| Project/Area Number |
13470339
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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 | 一般 |
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| Research Field |
Urology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
NAKAO Masahiro Department of Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 講師 (00188880)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUTANI Yoichi Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 講師 (10243031)
MIKI Tsuneharu Urology, Kyoto Prefectural Univ. of Med. Professor, 医学部, 教授 (10243239)
MATUDA Osamu Microbiology, Kyoto Prefectural Univ. of Med. Associat Professor, 医学部, 助教授 (00271164)
NOMOTO Takeshi Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 助手 (20301426)
UKIMURA Osamu Urology, Kyoto Prefectural Univ. of Med. Assistant Professor, 医学部, 助手 (70275220)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2002: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥7,400,000 (Direct Cost: ¥7,400,000)
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| Keywords | prostate cancer / EBV-based plasmid vector / Fas ligand / EBV / polyplex / lipoplex / 腎細胞癌 / 選択的COX-2阻害剤 / 抗Fas抗体 / JTE-522 / 遺伝子治療 / EBV-プラスミドベクター / Fas / アポトーシス / cationic polymer |
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| Research Abstract |
To accomplish efficient nonviral gene therapy against prostate cancer (PC), Epstein-Barr virus (EBV)-based plasmid vectors containing EBNA1 gene and oriP were employed and combined with a cationic polymer or cationic lipid. When EBV-plasmid/poly-amidoamine dendrimer complex was injected into PC-3-derived tumors established in severe combined immunodeficiency mice, a considerable expression of marker gene was obtained in the tumors, and the expression level was more than eight-fold higher than that achieved by conventional plasmid vector/dendrimer. Since most PC cells express the apoptotic signal molecule Fas (Apo-1/CD95) on their surface, Fas ligand (FasL) gene was transferred into PC cells to kill the tumor cell. In vitro transfection with pGEG.FasL (an EBV-plasmid with the FasL gene) significantly reduced the viability of PC cells, which subsequently underwent apoptosis. Intratumoral injection of pGEG.FasL into PC induced significant growth suppression of the xerograft tumors, in which typical characteristics of apoptosis were demonstrated by TUNEL staining and electron microscopic observations. When pGEG.FasL transfer was accompanied by systemic administrations of cisplatin, the tumors were inhibited even more remarkably, leading to prolonged survival of the animals. FasL gene transfection by means of EBV-based plasmid/cationic macromolecule complexes may provide a practical therapeutic strategy against PC.
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