title: Helicobacter pylori, cyclooxygenase-2 and evolution of gastric lesions: results from an intervention trial in China.
abstract: To investigate the role of cyclooxygenase (COX)-2/prostaglandin E2 (PGE2) in the process of Helicobacter pylori-induced gastric carcinogenesis, a prospective study based on an intervention trial was conducted in Linqu County, China. A total of 1401 subjects with histopathologic diagnosis were investigated at baseline, among those, 919 completed subsequent interventions (anti-H.pylori and/or celecoxib treatment). Expressions of COX-2 and Ki-67 were assessed by immunohistochemistry, and PGE2 levels were measured by enzyme immunoassay before and after interventions, respectively. We found a grade-response relationship between COX-2 expression level and risk of advanced gastric lesions at baseline. Stratified analysis indicated an additive interaction between COX-2 expression and H.pylori infection on the elevated risk of advanced gastric lesions. The odds ratios (ORs) for both factors combined were 9.31 [95% confidence interval (CI): 4.13-20.95] for chronic atrophic gastritis, 16.26 (95% CI: 7.29-36.24) for intestinal metaplasia and 21.13 (95% CI: 7.87-56.75) for dysplasia, respectively. After interventions, COX-2 expression and Ki-67 labeling index (LI) were decreased in anti-H.pylori group (OR: 1.65, 95% CI: 1.36-1.99 for COX-2; OR: 1.78, 95% CI: 1.49-2.12 for Ki-67) or anti-H.pylori followed by celecoxib group (OR: 1.41, 95% CI: 1.17-1.70 for COX-2; OR: 1.63, 95% CI: 1.37-1.94 for Ki-67). PGE2 levels were decreased in all treatment groups. Furthermore, the regression of gastric lesions was associated with the decrease of COX-2 expression or Ki-67 LI after interventions. Our findings indicate that H.pylori-induced COX-2/PGE2 pathways play an important role on the progression of precancerous gastric lesions in a Chinese population.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Pan
authors.forename: Lian
authors.initials: L
authors.lastname: Zhang
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Ma
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology and.
authors.forename: Ji-You
authors.initials: JY
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shen
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: You
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000068579:Celecoxib / Q000627:therapeutic use*; D002681:China; D017291:Clarithromycin / Q000627:therapeutic use; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D013270:Stomach / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D013274:Stomach Neoplasms / Q000201:enzymology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents; D052246:Cyclooxygenase 2 Inhibitors; D000658:Amoxicillin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D017291:Clarithromycin; D000068579:Celecoxib; D015232:Dinoprostone; D009853:Omeprazole