| Project/Area Number |
12557124
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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 |
Orthopaedic surgery
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| Research Institution | Hiroshima University |
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Principal Investigator |
SUGITA Takashi Hiroshima University, Faculty of Medicine, Assistant Prof., 医学部, 助教授 (40235883)
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| Co-Investigator(Kenkyū-buntansha) |
DEIE Masataka Hiroshima University, University Medical Hospital, Fellow, 医学部・附属病院, 医員
SHIMOSE Shoji Hiroshima University, University Medical Hospital, Assistant, 医学部・附属病院, 助手 (30304439)
MOCHIDUKI Yu Hiroshima University, Faculty of Medicine, Assistant, 医学部, 助手 (10284192)
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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 |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥11,500,000 (Direct Cost: ¥11,500,000)
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| Keywords | gene transfection / targeting / magnetic stealth liposome / external magnetic field / magnetic cationic liposome / osteosarcoma / 遺伝子治療 / p53遺伝子 |
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| Research Abstract |
We developed magnetic ADR liposomes which could be effectively delivered to solid tumors under magnetic force and indicated that intravenously administered magnetic ADR liposomes could be used to effectively deliver ADR to osteosarcoma implanted with a magnet. For clinical application of this DDS, we investigated the efficiency of stealth liposomes (magnetic ADR PEG-liposome) and that of magnetic field of extratumor by the controllable magnetic system not by the implantation of a magnet in a solid tumor. Furthermore we also developed magnetic cationic liposomes as a vector for gene therapy, and examined the efficiency of targeting of gene expression in vitro.
The concentration of ADR in blood after administration of magnetic ADR liposomes became decreased one hour later, but that of magnetic ADR PEG-liposomes was maintained comparatively. This result demonstrated the retainment in blood circulation would be improved. The magnetic field of extratumor caused the less efficiency of targeting to tumor than that of intratumor. We developed the magnetic cationic liposomes composed of DC-chol and DOPE (3 : 2 by molar ratio) and prepared DNA/liposome complex. We used plasmid LacZ as a reporter gene. These complexes were transfected to osteosarcoma cells under magnetic force. Compared the lebel of LacZ expression with that of under no magnetic force, the former was higher within 3 hours after transfection but the both lebels of 6 hours later were almost equal.
Our results suggested that the stealth liposomes by modificated of PEG resulted in the evasion from uptake by Kupffer cells of the liver and this system would reduce side effects of chemotherapy. For the clinical use of this treatment, we thought to have to examine the optimal condition of controllable magnet system. It was considered gene transfection became more efficient by magnetic cationic liposomes according to the high concentration of DNA/liposome complex around the targeted cells.
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