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2011 Fiscal Year Research-status Report

肝細胞癌の発癌・進展の分子機構:造影超音波クッパー相と遺伝子発現を用いた融合解析

Research Project

Project/Area Number 23650312
Research InstitutionKinki University

Principal Investigator

工藤 正俊  近畿大学, 医学部, 教授 (10298953)

Co-Investigator(Kenkyū-buntansha) 井上 達夫  近畿大学, 医学部, 講師 (20441024)
Project Period (FY) 2011-04-28 – 2013-03-31
Keywords超音波医科学 / ソナゾイド造影超音波 / 肝細胞癌 / クッパー細胞 / 遺伝子多型
Research Abstract

対象は、2008年2月から2010年9月の期間に、2回以上のEOB-MRIで評価しえた慢性肝障害・肝硬変患者の乏血性結節、53例121結節である。病変数は1例あたり平均2.2結節であった。エントリーは初回EOB-MRI検査日とし、対象を無治療にて経過観察し、多血化発生日はEOB-MRI、造影CT、肝動脈造影下CT(CT hepatic arteriography; CTHA)、造影超音波検査のうち、多血化が最も早く確認されたモダリティの検査日とした。観察期間中に多血化がみられた結節を多血化群、みられなかった結節を非多血化群とした。中央値343(76-937)日の経過観察期間中、53例中26例(49%)に多血化を認めた。病変ベースでは、121結節中39結節(32%)に多血化を認め、Kaplan-Meier法によって求めた6ヶ月、12ヶ月での累積多血化率は、それぞれ10%、28%であった。病理組織診断は13結節に得られ、多血化群は高分化肝細胞癌8結節、中分化肝細胞癌1結節、非多血化群は異型性結節2結節、高分化肝細胞癌2結節であった。多変量Cox回帰解析を行った。説明変数には、ベースラインMRIの画像所見(T2強調画像における信号強度、脂肪成分の有無、造影前および造影後のT1強調画像における造影効果比、肝細胞相で計測した最大径)と、このときの患者背景因子(年齢、性別、Child-Pugh分類、慢性肝障害の病因、血清AFP、多血性肝細胞癌の局所治療歴、多血性肝細胞癌の併存)を含め、これらのベースライン因子と多血化の無発生生存期間との関連を評価した。トランスポーターの解析結果については肝細胞相で低信号を呈するものについてはOATP1B3が低下していた。また、造影超音波Kupffer相で低信号を示す結節内のCD68は非癌部肝組織より低下していた。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

(1)EOB-MRI肝細胞相にて低信号を呈する結節の自然経過、(2)肝トランスポーターの発現解析あるいは、(3)造影超音波Kupffer相や低信号を示す結節内の生検組織のCD68染色の研究については順調に進行している。

Strategy for Future Research Activity

早期肝癌に発現されるとされる遺伝子を抽出し、それら遺伝子の発現変化を誘導した細胞のマイクロアレイ解析を行い、早期肝癌関連遺伝子の遺伝子発現プロファイルの変化を検討する。遺伝子発現変化が大きい分子についてはWestern blot によりタンパクの発現についても検討し、新しい分子マーカーの可能性についても検討する。当然、これらの所見を呈する結節の造影超音波所見も比較検討し、癌化のプロセスのどの段階で遺伝子発現プロファイルが変化し、Kupffer 細胞機能や数に影響を与えているのかについても検討する.

Expenditure Plans for the Next FY Research Funding

実験用消耗品にほとんどの研究費を使用予定

  • Research Products

    (38 results)

All 2012 2011

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (24 results)

  • [Journal Article] Double-contrast ultrasoud: a novel surveillance tool for hepatocellular carcinoma.2011

    • Author(s)
      Kudo M, Hatanaka K, Kumada T, Toyoda H, Tada T
    • Journal Title

      Am J Gastroenterol

      Volume: 106 Pages: 368-370

    • Peer Reviewed
  • [Journal Article] Antitumor activity of BIBF 1120, a vascular endothelial growth factor-2 inhibitor and use of VEGR2+pTYR+leucocyte as a pharmacodynamic biomarker.2011

    • Author(s)
      Kudo K, Arao T, Tanaka K, Kaneda H, Matsumoto K, Tamura D, Aomatsu K, Velasco M, Fujita Y, Saijo N, Kudo M, Nishio K
    • Journal Title

      Clin Cancer Res

      Volume: 17 Pages: 1373-1381

    • Peer Reviewed
  • [Journal Article] Recurrence-free survival more than 10 years after liver resection for hepatocellular carcinoma.2011

    • Author(s)
      Eguchi S, Kanematsu T, Arii S, Omata M, Kudo M, Sakamoto M, Takayasu K, Makuuchi M, Matsuyama Y, Monden M, for the Liver Cancer Study Group of Japan
    • Journal Title

      Brit J Surg

      Volume: 98 Pages: 552-557

    • Peer Reviewed
  • [Journal Article] Management of hepatocellular carcinoma in Japan: Consensus-based clinical practice guideline proposed by the Japan Society of Hepatology (JSH) 2010 updated version.2011

    • Author(s)
      Kudo M, Izumi N, Kokudo N, Matsui O, Sakamoto M, Nakashima O, Kojiro M, Makuuchi M
    • Journal Title

      Digest Dis

      Volume: 29 Pages: 339-364

    • Peer Reviewed
  • [Journal Article] Effect of vitamin K2 on the recurrence of hepatocellular carcinoma.2011

    • Author(s)
      Yoshida H, Shiratori Y, Kudo M, Shiina S, Mizuta T, Kojiro M, Yamamoto K, Koike Y, Saito K, Koyanagi N, Kawabe T, Kawazoe S, Kobashi H, Kasugai H, Osaki Y, Araki Y, Izumi N, Oka H, Tsuiji K, Toyota J, Seki T, Osawa T, Masaki N, Ichinose M, Seike M, Ishikawa A, Ueno Y, Tagawa K, Kuromatsu R, Sakisaka S, Ikeda H, Kuroda H, Hokuryu H, Yamashita T, Sakaida I, Katamoto T, Kikuchi K, Nomoto M, Omata M
    • Journal Title

      Hepatology

      Volume: 54 Pages: 532-540

    • Peer Reviewed
  • [Journal Article] Hepatocellular carcinoma in 2011 and beyond: From the pathogenesis to molecular targeted therapy.2011

    • Author(s)
      Kudo M
    • Journal Title

      Oncology

      Volume: 81 Pages: 1-10

    • Peer Reviewed
  • [Journal Article] Signaling pathways governing tumor angiogenesis.2011

    • Author(s)
      Sakurai T, Kudo M
    • Journal Title

      Oncology

      Volume: 81 Pages: 24-29

    • Peer Reviewed
  • [Journal Article] Usefulness of combination of imaging modalities in the diagnosis of hepatocellular carcinoma using Sonazoid-enhanced ultrasound, gadolinium diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging, and contrast-enhanced computed tomography.2011

    • Author(s)
      Alaboudy A, Inoue T, Hatanak K, Chung H, Hyodo T, Kumano S, Murakami T, Moustafa EFA, Kudo M
    • Journal Title

      Oncology

      Volume: 81 Pages: 66-72

    • Peer Reviewed
  • [Journal Article] Diagnostic imaging of hepatcocellular carcinoma: Recent progress.2011

    • Author(s)
      Kudo M
    • Journal Title

      Oncology

      Volume: 81 Pages: 73-85

    • Peer Reviewed
  • [Journal Article] Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma.2011

    • Author(s)
      Minami Y, Kudo M
    • Journal Title

      World J Gastroenterol

      Volume: 17 Pages: 4952-4959

    • Peer Reviewed
  • [Journal Article] Sorafenib inhibits the hepatocyte growth factor-mediated epithelial mesenchymal transition in hepatocellular carcinoma.2011

    • Author(s)
      Nagai T
    • Journal Title

      Mol Cancer Ther

      Volume: 10 Pages: 169-177

    • Peer Reviewed
  • [Journal Article] The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+pegylated interferon α-2b therapy against advanced hepatocellular carcinoma.2011

    • Author(s)
      Hagiwara S
    • Journal Title

      J Gastroenterol

      Volume: 46 Pages: 212-221

    • Peer Reviewed
  • [Journal Article] Optimal scanning protocol of arterial dominant phase for hypervascular hepatocellular carcinoma with gadolinium-ethoxybenzyl -diethylenetriamine pentaacetic acid-enhanced MR.2011

    • Author(s)
      Kagawa Y
    • Journal Title

      J Magn Reson Imaging

      Volume: 33 Pages: 864-872

    • Peer Reviewed
  • [Journal Article] stimation of liver function using T1 mapping onGd-EOB-DTPA-enhanced magnetic resonance imaging.2011

    • Author(s)
      Katsube T
    • Journal Title

      Invest Radiol

      Volume: 46 Pages: 277-283

    • Peer Reviewed
  • [Presentation] Management of hepatocellular carcinoma: Recent progress2012

    • Author(s)
      Kudo M
    • Organizer
      The 42nd Annual Meeting of the Gastroenterological Society of Taiwan (GEST) and The 21st Annual Meeting of the Digestive Endoscopy Society of Taiwan (DEST)(招待講演)
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      March 25, 2012
  • [Presentation] From JSH treatment guideline to combination therapy2012

    • Author(s)
      Kudo M
    • Organizer
      HCC Expert Meeting -New Advances in HCC Management(招待講演)
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      March 24, 2012
  • [Presentation] Evolving strategies on the treatment of HCC: Physician’s perspective2012

    • Author(s)
      Kudo M
    • Organizer
      The 22nd conference of the Asian Pacific Association for the Study of the Liver (APASL 2012)(招待講演)
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      February 16-19, 2012
  • [Presentation] Hepatocellular carcinoma2012

    • Author(s)
      Kudo M
    • Organizer
      The 22nd conference of the Asian Pacific Association for the Study of the Liver (APASL 2012)(招待講演)
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      February 16-19, 2012
  • [Presentation] Real life experience with Sorafenib: GIDEON, the largest prospective global study in HCC2012

    • Author(s)
      Kudo M
    • Organizer
      The 22nd conference of the Asian Pacific Association for the Study of the Liver (APASL 2012)(招待講演)
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      February 16-19, 2012
  • [Presentation] CEUS, EOB-MRI, targeted therapy and Japanese HCC guideline2012

    • Author(s)
      Kudo M
    • Organizer
      Cancer Genomics: a way to personalized medicine(招待講演)
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      February 15, 2012
  • [Presentation] Hepatocellular carcinoma: Recent development of molecular targeted agent2011

    • Author(s)
      Kudo M
    • Organizer
      The 49th Annual Meeting of Japan Society of Clinical Oncology(招待講演)
    • Place of Presentation
      Nagoya Congress Center, Aichi, Japan
    • Year and Date
      October 27-29, 2011
  • [Presentation] Establishing treatment algorithms for hepatocellular carcinoma: What tests do we need?2011

    • Author(s)
      Kudo M
    • Organizer
      19th United European Gastroenterology Week (UEGW)(招待講演)
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      October 24, 2011
  • [Presentation] Interventional EUS for pancreatobiliary tumors2011

    • Author(s)
      Kudo M
    • Organizer
      9th ABDA teaching course in conjunction with AFSUMB Workshop(招待講演)
    • Place of Presentation
      Bali, Indonesia
    • Year and Date
      November 17-19, 2011
  • [Presentation] Sonazoid-enhanced US in the management of HCC2011

    • Author(s)
      Kudo M
    • Organizer
      9th ABDA teaching course in conjunction with AFSUMB Workshop(招待講演)
    • Place of Presentation
      Bali, Indonesia
    • Year and Date
      November 17-19, 2011
  • [Presentation] Hepatocellular carcinoma: prevention and treatment by interferon2011

    • Author(s)
      Kudo M
    • Organizer
      The Japanese Society for Interferon and Cytokine Research-The Japanese Society for Macrophage Molecular and Cell Biology (JSICR-MMCB) 2011(招待講演)
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      May 25, 2011
  • [Presentation] Update on endoscopic USG: how much for imaging, needling, or therapy?2011

    • Author(s)
      Kudo M
    • Organizer
      The 42nd Annual Congress of the Korean Society of Ultrasound in Medicine (KSUM)(招待講演)
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      May 20, 2011
  • [Presentation] Sonazoid-enhanced US in the management of HCC2011

    • Author(s)
      Kudo M
    • Organizer
      The 42nd Annual Congress of the Korean Society of Ultrasound in Medicine (KSUM)(招待講演)
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      May 20, 2011
  • [Presentation] Sonazoid-enhanced US in the management of HCC2011

    • Author(s)
      Kudo M
    • Organizer
      XV Congress of the Latin American Federation for Ultrasound in Medicine and Biology (FLAUS)(招待講演)
    • Place of Presentation
      Asuncion, Paraguay
    • Year and Date
      June 22-25, 2011
  • [Presentation] RECICL2011

    • Author(s)
      Kudo M
    • Organizer
      The 2nd Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE)(招待講演)
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      July 1-3, 2011
  • [Presentation] EVOLVE-1 trial2011

    • Author(s)
      Kudo M
    • Organizer
      The 2nd Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE)(招待講演)
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      July 1-3, 2011
  • [Presentation] Current situation of HCC management in Japan2011

    • Author(s)
      Kudo M
    • Organizer
      The 2nd Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE)(招待講演)
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      July 1-3, 2011
  • [Presentation] Design and conduct of clinical trials for the design and rational of clinical trials for the combination of hepatic arterial infusion chemotherapy with molecular targeted agents2011

    • Author(s)
      Kudo M
    • Organizer
      The 2nd Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE)(招待講演)
    • Place of Presentation
      Osaka, Japan
    • Year and Date
      July 1-3, 2011
  • [Presentation] Molecular targeting therapy2011

    • Author(s)
      Kudo M
    • Organizer
      The 7th APASL single topic conference(招待講演)
    • Place of Presentation
      Makuhari Messe, Chiba, Japan
    • Year and Date
      December 18, 2011
  • [Presentation] Diagnosis of gross pathology of HCC: Value of Kupffer phase of Sonazoid-enhanced US2011

    • Author(s)
      Kudo M
    • Organizer
      3rd Asia-Pacific Conference on Ultrasound Contrast Imaging, 13th International Symposium on Ultrasound Contrast Imaging(招待講演)
    • Place of Presentation
      Kunming, China
    • Year and Date
      December 15-18, 2011
  • [Presentation] Clinical staging systems for HCC2011

    • Author(s)
      Kudo M
    • Organizer
      APASL 2nd Hepatocellular carcinoma conference (APASL STC)(招待講演)
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      December 1-3, 2011
  • [Presentation] US-guided ablation of HCC2011

    • Author(s)
      Kudo M
    • Organizer
      13th World Congress of the world federation for ultrasound in medicine and biology (WFUMB) 2011(招待講演)
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      August 26-29, 2011
  • [Presentation] Benefit and nonsense in oncologic follow-up imaging and the role of US2011

    • Author(s)
      Kudo M
    • Organizer
      13th World Congress of the world federation for ultrasound in medicine and biology (WFUMB) 2011(招待講演)
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      August 26-29, 2011
  • [Presentation] Future prospects of ultrasound diagnosis for diffuse liver disease2011

    • Author(s)
      Kudo M
    • Organizer
      13th World Congress of the world federation for ultrasound in medicine and biology (WFUMB) 2011(招待講演)
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      August 26-29, 2011

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Published: 2013-07-10  

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