It has previously been reported that Cdx2 is the useful prognostic and intestinal phenotypic marker in advanced gastric cancers (GC). In this study, Cdx2 expression and phenotype in early GC and non-neoplastic surrounding mucosa were examined. A total of 130 early GC (70 intramucosal and 60 submucosally invasive cancers) histologically and phenotypically were evaluated. The expression of Cdx2 was assessed by immunohistochemistry. The lesions were phenotypically divided into 44 gastric (G), 42 gastric and intestinal mixed (GI), 30 intestinal (I), and 14 null (N) types, independent of the histological classification. Most of the early GC were Cdx2-positive, nuclear staining being strongly associated with intestinal phenotypic expression. Early differentiated cancers tended to feature both Cdx2 and intestinal phenotypic expression, while their undifferentiated counterparts were more likely to demonstrate only gastric phenotypic expression (P < 0.05). The phenotypes of six intramucosal microcarcinomas did not correlate with those of adjacent normal glands. These data suggest that Cdx2 is expressed in the very early stage of gastric carcinogenesis in association with the shift from gastric to intestinal phenotypic expression. This appears to occur in differentiated cancers at an earlier stage than in undifferentiated ones, and may be linked to suppression of expansion of malignant cells.

Intake of salt and salty food is known as a risk factor for gastric carcinogenesis. To examine the dose-dependence and the mechanisms underlying enhancing effects, Mongolian gerbils were treated with N-methyl-N-nitrosourea (MNU), Helicobacter pylori and food containing various concentrations of salt, and were sacrificed after 50 weeks. Among gerbils treated with MNU and H. pylori, the incidences of glandular stomach cancers were 15% in the normal diet group and 33%, 36% and 63% in the 2.5%, 5% and 10% NaCl diet groups, showing dose-dependent increase (p < 0.01). Intermittent intragastric injection of saturated NaCl solution, in contrast, did not promote gastric carcinogenesis. In gerbils infected with H. pylori, a high salt diet was associated with elevation of anti-H. pylori antibody titers, serum gastrin levels and inflammatory cell infiltration in a dose-dependent fashion. Ten percent NaCl diet upregulated the amount of surface mucous cell mucin (p < 0.05), suitable for H. pylori colonization, despite no increment of MUC5AC mRNA, while H. pylori infection itself had an opposing effect, stimulating transcription of MUC6 and increasing the amount of gland mucous cell mucin (GMCM). High salt diet, in turn, decreased the amount of GMCM, which acts against H. pylori infection. In conclusion, the present study demonstrated dose-dependent enhancing effects of salt in gastric chemical carcinogenesis in H. pylori-infected Mongolian gerbils associated with alteration of the mucous microenvironment. Reduction of salt intake could thus be one of the most important chemopreventive methods for human gastric carcinogenesis. ' 2006 Wiley-Liss, Inc.

The extended Poole-Frenkel model presented here includes the variation of the barrier height with electric field in directions both opposite and forward to the electric force on an electron. The equation for the voltage-current characteristics based on this model gives not only the usual Poole-Frenkel equation at extremely high electric fields but also Ohm's law at low fields. Several published experimental data are in good agreement with this equation.

The Helicobacter pylori-infected Mongolian gerbil (MG) has been established as an appropriate animal model for studies of stomach cancer development. However, there have hitherto been no data on the phenotypic classification of glandular stomach cancers in H. pylori-infected and non-infected MG. We therefore examined the phenotypes of 50 and six advanced glandular stomach cancers in H. pylori-infected and non-infected MG, respectively, as well as adjacent non-neoplastic mucosa, using several gastrointestinal epithelial phenotypic markers. The lesions were divided phenotypically into 21 gastric, 24 gastric-and-intestinal mixed, four intestinal and one null types, with 90.0% of the lesions harboring gastric elements and 56.0% demonstrating intestinal phenotypic expression in H. pylori-infected MG. All six lesions were classified as gastric type in non-infected MG. There was no clear correlation with the presence of intestinal metaplasia in surrounding mucosa. In conclusion, our data suggest that most advanced adenocarcinomas retain a gastric cellular phenotype in the glandular MG stomach. Thus, it might be proposed that intestinal metaplasia is a paracancerous phenomenon rather than a premalignant condition. H. pylori infection may trigger intestinalization of both stomach cancers and non-neoplastic mucosa.