Identification of a histone modifier regulating hepatocarcinogenesis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590962
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: SHIINA Shuichiro 東京大学, 医学部附属病院, 臨床登録医 (70251238)
• Co-Investigator(Kenkyū-buntansha): TATEISHI Keisuke 東京大学, 医学部附属病院, 講師 (20396948) ; ASAOKA Yoshinari 東京大学, 医学部附属病院, 助教 (90431858)
• Project Period (FY): 2011 – 2013
• Keywords: 肝がん

Research Abstract

We established the Alb-Cre/PIK3CA-TG mice that showed hepatic fat deposition at 12w after birth and developed liver tumors including hepatocellular carcinoma by 52w. The PI3K activity was enhanced and tumor suppressor genes including PTEN, ARID3B, XPO4 and DLC1 were downregulated in the tumors. The tumors included a high amount of fatty acids, especially oleic acids. We showed that oleic acids exacerbate the colony formation of immortalized liver cells and reduce the expression of tumor suppressors described above. Furthermore, we have found a chromatin regulator that regulates the tumor formation of Alb-Cre/PIK3CA-TG mice.

Research Products

• [Journal Article] IL28B minor allele is associated with a younger age of onset of hepatocellular carcinoma in patients with chronic hepatitis C virus infection (2014)
  • Author(s): Sato M, Kato N, Tateishi R, Muroyama R, Kowatari N, Li W, Goto K, Otsuka M, Shiina S, Yoshida H, Omata M, Koike K
  • Journal Title: J Gastroenterol Volume: 49(4) Pages: 748-54
  • DOI: 10.1007/s00535-013-0826-x
• [Journal Article] Impact of PNPLA3 polymorphisms on the development of hepatocellular carcinoma in patients with chronic hepatitis C virus infection (2013)
  • Author(s): Sato M, Kato N, Tateishi R, Muroyama R, Kowatari N, Li W, Goto K, Otsuka M, Shiina S, Yoshida H, Omata M, Koike K
  • Journal Title: Hepatol Res
  • DOI: 10.1111/hepr.12258
• [Journal Article] Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma (2013)
  • Author(s): Fujiwara N, Tateishi R, Akahane M, Taguri M, Minami T, Mikami S, Sato M, Uchino K, Enooku K, Kondo Y, Asaoka Y, Yamashiki N, Goto T, Shiina S, Yoshida H, Ohtomo K, Koike K
  • Journal Title: PLoS One Volume: 8(10) Pages: e76018
  • DOI: 10.1371/journal.pone.0076018
• [Journal Article] Spontaneous clearance of serum hepatitis C virus RNA during the clinical course of hepatocellular carcinoma in patients with chronic hepatitis C (2013)
  • Author(s): Minami T, Tateishi R, Shiina S, Fujiwara N, Mikami S, Sato M, Uchino K, Enooku K, Asaoka Y, Kondo Y, Yoshida H, Koike K
  • Journal Title: Hepatol Res
  • DOI: 10.1111/hepr.12203
• [Journal Article] CT with hepatic arterioportography as a pretreatment examination for hepatocellular carcinoma patients : a randomized controlled trial (2013)
  • Author(s): Ohki T, Tateishi R, Akahane M, Mikami S, Sato M, Uchino K, Arano T, Enooku K, Kondo Y, Yamashiki N, Goto T, Shiina S, Yoshida H, Matsuyama Y, Omata M, Ohtomo K, Koike K
  • Journal Title: Am JGastroenterol Volume: 108(8) Pages: 1305-13
  • DOI: 10.1038/ajg.2013.109
• [Journal Article] Radiofrequency ablation for colorectal liver metastasis : 10-year outcome and future perspective (2013)
  • Author(s): Shiina S, Sato T, Kondo Y, Asaoka Y, Tateishi R, Koike K
  • Journal Title: Nihon Geka Gakkai Zasshi Volume: 114(2) Pages: 107-11
• [Journal Article] Frequency, risk factors and survival associated with an intrasubsegmental recurrence after radiofrequency ablation for hepatocellular carcinoma (2013)
  • Author(s): Tateishi R, Shiina S, Akahane M, Sato J, Kondo Y, Masuzaki R, Nakagawa H, Asaoka Y, Goto T, Otomo K, Omata M, Yoshida H, Koike K
  • Journal Title: PLoS One Volume: 8(4) Pages: e59040
  • DOI: 10.1371/journal.pone.0059040
• [Journal Article] IGF-II Producing Hepatocellular Carcinoma Treated with Sorafenib : Metabolic Complications and a Foresight to Molecular Targeting Therapy to the IGF Signal (2012)
  • Author(s): Okushin K, Asaoka Y, Fukuda I, Fujiwara N, Minami T, Sato M, Mikami S, Uchino K, Enooku K, Kondo Y, Tateishi R, Goto T, Shiina S, Yoshida H, Koike K
  • Journal Title: Case Rep Gastroenterol Volume: 6(3) Pages: 784-9
  • DOI: 10.1159/000346462
• [Journal Article] Computed tomography follow-up for the detection of hepatocellularcarcinoma recurrence after initial radiofrequency ablation : a single-centerexperience (2012)
  • Author(s): Mikami S, Tateishi R, Akahane M, Asaoka Y, Kondo Y, Goto T, Shiina S, Yoshida H, Koike K
  • Journal Title: J Vasc Interv Radiol Volume: 23(10) Pages: 1269-75
  • DOI: 10.1016/j.jvir.2012.06.032
• [Journal Article] Percutaneous ethanol injection for hepatocellular carcinoma : 20-year outcome and prognostic factors (2012)
  • Author(s): Shiina S, Tateishi R, Imamura M, Teratani T, Koike Y, Sato S, Obi S, Kanai F, Kato N, Yoshida H, Omata M, Koike K
  • Journal Title: Liver Int Volume: 32(9) Pages: 1434-42
  • DOI: 10.1111/j.1478-3231.2012.02838.x
• [Journal Article] Tumor markers for hepatocellular carcinoma (2012)
  • Author(s): Tateishi R, Enooku K, Shiina S, Koike K
  • Journal Title: Nihon Rinsho Volume: 70(5) Pages: 821-7
• [Journal Article] Increased activity of serum mitochondrial isoenzyme of creatine kinase in hepatocellular carcinoma patients predominantly with recurrence (2012)
  • Author(s): Soroida Y, Ohkawa R, Nakagawa H, Satoh Y, Yoshida H, Kinoshita H, Tateishi R, Masuzaki R, Enooku K, Shiina S, Sato T, Obi S, Hoshino T, Nagatomo R, Okubo S, Yokota H, Koike K, Yatomi Y, Ikeda H
  • Journal Title: J Hepatol Volume: 57(2) Pages: 330-6
  • DOI: 10.1016/j.jhep.2012.03.012
• [Journal Article] Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography (2012)
  • Author(s): Masuzaki R, Tateishi R, Yoshida H, Arano T, Uchino K, Enooku K, Goto E, Nakagawa H, Asaoka Y, Kondo Y, Goto T, Ikeda H, Shiina S, Omata M, Koike K
  • Journal Title: World J Gastroenterol Volume: 18(12) Pages: 1385-90
  • DOI: 10.3748/wjg.v18.i12.1385
• [Journal Article] Systemic combination therapy of intravenous continuous 5-fluorouracil and subcutaneous pegylated interferon alfa-2a for advanced hepatocellular carcinoma (2012)
  • Author(s): Uchino K, Obi S, Tateishi R, Sato S, Kanda M, Sato T, Arano T, Enooku K, Goto E, Masuzaki R, Nakagawa H, Asaoka Y, Kondo Y, Yamashiki N, Goto T, Shiina S, Omata M, Yoshida H, Koike K
  • Journal Title: J Gastroenterol Volume: 47(10) Pages: 1152-9
  • DOI: 10.1007/s00535-012-0574-3
• [Journal Article] Value of post-vascular phase (Kupffer imaging) by contrast-enhanced ultrasonography using Sonazoid in the detection of hepatocellular carcinoma (2012)
  • Author(s): Goto E, Masuzaki R, Tateishi R, Kondo Y, Imamura J, Goto T, Ikeda H, Akahane M, Shiina S, Omata M, Yoshida H, Koike K
  • Journal Title: J Gastroenterol Volume: 47(4) Pages: 477-85
  • DOI: 10.1007/s00535-011-0512-9
• [Journal Article] Evaluation of molecular targeted cancer drug by changes in tumor marker doubling times (2012)
  • Author(s): Enooku K, Tateishi R, Kanai F, Kondo Y, Masuzaki R, Goto T, Shiina S, Yoshida H, Omata M, Koike K
  • Journal Title: J Gastroenterol Volume: 47(1) Pages: 71-8
  • DOI: 10.1007/s00535-011-0462-2
• [Journal Article] Radiofrequency ablation for hepatocellular carcinoma : 10-year outcome and prognostic factors (2011)
  • Author(s): Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Nakagawa H, Asaoka Y, Sato T, Masuzaki R, Kondo Y, Goto T, Yoshida H, Omata M, Koike K
  • Journal Title: Am J Gastroenterol Volume: 107(4) Pages: 569-77
  • DOI: 10.1038/ajg.2011.425
• [Journal Article] Characteristics of hepatocellular carcinoma nodules newly detected by computed tomography during arteriography and arterial portography : preliminary report of a randomized controlled trial (2011)
  • Author(s): Ohki T, Tateishi R, Akahane M, Shiina S, Yamashiki N, Mikami S, Enooku K, Goto E, Masuzaki R, Kondo Y, Goto T, Inoo S, Ohtomo K, Omata M, Yoshida H, Koike K
  • Journal Title: Hepatol Int
• [Journal Article] Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C (2011)
  • Author(s): Ikeda H, Tateishi R, Enooku K, Yoshida H, Nakagawa H, Masuzaki R, Kondo Y, Goto T, Shiina S, Kume Y, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Ono T, Koike K, Yatomi Y
  • Journal Title: Cancer Epidemiol Biomarkers Prev Volume: 20(10) Pages: 2204-11
  • DOI: 10.1158/1055-9965.EPI-11-0464
• [Journal Article] HCC Expert Panel of Japan Society of Hepatology. Management of hepatocellular carcinoma in Japan : Consensus-Based Clinical Practice Guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version (2011)
  • Author(s): Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, Kojiro M, Makuuchi M
  • Journal Title: Dig Dis Volume: 29(3) Pages: 339-64
  • DOI: 10.1159/000327577
• [Journal Article] Altered composition of fatty acids exacerbates hepatotumorigenesis during activation of the phosphatidylinositol 3-kinase pathway (2011)
  • Author(s): Kudo Y, Tanaka Y, Tateishi K, Yamamoto K, Yamamoto S, Mohri D, Isomura Y, Seto M, Nakagawa H, Asaoka Y, Tada M, Ohta M, Ijichi H, Hirata Y, Otsuka M, Ikenoue T, Maeda S, Shiina S, Yoshida H, Nakajima O, Kanai F, Omata M, Koike K
  • Journal Title: J Hepatol Volume: 55(6) Pages: 1400-8
  • DOI: 10.1016/j.jhep.2011
• [Journal Article] Direct differentiation of hepatic cells from human induced pluripotent stem cells using a limited number of cytokines (2011)
  • Author(s): Takata A, Otsuka M, Kogiso T, Kojima K, Yoshikawa T, Tateishi R, Kato N, Shiina S, Yoshida H, Omata M, Koike K
  • Journal Title: Hepatol Int
• [Journal Article] Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation (2011)
  • Author(s): Goto T, Yoshida H, Tateishi R, Enooku K, Goto E, Sato T, Ohki T, Masuzaki R, Imamura J, Shiina S, Koike K, Omata M
  • Journal Title: Hepatol Int Volume: 5(3) Pages: 767-73
  • DOI: 10.1007/s12072-011-9255-1
• [Journal Article] Hepatocellular carcinoma with extrahepatic metastasis : clinical features and prognostic factors (2011)
  • Author(s): Uchino K, Tateishi R, Shiina S, Kanda M, Masuzaki R, Kondo Y, Goto T, Omata M, Yoshida H, Koike K
  • Journal Title: Cancer Volume: 117(19) Pages: 4475-83
  • DOI: 10.1002/cncr.25960
• [Journal Article] Serum level of adiponectin and the risk of liver cancer development in chronic hepatitis C patients (2011)
  • Author(s): Arano T, Nakagawa H, Tateishi R, Ikeda H, Uchino K, Enooku K, Goto E, Masuzaki R, Asaoka Y, Kondo Y, Goto T, Shiina S, Omata M, Yoshida H, Koike K
  • Journal Title: Int J Cancer Volume: 129(9) Pages: 2226-35
  • DOI: 10.1002/ijc.25861
• [Journal Article] Intrahepatic bile duct dilatation after percutaneous radiofrequency ablation for hepatocellular carcinoma : impact on patient's prognosis (2011)
  • Author(s): Kondo Y, Shiina S, Tateishi R, Arano T, Uchino K, Enooku K, Goto E, Nakagawa H, Masuzaki R, Asaoka Y, Fujie H, Goto T, Omata M, Yoshida H, Koike K
  • Journal Title: Liver Int Volume: 31(2) Pages: 197-205
  • DOI: 10.1111/j.1478-3231.2010.02415.x
• [Journal Article] Utility of contrast-enhanced ultrasonography with Sonazoid in radiofrequency ablation for hepatocellular carcinoma (2011)
  • Author(s): Masuzaki R, Shiina S, Tateishi R, Yoshida H, Goto E, Sugioka Y, Kondo Y, Goto T, Ikeda H, Omata M, Koike K
  • Journal Title: J Gastroenterol Hepatol Volume: 26(4) Pages: 759-64
  • DOI: 10.1111/j.1440-1746.2010.06559.x
• [Presentation] KDM4C regulates sphere formation by mediating the crosstalk between Wnt and Notch pathways in colonic cancer cells (2013)
  • Author(s): 山本信三、立石敬介、工藤洋太郎、山本恵介、砂河孝行、永江玄太、油谷浩幸、小池和彦
  • Organizer: Cell symposia
  • Place of Presentation: Spain
  • Year and Date: 20131006-08
• [Presentation] Contribution of TET1 to malignant characteristics in digestive cancer cells (2013)
  • Author(s): 工藤洋太郎、立石敬介、池上恒雄、山本恵介、永江玄太、米澤理人、関元昭、白井、油谷浩幸、小池和彦
  • Organizer: Cell symposia
  • Place of Presentation: Spain
  • Year and Date: 20131006-08
• [Presentation] ヒストン修飾酵素JHDM3CはWnt-Notchシグナルのメデイエーターとして大腸腫瘍形成能を制御する (2013)
  • Author(s): 山本信三、立石敬介、工藤洋太郎、山本恵介、砂河孝行、永江玄太、中塚拓馬、浅岡良成、伊地知秀明、小俣政男、油谷浩幸、小池和彦
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2013-10-04
• [Presentation] 大腸癌肝転移に対するラジオ波焼灼術(RFA)10年間の成績と今後の展開 (2012)
  • Author(s): 椎名秀一朗
  • Organizer: 第67回日本大腸肛門病学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 20120000
• [Presentation] Multimodality fusing imagingを用いた経皮的ラジオ波焼灼術(RFA) (2012)
  • Author(s): 椎名秀一朗、金井弓美子、南達也、佐藤雅哉、三神信太郎、内野康志、新野徹、榎奥健一郎、近藤祐嗣、浅岡良成、建石良介、後藤忠、吉田晴彦、佐藤隆久、小池和彦
  • Organizer: 第48回日本肝癌研究会
  • Place of Presentation: 金沢
  • Year and Date: 20120000
• [Presentation] 大腸癌肝転移に対するラジオ波焼灼術(RFA)10年間の成績と今後の展開 (2012)
  • Author(s): 椎名秀一朗
  • Organizer: 第48回日本肝癌研究会
  • Place of Presentation: 福岡
  • Year and Date: 20120000
• [Presentation] Pancreatic ductal adenocarcinoma can arise from Nestin- positive progenitor cells in the adult pancreas (2012)
  • Author(s): 伊地知秀明、宮林功至、多田素久、浅岡良成、池上恒雄、立石敬介、小俣政男、小池和彦
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120000
• [Presentation] Loss of 5-hydroxymethylcytosine is accompanied with malignant cellular transformation (2012)
  • Author(s): 工藤洋太郎、立石敬介、山本恵介、山本信三、浅岡良成、伊地知秀明、永江玄太、油谷浩幸、小池和彦
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120000
• [Presentation] 膵発癌モデルマウスを用いたゲムシタビンとエルロチニブの効果・メカニズムの検討膵癌:基礎研究 (2012)
  • Author(s): 宮林弘至,伊地知秀明,毛利大,多田素久,山本恵介,浅岡良成,池上恒雄,立石敬介,中井陽介,伊佐山浩通,多田稔,小池和彦
  • Organizer: 第43回日本膵臓学会大会
  • Place of Presentation: 山形
  • Year and Date: 2012-06-29
• [Presentation] 悪性形質転換におけるヒドロキシメチル化シトシンの低下 (2012)
  • Author(s): 工藤洋太郎,立石敬介,山本恵介,山本信三,浅岡良成,伊地知秀明,永江玄太,油谷浩幸,小池和彦
  • Organizer: 第6回日本エピジェネティクス研究会年会
  • Place of Presentation: 東京(ポスター討論)
  • Year and Date: 2012-05-15
• [Presentation] 肝細胞癌(HCC)に対するラジオ波焼灼術(RFA)10年間の成績 (2011)
  • Author(s): 椎名秀一朗、建石良介、小池和彦
  • Organizer: 第47回日本肝癌研究会
  • Place of Presentation: 静岡
  • Year and Date: 20110000
• [Presentation] 大腸癌肝転移に対するラジオ波焼灼術(RFA)10年間の治療成績と今後の展望 (2011)
  • Author(s): 椎名秀一朗、建石良介、小池和彦
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 20110000
• [Presentation] 大腸癌肝転移に対するラジオ波焼灼術(RFA)10年の成績 (2011)
  • Author(s): 椎名秀一朗、建石良介、小池和
  • Organizer: 第19回日本消化器病関連学会週間
  • Place of Presentation: 東京
  • Year and Date: 20110000
• [Presentation] ヒストン脱メチル化酵素JMJD3の発現低下は膵癌の進展を促進するエピジェネティクスと消化器癌 (2011)
  • Author(s): 山本恵介,立石敬介,宮林弘至,山本信三,工藤洋太郎,浅岡良成,伊地知秀明,小俣政男,小池和彦
  • Organizer: 第19回JDDW
  • Place of Presentation: 福岡
  • Year and Date: 20110000
• [Presentation] Hippoシグナル異常を伴う肝細胞癌における受容体型チロシンキナーゼに関する検討 (2011)
  • Author(s): 浅岡良成,池上恒雄,多田素久,建石良介,伊地知秀明,立石敬介,金井文彦,椎名秀一朗,吉田晴彦,小俣政男,小池和彦
  • Organizer: 第19回JDDW/第15回日本肝臓学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-20
• [Presentation] 膵癌微小環境におけるCXCケモカイン/CXCR2 Axis阻害の重要性Intercellular Interaction and Tumor Microenvironment (2011)
  • Author(s): 伊地知秀明,多田素久,宮林弘至,浅岡良成,立石敬介,池上恒雄,小俣政男,小池和彦
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 肝細胞癌におけるHippoシグナルの異常に関する検討肝発癌研究の新展開 (2011)
  • Author(s): 浅岡良成,池上恒雄,多田素久,後藤絵理子,建石良介,伊地知秀明,立石敬介,金井文彦,椎名秀一朗,吉田晴彦,小俣政男,小池和彦
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-03