| Project/Area Number |
16591376
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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 | Kurume University |
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Principal Investigator |
AOYAGI Keishiro Kurume University, Faculty of Medicine, Assistant Professor (20202492)
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| Co-Investigator(Kenkyū-buntansha) |
IMAIZUMI Takuya Kurume University, Faculty of Medicine, Assistant Professor (10421314)
KOGA Atsuhiiko Kurume University, Faculty of Medicine, Assistant Professor (90320217)
MIYAGI Motoshi Kurume University, Faculty of Medicine, Assistant Professor (80309806)
加藤 誠也 久留米大学, 医学部, 助教授 (60268844)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥270,000)
Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | gastric cancer / peritoneal dissemination / peritoneal metastasis model / VEGF / VEGF-C / MMPs / high-potential peritoneal metastasis cell line / moleculat targetting therapy / Western blotting / fibronectin / MMP阻害剤 / VEGF阻害剤 / OPB3206 / AVASTIN / MMP-2 / MKN-45 |
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| Research Abstract |
It has become clear in recent years that peritoneal metastasis takes place as the results of a multistep process involving attachment, invasion, proliferation, and angiogenesis. The aim of the present study was to evaluate the suppressive effect of MMP inhibitor and VEGF inhibitor as molecular targeting therapy on peritoneal dissemination.
We established a high-potential peritoneal metastasis cell line (MKN-45P), using the gastric cancer cell line MKN-45, and developed a peritoneal metastasis model in nude mice. The concentration of IL-6, IL-8, MMP-2 and VEGF on MKN-45 was significantly higher than those on MKN-45. Immunohistochemical staining for VEGF and MMP-2 was performed of slides of surgical specimens from patients with Stage II gastric cancer with serosal invasion. VEGF was correlated with peritoneal metastasis from gastric cancer, and that VEGF was a useful indicator of peritoneal recurrence. On in vivo study using peritoneal metastasis model, the frequency of hydronephrosis, mitosis index and survival rate of MMP inhibitor or VEGF inhibitor administrated group were significantly higher than those of control group, and ascites volume of VEGF administrated group was significantly higher than that of control group. These results suggested, these drugs, especially VEGF inhibitor were useful molecular targeting therapy for peritoneal dissemination.
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