The development of a novel genetherapy for pelitoneal dissemination of ovarian cancer using HSV-1 and its amplicon system.
| Project/Area Number |
15591791
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nagoya University (2005)
Aichi Cancer Center Research Institute (2003-2004) |
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Principal Investigator |
NAWA Akihiro Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90242859)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIYAMA Yukihiro Nagoya University, Graduated School of Medicine, Professor, 大学院・医学系研究科, 教授 (60115615)
TSURUMI Tatsuya Aichi Cancer Center, Research Institute, Director, 研究所, 部長 (90172072)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | HSV amplicon / rabbit-carboxyl esterase / taxol prodrug / MDR expressing cells / clear cell carcinoma cells of the ovary / rabbit-carboxlesterase / HSV / タキソール ブロドラック / アンプリコン / Rabbit carboxylesterase / MDR / タキソール プロドラッグ / Rabbit Carboxylesterase |
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| Research Abstract |
We demonstrated that oncolytic HSV 1 mutants very effectively treated peritoneally disseminated ovarian cancer in a mouse model.
To aid in the development of paclitaxel (TAX) prodrugs for gene-directed enzyme prodrug therapy (GDEPT), we examined the cytotoxicity of TAX-2'-Et in a human clear cell carcinoma of the ovary cell line (KOC-7c), which had been transfected with a rabbit carboxylesterase (Ra-CES) cDNA. Transfection of Ra-CES into MDR(P-gp)-expressing KOC-7c cells conferred a high level of TAX-2'-Et cytotoxicity via prodrug activation. The intracellular levels of TAX for a specific exposure time were significantly increased in cells treated with TAX-2'-Et in Ra-CES-positive KOC-7c cells over the levels seen in TAX-treated cells. In conclusion, TAX-2'-Et can circumvent P-gp-associated cellular efflux of TAX. TAX-2'-Et is converted into TAX by the Ra-CES, supporting its potential use as a theoretical GDEPT strategy for TAX therapy. The TAX-2'-Et prodrug efficiently increased the amount of intracellular TAX, which mediates tumor cell death. Moreover, we have developed a virus cocktail containing HSV1 HF-10 and HSV1 amplicon expressing Ra-CES in the ratio of 1:5. We are examining an efficacy of the combination of the cocktail and TAX-2'-Et to the KOC-7c cells, which reveal TAX-resistance markedly.
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Report
(4 results)
Research Products
(10 results)
