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2011 Fiscal Year Final Research Report

Identification of host genes responsible for the treatment response of interferon therapy for the patients with chronic hepatitis C

Research Project

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Project/Area Number 21390227
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HONDA Masao  金沢大学, 保健学系, 教授 (00272980)

Co-Investigator(Renkei-kenkyūsha) SAKAI Yoshio  金沢大学, 医学系, 准教授 (80401925)
HORIMOTO Katsuhisa  産業技術総合研究所, 生命情報工学研究センター, 研究チーム長 (40238803)
Project Period (FY) 2009 – 2011
KeywordsIFN / 遺伝子発現 / C型慢性肝炎
Research Abstract

This study demonstrated that the induction of interferon stimulated genes(ISGs) was closely related to the treatment response to IFN therapy. Up-regulated ISGs expression of in liver before treatment might impair the de novo ISGs induction in liver. Interestingly, up-regulated ISGs in liver before treatment were closely related to IL28 minor genotype. Therefore, Il28B genotype must be involved in different ISGs induction in liver. There was a significant correlation of ISGs expression between the liver and PBMC in patients with IL28B major genotype, while no correlation was found in patients with IL28B minor genotype. Detailed examination of liver biopsy specimen by laser capture micro dissection revealed the impaired infiltration of immune cells in liver lobules in patients with IL28B minor genotype. These immune regulatory imbalances of IL28B minor genotype might contribute to the poor response to IFN therapy

  • Research Products

    (47 results)

All 2012 2011 2010 2009

All Journal Article (32 results) (of which Peer Reviewed: 32 results) Presentation (15 results)

  • [Journal Article] Beneficial effect of branched-chain amino acid supplementation on glycemic control in chronic hepatitis C patients with insulin resistance : Implications for type 2 diabetes. Metabolism2012

    • Author(s)
      Honda M, (他12名, 12番目)
    • Journal Title

      Epub ahead of print

    • DOI

      DOI:10.1016/j.metabol.2012.03.011

    • Peer Reviewed
  • [Journal Article] Coexpression network analysis in chronic hepatitis B and C hepatic lesion reveals distinct patterns of disease progression to hepatocellular carcinoma2012

    • Author(s)
      He D, Liu ZP, Honda M, Kaneko S, Chen L.
    • Journal Title

      J Mol Cell Biol

    • DOI

      DOI:10.1093/jmcb/mjs011

    • Peer Reviewed
  • [Journal Article] Induction of elastin expression in vascular endothelial cells relates to hepatoportal sclerosis in idiopathic portal hypertension : possible link to serum anti-endothelial cell antibodies2012

    • Author(s)
      Honda M, (他8名, 7番目)
    • Journal Title

      Clin Exp Immunol

      Volume: 167(3) Pages: 532-42

    • DOI

      DOI:10.1111/j.1365-2249.2011.04530.x.

    • Peer Reviewed
  • [Journal Article] Heterogeneous nuclear ribonucleoprotein A2/B1 in association with hTERT is a potential biomarker for hepatocellular carcinoma2012

    • Author(s)
      Mizuno H, Honda M, 他5名
    • Journal Title

      Epub ahead of print

    • DOI

      DOI:10.1111/j.1478-3231.2012.02778.x.

    • Peer Reviewed
  • [Journal Article] Identification of blood biomarkers of aging by transcript profiling of whole blood2012

    • Author(s)
      Honda M, (他7名, 4番目)
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 418(2) Pages: 313-8

    • DOI

      DOI:10.1016/j.bbrc.2012.01.018

    • Peer Reviewed
  • [Journal Article] Randomized, phase II study comparing interferon combined with hepatic arterial infusion of fluorouracil plus cisplatin and fluorouracil alone in patients with advanced hepatocellularcar cinoma2011

    • Author(s)
      Honda M, (他10名, 10番目)
    • Journal Title

      Oncology

      Volume: 81(5-6) Pages: 281-90

    • DOI

      DOI:10.1159/000334439

    • Peer Reviewed
  • [Journal Article] Identification of a secretory protein c19orf10 activated in hepatocellular carcinoma2011

    • Author(s)
      Sunagozaka H, Honda M, 他7名
    • Journal Title

      Int J Cancer

      Volume: 129(7) Pages: 1576-85

    • DOI

      DOI:10.1002/ijc.25830

    • Peer Reviewed
  • [Journal Article] Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C2011

    • Author(s)
      Honda M, (他21名, 15番目)
    • Journal Title

      Hum Mol Genet

      Volume: 20(17) Pages: 3507-16

    • DOI

      DOI:10.1093/hmg/ddr249

    • Peer Reviewed
  • [Journal Article] Characterization of naturally occurring protease inhibitor-resistance mutations in genotype 1b hepatitis C virus patients2011

    • Author(s)
      Honda M, (他17名, 16番目)
    • Journal Title

      Hepatol Int Epub ahead of print

    • DOI

      DOI:10.1007/s12072-011-9306-7

    • Peer Reviewed
  • [Journal Article] Differentiation of Cancer Stem Cells2011

    • Author(s)
      Yamashita T, Honda M, Kaneko S.
    • Journal Title

      Chapter

      Volume: 17 Pages: 337-350

    • DOI

      DOI:10.5772/17268

    • Peer Reviewed
  • [Journal Article] Malnutrition Impairs Interferon Signaling Through mTOR and FoxO Pathways in Patients With Chronic Hepatitis C2011

    • Author(s)
      Honda M, 他19名
    • Journal Title

      Gastroenterology

      Volume: 141(1) Pages: 128-40

    • DOI

      DOI:10.1053/j.gastro.2011.03.051

    • Peer Reviewed
  • [Journal Article] Molecular mechanisms of hepatocarcinogenesis in chronic hepatitis C virus infection2011

    • Author(s)
      Yamashita T, Honda M, Kaneko S.
    • Journal Title

      J Gastroenterol Hepatol

      Volume: 26(6) Pages: 960-4

    • DOI

      DOI:10.1111/j.1440-1746.2011.06723.x.

    • Peer Reviewed
  • [Journal Article] Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma2011

    • Author(s)
      Honda M, (他9名, 9番目)
    • Journal Title

      Hepatology

      Volume: 53(4) Pages: 206-16

    • DOI

      DOI:10.1002/hep.24149.

    • Peer Reviewed
  • [Journal Article] Heterogeneity of Liver Cancer Stem Cells2011

    • Author(s)
      Yamashita T, Honda M, Kaneko S.
    • Journal Title

      Molecular Genetics of Liver Neoplasia

      Volume: 7 Pages: 301-317

    • DOI

      DOI:10.1007/978-1-4419-6082-5_16

    • Peer Reviewed
  • [Journal Article] Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors2011

    • Author(s)
      Honda M, (他20名, 6番目)
    • Journal Title

      J Hepatol

      Volume: 54(3) Pages: 439-48

    • DOI

      DOI:10.1016/j.jhep.2010.07.037

    • Peer Reviewed
  • [Journal Article] Comprehensive gene expression analysis of 5'-end of mRNA identified novel intronic transcripts associated with hepatocellular carcinoma2010

    • Author(s)
      Hodo Y, Hashimoto S, Honda M, 他7名
    • Journal Title

      Genomics

      Volume: 95(4) Pages: 217-23

    • DOI

      DOI:10.1016/j.ygeno.2010.01.004

    • Peer Reviewed
  • [Journal Article] Oncostatin m renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-Fluorouracil by inducing hepatocytic differentiation2010

    • Author(s)
      Yamashita T, Honda M, 他8名
    • Journal Title

      Cancer Res

      Volume: 70(11) Pages: 4687-97

    • DOI

      DOI:10.1158/0008-5472.CAN-09-4210

    • Peer Reviewed
  • [Journal Article] La proteinrequired for in ternal ribosome entry site-directed translation is a potential therapeutic target for hepatitis C virus replication2010

    • Author(s)
      Shirasaki T, Honda M, 他8名
    • Journal Title

      J Infect Dis

      Volume: 202(1) Pages: 75-85

    • DOI

      DOI:10.1086/653081

    • Peer Reviewed
  • [Journal Article] Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C2010

    • Author(s)
      Honda M, 他14名
    • Journal Title

      Gastroenterology

      Volume: 139(2) Pages: 499-509

    • DOI

      DOI:10.1053/j.gastro.2010.04.049

    • Peer Reviewed
  • [Journal Article] Differential gene expression profiling in blood from patients with digestive system cancers2010

    • Author(s)
      Honda M, 他11名
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 400(1) Pages: 7-15

    • DOI

      DOI:10.1016/j.bbrc.2010.07.123

    • Peer Reviewed
  • [Journal Article] Differential interferon signaling in liver lobule and portal area cells under treatment for chronic hepatitis C2010

    • Author(s)
      Honda M, 他10名
    • Journal Title

      J Hepatol

      Volume: 53(5) Pages: 817-26

    • DOI

      DOI:10.1016/j.jhep.2010.04.036

    • Peer Reviewed
  • [Journal Article] A liver-derived secretory protein, selenoprotein P, causes insulin resistance2010

    • Author(s)
      Honda M, (他26名, 15番目)
    • Journal Title

      Cell Metab

      Volume: 12(5) Pages: 483-95

    • DOI

      DOI:10.1016/j.cmet.2010.09.015

    • Peer Reviewed
  • [Journal Article] ITPA gene variant protects against anemia induced by pegylated interferon-αand ribavirin therapy for Japanese patients with chronic hepatitis C2010

    • Author(s)
      Honda M, (他14名, 12番目)
    • Journal Title

      Hepatol Res

      Volume: 40(11) Pages: 1063-1071

    • DOI

      DOI:10.1111/j.1872-034X.2010.00741.x.

    • Peer Reviewed
  • [Journal Article] Oncostatin M renders epithelial cell adhesion molecule-positive liver cancer stem cells sensitive to 5-fluorouracil by inducing hepatocytic differentiation2010

    • Author(s)
      Yamashita T, Honda M, 他7名
    • Journal Title

      Cancer Research

      Volume: 70(11) Pages: 4687-97

    • DOI

      DOI:10.1158/0008-5472.CAN-09-4210

    • Peer Reviewed
  • [Journal Article] La protein required for IRES-directed translation is a potential therapeutic target for hepatitis C virus replication2010

    • Author(s)
      Shirasaki T, Honda M, 他7名
    • Journal Title

      J Infect Dis

      Volume: 202(1) Pages: 75-85

    • DOI

      DOI:10.1086/653081

    • Peer Reviewed
  • [Journal Article] dUTP pyrophosphatase expression correlates with a poor prognosis in hepatocellular carcinoma2010

    • Author(s)
      Takatori H, Yamashita T, Honda M, 他7名
    • Journal Title

      Liver Int

      Volume: 30(3) Pages: 438-46

    • DOI

      DOI:10.1111/j.1478-3231.2009.02177.x

    • Peer Reviewed
  • [Journal Article] Altered hepatic gene expression profiles associated with myocardial ischemia2010

    • Author(s)
      Ootsuji H, Honda M, 他8名
    • Journal Title

      Circ Cardiovasc Genet

      Volume: 3(1) Pages: 68-77

    • DOI

      DOI:10.1161/CIRCGENETICS.108.795484

    • Peer Reviewed
  • [Journal Article] CD14+monocytes are vulnerable and functionally impaired under endoplasmic reticulum stress in patients with type 2 diabetes2010

    • Author(s)
      Komura T, Sakai Y, Honda M, 他3名
    • Journal Title

      Diabetes

      Volume: 59(3) Pages: 634-43

    • DOI

      DOI:10.2337/db09-0659

    • Peer Reviewed
  • [Journal Article] Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C2009

    • Author(s)
      Honda M, (他28名, 16番目)
    • Journal Title

      Nat Genet

      Volume: 41(10) Pages: 1105-9

    • DOI

      DOI:10.1038/ng.449

    • Peer Reviewed
  • [Journal Article] Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma2009

    • Author(s)
      Ura S, Honda M, 他8名
    • Journal Title

      Hepatology

      Volume: 49(4) Pages: 1098-112

    • DOI

      DOI:10.1002/hep.22749

    • Peer Reviewed
  • [Journal Article] EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features2009

    • Author(s)
      Honda M, (他15名, 13番目)
    • Journal Title

      Gastroenterology

      Volume: 136(3) Pages: 1012-24

    • DOI

      DOI:10.1053/j.gastro.2008.12.004

    • Peer Reviewed
  • [Journal Article] Endothelial to mesenchymal transition via transforming growth factor-beta1/Smad activation is associated with portal venous stenosis in idiopathic portal hypertension2009

    • Author(s)
      Honda M, (他9名, 8番目)
    • Journal Title

      Am J Pathol

      Volume: 175(2) Pages: 616-26

    • DOI

      DOI:10.2353/ajpath.2009.081061

    • Peer Reviewed
  • [Presentation] Malnutrition Impairs Interferon Signaling Through mTOR and FoxO Pathways in Patients With Chronic Hepatitis C. AASLD2011

    • Author(s)
      Honda M, 他13名
    • Organizer
      The 62st Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      TheMoscone Center(USA)
    • Year and Date
      2011-11-06
  • [Presentation] C型慢性肝炎に対するインターフェロン治療反応性と肝組織及び末梢血液ISGs発現の関連性2011

    • Author(s)
      本多政夫, 他2名
    • Organizer
      第15回日本肝臓学会大会
    • Place of Presentation
      福岡国際センター(福岡県)
    • Year and Date
      2011-10-20
  • [Presentation] 血小板由来増殖因子(PDGF)-C過剰発現マウスの肝線維化、発癌機構の解析2011

    • Author(s)
      本多政夫, 他4名
    • Organizer
      第47回日本肝癌研究会
    • Place of Presentation
      静岡県コンベンションアーツセンター(静岡県)
    • Year and Date
      2011-07-29
  • [Presentation] ウイルス性肝炎・肝癌のマイクロRNA解析2011

    • Author(s)
      本多政夫, 他2名
    • Organizer
      第97回日本消化器病学会総会
    • Place of Presentation
      京王プラザホテル(東京都)
    • Year and Date
      2011-05-13
  • [Presentation] Hepatic ISG Expression is Associated with Genetic Variation in Interleukin 28B and the Outcome of IFN Therapy for Chronic Hepatitis C2010

    • Author(s)
      Honda M, 他2名
    • Organizer
      The 7th APASL Single Topic Conference "Hepatitis CVirus"
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2010-12-18
  • [Presentation] Peretinoin, an acyclic retinoid, improves hepatic gene signature in patients with chronic hepatitis C following curative therapy of hepatocellular carcinoma. AASLD2010

    • Author(s)
      Honda M, 他10名
    • Organizer
      the 61st Annual Meeting of the American Association for the Study of Liver Diseases
    • Place of Presentation
      Hynes Convention Center(USA)
    • Year and Date
      2010-10-31
  • [Presentation] Hepatic ISGs are associated with genetic variation in IL28B and the outcome of IFN therapy for chronichepatitis C2010

    • Author(s)
      Honda M, 他13名
    • Organizer
      AASLD(the 61st Annual Meeting of the American Association for the Study of Liver Diseases)
    • Place of Presentation
      HynesConvention Center(USA)
    • Year and Date
      2010-10-31
  • [Presentation] C型慢性肝炎に対するインターフェロン治療抵抗性における肝内ISGs発現とIL28B遺伝子多型の役割2010

    • Author(s)
      本多政夫, 他2名
    • Organizer
      第14回日本肝臓学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2010-10-15
  • [Presentation] Hepatic ISGs is associated with genetic variation in 1L28B and the outcome of IFN therapy for chronic hepatitis C2010

    • Author(s)
      Honda M, 他13名
    • Organizer
      The 17th International Meeting on Hepatitis C Virus and Related Viruses
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2010-09-12
  • [Presentation] 肝内インターフェロン誘導遺伝子と治療抵抗性の分子機序2010

    • Author(s)
      本多政夫, 他2名
    • Organizer
      第96回日本消化器病学会総会
    • Place of Presentation
      新潟県民会館(新潟県)
    • Year and Date
      2010-04-23
  • [Presentation] 肝炎・肝癌におけるmiRNA発現解析2009

    • Author(s)
      本多政夫
    • Organizer
      第32回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2009-12-12
  • [Presentation] Pretreatment prediction of virological response to peginterferon plus ribavirin therapy inpatients with chronic hepatitis C using hepatic gene expression profiling2009

    • Author(s)
      Honda M, 他4名
    • Organizer
      AASLD(the 60th Annual Meeting of the American Association for the Study of Liver Diseases)
    • Place of Presentation
      Hynes Convention Center(USA)
    • Year and Date
      2009-11-01
  • [Presentation] C型慢性肝炎の治療抵抗性に関わる肝細胞及び肝浸潤リンパ球の役割2009

    • Author(s)
      本多政夫, 他2名
    • Organizer
      第13回日本肝臓学会大会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2009-10-15
  • [Presentation] Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in patients with chronic hepatitis C using hepatic gene expression profiling2009

    • Author(s)
      Honda M, 他4名
    • Organizer
      The 16th International symposium on Hepatitis C Virus & Related Viruses
    • Place of Presentation
      Nice Acropolis(FRANCE)
    • Year and Date
      2009-10-04
  • [Presentation] 肝組織・末梢血液遺伝子発現プロファイルを用いたインターフェロン応答・不応答の解析2009

    • Author(s)
      本多政夫, 他2名
    • Organizer
      第95回日本消化器病学会総会
    • Place of Presentation
      北海道厚生年金会館(北海道)
    • Year and Date
      2009-05-07

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Published: 2013-07-31  

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