| Gastric cancer is a major heath problem and remains the second most common cancer in the world. The environment factor, Helicobacter pylori infection is associated with divergent clinical outcomes that from simple asymptomatic gastritis to more serious conditions such as peptic ulcer disease and gastric cancer. The mechanism of H.pylori induced carcinogenesis is not clear. The host genetic factors, such as the polymorphism of IL-1B genes that affects IL-1 production may determine why some individuals infectedwith H.pylori develop gastric cancer while others do not. IL-1 is a powerful inhibitor of gastric acid secretion, and can determine the distribution of H.pylori in stomach. The O2production associated with H.pylori is also involved in the origin and development of gastric cancer. Survivin, a member of the inhibitors of apoptosis protein(IAP) family, isinvolved in regulation of apoptosis and cell division. Our study is to make clear ï¹–he connection of IL, (V and survivin in gastric cancer; (2)the cellular signal pathway ofCagA+H.pylori inducing IL-1 P secretion in human gastric epithelial (GES-l)cells; the effect of low concentration (V on the proliferation of GES-1 cells. (3)the correlationbetween IL and the exprssion of survivin in gastric epithelial cells, the effect of targeting survivin on the apoptosis of gastric cancer cells; (Dthe correlation between polymorphism of IL-1B genes and risk of gastric cancer and duodenal ulcer, the relationship between polymorphism of IL-1B genes and cliniaopathological factors inhuman gastric cancer. The final goal of this study is to find the possible role of IL-, O2 ?and survivin in gastric Cancer and supply new strategics in treatment of gastric cancer.Part 1 The cellular signal pathway of CagA+H. pylori inducing IL-1 protein secretion in GES-1 cells and the effect of IL-1 & on proliferation of GES-1 cells induced by superoxide anion in culture[Abstract] Objective H. pylori is the main risk factor for the development of gastric cancer. Increased proliferation of the gastric mucosa is a feature of H. pylori infection. The effect of CagA+H.pylori induceing IL-1 P protein secretion in GES-1 cells and various kinase inhibitors on CagA+H. pylori inducing IL-1 P protein secretion, and the effect of IL-lp on gastric epithelial cells proliferation induced by IL-1 Preceptor and superoxide anion in culture have been examined in this study. Metheds GES-1 cells were cultured with CagA+H.pylori in vitro. At the end of culture, IL-1 P protein secretion was assayed by ELISA kit. The effects of the inhibitors of protein kinase A,C,G ,protein tyrosine kinase were analyzed on IL-1 P protein secretion hi GES-1 cells by H.pylori stimulation. GES-1 cells were cultured with IL-1J3. DNA synthesis of GES-1 cells wasassessed by [3H]thymidine incorporation liquid scintillation counter and total viable cell numbers were analyzed by MTT methed. The concentration of 62 ?generated by GES-1cells and Hp were measured by Ferricytochrome C reduction. Results IL-1 P protein secretion induced by CagA+H.pylori in GES-1 cells was higher than that hi GES-1 cells of never stimulated. Further studied with GES-1 cells showed that IL-1 P protein secretion induced by CagA+ Hp was blocked by the PTK inhibitor (herbimycin A) but not by PKA inhibitor (H7), PKC inhibitor (Calphostin C) and PKG inhibitor (KT5823). IL-lp dose dependency increased DNA synthesis and cell numbers of GES-1 cells. The enhancedproliferation was blocked by IL-1 receptor antagonist, anti-IL-lp had no this action. Hp can generate CV spontaneously, and endure higher Oa ?concentration than GES-1 cells.GES-1 cells can also generate (V spontaneously. IL-lp promoted the proliferation of GES-1 cells by stimulating the generation of Ch . Proliferation of GES-1 cells was induced obviously by the physical concentration of C>2 . PMA promoted the proliferation of GES-1 cells by stimulating the generation of C>2 . DPL SOD inhibited the proliferation of GES-1 cells by decreasing the generation of O2 ?Conclusion CagA+ H.pyloris...
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