Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model. Issue 2 (10th April 2015)

• Record Type: Journal Article
• Authors: Zhang, Songhua; Lee, Dong Soo; Morrissey, Rhiannon; Aponte-Pieras, Jose R.; Rogers, Arlin B.; Moss, Steven F.
• Is Part Of: Cancer letters. Volume 359:Issue 2(2015)
• Page Start: 345
• Page End: 351
• Publication Date: 2015-04-10
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.01.028
• Languages: English
• ISSNs: 0304-3835

Abstract

<abstract abstract-type="author" id="ab0010"> <title id="st0010">Abstract</title> <sec> <p id="sp0010"> <italic>H. pylori</italic> infection causes gastritis, peptic ulcers and gastric cancer. Eradicating <italic>H. pylori</italic> prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. <italic>H. pylori</italic> infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of <italic>H. pylori</italic>-induced cancer. We infected p27-deficient mice with <italic>H. pylori</italic> strain SS1 at 6–8 weeks of age. Persistently <italic>H. pylori</italic>-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 <italic>H. pylori</italic> 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, <italic>H. pylori</italic> eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of <italic>H. pylori</italic>-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG.</p> </sec> </abstract>