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肝癌症例末梢血中の転移形成能力を有する癌細胞の検出

Research Project

Project/Area Number 21659319
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionOsaka University

Principal Investigator

永野 浩昭  大阪大学, 医学系研究科, 准教授 (10294050)

Co-Investigator(Kenkyū-buntansha) 丸橋 繁  大阪大学, 医学系研究科, 助教 (20362725)
小林 省吾  大阪大学, 医学系研究科, 助教 (30452436)
Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2010: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2009: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords肝細胞癌 / 微小転移 / 肝切除 / 肝移植 / 骨髄 / 末梢血 / 癌幹細胞
Research Abstract

肝細胞癌を有する患者で肝切除あるいは肝移植を行う症例を対象とし、骨髄液および末梢血を採取し、骨髄への微小転移(disseminated tumor cells, DTCs)および血中遊離細胞(Circulating tumor cells CTCs)の抽出と新規分子マーカーの探索を目的として研究を進めてきた。本年度施行した肝切除・肝移植症例全症例より、末梢血および骨髄液を術前・術後(骨髄液は術前のみ)に採取した。まず、これらの検体を用いて、density-gradient法およびCD45およびTer119でnegativesortをかけ、CD45(-)Ter119(-)細胞の分離抽出を開始し、本年度は特に、癌の分野でもその発現が発育・進展に関与している機能性non-coding RNAであるマイクロRNA(miRNA)の関与について、中心に研究を進めてきた。採取した臨床検体を用いて、まず関連するmiRNAについて約800のマイクロRNAアレイ解析を施行したところ、肝癌の転移に関して重要と考えられる十数種類の候補miRNAが同定された。これらの同定された候補miRNAについて、その発現量と臨床成績などについて比較検討し、絞り込みを行うともに、肝癌細胞株(HepG2、Huh7、PLC、MIHA、Hep3B、MHCC97Lなど)を用いてpre-miRの導入/anti-miRによる発現阻害により,転移形成能、浸潤能、増殖能、などについての解析を施行し、その可能性を確認した。

Report

(2 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (35 results)

All 2010 2009 Other

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (11 results)

  • [Journal Article] Treatment of advanced hepatocellular carcinoma : intraarterial infusion chemotherapy combined with interferon2010

    • Author(s)
      Nagano H
    • Journal Title

      Oncology

      Volume: 178(suppl 1) Pages: 142-147

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insulin-Like Growth Factor-Binding Protein 7 Alters the Sensitivity to Interferon-Based Anticancer Therapy in Hepatocellular Carcinoma Cells.2010

    • Author(s)
      Tomimaru Y., et al.
    • Journal Title

      B J Cancer

      Volume: 102(10) Pages: 1483-1490

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of preceding interferon therapy on outcome after surgery for hepatitis C virus-related hepatocellular carcinoma2010

    • Author(s)
      Tomimaru Y., et al.
    • Journal Title

      J of Surg Oncol

      Volume: 102 Pages: 308-314

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fresh frozen plasma transfusion does not affect outcomes following hepatic resection for hepatocellular carcinoma2010

    • Author(s)
      Tomimaru Y., et al.
    • Journal Title

      World J Gastroenterol

      Volume: 16(44) Pages: 5603-5610

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-21 induces resistance to the anti-tumor effect of interferon-α/5-fluorouracil in hepatocellular carcinoma cells2010

    • Author(s)
      Tomimaru Y., et al.
    • Journal Title

      Br J Cancer

      Volume: 103(10) Pages: 1617-1626

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tyrosine kinase inhibitor PTK/ZK enhances the anti-tumor effects of interferon-α/5-fluorouracil therapy for hepatocellular carcinoma cells2010

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

      Ann Surg Oncol

      Volume: 18(2) Pages: 589-596

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of preoperative transcatheter arterial chemoembolization for resectable hepatocellular carcinoma : Implication of circulating cancer cells by detection of alpha-fetoprotein mRNA2010

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

      Experimental and Therapeutic Medicine

      Volume: 1 Pages: 485-491

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolated Metastasis to the Gall Bladder from Hepatocellular Carcinoma2010

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

      Hepatology Research

      Volume: 40(8) Pages: 793-798

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocellular carcinoma : hepatocyte-selective enhancement at gadoxetic acid-enhanced MRImaging-correlation with expression of sinusoidal and canalicular transporters and bile accumulation2010

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

      Radiology

      Volume: 255(3) Pages: 824-833

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exploration of Potential Genomic Portraits Associated with Intrahepatic Recurrence in Human Hepatocellular Carcinoma.2010

    • Author(s)
      Kittaka N,., et al.
    • Journal Title

      Ann Surg Oncol

      Volume: 17(12) Pages: 3145-3154

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD13 is a therapeutic target in human liver cancer stem cells2010

    • Author(s)
      Haraguchi N., et al.
    • Journal Title

      J Clin Invest

      Volume: 120(9) Pages: 3326-3339

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognosis of hepatocellular carcinoma with biliary tumor thrombi following liver surgery2010

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

      Surgery

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular predicition of early recurrence after resection of hepatocellular carcinoma.2009

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

      Eur J Cancer 45

      Pages: 881-889

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of wnt/beta-catenin signalling pathway induces chemoresistance to interferon-alpha/5-fluorouracil combination therapy for hepatocellular carcinoma.2009

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

      Br J Cancer 100(10)

      Pages: 1647-1658

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene expression profiling of acute cellular rejection in rat liver transpla ntation using DNA microarrays.2009

    • Author(s)
      Hama N., et al
    • Journal Title

      Liver Transplantation 15

      Pages: 509-521

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential transcriptome patterns for acute cellular rejection in recipients with recurrent hepatitis C after liver transplantation2009

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

      Liver Transpl 15(12)

      Pages: 1738-1749

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Combination of interferon-alpha and 5-fluorouracil inhibits endothelial cell growth directly and by regulation of angiogenic factors released by tumor cells.2009

    • Author(s)
      Wada H., et al
    • Journal Title

      BMC Cancer 12(9)

      Pages: 361-361

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アンドロゲンレセプターは肝細胞治療の新たな分子標的となり得る.2009

    • Author(s)
      丸橋繁, 他
    • Journal Title

      Review of Gastroenterology & Clinical Gastroenterology and Hepatology 3(4)

      Pages: 57-61

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌幹細胞を標的とした治療法の開発.2009

    • Author(s)
      星野宏光, 他
    • Journal Title

      Surgery Frontier 16(1)

      Pages: 21-26

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌に対する分子標的治療の現状と展望2009

    • Author(s)
      永井健一, 他
    • Journal Title

      外科治療 100(4)

      Pages: 409-414

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 消化器癌における癌幹細胞研究の現状2009

    • Author(s)
      竹政伊知朗, 他
    • Journal Title

      日本外科学会雑誌 110(4)

      Pages: 207-212

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌幹細胞と間質細胞の相互作用-癌間質の重要性について.2009

    • Author(s)
      秋田裕史, 他
    • Journal Title

      肝胆膵 59(4)

      Pages: 631-638

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌幹細胞と薬剤耐性.2009

    • Author(s)
      永野浩昭, 他
    • Journal Title

      Cancer Frontier 11

      Pages: 100-105

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defined factors induced reprogramming of gastrointestinal cancer cells

    • Author(s)
      Miyoshi N., et al
    • Journal Title

      PNAS (In Press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 肝細胞癌術後再発への治療戦略 -長期予後を目指して-2010

    • Author(s)
      永野浩昭
    • Organizer
      第22回 日本消化器病外科学会総会
    • Place of Presentation
      下関
    • Related Report
      2010 Annual Research Report
  • [Presentation] Intraarterial Influsion Chemotherapy Combined with Interferon2010

    • Author(s)
      Nagano H
    • Organizer
      THE 2nd ASIA-PACIFIC PRIMARY LIVER CANCER EXPERT MEETING
    • Place of Presentation
      Incheon(韓国)(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Evaluation of potential allograft rejection biomarkers after liver transplantion.2009

    • Author(s)
      Asaoka T., et al
    • Organizer
      American Journal of Transplantation
    • Place of Presentation
      Boston(アメリカ)
    • Related Report
      2009 Annual Research Report
  • [Presentation] Effects of preceding interferon therapy on outcome after surgery for hepatitisc virusrelated hepatocellular carcinoma.2009

    • Author(s)
      Tomimaru Y., et al
    • Organizer
      3rd International Kobe Liver Symposium on HCC
    • Place of Presentation
      神戸
    • Related Report
      2009 Annual Research Report
  • [Presentation] IFN併用化学療法の感受性におけるWnt/beta-cateninシグナルの関与と感受性マーカーの同定2009

    • Author(s)
      野田剛広, 他
    • Organizer
      第109回日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肝細胞癌に対するIFN併用化学療法への分子標的治療薬併用による効果増強に関する検討2009

    • Author(s)
      村上昌裕, 他
    • Organizer
      第109回日本外科学会定期学術集会
    • Place of Presentation
      福岡
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肝細胞癌に対するIFN併用化学療法への分子標的治療薬併用による効果増強に関する検討2009

    • Author(s)
      村上昌裕, 他
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肝細胞癌に対するIFN併用化学療法の抵抗性におけるWnt/beta-cateninシグナルの関与2009

    • Author(s)
      野田剛広, 他
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      神戸
    • Related Report
      2009 Annual Research Report
  • [Presentation] 成人肝移植における胆汁Alanine aminopeptidase(AAp)の意義2009

    • Author(s)
      金致完, 他
    • Organizer
      第27回日本肝移植研究会
    • Place of Presentation
      静岡
    • Related Report
      2009 Annual Research Report
  • [Presentation] HCV陽性肝移植におけるpreemptive抗ウイルス療法の意義2009

    • Author(s)
      丸橋繁, 他
    • Organizer
      第51回日本消化器病学会大会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report
  • [Presentation] 高度進行肝細胞癌に対するインターフェロン併用化学療法の治療効果予測2009

    • Author(s)
      富丸慶人, 他
    • Organizer
      第71回日本臨床外科学会総会
    • Place of Presentation
      京都
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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