| Project/Area Number |
11671291
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KAWASAKI MEDICAL SCHOOL |
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Principal Investigator |
TSUNODA Tsukasa Kawasaki Medical School, Surgery, Professor, 医学部, 教授 (00110841)
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| Co-Investigator(Kenkyū-buntansha) |
IKI Katsumichi Kawasaki Medical School, Surgery, Faculty Assistant, 医学部, 助手 (00268608)
MAJIMA Toshimitsu Kawasaki Medical School, Surgery, Assistant Professor, 医学部, 講師 (80209428)
IWAMOTO Sueharu Kawasaki Medical School, Surgery, Assistant Professor, 医学部, 講師 (60168599)
YAMAMURA Masahiro Kawasaki Medical School, Surgery, Faculty Assistant, 医学部, 助手 (70299204)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Rapid production model for hamster pancreatic cancer / Matrix metalloproteinase (MMP) / Gelatin zymography / Chemoprevention / OPB-3206 / Immunohistochemistry / Serum / MMP / ハムスター / matrix metalloproteinase(MMP) / tissue inhibitor of MMP(TIMP) / 免疫染色 / 血清学的早期診断 |
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| Research Abstract |
In order to assess the significance of changes in metalloproteinase activity in pancreatic carcinogenesis, the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in a rapid production model for pancreatic duct carcinomas in hamsters initiated with N-nitrosobis (2-oxopropyl) amine (BOP) was investigated. Northern analysis revealed MMP-2 and MMP-9 mRNAs to be overexpressed in pancreatic duct carcinomas. Immunohistochemically, elevated levels of MMP-2 were apparent in early duct epithelial hyperplasias and staining increased from atypical hyperplasias to carcinomas. Gelatin zymography demonstrated clear activation of proMMP-2 but not proMMP-9 in primary tumors. Moreover we also invetigated that sera from hamsters with transplantable hamster pancreatic duct carcinoma (HPDt) possessed serum MMP-2 levels five times higher than the control sera as determined by gelatin zymographic analysis.
In our rapid production model, 0.1% and 0.2% OPB-3206, an inhibitor of MMPs, given in the diet after two cycles of augmentation pressures for 48 days decreased the incidence and number of carcinomas. Gelatin zymography demonstrated that OPB-3206 inhibited activation of proMMP-2 in pancreatic cancer tissues. These results indicate that over expression of MMP-2 and MMP-9 are involved in the development of pancreatic duct adenocarcinomas and that MMP-2 expression at the protein level appears in the early phase of pancreatic duct carcinogenesis. Serum MMPs may be useful markers for monitoring patients with pancreatic adenocarcinoma. OPB-3206 may be candidate chemopreventive agent for pancreatic ductal adenocarcinomas.
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