| Project/Area Number |
07457141
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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 | Nara Medical University |
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Principal Investigator |
KURIYAMA Shigeki Nara Medical University, Medicine, Assistant, 医学部, 講師 (50244710)
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| Co-Investigator(Kenkyū-buntansha) |
TOMINAGA Kentaro Nara Medical University, Medicine, Staff, 医学部, 医員
MASUI Kazuhiro Nara Medical University, Medicine, Assistant, 医学部, 助手 (10295800)
YOSHIKAWA Masahide Nara Medical University, Medicine, Assistant, 医学部, 助手 (50230701)
阪本 たけみ 奈良県立医科大学, 医学部, 医員
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1995: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | gene therapy / hepatoma / retrovirus / suicide gene / thymidine kinase / cytosine deaminase / アデノウイルス / アルブミン遺伝子 / アルブミン遺伝子プロモーター / bystander effect / チミジンキナーゼ遺伝子 / シトシンデアミナーゼ遺伝子 |
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| Research Abstract |
We have previously reported that a reporter gene directed by the albumin gene promoter in a retroviral vector is expressed solely in hepatoma cells but not in non-hepatoma cells. This year, we have got the following additional results.
1)Transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene under the control of albumin promoter can render hepatoma cells, but not non-hepatoma cells, susceptible to ganciclovir (GCV) toxicity.
2)Established subcutaneous tumors consisting of HSV-tk gene-transduced hepatoma cells were abrogated completely by GCV treatment in 11 of 14 mice. However, in the remaining 3 mice, tumors did not regress completely despite GCV treatment due to methylation of the HSV-tk gene.
3)Bacterial cytosine deaminase (CD) gene/5-fluorocytosine (5-FC) system can cause profound bystander killing on neighboring untransduced cells without direct cell-to-cell contact. This bystander killing effect was shown to be mediated by 5-fluorouracil (5-FU) produced from 5-FC by CD gene-transduced hepatoma cells.
4)CD-5-FC system can induce substantial bystander effect in vivo. This in vivo bystander effect was mainly caused by host's tumor immunity elicited by the CD/5-FC system but not by 5-FU produced by the CD/5-FC system.
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