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Production of interferon stimulated gene library and screening of new therapeutic drug for hepatitis viruses

Research Project

Project/Area Number 18390218
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

CHAYAMA Kazuaki  Hiroshima University, Graduate School of Biomedical Sciences, Professor (00211376)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥14,610,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2007: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2006: ¥8,500,000 (Direct Cost: ¥8,500,000)
Keywordsinterferon / hepatitis C virus / interferon stimulated genes / expression profile / microarray / mRNA / human hepatocyte chimeric mouse / therapeutic drug / 肝炎ウイルス / ゲノム / キメラマウス / 免疫
Research Abstract

We inflicted human hepatocyte chimerie mice with hepatitis B and hepatitis C viruses by injecting serum samples obtained from serum samples of chronic hepatitis B and hepatitis C virus carriers. After confirming the development of viremia in mice, we administered daily 7000 U/g of alpha interferon intramusculary. A rapid decrease in hepatitis C virus RNA levels was observed in all treated mice In contrast, only faint reduction of hepatitis B virus DNA was observed in mice infected with hepatitis B virus. We also administered the same amount of interferon to some human hepatocyte chimeric mice. We sacrificed and collected liver samples from each mice and extracted mRNA from each maim. Using them mRNA samples we performed microarray analysis. We obtained expression profiles from control, non-infected and non-interferon treated mice. We compared expression profiles of mice liver obtained from hepatitis B virus and hepatitis C virus infected mouse as well as interferon treated mice inflicted with hepatitis B and C viruses and treated with interferon. Up regulation of interferon stimulated genes ware observed in hepatitis C virus infected mice The up regulation of them genes was not so eminent in mice infected with hepatitis B virus. Interestingly, up regulation of some interferon stimulated genes were diminished in mice infected with hepatitis C virus compared with non-infected mouse. Further research is now in progress to analyze a mechanism underlining this suppression of interferon stimulated gene production.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (47 results)

All 2007 2006 Other

All Journal Article (43 results) (of which Peer Reviewed: 24 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] Eicosapentaenoic acid could permit maintenance of the original ribavirin dose in chronic hepatitis C virus patients during the first 12 weeks of combination therapy with pegylated interferon-alpha and ribavirin. A prospective randomized controlled trial2007

    • Author(s)
      Takaki S, Kawakami Y, Imamura M, Aikata H, Takahashi S, Ishihara H, Tsuji, Chayama K., et. al.
    • Journal Title

      Intervirology 50(6)

      Pages: 439-46

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Efficacy of percutaneous cementoplasty for bone metastasis from hepatocellular carcinoma.2007

    • Author(s)
      Kodama H, Aikata H, Uka K, Chayama K., et. al.
    • Journal Title

      Oncology 72(5-6):

      Pages: 285-92

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Susceptibility of chimeric mice with livers repopulated by serially subcultured human hepatocytes to hepatitis B virus.2007

    • Author(s)
      Utoh R, Tateno C, Cfiayama K, Yoshizato K., et. al.
    • Journal Title

      Hepatology 47(2)

      Pages: 435-46

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Pretreatment predictor of response, time to progression, and survival to intraarterial 5-fluorouracil/interferon combination therapy in patients with advanced hepatocellular carcinoma.2007

    • Author(s)
      Uka K, Aikata H, Takaki S, Miki D, Kawaoka T, Jeong SC, Chayama K., et. al.
    • Journal Title

      J Gastroenterol 42(10)

      Pages: 845-53

    • NAID

      10019970751

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Successful treatment of an entecavir-resistant hepatitis B virus variant.2007

    • Author(s)
      Yatsuji H, Hiraga N,, Kumada H, Chayama K., et. al.
    • Journal Title

      J Med Virol 79(12)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Similar effects of recombinant interferon-alpha-2b and natural interferon-alpha when combined with intra-arterial 5-fluorouracil for the treatment of advanced hepatocellular carcinoma2007

    • Author(s)
      Uka K, Aikata H, Takaki S, Chayama K., et. al.
    • Journal Title

      Liver Int. 27(9)

      Pages: 1209-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Effects of a 24-week course of interferon-alpha therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma.2007

    • Author(s)
      Jeong SC, Aikata H,, Chayama K., et. al.
    • Journal Title

      World J Gastroenterol. 28;13(40)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Balloon-occluded retrograde transvenous obliteration for portal-systemic encephalopathy due to superior mesenteric-caval shunt via the right gonadai vein2007

    • Author(s)
      Katamura Y, Aikata H, Azakami T, Chayama K., et. al.
    • Journal Title

      Intern Med 46(17):

      Pages: 1479-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The long-term outcome of patients with bleeding gastric varices after balloon-occluded retrograde transvenous obliteration.2007

    • Author(s)
      Hiraga N, Aikata H, Shirakawa H, Chayama K., et. al.
    • Journal Title

      J Gastroenterol 42(8)

      Pages: 663-72

    • NAID

      10019817220

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis C virus and its susceptibility to interferon.2007

    • Author(s)
      Hiraga N, Imamura M, Tsuge M, Chayama K., et. al.
    • Journal Title

      FEBS Lett 15;581(10)

      Pages: 1983-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Dual effect of APOBEC3G on Hepatitis B virus.2007

    • Author(s)
      Noguchi C, Chayama K., et. al.
    • Journal Title

      J Gen Virol 88(Pt 2)

      Pages: 432-40

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma.2007

    • Author(s)
      Uka K, Aikata H, Chayama K., et. al.
    • Journal Title

      World J Gastroenterol. 21;13(3)

      Pages: 414-20

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Eicosapentaenoic acid could permit maintenance of the original ribavirin dose in chronic hepatitis C virus patients during the first 12 weeks of combination therapy with pegylated interferon-alpha and ribavirin. A prospective randomized controlled trial2007

    • Author(s)
      Takaki, S., Kawakami, Y., Imamura, M., Aikata, H., Takahashi, S., Ishihara, H., Tsuji, Chayama, K., et. al.
    • Journal Title

      Intervirology 50(6)

      Pages: 439-46

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Efficacy of percutaneous cementoplasty for bone metastasis from hepatocellular carcinoma2007

    • Author(s)
      Kodama, H., Aikata, H., Uka, K., Chayama, K., et. al.
    • Journal Title

      Oncology 72(5-6)

      Pages: 285-92

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Susceptibility of chimeric mice with livers repopulated by serially subcultured human hepatocytes to hepatitis B virus2007

    • Author(s)
      Utoh, R., Tateno, C., Chayama, K., Yoshizato, K., et. al.
    • Journal Title

      Hepatology 47(2)

      Pages: 435-46

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Pretreatment predictor of response, time to progression, and survival to intraarterial 5-fluorouracil/ interferon combination therapy in patients with advanced hepatocellular carcinoma2007

    • Author(s)
      Uka, K., Aikata, H., Takaki, S., Miki, D., Kawaoka, T., Jeong, S.C., Chayama, K., et. al.
    • Journal Title

      J Gastroenterol 42(10)

      Pages: 845-53

    • NAID

      10019970751

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Successful treatment of an entecavir-resistant hepatitis B virus variant2007

    • Author(s)
      Yatsuji, H., Hiraga, N., Kumada, H., Chayama, K., et. al.
    • Journal Title

      J Med Virol 79(12)

      Pages: 1811-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Similar effects of recombinant interferon-alpha-2b and natural interferon-alpha when combined with intra-arterial 5-fluorouracil for the treatment of advanced hepatocellular carcinoma2007

    • Author(s)
      Uka, K., Aikata, H., Takaki, S., Chayama, K., et. al.
    • Journal Title

      Liver Int 27(9)

      Pages: 1209-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Effects of a 24-week course of interferon-alpha therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma2007

    • Author(s)
      Jeong, S.C., Aikata, H., Chayama, K., et. al.
    • Journal Title

      World J Gastroenterol 28, 13(40)

      Pages: 5343-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Balloon-occluded retrograde transvenous obliteration for portal-systemic encephalopathy due to superior mesenteric-caval shunt via the right gonadal vein2007

    • Author(s)
      Katamura, Y., Aikata, H., Azakami, T., Chayama, K., et. al.
    • Journal Title

      Intern Med 46(17)

      Pages: 1479-80

    • NAID

      130000076076

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The long-term outcome of patients with bleeding gastric varices after balloon-occluded etrograde transvenous obliteration2007

    • Author(s)
      Hiraga, N., Aikata, H., Shirakawa, H., Chayama, K., et. al.
    • Journal Title

      J Gastroenterol 42(8)

      Pages: 663-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis C virus and its susceptibility to interferon2007

    • Author(s)
      Hiraga, N., Imamura, M., Tsuge, M., Chayama, K., et. al.
    • Journal Title

      FEBS Lett 15 : 581(10)

      Pages: 1983-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Dual effect of APOBEC3G on Hepatitis B virus2007

    • Author(s)
      Noguchi, C., Chayama, K., et. al.
    • Journal Title

      J Gen Virol 88(pt2)

      Pages: 432-40

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma2007

    • Author(s)
      Uka, K., Aikata, H., Chayama, K., et. al.
    • Journal Title

      World J Gastroenterol 21, 13(3)

      Pages: 414-20

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Eicosapentaenoic acid could permit maintenance of the original ribavirin dose in chronic hepatitis C virus patients during the first 12 weeks of combination therapy with pegylated interferon-alpha and ribavirin. A prospective randomized controlled trial2007

    • Author(s)
      Takaki S, Kawakami Y, Imamura M, Aikata H, Takahashi S, Ishihara H, Tsuji, Chayama K, et. al.
    • Journal Title

      Intervirology 50(6)

      Pages: 439-46

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy of percutaneous cementoplasty for bone metastasis from hepatocellular carcinoma.2007

    • Author(s)
      Kodama H, Aikata H, Uka K, Chayama K, et. al.
    • Journal Title

      Oncology 72(5-6):

      Pages: 285-92

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Susceptibility of chimeric mice with livers repopulated by serially subcultured human hepatocytes to hepatitis B virus.2007

    • Author(s)
      Utoh R, Tateno C, Chayama K, Yoshizato K, et. al.
    • Journal Title

      Hepatology 47(2)

      Pages: 435-46

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pretreatment predictor of response, time to progression, and survival to intraarterial 5-fluorouracil/interferon combination therapy in patients with advanced hepatocellular carcinoma.2007

    • Author(s)
      Uka K, Aikata H, Takaki S, Miki D, Kawaoka T, Jeong SC, Chayama K, et. al.
    • Journal Title

      J Gastroenterol 42(10)

      Pages: 845-53

    • NAID

      10019970751

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful treatment of an entecavir-resistant hepatitis B virus variant.2007

    • Author(s)
      Yatsuji H, Hiraga N, Kumada H, Chayama K, et. al.
    • Journal Title

      J Med Virol 79(12)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Similar effects of recombinant interferon-alpha-2b and natural interferon-alpha when combined with intra-arterial 5-fluorouracil for the treatment of advanced hepatocellular carcinoma2007

    • Author(s)
      Uka K, Aikata H, Takaki S, Chayama K, et. al.
    • Journal Title

      Liver Int. 27(9)

      Pages: 1209-16

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of a 24-week course of interferon-alpha therapy after curative treatment of hepatitis C virus-associated hepatocellular carcinoma.2007

    • Author(s)
      Jeong SC, Aikata H, Chayama K, et. al.
    • Journal Title

      World J Gastroenterol. 28;13(40)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Balloon-occluded retrograde transvenous obliteration for portal-systemic encephalopathy due to superior mesenteric-caval shunt via the right gonadalvein2007

    • Author(s)
      Katamura Y, Aikata H, Azakami T, Chayama K, et. al.
    • Journal Title

      Intern Med 46(17):

      Pages: 1479-80

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The long-term outcome of patients with bleeding gastric varices after balloon-occluded retrograde transvenous obliteration.2007

    • Author(s)
      Hiraga N, Aikata H, Shirakawa H, Chayama K, et. al.
    • Journal Title

      J Gastroenterol 42(8)

      Pages: 663-72

    • NAID

      10019817220

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis C virus and its susceptibility to interferon.2007

    • Author(s)
      Hiraga N, Imamura M, Tsuge M, Chayama K, et. al.
    • Journal Title

      FEBS Lett 15;581(10)

      Pages: 1983-7

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual effect of APOBEC3G on Hepatitis B virus.2007

    • Author(s)
      Noguchi C, Chayama K, et. al.
    • Journal Title

      J Gen Virol 88(Pt2)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma.2007

    • Author(s)
      Uka K, Aikata H, Chayama K, et. al.
    • Journal Title

      World J Gastroenterol. 21;13(3)

      Pages: 414-20

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual effect of APOBEC3G on Hepatitis B virus2007

    • Author(s)
      Noguchi C, Chayama K..etal
    • Journal Title

      J Gen Virol 88

      Pages: 432-40

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Clinical features and prognosis of patients with extrahepatic metastases from hepatocellular carcinoma2007

    • Author(s)
      Uka K, Chayama K. etal
    • Journal Title

      World J Gastroenterol 21;13(3)

      Pages: 414-20

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Feasibility of freeze-dried sera for serological and molecular biological detection of hepatitis B and C viruses.2006

    • Author(s)
      Ohishi W, Chayama K. etal
    • Journal Title

      J Clin Microbiol 44(12)

      Pages: 4593-5

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Emergence of a el lamivudine-resistant hepatitis B virus variant with a substitution outside the YMDD motif.2006

    • Author(s)
      Yatsuji H, Chayama K. etal
    • Journal Title

      Antimicrob Agents Chemother 50(11)

      Pages: 3867-74

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prolonged negative HCV-RNA status led to a good outcome in chronic hepatitis C patients with genotype 1b and super-high viral load.2006

    • Author(s)
      Kohno H, Chayama K. etal
    • Journal Title

      Intervirology 49(6)

      Pages: 362-9

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Evolution of hepatitis C virus quasispecies during ribavirin and interferon-alpha-2b combination therapy and interferon-alpha-2b monotherapy.2006

    • Author(s)
      Arataki K, Chayama K. etal
    • Journal Title

      Intervirology. 49(6)

      Pages: 352-61

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Anti-fibrogenic function of angiotensin II type 2 receptor in CCl4-induced liver fibrosis.2006

    • Author(s)
      Nabeshi, Chayama K. etal
    • Journal Title

      Biochem Biophys Res Commun 4;346(3)

      Pages: 658-64

    • Related Report
      2006 Annual Research Report
  • [Presentation] 培養細胞および動物モデルを用いた肝炎ウィルスのインターフェロン感受性の検討2007

    • Author(s)
      今村 道雄
    • Organizer
      日本肝臓学会総会
    • Place of Presentation
      ホテルグランパシフィックメリディアン
    • Year and Date
      2007-05-31
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Assessment of interferon susceptibility of hepatitis viruses using cell culture and animal model2007

    • Author(s)
      Michio, Imamura
    • Organizer
      Annual Meeting of Japan Society of hepatology
    • Year and Date
      2007-05-31
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://home.hiroshima-u.ac.jp/naika1/

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://home.hiroshima-u.ac.jp/naika1/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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