Development of new therapy for elder women with chronic hepatitis C

• 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
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: C型慢性肝炎 / HCV / ラロキシフェン / スタチン剤 / 骨訴訟症 / 脂質代謝 / ゲラニルゲラニル化 / ビスフォスフォネート剤

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
  • 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, et al.
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Journal Article] An antioxidant resveratrol significantly enhanced replication of hepatitis C virus. (2010)
  • Author(s): Nakamura M, et al.
  • Journal Title: World J.Gastroenterol. Volume: 16 Pages: 184-192
  • Peer Reviewed
• [Journal Article] Hydroxyurea as an inhibitor of hepatitis C virus RNA replication. (2010)
  • Author(s): Nozaki A, et al.
  • Journal Title: Arch Virol Volume: 155 Pages: 601-605
  • Peer Reviewed
• [Journal Article] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development. (2010)
  • Author(s): Shigoka M, et al.
  • Journal Title: Path.Int. Volume: 60 Pages: 351-357
  • Peer Reviewed
• [Journal Article] Generation of single-chain Fvs against detergent-solubilized recombinant antigens with a simple coating procedure. (2010)
  • Author(s): Tanaka T, et al.
  • Journal Title: J.Biosci.Bioeng. Volume: 110 Pages: 374-376
  • Peer Reviewed
• [Journal Article] Hydroxyurea suppresses hepatitis C virus replication in human : a phase i trial of oral hydroxyurea in chronic hepatitis C patients. (2010)
  • Author(s): Nozaki A, et al.
  • Journal Title: Antiviral Therapy Volume: 15 Pages: 1179-1183
  • Peer Reviewed
• [Journal Article] Amino acid substitutions of hepatitis C virus core protein are not associated with intracellular antiviral response to interferon-a in vitro. (2010)
  • Author(s): Ikeda F, et al.
  • Journal Title: Liver Int. Volume: 9 Pages: 1324-1131
  • Peer Reviewed
• [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, et al.
  • Journal Title: Hepatology Res. Volume: 40 Pages: 1248-1253
  • Peer Reviewed
• [Journal Article] An antioxidant resveratrol significantly enhanced replication of hepatitis C virus. (2010)
  • Author(s): Nakamura M
  • Journal Title: World J Gastroenterol 16 Pages: 184-192
  • Peer Reviewed
• [Journal Article] Hydroxyurea as an inhibitor of hepatitis C virus RNA replication. (2010)
  • Author(s): Nozaki A
  • Journal Title: Arch Virol. 155 Pages: 601-605
  • 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] Genetic variability and diversity of intracellular genome-length hepatitis Cvirus RNA in long-term cell culture (2009)
  • Author(s): Kato N
  • Journal Title: Arch Virol 154 Pages: 77-85
  • 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
  • Journal Title: J Virol 83 Pages: 2338-2348
  • Peer Reviewed
• [Journal Article] HCV replication suppresses cellular glucose uptake through down-regulation of cell surface expression of glucose transporters (2009)
  • Author(s): Kasai D
  • Journal Title: J Hepatol. 50 Pages: 883-894
  • Peer Reviewed
• [Journal Article] Replicons from genotype 1b HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents (2009)
  • Author(s): Nishimura G
  • Journal Title: Antiviral Res. 82 Pages: 42-50
  • 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
  • Journal Title: Hepatol Res. 39 Pages: 898-909
  • Peer Reviewed
• [Journal Article] Double-stranded RNA-induced interferon-beta and inflammatory cytokine production modulated by hepatitis C virus serine proteases derived from natients with henatic diseases (2009)
  • Author(s): Dansako H
  • Journal Title: Arch Virol. 154 Pages: 801-810
  • Peer Reviewed
• [Journal Article] Oncostatin M synergistically inhibits HCV RNA replication in combination with interferon-α (2009)
  • Author(s): Ikeda M
  • Journal Title: FEBS Letters 583 Pages: 1434-1438
  • Peer Reviewed
• [Journal Article] Oxidative stress induces anti-hepatitis C virus status via the activation of extracellular signal-regulated kinase. (2009)
  • Author(s): Yano M
  • Journal Title: Hepatology 50 Pages: 678-688
  • Peer Reviewed
• [Journal Article] Efficient replication systems for hepatitis C virus using a new hepatoma cell line. (2009)
  • Author(s): Kato N
  • Journal Title: Virus Res 146 Pages: 41-50
  • Peer Reviewed
• [Journal Article] Interferon-alpha-induced mTOR activation is an anti-hepatitis C virus signal via the phosphatidylinositol 3-kinase-Akt-independent pathway. (2009)
  • Author(s): Matsumoto A
  • Journal Title: J. Gastroenterol. 44 Pages: 856-863
  • Peer Reviewed
• [Journal Article] HCV genotype 1b chimeric replicon with NS5B of JFH-1 exhibited resistance to cyclosporine A. (2009)
  • Author(s): Abe KI
  • Journal Title: Arch Virol 154 Pages: 1671-1677
  • Peer Reviewed
• [Journal Article] Oncostatin M synergistically inhibits HCV RNA replication in combination with interferon-α (2009)
  • Author(s): Ike da M
  • Journal Title: FEBS Letters in press
  • Peer Reviewed
• [Journal Article] Double-Stranded RNA-induced interferon-beta and inflammatory cytokine production modulated by hepatitis C virus serine proteases derived from (2009)
  • Author(s): Dansako H
  • Journal Title: Arch Virol. in press
  • Peer Reviewed
• [Journal Article] Development of an HCV relapse modal using genome-length HCV RNA-harboring cells possessing the IFN-a-resistance phenotype (2009)
  • Author(s): Kawai Y
  • Journal Title: Hepatol Res. in press
  • Peer Reviewed
• [Journal Article] Replicons from genotype lb HCV-positive sera exhibit diverse sensitivities to anti-HCV reagents (2009)
  • Author(s): Nishimura G
  • Journal Title: Antiviral Res. 82 Pages: 42-50
  • Peer Reviewed
• [Journal Article] HCV replication suppresses celluiar glucose uptake through down-regulation of cell surface expression of glucose transporters (2009)
  • Author(s): Kasai D
  • Journal Title: J Hepatol. in press
  • Peer Reviewed
• [Journal Article] Genetic variability and diversity of intracellular genome-length hepatitis Cvirus, RNA in long-term cell culture (2009)
  • Author(s): Kato N
  • Journal Title: Arch Virol 154 Pages: 77-85
  • 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
• [Journal Article] The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication (2008)
  • Author(s): Ariumi Y
  • Journal Title: J Virol. 82 Pages: 9639-9646
  • Peer Reviewed
• [Journal Article] A new living cell-based assay system for monitoring genome-length hepatitis Cvirus RNA replication (2008)
  • Author(s): Dansako H
  • Journal Title: Virus Res. 137 Pages: 72-79
  • Peer Reviewed
• [Journal Article] New efficient replication system with hepatitis C virus genome derived from apatient with acute hepatitis C (2008)
  • Author(s): Mori K
  • Journal Title: Biochem. Biophys. Res. Commun. 371 Pages: 104-109
  • Peer Reviewed
• [Journal Article] Differential effects of calclneurin inhibitors, tacrolimus and oyclosporln A, on interferon-induced antiviral protein in human hepatocyte cells (2008)
  • Author(s): Hirano K
  • Journal Title: Liver. Transpl. 14 Pages: 292-298
  • Peer Reviewed
• [Journal Article] Possible molecular mechanism of the relationship between NS5B polymorphisms and early clearance of hepatitis C virus during interferon plus ribavirin (2008)
  • Author(s): Nakamura M
  • Journal Title: J. Med. Virol. 80 Pages: 632-639
  • Peer Reviewed
• [Journal Article] Mitochondrial electron transport inhibition in full genomic hepatitis C virus replicon cells is restored by reducing viral replication. (2008)
  • Author(s): Ando M
  • Journal Title: Liver Int. 28 Pages: 1158-1166
  • 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 (2011)
  • Author(s): 池田正徳, 他
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2011-10-08
• [Presentation] リバビリンの抗HCV活性を決定する因子の解析 (2011)
  • Author(s): 森京子, 他
  • Organizer: 第58回日本ウイルス学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2011-10-08
• [Presentation] Mechanism of anti-HCV of ribavirin in novel HCV replication cell system (2011)
  • Author(s): Mori K, et al.
  • Organizer: 69th annual meeting of the Japanese Cancer Association
  • Place of Presentation: Yokohama
  • Year and Date: 2011-09-22
• [Presentation] Development of genome-length HCV RNA replication assay systems derived from different HCV strains using HuH-7 and Li23 cells. (2011)
  • Author(s): Ikeda M, et al.
  • Organizer: 17th international symposium on hepatitis C virus and related viruses
  • Place of Presentation: Yokohama
  • Year and Date: 2011-09-11
• [Presentation] Anti-HCV mechanism of ribavirin in novel HCV replication cell systems. (2011)
  • Author(s): Mori K, et al.
  • Organizer: 17th international symposium on hepatitis C virus and related viruses
  • Place of Presentation: Yokohama
  • Year and Date: 2011-09-11
• [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
• [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
• [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)
• [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)
• [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] Oncostatin M synergistically inhibits HCV RNA replication in combination with interferon-α. (2009)
  • Author(s): Masanori Ikeda
  • Organizer: 16th International Meeting on Hepatitis C Virus and Related Viruses
  • Place of Presentation: Nice, France
  • Year and Date: 2009-10-04
• [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
• [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
• [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
• [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
• [Presentation] 抗潰瘍剤によるC型慢性肝炎の新たな治療戦略-TeprenoneはStatinのゲラニルゲラニル化阻害を増強しHCV複製抑制効果を増強する- (2009)
  • Author(s): 河合良成
  • Organizer: 第13回日本肝臓学会大会
  • Place of Presentation: 京都
• [Presentation] 抗潰瘍剤によるC型慢性肝炎の新たな治療戦略-Teprenone(Selbex^(R))とPlaunotol(Kelnac^(R))のHCV複製抑制効果- (2009)
  • Author(s): 河合良成
  • Organizer: 第45回日本肝臓学会総会
  • Place of Presentation: 神戸
• [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
• [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
• [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)
• [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)
• [Presentation] Identification of 5-HETE as the anti-HCV molecule among the arachidonic acid metabolites. (2008)
  • Author(s): Ikeda M
  • Organizer: Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: San Antonio, USA
• [Presentation] New efficient replication system with HCV genome derived from a patient with acute hepatitis (2008)
  • Author(s): Mori K
  • Organizer: Symposium on Hepatitis C Virus and Related Viruses
  • Place of Presentation: San Antonio, USA
• [Presentation] 異なるHCV(b型)株由来の全長HCV RNA複製レポーターアッセイ系の開発 (2008)
  • Author(s): 池田 正徳
  • Organizer: 第67回 日本癌学会総会
  • Place of Presentation: 名古屋
• [Presentation] 急性C型肝炎患者由来の新しいC型肝炎ウイルスゲノム複製系 (2008)
  • Author(s): 森 京子
  • Organizer: 第67回 日本癌学会総会
  • Place of Presentation: 名古屋
• [Remarks] ホームページ
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