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. 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-2protein 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-2protein 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. 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.
RCT Entities:
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. 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. 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.
Authors: Jun Yu; Liang Qiao; Lars Zimmermann; Matthias P A Ebert; Hongxia Zhang; Wendy Lin; Christoph Röcken; Peter Malfertheiner; Geoffrey C Farrell Journal: Hepatology Date: 2006-01 Impact factor: 17.425
Authors: M Dinis-Ribeiro; M Areia; A C de Vries; R Marcos-Pinto; M Monteiro-Soares; A O'Connor; C Pereira; P Pimentel-Nunes; R Correia; A Ensari; J M Dumonceau; J C Machado; G Macedo; P Malfertheiner; T Matysiak-Budnik; F Megraud; K Miki; C O'Morain; R M Peek; T Ponchon; A Ristimaki; B Rembacken; F Carneiro; E J Kuipers Journal: Virchows Arch Date: 2011-12-22 Impact factor: 4.064
Authors: M Dinis-Ribeiro; M Areia; A C de Vries; R Marcos-Pinto; M Monteiro-Soares; A O'Connor; C Pereira; P Pimentel-Nunes; R Correia; A Ensari; J M Dumonceau; J C Machado; G Macedo; P Malfertheiner; T Matysiak-Budnik; F Megraud; K Miki; C O'Morain; R M Peek; T Ponchon; A Ristimaki; B Rembacken; F Carneiro; E J Kuipers Journal: Endoscopy Date: 2011-12-23 Impact factor: 10.093
Authors: Matthew Banks; David Graham; Marnix Jansen; Takuji Gotoda; Sergio Coda; Massimiliano di Pietro; Noriya Uedo; Pradeep Bhandari; D Mark Pritchard; Ernst J Kuipers; Manuel Rodriguez-Justo; Marco R Novelli; Krish Ragunath; Neil Shepherd; Mario Dinis-Ribeiro Journal: Gut Date: 2019-07-05 Impact factor: 23.059