title: Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.
abstract: H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG.
authors: Songhua
authors: S
authors: Zhang
authors: Dong Soo
authors: DS
authors: Lee
authors: Rhiannon
authors: R
authors: Morrissey
authors: Jose R
authors: JR
authors: Aponte-Pieras
authors: Arlin B
authors: AB
authors: Rogers
authors: Steven F
authors: SF
authors: Moss
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D054357:Chemokine CXCL10 / Q000097:blood / Q000235:genetics; D054370:Chemokine CXCL9 / Q000097:blood / Q000235:genetics; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D015870:Gene Expression; D016481:Helicobacter Infections / Q000150:complications* / Q000188:drug therapy; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D009853:Omeprazole / Q000494:pharmacology / Q000627:therapeutic use; D011230:Precancerous Conditions / Q000188:drug therapy / Q000382:microbiology; D013274:Stomach Neoplasms / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C485433:Cxcl10 protein, mouse; C485969:Cxcl9 protein, mouse; D008795:Metronidazole; D017291:Clarithromycin; D009853:Omeprazole