Multidisciplinary research for molecular mechanism of cancer progression and development of diagnostic and therapeutic tool
| 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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Report
(3 results)
Research Products
(84 results)
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[Journal Article] Aurora kinase B is a predictive factor for aggressive recurrence of hepa tocellular carcinoma after curative hepatectomy2008
Author(s)
Tanaka S, Arii S, Yasen M, Mogusi K, Su N-T, Zhao C, Imoto I, Eishi Y, Inazawa J, Miki Y, Tanaka H.
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Journal Title
Brit J Surg 95
Pages: 611-619
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] CREB3L4, INTS3, and SNAPAP are targets for the 1q21 amplicon frequently detected in hepatocellular carcinoma.2008
Author(s)
Inagaki Y, Yasui K, Endo M, Nakajima T, Zen K, Tsuji K, Minami M, Tanaka S, Taniwaki M, Itoh Y, Arii S, Okanoue T.
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Journal Title
Cancer Genet Cytogenet. 180
Pages: 30-36
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Aurora kinase B is a predictive factor for aggressive recurrence of hepatocellular carcinoma after curative hepatectomy2008
Author(s)
Tanaka S, Arii S, Yasen M, Mogusi K, Su N-T, Zhao C, Imoto I, Eishi Y, Inazawa J, Miki Y, Tanaka H.
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Journal Title
Brit J Surg 95
Pages: 611-619
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] CREB3L4, INTS3, and SNAPAP are targets for the 1q21 amplicon frequently detected in hepatocellular carcinoma2008
Author(s)
Inagaki Y, Yasui K, Endo M, Nakajima T, Zen K, Tsuji K, Minami M, Tanaka S, Taniwaki M, Itch Y, Arii S, Okanoue T.
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Journal Title
Cancer Genet Cytogenet 180
Pages: 30-36
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients.2006
Author(s)
Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, Matsuyama Y, Nakanuma Y, Kojiro M, Makuuchi M, Yamaoka Y, Liver Cancer Study Group of Japan
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Journal Title
Gastroenterology 131・2
Pages: 461-469
NAID
Related Report
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[Journal Article] Activation of B-Myb by E2F1 in hepatocellular carcinoma.
Author(s)
Nakajima T, Yasui K, Keika Z, Inagaki Y, Fujii H, Minami. M, Tanaka S, Taniwaki M, Itoh Y, Arii S, Inazawa J, Okanoue T.
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Journal Title
Hepatology Res. (in press)
NAID
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Activation of B-Myb by E2F1 in hepatocellular carcinoma
Author(s)
Nakajima T, Yasui K, Keika Z, Inagaki Y, Fujii H, Minami M, Tanaka S, Taniwaki M, Itoh Y, Arii S, Inazawa J, Okanoue T.
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Journal Title
Hepatology Res (in press)
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] 肝細胞癌の分子標的治療2007
Author(s)
田中真二, 藍原有弘, Mahmut Yasen, 茂櫛 薫, 工藤 篤, 中村典明, 伊東浩次, 稲澤譲治, 三木義男, 田中 博, 有井滋樹.
Organizer
第45回日本癌治療学会総会.
Place of Presentation
京都
Year and Date
2007-10-24
Description
「研究成果報告書概要(和文)」より
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[Presentation] 網羅的疾患分子病態データベースの構築2007
Author(s)
田中 博, 有井滋樹, 杉原健一, 三木義男, 稲澤譲治, 水島 洋.
Organizer
第66回日本癌学会学術総会
Place of Presentation
神奈川
Year and Date
2007-10-05
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] 肝細胞癌再発様式のオミックス解析による新規分子標的の同定2007
Author(s)
田中真二, Yasen Mahmut, 茂櫛 薫, 藍原有弘, 工藤 篤, 中村典明, 伊東浩次, 井本逸勢, 稲澤譲治, 三木義男, 水島 洋, 田中 博, 有井滋樹.
Organizer
第66回日本癌学会学術総会
Place of Presentation
神奈川
Year and Date
2007-10-04
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] 肝細胞癌における薪規1q21遺伝子増幅領域の検出とその標的遺伝子SNAPAP, INTS3およびCREB3L4の同定2007
Author(s)
遠藤美生, 安居幸一郎, 稲垣恭和, 中島知明, 全 圭夏, 辻 和宏, 玄 泰行, 田中真二, 谷脇雅史, 伊藤義人, 有井滋樹, 岡上 武.
Organizer
第66回日本癌学会学術総会
Place of Presentation
神奈川
Year and Date
2007-10-04
Description
「研究成果報告書概要(和文)」より
Related Report
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[Presentation] 肝細胞癌の進展機構解析による新規分子標的の同定2007
Author(s)
田中真二, Yasen Mahmut, 茂櫛 薫, 工藤 篤, 中村典明, 伊東浩次, 稲澤譲治, 三木義男, 田中 博, 有井滋樹.
Organizer
第62回日本消化器外科学会定期学術総会
Place of Presentation
東京
Year and Date
2007-07-19
Description
「研究成果報告書概要(和文)」より
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[Presentation] IKK2抑制による膵癌増殖抑制効果2007
Author(s)
落合高徳, 斉藤愛記, 斉藤達哉, Dewan Md. Zahidunnabi, 塩谷歩美, 小林真季, 河内 洋, 武藤 進, 板井昭子, 魚田 慎, 山本直樹, 田中真二, 山岡昇司, 有井滋樹.
Organizer
第107回日本外科学会定期学術集会
Place of Presentation
大阪
Year and Date
2007-04-12
Description
「研究成果報告書概要(和文)」より
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[Presentation] 膵癌の新規転移規定遺伝子の同定と分子標的治療の開発2006
Author(s)
田中真二, 落合高徳, Mahmut Yasen, 野口典男, 工藤 篤, 中村典明, 伊東浩次, 寺本研一, 有井滋樹.
Organizer
第10回がん分子標的治療研究会
Place of Presentation
東京
Year and Date
2006-06-16
Description
「研究成果報告書概要(和文)」より
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[Presentation] IKKβ神制による膵癌増殖抑制効果2006
Author(s)
落合高徳, 斉藤愛記, 斉藤達哉, 小林真季, 河内 洋, 武藤 進, 板井昭子, 魚田 慎, 山本直樹, 田中真二, 有井滋樹, 山岡昇司.
Organizer
第65回日本癌学会学術総会
Place of Presentation
横浜
Description
「研究成果報告書概要(和文)」より
Related Report
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