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Mechanisms on genesis of combined type small cell carcinoma; a study focusing on Notch signaling

Research Project

Project/Area Number 25460439
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Ito Takaaki  熊本大学, 生命科学研究部, 教授 (70168392)

Co-Investigator(Kenkyū-buntansha) NIIMORI Kanako  熊本大学, 大学院生命科学研究部, 助教 (30457600)
HASEGAWA Koki  京都薬科大学, 薬学部, 准教授 (50525798)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords小細胞肺癌 / 混合型 / Notchシグナル / エピジェネティクス / DNAメチル化 / ヒストン修飾 / 肺小細胞癌 / Notch1 / 神経内分泌分化 / 細胞接着 / epigenetics / histone修飾 / INSM-1 / エピジェネティックス / ヒストンアセチル化
Outline of Final Research Achievements

Combined type of small cell lung carcinoma (SCLC) has both small cell cancer and non-small cell carcinoma components such as adenocarcinoma and squamous cell carcinoma, which are positive for NOTCH1 and negative for INSM1, one of neuroendocrine transcription factor. Mechanisims of NOTCH1 expression in the process of genesis of the combined type SCLC could be epigenetically regulated. NOTCH1-negative classical SCLC cell lines expressed NOTCH1 after trichostatin A treatment, and Chip assay showed that level of acetylated histone H3 surrounding Notch1 promoter region was low in them. Taken together, genesis of combined type SCLC requires NOTCH expression, which could be regulated by histone modification.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (9 results)

All 2016 2015 2014

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 4 results,  Acknowledgement Compliant: 5 results) Presentation (1 results)

  • [Journal Article] Notch1 controls cell chemo-resistance in small cell lung carcinoma cells.2016

    • Author(s)
      Hassan WA, Yoshida R, Kudoh S, Kameyama H, Hasegawa K, Niimori-Kita K, Ito T
    • Journal Title

      Thoracic Cancer

      Volume: 7 Issue: 1 Pages: 123-128

    • DOI

      10.1111/1759-7714.12297

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Evaluation of role of Notch3 signaling pathway in human lung cancer cells.2016

    • Author(s)
      Hassan WA, Yoshida R, Kudoh S, Motooka Y, Ito T
    • Journal Title

      J. Cancer Res. Clin. Oncol.

      Volume: 142 Issue: 5 Pages: 981-993

    • DOI

      10.1007/s00432-016-2117-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Notch signaling and Tp53/RB1 pathway in pulmonary neuroendocrine tumorigenesis.2016

    • Author(s)
      Ito T, Hassa WA, Matsuo A
    • Journal Title

      Transl. Cancer Res.

      Volume: 5 Issue: 2 Pages: 213-219

    • DOI

      10.21037/tcr.2016.03.11

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Insulinoma-Associated protein 1 is a crucial regulator of neuroendocrine differentiation in lung cancer2015

    • Author(s)
      Fujino, Kosuke; Motooka, Yamato; Wael, Hassan; Ali Abdalla, Mohamed; Sato, Yonosuke; Kudoh, Shinji; Hasegawa, Koki; Niimori-Kita, Kanako; Kobayashi, Hironori; Kubota, Ichiro; Wakimoto, Joeji; Suzuki, Makoto; Takaaki, Ito
    • Journal Title

      The American Journal of Pathology

      Volume: 185 Issue: 12 Pages: 3164-3177

    • DOI

      10.1016/j.ajpath.2015.08.018

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma.2014

    • Author(s)
      Wael H, Yoshida R, Kudoh S, Hasegawa K, Kita-Niimori K, and Ito T
    • Journal Title

      Lung Cancer

      Volume: 85 Pages: 131-140

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines.2014

    • Author(s)
      Hassan WA, Yoshida R, Kudoh S, Hasegawa K, Niimori-Kita K, and Ito T
    • Journal Title

      Lung Cancer

      Volume: 86 Pages: 304-310

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma.2014

    • Author(s)
      Yoshida R, Nakayama H, Nagata Y, Hirosue A, Tanaka T, Kawahara K, Nakagawa Y, Matsuoka Y, Sakata J, Akita H, Hiraki A, Shinohara M, and Ito T
    • Journal Title

      Brit J Cancer

      Volume: 111 Issue: 12 Pages: 2308-2315

    • DOI

      10.1038/bjc.2014.539

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Notch1 Signaling Controls Cell Proliferation, Apoptosis and Differentiation in Lung Carcinoma2014

    • Author(s)
      Hassan W, Yoshida R, Kudoh S, Hasegawa K, Niimori-Kita K, and Ito T
    • Journal Title

      Lung Cancer

      Volume: 84

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 混合型小細胞肺癌におけるNotch1の発現意義と機構について2016

    • Author(s)
      伊藤隆明、本岡大和、藤野孝介、工藤信次、佐藤陽之輔
    • Organizer
      第105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-12
    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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