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Pathological and molecular study of lung pleomorphic carcinomas to clarify the pathogenesis and develop novel treatment strategy

Research Project

Project/Area Number 16K10699
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory surgery
Research InstitutionKeio University

Principal Investigator

Hishida Tomoyuki  慶應義塾大学, 医学部(信濃町), 准教授 (40544664)

Research Collaborator KURIYAMA Shoji  
NAKAGOMI Takahiro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords呼吸器外科学 / 病理学 / 腫瘍学
Outline of Final Research Achievements

We performed clinicopathological and molecular study to clarify pathogenesis of lung cancer with sarcomatous component (LCSC) including pleomorphic carcinoma, which has high-grade malignancy. We reviewed our medical record and identified 23 patients who underwent resection for LCSC from 1996 to 2011. The 5-year recurrence-free survival was 56%, and 8 (35%) patients developed recurrence. Among them, 7 had recurrence within 1 year after surgery, and median post-recurrence survival was only 3 months. On the other hand, 5-year recurrence-free survivors were found in 6 (26%) patients, which suggested that LCSC might have 2 groups in terms of biological behavior; the poor outcome group as shown in previous studies and the favorable outcome group. Next, we conducted molecular analysis to clarify biological signatures in sarcomatous component, a characteristic component associating with malignant behavior of LCSC, comparing with non-sarcomatous component and non-cancerous area of each case.

Academic Significance and Societal Importance of the Research Achievements

多形癌に代表される「肉腫様成分を含む肺癌」は、原発性肺癌の中でも増殖が速く、他臓器やリンパ節に転移しやすい悪性度が高い腫瘍である。完全切除されても、術後再発は高頻度であり、また、現状の化学療法や放射線療法には抵抗性で、肺腺癌におけるEGFR遺伝子変異やALK融合遺伝子などの有効な治療標的も同定されていない。本研究は、難治癌である「肉腫様成分を含む肺癌」の新規治療開発の足がかりとなる基盤を構築するものであり学術的かつ社会的意義は非常に大きい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (21 results)

All 2018 2017 2016

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (2 results)

  • [Journal Article] Genomic Characteristics of Invasive Mucinous Adenocarcinomas of the Lung and Potential Therapeutic Targets of B7-H3.2018

    • Author(s)
      Nakagomi T, Goto T, Hirotsu Y, Shikata D, Yokoyama Y, Higuchi R, Otake S, Amemiya K, Oyama T, Mochizuki H, Omata M.
    • Journal Title

      Cancers (Basel)

      Volume: 10 Issue: 12 Pages: 478-478

    • DOI

      10.3390/cancers10120478

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New therapeutic targets for pulmonary sarcomatoid carcinomas based on their genomic and phylogenetic profiles.2018

    • Author(s)
      Nakagomi T, Goto T, Hirotsu Y, Shikata D, Yokoyama Y, Higuchi R, Amemiya K, Okimoto K, Oyama T, Mochizuki H, Omata M.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 12 Pages: 10635-10649

    • DOI

      10.18632/oncotarget.24365

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A randomized Phase III trial of lobe-specific vs. systematic nodal dissection for clinical Stage I-II non-small cell lung cancer (JCOG1413)2018

    • Author(s)
      Hishida T, Saji H, Watanabe S, Asamura H, Aokage K, Mizutani T, Wakabayashi M, Shibata T, Okada M and Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group
    • Journal Title

      Jpn J Clin Oncol

      Volume: 48 Issue: 2 Pages: 190-194

    • DOI

      10.1093/jjco/hyx170

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Survival and prognostic factors after pulmonary metastasectomy of head and neck cancer: what are the clinically informative prognostic indicators?2018

    • Author(s)
      Oki T, Hishida T, Yoshida J, Goto M, Sekihara K, Miyoshi T, Aokage K, Ishii G, Tsuboi M.
    • Journal Title

      Eur J Cardiothorac Surg.

      Volume: Nov 23 Issue: 5 Pages: 942-947

    • DOI

      10.1093/ejcts/ezy384

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extended bronchoplasty for locally advanced left lower lobe lung cancer: surgical technique and outcomes2018

    • Author(s)
      Hishida T, Aokage K, Yoshida J, Miyoshi T, Tsuboi M
    • Journal Title

      Interact Cardiovasc Thorac Surg

      Volume: Apr 2 Issue: 4 Pages: 602-605

    • DOI

      10.1093/icvts/ivy081

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical and pathological characteristics of EGFR mutation in operable early-stage lung adenocarcinoma2017

    • Author(s)
      Yotsukura M, Yasuda H, Shigenobu T, Kaseda K, Masai K, Hayashi Y, Hishida T, Ohtsuka T, Naoki K, Soejima K, Betsuyaku T, Asamura H
    • Journal Title

      Lung Cancer

      Volume: 109 Pages: 45-51

    • DOI

      10.1016/j.lungcan.2017.04.014

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung2017

    • Author(s)
      Miyoshi T, Umemura S, Matsumura Y, Mimaki S, Tada S, Makinoshima H, Ishii G5, Udagawa H, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Aokage K, Hishida T, Yoshida J, Nagai K, Goto K, Tsuboi M, Tsuchihara K.
    • Journal Title

      Clini Cancer Res

      Volume: 23 Issue: 3 Pages: 757-765

    • DOI

      10.1158/1078-0432.ccr-16-0355

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological significance of caveolin-1 expression by cancer-associated fibroblasts in lung adenocarcinoma2017

    • Author(s)
      K.Shimizu, K.Kirita, K.Aokage, M.Kojima, T.Hishida, T.Kuwata, S.Fujii, A.Ochiai, K.Funai, J.Yoshida, M.Tsuboi, G.Ishii
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: 143 Issue: 2 Pages: 321-328

    • DOI

      10.1007/s00432-016-2285-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Who are appropriate surgical candidates among patients with oligometastatic non-small cell lung cancer?2017

    • Author(s)
      Hishida, T.
    • Journal Title

      J Thorac Dis

      Volume: 9 Issue: 2 Pages: E149-E151

    • DOI

      10.21037/jtd.2017.02.25

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] The association of intravascular stromal cells with prognosis in high-grade neuroendocrine carcinoma of the lung2016

    • Author(s)
      Sekihara K, Hishida T, Ikemura S, Saruwatari K, Morise M, Kuwata T, Fujii S, Kojima M, Ochiai A, Funai K, Aokage K, Yoshida J, Tsuboi M, Ishii G.
    • Journal Title

      J Cancer Res Clin Oncol

      Volume: 142 Issue: 5 Pages: 905-912

    • DOI

      10.1007/s00432-015-2098-8

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Postoperative oligo-recurrence of non-small-cell lung cancer: clinical features and survival2016

    • Author(s)
      Hishida T, Yoshida J, Aokage K, Nagai K, Tsuboi M.
    • Journal Title

      Eur J Cardiothorac Surg

      Volume: 49 Issue: 3 Pages: 847-853

    • DOI

      10.1093/ejcts/ezv249

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lobe-Specific Nodal Dissection for Clinical Stage I and II NSCLC: Japanese Multi-Institutional Retrospective Study Using a Propensity Score Analysis2016

    • Author(s)
      Hishida T, Miyaoka E, Yokoi K, Tsuboi M, Asamura H, Kiura K, Takahashi K, Dosaka-Akita H, Kobayashi H, Date H, Tada H, Okumura M, Yoshino I; Japanese Joint Committee of Lung Cancer Registry.
    • Journal Title

      J Thorac Oncol

      Volume: 11 Issue: 9 Pages: 1529-1537

    • DOI

      10.1016/j.jtho.2016.05.014

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Microenvironmental changes in the progression from adenocarcinoma in situ to minimally invasive adenocarcinoma and invasive lepidic predominant adenocarcinoma of the lung2016

    • Author(s)
      M.Naito, K.Aokage, K.Saruwatari, K.Hisakane, T.Miyoshi, T.Hishida, J.Yoshida, S.Masato, M.Kojima, T.Kuwata, S.Fujii, A.Ochiai, Y.Sato, M.Tsuboi, G.Ishii
    • Journal Title

      Lung Cancer

      Volume: 100 Pages: 53-62

    • DOI

      10.1016/j.lungcan.2016.07.024

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 当院における肺肉腫様癌切除例の予後2017

    • Author(s)
      栗山 翔司,菱田 智之,鈴木 陽太,坂巻 寛之,志満 敏行,政井 恭兵,加勢田 馨,大塚 崇,林 雄一郎,淺村 尚生
    • Organizer
      第58回日本肺癌学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 原発性肺癌に対する至適なリンパ節郭清とは-臨床試験とその先-2017

    • Author(s)
      菱田 智之
    • Organizer
      第79回日本臨床外科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] “TYPE C” EXTENDED BRONCHOPLASTY FOR LOCALLY-ADVANCED LUNG CANCER2017

    • Author(s)
      Hishida T, Aokage K, Yoshida J, Miyoshi T, Tsuboi M
    • Organizer
      25th European Society of Thoracic Surgeons (ETST) meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 臨床病期I-II 期非小細胞肺癌に対する選択的リンパ節郭清の現状 肺癌登録合同委員会第5次事業2016

    • Author(s)
      菱田智之, 宮岡悦良, 横井香平, 坪井正博, 淺村尚生, 木浦勝行, 高橋和久, 秋田弘俊, 小林英夫, 伊達洋至, 多田弘人, 奥村明之進, 吉野一郎
    • Organizer
      第57回日本肺癌学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-12-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Multicenter Observational Study of Patients with Resected Early-Staged NSCLC, Who Were Excluded from an Adjuvant Chemotherapy Trial2016

    • Author(s)
      Hishida T, Tsuboi M, Yoh K, Takamochi K, Sakurai H, Goto Y, Shukuya T, Ohashi Y, Kunitoh H
    • Organizer
      IASLC 17th World Conference on Lung Cancer
    • Place of Presentation
      ウィーン(オーストリア)
    • Year and Date
      2016-12-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 分子標的治療を受けた進行肺癌の残存/増悪原発巣に対するsalvage surgery2016

    • Author(s)
      菱田智之, 吉田純司, 青景圭樹, 坪井正博
    • Organizer
      第33回日本呼吸器外科学会総会,パネルディスカッション
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report
  • [Book] 【呼吸器ジャーナル 肺癌 最新の治療戦略と失敗しないための秘訣】 I. 総論 肺癌の新TNM分類(第8版)について2017

    • Author(s)
      菱田智之, 大塚 崇, 淺村尚生
    • Total Pages
      176
    • Publisher
      医学書院
    • ISBN
      4260028855
    • Related Report
      2017 Research-status Report
  • [Book] 【呼吸器外科テキスト~外科専門医・呼吸器外科専門医をめざす人のために~】 日本呼吸器外科学会/呼吸器外科専門医合同委員会編 第VI章 肺の腫瘍性疾患 1.原発性肺癌 肺癌の症状2016

    • Author(s)
      菱田智之, 永井完治
    • Total Pages
      4
    • Publisher
      南江堂(東京都文京区)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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