| Project/Area Number |
13307009
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
SUEISHI Katsuo KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (70108710)
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| Co-Investigator(Kenkyū-buntansha) |
YONEMITSU Yoshikazu KYUSHU UNIVERSITY, University Hospital, Lecturer, 講師 (40315065)
NAKAGAWA Kazunori KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Lecturer, 大学院・医学研究院, 講師 (50217668)
中島 豊 九州大学, 大学院・医学研究院, 助教授 (50135349)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥55,250,000 (Direct Cost: ¥42,500,000、Indirect Cost: ¥12,750,000)
Fiscal Year 2003: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
Fiscal Year 2002: ¥21,580,000 (Direct Cost: ¥16,600,000、Indirect Cost: ¥4,980,000)
Fiscal Year 2001: ¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000)
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| Keywords | vascular remodeling / atherosclerosis / angiogenesis / angiogenic hierarchy / FGF-2 / SeV / Gene transfer / tissue stem cell / 血管内皮細胞 / 血管平滑筋細胞 / ウイルスベクター / 遺伝子治療 / VEGF / 血管新生病 |
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| Research Abstract |
1.Endothelial function in physiological and pathological vascular remodeling
From studies concerning atherosclerosis, mechanism of functional angiogenesis, differentiation mechanism of hepatic stem cell, the main results obtained were as follows :
1)Atherosclerosis and angiogenesis : intimal neovascularization related to VEGF-A and -C expression was equivalent to a histopathological hallmark of active atherogenesis, and we propose "inflammation-repair hypothesis" for atherogenesis.
2)Molecular mechanism of functional angiogenesis : FGF-2 hierarchically enhanced the expression of VEGF,HGF,PDGF and others in a hypoxic tissues, leading to the integrated angiogenesis associated with structural and functional interaction between endothelial-pericytes(smooth muscle cells).
3)Differentiation mechanism of hepatic stem cells : FLK-1-positive cells in mouse fetuses possessed the pluripotent differentiation activities into hepatocytes and bile ducts, and blood vessels under HGF+EGF and VEGF+PDGF-BB stimulation, respectively.
2.Biological properties of novel gene transfer vectors and their clinical application
Using recombinant SeV and SIV vectors with several reporter and target genes(FGF-1,-2,-10,VEGF-A,PEDF,sprouty-2,soluble PDGF receptor etc), biological and pathbphysiological characteritics of spatial and time-sequential transfer/expression efficacy of these vectors were analyzed and we are exploiting the novel strategies on gene therapy.
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