Omics analysis of cancer vessel abnormalities as therapeutic targets

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390346
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TANAKA Shinji Tokyo Medical and Dental University, 医歯学総合研究科, 准教授 (30253420)
• Co-Investigator(Kenkyū-buntansha): ARII Shigeki 東京医科歯科大学, 医歯学総合研究科, 教授 (50151171)
• Project Period (FY): 2007 – 2009
• Keywords: 肝臓外科学

Research Abstract

Intraoperative contrast-enhanced ultrasonography revealed the relationship between the dynamic pattern of angiogenesis in hepatocellular carcinoma (HCC) and the cancer cell differentiation. According to the cDNA microarray, the pattern of angiogenesis was closely associated with the expression of Angiopoietin-2, one of the therapeutic targets evaluated in clinical trials for cancers. Along with the angiogenesis, vascular invasion of cancer cells is started and progressed to metastatic steps. Further transcriptional network analysis revealed the closed relationship between the Aurora B pathways and the vascular-invasion phenotype of HCC. Our preclinical studies using the Aurora-targeted agents indicated novel adjuvant therapy for aggressive HCC.

Research Products

• [Journal Article] Molecularly targeted therapy for hepatocellular carcinoma (2009)
  • Author(s): Tanaka S, Arii S.
  • Journal Title: Cancer Science 100(1) Pages: 1-8
• [Journal Article] Surgical contribution to recurrence-free survival in patients with macrovascular invasion-negative hepatocellular carcinoma (2009)
  • Author(s): Tanaka S, Mogushi K, Yasen M, Noguchi N, Kudo A, Kurokawa T, Nakamura N, Inazawa J, Tanaka H, Arii S.
  • Journal Title: Journal of the American College of Surgeons 208(3) Pages: 368-374
• [Journal Article] Surgical radiofrequency ablation for treatment of hepatocellular carcinoma : an endoscopic or open approach (2009)
  • Author(s): Tanaka S, Shimada M, Shirabe K, Taketomi A, Maehara Si, Tsujita E, Ito S, Kitagawa D, Maehara Y.
  • Journal Title: Hepatogastroenterology, Jul-Aug 56(93) Pages: 1169-73
• [Journal Article] Expression of Aurora B and their alternative variant forms in hepatocellular carcinoma and the adjacent tissue (2009)
  • Author(s): Yasen M, Mizushima H, Mogushi K, Obulhasim G, Miyaguchi K, Inoue K, Nakahara I, Ohta T, Aihara A, Tanaka S, Arii S, Tanaka H.
  • Journal Title: Cancer Science 100(3) Pages: 368-74
• [Journal Article] Decreased Mrp2-dependent bile flow in the post-warm ischemic rat liver (2009)
  • Author(s): Ban D, Kudo A, Sui S, Tanaka S, Nakamura N, Ito K, Suematsu M, Arii S.
  • Journal Title: Journal of Surgical Research 153(2) Pages: 310-6
• [Journal Article] Small agarose microcapsules with cell-enclosing hollow core for cell therapy : Transplantation of ifosfamide-activating cells to the mice with pre-established subcutaneous tumor (2009)
  • Author(s): Sakai S, Hashimoto I, Tanaka S, Salmons B, Kawakami K.
  • Journal Title: Cell Transplantation 18(8) Pages: 933-9
• [Journal Article] Infrequent amplification of JUN in hepatocellular carcinoma (2009)
  • Author(s): Endo M, Yasui K, Nakajima T, Gen Y, Tsuji K, Dohi O, Zen K, Mitsuyoshi H, Minami M, Yoshito Itoh, Taniwaki M, Tanaka S, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Anticancer Res 29(12) Pages: 4989-94
• [Journal Article] ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry (2009)
  • Author(s): Zen K, Yasui K, Nakajima T, Zen Y, Zen K, Gen Y, Mitsuyoshi H, Minami M, Mitsufuji S, Tanaka S, Itoh Y, Nakanuma Y, Taniwaki M, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Genes, Chromosomes and Cancer 48(2) Pages: 109-20
• [Journal Article] A novel amplification target, ARHGAP5, promotes cell spreading and migration by negatively regulating RhoA in Huh-7 hepatocellular carcinoma cells (2009)
  • Author(s): Gen Y, Yasui K, Zen K, Nakajima T, Tsuji K, Endo M, Mitsuyoshi H, Minami M, Itoh Y, Tanaka S, Minami M, Arii S, Okanoue T, Yoshikawa T.
  • Journal Title: Cancer Letters 275(1) Pages: 27-34
• [Journal Article] Aurora kinase B is a predictive factor for aggressive recurrence of hepatocellular carcinoma after curative hepatectomy (2008)
  • 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
  • Journal Title: British Journal of Surgery 95(5) Pages: 611-9
• [Journal Article] Anterior approach for left-sided hepatic resection (2008)
  • Author(s): Tanaka S, Taira K, Kudo A, Nakamura N, Ito K, Arii S.
  • Journal Title: Hepatogastroenterology 55(86-87) Pages: 1760-3
• [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 A, Okanoue T.
  • Journal Title: Cancer Genetics and Cytogenetics 180(1) Pages: 30-36
• [Journal Article] Left-sided portal hypertension caused by serous cystadenoma of the pancreas : Report of a case (2008)
  • Author(s): Ito K, Kudo A, Nakamura N, Tanaka S, Teramoto K, Arii S.
  • Journal Title: Surgery Today 38(2) Pages: 184-7
• [Journal Article] Strong association between frequency of intermittent inflow occlusion and transient increase in serum liver enzymes after hepatic resection (2008)
  • Author(s): Teramoto K, Nakamura N, Ito K, Kudo A, Noguchi N, Takamatsu S, Kawamura T, Tanaka S, Arii S.
  • Journal Title: Hepatogastroenterology 55(82-83) Pages: 636-40
• [Journal Article] Prognosis of early hepatocellular carcinoma after hepatic resection (2008)
  • Author(s): Maeda T, Shimada M, Harimoto N, Tsujita E, Aishima S, Tanaka S, Shirabe K, Maehara Y.
  • Journal Title: Hepatogastroenterology 55(85) Pages: 1428-32
• [Journal Article] Activation of B-Myb by E2F1 in hepatocellular carcinoma (2008)
  • Author(s): Nakajima T, Yasui K, Zen K, Inagaki Y, Fujii H, Minami M, Tanaka S, Taniwaki M, Itoh Y, Arii S, Inazawa J, Okanoue T.
  • Journal Title: Hepatology Research 38(9) Pages: 886-95
• [Journal Article] Inhibition of IkappB kinase beta restrains oncogenic proliferation of pancreatic cancer cells (2008)
  • Author(s): Ochiai T, Saito Y, Saitoh T, Dewan MZ, Shioya A, Kobayashi K, Kawachi Hi, Muto S, Itai A, Uota S, Eishi Y, Yamamoto N, Tanaka S, Arii S, Yamaoka S.
  • Journal Title: J Med Dent Sci 55 Pages: 49-59
• [Journal Article] Outcomes and recurrence of initially resection of hepatocellular carcinoma meeting Milan criteria : Rationale for partial hepatectomy as first strategy (2007)
  • Author(s): Tanaka S, Noguchi N, Ochiai T, Kudo A, Nakamura N, Ito K, Kawamura T, Teramoto K, Arii S.
  • Journal Title: Journal of the American College of Surgeons 204(1) Pages: 1-6
• [Journal Article] Mucinous cystadenocarcinoma of the pancreas developing during hormone replacement therapy (2007)
  • Author(s): Tanaka S, Kawamura T, Nakamura N, Teramoto K, Arii S.
  • Journal Title: Digestive Diseases and Sciences 52(5) Pages: 1326-8
• [Journal Article] Molecular targeting therapy against a novel metastasis regulator of pancreatic cancer (2007)
  • Author(s): Tanaka S.
  • Journal Title: Recent Advances and Research Updates 8(1) Pages: 230-239
• [Journal Article] Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes (2007)
  • Author(s): Yanagita T, Kubota S, Kwaki H, Kawata K, Kondo S, Takano-Yamamoto T, Tanaka S, Takagawa M.
  • Journal Title: FEBS Journal 274(7) Pages: 1655-6
• [Journal Article] Characteristic gene expression induced by polyurethane foam/spheroid culture of hepatoma cell line, HepG2 as a promising cell source for bioartificial liver (2007)
  • Author(s): Shimada M, Yamashita Y, Tanaka S, Shirabe K, Nakazawa K, Ijima H, Sakiyama R, Fukuda J, Funatsu K, Sugimachi K.
  • Journal Title: Hepatogastroenterology 54(75) Pages: 814-20
• [Journal Article] Clinical and biological significance of growth factor receptor bound protein 7 (Grb7) in hepatocellular carcinoma (2007)
  • Author(s): Ito S, Taketomi A, Tanaka S, Harimoto N, Aishima Si, Maeda T, Shirabe K, Shimada M, Maehara Y.
  • Journal Title: Molecular Cancer Research 5(7) Pages: 667-73
• [Journal Article] Clinical usefulness of biliary scope for Pringle's maneuver in laparoscopic hepatectomy (2007)
  • Author(s): Maehara S, Adachi E, Shimada M, Taketomi A, Shirabe K, Tanaka S, Maeda T, Ikeda K, Higashi H, Maehara Y.
  • Journal Title: Journal of the American College of Surgeons 205(6) Pages: 816-8
• [Presentation] 系統的肝切除および Surgical Margin の意義と術中造影超音波検査の有効性 (2009)
  • Author(s): 田中真二, 光法雄介, 岡島千怜, 佐藤公太, 村松俊輔, Rama Adikrisna, 吉武健一郎, 村形綾乃, 松村聡, 藍原有弘, 野口典男, 入江工, 工藤篤, 中村典明, 有井滋樹
  • Organizer: 第71回日本臨床外科学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-11-19
• [Presentation] 高度進行肝癌に対する集学的治療の試み : neoadjuvant therapy と分子標的治療への展開 (2009)
  • Author(s): 田中真二, 松村聡, 藍原有弘, 茂櫛薫, Mahmut Yasen, 野口典男, 入江工, 工藤篤, 中村典明, 田中博, 有井滋樹
  • Organizer: 第47回日本癌治療学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-24
• [Presentation] 進行肝癌に対する集学的治療 : neoadjuvant therapy と分子標的治療への展開 (2009)
  • Author(s): 田中真二, 松村聡, 有井滋樹
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-15
• [Presentation] Aurora kinase B addiction as a novel molecular target in hepatocellular carcinoma with aggressive recurrence (2009)
  • Author(s): Tanaka S, Aihara A, Mogushi K, Yasen M, Noguchi N, Irie T, Kudo A, Nakamura N, Imoto I, Miki Y, Inazawa J, Tanaka H, Arii S.
  • Organizer: 第68回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] 肝細胞癌の遺伝子ネットワーク解析に基づく新しい分子標的の同定と前臨床試験への展開 (2009)
  • Author(s): 田中真二, 藍原有弘, Mahmut Yasen, 野口典男, 工藤篤, 黒川敏昭, 中村典明, 稲澤譲治, 田中博, 有井滋樹
  • Organizer: 第64回日本消化器外科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-18
• [Presentation] 癌臨床検体の遺伝子ネットワーク解析に基づく新しい分子標的の同定と前臨床試験への展開 (2009)
  • Author(s): 田中真二, 藍原有弘, Mahmut Yasen, 野口典男, 工藤篤, 黒川敏昭, 中村典明, 田中博, 有井滋樹
  • Organizer: 第13回日本がん分子標的治療学会
  • Place of Presentation: 徳島
  • Year and Date: 2009-06-25
• [Presentation] 大腸癌肝転移に対する肝切除 : Bevacizumab 併用化学療法と術中造影超音波検査の有用性 (2009)
  • Author(s): 田中真二, 植竹裕之, 安野正道, 石川敏昭, 小林宏寿, 光法雄介, 野口典男, 工藤篤, 黒川敏昭, 中村典明, 杉原健一, 有井滋樹
  • Organizer: 第21回日本肝胆膵外科学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-12
• [Presentation] 肝癌脈管侵襲の遺伝子プロファイル・ネットワーク解析を基盤とする分子標的治療への展開 (2009)
  • Author(s): 田中真二, 藍原有広, 茂櫛薫, Mahmut Yasen, 野口典男, 工藤篤, 黒川敏昭, 中村典明, 田中博, 有井滋樹
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2009-06-05
• [Presentation] Aurora kinase B pathway as a novel molecular target in invasive hepatocellular carcinoma (2009)
  • Author(s): Tanaka S, Mogushi K, Aihara A, Yasen M, Noguchi N, Kudo A, Nakamura N, Miki Y, Inazawa J, Tanaka H, Arii S.
  • Organizer: 100th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Denver, CO, USA
  • Year and Date: 2009-04-20
• [Presentation] 肝細胞癌の遺伝子ネットワーク解析に基づいた分子標的治療の開発と mitotic catastrophe による抗癌剤抵抗性の克服 (2009)
  • Author(s): 田中真二, 藍原有弘, Mahmut Yasen, 野口典男, 工藤篤, 黒川敏昭, 中村典明, 稲澤譲治, 田中博, 有井滋樹
  • Organizer: 第109回日本外科学会定期学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2009-04-02
• [Presentation] 肝細胞癌 基準外再発のオミックス解析に基づく新規分子標的治療の開発 (2008)
  • Author(s): 田中真二, 藍原有弘, Mahmut Yasen, 茂櫛薫, 野口典男, 工藤篤, 中村典明, 伊東浩次, 三木義男, 稲澤譲治, 田中博, 有井滋樹
  • Organizer: 第46回日本癌治療学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-31
• [Presentation] Gene expression phenotypes of vascular invasion and novel molecular targets of hepatocellular carcinoma (2008)
  • Author(s): Tanaka S, Mogushi K, Aihara A, Yasen M, Mizushima H, Miki Y, Inazawa J, Tanaka H, Arii S.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] 「肝癌の分子標的治療」肝細胞癌の再発規定分子解析に基づく新規分子標的の同定 (2008)
  • Author(s): 田中真二, 藍原有弘, 有井滋樹
  • Organizer: 第12回日本肝臓学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-10-01
• [Presentation] 分子機序に基づく肝胆膵癌の治療戦略 (2008)
  • Author(s): 田中真二
  • Organizer: 第19回日本消化器癌発生学会総会
  • Place of Presentation: 別府
  • Year and Date: 2008-08-29
• [Presentation] 再発肝細胞癌に対する治療戦略と新規分子標的の同定 (2008)
  • Author(s): 田中真二, 藍原有弘, 野口典男, 工藤篤, 中村典明, 伊東浩次, 有井滋樹
  • Organizer: 第63回日本消化器外科学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-07-16
• [Presentation] 肝癌脈管侵襲の遺伝子プロファイルから見た系統的切除の有効性と術後補助分子標的治療への展開 (2008)
  • Author(s): 田中真二, 茂櫛薫, Mahmut Yasen, 平良薫, 工藤篤, 中村典明, 伊東浩次, 三木義男, 田中博, 有井滋樹
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 松山
  • Year and Date: 2008-06-06
• [Presentation] 肝細胞癌進展規定遺伝子の解析と新規分子標的治療の開発 (2008)
  • Author(s): 田中真二, 藍原有弘, 野口典男, 工藤篤, 中村典明, 伊東浩次, 有井滋樹
  • Organizer: 第20回日本肝胆膵外科学会
  • Place of Presentation: 山形
  • Year and Date: 2008-05-29
• [Presentation] 肝細胞癌再発のオミックス解析による新規分子標的治療の開発 (2008)
  • Author(s): 田中真二, 藍原有弘, Mahmut Yasen, 平良薫, 工藤篤, 中村典明, 伊東浩次, 有井滋樹
  • Organizer: 第108回日本外科学会総会
  • Place of Presentation: 長崎
  • Year and Date: 2008-05-16
• [Presentation] Aurora kinase B is a novel target for treatment of hepatocellular carcinoma (2008)
  • Author(s): Tanaka S, Airahara A, Yasen M, Mogushi K, Kudo A, Nakamura N, Ito K, Imoto I, Inazawa J, Miki Y, Mizushima H, Tanaka H, Arii S.
  • Organizer: 99th Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2008-04-15
• [Presentation] 肝癌の分子標的治療 (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
• [Presentation] 血管新生因子 Angiopoietin-2 の解析による肝癌進展機構の解明 (2007)
  • Author(s): 田中真二, 藍原有弘, 有井滋樹
  • Organizer: 第11回日本肝臓学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2007-10-18
• [Presentation] Omics analysis to predict aggressive recurrence of hepatocellular carcinoma after curative hepatectomy (2007)
  • Author(s): Tanaka S, Yasen M, Mogushi K, Airahara A, Kudo A, Nakamura N, Ito K, Imoto I, Inazawa J, Miki Y, Mizushima H, Tanaka H, Arii S.
  • Organizer: 第66回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-04
• [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, 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62回日本消化器外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-07-19
• [Presentation] 切除可能/ミラノ基準内肝細胞癌に対する初回治療選択の妥当性とその分子生物学的解析 (2007)
  • Author(s): 田中真二, 野口典男, 藍原有広, 落合高徳, 入江工, 工藤篤, 中村典明, 伊東浩次, 寺本研一, 有井滋樹
  • Organizer: 第43回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-31
• [Presentation] 臨床検体を用いた転移規定遺伝子の同定と機能解析による分子標的治療の開発 (2007)
  • Author(s): 田中真二, 落合高徳, Mahmut Yasen, 工藤篤, 中村典明, 伊東浩次, 寺本研一, 有井滋樹
  • Organizer: 第107回日本外科学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-04-11
• [Presentation] Outcomes of initially resectable hepatocellular carcinoma meeting Milan criteria (2007)
  • Author(s): Tanaka S, Noguchi N, Ochiai T, Kudo A, Nakamura N, Ito K, Kawamura T, Teramoto K, Arii S.
  • Organizer: 17th APASL Conference
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2007-03-28
• [Book] NASH診療 best approach (2008)
  • Author(s): 田中真二, 有井滋樹
  • Total Pages: 110-114
  • Publisher: 中外医学社
• [Book] 消化器研修ハンドブック (2008)
  • Author(s): 田中真二
  • Total Pages: 236-250
  • Publisher: 海馬書房