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• W4361262304 abstract "<div>Abstract<p><i>Helicobacter pylori</i> infection causes severe dysplasia manifested as gastrointestinal intraepithelial neoplasia (GIN) after 28 weeks post–<i>H. pylori</i> infection (WPI) in cancer-prone, hypergastrinemic male INS-GAS mice. We examined the efficacy of the nonsteroidal anti-inflammatory drug sulindac (400 ppm in drinking water) alone, the CCK2/gastrin receptor antagonist YM022 (45 mg/kg/wk) alone, and sulindac or YM022 combined with <i>H. pylori</i> eradication therapy to prevent <i>H. pylori</i>–associated gastric cancer in male INS-GAS mice. Treatments started at 22 WPI, and mice were euthanized at 28 WPI. In uninfected mice, all treatments significantly delayed development of spontaneous GIN (<i>P</i> < 0.05). In <i>H. pylori</i>–infected mice, sulindac alone or YM022 alone had no protective effect on <i>H. pylori</i>–associated GIN. Importantly, sulindac exacerbated the severity of <i>H. pylori</i>–associated gastritis despite decreased gastric prostaglandin E₂ levels. However, sulindac combined with <i>H. pylori</i> antimicrobial eradication reduced the incidence of GIN (<i>P</i> < 0.05), whereas YM022 combined with antimicrobial eradication did not reduce GIN. In infected mice, sulindac or YM022 treatment did not alter gastric expression of the proinflammatory cytokines <i>Ifn-γ</i> and <i>Tnf-α</i> and mucosal cell proliferation. Sulindac or YM022 combined with antimicrobial eradication down-regulated mRNA levels of <i>Ifn-γ</i> and <i>Tnf-α</i> and mucosal cell proliferation (<i>P</i> < 0.05). We conclude that sulindac enhances <i>H. pylori</i> gastritis and may promote inflammation-mediated gastric carcinogenesis. The combination of sulindac and antimicrobial <i>H. pylori</i> eradication was beneficial for reducing proinflammatory cytokine mRNA in the stomach and preventing progression from severe dysplasia to gastric cancer in <i>H. pylori</i>–infected INS-GAS mice. [Cancer Res 2009;69(20):8166–74]</p></div>" @default.
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• W4361262304 date "2023-03-30" @default.
• W4361262304 modified "2023-10-18" @default.
• W4361262304 title "Data from Combination of Sulindac and Antimicrobial Eradication of <i>Helicobacter pylori</i> Prevents Progression of Gastric Cancer in Hypergastrinemic INS-GAS Mice" @default.
• W4361262304 doi "https://doi.org/10.1158/0008-5472.c.6499407" @default.
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