Reduction of prostaglandin transporter predicts poor prognosis associated with angiogenesis in gastric adenocarcinoma.

BACKGROUND AND AIM: Prostaglandin (PG) E2 promotes gastrointestinal carcinogenesis and tumor progression. The total amount of biologically active PGE2 in tissues is determined by a balance of PG biosynthesis and degradation pathways, which involve the PG transporter (PGT). We investigated PGT in gastric adenocarcinoma by determining its expression pattern and examining associations of PGT with prognosis and tumor angiogenesis. METHODS: PGT expression was determined by immunohistochemistry in advanced gastric adenocarcinoma specimens obtained from 96 patients who underwent surgical resection. Correlations between PGT expression level and clinicopathological factors were statistically analyzed. Angiogenesis in the tumor tissue was evaluated by counting the number of microvessels. The role of PGT in mRNA and protein expression of vascular endothelial growth factor (VEGF) was examined in gastric cancer cells stimulated by PGE2 . RESULTS: Based on multivariate and Kaplan-Meier analyses, negativity for PGT expression was an independent poor prognostic factor. There were more microvessels in PGT-negative tumors than in PGT-positive tumors. Transfection of AGS and MKN7 gastric cancer cells with PGT-specific siRNA led to increased VEGF mRNA and protein expression accompanied by increased PGE2 in the culture media. CONCLUSIONS: PGT expression is an independent predictor of poor survival and is associated with tumor angiogenesis in gastric adenocarcinoma.

A multicenter study on the prevalence of eosinophilic esophagitis and PPI-responsive esophageal eosinophilic infiltration.

OBJECTIVE: Eosinophilic esophagitis (EoE) is diagnosed by the presence of dysphagia and intraepithelial eosinophilic infiltration of ≥15 per high-power field (HPF). EoE should be distinguished from proton pump inhibitor-responsive esophageal eosinophilic infiltration (PPI-R EEI) in patients that are responsive to PPI treatment. The aim of this study was to determine the prevalence of EoE and PPI-R EEI in Japanese patients in a multicenter study. METHODS: Ten hospitals participated in this study. Esophageal biopsy was performed when the patients had typical EoE symptoms or when endoscopic findings revealed a typical EoE appearance. EEI was defined as the intraepithelial eosinophilic infiltration of ≥15 per HPF. Patients with EEI received rabeprazole for 8 weeks to distinguish EoE from PPI-R EEI. RESULTS: A total of 13,634 subjects that underwent upper gastrointestinal endoscopy because of further examination or as a routine checkup were enrolled. Seventy-one (0.5%) patients suspected with EoE were examined by biopsy. A histological examination of 7 (9.9%) cases revealed EEI. Two of these 7 patients showed no symptoms and the other 5 were treated with PPI. Two (0.01%) patients were diagnosed with EoE and 3 (0.02%) with PPI-R EEI. CONCLUSION: EoE and PPI-R EEI were rare in Japanese patients that underwent upper gastrointestinal endoscopy.

Reduction of 15-hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma.

Prostaglandin (PG) E(2) promotes gastrointestinal carcinogenesis and tumor progression. We determined the correlations between pattern of expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a catabolic enzyme for biological inactivation of PGE(2), in gastric adenocarcinoma and various clinicopathological factors and patient outcome in an attempt to elucidate its biological significance. In 35 of 71 cases of gastric adenocarcinoma, expression of 15-PGDH protein was reduced in tumor tissues. Multivariate analysis revealed reduction of 15-PGDH expression to be an independent predictor of poor survival. The proportion of Ki67-positive cells in 15-PGDH-negative adenocarcinoma was higher than that in 15-PGDH-positive adenocarcinoma. No differences were found in clinicopathological parameters between patients with cyclooxygenase-2 (COX-2)-positive tumors and those with COX-2 negative tumors. In an in vitro study, use of specific siRNA to silence 15-PGDH or a specific inhibitor of 15-PGDH enhanced cell proliferation in the gastric cancer cell line AGS, which expresses 15-PGDH. These findings suggest that reduction of 15-PGDH is an independent predictor of poor survival associated with enhancement of cell proliferation in gastric adenocarcinoma.