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Investigation of chemoradiation sensitivity based on the DNA repair mechanism in esophageal carcinoma

Research Project

Project/Area Number 26461980
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

Ito Shuhei  九州大学, 大学病院, 講師 (10706914)

Co-Investigator(Kenkyū-buntansha) 岡野 慎士  九州大学, 医学研究院, 准教授 (10380429)
森田 勝  独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 消化器外科部長 (30294937)
北尾 洋之  九州大学, 医学研究院, 准教授 (30368617)
池田 哲夫  九州大学, 大学病院, 准教授 (60585701)
沖 英次  九州大学, 大学病院, 講師 (70380392)
佐伯 浩司  九州大学, 医学研究院, 准教授 (80325448)
中島 雄一郎  九州大学, 医学研究院, 助教 (40733564)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsDNA2重鎖修復 / 染色体不安定性 / 姉妹染色分体交換 / PARP阻害剤 / 腫瘍免疫 / PD-L1 / HLA ClassⅠ / 食道癌 / 化学放射線療法
Outline of Final Research Achievements

We quantified cytogenetic alterations of human cells exposed to PARPi by both sister chromatid exchange (SCE) assays and chromosome spreading. Clinically relevant doses of the FDA-approved olaparib led to a marked increase of SCEs (5-10-fold) and chromatid aberrations (2-6-fold). Genomic instability arising from PARPi warrants consideration, especially if these agents will be used in people with early stage cancers, in prevention strategies or for non-oncologic indications.
Programmed cell death 1 ligand 1 (PD-L1) and human leukocyte antigen (HLA) class I molecules on malignant cell surfaces are pivotal for tumor immunity. PD-L1 and HLA class I protein expression was investigated by immunohistochemical staining of resected specimens from 90 ESCC patients who underwent radical surgery without preoperative therapy. High PD-L1 expression was a significant independent prognostic factor in ESCC patients with high HLA class I expression.

Report

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

    (6 results)

All 2016 2015

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

  • [Journal Article] PARP Inhibitors in Clinical Use Induce Genomic Instability in Normal Human Cells2016

    • Author(s)
      Shuhei Ito, Conleth G. Murphy, Ekaterina Doubrovina, Maria Jasin, Mary Ellen Moynahan
    • Journal Title

      PLOS ONE

      Volume: 11 Issue: 7 Pages: e0159341-e0159341

    • DOI

      10.1371/journal.pone.0159341

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression of PD-L1 and HLA Class I in Esophageal Squamous Cell Carcinoma: Prognostic Factors for Patient Outcome.2016

    • Author(s)
      Ito S, Okano S, Morita M, Saeki H, Tsutsumi S, Tsukihara H, Nakashima Y, Ando K, Imamura Y, Ohgaki K, Oki E, Kitao H, Mimori K, Maehara Y.
    • Journal Title

      Ann Surg Oncol.

      Volume: 23(Suppl 4) Issue: S4 Pages: 508-515

    • DOI

      10.1245/s10434-016-5376-z

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical and biological significance of circulating tumor cells in cancer.2016

    • Author(s)
      Masuda T, Hayashi N, Iguchi T, Ito S, Eguchi H, Mimori K.
    • Journal Title

      Mol Oncol.

      Volume: 10 Issue: 3 Pages: 408-17

    • DOI

      10.1016/j.molonc.2016.01.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 食道扁平上皮癌におけるZNF750発現の意義について2015

    • Author(s)
      南原翔、澤田元太、新井田厚司、内龍太郎、新田吉陽、井口友宏、江口英利、伊藤修平、増田隆明、杉町圭史、前原喜彦、三森功士
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] 食道癌におけるPD-L1、HLA classⅠ発現を用いた腫瘍免疫能評価と予後の関連性に関する検討2015

    • Author(s)
      伊藤 修平
    • Organizer
      第70回 日本消化器外科学会定期学術集会
    • Place of Presentation
      浜松
    • Year and Date
      2015-07-15
    • Related Report
      2015 Research-status Report
  • [Presentation] 食道扁平上皮癌におけるPD-L1、HLA classⅠ発現の臨床的意義2015

    • Author(s)
      伊藤 修平
    • Organizer
      第115回日本外科学会定期学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-04-16 – 2015-04-18
    • Related Report
      2014 Research-status Report

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

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