No abstract

Background and aim: It is known that bile acids can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. A large body of genetic and biochemical evidence indicate that the biosynthetic pathway of prostaglandin E 2 (PGE 2 ) may play an important role in human and rodent tumours. Therefore, we examined the expression pattern of cyclooxygenase 1 (COX-1), COX-2, and microsomal prostaglandin E synthase 1 (mPGES-1), as well as EP receptor subtypes in rat oesophageal lesions induced by duodenal contents reflux. Methods: Oesophagoduodenal anastomosis was performed in rats to induce duodenal contents reflux. We examined histological changes and expression of COX-1, COX-2, mPGES-1, and EP receptor subtypes in the oesophagus by immunohistochemistry and reverse transcription-polymerase chain reaction. Results: Normal control oesophageal tissues showed COX-1 expression in subepithelial stromal cells, including endothelial cells and muscular cells, and did not reveal expression of COX-2 or mPGES-1. In the case of squamous cell lesions, immunoreactivity of COX-1 was similar to that of normal lesions, and COX-2 was maximally expressed around the vascular papillae of tissues showing dysplasia and surrounding epithelial layer and basal layer. mPGES-1 was highly expressed in stromal cells with COX-2 expression. In the case of Barrett's oesophagus, COX-2 and mPGES-1 were predominantly in subepithelial stromal cells. mRNA levels of COX-2, mPGES-1, EP 2 , EP 3 , and EP 4 were higher in the experimental groups than in controls. Conclusions: We suggest that the biosynthetic pathway of PGE 2 may play an important role in oesophageal squamous cell dysplasia and glandular metaplasia induced by duodenal contents reflux.

The p16INK4a tumor suppressor gene can be inactivated by promoter region hypermethylation in many tumor types including gastric cancers. However, p16INK4a promoter hypermethylation in the surrounding non-tumorous tissues of gastric cancers has not been studied in detail. We therefore examined 46 gastric cancers, corresponding adjacent nontumorous tissue samples and 8 gastric tissue samples of chronic gastritis by performing methylation-specific polymerase chain reaction, and we analyzed p16INK4a protein expression using immunohistochemistry and Western blot. p16INK4a promoter hypermethylation was observed in 43% of gastric cancers and 59% of adjacent non-tumorous tissues; however, none of the samples retrieved from the chronic gastritis patients displayed p16INK4a promoter hypermethylation. Gastric cancers showed an inverse correlation between vascular invasion and p16INK4a promoter hypermethylation, and adjacent non-tumorous tissues displayed a close association among the grade of chronic inflammation, presence of glandular atrophy and p16INK4a promoter hypermethylation. p16INK4a expression was markedly decreased in samples with p16INK4a promoter hypermethylation when compared with samples without p16INK4a promoter hypermethylation. These results suggest that p16INK4a promoter hypermethylation is an early and frequent event in gastric carcinogenesis and may serve as a new prognostic biomarker for the risk of gastric cancers.

We measured cell proliferation and apoptosis in the antral epithelial cells of Helicobacter pylori-infected and H. pylori-uninfected persons, and examined these processes in relation to diagnosis and the histologic parameters of inflammation to investigate their role in cellular turnover in diseases of the upper gastrointestinal tract. The subjects were: 25 patients with antral gastric cancers, 20 with antral gastric ulcers, 18 with duodenal ulcers, and 28 with chronic gastritis, and 4 subjects with normal gastric mucosa. Seventy-two subjects were infected with H. pylori, and 23 subjects, including the 4 with normal gastric mucosa, were uninfected. H. pylori infection was associated with increased apoptosis and cell proliferation in the gastric mucosa, which correlated with the degree of acute inflammation and the density of H. pylori, and these latter two factors correlated with each other. Intestinal metaplasia and glandular atrophy were significantly higher in gastric cancers and gastric ulcers than in duodenal ulcers. Cell proliferation was significantly lower in gastric cancers than in gastric ulcers, but the apoptotic count did not show a significant difference between these diseases. This decreased proliferation in the adjacent mucosa in gastric cancers compared with findings in the other diseases is thought to be closely related to the relatively decreased acute inflammation, which may, partly, contribute to glandular atrophy in the adjacent mucosa of gastric cancer.