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2013 Fiscal Year Final Research Report

Translational research focusing on the regulation of proteasome by Gankyrin

Research Project

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Project/Area Number 23590998
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionKinki University

Principal Investigator

SAKURAI Toshiharu  近畿大学, 医学部, 講師 (90397539)

Co-Investigator(Kenkyū-buntansha) KUDO Masatoshi  近畿大学, 医学部, 教授 (10298953)
Co-Investigator(Renkei-kenkyūsha) FUJITA Jun  京都大学, 医学研究科, 教授 (50173430)
Project Period (FY) 2011 – 2013
Keywordsガンキリン / 幹細胞 / 炎症と発癌
Research Abstract

Liver-specific p38-alpha ablation was found to enhance ROS accumulation, because it reduced the expression ofHSP25. p38-alpha-deficiency also increased the expression of SOX2, c-Jun and Gankyrin and led to enhanced TAA-induced hepatocarcinogenesis. The up-regulation of SOX2 and c-Jun was prevented by administration of the antioxidant butylated hydroxyanisole. The risk of human HCC recurrence is positively correlated with ROS accumulation in the liver. Augmented oxidative stress of liver parenchymal cells may explain the close relationship between liver fibrosis and hepatocarcinogenesis. In addition, expression of CD133, a cancer stem cell marker, was significantly correlated with Gankyrin expression. Gankyrin knockdown decreased the expression of vascular endothelial growth factor (VEGF) and stemness factors such as Nanog and Oct-4 in colorectal and liver cancer cells.

  • Research Products

    (36 results)

All 2013 2012 2011

All Journal Article (28 results) (of which Peer Reviewed: 28 results) Presentation (6 results) Book (2 results)

  • [Journal Article] Molecular Link between Liver Fibrosis and Hepatocellular Carcinoma2013

    • Author(s)
      Sakurai T, Kudo M
    • Journal Title

      Liver Cancer

      Volume: 2 Pages: 365-366

    • Peer Reviewed
  • [Journal Article] Reactive Oxygen Species Induce Epigenetic Instability through the Formation of 8-Hydroxydeoxyguanosine in Human Hepatocarcinogenesis2013

    • Author(s)
      Nishida N, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Kudo M
    • Journal Title

      Dig Dis

      Volume: 31(5-6) Pages: 459-66

    • Peer Reviewed
  • [Journal Article] Hypothermia Protects against Fulminant Hepatitis in Mice by Reducing Reactive Oxygen Species Production2013

    • Author(s)
      Sakurai T, Kudo M, Watanabe T, Itoh K, Higashitsuji H, Arizumi T, Inoue T, Hagiwara S, Ueshima K, Nishida N, Fukumoto M, Fujita J
    • Journal Title

      Dig Dis

      Volume: 31(5-6) Pages: 440-6

    • Peer Reviewed
  • [Journal Article] Unique Association between Global DNA Hypomethylation and Chromosomal Alterations in Human Hepatocellular Carcinoma2013

    • Author(s)
      Nishida N, Kudo M, Nishimura T, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Yokomichi N, Nagasaka T, Goel A
    • Journal Title

      PLoS One

      Volume: 8(9) Pages: 72312

    • Peer Reviewed
  • [Journal Article] Impact of peginterferon alpha-2b and entecavir hydrate combination therapy on persistent viral suppression in patients with chronic hepatitis B2013

    • Author(s)
      Hagiwara S, Kudo M, Osaki Y, Matsuo H, Inuzuka T, Matsumoto A, Tanaka E, Sakurai T, Ueshima K, Inoue T, Yada N, Nishida N
    • Journal Title

      J Med Virol

      Volume: 85(6) Pages: 987-95

    • Peer Reviewed
  • [Journal Article] Association of Gankyrin and stemness factor expression in human colorectal cancer2013

    • Author(s)
      Mine H, Sakurai T, Kashida H, Matsui S, Nishida N, Nagai T, Hagiwara S, Watanabe T, Kudo M
    • Journal Title

      Dig Dis Sci

      Volume: 58(8) Pages: 2337-44

    • Peer Reviewed
  • [Journal Article] Overexpression of gankyrin in mouse hepatocytes induces hemangioma by suppressing factor inhibiting hypoxia-inducible factor-1 (FIH-1) and activating hypoxia-inducible factor-12013

    • Author(s)
      Liu Y, Higashitsuji H, Higashitsuji H, Itoh K, Sakurai T, Koike K, Hirota K, Fukumoto M, Fujita J
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 432 Pages: 22-7

    • Peer Reviewed
  • [Journal Article] p38αInhibits Liver Fibrogenesis and Consequent Hepatocarcinogenesis by Curtailing Accumulation of Reactive Oxygen Species2013

    • Author(s)
      Sakurai T, Kudo M, Umemura A, He G, Elsharkawy AM, Seki E, Karin M
    • Journal Title

      Cancer Res

      Volume: 73(1) Pages: 215-24

    • Peer Reviewed
  • [Journal Article] Heat shock protein 27 expression is inversely correlated with atrophic gastritis and intraepithelial neoplasia2013

    • Author(s)
      Nagata Y, Kudo M, Nagai T, Watanabe T, Kawasaki M, Asakuma Y, Hagiwara S, Nishida N, Matsui S, Kashida H, Sakurai T
    • Journal Title

      Dig Dis Sci

      Volume: 58 Pages: 381-8

    • Peer Reviewed
  • [Journal Article] FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma2013

    • Author(s)
      Arao T, Ueshima K, Matsumoto K, Nagai T, Kimura H, Hagiwara S, Sakurai T, Haji S, Kanazawa A, Hidaka H, Iso Y, Kubota K, Shimada M, Utsunomiya T, Hirooka M, Hiasa Y, Toyoki Y, Hakamada K, Yasui K, Kumada T, Toyoda H, Sato S, Hisai H, Kuzuya T, Tsuchiya K, Izumi N, Arii S, Nishio K, Kudo M
    • Journal Title

      Hepatology

      Volume: 57 Pages: 1407-15

    • Peer Reviewed
  • [Journal Article] Quantification of tumor DNA in serum and vascular invasion of human hepatocellular carcinoma2013

    • Author(s)
      Nishida N, Arizumi T, Takita M, Nagai T, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Ida H, Kudo M
    • Journal Title

      Oncology

      Volume: 1 Pages: 82-7

    • Peer Reviewed
  • [Journal Article] Usefulness of Contrast-Enhanced Ultrasonography to Evaluate the Post-Treatment Responses of Radiofrequency Ablation for Hepatocellular Carcinoma : Comparison with Dynamic CT2013

    • Author(s)
      Inoue T, Kudo M, Hatanaka K, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Minami Y, Sakurai T, Ueshima K, Nishida N
    • Journal Title

      Oncology

      Volume: 1 Pages: 51-7

    • Peer Reviewed
  • [Journal Article] Risk of Hepatocellular Carcinoma Development in Cases of Hepatitis C Treated by Long-Term, Low-Dose PEG-IFNα-2a2012

    • Author(s)
      Hagiwara S, Sakurai T, Takita M, Ueshima K, Minami Y, Inoue T, Yada N, Kitai S, Nagai T, Hayaishi S, Arizumi T, Nishida N, Kudo M
    • Journal Title

      Dig Dis

      Volume: 30 Pages: 561-7

    • Peer Reviewed
  • [Journal Article] Gender differences in the livers of patients with hepatocellular carcinoma and chronic hepatitis C infection2012

    • Author(s)
      Nishida N, Arizumi T, Hayaishi S, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Ikai I, Kudo M
    • Journal Title

      Dig Dis

      Volume: 30 Pages: 547-53

    • Peer Reviewed
  • [Journal Article] Characteristic Pattern of Reactivation of Hepatitis B Virus during Chemotherapy for Solid Cancers2012

    • Author(s)
      Hagiwara S, Sakurai T, Nishina S, Tanaka K, Ikeda M, Ueshima K, Minami Y, Inoue T, Yada N, Kitai S, Takita M, Nagai T, Hayaishi S, Arizumi T, Park AM, Munakata H, Nishida N, Kudo M
    • Journal Title

      Dig Dis

      Volume: 30 Pages: 541-6

    • Peer Reviewed
  • [Journal Article] Identification of a novel enhancer that binds Sp1 and contributes to induction of cold-inducible RNA-binding protein (cirp) expression in mammalian cells2012

    • Author(s)
      Sumitomo Y, Higashitsuji H, Higashitsuji H, Liu Y, Fujita T, Sakurai T, Candeias MM, Itoh K, Chiba T, Fujita J
    • Journal Title

      BMC Biotechnol

      Volume: 12 Pages: 72

    • Peer Reviewed
  • [Journal Article] Cold-inducible RNA-binding protein (Cirp) interacts with Dyrk1b/Mirk and promotes proliferation of immature male germ cells in mice2012

    • Author(s)
      Masuda T, Itoh K, Higashitsuji H, Higashitsuji H, Nakazawa N, Sakurai T, Liu Y, Tokuchi H, Fujita T, Zhao Y, Nishiyama H, Tanaka T, Fukumoto M, Ikawa M, Okabe M, Fujita J
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 109 Pages: 10885-90

    • Peer Reviewed
  • [Journal Article] Toll-like receptor activation in basophils contributes to the development of IgG4-related disease2012

    • Author(s)
      Watanabe T, Yamashita K, Sakurai T, Kudo M, Shiokawa M, Uza N, Kodama Y, Uchida K, Okazaki K, Chiba T
    • Journal Title

      J Gastroenterol

      Volume: 48 Pages: 247-53

    • Peer Reviewed
  • [Journal Article] Activation of JNK and High Expression Level of CD133 Predict a Poor Response to Sorafenib in Hepatocellular Carcinoma2012

    • Author(s)
      Hagiwara S, Kudo M, Nagai T, Inoue T, Ueshima K, Nishida N, Watanabe T, Sakurai T
    • Journal Title

      Br J Cancer

      Volume: 106 Pages: 1997-2003

    • Peer Reviewed
  • [Journal Article] p38MAPK suppresses chronic pancreatitis by regulating HSP27 and BAD expressions2012

    • Author(s)
      Park AM, Kudo M, Hagiwara S, Tabuchi M, Watanabe T, Munakata H, Sakurai T
    • Journal Title

      Free Radical Biol Med

      Volume: 52 Pages: 2284-2291

    • Peer Reviewed
  • [Journal Article] Assessment of Gd-EOB-DTPA-enhanced MRI for HCC and dysplastic nodules and comparison of detection sensitivity versus MDCT2012

    • Author(s)
      Inoue T, Kudo M, Komuta M, Hayaishi S, Ueda T, Takita M, Kitai S, Hatanaka K, Yada N, Hagiwara S, Chung H, Sakurai T, Ueshima K, Sakamoto M, Maenishi O, Hyodo T, Okada M, Kumano S, Murakami T
    • Journal Title

      J Gastroenterol

      Volume: 47(9) Pages: 1036-47

    • Peer Reviewed
  • [Journal Article] Activation of JNK in the non-cancerous liver tissue predicts a high risk of recurrence after hepatic resection2012

    • Author(s)
      Hagiwara S, Kudo M, Chung H, Ueshima K, Haji S, Watanabe T, Park AM, Munakata H, Sakurai T
    • Journal Title

      Hepatol Res

      Volume: 42 Pages: 394-400

    • Peer Reviewed
  • [Journal Article] Adriamycin Enhances Proteasome-Mediated Generation of the Proapoptotic Processed Form of MAGE-A4 in Hepatoma Cells2011

    • Author(s)
      Sakurai T, Kudo M, Itoh K, Ryu U, Higashitsuji H, Fujita J
    • Journal Title

      Oncology

      Volume: 81 (Suppl 1) Pages: 30-5

    • Peer Reviewed
  • [Journal Article] Signaling pathways governing tumor angiogenesis2011

    • Author(s)
      Sakurai T, Kudo M
    • Journal Title

      Oncology

      Volume: 81 (Suppl 1) Pages: 24-9

    • Peer Reviewed
  • [Journal Article] Association of interleukin-28B and hepatitis C genotype 1 with a high viral load and response to pegylated interferon plus ribavirin therapy2011

    • Author(s)
      Sakurai T, Kudo M
    • Journal Title

      Digestion

      Volume: 84 (Suppl 1) Pages: 56-61

    • Peer Reviewed
  • [Journal Article] Involvement of activation of toll-like receptors and NOD-like receptors is involved in enhanced IgG4 responses in autoimmune pancreatitis2011

    • Author(s)
      Watanabe T, Yamashita K, Fujikawa S, Sakurai T, Kudo M, Shiokawa M, Kodama Y, Uchida K, Okazaki K, Chiba T
    • Journal Title

      Arthritis Rheum

      Volume: 64 Pages: 914-24

    • Peer Reviewed
  • [Journal Article] Des-γ-Carboxyprothrombin May Be a Promising Biomarker to Determine the Therapeutic Efficacy of Sorafenib for Hepatocellular Carcinoma2011

    • Author(s)
      Ueshima K, Kudo M, Takita M, Nagai T, Tatsumi C, Ueda T, Kitai S, Ishikawa E, Yada N, Inoue T, Hagiwara S, Minami Y, Chung H, Sakurai T
    • Journal Title

      Digestion

      Volume: 29 Pages: 321-325

    • Peer Reviewed
  • [Journal Article] Involvement of angiotensin II and reactive oxygen species in pancreatic fibrosis2011

    • Author(s)
      Sakurai T, Kudo M, Fukuta N, Nakatani T, Kimura M, Park AM, Munakata H
    • Journal Title

      Pancreatology

      Volume: 11 (suppl 2) Pages: 7-13

    • Peer Reviewed
  • [Presentation] 肝発癌および治療抵抗性獲得における幹細胞の役割2013

    • Author(s)
      櫻井俊治, 他
    • Organizer
      Japan Digestive Disease Week 2013ワークショップ
    • Place of Presentation
      東京
    • Year and Date
      2013-10-11
  • [Presentation] 大腸発癌における幹細胞の制御機構2013

    • Author(s)
      櫻井俊治, 他
    • Organizer
      日本消化器癌発生学会総会シンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2013-09-05
  • [Presentation] 胃粘膜上皮のHSPA27発現は上皮内癌の発生リスクと負の相関を示す2013

    • Author(s)
      永田嘉昭、櫻井俊治, 他
    • Organizer
      第99回日本消化器病学会総会
    • Place of Presentation
      鹿児島
    • Year and Date
      2013-03-23
  • [Presentation] 慢性膵炎におけるp38MAPK, HSPA27の役割2013

    • Author(s)
      櫻井俊治, 他
    • Organizer
      第99回日本消化器病学会総会
    • Place of Presentation
      鹿児島
    • Year and Date
      2013-03-21
  • [Presentation] Activation of JNK in the non-cancerous liver tissue predicts a high risk of recurrence after hepatic resection for hepatocellular carcinoma2012

    • Author(s)
      櫻井俊治, 他
    • Organizer
      Digestive Disease Week 2012
    • Place of Presentation
      米国サンディエゴ
    • Year and Date
      2012-05-21
  • [Presentation] 肝細胞癌治療におけるJNK活性の重要性2011

    • Author(s)
      萩原智、櫻井俊治、工藤正俊
    • Organizer
      日本肝臓学会総会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2011-06-02
  • [Book] シグナル伝達異常とバイオマーカー探索2012

    • Author(s)
      櫻井俊治, 他
    • Total Pages
      35-39
    • Publisher
      The Liver Cancer Journal
  • [Book] トップランナーに聞く2011

    • Author(s)
      櫻井俊治, 他
    • Total Pages
      1207-1210
    • Publisher
      最新医学社

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Published: 2015-07-16  

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