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Anti-Helicobacter pylori therapy followed by celecoxib on progression of gastric precancerous lesions.
- Source :
-
World journal of gastroenterology [World J Gastroenterol] 2009 Jun 14; Vol. 15 (22), pp. 2731-8. - Publication Year :
- 2009
-
Abstract
- Aim: 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.<br />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.<br />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.<br />Conclusion: 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.
- Subjects :
- Adult
Aged
Apoptosis drug effects
Celecoxib
Cell Proliferation
Cyclooxygenase 2 genetics
Cyclooxygenase 2 metabolism
Disease Progression
Helicobacter Infections complications
Humans
Ki-67 Antigen genetics
Ki-67 Antigen metabolism
Middle Aged
Neovascularization, Pathologic
PPAR gamma genetics
PPAR gamma metabolism
Placebos
Precancerous Conditions microbiology
Precancerous Conditions pathology
Stomach Neoplasms drug therapy
Stomach Neoplasms etiology
Stomach Neoplasms microbiology
Stomach Neoplasms pathology
Cyclooxygenase 2 Inhibitors pharmacology
Cyclooxygenase 2 Inhibitors therapeutic use
Helicobacter Infections drug therapy
Helicobacter pylori drug effects
Precancerous Conditions drug therapy
Pyrazoles pharmacology
Pyrazoles therapeutic use
Sulfonamides pharmacology
Sulfonamides therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 2219-2840
- Volume :
- 15
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- World journal of gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 19522023
- Full Text :
- https://doi.org/10.3748/wjg.15.2731