2001 Fiscal Year Final Research Report Summary
Nobel antimetastatic therapy by MMP inhibitor for peritoneal dissemination of gastric carcinoma
| Project/Area Number |
12671260
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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 School of Medicine, Keio University, Assistant Professor, 医学部, 専任講師 (20168983)
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| Project Period (FY) |
2000 – 2001
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| Keywords | gastric cancer / peritoneal dissemination / metartasis / invasion / matrix metalloproteinased / 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 (MMPs) in invasion and metastasis using gastrointestinal tract and head and neck cancers. Postoperative survival rate of gastric cancer patients with peritoneal, dissemination is very poor. We investigated therapeutic efficacy of newly developed MMP inhibitors.
First, SCID mice model of peritoneal dissemination of human gastric cancer cell line was established. Gastric carcinoma cells (TMK-1,5 x 10^5/body) were injected intraperitoneally into SCID mice. Subsequently, MMP inhibitors, marimastat or nobiletin were injected. The mice were sacrificed 5 weeks after the injection, and therapeutic efficacy was evaluated by measuring the total weight of peritoneal nodules. Both marimastat and nobiletin significantly decreased the formation of peritoneal nodules.
In conclusion, MMP inhibitor suppressed the peritoneal metastasis of human gastric carcinoma in SCID mice model. The possibility of clinical application of MMP inhibitors was evidenced in this study.
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