confirmed all of the 31 adult hair samples positive to the screening test using internationally established cut-offs, and identified and quantified drugs of abuse in 32 pediatric hair samples, applying lower limits of quantification from 0.01 to 0.1 ng analyte per mg hair. Analytical recovery was between 70.9% and 100.7%. Intra-and inter-assay imprecision and inaccuracy were always lower than 10%. Conclusions: Rapid extraction, identification and quantification of drugs of abuse in hair by immunoassay and UPLC-MS/MS was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in hair in epidemiological studies. © 2014 by Walter de Gruyter Berlin/Boston.

Cerutti A.,Catalan Institution for Research and Advanced Studies | Cerutti A.,Institute Of Recerca Hospital Del Mar Imim | Cerutti A.,Mount Sinai School of Medicine | Cols M.,Mount Sinai School of Medicine | Puga I.,Institute Of Recerca Hospital Del Mar Imim
EMBO Reports | Year: 2012

Cognate interaction between T and B lymphocytes of the adaptive immune system is essential for the production of high-affinity antibodies against microbes, and for the establishment of long-term immunological memory. Growing evidence shows that-in addition to presenting antigens to T and B cells-macrophages, dendritic cells and other cells of the innate immune system provide activating signals to B cells, as well as survival signals to antibody-secreting plasma cells. Here, we discuss how these innate immune cells contribute to the induction of highly diversified and temporally sustained antibody responses, both systemically and at mucosal sites of antigen entry. © 2012 European Molecular Biology Organization.

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