Project/Area Number |
15590664
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | First department of internal medicine, Sapporo Medical University |
Principal Investigator |
ENDO Takao Sapporo Medical University, First department of internal medicine, Associate professor, 医学部, 助教授 (40191928)
|
Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Hiroyuki Sapporo Medical University, First department of internal medicine, Assistant professor, 医学部, 助手 (40332910)
|
Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Barrett's esophagus / PPI / chemo prevention / proton pump inhibitor(PPI) / Barrett粘膜 / 細胞増殖能 / 酸分泌抑制剤 |
Research Abstract |
We examined whether proton pump inhibitor(PPI) may diminish the risk of carcinogenesis. in Barrett's esophagus (BE). In our study, endoscopic biopsy specimens of BE was analyzed for change in the expression of Ki-67, COX-2, CDX-2, sulfo-Lewisa by immunohistochemistry before and after treatment with PPI. 6 months after treatment with PPI, there was a significant decrease in the expression of Ki-76 (cell proliferation maker) and COX-2 (proliferation-related agent). And there was a tendency to decrease in the expression of CDX-2(intestinal transcription factor) and sulfo-Lewisa (intestinal mucin). In contrast, treatment with histamin2 receptor antagonist (H2RA) showed no significant decrease in the expression of Ki-67, COX-2, CDX-2, sulfo-Le^a. We evaluated that treatment with PPI would reduce the expression of COX-2 and consequently cell proliferation would decrease. It was reported that the expression of between COX-2 and CDX-2 would be associated with p38 MAPK pathway. Accordingly, we examined the expression of Phospho-p38 in BE before and after treatment with PPI. There was a significant decrease in the expression of -Phospho-p38 in both epithelial cells and stromal cells in BE before and-after treatment with- PPL. Therefore, we concluded- that PPI- would inhibit- the- expression of both COX-2 and CDX-2 via p38. MAPK pathway and that consequently cell proliferation and intestinal metaplasia. would. diminish.
|