| Project/Area Number |
11671308
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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 |
Thoracic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
TANAKA Hiroyuki Tokyo Medical Dental University, Dept.of Thoracic Surg, Associate Prof., 大学院・医歯学総合研究科, 助教授 (70197466)
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| Co-Investigator(Kenkyū-buntansha) |
SHICHIRI Masayoshi Tokyo Medical Dental University, Dept.of Int medicine, Assistant Prof., 医学部・附属病院, 講師 (10206097)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | gene transfer / liposome / fibrin glue / vein graft / Adrenomedullin / リボゾーム / 静脈グラフト / リポソーム |
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| Research Abstract |
Gene therapy using adenovirus is one of the popular tool for gene transfer into the target cells. However, toxic side effects by viral infection such as induction of inflammation etc. are one of the problems in this method. This study was mainly aimed to the efficacy of the new method of gene transfer without virus into the vascular wall of vein graft. We also studied the pathophysiology of vascular restenosis, especially a role of a stimulus from outside of vessels.
We developed the new method of gene transfer mediated liposome-DNA conjugated ligand for transfferin in vitro cultured cell system. We tested the efficiency of this method in vivo by injecting into directly into liver. However, we could not find the suuficient gene transfer in the liver tissue. We tried the concentration of liposome and DNA, and other conditions in our method. However, efficiency of this method could not be improved. We concluded that this method has no advantage compared to the conventional method for gene transfer such as HVJ-liposome or adenovirus method.
We also tested the role of blockade of imflammatory simulus from outside by fibrin glue coating on an anastomotic side in inhibition of neointimal formation. We observed fibrin glue blocked the direct infiltration of leukocytes into vascular wall and around the suture itself resulting in neointimal thickening on the anastomotic site. Also we found that adrenomedullin played a role in neointimal thickening in balloon injured rat carotid artery. It maybe a target of pharmacological or gene therapy to inhibit vascular restenosis.
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