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Demir E.,Akdeniz University | Kaya B.,Akdeniz University | Marcos R.,Autonomous University of Barcelona | Marcos R.,Biomedical Research Center Network for Epidemiology and Public Health | And 2 more authors.
Turkish Journal of Biology | Year: 2013

In this study, essential oils extracted from 2 species of oregano, Origanum onites L. and Origanum minutiflorum O.Schwarz & P.H.Davis, were assayed for genotoxicity using the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Results indicated that there is no significant genotoxic effect of the 2 oils tested. In addition, the antigenotoxic activities of these oils against potassium dichromate (K2Cr2O7) and cobalt chloride (CoCl2) were tested. Results indicated that essential oil cotreatments were able to abolish the genotoxic effects induced by the 2 metal compounds. It is suggested that the observed effects can be linked to the antioxidant properties of the selected essential oils. Moreover, these in vivo results will contribute to the antigenotoxicity database of the 2 Origanum species used in this study. © Tübitak.

Zubero M.B.,Cruces University Hospital | Arana-Arri E.,Cruces University Hospital | Arana-Arri E.,Biocruces Health Research Institute | Pijoan J.I.,Cruces University Hospital | And 10 more authors.
Frontiers in Pharmacology | Year: 2014

Background: The aim of screening for colorectal cancer is to improve prognosis by the detection of cancer at its early stages. In order to inform the decision on the specific test to be used in the population-based program in the Basque Autonomous Region (Spain), we compared two immunochemical fecal occult blood quantitative tests (I-FOBT). Methods:Residents of selected study areas, aged 50-69 years, were invited to participate in the screening. Two tests based on latex agglutination (OC-Sensor and FOB Gold) were randomly assigned to different study areas. A colonoscopy was offered to patients with a positive test result. The cut-off point used to classify a result as positive, according to manufacturer's recommendations, was 100 ng/ml for both tests. Results: The invited population included 37,999 individuals. Participation rates were 61.8% (n = 11,162) for OC-Sensor and 59.1% (n = 11,786) for FOB Gold (p = 0.008). Positive rate for OC-Sensor was 6.6% (n = 737) and 8.5% (n = 1,002) for FOB Gold (p < 0.0001). Error rates were higher for FOB gold (2.3%) than for OC-Sensor (0.2%; p < 0.0001). Predictive positive value (PPV) for total malignant and premalignant lesions was 62.4% for OC-Sensor and 58.9% for FOB Gold (p = 0.137), respectively. Conclusion: OC-Sensor test appears to be superior for I-FOBT-based colorectal cancer screening, given its acceptance, ease of use, associated small number of errors and its screening accuracy. FOB Gold on the other hand, has higher rate of positive values, with more colonoscopies performed, it shows higher detection incidence rates, but involves more false positives. © 2014 Zubero, Arana-Arri, Pijoan, Portillo, Idigoras, López-Urrutia, Samper, Uranga, Rodríguez and Bujanda.

Maxwell C.A.,Catalan Institute of Nanoscience and Nanotechnology | Maxwell C.A.,Child and Family Research Institute | Benitez J.,Spanish National Cancer Research Center | Benitez J.,Biomedical Research Center Network for Rare Diseases | And 155 more authors.
PLoS Biology | Year: 2011

Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio (wHR) = 1.09 (95% CI 1.02-1.16), ptrend = 0.017; and n = 3,965, wHR = 1.04 (95% CI 0.94-1.16), ptrend = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM. © 2011 Maxwell et al.

Gomez-Baldo L.,Bellvitge Institute for Biomedical Research | Gomez-Baldo L.,Biomedical Research Center Network for Epidemiology and Public Health | Schmidt S.,Heinrich Heine University Dusseldorf | Maxwell C.A.,Bellvitge Institute for Biomedical Research | And 19 more authors.
Cell Cycle | Year: 2010

Studies of the role of tuberous sclerosis complex (TSC) proteins (TSC1/TSC2) in pathology have focused mainly on their capacity to regulate translation and cell growth, but their relationship with alterations of cellular structures and the cell cycle is not yet fully understood. the transforming acidic coiled-coil (TACC) domain-containing proteins are central players in structures and processes connected to the centrosome. Here, TACC3 interactome mapping identified TSC2 and 15 other physical interactors, including the evolutionary conserved interactions with ch-ToG/CKAP5 and FAM161B. TACC3 and TSC2 co-localize and co-purify with components of the nuclear envelope, and their deficiency causes morphological alterations of this structure. During cell division, TACC3 is necessary for the proper localization of phospho-Ser939 TSC2 at spindle poles and cytokinetic bridges. Accordingly, abscission alterations and increased frequency of binucleated cells were observed in Tacc3- and Tsc2-deficient cells relative to controls. In regulating cell division, TSC2 acts epistatically to TACC3 and, in addition to canonical TSC/mTOR signaling and cytokinetic associations, converges to the early mitotic checkpoint mediated by CHFR, consistently with nuclear envelope associations. our findings link TACC3 to novel structural and cell division functions of TSC2, which may provide additional explanations for the clinical and pathological manifestations of lymphangioleiomyomatosis (LAM) disease and tSC syndrome, including the greater clinical severity of TSC2 mutations compared to TSC1 mutations. © 2010 Landes Bioscience.

Espelt A.,Agencia de Salut Publica de Barcelona | Espelt A.,Autonomous University of Barcelona | Espelt A.,Institute of Biomedical Research | Espelt A.,Biomedical Research Center Network for Epidemiology and Public Health | And 8 more authors.
European Journal of Public Health | Year: 2012

Background: To analyse trends in socio-economic inequalities in the prevalence of diabetes among men and women aged 35 years in Spain during the period 1987-2006. Methods: We analysed trends in the age-standardized prevalence of self-reported diabetes and obesity in relation to level of education using data from the Spanish National Health Survey for the years 1987, 1993, 1995, 1997, 2001, 2003 and 2006 (86 345 individuals aged ≥35 years). To assess the relationship between education level and diabetes and obesity, we computed the Slope Index of Inequality and the Relative Index of Inequality (RII) for each year. Additional models were fit to take into account mediator variables in socio-economic position (SEP) diabetes inequalities. Results: The prevalence of self-reported diabetes was higher among persons of low educational level, increasing more rapidly over time among people with lower education level (5.0-12.6 in men, and 8.4-13.1 in women between 1987 and 2006) than among those with higher education level (6.3-8.7 in men and 3.8-4.0 in women). Relative inequalities showed a weak tendency to increase. In women, the RII of self-reported diabetes increased from 3.04 (1.95-4.74) in 1987 to 4.28 (2.98-6.13) in 2006, while in men were constant since 1993. Trends in SEP inequalities in diabetes prevalence were attenuated when mediator variables were taken into account in women but not in men. Conclusion: SEP inequalities in diabetes existed >20 years ago and have increased, especially among women. These patterns may be explained by trends in health behaviours and obesity, but only to a limited extent. © 2011 The Author 2011.

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