| Project/Area Number |
59480275
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Institute of Medical Science, University of Tokyo |
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Principal Investigator |
FUJII Genshichiro Institute of Medical Science, University of Tokyo, 医科学研究所, 教授 (50012696)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Tsukasa Institute of Medical Science, University of Tokyo, 助手 (90143510)
FUJII Yuzo Institute of Medical Science, University of Tokyo, 助手 (40143515)
HAGIWARA Tetsuro Institute of Medical Science, University of Tokyo, 元助手 (40114607)
MIYAMOTO Yoju Institute of Medical Science, University of Tokyo, 助手 (80012780)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1985: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1984: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | residual minimum tumor / DHR / fatty acid synthesis / immune cytolysis / 治癒手術 / 脂質代謝阻害剤免疫細胞溶解 |
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| Research Abstract |
In order to increase cure rate after curative operation for advanced gastrointestinal cancers, effective strategy against residual minimum tumor is thought to be essential. For the purpose, we investigated antitumor effect of delayed hypersensitivity reaction in the peritoneum, and effect of inhibitors of fatty acid synthesis on immunocytolysis of tumor cells.
1. In C3H/He mice inoculated with isologous MM2 or MH134 cells, immunization with BCG and intraperitoneal injection of 50 <mu> g PPD resulted in significant prolongation of survival time. In the BCG-PPD induced DHR in the peritoneal cavity, peritoneal cells, especially activated macrophages, and ascites also revealed cytotoxic activity against the tumor cells in vitro. Humoral cytotoxic factors were suggested to be produced by macrophages and lymphocytes collected during DHR. Such cytotoxic cytokines will be useful for the treatment of minimum intraperitoneal tumor.
2. MH134 cells pretreated with cerulenin, an inhibitor of fatty acid synthesis, of a low dose giving a slight cell damage were lysed with anti MH134 antiserum in the presence of C' in higher rates than control without pretreatment. C3H/He mice inoculated i.p. Ith 5 X <10^5> MH134 cells, when injected i.p. with cerulenin and 1 day later anti-MH134 serum survived significantly longer than mice treated with cerulenin only or antiserum only. Compactin, an specific inhibitor of sterol synthesis that is currently used clinically for hyper-cholesteremia, showed the similar effect both in vitro and in vivo. Inhibition of repair mechanism of cell surface membrane was indicated to cause the higher susceptibility of cancer cell to immune cytolysis. Intraperitoneal administration of such inhibitors of fatty acid synthesis with only mild side effect may be useful to amplify the cytotoxic effect of monoclonal antibodies against tumor-associated antigens.
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