Project/Area Number |
14350439
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
生物・生体工学
|
Research Institution | SOJO University |
Principal Investigator |
UEOKA Ryuichi SOJO University, Engineering, Professor, 工学部, 教授 (70099076)
|
Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Yoko SOJO University, Engineering, Professor, 工学部, 教授 (00133562)
MATSUSHITA Taku SOJO University, Engineering, Assistant Professor, 工学部, 助教授 (10209538)
KANNO Akihiro Drug Safety Testing Center, Chief Director, 薬理研究所, 部長
金野 明宏 (株)薬物安全性試験センター薬理研究所, 部長
|
Project Period (FY) |
2002 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥8,700,000 (Direct Cost: ¥8,700,000)
|
Keywords | Hybrid Liposomes / Anticancer Mechanism / Clinical Chemotherapy / Dimyristoylphosphatidylcholine / No Side Effect / Caspases / Apoptosis / Life Prolongation / 担がんマウス / 肝臓がん / 膜融合 / 悪性黒色腫 |
Research Abstract |
Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity phase transition temperature, and hydrophobicity can be controlled by changing the composition. In the course of our study, remarkably high inhibitory effects of hybrid liposomes on tumor growth in vitro without drugs have been obtained. No toxicity of the hybrid liposomes was observed in normal cells in vitro and in normal rats in vivo without any side effect. In this study, we report on the uniform and stable hybrid liposomes composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (C_<12>(EO)n; n=10-25) having inhibitory effects on the growth of tumor cells in vitro, in vivo and clinical chemotherapy. Asummary of the noteworthy aspects of this study is as follows : (a) the uniform and stable structure of hybrid liposomes composed of DMPC and C_<12>(EO)_n was obtained. (b) Highly inhibitory effects of hybrid liposomes were obtained on the growth of many kinds of tumor cells in vitro. (c) Induction of apoptosis by hybrid liposomes through activation of death domains and some kind of caspases was verified for the first time. (d) Significantly prolonged survival was obtained in mice inoculated tumor cells after the treatment with hybrid liposomes without any side effect. (e) In clinical application, the prolonged survival was attained in patient with lymphoma and other tumors after the intravenous injection of hybrid liposomes without drugs and the remarkable reduction of solid tumor was obtained after the local administration of hybrid liposomes.
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