| Project/Area Number |
12671359
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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 |
Cerebral neurosurgery
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
ONO Yasuhiro OKAYAMA UNIVERSITY GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSISTANT, 大学院・医歯学総合研究科, 助手 (40294409)
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| Co-Investigator(Kenkyū-buntansha) |
TAMIYA Takashi OKAYAMA UNIVERSITY GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (50252953)
松本 健五 岡山大学, 医学部, 助教授 (10190521)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | adenovirus vector / gene therapy / brain tumors / シトシンデアミナーゼ / ウラシルホスホリボシルトランスフェラーゼ / 5-フルオロシトシン / 5-フルオロウラシル |
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| Research Abstract |
One of the transduction methods, adenovirus vector, was shown to transduce exogenous genes successfully into tumor cells both in vitro and in vivo. We have investigated the feasibility of gene transduction for brain tumors using adenovirus vector. Transduction of the cytosine deaminase (CD) gene into tumor cells followed by administration of 5-fluorocytosine (5-FC), called 5-FC/CD gene therapy, was created as a suicide gene therapy for various cancers. We also reported the usefulness of 5-FC/CD gene therapy for malignant glioma and pointed out its toxicity for normal brain tussues. The improvement of this therapy was required for the safe treatment of glioma patients.
The purpose of our research was to improve adenovirus vector for the effective delivery of exogenous gene. We used newly constructed replication-competent adenovirus instead of replication-incompetent adenovirus, resulted in a higher transduction rate of glioma cells. The next purpose was to analyze the apoptotic mechanism of 5-FC/CD gene therapy in glioma cells. We examined the expression of cell-cycle regulators and apoptosis-related factors after 5-FC/CD gene therapy in mRNA and protein level. Our results suggested that the apoptotic cell death was mediated by the activation of mitochondrial caspase cascades. These results have been reported in some meeting and papers.
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