| Project/Area Number |
06044179
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KUWANO Michihiko Kyushu University, MD.Ph.D., 医学部, 教授 (80037431)
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| Co-Investigator(Kenkyū-buntansha) |
KOHNO Kimitoshi Kyushu University, MD.Ph.D., 医学部, 助教授 (00153479)
SATO Yasufummi Tohoku University, MD.Ph.D., 教授 (50178779)
ONO Mayumi Kyushu University, Ph.D., 医学部, 講師 (80128347)
KUNG Hsiang-fu National Institute of Heaith, National Cancer Institute.Ph.D., 主任
RIFKIN Daniel b New York University, Ph.D., 医学部, 教授
宮園 浩平 ルードウィヒ癌研究所, 研究主任
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 1995: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1994: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | Angiogenesis / Vascular endothelial cells / Plasminogen Activator / EGF / TGFalpha / HB-EGF / TGFbeta / VEGF-VPF / IL-8 / TNFalpha / IL-8 / bFGF / 管腔形成 / 血管新生因子 |
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| Research Abstract |
M.Kuwano, M.Ono, Y.Sato and K.Kohno have done the joint study on angiogenesis and growth factor responses in collaboration with K.Miyazono, D.Rifkin and H-f.Kung, and we obtained results as described below.
1. We have recently established angiogenesis model in vitro in wihch vascular endothelial cells on type I collagen gel in an inner chamber are co-cultured with other types of cells in an outer chamber. EGF/TGFalpha dependent tube formation of vascular endothelial cells was inhibited when human chondrocytes were co-cultured in the outer chamger. This chondrocype-induced inhibition of tube fomation was partly abrogated by administraion of anti-TGF beta antibody, suggesting that TGF beta is partly involved in the human chondrocyte-dependent avascularily.
2. Introduction of H-ras oncogene decreased the EGF binding activity to all surface EGF receptor in mouse Balb/3T3 cells. EGF receptor gene expression was abrogated in the H-ras transfectants, but co-introduction of V-myc restored the EG
… More
F receptor to normal levels.Introduction of dominant-negative c-jun mutant encoding a transcriptionally inactive product inhibited the H-ras dependent AP-1 (Jun/Fos) induction, and also restored down-regulation of EGF binding by H-ras oncogene.
3. Oxygen radicals are induced under various pathological conditions including inflamation. Treatment with hydrogen peroxide (H_2O_2) of human microvascular endothelial cells induced development of tube-like structres, and co-administration of antisense sequence of NFkB inhibited the H_2O_2 dependent tubular morphogenesis was almost completely abrogated when anti-IL8 antibody was present. Tubular morphogenesis of vascular endothelial cells after the oxidative stimuli appeared to be associated with NFkB and IL8.
4. Irogladine used clinically as an anti-gasTriculcer agent at 10 ^<-6> to 10^<-4>M inhibited specifically cell proliferation and tube formation of vascular endothelial cells. Oral administration of irsogladine at 30 to 120 mg/kg/day inhibited both tumor growth and tumor angiogenesis when human tumor cells were transplanted in mice. Less
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