| Project/Area Number |
14370379
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ARII Shigeki Tokyo Medical and Dental University, School of medicine, assistant professor, 大学院・歯学総合研究科, 教授 (50151171)
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| Co-Investigator(Kenkyū-buntansha) |
MORI Akira Kyoto University, Graduate School of medicine, Faculty of medicine assistant, 医学研究科, 助手 (60324646)
KAWAMURA Toru Tokyo Medical and Dental University, School of medicine, assistant, 医学部附属病院, 助手 (90322081)
TERAMOTO Kenichi Tokyo Medical and Dental University, School of medicine, assistant, 大学院・歯学総合研究科, 助教授 (80197813)
SHIBATA Toru Kyoto University, Graduate School of medicine, Faculty of Medicine assistant, 医学研究科, 助手 (40293857)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2003: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2002: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | angiogenesis / order-made medicine / glycolysis / aerobic metabolism / anaerobic metabolism / vascular endothelial growth factor / hexokinase-II / hypoxia inducible factor-1 / 転移性肝癌 / 解糖系 / ヘキソキナーゼ / VEGF(vascular endothelial growth factor) / 遺伝子治療 |
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| Research Abstract |
It has been thought that solid tumors require tumor angiogenesis in their growth. However, we sometimes encounter the tumors that grow rapidly despite their poor vascularity. This clinical observation suggest.s the existence of tumors that require little neoangiogenesis for their growth. In this research project, we analyzed the expressions of hexokinase, a key enzyme in glycolysis, and VEGE in hepatocellular carcinoma and rnetastatic liver cancer in relation to tumor vascularity, and the participation of hypoxia-inducible factor-1(HIF-1) was studied. Consequently, we obtained some informative evidence. In HCC, main energy source of the growth was derived from angiogenesis, whereas in metastatic tumors glycolysis induced by HIF-1 is the predominant energy source. In addition, it was suggested that cancer cells obtain energy for growth by switching the metabolic profile to glycolysis through HIP-i in hypoxic condition. Although many kinds of antiangiogenic therapies have been reported to be effective, it is assumed that some tumors might resist these therapies by acquiring energy for growth through increased glycolysis induced by HIF-1.
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