| Project/Area Number |
01580165
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
物質生物化学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YOSHIMURA Tetsuro Institute for Enzyme Research, University of Tokushima, Associate Professor, 酵素科学研究センター, 助教授 (30035472)
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| Co-Investigator(Kenkyū-buntansha) |
MAEZAWA Shigenori Institute for Enzyme Research, University of Tokushima, Research Associate, 酵素科学研究センター, 助手 (70173698)
SONE Saburo School of Medicine, University of Tokushima, Assistant Professor, 医学部附属病院, 講師 (40145024)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1989: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Cytotoxic action / Membrane action / Antitumor cytokine / Liposome / Phosphatidylserine / Macrophage / Intracellular behavior / Liposome-bound cytokine / リポソ-ム膜結合型サイトカイン / インタ-ロイキンー4 / 腫瘍壊死因子 / インタ-フェロン / 膜脂質組成 |
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| Research Abstract |
Studies on the Mechanism of Membrane Action of Antitumor Cytokines Using Liposomal Membrane Systems : TNF and IFN show cytotoxic action on tumor cells. We first examined the effect of membrane lipid composition on the membrane actions of these cytokines, found that membrane Phosphatidylserine (PS) modulates their membrane actions, and suggested that the PS content in the cellular membranes of tumor cells might be responside for their sensitivity to cytokines. We next examined the relationship between the bound state and membrane activity of the two cytokines, and found that the extent of penetration of these cytokines into membranes is correlated with their membrane activities, which could result in the difference in their antitumor activities.
Studies on the Mechanism of Cytotoxic Action of Antitumor Cytokines by the Procedure to Introduce Liposomes into Tumor Cells : To achieve this project smoothly, we first prepared liposomes containing effective fluorescent probes and used macrophage cell systems. We then examined the intracellular behavior of the liposomes in single macrophage cells using a fluorescence microscope, and established the systems to detect and kinetically analyze endocytosis and intracellular fate of liposomes. We have studied the principal pathway and reaction for expression of the cytotoxic actions of cytokines by applying the systems to tumor cells.
Studies on the Mechanism of Action of Antitumor Cytokines Using Liposome-Bound Cytokine Preparation : We have already found that IL-4 inhibits production of TNF and IL-1 in human blood monocytes and suppresses monocyte activation to tumoricidal state, and that liposome-encapsulated IL-4 expresses similar effects. Therefore, we have prepared liposome-bound IL-4 and studied the mechanism of these IL-4 effects.
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