HELICOBACTER GASTRITIS AND GASTRIC CARCINOMA

螺杆菌胃炎和胃癌

• 批准号: 2330943
• 负责人: KATHRYN A. EATON
• 金额: $ 20.61万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2330943
• 关键词: Helicobacter; N methyl N' nitro N nitrosoguanidine; T lymphocyte; cell sorting; disease /disorder model; gastritis; gastrointestinal neoplasms; gene induction /repression; gene mutation; immunocytochemistry; infection related neoplasm /cancer; laboratory mouse; polymerase chain reaction

Recent epidemiologic evidence has suggested a link between persistent gastric infection with H. pylori in human patients and the development of gastric carcinoma, but a direct causal relationship has not been established, and the mechanism by which bacterial infection leads to malignant transformation is not known. The suggestion that primary bacterial infection can lead to carcinogenesis is an important one, however, and new approaches to test this hypothesis are necessary. The primary goal of this proposal is use an animal model to determine if there is a direct causal link between gastric helicobacter infection and gastric carcinogenesis. The overall hypothesis addressed is that chronic persistent helicobacter gastritis leads to premalignant changes and that contact with a primary carcinogen (mutagen) leads to eventual malignant transformation of gastric epithelial cells. The proposed mechanism for such transformation is the secretion of specific inflammatory mediators which lead to non-neoplastic epithelial proliferation. This proliferation allows fixation of mutations induced by a primary carcinogen. An established model of helicobacter gastritis in mice will be used to determine if chemically-induced carcinogenesis is dependent upon helicobacter-associated gastritis, and to test the hypothesis that malignant transformation is dependent on release of T cell mediators leading to epithelial hyperplasia and dysplasia.

最近的流行病学证据表明，持续的 人类患者胃部幽门螺杆菌感染及其发展 胃癌，但尚未发现直接因果关系 建立了细菌感染导致的机制 恶变尚不清楚。 建议主要 细菌感染是导致癌变的重要原因之一， 然而，需要新的方法来检验这一假设。 该提案的主要目标是使用动物模型来确定是否 胃幽门螺杆菌感染与胃幽门螺杆菌感染之间有直接的因果关系。 胃癌发生。 所讨论的总体假设是慢性 持续性幽门螺杆菌胃炎会导致癌前病变 接触主要致癌物（诱变剂）最终会导致恶性 胃上皮细胞的转化。 拟议的机制 这种转化就是特定炎症介质的分泌 从而导致非肿瘤性上皮增殖。 这种扩散 允许固定由主要致癌物诱导的突变。 一个 建立的小鼠螺杆菌胃炎模型将用于 确定化学诱发的致癌作用是否取决于 幽门螺杆菌相关性胃炎，并检验以下假设： 恶性转化依赖于T细胞介质的释放 导致上皮增生和异型增生。