Roles of Helicobacter pylori infection and cyclooxygenase-2 expression in gastric carcinogenesis

AIM: Cyclooxygenase (COX)-2 is over expressed ingastrointestinal neoplasm. Helicobacter pylori ( H pylon)infection is causally linked to gastric cancer. However, theexpression of COX-2 in various stages of Hpylori-associatedgastric carcinogenesis pathway has not been elucidated.Therefore, the aim of this study was to clarify the role ofH pyloriinduced COX-2 expression during carcinogenesisin the stomach.METHODS: Gastric biopsies from 138 subjects [30 casesof chronic superficial gastritis (CSG), 28 cases of gastricglandular atrophy (GA), 45 cases of gastric mucosal intestinalmetaplasia (IM), 12 cases of moderate gastric epithelialdysplasia and 23 cases of gastric cancer] were enrolled.Hpyloriinfection was assessed by a rapid urease test andhistological examination (modified Giemsa staining). Theexpression of COX-1 and COX-2 in human gastric mucosawas detected by immunohistochemical staining.I^7~I_~: Hpyloriinfeddon rate was 64.3% in GA and 69.5%in gastric cancer, which was significantly higher than that(36.7%) in CSG (P<0.05). The positive expression rates ofCOX-2 were 10.0%, 35.7%, 37.8%, 41.7% and 69.5% inCSG, GA, IM, dysplasia and gastric cancer, respectively.From CSG to GA, IM, dysplasia and finally to gastric cancer,expression of COX-2 showed an ascending tendency, whereasCOX-1 expression did not change significantly in the gastricmucosa. The level of COX-2 expression in IM and dysplasiawas significantly higher in H pylon:positive than in H pylor/-negative subjects (P<0.01).

Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions

AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions.METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia(IM)and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1 000 mg thrice daily for 3 mo. All patients undervvent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy.Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay.RESULTS: The mean of folate concentration in gastric mucosa was 9.03±3.37 μg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83±3.02 μg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2oncogene protein decreased after folic acid therapy.CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.

Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients

AIM: One-week triple therapy with proton pump inhibitors, clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori(H pylori) infection; however, data regarding the effects of this regimen in China are scarce. The aim of this prospective and randomized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H pylori and ulcer healing in Chinese peptic ulcer patients.METHODS: A total of 103 subjects with H pylori-positive peptic ulcer were randomly divided into two groups, and accepted triple therapy with omeprazole 20 mg, amoxicillin 1 000 mg and either clarithromycin 500 mg (OAC group,n = 58) or metronidazole 400 mg (OAM group, n = 45).All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2-4 wk after anti-H pylori therapy. Six to eight weeks after omeprazole therapy, all patients underwent endoscopies and four biopsies (two from the antrum and two others from the corpus of stomach) were taken for rapid urease test and histological analysis (with modified Giemsa staining) to examine H pylori. Successful eradication was defined as negative results from both examination methods.RESULTS: One hundred patients completed the entire course of therapy and returned for follow-up. The eradication rate of H pylori for the per-protocol analysis was 89.3% (50/56) in OAC group and 84.1% (37/44) in OAM group. Based on the intention-to-treat analysis, the eradication rate of H pylori was 86.2% (50/58) in OAC group and 82.2% (37/45) in OAM group. There were no significant differences in eradication rates between the two groups on either analysis. The active ulcer-healing rate was 96.7% (29/30) in OAC group and 100% (21/21)in OAM group (per-protocol analysis, P＞0.05). Six patients in OAC group (10.3%) and five in OAM group (11.1%)reported adverse events (P＞0.05).CONCLUSION: One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H pylori. The therapeutic regimen comprising metronidazole with low cost, good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H pylori infection in China.