| Project/Area Number |
17591511
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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 | Osaka University |
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Principal Investigator |
IZUMOTO Shuichi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 講師 (40324769)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Naoya Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (90315945)
MARUNO Motohiko Osaka Medical Center for Cancer and Cardiovascular Diseases, Researcher, 特別研究員 (10263287)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | gene / protein / TAT protein / blood-brain barrier / malignant glioma |
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| Research Abstract |
TAT chimera proteins have the potential as a carrier for delivering proteins through the blood-brain barrier and enable the target substance to reach the brain parenchyma by systemic administration. We have investigated the possibility of using blood-brain barrier (BBB) permeable TAT chimera Interferon-β for the treatment of malignant gliomas. We have performed an RT-PCR of human Interferon-β (HuIFN-β) with His-tag and TAT-protein transduction domain (PTD) attached on the C-terminus. The DNA sequence was confirmed and subcloned into a plasmid expression vector. The designed plasmid was transformed into E.coli and large scale protein expression was performed. TAT-HuIFN-β was extracted as insoluble fraction and solublized by SB3-l4. TAT-HuIFN-β was purified by Ni matrix, with protein refolding. As a control study, TAT-HA peptide was injected into a rat by i.p. and high concentration of HA antigen was detected in the rat brain compared to injection of HA alone. This result supports the hypothesis that TAT chimera proteins can be a useful tool of drug delivery into the brain. However, when TAT-HuIFN-β was injected into rats by i.p. increased we failed to demonstrate the enhanced delivery of HuIFN-β into the brain. This was also the same when the concentration of the injected drug was changed. We conclude that HuIFN-β cannot penetrate the BBB and exert an enough anti-tumoral effect for the treatment of malignant brain tumors
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