Epithelial-Refluxate Interactions in Barrett's Esophagus
巴雷特食管上皮反流相互作用
基本信息
- 批准号:7114259
- 负责人:
- 金额:$ 39.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-09-30 至 2008-06-05
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): The major objective of our studies is to understand the molecular changes that occur in response to acid and bile exposure in normal and Barrett's esophagus (BE). BE is a metaplastic premalignant condition of the esophagus that is associated with an increased risk of up to 30-fold of developing esophageal adenocarcinoma. Exposure of the esophagus to the duodeno-gastro-esophageal (DGE) refluxate, important constituents of which include acid and bile, is a major risk factor for the development of BE and subsequent esophageal adenocarcinoma. Our overall hypothesis is that identifying acid and bile stimulated up- or down regulated genes in the normal esophagus and Barrett's epithelium, and characterizing the signaling pathways that are involved, should provide potential diagnostic and therapeutic targets and essential clues regarding the mechanisms of esophageal metaplasia and abnormal cell proliferation in BE.
Our specific aims and hypotheses are: (i) Use a human microarray approach, ex vivo, to identify the genes that are modified in response to acid or bile in normal esophagus, BE and duodenum. This aim is based on the hypothesis that the DGE refluxate modulates the genetic program of normal esophageal, BE and duodenal epithelia differently, in a refluxate constituent-dependent fashion. (ii) Identify the acid or bile-induced modified genes in squamous esophageal and Barrett's cell lines. This aim is based on the hypothesis that tissue cultured cell lines, due to their ability to provide an unlimited supply of RNA for gene profile analysis, may provide complimentary information to that obtained using ex vivo biopsies. (iii) Study the signaling cascades of protein kinase C, Cox-2, and Src kinase that are involved in acid/bile-induced stimulation, and define their potential interactions. This aim is based on the hypothesis that characterizing the signaling pathways that are involved in acid and bile stimulated cell proliferation complements the microarray gene profiling strategies and may provide potential complimentary targets for decreasing the risk of dysplasia and adenocarcinoma in BE. Overall, our study seeks to define the molecular signals that play a role in developing metaplasia and that regulate the acid- and bile-mediated responses in the esophagus.
描述(由申请人提供):我们研究的主要目的是了解在正常和Barrett‘s食道(BE)中酸和胆汁暴露所发生的分子变化。BE是一种食管化生性癌前病变,与发生食管腺癌的风险增加30倍有关。食道暴露在十二指肠-胃-食道(DGE)反流中,其重要成分包括酸和胆汁,是BE和随后的食管腺癌的主要危险因素。我们的总体假设是,识别酸和胆汁刺激的正常食道和Barrett‘s上皮中上调或下调的基因,并表征相关的信号通路,将为BE的食管化生和异常细胞增殖机制提供潜在的诊断和治疗靶点和基本线索。
我们的具体目标和假设是:(I)使用体外人类微阵列方法,识别正常食道、BE和十二指肠中对酸或胆汁反应的修饰基因。这一目的是基于这样的假设,即DGE回流以回流成分依赖的方式不同地调节正常食道、BE和十二指肠上皮的遗传程序。(Ii)鉴定鳞状细胞系、食管系和巴雷特细胞系中酸或胆汁诱导的修饰基因。这一目标是基于这样一种假设,即组织培养的细胞系由于能够为基因图谱分析提供无限的RNA供应,可能会提供与体外活组织检查所获得的信息互补的信息。(Iii)研究与酸/胆汁刺激有关的蛋白激酶C、环氧合酶-2和Src激酶的信号级联反应,并确定它们之间的相互作用。这一目的是基于这样一种假设,即表征酸和胆汁刺激的细胞增殖所涉及的信号通路是对微阵列基因谱策略的补充,并可能为降低BE中不典型增生和腺癌的风险提供潜在的有益靶点。总体而言,我们的研究试图定义在发生化生过程中发挥作用的分子信号,以及调节食管酸和胆汁介导的反应的分子信号。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ANSON W LOWE其他文献
ANSON W LOWE的其他文献
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{{ truncateString('ANSON W LOWE', 18)}}的其他基金
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- 资助金额:
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The Role of AGR2 in a Murine Model of Pancreatic Adenocarcinoma
AGR2 在小鼠胰腺癌模型中的作用
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Determinants of AGR2 effects in Barrett's esophagus and esophageal adenocarcinoma
Barrett 食管和食管腺癌中 AGR2 作用的决定因素
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7792335 - 财政年份:2002
- 资助金额:
$ 39.06万 - 项目类别:
Determinants of AGR2 effects in Barrett's esophagus and esophageal adenocarcinoma
Barrett 食管和食管腺癌中 AGR2 作用的决定因素
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7523291 - 财政年份:2002
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$ 39.06万 - 项目类别:
Determinants of AGR2 effects in Barrett's esophagus and esophageal adenocarcinoma
Barrett 食管和食管腺癌中 AGR2 作用的决定因素
- 批准号:
8059699 - 财政年份:2002
- 资助金额:
$ 39.06万 - 项目类别:
Epithelial-Refluxate Interactions in Barrett's Esophagus
巴雷特食管上皮反流相互作用
- 批准号:
6787772 - 财政年份:2002
- 资助金额:
$ 39.06万 - 项目类别:
Epithelial-Refluxate Interactions in Barrett's Esophagus
巴雷特食管上皮反流相互作用
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6947280 - 财政年份:2002
- 资助金额:
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Determinants of AGR2 effects in Barrett's esophagus and esophageal adenocarcinoma
Barrett 食管和食管腺癌中 AGR2 作用的决定因素
- 批准号:
7633336 - 财政年份:2002
- 资助金额:
$ 39.06万 - 项目类别:
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