title: Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions.
abstract: OBJECTIVE
  To evaluate whether celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, could reduce the severity of gastric precancerous lesions following Helicobacter pylori (H pylori) eradication.
  
  
  METHODS
  H pylori-eradicated patients with gastric precancerous lesions randomly received either celecoxib (n = 30) or placebo (n = 30) for up to 3 mo. COX-2 expression and activity was determined by immunostaining and prostaglandin E(2) (PGE(2)) assay, cell proliferation by Ki-67 immunostaining, apoptosis by TUNEL staining and angiogenesis by microvascular density (MVD) assay using CD31 staining.
  
  
  RESULTS
  COX-2 protein expression was significantly increased in gastric precancerous lesions (atrophy, intestinal metaplasia and dysplasia, respectively) compared with chronic gastritis, and was concomitant with an increase in cell proliferation and angiogenesis. A significant improvement in precancerous lesions was observed in patients who received celecoxib compared with those who received placebo (P < 0.001). Of these three changes, 84.6% of sites with dysplasia regressed in patients treated with celecoxib (P = 0.002) compared with 60% in the placebo group, suggesting that celecoxib was effective on the regression of dysplasia. COX-2 protein expression (P < 0.001) and COX-2 activity (P < 0.001) in the gastric tissues were consistently lower in celecoxib-treated patients compared with the placebo-treated subjects. Moreover, it was also shown that celecoxib suppressed cell proliferation (P < 0.01), induced cell apoptosis (P < 0.01) and inhibited angiogenesis with decreased MVD (P < 0.001). However, all of these effects were not seen in placebo-treated subjects. Furthermore, COX-2 inhibition resulted in the up-regulation of PPARgamma expression, a protective molecule with anti-neoplastic effects.
  
  
  CONCLUSIONS
  H pylori eradication therapy followed by celecoxib treatment improves gastric precancerous lesions by inhibiting COX-2 activity, inducing apoptosis, and suppressing cell proliferation and angiogenesis.
authors.affiliation: Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Shi-Yan
authors.initials: SY
authors.lastname: Wang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Huo
authors.forename: Zhen-Long
authors.initials: ZL
authors.lastname: Zhu
authors.forename: Jian-Kun
authors.initials: JK
authors.lastname: Chu
authors.forename: Jin-Cheng
authors.initials: JC
authors.lastname: Ma
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Cui
authors.forename: Ping
authors.initials: P
authors.lastname: Gu
authors.forename: Zeng-Ren
authors.initials: ZR
authors.lastname: Zhao
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018450:Disease Progression; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010919:Placebos; D011230:Precancerous Conditions / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D019394:Ki-67 Antigen; D047495:PPAR gamma; D010919:Placebos; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib