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Analysis of mechanisms by which malignant pleural mesothelioma grows and invades: application to pathological diagnosis and development of a new therapy

Research Project

Project/Area Number 23590438
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionHyogo Medical University

Principal Investigator

TSUJIMURA Tohru  兵庫医科大学, 医学部, 教授 (20227408)

Co-Investigator(Kenkyū-buntansha) TORII Ikuko  兵庫医科大学, 医学部, 准教授 (70207661)
SATO Ayuko  兵庫医科大学, 医学部, 講師 (20419823)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords悪性胸膜中皮腫 / 上皮間葉転換 / 浸潤 / Polycomb遺伝子群 / EZH2 / 予後
Research Abstract

Malignant mesothelioma is characterized by diffuse growth in the thoracic cavity and invasive proliferation in the chest wall, leading to poor prognosis. To clarify the mechanism by which malignant mesothelioma develops these features, we compared the gene expression profiling between malignant mesothelioma and mesothelial cells. We found that EZH2, which contributes to epigenetic silencing of target genes, was expressed at higher levels in malignant mesothelioma than in mesothelial cells. When EZH2 expression in mesothelioma cells was suppressed by the introduction of EZH2-siRNA, proliferation of these cells decreased. Immunohistochemical analysis of EZH2 expression in surgical specimens of malignant mesothelioma revealed correlation between higher expression of EZH2 and shorter overall survival of patients. It seems that epigenetics participates in biological characteristics of malignant mesothelioma, such as the growth in the thoracic cavity and the invasion into the chest wall.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (34 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 13 results,  Open Access: 2 results) Presentation (16 results) Book (4 results)

  • [Journal Article] LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascad2014

    • Author(s)
      Tanaka I, Osada H, Fujii M, Fukatsu A, Hida T, Horio Y, Kondo Y, Sato A, Hasegawa Y, Tsujimura T, Sekido Y
    • Journal Title

      Oncogene

      Volume: 34 Issue: 1 Pages: 73-83

    • DOI

      10.1038/onc.2013.528

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Significant increase in circulating tumour cells in pulmonary venous blood during surgical manipulation in patients with primary lung cancer.2014

    • Author(s)
      Hashimoto M, Tanaka F, Yoneda K, Takuwa T, Matsumoto S, Okumura Y, Kondo N, Tsubota N, Tsujimura T, Tabata C, Nakano T, Hasegawa S.
    • Journal Title

      Interact Cardiovasc Thorac Surg

      Volume: 18 Issue: 6 Pages: 775-783

    • DOI

      10.1093/icvts/ivu048

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Circulating tumor cells(CTCs)in malignant pleural mesothelioma(MPM)2013

    • Author(s)
      Yoneda K, Sato A, Tsujimura T et al
    • Journal Title

      Ann Surg Oncol

      Volume: 4 Issue: 13 Pages: 4229-4237

    • DOI

      10.1245/s10434-012-2506-0

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD146 and insulin-like growth factor 2 mRNA-binding protein 3 predict prognosis of asbestos-induced rat mesothelioma2013

    • Author(s)
      Okazaki Y, Tsujimura T, Toyokuni S et al
    • Journal Title

      Cancer Sci

      Volume: 104 Issue: 8 Pages: 989-995

    • DOI

      10.1111/cas.12185

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Morphology of 9p21 homozygous deletion-positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology.2013

    • Author(s)
      Matsumoto S et al
    • Journal Title

      Cancer Cytopathol

      Volume: 28 Issue: 8 Pages: 415-422

    • DOI

      10.1002/cncy.21269

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Circulating Tumor Cells (CTCs) in Malignant Pleural Mesothelioma (MPM).2013

    • Author(s)
      Yoneda K, Tanaka F, Kondo N, Hashimoto M, Takuwa T, Matsumoto S, Okumura Y, Tsubota N, Sato A, Tsujimura T, Kuribayashi K, Fukuoka K, Tabata C, Nakano T, Hasegawa S.
    • Journal Title

      Ann Surg Oncol

      Volume: - Issue: S4 Pages: 472-480

    • DOI

      10.1245/s10434-013-3399-2

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathological and molecular biological approaches to early mesothelioma2012

    • Author(s)
      Tsujimura T, Torii I, Sato A, et al
    • Journal Title

      Int J Clin Oncol

      Volume: 17 Issue: 1 Pages: 40-47

    • DOI

      10.1007/s10147-011-0369-1

    • NAID

      10030548318

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] TGF-β synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth2012

    • Author(s)
      Fujii M, Toyoda T, Nakanishi H, Yatabe Y, Sato A, Matsudaira Y, Ito H, Murakami H, Kondo Y, Kondo E, Hida T, Tsujimura T, Osada H, Sekido Y.
    • Journal Title

      J Exp Med

      Volume: VOL.209(3) Issue: 3 Pages: 479-494

    • DOI

      10.1084/jem.20111653

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma2012

    • Author(s)
      Yoshikawa Y, Sato A, Tsujimura T et al
    • Journal Title

      Cancer Sci

      Volume: 103 Issue: 5 Pages: 868-874

    • DOI

      10.1111/j.1349-7006.2012.02223.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Practical approaches to diagnose and treat for T0 malignant pleural mesothelioma : a proposal for diagnostic total parietal pleurectomy2012

    • Author(s)
      Hasegawa S, Torii I, Tsujimura T et al
    • Journal Title

      Int J Clin Oncol

      Volume: 17 Issue: 1 Pages: 33-39

    • DOI

      10.1007/s10147-011-0368-2

    • NAID

      10030548244

    • Related Report
      2013 Final Research Report
  • [Journal Article] TGF-β synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth2012

    • Author(s)
      Fujii M et al
    • Journal Title

      J Exp Med

      Volume: 209 Pages: 479-494

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Practical approaches to diagnose and treat for T0 malignant pleural mesothelioma: a proposal for diagnostic total parietal pleurectomy2012

    • Author(s)
      Hasegawa S et al
    • Journal Title

      Int J Clin Oncol

      Volume: 17 Pages: 33-39

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignantmesothelioma cells2011

    • Author(s)
      Yoshikawa Y, Sato A, Tsujimura T, Morinaga T, Fukuoka K, Yamada S, Murakami A, Kondo N, Matsumoto S, Okumura Y, Tanaka F, Hasegawa S, Hashimoto-Tamaoki T, and Nakano T.
    • Journal Title

      Int J Oncol.

      Volume: 39(6) Pages: 1365-74

    • DOI

      10.3892/ijo.2011.1158

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of a cell line from a Japanese patient useful for generating an in vivo model of malignant pleural mesothelioma2011

    • Author(s)
      Sato A, Torii I, Tao LH, Song M, Kondo N, Yoshikawa Y, Hashimoto-Tamaoki T, Hasegawa S, Nakano T, and Tsujimura T.
    • Journal Title

      Cancer Sci.

      Volume: 102(3) Issue: 3 Pages: 648-655

    • DOI

      10.1111/j.1349-7006.2010.01827.x

    • NAID

      10029291525

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 悪性胸膜中皮腫における組織レベルの3次元形態解析法の構築浸潤形態と腫瘍微小環境の関連性2013

    • Author(s)
      工藤朝雄, 佐藤鮎子, 鳥井郁子, 辻村亨, 他(全7名)
    • Organizer
      第54回日本組織細胞化学会総会・学術集会
    • Place of Presentation
      航空会館(東京)
    • Year and Date
      2013-09-27
    • Related Report
      2013 Final Research Report
  • [Presentation] 悪性胸膜中皮腫における可溶型CD146の診断バイオマーカーとしての有用性2013

    • Author(s)
      佐藤鮎子, 鳥井郁子, 辻村亨, 他(全5名)
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      ロイトン札幌・さっぽろ芸文館(札幌)
    • Year and Date
      2013-06-07
    • Related Report
      2013 Final Research Report
  • [Presentation] 悪性胸膜中皮腫の病理診断における胸水細胞診の現状と問題点2013

    • Author(s)
      辻村亨, 鳥井郁子, 佐藤鮎子, 他(全6名)
    • Organizer
      第54回日本臨床細胞学会総会春期大会
    • Place of Presentation
      グランドプリンスホテル新高輪・国際館パミール(東京)
    • Year and Date
      2013-06-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 胸水細胞診で早期中皮腫を診断するにあたり知っておくべき問題点2012

    • Author(s)
      辻村亨, 鳥井郁子, 佐藤鮎子, 他(全8名)
    • Organizer
      第51回日本臨床細胞学会秋期大会
    • Place of Presentation
      朱鷺メッセ, 新潟コンベンションセンター(新潟)
    • Year and Date
      2012-11-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Circulating tumor cell (CTC) as a significant clinical marker in epithelioid-type malignant pleural mesothelioma (MPM)2012

    • Author(s)
      Yoneda K, Sato A, Tsujimura T et al(全15名)
    • Organizer
      2012 Annual Meeting, American Society of Clinical Oncology
    • Place of Presentation
      Chicago
    • Year and Date
      2012-06-02
    • Related Report
      2013 Final Research Report
  • [Presentation] Differential diagnosis of malignant pleural mesothelioma and reactive mesothelium in pleural effusion cytology -molecular biological approach2012

    • Author(s)
      Tsujimura T.
    • Organizer
      The 19th Thai-Japanese Workshop in Diagnostic Cytopathology
    • Place of Presentation
      Sukhothai Treasure Resort & Spa. Thailand(Sukhothai)
    • Year and Date
      2012-01-18
    • Related Report
      2013 Final Research Report
  • [Presentation] Circulating tumor cell (CTC) as a significant clinical marker in epithelioid-type malignant pleural mesothelioma (MPM)2012

    • Author(s)
      Yoneda K et al
    • Organizer
      American Society of Clinical Oncology (ASCO 2012)
    • Place of Presentation
      Chicago, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] 胸水細胞診で早期中皮腫を診断するにあたり知っておくべき問題点2012

    • Author(s)
      辻村亨 他
    • Organizer
      第51回日本臨床細胞学会秋期大会
    • Place of Presentation
      新潟
    • Related Report
      2012 Research-status Report
  • [Presentation] 肉腫型悪性胸膜中皮腫の細胞学的検討2011

    • Author(s)
      鳥居良貴, 石田誠実, 辻村亨, 他(全9名)
    • Organizer
      第50回日本臨床細胞学会秋期大会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2011-10-23
    • Related Report
      2013 Final Research Report
  • [Presentation] 悪性中皮腫細胞における3p21.1領域の欠失およびセマフォリン3ファミリー遺伝子の発現抑制2011

    • Author(s)
      吉川良恵, 佐藤鮎子, 辻村亨, 他(全8名)
    • 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)
    • Year and Date
      2011-10-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 悪性中皮腫の鑑別診断におけるCD146免疫染色の有用性2011

    • Author(s)
      佐藤鮎子, 鳥井郁子, 辻村亨, 他(全6名)
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2011-04-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Circulating tumor cell (CTC) as a clinical marker in malignant pleural mesothelioma (MPM)2011

    • Author(s)
      Tanaka F, Tsujimura T, Nakano T et al(全11名)
    • Organizer
      2011 Annual Meeting, American Society of Clinical Oncology
    • Place of Presentation
      Chicago
    • Related Report
      2013 Final Research Report
  • [Presentation] Circulating endothelial cell (CEC), a surrogate of tumor angiogenesis, as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM)2011

    • Author(s)
      Yoneda K, Sato A, Tsujimura T et al(全15名)
    • Organizer
      2011 Annual Meeting, American Society of Clinical Oncology
    • Place of Presentation
      Chicago
    • Related Report
      2013 Final Research Report
  • [Presentation] 悪性胸膜中皮腫の病理診断における胸水細胞診の現状と問題点

    • Author(s)
      辻村亨, 鳥井郁子, 佐藤鮎子, 鳥居良貴, 鍋島一樹, 亀井敏昭
    • Organizer
      第54回日本臨床細胞学会総会春期大会
    • Place of Presentation
      グランドプリンスホテル新高輪・国際館パミール
    • Related Report
      2013 Annual Research Report
  • [Presentation] 悪性胸膜中皮腫における可溶型CD146の診断バイオマーカーとしての有用性

    • Author(s)
      佐藤鮎子, 鳥井郁子, 中野孝司, 長谷川誠紀, 辻村亨
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      ロイトン札幌・さっぽろ芸文館
    • Related Report
      2013 Annual Research Report
  • [Presentation] 悪性胸膜中皮腫における組織レベルの3次元形態解析法の構築 浸潤形態と腫瘍微小環境の関連性

    • Author(s)
      工藤朝雄, 島津徳人, 佐藤鮎子, 篠原義康, 鳥井郁子, 青葉孝昭, 辻村亨
    • Organizer
      第54回日本組織細胞化学会総会・学術集会
    • Place of Presentation
      航空会館
    • Related Report
      2013 Annual Research Report
  • [Book] 胸膜全書‐胸膜疾患のグローバルスタンダード‐2013

    • Author(s)
      辻村亨, 佐藤鮎子, 他
    • Publisher
      医薬ジャーナル社
    • Related Report
      2013 Final Research Report
  • [Book] 胸膜全書‐胸膜疾患のグローバルスタンダード‐2013

    • Author(s)
      中野孝司 編, 辻村亨, 佐藤鮎子 他
    • Total Pages
      400
    • Publisher
      医薬ジャーナル社
    • Related Report
      2013 Annual Research Report
  • [Book] 癌診療指針のための病理診断プラクティス2011

    • Author(s)
      辻村亨, 鳥井郁子, 佐藤鮎子, 他
    • Publisher
      中山書店
    • Related Report
      2013 Final Research Report
  • [Book] 癌診療指針のための病理診断プラクティス 肺癌 (青笹克之 総編集、松原修 専門編集)、4章 胸膜腫瘍の概要と鑑別診断 中皮腫の初期病変2011

    • Author(s)
      辻村 亨 (分担執筆)
    • Total Pages
      376
    • Publisher
      中山書店
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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