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2013 Fiscal Year Annual Research Report

進行肝細胞癌に対する鉄キレート剤と分子標的治療薬併用による新規治療法の開発

Research Project

Project/Area Number 23590978
Research InstitutionYamaguchi University

Principal Investigator

山崎 隆弘  山口大学, 医学(系)研究科(研究院), 教授 (00304478)

Co-Investigator(Kenkyū-buntansha) 山本 直樹  山口大学, 大学教育機構, 講師 (90448283)
寺井 崇二  山口大学, 医学(系)研究科(研究院), 准教授 (00332809)
坂井田 功  山口大学, 医学(系)研究科(研究院), 教授 (80263763)
Keywords鉄キレート剤 / Deferasirox / Sorafenib / DEN発癌モデル / Deferoximine / CDAAモデル
Research Abstract

HepG2、HuH7、Hep3B等肝細胞癌株を用いて、Sorafenib,Sorafenib+Deferasirox,Deferasiroxの投与によるMTSアッセイ解析では、単剤投与によって細胞増殖を抑制していたが、併用群ではさらに細胞増殖を抑制していた。
CDAA(Choline-deficient L-amino acid-defined diet:コリン欠乏食)による肝線維化・発癌ラットモデルで経口鉄キレート剤であるDeferasirox投与群とSorafenib投与群(通常量,半量), Deferasirox+ Sorafenib投与群、コントロール(非投与群)に分けて、肝臓の解析を行ったところ、肝線維化は単剤群でも抑制効果を認めたが、併用群の方がさらに線維化抑制効果を認めた。肝前癌病変の解析でも同様に単剤群でも抑制効果を認めたが、併用群の方がさらに発癌抑制効果を認めた。酸化ストレスマーカー4HNE,8OhdGも同様に併用群の方が有意に抑制効果を認めた。さらにSorafenibの様々な副作用もDeferasiroxとの併用投与によって抑制していた。DENによる発癌マウスモデルを利用した解析では、Deferasirox+ Sorafenib併用投与群が最も発癌抑制効果を示し、肝組織DNAアレイの解析結果でも、細胞周期関連遺伝子・増殖関連遺伝子・酸化ストレス関連遺伝子等の発現をDeferasirox投与群とSorafenib投与群で単独でも抑制効果を認めたが、併用した方がさらに有意に抑制効果を認めた。また細胞transpoter等関連遺伝子や糖代謝関連遺伝子・脂質関連遺伝子も大きく変化していた。

  • Research Products

    (19 results)

All 2014 2013 Other

All Journal Article (7 results) (of which Peer Reviewed: 5 results) Presentation (10 results) (of which Invited: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Systemic gemcitabine combined with hepatic arterial infusion chemotherapy with cisplatin, 5-fluorouracil, and isovorin for the treatment of advanced intrahepatic cholangiocarcinoma: A pilot study2014

    • Author(s)
      Marumoto M, Yamasaki T, Marumoto Y, Saeki I, Harima Y, Urata Y, Hidaka I, Ishikawa T, Takami T, Segawa M, Yamaguchi Y, Uchida K, Terai S, Sakaida I.
    • Journal Title

      Hepatogastroenterology

      Volume: 印刷中 Pages: 印刷中

  • [Journal Article] Efficacy of iron chelator deferoxamine for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma patients refractory to current treatments2014

    • Author(s)
      Yamasaki T, Saeki I, Sakaida I.
    • Journal Title

      Hepatol Int.

      Volume: 印刷中 Pages: 印刷中

  • [Journal Article] A Case of Hepatocellular Carcinoma-induced Hemobilia2014

    • Author(s)
      Ooishi T, Saeki I, Yamasaki T, Sakaida I
    • Journal Title

      Intern Med.

      Volume: 印刷中 Pages: 印刷中

    • Peer Reviewed
  • [Journal Article] Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension.2013

    • Author(s)
      Ishikawa T, Shiratsuki S, Matsuda T, Iwamoto T, Takami T, Uchida K, Terai S, Yamasaki T, Sakaida I
    • Journal Title

      J Gastroenterol.

      Volume: Oct 5 Pages: -

    • Peer Reviewed
  • [Journal Article] Association of tyrosine with insulin resistance in hepatitis C virus-related chronic liver disease.2013

    • Author(s)
      Oono T, Yamasaki T, Zaitsu J, Saeki I, Iwamoto T, Harima Y, Marumoto Y, Hidaka I, Urata Y, Ishikawa T, Takami T, Segawa M, Uchida K, Terai S, Kunitugu I, Tanabe T, Sakaida I
    • Journal Title

      Hepatol Res.

      Volume: Aug 1 Pages: -

    • DOI

      10.1111/hepr.12213.

    • Peer Reviewed
  • [Journal Article] Serum transferrin as a predictor of prognosis for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma.2013

    • Author(s)
      Zaitsu J, Yamasaki T, Saeki I, Harima Y, Iwamoto T, Harima Y, Matsumoto T, Urata Y, Hidaka I, Marumoto Y, Ishikawa T, Takami T, Yamamoto N, Kaino S, Uchida K, Terai S, Sakaida I.
    • Journal Title

      Hepatol Res.

      Volume: 44(5) Pages: 481-90

    • DOI

      10.1111/hepr.12141

    • Peer Reviewed
  • [Journal Article] Bortezomib induces tumor-specific cell death and growth inhibition in hepatocellular carcinoma and improves liver fibrosis.2013

    • Author(s)
      Saeki I, Terai S, Fujisawa K, Takami T, Yamamoto N, Matsumoto T, Hirose Y, Murata Y, Yamasaki T, Sakaida I.
    • Journal Title

      J Gastroenterol.

      Volume: 48(6) Pages: 738-50

    • DOI

      10.1007/s00535-012-0675-z.

    • Peer Reviewed
  • [Presentation] 進行肝癌の集学的治療における肝動注化学療法(HAIC)の再評価ーResponse guided therapy of HAICの提言2013

    • Author(s)
      佐伯 一成、山崎 隆弘、坂井田 功
    • Organizer
      第40回 日本肝臓学会西部会
    • Place of Presentation
      長良川国際会議場(岐阜)
    • Year and Date
      20131206-20131207
  • [Presentation] Iron chelator therapy for advanced hepatocellular carcinoma2013

    • Author(s)
      Takahiro Yamasaki, Isao Sakaida
    • Organizer
      8th International Symposium on Alcohlic Liver and Pancreatic Diseases and Cirrhosis, ALPD2013
    • Place of Presentation
      The Ashok (New Delhi, India)
    • Year and Date
      20131116-20131117
    • Invited
  • [Presentation] Association of tyrosine with insulin resistance in hepatitis C virus-related chronic liver disease2013

    • Author(s)
      Takahiro Yamasaki, Takashi Oono, Junichi Zaitsu, Issei Saeki, Yoshio Marumoto, Isao Hidaka, Yohei Urata, Tsuyoshi Ishikawa, Taro Takami, Koichi Uchida, Shuji Terai, Isao Sakaida
    • Organizer
      64th Annual Liver Meeting in AASLD 2013
    • Place of Presentation
      Washington Convention Center(Washington DC USA)
    • Year and Date
      20131101-20131105
  • [Presentation] The new oral iron chelator, Deferasirox, is the new drug to prevent Liver Fibrosis and Hepatocarcinogenesis2013

    • Author(s)
      Naoki Yamamoto, Takahiro Yamasaki, Koichi Uchida, Norikazu Tanabe, Taro Takami, Issei Saeki, Koichi Fujisawa, Masaki Maeda, Shuji Terai, Isao Sakaida
    • Organizer
      64th Annual Liver Meeting in AASLD 2013
    • Place of Presentation
      Washington Convention Center(Washington DC USA)
    • Year and Date
      20131101-20131105
  • [Presentation] The new oral iron chelator prevents liver fibrosis and preneoplastic lesions in liver cancer and liver cirrhosis model2013

    • Author(s)
      Naoki Yamamoto, Takahiro Yamasaki, Koichi Uchida, Taro Takami, Koichi Fujisawa, Masaki Maeda, Issei Saeki, Shuji Terai, Isao Sakaida
    • Organizer
      The 21st United European Gastroenterology Week (UEGW /Gastro 2013 )
    • Place of Presentation
      ICC Berlin(Germany)
    • Year and Date
      20131012-20131016
  • [Presentation] HCCに対するソラフェニブ治療の予後因子の検討ー治療前、治療1か月後の臨床的parameterの変化に着目してー2013

    • Author(s)
      浦田 洋平、山崎 隆弘、佐伯 一成、内田 耕一、寺井 崇二、沖田 幸祐、山下智省、沖田 極、坂井田 功
    • Organizer
      第49回 日本肝癌研究会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      20130711-20130712
  • [Presentation] The new oral iron chelator Deferasirox prevents liver fibrosis and preneoplastic lesions in rat liver cirrhosis induced2013

    • Author(s)
      Naoki Yamamoto, Takahiro Yamasaki, Teiichi Hirose, Taro Takami, Koichi Fujisawa, Masaki Maeda, Koichi Uchida, Issei Saeki, Shuji Terai, Isao Sakaida
    • Organizer
      The 23rd Conference of the Asian Pacific Association for the Study of the Liver(APASL) 2013
    • Place of Presentation
      Suntec Singapole(Singapole)
    • Year and Date
      20130606-20130609
  • [Presentation] Serum transferrin as a predictor of prognosis for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma2013

    • Author(s)
      Takahiro Yamasaki, Issei Saeki, Junichi Zaitsu, Yohei Harima, Takuya Iwamoto, Yumiko Harima, Toshihiko Matsumoto, Yohei Urata, Isao Hidaka, Yoshio Marumoto, Tsuyoshi Ishikawa, Taro Takami, Naoki Yamamoto, Seiji Kaino, Koichi Uchida, Shuji Terai, Isao Sakaida
    • Organizer
      The 23rd Conference of the Asian Pacific Association for the Study of the Liver(APASL) 2013
    • Place of Presentation
      Suntec Singapole(Singapole)
    • Year and Date
      20130606-20130609
  • [Presentation] 進行肝細胞癌に対する鉄代謝からみた肝動注化学療法の適応と限界2013

    • Author(s)
      佐伯 一成、山崎 隆弘、坂井田 功
    • Organizer
      第49回 日本肝臓学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      20130606-20130607
  • [Presentation] 血清トランスフェリンは進行肝癌治療前の予測因子となる2013

    • Author(s)
      佐伯 一成、山崎 隆弘、在津 潤一、浦田 洋平、内田 耕一、寺井 祟二、坂井田 功
    • Organizer
      第110回 日本内科学会総会
    • Place of Presentation
      東京国際フォーラム(東京)
    • Year and Date
      20130412-20130414
  • [Book] コンセンサス癌治療 (最新の肝細胞癌の診断と治療)2013

    • Author(s)
      山﨑隆弘、佐伯一成、在津潤一、浦田洋平、高見太郎、山本直樹、寺井崇二、坂井田 功
    • Total Pages
      116
    • Publisher
      へるす出版
  • [Remarks] i-MM therapy(鉄キレート剤治療)

    • URL

      http://www.ichinai-yamaguchi.jp/contents4/?categoryId=12

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Published: 2015-05-28  

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