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In vivo models for understanding the cellular and molecular pathogenesis of Barrett's Oesophagus

用于了解巴雷特食管细胞和分子发病机制的体内模型

基本信息

批准号：
nhmrc : 400100
负责人：
A/Pr Pritinder Kaur
金额：
$ 18.92万
依托单位：
The University of Melbourne
依托单位国家：
澳大利亚
项目类别：
NHMRC Project Grants
财政年份：
2006
资助国家：
澳大利亚
起止时间：
2006-01-01 至 2008-12-31
项目状态：
已结题

来源：
https://researchdata.edu.au/vivo-models-understanding-barretts-oesophagus/77669
关键词：
vivo models understanding cellular molecular

项目摘要

The incidence of oesophageal adenocarcinoma, a malignancy that is almost invariably fatal, has doubled in recent years and continues to increase at an alarming rate. Oesophageal adenocarcinoma arises from Barrett's oesophagus, a premalignant condition that effects up to 2% of the population. In Barrett's, the normal cells of the oesophageal lining are changed to become more like cells that line the intestine. We have developed novel 3-dimensional cell culture models that allow us to reproduce the normal layered structure of the human oesophageal lining in the laboratory and we propose to use these models to address key issues in the biology of Barrett's oesophagus. In aim 1, we wish to determine if the cells in patients with Barrett's have been permanently, or only transiently, altered and to understand the role of gastric acid- bile and accessory cells in this transformation. In aim 2 we will look more closely at the molecular changes that drive the cellular transformation characteristic of Barrett's. We will do this by manipulating the expression of selected genes in human oesophageal cells and assessing the effects of these genes on cell growth and differentiation using our cell culture models. The results of these studies will pave the way for the design of appropriate clinical strategies to treat Barrett's oesophagus and prevent the progression of this premalignant condition to oesophageal adenocarcinoma.

食管腺癌是一种几乎总是致命的恶性肿瘤，其发病率近年来翻了一番，并继续以惊人的速度增长。食管腺癌起源于Barrett食管，这是一种癌前病变，影响高达2%的人群。在巴雷特氏病中，食管衬里的正常细胞变得更像肠道衬里的细胞。我们已经开发了新的三维细胞培养模型，使我们能够在实验室中重现人类食管衬里的正常分层结构，我们建议使用这些模型来解决巴雷特食管生物学中的关键问题。在目标1中，我们希望确定巴雷特氏病患者的细胞是否已经永久地或仅暂时地改变，并了解胃酸-胆汁和辅助细胞在这种转化中的作用。在目标2中，我们将更仔细地研究驱动巴雷特氏病细胞转化特征的分子变化。我们将通过操纵人类食管细胞中选定基因的表达并使用我们的细胞培养模型评估这些基因对细胞生长和分化的影响来实现这一点。这些研究的结果将为设计适当的临床策略来治疗巴雷特食管和防止这种癌前病变进展为食管腺癌铺平道路。