RESUMEN
The Wnt/ß-catenin pathway plays multiple and diverse roles in development by regulating gene expression via T-cell factor/Lymphoid enhancer-binding factor (Tcf/Lef) DNA binding factors. Misregulation of this pathway is thought to initiate colon adenoma formation. It is controversial whether Tcf4 (Tcf7L2) functions as an oncogene or tumor suppressor gene in colon carcinogenesis. We show here that Tcf4 haploinsufficiency results in colon tumor formation in a mouse tumor model that normally only develops small intestinal tumors. Further, we show that loss of Tcf4 early in development and in adult colon results in increased cell proliferation. These findings strongly suggest that Tcf4 normally modulates proliferation of the colonic epithelium and that disruption of Tcf4 activity increases proliferation, leading to colon tumorigenesis. Taken together, our in vivo studies favor a tumor suppressor function for Tcf4.
Asunto(s)
Proliferación Celular , Colon/metabolismo , Neoplasias del Colon/metabolismo , Neoplasias Experimentales/metabolismo , Proteína 2 Similar al Factor de Transcripción 7/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Neoplasias del Colon/genética , Humanos , Ratones , Ratones Transgénicos , Neoplasias Experimentales/genética , Proteína 2 Similar al Factor de Transcripción 7/genética , Proteínas Supresoras de Tumor/genética , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
This article describes the history, current status, advantages of and opposition to the implementation of e-procurement in hospitals and examines the results of its implementation in a psychiatric hospital.
Asunto(s)
Internet , Departamento de Compras en Hospital/métodos , Unión Europea , Hospitales PsiquiátricosRESUMEN
Several recent studies have illustrated the beneficial effects of living in an enriched environment on improving human disease. In mice, environmental enrichment (EE) reduces tumorigenesis by activating the mouse immune system, or affects tumor bearing animal survival by stimulating the wound repair response, including improved microbiome diversity, in the tumor microenvironment. Provided here is a detailed procedure to assess the effects of environmental enrichment on the biodiversity of the microbiome in a mouse colon tumor model. Precautions regarding animal breeding and considerations for animal genotype and mouse colony integration are described, all of which ultimately affect microbial biodiversity. Heeding these precautions may allow more uniform microbiome transmission, and consequently will alleviate non-treatment dependent effects that can confound study findings. Further, in this procedure, microbiota changes are characterized using 16S rDNA sequencing of DNA isolated from stool collected from the distal colon following long-term environmental enrichment. Gut microbiota imbalance is associated with the pathogenesis of inflammatory bowel disease and colon cancer, but also of obesity and diabetes among others. Importantly, this protocol for EE and microbiome analysis can be utilized to study the role of microbiome pathogenesis across a variety of diseases where robust mouse models exist that can recapitulate human disease.
Asunto(s)
Neoplasias del Colon/microbiología , Microbioma Gastrointestinal/inmunología , Microbiota/inmunología , Animales , Modelos Animales de Enfermedad , Ratones , Microambiente TumoralRESUMEN
Environmental enrichment (EE) replicates mind-body therapy by providing complex housing to laboratory animals to improve their activity levels, behavior, and social interactions. Using a Tcf4Het/+ApcMin/+-mediated model of colon tumorigenesis, we found that EE vastly improved the survival of tumor-bearing animals, with differential effect on tumor load in male compared to female animals. Analysis of Tcf4Het/+ApcMin/+ males showed drastically reduced expression of circulating inflammatory cytokines and induced nuclear hormone receptor (NHR) signaling, both of which are common in the wound repair process. Interestingly, EE provoked tumor wound repair resolution through revascularization, plasma cell recruitment and IgA secretion, replacement of glandular tumor structures with pericytes in a process reminiscent of scarring, and normalization of microbiota. These EE-dependent changes likely underlie the profound improvement in survival of colon-tumor-bearing Tcf4Het/+ApcMin/+ males. Our studies highlight the exciting promise of EE in the design of future therapeutic strategies for colon cancer patients.
Asunto(s)
Neoplasias del Colon/patología , Ambiente , Inmunoglobulina A/metabolismo , Cicatrización de Heridas/fisiología , Proteína de la Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Alphaproteobacteria/aislamiento & purificación , Alphaproteobacteria/fisiología , Animales , Colon/microbiología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/mortalidad , Citocinas/sangre , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones , Microbiota , Neovascularización Fisiológica , Pericitos/citología , Pericitos/metabolismo , Proteobacteria/aislamiento & purificación , Proteobacteria/fisiología , Receptores Citoplasmáticos y Nucleares/metabolismo , Transducción de Señal , Tasa de Supervivencia , Factor de Transcripción 4/genética , Factor de Transcripción 4/metabolismoRESUMEN
Abstract Introduction: a new epoxy resin-based root-canal sealer (AdSeal™) recently appeared on the market. The aim of this study was to evaluate the radiopacity, flow rate, and film thickness of this sealant compared to Topseal®. Methods: the tests were conducted in compliance with ISO 6876:2012 standards. To evaluate radiopacity, 5 discs of each sealant measuring 10 mm in diameter by 1 mm thick were crafted, comparing their radiographic density in mm of aluminum (Al). For flow rate analysis, 0.05 ml of sealant were placed between 2 glass plates under a weight of 120 g for 10 minutes. The diameters of the formed discs were measured with a calibrator and analyzed with the imageJ software. For film thickness analysis, the sealants were placed between 2 glass plates, applying a load of 150N with a universal testing machine (AGIS 5KN) for 10 minutes. Distance between the glass plates was measured using a stereomicroscope at three equidistant points. Results: Topseal® showed more radiopacity (Wilcoxon p < 0.05) and less flow rate than AdSeal™, with statistically significant differences (Anova p = 0.0001863). The film thickness values are above the limit allowed by standard 6876, possibly because of the methodology used in this study; however, no statistically significant difference was found between the sealants (Anova p = 0.4927). Conclusions: the radiopacity and flow rate of AdSeal™ and Topseal® sealants comply with the ISO 6876:2012 standard, but the film thickness values fail to meet the standard.
Resumen Introducción: un nuevo sellador de conductos radiculares a base de resina epóxica (AdSeal™) apareció recientemente en el mercado. El objetivo de este estudio consistió en evaluar la radiopacidad, fluidez y espesor de película de este sellador comparado con el Topseal®. Métodos: las pruebas fueron realizadas en concordancia con la norma ISO 6876:2012. Para evaluar la radiopacidad se elaboraron 5 discos de cada sellador de 10 mm de diámetro por 1 mm de espesor, comparando su densidad radiográfica en mm de aluminio (Al). Para el análisis de fluidez se colocaron 0,05 ml de sellador entre 2 placas de vidrio bajo un peso de 120 g por 10 minutos; los diámetros de los discos formados se midieron con un calibrador y fueron analizados con el software imageJ. Para el análisis de espesor de película los selladores se colocaron entre 2 placas de vidrio, se aplicó una carga de 150 N con una máquina universal de ensayos (AGIS 5KN) por 10 minutos, y la distancia entre las placas de vidrio fue medida con ayuda de un estereomicroscopio en tres puntos equidistantes. Resultados: el Topseal® tuvo mayor radiopacidad (Wilcoxon p < 0,05) y menor fluidez que el AdSeal™ con diferencias estadísticamente significativas (Anova p = 0,0001863). Los valores de espesor de película están por encima del límite permitido por la norma 6876, posiblemente por la metodología utilizada en el estudio; sin embargo, no se encontró diferencia estadísticamente significativa entre los selladores (Anova p = 0,4927). Conclusiones: la radiopacidad y fluidez de los selladores AdSeal™ y Topseal® cumplen con la Norma ISO 6876:2012, pero los valores de espesor de película no cumplen con la norma.