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Identification of a factor determining invasion and metastasis in non-small cell lung cancer and its therapeutic application based on comprehensive microRNA analysis

Research Project

Project/Area Number 26461195
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionJichi Medical University

Principal Investigator

NOBUYUKI KOYAMA  自治医科大学, 医学部, 非常勤講師 (30353460)

Co-Investigator(Renkei-kenkyūsha) ENDOU Shunsuke  自治医科大学, 医学部, 教授 (10245037)
ISHIKAWA Yuichi  癌研究会, 病理部, 部長 (80222975)
TSUBOCHI Hiroyoshi  自治医科大学, 医学部, 准教授 (50406055)
Research Collaborator WATANABE Yasutaka  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords肺癌 / EZH2 / siRNA / マイクロRNA / 網羅的発現解析 / miR-4448 / 小細胞肺癌 / EMT / 網羅解析 / 転移 / 癌性胸膜炎 / EZH2発現 / マイクロRNA発現 / 非小細胞肺癌
Outline of Final Research Achievements

High protein expressions of enhancer of zeste homolog 2 (EZH2) and the induction of epithelial-mesenchymal transition (EMT).were observed in most cases of small cell lung cancer (SCLC). EZH2 siRNA was transfected into SCLC cell lines, SBC3 and SBC5 cells with high EZH2 expression, consequently leading to the repression of EMT. Comprehensive microRNA (miRNA) expression analysis detected increased or decreased expressions of multiple miRNAs in SBC3 and SBC5 cells transfected with EZH2 siRNA. Of these miRNAs, miR-4448 that showed the most significant increase of expression was defined as a candidate miRNA for the target of EZH2.
Functional analyses for miR-4448 showed that along with EMT, cellular proliferative, invasive, and metastatic potentials were significantly repressed in SBC3 and SBC5 cells transfected with mimics of miR-4448, compared to those transfected with negative controls. EZH2 may serve as an oncogene that induces EMT through repressing miR-4448 expression and its function.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (32 results)

All 2017 2016 2015 2014

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (21 results) (of which Int'l Joint Research: 2 results) Book (4 results)

  • [Journal Article] Distinct benefit of overall survival between patients with non-small cell lung cancer harboring EGFR exon 19 deletion and exon 21 L858R substitution.2017

    • Author(s)
      Koyama N, Watanabe Y, Iwai Y, Kawamura R, Miwa C, Nagai Y, Hagiwara K, Koyama S.
    • Journal Title

      Chemotherapy

      Volume: 62 Issue: 3 Pages: 151-8

    • DOI

      10.1159/000454944

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment and outcomes of advanced/recurrent non-small cell lung cancer harboring the EGFR T790M mutation: a retrospective observational study of 141 patients in Japan.2016

    • Author(s)
      Yamane Y, Shiono A, Ishii Y, Isobe K, Miyauchi E, Kishi K, Nishino M, Sugawara S, Ko R, Koyama N, Yabuki Y, Kobayashi K.
    • Journal Title

      Japanese Journal of Clinical Oncology

      Volume: 46 Pages: 1135-42

    • DOI

      10.1093/jjco/hyw124

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EGFR遺伝子変異陽性進行非小細胞肺癌に対する治療戦略2016

    • Author(s)
      小山信之
    • Journal Title

      東京医科大学雑誌

      Volume: 74 Pages: 256-67

    • NAID

      40020988214

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful alectinib treatment for a mechanically ventilated patient with ALK-positive non-small cell lung cancer.2016

    • Author(s)
      Watanabe Y, Koyama N, Iwai Y, Kawamura R, Miwa C, Nagai Y, Koyama S.
    • Journal Title

      Annals of Cancer Research and Therapy

      Volume: 24 Pages: 47-51

    • NAID

      130005285070

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] メトトレキサート関連リンパ腫様肉芽腫症の一剖検例2016

    • Author(s)
      伊藤祥子,白石守,岩井悠希,三輪千尋,渡辺恭孝,小山信之,野首光弘,賀古真一,小山信一郎
    • Journal Title

      自治医科大学紀要

      Volume: 38 Pages: 65-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and biological significance of erlotinib therapy after pemetrexed in non-small cell lung cancer with wild-type EGFR.2015

    • Author(s)
      Koyama N, Suzuki M.
    • Journal Title

      Neoplasma

      Volume: 62 Issue: 06 Pages: 996-1004

    • DOI

      10.4149/neo_2015_121

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] 一過性肺浸潤を認めた血管内悪性リンパ腫の1例2015

    • Author(s)
      川村留美、渡辺恭孝、岩井悠希、白石守、三輪千尋、小山信之、小山信一郎
    • Journal Title

      気管支学

      Volume: 37 Pages: 649-55

    • NAID

      110010015649

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 当院の進展型肺小細胞癌における間質性肺炎の有無の影響および予後因子の検討2016

    • Author(s)
      岩井悠希、渡辺恭孝、工藤史明、三輪千尋、長井良昭、太田洋充、小山信一郎、萩原弘一、小山信之
    • Organizer
      第57回日本肺癌学会学術集会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] EGFR遺伝子変異非小細胞肺癌におけるExon1 9欠失の全生存期間延長2016

    • Author(s)
      小山信之、渡辺恭孝、長井良昭、岩井悠希、川村留美、三輪千尋、工藤史明、萩原弘一、小山信一郎
    • Organizer
      第57回日本肺癌学会学術集会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 進行肺扁平上皮癌に対するnedaplatin+nab-paclitaxel併用第I/II相試験KRSG(関東呼吸器研究会)1302 study2016

    • Author(s)
      笠井尚、森清志、小山信之、星永進、中山光男、小林国彦
    • Organizer
      第57回日本肺癌学会学術集会
    • Place of Presentation
      福岡市
    • Year and Date
      2016-12-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] Effectiveness of nab-paclitaxel for malignant effusion in non-small cell lung cancer.2016

    • Author(s)
      Iwai Y, Koyama N, Watanabe Y, Miwa C, Nagai Y, Koyama S.
    • Organizer
      ESMO Asia 2016 Congress
    • Place of Presentation
      シンガポール
    • Year and Date
      2016-12-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 町田市と南町田病院における乳癌検診の現状2016

    • Author(s)
      石川裕子、小山信之、後藤哲宏、佐々木健志、天谷圭吾、矢野正雄
    • Organizer
      第26回日本乳癌検診学会学術総会
    • Place of Presentation
      福岡県久留米市
    • Year and Date
      2016-11-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] 乳癌化学療法におけるペグフィルグラスチム使用に対する後ろ向き検討2016

    • Author(s)
      石川裕子、小山信之、高坂聡、天谷圭吾、柴崎ゆかり、森田春菜、吉元公一、奥山清、三坂武温、林光弘
    • Organizer
      第54回日本癌治療学会学術集会
    • Place of Presentation
      横浜市
    • Year and Date
      2016-10-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] Overall survival benefit in non-small cell lung cancer harboring EGFR exon 19 deletion.2016

    • Author(s)
      Watanabe Y, Hagiwara K, Koyama N.
    • Organizer
      The 75th Annual Meeting of the Japanese Cancer Association
    • Place of Presentation
      横浜市
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 進行非小細胞肺癌胸腹水貯留例のnab-PTXの効果の検討2016

    • Author(s)
      岩井悠希、渡辺恭孝、川村留美、三輪千尋、長井良昭、萩原弘一、小山信一郎、小山信之
    • Organizer
      第14回日本臨床腫瘍学会学術集会
    • Place of Presentation
      神戸市
    • Year and Date
      2016-07-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 経気管支肺生検で診断された血管内大細胞型リンパ腫の2例2016

    • Author(s)
      岩井悠希、渡辺恭孝、川村留美、三輪千尋、長井良昭、小山信之、小山信一郎、野首光弘
    • Organizer
      第39回日本呼吸器内視鏡学会学術集会
    • Place of Presentation
      名古屋市
    • Year and Date
      2016-06-23
    • Related Report
      2016 Annual Research Report
  • [Presentation] Prognostic factors in patients with advanced thymic carcinoma treated with chemotherapy: a retrospective analysis of 289 patients from NEJ023 Study.2016

    • Author(s)
      Okuma Y, Ko R, Shukuya T, Tateishi K, Imai H, Miyauchi E, Fujiwara A, Sugiyama T, Azuma K, Muraki K, Yamasaki M, Tanaka H, Takashima Y, Soda S, Ishimoto O, Koyama N, Kuyama S, Murase K, Morita S, Takahashi K.
    • Organizer
      The 2016 Annual Meeting of the American Society of Clinical Oncology
    • Place of Presentation
      アメリカ イリノイ州 シカゴ
    • Year and Date
      2016-06-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 間質性肺炎合併小細胞肺癌における治療の検討2016

    • Author(s)
      岩井悠希、小山信之、渡辺恭孝、三輪千尋、長井良昭、萩原弘一、小山信一郎
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      京都市
    • Year and Date
      2016-04-08
    • Related Report
      2016 Annual Research Report
  • [Presentation] 当院における短時間少量補液(short hydration [SH])を用いたシスプラチン併用化学療法の安全性・有効性の検討2015

    • Author(s)
      岩井悠希、小山信之、川村留美、三輪千尋、渡辺恭孝、長井良昭、萩原弘一、小山信一郎、鈴木栄
    • Organizer
      第56回日本肺癌学会総会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
  • [Presentation] EGFR遺伝子変異陽性非小細胞肺癌に対しEGFR-TKI投与後の再燃部位の検討2015

    • Author(s)
      長井良昭、渡辺恭孝、岩井悠希、野村基子、川村留美、三輪千尋、小山信之、萩原弘一、小山信一郎
    • Organizer
      第56回日本肺癌学会総会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 人工呼吸器管理中にアレクチニブを開始し著効したALK陽性肺腺癌の1例2015

    • Author(s)
      渡辺恭孝,小山信之,岩井悠希,川村留美,三輪千尋,長井良昭,萩原弘一,小山信一郎
    • Organizer
      第56回日本肺癌学会総会
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Relationship between expression of enhancer of EZH2 and EMT in small cell lung cancer.2015

    • Author(s)
      Watanabe Y, Koyama N, Muto Y, Suzuki K, Ishikawa Y, Hagiwara K.
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] エルロチニブによる皮膚障害対策に対する予防効果の検討2015

    • Author(s)
      鈴木栄、新津京介、北弥生、小山信之、堀口久光
    • Organizer
      第45回日本病院薬剤師会学術大会
    • Place of Presentation
      茨城県つくば市
    • Year and Date
      2015-08-01
    • Related Report
      2015 Research-status Report
  • [Presentation] EGFR-TKIが投与されたEGFR遺伝子変異陽性非小細胞肺癌の再燃の検討2015

    • Author(s)
      渡辺恭孝、小山信之、岩井悠希、川村留美、三輪千尋、小山信一郎
    • Organizer
      第13回日本臨床腫瘍学会学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2015-07-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Abundant expression of enhancer of zeste homolog 2 in small cell lung cancer2015

    • Author(s)
      Yasutaka Watanabe, Nobuyuki Koyama, Yuki Iwai, Chihiro Miwa, Shinichiro Koyama
    • Organizer
      American Association for Cancer Research Annual Meeting 2015
    • Place of Presentation
      Philadelphia, PA, USA
    • Year and Date
      2015-04-19
    • Related Report
      2014 Research-status Report
  • [Presentation] 当院における高齢者非小細胞肺癌に対するEGFR-TKI使用症例の検討2015

    • Author(s)
      岩井悠希、渡辺恭孝、野村基子、川村留美、三輪千尋、長井良昭、小山信之、小山信一郎
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      東京
    • Year and Date
      2015-04-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 小細胞肺癌切除34症例の臨床的検討2014

    • Author(s)
      渡辺恭孝、小山信之、岩井悠希、白石守、川村留美、三輪千尋、坪地宏嘉、遠藤俊輔、小山信一郎
    • Organizer
      第55回日本肺癌学会学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] 小細胞肺癌切除34症例の臨床的検討2014

    • Author(s)
      渡辺恭孝、小山信之、岩井悠希、白石守、三輪千尋、坪地宏嘉、遠藤俊輔、小山信一郎
    • Organizer
      第54回日本呼吸器学会学術講演会
    • Place of Presentation
      大阪市
    • Year and Date
      2014-04-26
    • Related Report
      2014 Research-status Report
  • [Book] Drug-Induced Lung Injury2017

    • Author(s)
      Koyama N.
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] 気管支喘息の診断と治療〜COPD合併例を含めて〜2016

    • Author(s)
      小山信之
    • Total Pages
      6
    • Publisher
      北足立郡市医師会
    • Related Report
      2015 Research-status Report
  • [Book] 肺癌薬物療法の進歩と支持療法2016

    • Author(s)
      長井良昭、小山信之
    • Total Pages
      5
    • Publisher
      医学書院
    • Related Report
      2015 Research-status Report
  • [Book] Chapter 14 Common pathways in IPF and lung cancer. Idiopathic Pulmonary Fibrosis - Advances in Diagnostic Tools and Disease Management2015

    • Author(s)
      Koyama N.
    • Total Pages
      11
    • Publisher
      Spiringer
    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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