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.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Songhua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Biology and Biomedical Sciences, Salve Regina University, Newport, RI 02840, USA.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Morrissey
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Aponte-Pieras
authors.affiliation: Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA.
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Rogers
authors.affiliation: Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Electronic address: steven_moss@brown.edu.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Moss
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001284:Atrophy; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000172:deficiency / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005753:Gastric Mucosa / Q000378:metabolism; D005756:Gastritis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000472:pathogenicity; D006965:Hyperplasia; D018836:Inflammation Mediators / Q000378:metabolism; D008679:Metaplasia; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054328:Proton Pump Inhibitors / Q000008:administration & dosage; D013270:Stomach / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; C493961:Cdkn1b protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D054328:Proton Pump Inhibitors; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Chemokines; Gastric cancer; Helicobacter pylori; Inflammation; Mouse model