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Development of therapeutic strategry breaking resistance to oxidative stress in glioma

Research Project

Project/Area Number 16K18454
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionKyushu University

Principal Investigator

Tsuchihashi Kenji  九州大学, 大学病院, 助教 (20773675)

Research Collaborator OKAZAKI Shogo  
OHMURA Mitsuyo  
ISHIKAWA Miyuki  
SAMPETREAN. Oltea  
ONISHI Nobuyuki  
WAKIMOTO Hiroaki  
YOSHIKAWA Momoko  
SEISHIMA Ryo  
IWASAKI Yoshimi  
MORIKAWA Takayuki  
ABE Shinya  
TAKAO Ayumi  
SHIMIZU Misato  
MASUKO Takashi  
NAGANE Motoo  
Frank Furnari  
AKIYAMA Tetsu  
SUEMATSU Makoto  
BABA Eishi  
AKASHI Koichi  
SAYA Hideyuki  
NAGANO Osamu  
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脳腫瘍 / xCT / 酸化ストレス / グルタチオン / グルタミン酸 / EGFR / 還元型グルタチオン
Outline of Final Research Achievements

Malignant glioma such as glioblastoma is a cancer still difficult to treat. xCT functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. Epidermal growth factor receptor (EGFR) interacts with xCT and thereby promotes its cell surface expression and function in human glioma cells. EGFR-expressing glioma cells manifested both enhanced antioxidant capacity as a result of increased cystine uptake as well as increased extracellular glutamate which promotes glioma matrix invasion. Targeted inhibition of xCT suppressed the EGFR-dependent enhancement of antioxidant capacity in glioma cells as well as tumor growth and invasiveness. Our findings propose that xCT is a promising therapeutic target in EGFR-overexpressing malignant glioma.

Report

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

    (5 results)

All 2017 2016 Other

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

  • [Int'l Joint Research] Harvard Medical School/UC San Diego(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Programmed death-ligand 1 expression is associated with fibrosarcomatous transformation of dermatofibrosarcoma protuberans2017

    • Author(s)
      K Tsuchihashi, H Kusaba, Y Yamada, Y Okumura, H Kumagai, M  Komoda, K Uchino, T Yoshihiro, N Tsuruta, F Hanamura, K  Inadomi, M Ito, K Sagara, M Nakano, K Nio, K Kohashi, S Arita, H Ariyama, R Tominaga, Y Oda, K Akashi, E Baba
    • Journal Title

      Molecular and Clinical Oncology

      Volume: 印刷中 Issue: 5 Pages: 665-668

    • DOI

      10.3892/mco.2017.1197

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-)2016

    • Author(s)
      Tsuchihashi K, Okazaki S, Ohmura M, Ishikawa M, Sampetrean O, Onishi N, Wakimoto H, Yoshikawa M, Seishima R, Iwasaki Y, Morikawa T, Abe S, Takao A, Shimizu M, Masuko T, Nagane M, Furnari FB, Akiyama T, Suematsu M, Baba E, Akashi K, Saya H, Nagano O.
    • Journal Title

      Cancer Research

      Volume: in press Issue: 10 Pages: 2954-2963

    • DOI

      10.1158/0008-5472.can-15-2121

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Glutaminolytic metabolism on CD44vhigh undifferentiated HNSCC cells enhances xCT dependency2017

    • Author(s)
      岡崎 章悟、新谷 昴、土橋 賢司、佐谷 秀行、永野 修
    • Organizer
      第76回日本癌学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-)2016

    • Author(s)
      土橋賢司、永野修、岡崎章悟、大村光代、サンペトラオルテア、吉川桃子、清島亮、大西伸幸、益子高、末松誠、馬場英司、赤司浩一、佐谷秀行
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-09
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-16  

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