Antimetastatic therapy by matrix metalloproteinase inhibitors
| Project/Area Number |
10671216
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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 | Keio University |
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Principal Investigator |
OTANI Yoshihide Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (20168983)
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| Co-Investigator(Kenkyū-buntansha) |
KAMEYAMA Kaori Keio University, School of Medicine, Instructor, 医学部, 助手 (10245467)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Gastric cancer / peritoneal dissemination / metastasis / invasion / matrix metalloproteinases / MMP / G.I.tract cancer / tumor |
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| Research Abstract |
Cancer cells degradate extracellular matrix around cancer nests during invasion and metastasis. We have reported the role of matrix metalloproteinases in invasion and metastasis using gastrointestinal tract cancers. Postoperative survival of gastric cancer patients with peritoneal dissemination is very poor. We investigated therapeutic efficacy of newly developed, synthetic MMP inhibitors.
First, nude mice peritoneal dissemination model of human gastric cancer cell line was established. A gastric carcinoma cell line (TMK-1;5x10ィイD15ィエD1/body) was injected intraperitoneally into nude mice. Subsequently, R-94138 (30 mg/kg), CDDP (3 mg/kg) and MMC (2 mg/kg) were administered alone or in combination of two of these agents into the mice. They were sacrificed 5 weeks after the injection, and therapeutic efficacy was evaluated by counting the number of peritoneal nodules. R-94138 significantly decreased the formation of peritoneal nodules and the combination of R-94138 and MMC significantly decreased the number of peritoneal nodules compared with a control or other combination groups.
In conclusion, MMP inhibitor suppressed the peritoneal metastasis in nude mice model. The possibility of clinical application of MMP inhibitor was evidenced in this study.
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Report
(3 results)
Research Products
(16 results)
