| Project/Area Number |
16390375
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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, Dept.of Hepato-Biliary-Pancreatic Surgery, Professor, 大学院・医歯学総合研究科, 教授 (50151171)
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| Co-Investigator(Kenkyū-buntansha) |
TERAMOTO Kenichi Tokyo Medical and Dental University, Dept.of Hepato-Biliary-Pancreatic Surgery, Associate professor, 大学院・医歯学総合研究科, 助教授 (80197813)
NAKAMURA Noriaki Tokyo Medical and Dental University, Dept.of Hepato-Biliary-Pancreatic Surgery, Instructor, 医学部附属病院, 助手 (10372442)
INAZAWA Jyoji Tokyo Medical and Dental University, Medical Research Institute, Professor, 難治疾患研究所, 教授 (30193551)
TANAKA Shinji Tokyo Medical and Dental University, Information Center for Medical Sciences, Associate Professor, 情報処理センター, 特任助教授 (30253420)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2004: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | hepatocellular carcinoma / invasion and metastasis / DNA binding protein / angiopoietin-2 / hexisokinas-II / COX-2 / VEGF / Skp-2 / 浸潤・転移 / dbpA / YB-1 / Angiopioietin / Cox-2 / 慢性肝障害 / dbpa / 解糖系 / 低酸素状態 / 血管新生 / 高癌化状態 |
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| Research Abstract |
1) Based on the previous studies, we focused on DNA binding protein A (dbpA) to investigate the candidate gene for occurrence and development of HCC. By the analyses of immunostaining of 82 resected specimen of HCC we clarified that dbpA was closely related to the portal invasion, venous invasion, differentiation grade of cancer cell and serum level of α fetoprotein, and further showed that transformation of T to G in the promoter region may be associated with poor prognosis. These findings suggested that dbpA might be not only a biomarker for invasion of HCC, but also a candidate gene of molecular-targeting therapy.
2) Based on the previous studies showing that angiopoietin-2 is an important angiogenic factor in HCC, we studied the mechanism on the induction of this molecule. Consequently, we found that PGE2 and COX-2 is strong inducers for angiopoietin-2, and that COX-2 inhibitor suppressed the tumor growth in vivo through inhibiting the tumor angiogenesis. We also suggested that angiopoietin-2 and its receptor Tie-2 may be candidate molecules for targeting therapy.
3) We found that not only VEGF but also anaerobic glycolysis- related enzyme of hexisokinase-II was enhanced under the hypoxic environment in HCC, suggesting the limitation of antiangiogenic therapy.
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