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Research on the mechanism of hepatocarcinogenesis by long-term replication of hepatitis virus

Research Project

Project/Area Number 16H05196
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionOkayama University

Principal Investigator

Kato Nobuyuki  岡山大学, 医歯薬学総合研究科, 教授 (40150883)

Co-Investigator(Kenkyū-buntansha) 金 惠淑  岡山大学, 医歯薬学総合研究科, 准教授 (70314664)
佐藤 伸哉  岡山大学, 医歯薬学総合研究科, 助教 (80333558)
團迫 浩方  岡山大学, 医歯薬学総合研究科, 准教授 (80379841)
上田 優輝  岡山大学, 医歯薬学総合研究科, 助教 (90756074)
Research Collaborator SEJIMA Hiroe  
KOKU Irin  
ONOMURA Daichi  
HIRAMOTO Hiroki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsC 型肝炎ウイルス / B型肝炎ウイルス / 長期HCV複製細胞 / 遺伝子発現変動 / HBV感受性 / Exosome / C型肝炎ウイルス(HCV) / B型肝炎ウイルス(HBV) / HCV長期複製細胞 / HBV長期複製細胞 / ウイルス / 遺伝子 / 発現制御 / 感染症 / 癌 / C型肝炎ウイルス / 長期HBV複製細胞
Outline of Final Research Achievements

We studied to clarify the relation of long-term replication of HBV or HCV and hepatocarcinogenesis, and then obtained the following results. (1) We clarified that VCX2 and AGR2 contributed to the expression control of the CPB2 gene whose expression level was remarkably decreased by the long-term HCV replication. (2) We successfully established two cloned cell lines exhibiting high HBV susceptibility by the subcloning of human immortalized hepatocyte NKNT-3 cells and human hepatoma Li23 cells. (3) We identified several genes whose expression levels significantly changed before and after HBV infection. (4) We developed the purification and quantitative methods for exosome produced from cultured cells. We demonstrated that the amount of exosome produced from HBV insusceptible cells was significantly higher than that of HBV susceptible cells.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、HCVやHBV感染により高頻度に生じる肝癌の発症を未然に防ぐ方法の開発に資する知見となるので、学術的意義があるばかりでなく、難治癌の1つで我が国に多い肝癌肝癌患者に対する社会的意義も大きい。今後も継続してこの関連の研究を展開していく必要性を示す研究成果になったことは、この研究課題の大きさを物語っていると言える。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (40 results)

All 2019 2018 2017 2016 Other

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 8 results,  Acknowledgement Compliant: 1 results) Presentation (25 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Journal Article] High‐level expression of STING restricts susceptibility to HBV by mediating type III IFN induction.2019

    • Author(s)
      Dansako H, Imai H, Ueda Y, Satoh S, Shimotohno K, Kato N.
    • Journal Title

      FASEB BioAdvances

      Volume: 1 Pages: 67-80

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acidic polysaccharides isolated from marine algae inhibit the early step of viral infection.2019

    • Author(s)
      Ueno M, Nogawa M, Siddiqui R, Watashi K, Wakita T, Kato N, Ikeda M, Okimura T, Isaka S, Oda T, Ariumi Y.
    • Journal Title

      Int J Biol Macromol

      Volume: 124 Pages: 282-290

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Multiple antiviral activities of the antimalarial and anti-hepatitis C drug candidates N-89 and N-2512018

    • Author(s)
      Ueda Youki、Gu Weilin、Dansako Hiromichi、Kim Hye-Sook、Yoshizaki Sayaka、Okumura Nobuaki、Ishikawa Tomohiro、Nishitsuji Hironori、Kato Fumihiro、Hishiki Takayuki、Satoh Shinya、Ishii Koji、Masuda Michiaki、Shimotohno Kunitada、Ikeda Masanori、Kato Nobuyuki
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 15 Pages: 1-6

    • DOI

      10.1016/j.bbrep.2018.05.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Daunorubicin, a topoisomerase II poison, suppresses viral production of hepatitis B virus by inducing cGAS-dependent innate immune response2018

    • Author(s)
      Imai Hirotaka、Dansako Hiromichi、Ueda Youki、Satoh Shinya、Kato Nobuyuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 504 Issue: 4 Pages: 672-678

    • DOI

      10.1016/j.bbrc.2018.08.195

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of interferon signaling and HCV-RNA replication by extracellular matrix.2018

    • Author(s)
      Kuwashiro T, Iwane S, Jinghe X, Matsuhashi S, Eguchi Y, Anzai K, Fujimoto K, Mizuta T, Sakamoto N, Ikeda M, Kato N, Ozaki I.
    • Journal Title

      Int J Mol Med

      Volume: 42 Pages: 957-965

    • DOI

      10.3892/ijmm.2018.3693

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual effects of the Nrf2 inhibitor for inhibition of hepatitis C virus and hepatic cancer cells.2018

    • Author(s)
      Murakami Y, Sugiyama K, Ebinuma H, Nakamoto N, Ojiro K, Chu PS, Taniki N, Saito Y, Teratani T, Koda Y, Suzuki T, Saito K, Fukasawa M, Ikeda M, Kato N, Kanai T, Saito H.
    • Journal Title

      BMC Cancer.

      Volume: 3 Issue: 1 Pages: 680-680

    • DOI

      10.1186/s12885-018-4588-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ribavirin-induced down-regulation of CCAAT/enhancer-binding protein α leads to suppression of lipogenesis2018

    • Author(s)
      Satoh Shinya、Onomura Daichi、Ueda Youki、Dansako Hiromichi、Honda Masao、Kaneko Shuichi、Kato Nobuyuki
    • Journal Title

      Biochemical Journal

      Volume: 476 Issue: 1 Pages: 137-149

    • DOI

      10.1042/bcj20180680

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ULBP1 is induced by hepatitis C virus infection and is the target of the NK cell-mediated innate immune response in human hepatocytes2018

    • Author(s)
      Dansako Hiromichi、Imai Hirotaka、Ueda Youki、Satoh Shinya、Wakita Takaji、Kato Nobuyuki
    • Journal Title

      FEBS Open Bio

      Volume: 8 Issue: 3 Pages: 361-371

    • DOI

      10.1002/2211-5463.12373

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ribavirin suppresses hepatic lipogenesis through inosine monophosphate dehydrogenase inhibition: Involvement of adenosine monophosphate-activated protein kinase-related kinases and retinoid X receptor α.2017

    • Author(s)
      S Satoh, K Mori, D Onomura, Y Ueda, H Dansako, M Honda, S Kaneko, M Ikeda, N Kato.
    • Journal Title

      Hepatol Commun

      Volume: 1 Issue: 6 Pages: 550-563

    • DOI

      10.1002/hep4.1065

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of oncolytic adenovirus-mediated hepatotoxicity by liver-specific inhibition of NF-κB.2017

    • Author(s)
      Machitani M., Sakurai F., Wakabayashi K., Nakatani K., Tachibana M., Kato N., Fujiwara T., Mizuguchi H.
    • Journal Title

      Mol. Ther. Oncolysis.

      Volume: 7 Pages: 76-85

    • DOI

      10.1016/j.omto.2017.10.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of preclinical antimalarial drugs, which can overcome direct-acting antivirals-resistant hepatitis C viruses, using the viral reporter assay systems.2017

    • Author(s)
      Ueda Y, Dansako H, Sato S, Kim HS, Wataya Y, Doi H, Ikeda M, Kato N.
    • Journal Title

      Virus Res

      Volume: 235 Pages: 37-48

    • DOI

      10.1016/j.virusres.2017.03.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular mechanism underlying the suppression of CPB2 expression caused by persistent hepatitis C virus RNA replication.2016

    • Author(s)
      Sejima H, Satoh S, Dansako H, Honda M, Kaneko S, Ikeda M, Kato N.
    • Journal Title

      Acta Med Okayama

      Volume: 70 Pages: 75-88

    • NAID

      120005749825

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of resistance-associated NS5A mutations in hepatitis C virus on viral production and susceptibility to antiviral reagents.2016

    • Author(s)
      Nitta S, Asahina Y, Matsuda M, Yamada N, Sugiyama R, Masaki T, Suzuki R, Kato N, Watanabe M, Wakita T, Kato T.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 34652-34652

    • DOI

      10.1038/srep34652

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rab13 is involved in the entry step of hepatitis C virus infection.2016

    • Author(s)
      Takeda M, Ikeda M, Satoh S, Dansako H, Wakita T, Kato N.
    • Journal Title

      Acta Med Okayama

      Volume: 70 Pages: 111-118

    • NAID

      120005749829

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 抗マラリア及び抗HCV薬候補N-89とN-251が有する幅広い抗ウイルス活性2018

    • Author(s)
      上田 優輝, 谷イ琳, 團迫 浩方, 金 惠淑, 吉崎 佐矢香, 奥村 暢章, 石川 知弘, 西辻 裕紀, 加藤 文博, 日紫喜 隆行, 佐藤 伸哉, 石井 孝司, 増田 道明, 下遠野 邦忠, 池田 正徳, 加藤 宣之
    • Organizer
      第28回抗ウイルス療法学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Suppression of oncolytic adenovirus-mediated hepatotoxicity by liver-specific inhibition of NF-κB2018

    • Author(s)
      Mitsuhiro Machitani, Fuminori Sakurai, Keisaku Wakabayashi, Masashi Tachibana, Nobuyuki Kato, Toshiyoshi Fujiwara, Hiroyuki Mizuguchi
    • Organizer
      第24回日本遺伝子細胞治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] B型肝炎ウイルス感染ヒト不死化肝NKNT-3細胞由来のエクソソーム内タンパク質の解析2018

    • Author(s)
      團迫 浩方、今井 大誉、上田 優輝、佐藤 伸哉、加藤 宣之
    • Organizer
      第5回日本細胞外小胞学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of the new host factors necessary for susceptibility to HBV using plural human cell lines2018

    • Author(s)
      Youki Ueda, Hiromichi Dansako, Shinya Satoh, Kunitada Shimotohno, Nobuyuki Kato
    • Organizer
      2018 International Meeting on Molecular Biology of Hepatitis B Virus
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Topoisomerase II inhibitor triggers cyclic GMP-AMP synthase-dependent innate immune response in human immortalized hepatocyte NKNT-32018

    • Author(s)
      Hirotaka Imai, Hiromichi Dansako, Youki Ueda, Shinya Satoh, Nobuyuki Kato
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Drug screening for suppression of lipogenesis through downregulation of C/EBPα2018

    • Author(s)
      Shinya Satoh, Daichi Onomura, Koichi Watashi, Youki Ueda, Hiromichi Dansako, Masao Honda,, Shuichi Kaneko, Nobuyuki Kato
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mechanism of GPAM suppression by Anti-HCV drug ribavirin2018

    • Author(s)
      Daichi Onomura, Shinya Satoh, Youki Ueda, Hiromichi Dansako, Nobuyuki Kato
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Screening of the new host factors necessary for HBV proliferation using plural human cell lines2018

    • Author(s)
      Youki Ueda, Hiromichi Dansako, Shinya Satoh, Kunitada Shimotohno, Nobuyuki Kato
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Analysis of host and viral factors contributing to resistant acquisition for the preclinical anti-HCV drugs, N-89 and N-2512018

    • Author(s)
      Weilin Gu, Youki Ueda, Shinya Satoh, Hiromichi Dansako, Nobuyuki Kato
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Highly expression of STING restricts HBV infection by mediating the induction of type III interferon in human immortalized hepatocyte NKNT-32018

    • Author(s)
      Hiromichi Dansako, Hirotaka Imai, Youki Ueda, Shinya Satoh, Kunitada Shimotohno, Nobuyuki Kato
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Perospirone, an antipsychotics, exhibits anti-hepatitis C virus activity2018

    • Author(s)
      Midori Takeda, Tomoka Taniguchi, Matsue Maezono, Takaji Wakita, Nobuyuki Kato, Masanori Ikeda
    • Organizer
      第66回日本ウイルス学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 抗HCV剤としての抗精神病薬ペロスピロンの可能性について2018

    • Author(s)
      武田 緑、谷口 智香、前園 夏絵、脇田 隆字、加藤 宣之、池田 正徳
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] HCVポリメラーゼ/プロテアーゼ二重阻害活性を有するフラーレン誘導体の細胞内HCV複製阻害及び酸化ストレス抑制効果2017

    • Author(s)
      片岡 裕樹、上田 優輝、髙橋 恭子、中村 成夫、大江 知之、 加藤 宣之、増野 匡彦
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] クロファラビンはドラッグリポジショニングにより見いだされた 抗HBV活性と抗HCV活性を有する治療剤候補である2017

    • Author(s)
      武田 緑、加藤 宣之、池田 正徳
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of human hepatoma cell line, Li23-derived cells possessing high susceptibility to HBV2017

    • Author(s)
      Youki Ueda, Hiromichi Dansako, Shinya Satoh, Kunitada Shimotohno, Nobuyuki Kato
    • Organizer
      2017 International Meeting on Molecular Biology of Hepatitis B Virus
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Downregulation of C/EBPα by anti-HCV drug ribavirin leads to the suppression of triglyceride synthesis pathway2017

    • Author(s)
      Shinya Satoh, Daichi Onomura, Youki Ueda, Hiromichi Dansako, Masao Honda, Shuichi Kaneko, Nobuyuki Kato
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification of new amino acid substitutions contributing to DAA-resistance, using HCV reporter assay systems2017

    • Author(s)
      Youki Ueda, Hiromichi Dansako, Shinya Satoh, Masanori Ikeda, Nobuyuki Kato
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Resistant acquisition mechanism for anti-HCV drug candidates, N-89 and its derivative N-2512017

    • Author(s)
      Weilin Gu, Youki Ueda, Shinya Satoh, Hiromichi Dansako, Nobuyuki Kato
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 交感神経遮断薬であるグアンファシンは抗HCV活性を示す2017

    • Author(s)
      武田 緑、前園 夏絵、上高原 美奈、脇田 隆字、加藤 宣之、 池田 正徳
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of HBV infection system using human immortalized hepatocyte NKNT-3 cells2017

    • Author(s)
      Hiromichi Dansako, Hirotaka Imai, Youki Ueda, Shinya Satoh, Kunitada Shimotohno, Nobuyuki Kato
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Both host and viral factors contribute to the resistance to preclinical anti-HCV drugs, N-89 and N-251.2016

    • Author(s)
      Gu W, Ueda Y, Dansako H, Satoh S, Kato N.
    • Organizer
      The 64th Annual Meeting of The Japanese Society for Virology
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Genetic characterization of HCVs obtained from HCV-RNA-replicating cells possessing a DAA-, N-89-, or N-251-resistant phenotype.2016

    • Author(s)
      Ueda Y, Dansako H, Satoh S, Ikeda M, Kato N.
    • Organizer
      The 64th Annual Meeting of The Japanese Society for Virology
    • Place of Presentation
      札幌コンベンションセンター、札幌
    • Year and Date
      2016-10-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA-PKcs and Rad18 are required for HCV replication.2016

    • Author(s)
      Ariumi Y, Tateishi S, Wakita T, Kato N.
    • Organizer
      23rd International Symposium on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      国際会議場、京都
    • Year and Date
      2016-10-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HBVとHCVに対する抗ウイルス剤の探索2016

    • Author(s)
      武田 緑、團迫 浩方、馬場 昌範、加藤 宣之、池田 正徳
    • Organizer
      第53回日本ウイルス学会九州支部会
    • Place of Presentation
      宮崎市民プラザ、宮崎
    • Year and Date
      2016-09-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] DAA製剤によるHCV治療におけるN-89/N-251の有用性とそれらの作用機序の解析2016

    • Author(s)
      上田 優輝、團迫 浩方、佐藤 伸哉、池田 正徳、加藤 宣之
    • Organizer
      第26回抗ウイルス療法学会総会
    • Place of Presentation
      名古屋市立大学、名古屋
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
  • [Remarks] 腫瘍ウイルス学分野Research

    • URL

      http://www.okayama-u.ac.jp/user/med/dmb/research.html

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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