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血清miRNAによる超早期癌診断法の開発

Research Project

Project/Area Number 21659091
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Human pathology
Research InstitutionTokyo Medical University

Principal Investigator

黒田 雅彦  東京医科大学, 医学部, 教授 (80251304)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2010: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2009: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsmiRNA / 血清 / 白血病 / 乳癌 / 再発予測 / フォローアップマーカー
Research Abstract

癌の医療において早期癌の根治治療が可能になった今日、特に早期に癌を診断することの重要性が再認識されている.現在、癌のスクリーニングには、PET検査や高解像度CTを用いた画像検査の一方、血液検査として腫瘍マーカーによる検査が一般に行われている.しかし、我が国で頻度の高い胃癌や、女性で問題となる乳癌などには、有効な血液中での早期の癌のマーカーが存在しないのが現状である.近年、マイクロRNA(miRNA)が注目され、様々な生物学的プロセスへの関与が明らかになってきた.特に、癌との関連においては、癌遺伝子を分解し癌抑制遺伝子のように働くmiRNAや、逆に癌抑制遺伝子を分解し癌遺伝子のように作用するoncogenic miRNAの存在も明らかになってきた.そこで本研究では、癌に関連する血清中のmiRNAを検出することによる癌の早期診断を目指している。今年度は、急性白血病、肝癌、乳癌患者の血清中のmiRNAの検討を行った。その結果、miR-92aが癌患者の血清中で極端に減少していることが明らかになった。一方で、血清中にはRNase活性が存在するため、時間の経過とともにmiRNAの分解される可能性がある。従って、血清中miRNAの分解、変性に関して検討を行った。その結果、血清中に存在するmiRNAは,室温で2週間放置していても安定であることがわかった。また、我々はmiR-92aが癌のフォローアップマーカーや再発予測に用いることができるかどうか検討した。そして、肝癌において、再発予測が出来ることが明らかになった。また、悪性リンパ腫においてもmiR-92aの検討を行った。その結果,ろ胞性リンパ腫,DLBCL,T細胞性リンパ腫においてmiR-92aの減少が明らかになった。さらに、リンパ腫の治療後寛解時にmiR-92aを計測すると、この時のmiR-92aの値によって、再発の危険度を推定できることが明らかになった。今後、これらのmiRNAの測定法の臨床応用を目指していく。

Report

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

    (49 results)

All 2011 2010 2009 Other

All Journal Article (19 results) (of which Peer Reviewed: 18 results) Presentation (28 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Dysregulation of IFN system can lead to poor response to pegylated interferon and ribavirin therapy in chronic hepatitis C.2011

    • Author(s)
      Onomoto K
    • Journal Title

      PLoS One

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The progression of liver fibrosis is related with overexpression of the miR-199 and 200 families.2011

    • Author(s)
      Murakami Y
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Impact of Down-regulated Plasma miR-92a Levels in Non-Hodgkin's Lymphoma.2011

    • Author(s)
      Ohyashiki K
    • Journal Title

      PLoS One

      Volume: 6

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact on cell to plasma ratio of miR-92a in patients with acute leukemia : in vivo assessment of cell to plasma ratio of miR-92a.2010

    • Author(s)
      Ohyashiki J H
    • Journal Title

      BMC Res Notes

      Volume: 3 Pages: 347-347

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic microRNA expression is associated with the response to interferon treatment of chronic hepatitis C2010

    • Author(s)
      Murakami Y
    • Journal Title

      BMC Med Genomics

      Volume: 3 Pages: 48-48

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development.2010

    • Author(s)
      Shigoka M
    • Journal Title

      Pathology Intarnational

      Volume: 60 Pages: 351-357

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FRS2beta, a potential prognostic gene for non-small cell lung cancer, encodes a feedback inhibitor of EGF receptor family members by ERK binding.2010

    • Author(s)
      Iejima D
    • Journal Title

      Oncogene

      Volume: 29 Pages: 3087-3099

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FRS2beta, a potential prognostic gene for non-small cell lung cancer, encodes a feedback inhibitor of EGF receptor family members by ERK binding.2010

    • Author(s)
      Iejima D
    • Journal Title

      Oncogene (Epub ahead of print)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells via activation of aryl hydrocarbon receptor.2010

    • Author(s)
      Zhang L
    • Journal Title

      Invest Ophthalmol Vis Sci. 51

      Pages: 2109-2117

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoprotective Effect of Imatinib Mesylate in Non-BCR-ABL-expressing Cells and Autophagosome Formation.2010

    • Author(s)
      Ohtomo T
    • Journal Title

      Biochem Biophys Res Commun 1

      Pages: 310-315

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene set enrichment analysis provides insight into novel signaling pathways in breast cancer stem cells.2010

    • Author(s)
      Murohashi M
    • Journal Title

      British journal of cancer 5

      Pages: 206-212

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Environmental Chemicals on Cell Division and Chromosomal Positioning.2009

    • Author(s)
      Oikawa K
    • Journal Title

      Reproductive Immunology and Biology 24

      Pages: 70-76

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma.2009

    • Author(s)
      Yamamoto Y
    • Journal Title

      Biomarkers 14

      Pages: 529-538

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] USP15 plays an essential role for caspase-3 activation during Paclitaxel-induced apoptosis.2009

    • Author(s)
      Xu M
    • Journal Title

      Biochem Biophys Res Commun 14

      Pages: 529-538

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic silencing of an endogenous gene by the siRNA cream in an arthritis model mouse.2009

    • Author(s)
      Takanashi M
    • Journal Title

      Gene Therapy 16

      Pages: 982-989

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Dioxin on Vascular Endothelial Growth Factor(VEGF) Production in the Retina Associated with Chroidal Neavascularization.2009

    • Author(s)
      Takeuvhi A
    • Journal Title

      Invest Ophthalmol Vis Sci. 50

      Pages: 3410-3416

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Down-regulation of miR-92 in human plasma is a novel marker foracute leukemia natients.2009

    • Author(s)
      Tanaka M
    • Journal Title

      PloS ONE 4

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌のバイオマーカーとしてのmicroRNA2009

    • Author(s)
      黒田雅彦
    • Journal Title

      実験医学 27

      Pages: 1223-1227

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development.

    • Author(s)
      Shigoka M
    • Journal Title

      Pathology International (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ビルベリー抽出液による脂肪分化阻害効果2010

    • Author(s)
      鈴木理英子
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] Deregulation of miR-92a expression is implicated in colon cancer development.2010

    • Author(s)
      Shin-Ichiro Ohno
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] エキソソーム内のマイクロRNAによる細胞間情報伝達効率2010

    • Author(s)
      田中正視
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] The PRG4 variants associated with sarcoma development have a potential to be therapeutic targets.2010

    • Author(s)
      Kosuke Oikawa
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] マイクロRNA-199,200ファミリ-の発現異常は肝線維化進展に関係する2010

    • Author(s)
      村上善基
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 大腸癌におけるmiR-17-92クラスターの解析2010

    • Author(s)
      那日蘇
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] miR-92aの発現は大腸癌の増殖に関与する2010

    • Author(s)
      大野慎一郎
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] microRNAプロファイルとC型慢性肝炎へのインターフェロン治療効果2010

    • Author(s)
      田中正視
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 前立腺癌患者における血清マイクロRNA解析2010

    • Author(s)
      佐竹直哉
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] EGFR遺伝子を標的とするmiRNAの単離と解析2010

    • Author(s)
      山口学
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 大腸癌におけるmiR-17-92クラスターの解析2010

    • Author(s)
      黒田雅彦
    • Organizer
      第2回日本RNAi研究会
    • Place of Presentation
      広島
    • Year and Date
      2010-08-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] 癌研究の新展開2010

    • Author(s)
      黒田雅彦
    • Organizer
      第165回東京医科大学医学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-06-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] 髄間葉系幹細胞による皮膚炎モデルマウスへの症状の抑制効果について2010

    • Author(s)
      高梨正勝
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] LNA probeを用いたin situ hybridizationによるmiRNAの検出2010

    • Author(s)
      藤田浩司
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2010-04-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] Potential roles of NF-kaooa B pathways in breast cancer-initiating cells.2010

    • Author(s)
      Kunihiko Hinohara
    • Organizer
      AACR, 101^<st> Annual Meeting
    • Place of Presentation
      Washington, DC USA
    • Year and Date
      2010-04-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development2010

    • Author(s)
      Masami Tanaka
    • Organizer
      AACR, 101^<st> Annual Meeting
    • Place of Presentation
      Washington, DC USA
    • Year and Date
      2010-04-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] The chimeric oncoprotein TLS-CHOP represses the expression of an anticancer molecule through induction of specific microRNAs.2009

    • Author(s)
      及川恒輔
    • Organizer
      第32回日本分子生物学会年会(MBSJ2009)
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Therapic silencing of an endogenous gene by siRNA cream in an arthritis model mouse.2009

    • Author(s)
      高梨正勝
    • Organizer
      第32回日本分子生物学会年会(MBSJ2009)
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Bilberry extract inhibits adipocyte diffentiation.2009

    • Author(s)
      鈴木理英子
    • Organizer
      第32回日本分子生物学会年会(MBSJ2009)
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Potential roles of NF-kB pathways in breast cancer-initiating cells.2009

    • Author(s)
      日野原邦彦
    • Organizer
      第32回日本分子生物学会年会(MBSJ2009)
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] 新規バイオマーカーとしての血清中microRNA.2009

    • Author(s)
      田中正視
    • Organizer
      第32回日本分子生物学会年会(MBSJ2009)
    • Place of Presentation
      横浜
    • Year and Date
      2009-12-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] Oncofetal microRNA as a potential diagnostic marker for hepatocellular carcinoma.2009

    • Author(s)
      小坂展慶
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Autophagy Inducing Effect of Imatinib Mesylate in Non-BCR-ABL Expressing Cells along with Suppression of ER Stress.2009

    • Author(s)
      大友理
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Molecular signatures of tumor-intiating cells in human breast cancer cell lines.2009

    • Author(s)
      室橋道子
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Down-regulation of miR- in human plasma is a novel marker for acureleukemia patients.2009

    • Author(s)
      田中正視
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] miRNAによる癌診断の臨床応用(招待講演)2009

    • Author(s)
      黒田雅彦
    • Organizer
      第1回日本RNA研究会
    • Place of Presentation
      広島
    • Year and Date
      2009-08-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 乳癌におけるG protein-coupled Receptor Kinase 4の役割とその関連分子の同定2009

    • Author(s)
      黒田雅彦
    • Organizer
      第5回日本臨床プロテオーム研究会
    • Place of Presentation
      東京
    • Year and Date
      2009-05-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] A functional genomic screen identifies a role of USP15 and Septin 10 in spindle-checkpoint and Paclitaxel-resistance in human cancers.2009

    • Author(s)
      Kuroda M
    • Organizer
      AACR, 100^<th> Annual Meeting
    • Place of Presentation
      Denver, Colorado USA
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 発現ベクター、それを用いたキャリアの製造方法およびその用途2010

    • Inventor(s)
      黒田雅彦
    • Industrial Property Rights Holder
      黒田雅彦
    • Industrial Property Number
      2010-292542
    • Filing Date
      2010-12-28
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] キャリア、その製造方法およびその用途2010

    • Inventor(s)
      黒田雅彦
    • Industrial Property Rights Holder
      黒田雅彦
    • Industrial Property Number
      2009-262938
    • Filing Date
      2010-11-18
    • Related Report
      2010 Annual Research Report

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

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