| Project/Area Number |
11671253
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
KATANO Mitsuo Graduate School of Medical Sciences, KYUSHU UNIVERSITY Prof., 大学院・医学研究院, 教授 (10145203)
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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 |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | cancerous peritonitis / cyclosporin-A / interferon-gamma / carcineurin / apoptosis / JAK / STAT pathway / NF-AT / NF-κB / 胃癌細胞 / インターフェロンーガンマ / FK506 / カルシウム |
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| Research Abstract |
The prognois of cancerous peritonitis originated from digestive organ cancer is very poor. This study was planned to develop new treatment for cancer patients with cancerous peritonitis. For this purpose, we used cyclosporin-A (CsA) which is a clinically important immunosuppressive drug widely used to prevent graft rejection following organ or bone marrow transplantation. Results obtained during this observation period are as follows. (1) Combination of CsA and interferon-gamma (IFN-γ) induces significant apoptosis in various types of human carcinoma cells. (2) Proposed mechamism : IFN-γ activates not only JAK/STAT pathway and caspase cascade (apotosis pathway) but also NF-AT and/or NF-κB through activastion the Ca^<2+>-/CaM-dependent carcineurin pathway (anti-apotosis pathway). Suppression of anti-apoptosis pathway by CsA induces predominance of apoptosis pathway. (3) Intraperitoneal injection of OK-432 for managenent of cancerous peritonitis induces a detectable IFN-γ production in ascitic fluids. A combination of CsA with IFN-γ-containing ascitic fluids after but not before OK-432 injection induced significant apoptosis in carcinoma cells existing in the fluids. These results indicate that a combination of CsA and the OK-432 therapy or IFN-γ may, in the near future, be a useful therapeutic strategy for gastrointestinal cancer patients with cancerous peritonitis.
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