| Project/Area Number |
12555232
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
生物・生体工学
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| Research Institution | Sojo University |
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Principal Investigator |
UEOKA Ryuichi Sojo university, Professor, 工学部, 教授 (70099076)
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| Co-Investigator(Kenkyū-buntansha) |
KANNO Akihiro Drug Safety Testing Center, Maneger, 薬理研究所, 部長
MATSUMOTO Yoko Sojo university, Associate Professor, 工学部, 助教授 (00133562)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 2001: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | liposome / chemotherapy / lymphoma / apoptosis / caspase / clinical application / がん化学療法 / 体内動態 / 腫瘍縮小 / 肺がん / 延命効果 / 担がんマウス |
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| Research Abstract |
1. Antitumor Mechanism of Hybrid Liposomes
We examined mitochondrial pathway for apoptosis induced by hybrid liposomes. Mitochondrial membrane potential was decreased by adding hybrid liposomes, suggesting that hybrid liposomes should induce apoptosis through mitochondria. Release of cytochrome c and activation of caspase-9 were observed using western blotting analysis. Concentration dependence of caspase-9 inhibitor on the apoptotic DNA rates was also obtained. These results suggest that hybrid liposomes should induce apoptosis through mitochondria and activation of caspase-9.
2. Inhibitory Effects of Three-Component Hybrid Liposomes Including Sugar Surfactants
We successfully produced sugar-type micellar surfactants, lactonoalkylamide (LacCn), for the first time. Spherical vesicles, three-component hybrid liposomes, were obtained after sonication of mixture of L-α-dimyristoylphosphtidylcholine (DMPC), Tween 20 and LacCn (DMPC : Tween 20 : LacCn = 65 : 7 : 28). It is noteworthy that high
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inhibitory effects of the three-component hybrid liposomes composed of DMPC, Tween 20, and LacCn (DMPC : Tween 20 : LacCn = 65 : 7 : 28) on the growth ofglioma (U251) and lung adenocarcinoma (RERF-LC-OK) cells were attained in vitro without any drug, although no significant inhibitory effects of any individual component (DMPC, Tween 20, LacCn) or the two-component hybrid liposomes of DMPC and Tween 20 on the growth of tumor cells examined were obtained.
3.Clinical Application of Hybrid Liposomes
Patients with lymphoma were selected for the clinical application of hybrid liposomes composed of DMPC and C_<12>(EO)_<23> without any drug after passing the committee of bioethics. The hybrid liposomes were administered intravenously every day. There were not abnormal findings on routine blood test and hematochemistry. Prolonged survival was attained in patient with lymphoma after the intravenous injection of hybrid liposomes without any side effect and the remarkable reduction of neoplasm (solid tumor) was obtained after the local administration of hybrid liposomes. Such a successful clinical application of hybrid liposomes without drugs was for the first time in the world. Less
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