title: Helicobacter pylori eradication prevents progression of gastric cancer in hypergastrinemic INS-GAS mice.
abstract: Helicobacter pylori infection results in chronic gastritis, which may progress to gastric cancer. In this study, we investigated the efficacy of H. pylori eradication in preventing the progression of gastritis to gastric cancer in H. pylori-infected transgenic INS-GAS mice. H. pylori infection induced severe dysplasia and gastric cancer classified as high-grade and low-grade gastrointestinal intraepithelial neoplasia (GIN) in INS-GAS mice at 28 weeks postinfection (WPI). H. pylori eradication therapy using omeprazole, metronidazole, and clarithromycin was administered p.o. at 8, 12, or 22 WPI. Compared with untreated infected mice, H. pylori eradication at 8, 12, and 22 WPI significantly reduced the severity of dysplasia (P < 0.01). Moreover, H. pylori eradication at 8 WPI completely prevented the development of GIN (P < 0.001). Although not as effective as early antimicrobial treatment, prevention of progression to high-grade GIN was achieved by H. pylori eradication at 12 and 22 WPI (P < 0.05). Consistent with reduced gastric pathology, H. pylori eradication at all time points significantly down-regulated gastric Interferon-gamma, tumor necrosis factor-alpha, inducible nitric oxide synthase, and Reg 1 mRNA levels (P < 0.05) and reduced epithelial proliferation in the corpus (P < 0.01) compared with untreated infected mice. We concluded that H. pylori eradication prevented gastric cancer to the greatest extent when antibiotics are given at an early point of infection, but that eradication therapy given at a later time point delayed the development of severe dysplastic lesions.
authors.affiliation: Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Chung-Wei
authors.initials: CW
authors.lastname: Lee
authors.forename: Barry
authors.initials: B
authors.lastname: Rickman
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Rogers
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Ge
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Wang
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage; D000897:Anti-Ulcer Agents / Q000008:administration & dosage; D002278:Carcinoma in Situ / Q000209:etiology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D017291:Clarithromycin / Q000008:administration & dosage; D018450:Disease Progression; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D051847:Lithostathine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage; D011230:Precancerous Conditions / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D013276:Stomach Ulcer / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D000897:Anti-Ulcer Agents; D051847:Lithostathine; C497615:Reg1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017291:Clarithromycin; D009853:Omeprazole