| Project/Area Number |
16590118
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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 |
Medical pharmacy
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| Research Institution | Himeji Dokkyo University (2005-2006)
Josai University (2004) |
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Principal Investigator |
KOMADA Fusao Himeji Dokkyo University, New Faculty Foundation Preparation Room, Professor, 新学部創設準備室, 教授 (50306247)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAI Midori Kobe Pharmaceutical University, Faculty of Pharmaceutics, Professor, 薬学部, 教 (70228766)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | gene therapy / regulation of expression / anticancer drug / transcriptional activating factor / AP-1 / アドリアマイシン / c-fos 37 / c-jun / CMV-LTR |
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| Research Abstract |
Generally, peptide and protein drugs have problems in drug delivery (low absorption, difficult targeting, fast elimination, etc.). Gene therapy is a novel drug delivery system for peptide or protein drugs. However, the regulation of gene expression after the introduction of an exogenous gene is a problematic aspect of gene therapy. The purpose of this study was the gene therapy for the prevention of anti-cancer agent-mediated adverse reactions to use anti-cancer agents to regulate exogenous gene expression in genetically modified cells.
Following expose of paraquat (PQ) and doxorubicin (ADM), the level of cytomegalovirus (CMV) promoter-driven exogenous gene expression increased in time-and dose-dependent manners. Although no increased level of exogenous gene expression showed following exposure to methotrexate and cisplatin. Therefore, these findings suggested that ADM induced activator protein 1 (AP-1) activity as AMD generated reactive oxygen species, and AP-1 affected CMV long terminal repeat contains TPA response element. The level of CMV promoter-driven exogenous gene expression increased following expose of 5-FU, however the increased levels of exogenous gene expression seen after treatment of ADM had not reduced by co-exposure to a tocopherol as free radical scavenger. We assumed that the mechanism for the increased level of CMV-promoter-driven exogenous gene expression by treatment of 5-FU was different from that of treatment of PQ and ADM.
On the basis of these results, the levels of CMV-promoter-driven exogenous gene expression could be regulated by anti-cancer agents, while optimization of gene therapy for the adverse reactions of anti-cancer agents would make the system more feasible.
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