| Project/Area Number |
14370174
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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 |
Gastroenterology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
TANAKA Naomi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院・人間総合科学研究科, 教授 (60111530)
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| Co-Investigator(Kenkyū-buntansha) |
ABEI Masato University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor, 大学院・人間総合科学研究科, 講師 (20261802)
YOKOYAMA Kazunari Bio Resourse Center, RIKEN Institute, Director, バイオリソースセンター・遺伝子材料開発室, 主任 (80182707)
TODOROKI Takeshi University of Tsukuba, Graduate School of Comprehensive Human Sciences, Associate Professor, 大学院・人間総合科学研究科, 助教授 (70114105)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | gallbladder cancer / gene therapy / adenovirus / 5-フルオロウラシル / ウラシルフォスフォリボシルトランスフェラーゼ / 胆道癌 / 胆管癌 / ウラシルホスホリボシルトランスフェラーゼ |
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| Research Abstract |
New treatments, such as gene therapy, are necessary for advanced gallbladder cancer (GBC) but little has been studied. Recent studies have introduced El mutated adenoviruses (Ads), which show tumor-specific replication and promising clinical results. We studied the efficacy and safety of El mutated Ads and their application to gene therapy for GBC. El mutated Ads selectively replicated in and caused oncolysis of several GBC cell lines as well as wild-type Ad, while they caused only mild cytopathy in normal cells. The El mutated Ads also suppressed the growth of GBC xenografts and prolonged the survival of mice with peritoneally disseminated GBC. We further studied the efficacy of AxE1CAUP, an El mutated Ad expressing uracil phosphoribosyltransferase (UPRT), which greatly enhances the cytotoxicity of 5-fluorouracil (5-FU). AxE1CAUP selectively replicated in and provided GBC cells with stronger UPRT expression and greater 5-FU sensitivity than AxCAUP, a non-replicative Ad expressing UPRT. AxE1CAUP did not change the 5-FU sensitivity in normal cells. In vivo efficacy of AxE1CAUP/5-FU was also superior to that of AxCAUP/5-FU if timing of 5-FU administration was appropriately chosen. Our study showed efficacy, safety, and application of El mutated Ads to gene therapy of GBC.
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