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Acquired resistance to HDAC inhibitors

Research Project

Project/Area Number 22791076
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionOkayama University

Principal Investigator

FUJII Kazuyasu  岡山大学, 岡山大学病院, 助教 (70452571)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsHDAC阻害剤 / 獲得耐性 / 薬剤感受性
Research Abstract

Histone deacetylase(HDAC) inhibitors are new class drug for cutaneous T cell lymphoma. However, the majority of patients will eventually develop resistance. To clarify the mechanisms of acquired resistance to HDAC inhibitor, we established the acquired resistant cell lines against valproic acid, from 5 individual cell lines. IC50 values of these sublines were more than 2-fold resistant to not only valproic acid but vorinostat, compared to their parent cell lines. HDAC inhibitor-induced apoptosis were diminished in all 5 sub-lined compared to their own counterpart.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (44 results)

All 2012 2011 2010 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (34 results) Book (2 results)

  • [Journal Article] Proteomic study identified HSP 70 kDa protein 1A as a possible therapeutic target, in combination with histone deacetylase inhibitors, for lymphoid neoplasms2012

    • Author(s)
      Fujii K, Suzuki N, Ikeda K, Hamada T, Yamamoto T, Kondo T, Iwatsuki K
    • Journal Title

      J Proteomics

      Volume: 75(4) Pages: 1401-10

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Proteomic study identified HSP 70 kDa protein 1A as a possible therapeutic target, in combination with histone deacetylase inhibitors, for lymphoid neoplasms2012

    • Author(s)
      Fujii K
    • Journal Title

      Journal of Proteomics

      Volume: 75 Pages: 1401-10

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of lymphangiogenic markers in Sezary Syndrome2011

    • Author(s)
      Karpova MB, Fujii K, Jenni D, Dummer R, Urosevic-Maiwald M
    • Journal Title

      Leuk Lymphoma

      Volume: 52(3) Pages: 491-501

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Production of proinflammatory cytokines without invocation of cytotoxic effects by an Epstein-Barr virus-infected natural killer cell line established from a patient with hypersensitivity to mosquito bites2010

    • Author(s)
      Suzuki D, Tsuji K, Yamamoto T, Fujii K, Iwatsuki K
    • Journal Title

      Exp Hematol

      Volume: 38(10) Pages: 933-44

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutation analyses of patients with dyschromatosis symmetrica hereditaria : five novel mutations of the ADAR1 gene.2010

    • Author(s)
      Murata I
    • Journal Title

      7 Dermatol Sci.

      Volume: 58 Pages: 218-220

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Production of proinflammatory cytokines without invocation of cytotoxic effects by an Epstein-Barrvirus-infected natural killer cell line established from a patient with hypersensitivity to mosquitobites.2010

    • Author(s)
      Suzuki D
    • Journal Title

      Exp Hematol.

      Volume: 38 Pages: 933-944

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A prospective analysis of anti-desmoglein antibody profiles in patients with rheumatoid arthritis treated with thiol compounds.2010

    • Author(s)
      Yamamoto T
    • Journal Title

      J Dermatol Sci.

      Volume: 59 Pages: 170-175

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydroa vacciniforme is associated with increased numbers of Epstein-Barr virus-infectedγδT-cells

    • Author(s)
      Hirai Y, Yamamoto T, Kimura H, Ito Y, Tsuji K, Miyake T, Morizane S, Suzuki D, Fujii K, Iwatsuki K
    • Journal Title

      J Invest Dermatol

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] 蛍光標識二次元電気泳動を用いたヒストン脱アセチル化酵素阻害剤の感受性に関わる分子の探索2011

    • Author(s)
      藤井一恭
    • Organizer
      第6回中国研究皮膚科セミナー
    • Place of Presentation
      広島市
    • Year and Date
      2011-11-13
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Comparative proteomic analysis identified HSPA1A as a candidate target for enhancing apoptosis induced by histone deacetylase inhibitor2011

    • Author(s)
      Fujii K
    • Organizer
      The 36th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      Kyoto
    • Related Report
      2011 Final Research Report
  • [Presentation] Distinct distribution of dendritic cell subsets in the lymph nodes in patients with mycosis fungoides2011

    • Author(s)
      Tada K
    • Organizer
      The 36th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      Kyoto
    • Related Report
      2011 Final Research Report
  • [Presentation] 蛍光標識二次元電気泳動を用いたヒストン脱アセチル化酵素阻害剤の併用療法の新規標的同定2011

    • Author(s)
      藤井一恭
    • Organizer
      第62回日本電気泳動学会総会
    • Place of Presentation
      横浜市
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] プロテオミクスによるHDAC阻害剤の感受性にかかわる分子の探索2011

    • Author(s)
      藤井一恭
    • Organizer
      第70回日本癌学会総会
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Final Research Report
  • [Presentation] HSPA1A inhibits the cytotoxic effect of HDAC inhibitor2011

    • Author(s)
      Fujii K
    • Organizer
      41st Annual ESDR Meeting
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2011 Final Research Report
  • [Presentation] Proteomic analysis of histone deacetylase inhibitor sensitivity in lymphoid malignancies2011

    • Author(s)
      Fujii K
    • Organizer
      HUPO2011 10th World congress
    • Place of Presentation
      Geneva, Swiss
    • Related Report
      2011 Final Research Report
  • [Presentation] HSPA1AはHDAC阻害剤感受性を阻害する2011

    • Author(s)
      藤井一恭
    • Organizer
      日本プロテオーム学会2011年大会
    • Place of Presentation
      新潟市
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Minimal hematological alterations of circulating T-cells in mycosis fungoides2011

    • Author(s)
      Ikeda K
    • Organizer
      22nd World Congress of Dermatology
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2011 Final Research Report
  • [Presentation] 蛍光標識二次元電気泳動を用いたリンパ腫細胞株のHDAC阻害剤感受性分子の探索2011

    • Author(s)
      藤井一恭
    • Organizer
      第110回日本皮膚科学会総会
    • Place of Presentation
      横浜市
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular mechanisms of HDAC inhibitor-resistance in lymphoid malignancies determined by proteomic analysis2011

    • Author(s)
      Fujii K
    • Organizer
      5TH INTERNATIONAL SYMPOSIUM on the Biology and Immunology of Cutaneous Lymphomas
    • Place of Presentation
      Berlin, Germany
    • Related Report
      2011 Final Research Report
  • [Presentation] 蛍光標識二次元電気泳動を用いたリンパ腫細胞株のHDAC阻害剤感受性分子の探索2011

    • Author(s)
      藤井一恭
    • Organizer
      第110回日本皮膚科学会総会
    • Place of Presentation
      京都市
    • Related Report
      2011 Annual Research Report
  • [Presentation] Differences in epitopes of non-pathogenic autoantibodies to desmogleinl in pemphigus foliaceus in comparison with those in pemphigus vulgaris and rheumatoid arthritis2011

    • Author(s)
      Aoyama Y
    • Organizer
      SID 71st Annual Meeting
    • Place of Presentation
      Phoenix (USA)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Eccrine poromatosis associated with polychemotherapy2011

    • Author(s)
      Fujii K
    • Organizer
      22nd World Congress of Dermatology
    • Place of Presentation
      Seoul (Korea)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Proteomic analysis of histone deacetylase inhibitor sensitivity in lymphoid malignancies2011

    • Author(s)
      Fujii K
    • Organizer
      HUP02011 10th World congress
    • Place of Presentation
      Geneve (Switzerland)
    • Related Report
      2011 Annual Research Report
  • [Presentation] HSPA1A inhibits the cytotoxic effect of HDAC inhibitor2011

    • Author(s)
      Fujii K
    • Organizer
      41st Annual ESDR Meeting
    • Place of Presentation
      Barcelona (Spain)
    • Related Report
      2011 Annual Research Report
  • [Presentation] プロテオミクスによるHDAC阻害剤の感受性にかかわる分子の探索2011

    • Author(s)
      藤井一恭
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Related Report
      2011 Annual Research Report
  • [Presentation] Comparative proteomic analysis identified HSPA1A as a candidate target for enhancing apoptosis induced by histone deacetylase inhibitor2011

    • Author(s)
      Fujii K
    • Organizer
      日本研究皮膚科学会第36回年次学術大会
    • Place of Presentation
      京都市
    • Related Report
      2011 Annual Research Report
  • [Presentation] Molecular mechanisms of HDAC inhibitor-resistance in lymphoid malignancies determined by proteomic analysis2011

    • Author(s)
      Fujii K
    • Organizer
      5TH INTERNATIONAL SYMPOSIUM on the Biology and Immunology of Cutaneous Lymphomas
    • Place of Presentation
      ベルリン(ドイツ)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 癌研究におけるプロテオミクス解析の応用2010

    • Author(s)
      藤井一恭
    • Organizer
      第4回病態制御シンポジウム
    • Place of Presentation
      岡山大学
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] 癌研究におけるプロテオミクス解析の応用2010

    • Author(s)
      藤井一恭
    • Organizer
      第4回病態制御シンポジウム
    • Place of Presentation
      岡山市
    • Year and Date
      2010-06-05
    • Related Report
      2011 Final Research Report
  • [Presentation] Establishment of acquired resistance to HDAC inhibitors2010

    • Author(s)
      Fujii K
    • Organizer
      The 35th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      Wakayama
    • Related Report
      2011 Final Research Report
  • [Presentation] バルプロ酸はG1期において細胞周期を止めることによりEBウイルス感染NK細胞の増殖を抑制する2010

    • Author(s)
      藤井一恭
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪市
    • Related Report
      2011 Final Research Report 2010 Annual Research Report
  • [Presentation] Proteomics identified biomarker candidates to predict the effects of histone decetylase inhibitors on lymphoid neplasm cell lines2010

    • Author(s)
      Fujii K
    • Organizer
      40th Annual ESDR meeting
    • Place of Presentation
      Helsinki, Finland
    • Related Report
      2011 Final Research Report
  • [Presentation] 2D-DIGEを用いたヒストン脱アセチル化酵素阻害剤の感受性に関わる分子の探索2010

    • Author(s)
      藤井一恭
    • Organizer
      日本ヒトプロテオーム機構第8回大会(日本プロテオーム学会2010年会)
    • Place of Presentation
      浦安市
    • Related Report
      2011 Final Research Report
  • [Presentation] 真菌浸潤を合併した重症型種痘様水庖症:副腎皮質ステロイドとVP16間歇療法による治療例2010

    • Author(s)
      平井陽至
    • Organizer
      第26回日本皮膚悪性腫瘍学会学術大会
    • Place of Presentation
      東京都新宿区
    • Related Report
      2010 Annual Research Report
  • [Presentation] 2D-DIGEを用いたヒストン脱アセチル化酵素阻害剤の感受性に関わる分子の探索2010

    • Author(s)
      藤井一恭
    • Organizer
      日本ヒトプロテオーム機構第8回大会(日本プロテオーム学会2010年会)
    • Place of Presentation
      千葉県浦安市
    • Related Report
      2010 Annual Research Report
  • [Presentation] Proteomics identified biomarker candidates to predict the effects of histone decetylase inhibitors on lymphoid neplasm cell lines2010

    • Author(s)
      Fujii K
    • Organizer
      40th Annual ESDR meeting
    • Place of Presentation
      ヘルシンキ(フィンランド)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Severe hydroa vacciniforme with myocardial infiltration of EB virus-infected T-cells~effective therapy with prednisolone and intermittent etoposide~2010

    • Author(s)
      Hirai H
    • Organizer
      First World Congress of Cutaneous Lymphomas
    • Place of Presentation
      シカゴ(米国)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Severe hydroa vacciniforme with myocardial infiltration of EB virus-infected T-cells2010

    • Author(s)
      Hirai Y
    • Organizer
      The First Eastern Asia Dermatology Congress
    • Place of Presentation
      福岡市
    • Related Report
      2010 Annual Research Report
  • [Presentation] 化学療法後に生じたeccrine poromatosisの3例2010

    • Author(s)
      藤井一恭
    • Organizer
      第62回日本皮膚科学会西部支部学術大会
    • Place of Presentation
      岡山県倉敷市
    • Related Report
      2010 Annual Research Report
  • [Presentation] 菌状息肉症/セザリー症候群における、末梢血CD4/8比上昇例の臨床的特徴2010

    • Author(s)
      池田佳寿子
    • Organizer
      第62回日本皮膚科学会西部支部学術大会
    • Place of Presentation
      岡山県倉敷市
    • Related Report
      2010 Annual Research Report
  • [Presentation] Establishment of acquired resistance to HDAC inhibitors2010

    • Author(s)
      Fujii K
    • Organizer
      The 35th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      和歌山市
    • Related Report
      2010 Annual Research Report
  • [Presentation] Distinct infiltrating cell types of the lesional skin and the peripheral blood in EBV-associated T/NK lymphoproliferative disorders2010

    • Author(s)
      Hirai Y
    • Organizer
      The 35th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      和歌山市
    • Related Report
      2010 Annual Research Report
  • [Book] ウイルス性皮膚疾患ハンドブック2011

    • Author(s)
      藤井一恭, 他
    • Publisher
      中山書店
    • Related Report
      2011 Final Research Report
  • [Book] 皮膚悪性腫瘍取扱い規約第2版2010

    • Author(s)
      藤井一恭, 他
    • Publisher
      金原出版
    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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