Development of carcinoid tumors of the glandular stomach and effects of eradication in Helicobacter pylori-infected Mongolian gerbils.

The relation between Helicobacter pylori (Hp) eradication and prevention of stomach carcinoid development has hitherto remained unclear. We therefore examined this problem using an Hp-infected and Hp-eradicated Mongolian gerbil (MG) model. Enterochromaffin-like (ECL) lesions (hyperplasia/dysplasia and carcinoid) were histopathologically evaluated in the glandular stomachs of Hp-infected and Hp-eradicated MGs. In addition, serum gastrin levels were analyzed. Hp infection induced significant increase in the development of ECL lesions in the glandular stomach, as well as serum gastrin levels as compared with non-infected MGs, while Hp eradication was associated with significant alleviation. The development of ECL lesions in the glandular stomach strongly correlated with titers of anti-Hp antibodies and serum gastrin levels in MGs. In conclusion, Hp infection induces carcinoid development, and Hp eradication prevents its occurrence in the glandular MG stomach, this being strongly linked with reduction in serum gastrin levels.

Intestinal phenotypes of stomach cancers arising after Helicobacter pylori eradication in carcinogen-treated Mongolian gerbils.

AIMS: We have previously demonstrated the importance of gastric and intestinal phenotypic expression for the histogenesis of stomach cancer. However, the phenotypes of stomach cancers arising after Helicobacter pylori (Hp) eradication have hitherto remained unclear. We therefore examined a series of lesions occurring after Hp eradication in the Mongolian gerbil (MG) model. METHODS: Totals of 6 and 20 advanced glandular stomach cancers were evaluated in Hp-eradicated and Hp-infected MGs treated with N-methyl-N-nitrosourea (MNU-MGs), using several gastrointestinal epithelial phenotypic markers. The lesions were divided phenotypically into gastric (G type), gastric-and-intestinal mixed (GI type), intestinal (I type), and null (N type) phenotypes. RESULTS: All 4 differentiated type lesions in Hp-eradicated MNU-MGs were classified as G type, while both of the undifferentiated lesions exhibit the GI type. In Hp-infected MNU-MGs, the lesions were classified as 10 G, 8 GI, and 2 I types, with undifferentiated type lesions having more intestinal phenotypic expression than their differentiated counterparts (P< 0.01). CONCLUSIONS: Our data suggest that the differentiated stomach cancers exhibit the G type in Hp-eradicated MNU-MGs, suggesting that a kind of non-neoplastic G type gland may be precancerous. Intestinalization may still occur, especially in undifferentiated stomach cancers, even if Hp eradication is successful.

Suppressive effects of fruit-juice concentrate of Prunus mume Sieb. et Zucc. (Japanese apricot, Ume) on Helicobacter pylori-induced glandular stomach lesions in Mongolian gerbils.

Helicobacter pylori (Hp) infection is an important factor in human gastric disorders, including chronic active gastritis, peptic ulcers, intestinal metaplasia and cancer. Since epidemiologic studies overwhelmingly agree on a protective influence of fruits and vegetables in reducing the risk of gastric neoplasia and processed foods made from Prunus mume Sieb. et Zucc. (Japanese apricot or "Ume" in Japanese) are traditionally known for their miscellaneous medical effects, in the present study we investigated the efficacy of a fruit-juice concentrate of Japanese apricot (CJA) in the glandular stomach of Hp-infected Mongolian gerbils. Hp-inoculated gerbils were given CJA in their drinking water at concentrations of 1 and 3% for 10 weeks. The microscopic scores for gastritis and mucosal hyperplasia in the CJA groups were significantly lower than in the Hp-inoculated control group, with dose-dependence. Real-time PCR was performed to quantitate Hp by demonstrating urease A gene amount using gerbils glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene as an internal control. Average relative urease A gene dosage in the glandular stomach in the 1 and 3% CJA and Hp-inoculated control groups was 26.6 +/- 11.6% (average +/- SE), 30.3 +/- 10.5%, 100 +/- 40.9%, respectively, the fruit-juice concentrate causing significant lowering (P<0.01 and P<0.05, respectively, with 1 and 3%). These findings suggest that suppressive effects on gastric cancer development might also be expected as a result of decreased numbers of Hp and improvement of Hp-induced chronic active gastritis on administration of CJA.