2000 Fiscal Year Final Research Report Summary
Combined gene therapy for malignant brain tumors based on the mutant viruses.
| Project/Area Number |
11470298
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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 |
Cerebral neurosurgery
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| Research Institution | Keio University |
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Principal Investigator |
YAZAKI Takahito Keio University, School of Medicine, Assistant Professor, 医学部, 専任講師 (80200484)
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| Co-Investigator(Kenkyū-buntansha) |
SHINODA Atsuo Keio University, School of Medicine, Instructor, 医学部, 助手 (60306719)
IKEDA Keiro Keio University, School of Medicine, Instructor, 医学部, 助手 (10222879)
KAWASE Takeshi Keio University, School of Medicine, Professor, 医学部, 教授 (40095592)
SUGAWA Makoto Chugai Pharmaceutical Co, Ltd., Research Chief, 主任研究員
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| Project Period (FY) |
1999 – 2000
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| Keywords | brain tumors / Herpes simplex virus / TIMP2 / Anti-viral immunity / specific promotor / Musashi-1 |
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| Research Abstract |
First we analyzed safety of the HSV vectors expressing TIMP2 in mice. Most of organs of intracranially virus-injected mice were normal. Next, we focused anti-viral immune sysytem that inactivate therapeutic vvirus activity. Patient plasma inactivated virus viability siginificantlly within 24 ours whereas that receiving chemotherapy (MCNU+VCN) did not inactivate. In vivo, co-injection of cyclophosphamide elongated virus viability and enhanced anti-tumor activity of the viral vectors. These results suspected that syncronous virus therapy with chemotherapy is appropriate approach for malignant gliomas. Next, we analyzed Musashi-1 promotor activity in the malignant gliomas. It was significantlly active in the glioma cell lines compared to the other cell lines. Musashi-1 promoter should be valuable to regulate viral replication for the tumor-specific viral therapy.
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