Development of new therapy for elder women with chronic hepatitis C

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Virology
• Research Institution: Okayama University
• Principal Investigator: IKEDA Masanori Okayama University, 大学院・医歯薬学総合研究科, 准教授 (30315767)
• Project Period (FY): 2008 – 2010
• Keywords: C型慢性肝炎 / HCV / ラロキシフェン / スタチン剤

Research Abstract

Interferon and ribavirin therapy is a standard medication for chronic hepatitis C. However, the effect of the therapy is approximately 50%. The elder female patients are especially resistant to the therapy. To overcome this problem, we investigated the anti-hepatitis C virus (HCV) activity of osteoporosis reagent, raloxifene. Raloxifene exhibited anti-HCV activity by itself in cell culture system and enhanced anti-HCV activity of interferon. On the other hand, raloxifene reduced anti-HCV activity of cholesterol lowering reagent, statins.

Research Products

• [Journal Article] Gene expression profile of Li23, a new human hepatoma cell line enables robust epatitis C virus replication : Comparison with HuH-7 and other hepatic cell lines. (2010)
  • Author(s): Mori K, Ikeda M, Ariumi Y, Kato N.
  • Journal Title: Hepatology Res. 40 Pages: 1248-1253
  • Peer Reviewed
• [Journal Article] An antioxidant resveratrol significantly enhanced replication of hepatitis C virus. (2010)
  • Author(s): Nakamura M, Saito H, Ikeda M, Hokari R, Kato N, Hibi T, Miura S.
  • Journal Title: World J.Gastroenterol. 16 Pages: 184-192
  • Peer Reviewed
• [Journal Article] Hepatitis C virus core protein abrogates the DDX3 function that enhances IPS-1-mediated IFN-b induction. (2010)
  • Author(s): Oshiumi H, Ikeda M, Matsumoto M, Watanabe A, TakeuchI O, Akira S, Kato N, Shimotohno K, Seya T.
  • Journal Title: PLoS One 5 Pages: e14258
  • Peer Reviewed
• [Journal Article] Efficient replication systems for hepatitis C virus using a new human hepatoma cell line. (2009)
  • Author(s): Kato N, Mori K, Abe K, Dansako H, Kuroki M, Ariumi Y, Wakita T, IkedaM.
  • Journal Title: Virus Res 146 Pages: 41-50
  • Peer Reviewed
• [Journal Article] HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A. (2009)
  • Author(s): Abe K, Ikeda M, Ariumi Y, D Hiromichi, Wakita T, Kato N.
  • Journal Title: Arch Virol. 154 Pages: 1671-1677
• [Journal Article] Oxidative stress induces anti-hepatitis C virus status via the activation of extracellular signal-regulated kinase. (2009)
  • Author(s): Yano M, Ikeda M, Abe K, Kawai Y, Kuroki M, Mori K, Dansako H, Ariumi Y, Ohkoshi S, Aoyagi Y, Kato N.
  • Journal Title: Hepatology 20 Pages: 678-688
• [Journal Article] Oncostatin M synergistically inhibits HCV RNA replication in combination with interferon-a. (2009)
  • Author(s): Ikeda M, Mori K, Ariumi Y, Dansako H, Kato N.
  • Journal Title: FEBS Letters 583 Pages: 1434-1438
• [Journal Article] Double-stranded RNA-induced interferon-beta and inflammatory cytokine production modulated by hepatitis C virus serine proteases derived from patients with hepatic diseases. (2009)
  • Author(s): Dansako H, Ikeda M, Ariumi Y, Wakita T,Kato N.
  • Journal Title: Arch Virol. 154 Pages: 801-810
  • Peer Reviewed
• [Journal Article] Development of an HCV relapse model using genome-length HCV RNA-harboring cells possessing the IFN-a-resistance phenotype. (2009)
  • Author(s): Kawai Y, Ikeda M, Abe KI, Yano M, Ariumi Y, Dansako H, Yamamoto K, Kato N.
  • Journal Title: Hepatol Res. 39 Pages: 898-909
  • Peer Reviewed
• [Journal Article] Arsenic trioxide inhibits hepatitis C virus RNA replication through modulation of the glutathione redox system and oxidative stress. (2009)
  • Author(s): Kuroki M, Ariumi Y, Ikeda M, Dansako H, Wakita T, Kato N.
  • Journal Title: J Virol. 83 Pages: 2338-2348
  • Peer Reviewed
• [Journal Article] Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents. (2009)
  • Author(s): Nishimura G, Ikeda M, Mori K, Nakazawa T, Ariumi Y, Dansako H, Kato N.
  • Journal Title: Antiviral Res. 82 Pages: 42-50
  • Peer Reviewed
• [Journal Article] A new living cell-based assay system for monitoring genome-length hepatitis C virus RNA replication. (2008)
  • Author(s): Dansako H, Ikeda M, Abe K, Mori K, Takemoto K, Ariumi Y, Kato N.
  • Journal Title: Virus Res. 137 Pages: 72-79
  • Peer Reviewed
• [Journal Article] Possible molecular mechanism of the relationship between NS5B polymorphisms and early clearance of hepatitis C virus during interferon plus ribavirin treatment. (2008)
  • Author(s): Nakamura M, Saito H, Ikeda M, Tada S, Kumagai N, Kato N, Shimotohno K, Hibi T.
  • Journal Title: J. Med.Virol. 80 Pages: 632-639
  • Peer Reviewed
• [Presentation] 異なるHCV株、細胞株を用いたHCV RNA複製培養細胞での薬剤評価 (2010)
  • Author(s): 池田正徳、森京子、武田緑、中澤貴秀、有海康雄、團迫浩方、加藤宣之
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 20101107-20101109
• [Presentation] リバビリンの抗HCV活性を決定する因子の解析 (2010)
  • Author(s): 森京子、池田正徳、有海康雄、團迫浩方、脇田隆字、加藤宣之
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 20101107-20101109
• [Presentation] Development of genome-length HCV RNA replication assay systems derived from different HCV strains using HuH-7 and Li23 cells. (2010)
  • Author(s): 池田正徳, 森京子, 中澤貴秀, 有海康雄, 團迫浩方, 加藤宣之
  • Organizer: 17th international symposium on hepatitis C virus and related viruses
  • Place of Presentation: Yokohama (Japan)
  • Year and Date: 20100911-20100915
• [Presentation] Anti-HCV mechanism of ribavirin in novel HCV replication cell systems. (2010)
  • Author(s): 森京子, 池田正徳, 有海康雄, 團迫浩方, 脇田隆字, 加藤宣之
  • Organizer: 17th international symposium on hepatitis C virus and related viruses
  • Place of Presentation: Yokohama (Japan)
  • Year and Date: 20100911-20100915
• [Presentation] Involvement of the MEK-ERK1/2 Signaling Pathway in the Anti-HCV Mechanism of Oxidative Stress. (2009)
  • Author(s): Yano M, Ikeda M, Abe K, Kawai Y, Kuroki M, Mori K, Dansako H, Ariumi Y, Matsuda Y, Ohkoshi S, Aoyagi Y, Kato N
  • Organizer: The Liver Meeting 2009, AASLD
  • Place of Presentation: Boston, Massachusetts, USA
  • Year and Date: 20091030-20091103
• [Presentation] オンコスタチンMはインターフェロンの抗HCV活性を相乗的に増強する (2009)
  • Author(s): 池田正徳、森京子、有海康雄、團迫浩方、加藤宣之
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20091025-20091027
• [Presentation] リバビリンの抗HCV活性を解析評価できるLi23細胞由来のHCV-RNA複製システム (2009)
  • Author(s): 森京子、池田正徳、有海康雄、團迫浩方、加藤宣之
  • Organizer: 第57回日本ウイルス学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20091025-20091027
• [Presentation] Oncostatin M synergistically inhibits HCV RNA replication in combination with interferon-a. (2009)
  • Author(s): 池田正徳, 森京子, 有海康雄, 團迫浩方, 加藤宣之
  • Organizer: 16th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Nice, France
  • Year and Date: 20091003-20091007
• [Presentation] Li23 cell-derived HCV-RNA replicating systems enabling analysis for anti-HCV mechanism of Ribavirin. (2009)
  • Author(s): 森京子, 池田正徳, 有海康雄, 團迫浩方, 加藤宣之
  • Organizer: 16th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Nice, France
  • Year and Date: 2009-10-04
• [Presentation] Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents. (2009)
  • Author(s): Nishimura G, Ikeda M, Mori K, Nakazawa T, Ariumi Y, Dansako H, Kato N
  • Organizer: 16th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Nice, France
  • Year and Date: 2009-10-04
• [Presentation] 異なる1b型HCV陽性血清由来の全長HCV RNAレポーターアッセイ系の開発 (2008)
  • Author(s): 池田正徳、森京子、西村剛、阿部健一、有海康雄、團迫浩方、中沢貴之、加藤宣之
  • Organizer: 第56回日本ウイルス学会
  • Place of Presentation: 岡山
  • Year and Date: 20081026-20081028
• [Presentation] 新しいヒト肝癌細胞株Li23由来の全長HCV-RNA複製細胞を用いた薬剤評価システム (2008)
  • Author(s): 森京子、加藤宣之、阿部健一、有海康雄、團迫浩方、池田正徳
  • Organizer: 第56回日本ウイルス学会
  • Place of Presentation: 岡山
  • Year and Date: 20081026-20081028
• [Presentation] Identification of 5-HETE as the anti-HCV molecule among the arachidonic acid metabolites. (2008)
  • Author(s): Ikeda M, Abe K, Kuroki M, Ariumi Y, Dansako H, Kato N
  • Organizer: 15th international symposium on hepatitis C virus & related viruses
  • Place of Presentation: San Antonio (U.S.A)
  • Year and Date: 20081005-20081009
• [Presentation] A new human hepatoma cell line enabling persistent reproduction of HCV life cycle and assay for anti-HCV reagents (2008)
  • Author(s): 加藤宣之, 森京子, 阿部健一, 團迫浩方, 有海康雄, 脇田隆字, 池田正徳
  • Organizer: 15th international symposium on hepatitis c virus & related viruses
  • Place of Presentation: San Antonio (U.S.A)
  • Year and Date: 20081005-20081009
• [Remarks] ホームページ
  • URL: http://www.okayama-u.ac.jp/user/med/dmb/index.html