2001 Fiscal Year Final Research Report Summary
Modification of Cell Signaling in EBV Infected Gastric Epithelial Cells by H. pylori.
| Project/Area Number |
11670297
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Virology
|
|---|
| Research Institution | Hokkaido University (2000-2001)
Yamaguchi University (1999) |
|---|
Principal Investigator |
YOSHIYAMA Hironori Hokkaido Univ. Inst. for Genetic Med., Asso. prof., 遺伝子病制御研究所, 助教授 (10253147)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKADA Kenzo Hokkaido Univ. Inst. for Genet. Med., Prof., 遺伝子病制御研究所, 教授 (30133721)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Keywords | EB virus / Helicobacter pylori / Gastric cancer / Cell signaling |
|---|
| Research Abstract |
EB virus (EBV) causes Burkitt's lymphoma and nasopharyngeal carcinoma, though EBV is a ubiquitous human herpes virus that infects greater than 90 % of the world's population. Cofactors or risk factors has been considered to be important for the clinical expression of the potentially oncogenic EBV infection. Latent EBV-infection has recently been detected in the tissue of about 10 % of gastric carcinoma cases, which suggests that EBV plays an important role in the development of EBV-associated gastric carcinomas. We have reported EBV infection in noncarcinomatous epithelium(J. Pathol. 183 : 293, 1997). Since Helicobacter pylori (H. pylori) is thought to be related to gastric carcinogenesis through the development of chronic atrophic gastritis, it should be elucidated whether the carcinogenic process of EBV-associated gastric carcinoma requires the presence of H. pylori-caused atrophic gastritis.
We have evaluated the degree of gastritis in the background gastric mucosa of 8 EBV-associate
… More
d and 16 -unassociated gastric carcinoma cases. The background gastric mucosa for EBV-associated gastric carcinoma was rich (87.5 %) in atrophic changes compared with EBV-unassociated gastric carcinoma (62.5 %). Moreover, EBV-positive gastric carcinoma lesions were located near the atrophic border at which the glandular structure changes from fundic glands to intestinal-type metastatic glands or mucous glands, where the regular epithelial cell kinetics of the generative zone can be disturbed. Accordingly, chronic atrophic gastritis caused by H. pylori may be a possible cofactor in EBV-associated gastric carcinogenesis (J. Clin. Gastroenterol. 29 : 39, 1999).
We have then studied the mutual action of H. pylori and gastric epithelia. We have shown that urease activity of H. pylori is important for its colonization in the gastric mucosa(Microb. Infet. 2 : 1,2000). We have also studied the mechanism by which H.pylori infection induces apoptosis in epithelial cells of the stomach in H. pylori-infected patients. Human gastric epithelial cell lines were cocultured with H. pylori. and the level of apoptosis and ammonia production was measured. While a large amount of ammonia (> 30 mM) accumulated in the coculture, no significant degree of apoptosis occurred. In the presence of tumor necrosis factor alpha (TNF-α), however, a marked acceleration of apoptosis was found. This enhancement of apoptosis was found in the cell culture containing TNF-α by the addition of as low as 4 to 8 mM ammonia. As a result, it was demonstrated that the ammonia generated from the urea markedly accelerated the apoptosis induced by TNF-α, which can be produced by gastric epithelia(Infect. Immun. 69 : 816,2001).
Possible interaction between EBV and H. pylori for cancer formation in the gastric epithelia through a cross talk mechanism appears to be warranted. Less
|
Research Products
(12 results)
