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2013 Fiscal Year Final Research Report

Radio-immune fusion therapy for cancer; ER stress loading with radiation and celecoxib

Research Project

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Project/Area Number 24659644
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionUniversity of Tsukuba

Principal Investigator

TSUBOI Koji  筑波大学, 医学医療系, 教授 (90188615)

Co-Investigator(Renkei-kenkyūsha) OHNO Tadao  早稲田大学, 理工学術院, 客員教授 (90160580)
Project Period (FY) 2012-04-01 – 2014-03-31
Keywords悪性脳腫瘍 / 放射線 / 腫瘍免疫 / ERストレス / Celecoxib
Research Abstract

We found that the anti-inflammatory drug celecoxib significantly enhanced the radiosensitivity of mouse glioblastoma cells GL261 by loading ER stress. Based on this, we established GL261 cells constitutively expressing monomeric Kusabira-Orange (GL261-mKO) that were used to generate a mouse thigh subcutaneous tumor model in syngenic albino C57BL/6 mice, in which tumor size can be monitored by an in vivo imaging system. In experiments with local X-ray irradiation (IR) to tumors in this system, the cure rate was significantly higher with the concomitant oral administration of 5mg/kg of celecoxib as compared to IR alone. Furthermore, the same tumor cells that were re-challenged to the brain in the cured mice were all rejected, while they grew rapidly in mice that showed tumor regrowth after IR. ELISPOT assay demonstrated that IFN-gamma level was significantly elevated in mice that rejected re-challenged tumor cells, indicating that anti-tumor cellular immunity was established.

  • Research Products

    (10 results)

All 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (5 results)

  • [Journal Article] Homologous recombination pathway may play a major role in high-LET radiation-induced DNA double-strand break repair2014

    • Author(s)
      Gerelchuluun A, Zhu J, Su F, Asaithamby A, Chen DJ, Tsuboi K
    • Journal Title

      J Radiat Res

      Volume: 55 Suppl 1 Pages: i83-i84

    • DOI

      10.1093/jrr/rrt181

    • Peer Reviewed
  • [Journal Article] A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma2013

    • Author(s)
      Abei M, Okumura T, Fukuda K, Hashimoto T, Araki M, Ishige K, Hyodo I, Kanemoto A, Numajiri H, Mizumoto M, Sakae T, Sakurai H, Zenkoh J, Ariungerel G, Sogo Y, Ito A, Ohno T, Tsuboi K
    • Journal Title

      Radiat Oncol

      Volume: 8(1) Pages: 239

    • DOI

      10.1186/1748-717X-8-239

    • Peer Reviewed
  • [Journal Article] Celecoxib enhances radiosensitivity of hypoxic glioblastoma cells through endoplasmic reticulum stress2013

    • Author(s)
      Suzuki K, Gerelchuluun A, Hong Z, Sun L, Zenkoh J, Moritake T, Tsuboi K
    • Journal Title

      Neuro Oncol

      Volume: 15(9) Pages: 1186-99

    • DOI

      10.1093/neuonc/not062

    • Peer Reviewed
  • [Journal Article] Reirradiation for recurrent malignant brain tumor with radiotherapy or proton beam therapy : Technical considerations based on experience at a single institution2013

    • Author(s)
      Mizumoto M, Okumura T, Ishikawa E, Yamamoto T, Takano S, Matsumura A, Oshiro Y, Ishikawa H, Sakurai H, Tsuboi K
    • Journal Title

      Strahlenther Onkol

      Volume: 189(8) Pages: 656-663

    • DOI

      10.1007/s00066-013-0390-6

    • Peer Reviewed
  • [Journal Article] Proton beam therapy for intracranial and skull base tumors2013

    • Author(s)
      Mizumoto M, Oshiro Y, Tsuboi K
    • Journal Title

      Transl Cancer Res

      Volume: 2(2) Pages: 87-96

    • DOI

      10.3978/j.issn.2218-676X

    • Peer Reviewed
  • [Presentation] エックス線照射による腫瘍免疫応答的細胞死が脳内へ及ぼす影響2014

    • Author(s)
      善光純子、ゲレルチュルン・アリウンゲレル、洪正善、鈴木健之、孫略、伊東一也、三輪佳宏、坪井康次
    • Organizer
      第4回国際放射線神経生物学会大会
    • Place of Presentation
      高崎シティーギャラリー、高崎、群馬
    • Year and Date
      2014-01-17
  • [Presentation] 治療用陽子線とエックス線によるclustered DNA damageの形成2013

    • Author(s)
      石川隆昭、ゲレルチュルン・アリウンゲレル、洪正善、孫略、鈴木健之、善光純子、盛武敬、Aroumougame Asaithamby, David J. Chen、坪井康次
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜、神奈川
    • Year and Date
      20131003-05
  • [Presentation] 治療用陽子線とガンマ線によるDNA損傷修復メカニズムにおけるNHEJとHRの役割2013

    • Author(s)
      ゲレルチュルン・アリウンゲレル、石川隆昭、鈴木健之、洪正善、孫略、伊東一也、真鍋絵梨、善光純子、榮武二、盛武敬、Asaithamby A, David JC、坪井康次
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜、横浜、神奈川
    • Year and Date
      20131003-05
  • [Presentation] Lineal energy-based evaluation of oxidative DNA damage induced by proton beams and X-rays2013

    • Author(s)
      Zhengshan Hong, Yuki Kase, Takashi Moritake, Ariungerel Gerelchuluun, Lue Sun, Kenshi Suzuki, Kazunori Anzai, Takeji Sakae, Koji Tsuboi
    • Organizer
      52nd Annual Conference of the Particle Therapy Co-Operative Group (PTCOG 52)
    • Place of Presentation
      エッセンドイツ
    • Year and Date
      20130603-08
  • [Presentation] セレコキシブは、小胞体ストレスを負荷して低酸素下の膠芽腫細胞の放射線感受性を上げる2013

    • Author(s)
      鈴木健之、ゲレルチュルン・アリウンゲレル、洪正善、孫略、盛武敬、坪井康次
    • Organizer
      第19回癌治療増感研究会
    • Place of Presentation
      東京医科歯科大学、文京区、東京
    • Year and Date
      2013-06-08

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Published: 2015-06-25  

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