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Comprehensive analysis for epigenetic modulation of the effects of anticancer agents on cancer stem cells

Research Project

Project/Area Number 22659233
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionThe University of Tokushima

Principal Investigator

UTSUNOMIYA Tohru  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (30304801)

Co-Investigator(Kenkyū-buntansha) SHIMADA Mitsuo  徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (10216070)
SUGIMOTO Koji  徳島大学, 病院, 医員 (20448327)
SHUICHI Iwahashi  徳島大学, 病院, 医員 (30531751)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,230,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsエピジェネティック修飾 / がん幹細胞 / 幹細胞マーカー / ヒストン脱アセチル化 / 抗癌剤抵抗性 / 分化誘導 / DNAマイクロアレイ解析 / ネットワーク解析
Research Abstract

We investigated the significance of epigenetic modulation of the effects of anticancer agents on cancer stem cells. We found that combination therapy of anticancer agents and histone deacetylase inhibitor(HDACi) markedly reduced cancer cell viability compared to that of each single agent alone. We confirmed that HDACi induced cell differentiation of cancer cell lines in terms of stemness genes and cancer stem cell markers. Finally, we identified the candidate genes, which might be responsible to the synergistic effects of HDACi, using a DNA microarray analysis and a gene network analysis.

Report

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

    (46 results)

All 2012 2011 2010

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (27 results)

  • [Journal Article] Role of histone deacetylase expression in intrahepatic cholangiocarcinoma2012

    • Author(s)
      Morine Y, et al
    • Journal Title

      Surgery

      Volume: 151 Pages: 412-419

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Impact of Pegylated-Interferon alpha-2b on Partial and Massive Hepatectomy Model in Rats2011

    • Author(s)
      Utsunomiya T, et al.(12人中4番目)
    • Journal Title

      Hepatogastroenterology

      Volume: (in press)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modified liver hanging maneuver focusing on the ligamentum venosum in left hepatic lobectomy2011

    • Author(s)
      Utsunomiya T, et al.(10人中3番目)
    • Journal Title

      World J Surg

      Volume: (in press) Issue: 8 Pages: 720-723

    • DOI

      10.1007/s00595-011-0051-2

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human adipose-derived stem cells : potential clinical applications in surgery2011

    • Author(s)
      Utsunomiya T, et al.(9人中1番目)
    • Journal Title

      Surg Today

      Volume: 41(1) Issue: 1 Pages: 18-23

    • DOI

      10.1007/s00595-010-4415-9

    • NAID

      10027818310

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modified hanging method for liver resection and liver mobilization2011

    • Author(s)
      Utsunomiya T, et al.(2人中1番目)
    • Journal Title

      J Hepatobiliary Pancreat Surg

      Volume: 19 Issue: 1 Pages: 19-24

    • DOI

      10.1007/s00534-011-0442-1

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Pegylated Interferonα2b on Metastasis of Hepatocellular Carcinoma2011

    • Author(s)
      Utsunomiya T, et al.(6人中3番目)
    • Journal Title

      J Surg Res

      Volume: 172 Issue: 1 Pages: 95-101

    • DOI

      10.1016/j.jss.2010.07.023

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia inducible factor expression in intrahepatic cholangiocarcinoma2011

    • Author(s)
      Utsunomiya T, et al.(10人中3番目)
    • Journal Title

      Hepatogastroenterology

      Volume: 58 Issue: 110-111 Pages: 1439-1444

    • DOI

      10.5754/hge11156

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone deacetylase inhibitor augments anti-tumor effect of gemcitabine and pegylated interferon-αon pancreatic cancer cells2011

    • Author(s)
      Utsunomiya T, et al.(10人中3番目)
    • Journal Title

      Int J Clin Oncol

      Volume: 16 Issue: 6 Pages: 671-678

    • DOI

      10.1007/s10147-011-0246-y

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of dihydropyrimidine dehydrogenase and thymidylate synthase expression in immunohistochemistry of intrahepatic cholangiocarcinoma2011

    • Author(s)
      Utsunomiya T, et al.(9人中3番目)
    • Journal Title

      Hepatol Res

      Volume: 41(1) Pages: 64-70

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines2011

    • Author(s)
      Utsunomiya T, et al.(10人中3番目)
    • Journal Title

      J Med Invest

      Volume: 58 Pages: 106-9

    • NAID

      130004465230

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular characteristics of non-cancerous liver tissue in non-B non-C hepatocellular carcinoma2011

    • Author(s)
      Utsunomiya T, et al.(2人中1番目)
    • Journal Title

      Hepatol Res

      Volume: 41(8) Pages: 711-721

    • NAID

      10031144143

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer2011

    • Author(s)
      Utsunomiya T, et al.(7人中6番目)
    • Journal Title

      Int J Clin Oncol

      Volume: 16 Issue: 2 Pages: 145-52

    • DOI

      10.1007/s10147-010-0147-5

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone deacetylase inhibitor enhances the anti-tumor effect of gemcitabine : A special reference to gene-expression microarray analysis2011

    • Author(s)
      Utsunomiya T, et al.(9人中1番目)
    • Journal Title

      Oncol Rep

      Volume: 26 Pages: 1057-1062

    • DOI

      10.3892/or.2011.1407

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholanglocarcinoma cell lines2011

    • Author(s)
      Iwahashi S, et al
    • Journal Title

      J Med Invest

      Volume: 58 Pages: 106-109

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines.2011

    • Author(s)
      Iwahashi S, et al.
    • Journal Title

      J Med Invest

      Volume: 58 Pages: 106-109

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human adipose-derived stem cells : potential clinical applications in surgery.2011

    • Author(s)
      Utsunomiya T, et al.
    • Journal Title

      Surg Today

      Volume: 41 Pages: 18-23

    • NAID

      10027818310

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of splenectomy in patients with liver cirrhosis : Results from 18 patients in a single center experience2010

    • Author(s)
      Utsunomiya T, et al.(11人中3番目)
    • Journal Title

      Hepatol Res

      Volume: 40(9) Issue: 9 Pages: 894-900

    • DOI

      10.1111/j.1872-034x.2010.00688.x

    • NAID

      10026696793

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular signatures of noncancerous liver tissue can predict the risk for late recurrence of hepatocellular carcinoma2010

    • Author(s)
      Utsunomiya T, et al(6人中1番目)
    • Journal Title

      J Gastroenterol

      Volume: 45(2) Issue: 2 Pages: 146-52

    • DOI

      10.1007/s00535-009-0164-1

    • NAID

      10027214321

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] CD133 expression is a potential prognostic indicator in intrahepatic cholangiocarcinoma.2010

    • Author(s)
      Shimada M, et al.
    • Journal Title

      J Gastroenterol

      Volume: 45 Pages: 896-902

    • NAID

      10026611089

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] ffects of gemcitabine combined with 5-fluorouracil and cisplatin(GFP) for patients with unresectable biliary carcinoma and its possible usefulness for postoperative adjuvant chemotherapy2011

    • Author(s)
      Utsunomiya T, et al.(12人中1番目)
    • Organizer
      21^<st> World Congress of the International Association of surgeons, Gastroenterologists and Oncologigts
    • Place of Presentation
      Tokyo
    • Related Report
      2011 Final Research Report
  • [Presentation] Molecular signatures of noncancerous liver tissue can predict the risk for late recurrence of hepatocellular carcinoma2011

    • Author(s)
      Utsunomiya T, et al.(12人中1番目)
    • Organizer
      21^<st> World Congress of the International Association of surgeons, Gastroenterologists and Oncologigts
    • Place of Presentation
      Tokyo
    • Related Report
      2011 Final Research Report
  • [Presentation] CD44 Expression Can Predict Prognosis of Intrahepatic Cholangiocarcinoma2011

    • Author(s)
      Utsunomiya T, et al.(10人中3番目)
    • Organizer
      97^<th> Clinical Congress of American college of Srgeons
    • Place of Presentation
      San Francisco
    • Related Report
      2011 Final Research Report
  • [Presentation] C型肝硬変に対するABO不適合肝移植後の低用量Peg-IFN/ RBV療法の有用性2011

    • Author(s)
      宇都宮徹, ほか(3人中3番目)
    • Organizer
      JDDW(日本消化器関連学会集会)
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Related Report
      2011 Final Research Report
  • [Presentation] 肝虚血再灌流傷害におけるヒト脂肪由来幹細胞homing effectの機序解明2011

    • Author(s)
      宇都宮徹, ほか(3人中3番目)
    • Organizer
      JDDW(日本消化器関連学会集会)
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Related Report
      2011 Final Research Report
  • [Presentation] 消化器癌における癌幹細胞マーカー発現の意義とエピジェネティック修飾による制御の可能性2011

    • Author(s)
      宇都宮徹, ほか(3人中3番目)
    • Organizer
      JDDW(日本消化器関連学会集会)
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of histone deacetylase expression in IHCC : A possible epigenetic regulation of cancer stem cell2011

    • Author(s)
      Utsunomiya T, et al.(10人中3番目)
    • Organizer
      8^<th> International Smposium on Minimal Residual Cancer
    • Place of Presentation
      Osaka
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胆管細胞癌は肝幹細胞由来の原発性肝腫瘍の特徴を有する2011

    • Author(s)
      宇都宮徹, ほか(13人中3番目)
    • 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(静岡市)
    • Related Report
      2011 Final Research Report
  • [Presentation] ヒストンアセチル化に基づく消化器癌幹細胞制御の可能性2011

    • Author(s)
      宇都宮徹, ほか(12人中3番目)
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      震災のため紙面発表
    • Related Report
      2011 Final Research Report
  • [Presentation] 胆管癌細胞においてHDAC阻害剤はGemcitabineの抗腫瘍効かを増強する-Ingenuity Pathways AnalysisによるGene networkに着目してー2011

    • Author(s)
      宇都宮徹, ほか(11人中3番目)
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      震災のため紙面発表
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胆管細胞癌は肝幹細胞由来の原発性肝腫瘍の特徴を有するー幹細胞マーカーの発現パターンに着目してー2011

    • Author(s)
      宇都宮徹, ほか(12人中3番目)
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      震災のため紙面発表
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of histone deacetylase expression in intrahepatic cholangiocarcinoma2011

    • Author(s)
      Utsunomiya T, et al.(12人中3番目)
    • Organizer
      102^<nd> American Association for Cancer Research
    • Place of Presentation
      Orlando
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of histone deacetylase expression in intrahepatic cholangiocarcinoma2011

    • Author(s)
      Utsunomiya T, et al.(12人中3番目)
    • Organizer
      102^nd> American Association for Cancer Research
    • Place of Presentation
      Orlando
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell line2011

    • Author(s)
      Utsunomiya T, et al.(12人中3番目)
    • Organizer
      102^<nd> American Association for Cancer Research
    • Place of Presentation
      Orlando
    • Related Report
      2011 Final Research Report
  • [Presentation] Effect of a histone deacetylase inhibitor on antitumor effect of gemcitabine to focus the gene network of ingenuity pathways analysis2011

    • Author(s)
      Utsunomiya T, et al.(9人中3番目)
    • Organizer
      Gastrointestinal Cancers Symposium : Science and Multidiscriplinary Management of GI Malignancies
    • Place of Presentation
      San Francisco
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of histone deacetylase expression on regulating cancer stem cells in intrahepatic cholangiocarcinoma2011

    • Author(s)
      Utsunomiya T, et al.(9人中5番目)
    • Organizer
      Gastrointestinal Cancers Symposium : Science and Multidiscriplinary Management of GI Malignancies
    • Place of Presentation
      San Francisco
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of histone deacetylase expression in intrahepatic cholamgiocarcinoma2011

    • Author(s)
      Morine Y, et al
    • Organizer
      American Association for Cancer Research
    • Place of Presentation
      Orange County Convention Center (Orlando)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 癌幹細胞のepigenetic修飾と癌根治療法への可能性2011

    • Author(s)
      森根裕二
    • 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)
    • Related Report
      2011 Annual Research Report
  • [Presentation] バルプロ酸は膵癌細胞に対するインターフェロンαの作用を増強する2011

    • Author(s)
      杉本光司
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 消化器癌における癌幹細胞マーカー発現の意義とエピジェネティック修飾による制御の可能性2011

    • Author(s)
      山田眞一郎
    • Organizer
      JDDW 2011
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2011 Annual Research Report
  • [Presentation] 肝内胆管癌における癌幹細胞を中心とした分子治療の可能性2010

    • Author(s)
      森根裕二
    • Organizer
      第21回日本消化器癌発生学会総会
    • Place of Presentation
      軽井沢
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] がん幹細胞のepigenetic修飾とがん根治療法への可能性2010

    • Author(s)
      宇都宮徹
    • Organizer
      第48回日本癌治療学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-10-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 肝内胆管癌における癌幹細胞を中心とした分子治療の可能性2010

    • Author(s)
      宇都宮徹, ほか(11人中3番目)
    • Organizer
      第21回日本消化器癌発生学会総会
    • Place of Presentation
      軽井沢プリンスホテル(軽井沢市)
    • Related Report
      2011 Final Research Report
  • [Presentation] 癌幹細胞マーカーからみた細胆管細胞癌及び胆管細胞癌の発生2010

    • Author(s)
      宇都宮徹, ほか(13人中13番目)
    • Organizer
      第21回日本消化器癌発生学会総会
    • Place of Presentation
      軽井沢プリンスホテル(軽井沢市)沢
    • Related Report
      2011 Final Research Report
  • [Presentation] Histone deacetylase inhibitor enhances anti-tumor effect of gemcitabine on pancreatic cancer and cholangiocarcinoma cell line2010

    • Author(s)
      Utsunomiya T, et al.(10人中3番目)
    • Organizer
      20^<th> World Congress of the International Association of Surgeons
    • Place of Presentation
      Gastroenterologists and Oncologists. Egypt
    • Related Report
      2011 Final Research Report
  • [Presentation] 胆管癌におけるHDAC阻害剤の有用性の検討2010

    • Author(s)
      宇都宮徹, ほか(3人中3番目)
    • Organizer
      JDDW(日本消化器関連学会集会)
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2011 Final Research Report
  • [Presentation] The correlation between cancer stem like cells and epigenetic alteration in intrahepatic cholangiocarcinoma2010

    • Author(s)
      Utsunomiya T, et al.(9人中3番目). Saito Y, Shimada M, Utsunomiya T, Morine Y, Imura S, Ikemoto T, Mori H, Hanaoka J, Iwahashi S
    • Organizer
      The 9th International Conference of The Asian Clinical Oncology Society
    • Place of Presentation
      Gihu
    • Related Report
      2011 Final Research Report

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

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