2004 Fiscal Year Final Research Report Summary
Novel threrapy for malignant brain tumors using neural stem cell and HSV
| Project/Area Number |
14370446
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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, Department of Medicine, Assistant Professor, 医学部, 講師 (80200484)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASE Takeshi Keio University, Department of Medicine, Professor, 医学部, 教授 (40095592)
OKANO Hideyuki Keio University, Department of Medicine, Professor, 医学部, 教授 (60160694)
SHINODA Atsuo Keio University, Department of Medicine, Instructor, 医学部, 助手 (60306719)
ISHIHARA Jun Japan Tobacco Co. Ltd., Investigator, 主任研究員
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| Project Period (FY) |
2002 – 2004
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| Keywords | Neural Stem Cells / Herpes Virus / Brain Tumors / Viral Therapy / Cell Therapy / Glioma |
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| Research Abstract |
We have first studied an ability of Neural Stem Cells (NSCs) for decreasing tumor proliferation and migration to tumor site and have shown those data. Next, we have studied using HSV mutant G207 with tumor stecific fashion using Musashi promoter. G207 exhibits an efficient oncolytic activity in vitro and in vivo studies, yet minimal toxicity in normal tissue, and is now in clinical trial for malignant glioma. Deletion of the γ 34.5 gene coding for virulence made G207 extremely safe, but it markedly reduced cytotoxicity mediated by HSV type 1. To enhance the therapeutic efficacy of G207 without deminishing its safety, we reintroduced γ 34.5 gene into G207 in the form of defective virus (dvM345) under transcriptional control of musashi1 promotor (P/musashi1). Musashi1, an evolutionarily conserved neural RNA-binding protein, has recently been shown to be expressed in human malignant gliomas and be used as a marker for them. Its promotor, P/musashi1 was functional selectively in human glioma cell lines (U87MG, U251, T98G) in this study and dvM345 showed much higher therapeutic efficacy both in culture and in vivo glioma model, compared to G207 alone, without diminishing a favorable toxicity profile.
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