Anti-angiogenic Therapy on Gastrointestinal Cancer
| Project/Area Number |
11671225
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
TANAKA Tatsuo Department of Surgery II, Hamamatsu University School of Medicine, Research Associate, 医学部, 助手 (90273185)
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| Co-Investigator(Kenkyū-buntansha) |
KONNO Hiroyuki Department of Surgery II, Hamamatsu University School of Medicine, Associate Professor, 医学部, 助教授 (00138033)
神谷 欣志 浜松医科大学, 医学部・附属病院, 助手 (20324361)
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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 |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | anti-angigenic therapy / human colon cancer / nude mouse model / liver metastasis / metalloproteinase inhibitor / ヌードマウスモデル / MMP阻害剤 / 血管新生阻害 / 大腸癌肝転移 / ヒト大腸癌TK4 / 大腸癌同所移植モデル |
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| Research Abstract |
Several synthetic inhibitors of matrix metalloproteinases (MMPs) have been designed and have revealed anti-tumor, anti-metastasis and anti-angiogenesis effects in various models. Synergistic effects of the combination with conventional cytotoxic agents were reported previously. In this study, we cxamined the effects of a new selective MMP inhibitor, MMI-166, on tumor growth, angiogenesis and metastasis in a liver metastatic model of human xenotransplanted colon cancer (TK-4). We also investigated the synergistic effects of MMI-166 and a conventional cytotoxic agent, mitomycin C (MMC) in this model. Mice transplanted with TK-4 orthotopically were divided into 4 groups ; a control group (treated by vehicle solution), MMI-166 group in which MMI-166 was orally administered (p.o.) at a dose of 200mg/kg, 6days/week for 5 weeks, MMC group in which MMC was administered intraperitoneally (i.p.) at a dose of 2mg/kg/week for 5 weeks, and a combination group (treated by MMI-166 and MMC). MMI-166 did not inhibit transplanted tumor growth, but significantly inhibited liver metastasis compared with the control group and MMC group (P<0.01). Significant antitumor and antimetastatic effects were demonstrated by the combination therapy. The microvessel density (MVD) detected by immunohistochemical staining with ER-MP12 antibody had a tendency to be low in the MMI-166and the combination groups. These results suggest that MMI-166 has the potential anti-metastatic ability and a synergistic effect with MMC.
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Report
(3 results)
Research Products
(3 results)
