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Development of a novel method of radiotherapy for esophageal carcinoma by synergy effect with the selective inhibitor of cancer stem cells

Research Project

Project/Area Number 17K16454
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Radiation science
Research InstitutionKyushu University

Principal Investigator

WAKIYAMA Hiroaki  九州大学, 大学病院, 助教 (70758375)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords放射線治療 / 食道扁平上皮癌 / 活性酸素 / CD44v / 癌幹細胞 / スルファサラジン / ROS / 放射線増感剤 / 放射線 / 放射線治療生物学 / 放射線治療増感剤
Outline of Final Research Achievements

Identification of new radiosensitizers for esophageal squamous cell carcinoma (ESCC) is required. CD44v is recognized as a marker for cancer stem cells and regulates redox status in cancer cells by stabilizing the xCT. In this study, we investigated the radiosensitizing effect of sulfasalazine that is an inhibitor of xCT. We found that sulfasalazine improved radiosensitivity in ESCC. Moreover, we found that the association of elevated CD44v expression level with radiotherapy resistance in ESCC. These results suggest that combining radiotherapy with sulfasalazine could be a therapeutic option for ESCC and ectopic expression CD44v could be a novel biomarker of radiotherapy resistance.

Academic Significance and Societal Importance of the Research Achievements

食道扁平上皮癌への化学放射線療法は手術と並ぶ標準治療として確立しているが、放射線抵抗性の改善が喫緊の課題である。放射線による抗腫瘍効果は活性酸素(Reactive oxygen species:ROS)産生によるものが主である。癌幹細胞はROS を抑制するCD44v を発現しており、放射線抵抗性の原因と考えられている。本研究ではスルファサラジンの併用で、食道扁平上皮癌細胞で放射線感受性が増加することや、CD44vの高発現と食道扁平上皮癌の放射線治療抵抗性との関連を示した。スルファサラジンは有望な放射線増感剤であり、今後は前臨床試験としての位置づけで有効性に関するエビデンスを蓄積していきたい。

Report

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

    (5 results)

All 2018 2017

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

  • [Journal Article] Cytolytic Activity (CYT) Score Is a Prognostic Biomarker Reflecting Host Immune Status in Hepatocellular Carcinoma (HCC).2018

    • Author(s)
      Wakiyama H, Masuda T, Motomura Y, Hu Q, Tobo T, Eguchi H, Sakamoto K, Hirakawa M, Honda H, Mimori K.
    • Journal Title

      Anticancer Res

      Volume: 38(12) Issue: 12 Pages: 6631-6638

    • DOI

      10.21873/anticanres.13030

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b-SM esophageal squamous cell carcinoma improves locoregional control.2018

    • Author(s)
      Hisano O, Nonoshita T, Hirata H, Sasaki T, Watanabe H, Wakiyama H, Ono M, Ohga S, Honda H.
    • Journal Title

      Radiation Oncology

      Volume: 29 Issue: 1 Pages: 14-14

    • DOI

      10.1186/s13014-018-0960-y

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Cytolytic act ivity (CYT) is a prognostic biomarker reflecting host immune status of hepatocellular carcinoma (HCC)2018

    • Author(s)
      Wakiyama H, Masuda T, Kouyama Y, Yoshikawa Y, Sato K, Tsuruda Y, Otsu H, Kuroda Y, Eguchi H, Mimori K
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 胃癌及び 肝細胞癌におけるCytolytic activity (CYT)の臨床的意義2018

    • Author(s)
      脇山 浩明、増田 隆明、胡 慶江、鶴田 祐介、黒田 陽介、伊藤 修平、江口 英利、平川 雅和、松本 圭司、坂本 勝美、本田 浩、三森 功士
    • Organizer
      第39回癌免疫外科研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cytolytic activity (CYT)scoreは肝細胞癌の独立予後規定因子である2017

    • Author(s)
      脇山浩明、増田隆明、神山勇太、吉川幸宏、胡慶江、佐藤晋彰、齋藤衆子、林直樹、黒田陽介、伊藤修平、江口英利、三森功士
    • Organizer
      第76回日本癌学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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