| Project/Area Number |
18209043
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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 |
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, Hepato-Biliary -Pancreatic Surgery, Professor (50151171)
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| Co-Investigator(Kenkyū-buntansha) |
INAZAWA Johji Tokyo Medical and Dental University, Molecular Cytogenetics, Professor (30193551)
TANAKA Hiroshi Tokyo Medical and Dental University, School of Biomedical Sciences, Systems Biology and Bioinformati, Professor (60155158)
MIKI Yoshio Tokyo Medical and Dental University, Molecular Cytogenetics, Professor (10281594)
TANAKA Shinji Tokyo Medical and Dental University, Hepato-Biliary-Pancreatic Surgery, Associate Professor (30253420)
NAKAMURA Noriaki Tokyo Medical and Dental University, Hepato-Biliary-Pancreatic Surgery, assistant Professor (10372442)
寺本 研一 東京医科歯科大学, 大学院医歯学総合研究科, 助教授 (80197813)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥50,050,000 (Direct Cost: ¥38,500,000、Indirect Cost: ¥11,550,000)
Fiscal Year 2007: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2006: ¥30,810,000 (Direct Cost: ¥23,700,000、Indirect Cost: ¥7,110,000)
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| Keywords | Hepatocellular carcinoma / Pancreas cancer / Recurrence / Molecular target / Aurora kinase B / Conexin 43 / Grb7 / Iκkinase B / オミックス解析 / cDNA Microarray / Array-CGH / 肝癌 / ミラノ基準 / 分子標的剤 |
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| Research Abstract |
This research project yielded the following results.
1) Predictive factors for aggressive recurrence of hepatocellular carcinoma (HCC) and identification of a novel molecular target: A prognosis of HCC patients was found to depend on the mode of recurrence, and prognostic indicators were tumor differentiation, tumor size, and aurora kinase B (ARKB) which plays a key role in genome instability. ARKB is considered to be a promising molecular target for HCC treatment.
2) Clinical implication of Gap junctional intercellular communication, Conexin (Cg) 43:
3) Cx 43 was found to facilitate the growth of HCC, and to be a possible molecular target, and also Vitamin K 2 was found to suppress HCC growth through upregulation of Cx32 and downregulation of Cx43.
4) Identification of genes responsible for carcinogenesis and development of HCC : We identified CREB3L4, INTS3, SNAPAP located at 1q 21.
5) Identification of genes responsible for pancreatic cancer metastasis : We identified Gr7 which is phospholylated with FAK, thereby inducing cell invasion. We synthesized a peptide, G7-18NATE-P which inhibits phospholylation of Grb7, thereby clarifying the inhibitory effect on the peritoneal dissemination model of pancreas cancer.
6) Effect of Iκ B kinase (IKKB) inhibition on pancreas cancer: SiRNA and synthesized compound, IMD-0354 for IKKB inhibitor were found to suppress the growth of pancreas cancer in the xenograft model.
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