| Project/Area Number |
07671529
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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 | SAGA MEDICAL SCHOOL |
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Principal Investigator |
FUKUYAMA Kouzou SAGA MEDICAL,SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (60238516)
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| Co-Investigator(Kenkyū-buntansha) |
HAGIHARA Naoshi SAGA MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (90281203)
MINETA Toshihiro SAGA MEDICAL SCHOOL,FACULTY OF MEDICINE,LECTURER, 医学部, 助手 (20264187)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | glioma / gene therapy / adenovirus / GFAP / p53 / p21 / レトロウィルスベクター / p16 / プロモーター / 神経膠腫 |
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| Research Abstract |
We investigated the efficacy and the side effect of the gene therapy using adenovirus and retroviruses for the treatment of malignant gliomas. The recombinant adenovirus and retrovirus were injected into the brain of Wistar rats, and the efficiency of gene expression and the immune response of hosts were monitored with lac Z gene as a reporter gene. Adenoviruses could be concentrated at the titer of 1010 pfu/ml, and the expression of lac Z was extremely strong. It was observed that the lac Z expression was continued upto 6 weeks after injection. On the contrary the titer of retrovirus solution was only at 106 pfu/ml. The transferred gene expression was very localized at the injected area. In both vector system, there occurred only little infiltration of immune cells, nor allergic reactions. There was slight gliosis and the diminish of ependymal cells at 6 weeks after the injection. We considered adenovirus system was superior to retrovirus system for the purpose of the gene therapy of malignant gliomas, which requires high efficiency of gene transduction.
Adenovirus bearing lacz, p53, and p21 genes were infected into cultured glioma cells. In p53 wild type cells, the cell growth was inhibited by the induction of p21. On the other hand, in p53 mutant and deleted cells, the growth inhibition were induced by the up regulation of p53. In the subcutaneously transplanted glioma cells in nude mice, in infection of p21 bearing adenovirus resulted the tumor growth inhibition.
The astrocytes specific expression vector was constructed with the tandem ligation of enhancer sequences of GFAP gene into adenovirus. The lac Z gene and p53, p16, and p21 genes were inserted in the downstream of this enhancer unit. These viruses were only expressed the expected genes in the astrocytes. The astrocytes specific expression adenovirus can be a useful arms for the treatment of malignant gliomas.
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