Principios del entrenamiento que utilizan los entrenadores en la iniciación deportiva de los niños de 10 a 12 años de las escuelas de fútbol de Ibarra en el año 2014.

Analizar los principios del entrenamiento que utilizan los entrenadores en la iniciación deportiva de los niños de 10 a 12 años de las escuelas de fútbol de Ibarra en el año 2014.El propósito del presente Trabajo de Grado es determinar los fundamentos teórico y técnicos de los principios del entrenamiento que orientan y aplican los entrenadores en la iniciación deportiva de los niños de 10 a 12 años de edad que practican fútbol en la ciudad de Ibarra. Medir las capacidades coordinativas para determinar en qué condiciones se encuentran los niños al tratar los fundamentos técnicos básicos. El marco teórico está sustentado por una amplia revisión bibliográfica relacionada con los principios de entrenamiento, test de capacidades coordinativas para la iniciación deportiva del fútbol en niños de 10 a 12 años de edad. La metodología se enmarca en la modalidad de investigación de campo, de tipo descriptivo, bibliográfica, y propositiva .Por el problema y los objetivos la investigación se orientó por el diseño no experimental, es de corte transversal. De acuerdo con el tipo y diseño, la investigación corresponde a la variante multimétodo; es decir, una combinación de las investigaciones cuantitativa y cualitativa. A los sujetos de estudio entrenadores se les aplicó una encuesta, por los resultados se evidencia un bajo dominio de conocimientos teórico-prácticos sobre los principios que orientan la iniciación deportiva en el fútbol infantil; se profundiza la problemática cuando los test y los resultados evidencia un deficiente desarrollo de las capacidades coordinativa. A partir de esto se plantea una propuesta factible: Guía de principios pedagógicos y didácticos que orientan a los entrenadores de iniciación deportiva del fútbol en niños de 10 a 12 años. La propuesta tiene una amplia aceptación y será socializada en diferentes eventos.Licenciatur

Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide

INTRODUCTION: The androgen receptor (AR) is widely expressed in breast cancers and has been proposed as a therapeutic target in estrogen receptor alpha (ER) negative breast cancers that retain AR. However, controversy exists regarding the role of AR, particularly in ER + tumors. Enzalutamide, an AR inhibitor that impairs nuclear localization of AR, was used to elucidate the role of AR in preclinical models of ER positive and negative breast cancer. METHODS: We examined nuclear AR to ER protein ratios in primary breast cancers in relation to response to endocrine therapy. The effects of AR inhibition with enzalutamide were examined in vitro and in preclinical models of ER positive and negative breast cancer that express AR. RESULTS: In a cohort of 192 women with ER + breast cancers, a high ratio of AR:ER (≥2.0) indicated an over four fold increased risk for failure while on tamoxifen (HR = 4.43). The AR:ER ratio had an independent effect on risk for failure above ER % staining alone. AR:ER ratio is also an independent predictor of disease-free survival (HR = 4.04, 95% CI: 1.68, 9.69; p = 0.002) and disease specific survival (HR = 2.75, 95% CI: 1.11, 6.86; p = 0.03). Both enzalutamide and bicalutamide inhibited 5-alpha-dihydrotestosterone (DHT)-mediated proliferation of breast cancer lines in vitro; however, enzalutamide uniquely inhibited estradiol (E2)-mediated proliferation of ER+/AR + breast cancer cells. In MCF7 xenografts (ER+/AR+) enzalutamide inhibited E2-driven tumor growth as effectively as tamoxifen by decreasing proliferation. Enzalutamide also inhibited DHT- driven tumor growth in both ER positive (MCF7) and negative (MDA-MB-453) xenografts, but did so by increasing apoptosis. CONCLUSIONS: AR to ER ratio may influence breast cancer response to traditional endocrine therapy. Enzalutamide elicits different effects on E2-mediated breast cancer cell proliferation than bicalutamide. This preclinical study supports the initiation of clinical studies evaluating enzalutamide for treatment of AR(+) tumors regardless of ER status, since it blocks both androgen- and estrogen- mediated tumor growth

Frecuencia de los genotipos babA2, oipA y cagE de Helicobacter pylori en pacientes colombianos con enfermedades gastroduodenales.

Introduction. Helicobacter pylori infection is associated with the development of several gastroduodenal diseases. Bacterial virulence genes have been found associated with an increased risk for gastric disease.Objectives. Herein, associations were made between the presence of vacA, cagA, cagE, babA2 and oipA genes in H. pylori isolates and the range of clinical consequences of the infection.Methods. PCR was used to amplify vacA, cagA, cagE, babA2 and oipA genes in 166 isolates-50 patients with peptic ulcer, 39 with non-atrophic gastritis, 26 with atrophic gastritis, 26 with intestinal metaplasia and 25 with gastric adenocarcinoma.Results. cagA, cagE, babA2 and oipA genes were found in 73%, 75%, 48% and 74% of isolates, respectively. The cytotoxic vacA s1m1/cagA positive/cage positive genotype was present in 64% (100/157) of isolates. A higher frequency of cytotoxic strains was observed in cancer patients (84%), intestinal metaplasia (91%) and peptic ulcer (81%) in comparison with gastritis patients (50%) (p=0.002, 0.008, 0.007, respectively). The oipA and babA2 frequency was higher in cytotoxic isolates than in non-cytotoxic isolates (oipA: 81% vs. 52%, P=0,003; babA2: 58% vs. 12% (pIntroducción. La infección con Helicobacter pylori está asociada con el desarrollo de diferentes enfermedades gastroduodenales. Varios genes de virulencia de H. pylori se han relacionado con mayor riesgo de enfermedad gástrica. Objetivos. El propósito de este trabajo fue determinar las posibles asociaciones entre la presencia de los genes vacA, cagA, cagE, babA2 y oipA en aislamientos de H. pylori de pacientes colombianos y las diferentes consecuencias clínicas de la infección. Materiales y métodos. Mediante PCR se evaluaron los genotipos cagA, vacA, cagE, oipA y babA2 en 166 aislamientos de H. pylori provenientes de 50 pacientes con úlcera péptica, 39 con gastritis crónica no atrófica, 26 con gastritis crónica atrófica, 26 con metaplasia intestinal y 25 con adenocarcinoma gástrico. Resultados. La frecuencia de los genotipos cagA, cagE, babA2 y oipA fue de 73%, 75%, 48% y 74%, respectivamente. El 64% (100/157) de los aislamientos presentó el genotipo citotóxico vacAs1m1/cagA positivo/cagE positivo. Se observó una mayor frecuencia de cepas citotóxicas en pacientes con cáncer (84%), metaplasia (91%) y úlcera (81%) en comparación con pacientes con gastritis no atrófica (50%) (p=0,002, 0,008 y 0,007, respectivamente). La frecuencia de oipA y babA2 fue mayor en cepas citotóxicas que en cepas no citotóxicas (oipA: 81% vs. 52%, p=0,003; babA2: 58% vs. 12%, p=0,000). No se observaron diferencias significativas en la frecuencia de los genes oipA o babA2 solos o en asociación con vacA y cagA/cagE y las diferentes enfermedades gastroduodenales. Conclusiones. No se encontraron evidencias que sugieran que los genes babA2 u oipA puedan servir como marcadores de ulcerogénesis o carcinogénesis en esta población, solos o en asociación con cagA, cagE o vacA

Downregulation of miR-342 is associated with tamoxifen resistant breast tumors

<p>Abstract</p> <p>Background</p> <p>Tumor resistance to the selective estrogen receptor modulator tamoxifen remains a serious clinical problem especially in patients with tumors that also overexpress HER2. We have recently demonstrated that the clinically important isoform of HER2, HERΔ16, promotes therapeutically refractory breast cancer including resistance to endocrine therapy. Likewise additional breast tumor cell models of tamoxifen resistance have been developed that do not involve HER2 overexpression. However, a unifying molecular mechanism of tamoxifen resistance has remained elusive.</p> <p>Results</p> <p>Here we analyzed multiple cell models of tamoxifen resistance derived from MCF-7 cells to examine the influence of microRNAs (miRNAs) on tamoxifen resistance. We compared miRNA expression profiles of tamoxifen sensitive MCF-7 cells and tamoxifen resistant MCF-7/HER2Δ16 cells. We observed significant and dramatic downregulation of miR-342 in the MCF-7/HER2Δ16 cell line as well as the HER2 negative but tamoxifen resistant MCF-7 variants TAMR1 and LCC2. Restoring miR-342 expression in the MCF-7/HER2Δ16 and TAMR1 cell lines sensitized these cells to tamoxifen-induced apoptosis with a dramatic reduction in cell growth. Expression of miR-342 was also reduced in a panel of tamoxifen refractory human breast tumors, underscoring the potential clinical importance of miR-342 downregulation. Towards the goal of identifying direct and indirect targets of miR-342 we restored miR-342 expression in MCF-7/HER2Δ16 cells and analyzed changes in global gene expression by microarray. The impact of miR-342 on gene expression in MCF-7/HER2Δ16 cells was not limited to miR-342 <it>in silica </it>predicted targets. Ingenuity Pathways Analysis of the dataset revealed a significant influence of miR-342 on multiple tumor cell cycle regulators.</p> <p>Conclusions</p> <p>Our findings suggest that miR-342 regulates tamoxifen response in breast tumor cell lines and our clinical data indicates a trend towards reduced miR-342 expression and tamoxifen resistance. In addition, our results suggest that miR-342 regulates expression of genes involved in tamoxifen mediated tumor cell apoptosis and cell cycle progression. Restoring miR-342 expression may represent a novel therapeutic approach to sensitizing and suppressing the growth of tamoxifen refractory breast tumors.</p

Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer

Background Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.info:eu-repo/semantics/publishedVersio

Ovarian steroid hormones: what's hot in the stem cell pool?

The vital role of ovarian hormones in the development of the normal breast foreshadowed their importance in mammary stem cell regulation. Two recent papers reveal that 17β-estradiol and progesterone control the size and repopulating ability of the mammary stem cell compartment. This likely occurs via paracrine signaling from steroid receptor-positive luminal cells to steroid receptor-negative stem cells. These findings illuminate roles for the female sex steroids in mobilizing the stem cell pool in the normal breast, and also provide a crucial link between the known hormonal risks of breast cancer and the potential stem cell origin of this disease

Oncogenic HER2Δ16 suppresses miR-15a/16 and deregulates BCL-2 to promote endocrine resistance of breast tumors

Tamoxifen is the most commonly prescribed therapy for patients with estrogen receptor (ER)α-positive breast tumors. Tumor resistance to tamoxifen remains a serious clinical problem especially in patients with tumors that also overexpress human epidermal growth factor receptor 2 (HER2). Current preclinical models of HER2 overexpression fail to recapitulate the clinical spectrum of endocrine resistance associated with HER2/ER-positive tumors. Here, we show that ectopic expression of a clinically important oncogenic isoform of HER2, HER2Δ16, which is expressed in >30% of ER-positive breast tumors, promotes tamoxifen resistance and estrogen independence of MCF-7 xenografts. MCF-7/HER2Δ16 cells evade tamoxifen through upregulation of BCL-2, whereas mediated suppression of BCL-2 expression or treatment of MCF-7/HER2Δ16 cells with the BCL-2 family pharmacological inhibitor ABT-737 restores tamoxifen sensitivity. Tamoxifen-resistant MCF-7/HER2Δ16 cells upregulate BCL-2 protein levels in response to suppressed ERα signaling mediated by estrogen withdrawal, tamoxifen treatment or fulvestrant treatment. In addition, HER2Δ16 expression results in suppression of BCL-2-targeting microRNAs miR-15a and miR-16. Reintroduction of miR-15a/16 reduced tamoxifen-induced BCL-2 expression and sensitized MCF-7/HER2Δ16 to tamoxifen. Conversely, inhibition of miR-15a/16 in tamoxifen-sensitive cells activated BCL-2 expression and promoted tamoxifen resistance. Our results suggest that HER2Δ16 expression promotes endocrine-resistant HER2/ERα-positive breast tumors and in contrast to wild-type HER2, preclinical models of HER2Δ16 overexpression recapitulate multiple phenotypes of endocrine-resistant human breast tumors. The mechanism of HER2Δ16 therapeutic evasion, involving tamoxifen-induced upregulation of BCL-2 and suppression of miR-15a/16, provides a template for unique therapeutic interventions combining tamoxifen with modulation of microRNAs and/or ABT-737-mediated BCL-2 inhibition and apoptosis