HELICOBACTER GASTRITIS AND GASTRIC CARCINOMA

最近的流行病学证据表明，持续存在的 幽门螺杆菌在人类胃中的感染及其发生发展 胃癌，但没有直接的因果关系 以及细菌感染导致 恶变尚不清楚。关于初选的建议 细菌感染是导致癌症发生的重要原因之一， 然而，检验这一假设的新方法是必要的。 这项提议主要目标是使用动物模型来确定 胃幽门螺杆菌感染和胃炎之间有直接的因果联系 胃癌的发生。提出的总体假设是，慢性 持续性幽门螺杆菌胃炎导致癌前病变 接触原生致癌物(诱变剂)会导致最终的恶性 胃上皮细胞的转化。建议的机制 这种转化是特定炎症介质的分泌。 这会导致非肿瘤性上皮细胞增殖。这种扩散 允许固定由主要致癌物引起的突变。一个 已建立的小鼠幽门螺杆菌胃炎模型将用于 确定化学诱导的致癌是否依赖于 幽门螺杆菌相关性胃炎，并检验假设 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。

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.