Suchergebnisse

The article presents an analysis of some of the results obtained in the characterization of the professional profile of educators attending early childhood in Zone 1 (Northeast) and Zone 2 (North West) of the City of Medellin, focused on knowledge of childhood these agents have a historical perspective, politics, development and rights, for which a survey of teachers, paraprofessionals, community mothers, managers and support professionals belonging to institutions offering the Buen Comienzo program, officers and private was applied of the zones in question. The research is focused on the quantitative paradigm of non experimental, descriptive correlational. The results show, with respect to knowledge of childhood, that there is not widespread ignorance of the category of childhood, elements of the historical, development, participation but not widely known, but focused on some agents educational. ; El artículo presenta el análisis de algunos de los resultados obtenidos en la caracterización del perfil profesional de los agentes educativos que atienden primera infancia en la Zona 1 (Nororiental) y Zona 2 (Noroccidental) de la ciudad de Medellín, enfocados en el conocimiento de la infancia que dichos agentes tienen desde una perspectiva histórica, política, de desarrollo y de derechos; para lo cual se aplicó una encuesta a docentes, auxiliares docentes, madres comunitarias, directivos y profesionales de apoyo pertenecientes a instituciones oficiales y privadas de las zonas en mención que ofrecen el Programa Buen Comienzo. La investigación se enfocó en el paradigma cuantitativo de tipo no experimental, descriptivo correlacional. Los resultados muestran, con respecto al conocimiento de la infancia, que existe un desconocimiento no generalizado de la categoría de infancia, es decir, se conocen elementos históricos, del desarrollo y la participación, pero no de manera amplia.

To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature ; This study was supported by grants from the Instituto de Salud Carlos III co-funded by European Regional Development Funds (ERDF/FEDER) a way to build Europe (PI10/02267 to M.B.; PI10/01089 to C.A.G.; PI10/01203 to S.L.) and COST CM1406 (to M.B.). D.J.H. has received funding from the People Program (MSCA-ITN-2014-ETN) of the European Union's Horizon 2020 Program under Chromatin 3D project (nº SEP-210147404), and O.C. has received funding from Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) (Ph.D. scholarship to O.C.)

INTRODUCTION: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor alpha (ERalpha) are among the most effective systemic treatments for ERalpha-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERalpha transcriptional regulatory plasticity. Here, we identify VAV3 as a critical component in this process. METHODS: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERalpha was evaluated by molecular docking analyses, an agonist fluoligand assay, and short-hairpin (sh) RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot of signaling and proliferation markers and shRNA-mediated protein depletion in viability and clonogenic assays were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine the association with therapy response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression. RESULTS: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase) but instead a result of binding to ERalpha. VAV3 was selectively reduced upon exposure to YC-1 or ERalpha depletion and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 x 10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy. CONCLUSIONS: This study proposes VAV3 as a biomarker and rationale signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer. ; We wish to thank all study participants and their clinicians for their valuable contributions. This work was supported by grants from the Eugenio Rodriguez Pascual Foundation (2012, to MAP), the Government of Catalonia (2009-SGR283, to AV and MAP), the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (R01 DK015556, to JAK), the Red Cooperative Research Thematic Network on Cancer (RTICC) (12/0036/0002 to XRB and 12/0036/0008 to XRB and MAP) and the Spanish Ministry of Health, Fund for Health Research-Institute of Health Carlos III (11/00951 to AU and 12/01528 to MAP).