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Mre11-Rad50-Nbs1 complex inhibitor Mirin enhances radiosensitivity in human glioblastoma cells

Research Project

Project/Area Number 24592171
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cerebral neurosurgery
Research InstitutionSaitama Medical University

Principal Investigator

MISHIMA KAZUHIKO  埼玉医科大学, 医学部, 教授 (00282640)

Co-Investigator(Kenkyū-buntansha) KAWATA Tetsuya  慶應義塾大学, 医学部, 講師 (60234077)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsglioma / radiation therapy / radiosensitivity / Mre11-Rad50-Nbs1 / DNA damage / 放射線治療 / DNA 損傷 / 放射線増感 / MER11-RAD50-NBS1 / グリオーマ / DNA損傷 / MRE11-RAD50-NBS1 / DNA損傷
Outline of Final Research Achievements

Radiation therapy plays a central part in the treatment of glioblastoma, however, it is not curative due to the high tumor radioresistance. The Mre11, Rad 50 and Nbs1 proteins form a complex (MRN) that has a critical role in DNA damage detection and signaling. Here, we investigated the effects of the MRN complex inhibitor, Mirin, on radiation response of human glioma cells. Glioma cell lines were irradiated with and without Mirin and then clonogenicity, apoptosis, and cell cycle change were examined. Glioblastoma cells pretreated with Mirin demonstrated an enhanced sensitivity to radiation. FACS analysis revealed that the combination of Mirin and radiation treatments significantly increased the G2/M fraction of the glioma cells. Mirin enhanced radiation-induced apoptotic cell death and mitotic catastrophe. These results indicate that Mirin can effectively enhance glioma cell radiosensitivity. It suggests that Mirin is a potent radiosensitizer for treating glioma cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (36 results)

All 2015 2014 2013 2012 Other

All Journal Article (19 results) (of which Open Access: 5 results,  Peer Reviewed: 15 results) Presentation (17 results) (of which Invited: 6 results)

  • [Journal Article] Brainstem oligodendroglial tumors in children: two case reports and review of literatures.2015

    • Author(s)
      Fukuoka K, Yanagisawa T, Watanabe Y, Suzuki T, Shirahata M, Adachi J, Mishima K. et al
    • Journal Title

      Childs Nerv Syst.

      Volume: 31 Issue: 3 Pages: 449-455

    • DOI

      10.1007/s00381-014-2563-8

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 中枢神経系原発悪性リンパ腫2014

    • Author(s)
      三島一彦
    • Journal Title

      神経症候群 (第2版) 日本臨床

      Volume: 28 Pages: 323-331

    • Related Report
      2014 Annual Research Report
    • Open Access
  • [Journal Article] 高齢者初発中枢神経系原発悪性リンパ腫に対する照射回避免疫化学療法の治療成績2014

    • Author(s)
      三島一彦, 甲賀智之、白畑充章、鈴木智成、安達淳一、福岡講平、柳澤隆昭、渡辺裕子、西川 亮
    • Journal Title

      Geriatric Neurosurgery

      Volume: 26 Pages: 71-76

    • NAID

      40020904640

    • Related Report
      2014 Annual Research Report
  • [Journal Article] A Multicenter Phase I/II Study of the BCNU Implant (Gliadel<sup>®</sup> Wafer) for Japanese Patients with Malignant Gliomas2014

    • Author(s)
      Aoki T, Nishikawa R, Sugiyama K, Nonoguchi N, Kawabata N, Mishima K.et al
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 54 Issue: 4 Pages: 290-301

    • DOI

      10.2176/nmc.oa2013-0112

    • NAID

      130003383270

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MRE11-RAD50-NBS1 COMPLEX INHIBITOR MIRIN ENHANCES RADIOSENSITIVITY IN HUMAN GLIOBLASTOMA CELLS2014

    • Author(s)
      Mishima K, Masayo Mishima-Kaneko M, Saya H, Naozumi Ishimaru N, Yamada K, Fukada J, Nishikawa R, Kawata T
    • Journal Title

      Neuro-Oncology

      Volume: 16

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutually exclusive mutations of KIT and RAS are associated with KIT mRNA expression and chromosomal instability in primary intracranial pure germinomas.2014

    • Author(s)
      Fukushima S, Otsuka A, Suzuki T, Yanagisawa T, Mishima K. et al.
    • Journal Title

      Acta Neuropatholgica

      Volume: 127 Issue: 6 Pages: 911-925

    • DOI

      10.1007/s00401-014-1247-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Duration between onset and diagnosis in CNS tumors: impact on prognosis and functional outcome.2014

    • Author(s)
      Fukuoka K, Yanagisawa T, Suzuki T, Shirahata M, Adachi JI, Mishima K. et al
    • Journal Title

      Pediatr Int

      Volume: 56 Issue: 6 Pages: 829-833

    • DOI

      10.1111/ped.12369

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Multicenter Phase I/II Study of the BCNU Implant (Gliadel® Wafer) for Japanese Patients with Malignant Gliomas.2014

    • Author(s)
      Aoki T, Nishikawa R, Sugiyama K, Nonoguchi N, Kawabata N, Mishima K, Adachi JI, Kurisu K, Yamasaki F, Tominaga T, Kumabe T, Ueki K, Higuchi F, Yamamoto T, Ishikawa E, Takeshima H, Yamashita S, Arita K, Hirano H, Yamada S, Matsutani M.
    • Journal Title

      Neurol Med Chir (Tokyo)

      Volume: 54 Pages: 290-301

    • NAID

      130003383270

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 中枢神経系原発悪性リンパ腫治療 update2013

    • Author(s)
      三島一彦
    • Journal Title

      Clinical Neuroscience

      Volume: 31 Pages: 1205-1208

    • Related Report
      2013 Research-status Report
  • [Journal Article] Cadherin 13 overexpression as an important factor related to the absence of tumor fluorescence in 5-aminolevulinic acid-guided resection of glioma.2013

    • Author(s)
      Suzuki T, Wada S, Eguchi H, Adachi J, Mishima K, Matsutani M, Nishikawa R, Nishiyama M.
    • Journal Title

      J. Neurosurgery

      Volume: 119 Pages: 1331-1339

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunochemotherapy with rituximab and methotorexate with deferred radiotherapy for newly diagnosed primary CNS lymphoma (PCNSL) in the elderly2013

    • Author(s)
      Mishima K, Adachi J, Suzuki T, Uchida E, Yanagawa T, Watanabe Y, Fukuoka K, Yanagisawa T, Wakiya K, Fujimaki T, Nishikawa R.
    • Journal Title

      Neuro-Oncology

      Volume: 15

    • NAID

      40020904640

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Application of rapid IDH1 gene mutation analysis for pathological diagnosis during glioma surgery2013

    • Author(s)
      Adachi J, Totake K, Shirahata M, Mishima K, Nishikawa R.
    • Journal Title

      Neuro-Oncology

      Volume: 15

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Randomized trial of chemoradiotherapy and adjuvant chemotherapy with nimustine versus nimustine plus procarbazine for newly diagnosed anaplastic astrocytoma and glioblastoma .2013

    • Author(s)
      Shibui S, Narita Y, Mizusawa J, Beppu T, Ogasawara K, Sawamura Y, Kobayashi H, Nishikawa R, Mishima K, Muragaki Y, Maruyama T, Kuratsu J, Nomura K etl .
    • Journal Title

      Cancer Chemother Pharmacol.

      Volume: 71(2) Issue: 2 Pages: 511-21

    • DOI

      10.1007/s00280-012-2041-5

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Central Nervous System Lymphoma Initially Diagnosed as Tumefactive Multiple Sclerosis after Brain Biopsy2013

    • Author(s)
      Ohe Y, Hayashi T, Mishima K, Nishikawa R, Sasaki A, Matsuda H, Uchino A, Tanahashi N.
    • Journal Title

      Internal Medicine

      Volume: 52 Issue: 4 Pages: 483-488

    • DOI

      10.2169/internalmedicine.52.8531

    • NAID

      130003365894

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 再発中枢神経系原発悪性リンパ腫の治療2012

    • Author(s)
      三島一彦
    • Journal Title

      癌と化学療法

      Volume: 39 Pages: 898-905

    • Related Report
      2012 Research-status Report
  • [Journal Article] Higher incidence of epilepsy in meningiomas located on the premotor cortex: a voxel-wise statistical analysis.2012

    • Author(s)
      Hamasaki T, Yamada K, Yano S, Nakamura H, Makino K, Hide T, Hasegawa Y, Kuroda J, Hirai T, Kuratsu J.
    • Journal Title

      Acta Neurochir (Wien)

      Volume: 154(12) Issue: 1 Pages: 1-7

    • DOI

      10.1007/s00701-012-1514-y

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pineal parenchymal tumor of intermediate differentiation with marked elevation of MIB-1 labeling index.2012

    • Author(s)
      Fukuoka K, Sasaki A, Yanagisawa T, Suzuki T, Wakiya K, Adachi J, Mishima K, Fujimaki T, Matsutani M, Nishikawa R
    • Journal Title

      Brain Tumor Pathol

      Volume: 29 Issue: 4 Pages: 229-234

    • DOI

      10.1007/s10014-012-0089-x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Salvage immuno-chemotherapy with a combination of rituximab and high-dose methotrexate for patients with primary CNS lymphoma2012

    • Author(s)
      Mishima K, Suzuki T, Adachi J, Koga T, Fukuoka K, Yanagisawa T, Fujimaki T, Nishikawa R.
    • Journal Title

      Neuro-oncology

      Volume: 14

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical analysis-based proteomic subclassification of newly diagnosed glioblastomas with integrated genomic and epigenetic profiles2012

    • Author(s)
      Motomura K, Natsume A, Watanabe R, Ito I, Kato Y, Momota H, Nishikawa R, Mishima K, Nakasu Y, Abe T, Namba H, Nakazato Y, Tashiro H, Takeuchi I, Mori T, Wakabayash T.
    • Journal Title

      Cancer Sci.

      Volume: 103(10) Issue: 10 Pages: 1871-1879

    • DOI

      10.1111/j.1349-7006.2012.02377.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 再発・治療抵抗性中枢神経原発悪性リンパ腫に対する治療:Pemetresed療法の有効性2014

    • Author(s)
      三島一彦、白畑充章、鈴木智成、安達淳一、内田栄太、藤巻高光、西川 亮
    • Organizer
      第32回日本脳腫瘍学会学術集会
    • Place of Presentation
      シェラトン・グランデ・トウキョーベイホテル(千葉県浦安市)
    • Year and Date
      2014-11-30 – 2014-12-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] BCNU wafers留置後の留意点と使用経験2014

    • Author(s)
      三島一彦
    • Organizer
      第32回日本脳腫瘍学会
    • Place of Presentation
      シェラトン・グランデ・トウキョーベイホテル(千葉県浦安市)
    • Year and Date
      2014-11-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Mre11-Rad50-Nbs1 complex inhibitor Mirin enhances radiosensitivity in human glioblastoma cells.2014

    • Author(s)
      Mishima K, Mishima-Kaneko M, Saya H , Ishimara N, Yamada K, Fukada J, Nishikawa R, Kawata T.
    • Organizer
      19th Annual Scientific Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      Miami, Florida, USA
    • Year and Date
      2014-11-13 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 悪性神経膠腫に対するアバスチン治療2014

    • Author(s)
      三島一彦
    • Organizer
      北総脳腫瘍研究会
    • Place of Presentation
      成田ヒルトン (千葉県成田市)
    • Year and Date
      2014-10-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 再発・治療抵抗性中枢神経原発悪性リンパ腫に対するPemetrexed療法の経験2014

    • Author(s)
      三島一彦、白畑充章、鈴木智成、安達淳一、内田栄太、藤巻高光、西川 亮
    • Organizer
      第73回日本脳神経外科学会総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都港区)
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Mre11-Rad50-Nbs1 complex inhibitor Mirin enhances radiosensitivity in human glioblastoma cells.2014

    • Author(s)
      Mishima K, Mishima-Kaneko M, Kawata T, Saya H, Ishimara N, Yamada K, Nishikawa R, Shigematsu N.
    • Organizer
      20th International Conference on Brain Tumor Research and Therapy.
    • Place of Presentation
      Lake Tahoe,California, USA
    • Year and Date
      2014-07-20 – 2014-07-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 悪性神経膠腫に対するアバスチン治療2014

    • Author(s)
      三島一彦
    • Organizer
      第34回日本脳神経外科コングレス総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2014-05-16
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Immunochemotherapy with rituximab and methotorexate with deferred radiotherapy for newly diagnosed primary CNS lymphoma (PCNSL) in the elderly2013

    • Author(s)
      Mishima K, Adachi J, Suzuki T, Uchida E, Yanagawa T, Watanabe Y, Fukuoka K, Yanagisawa T, Wakiya K, Fujimaki T, Nishikawa R.
    • Organizer
      4th Quadrennial Meeting of the World Federation of Neuro-Oncology
    • Place of Presentation
      San Francisco, 米国
    • Related Report
      2013 Research-status Report
  • [Presentation] 悪性神経膠腫摘出術におけるBCNU Implant (Gliadel® Wafer)の使用経験2013

    • Author(s)
      三島一彦、安達淳一、白畑充章、鈴木智成、内田栄太、渡辺 祐子、福岡講平、柳澤隆昭、西川 亮
    • Organizer
      第31回日本脳腫瘍学会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Research-status Report
  • [Presentation] 中枢神経原発悪性リンパ腫の治療:Up to date2013

    • Author(s)
      三島一彦
    • Organizer
      日本脳神経外科学会 第72回学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 5-ALAを用いた神経膠腫摘出術・脳神経外科領域での有用性2013

    • Author(s)
      三島一彦
    • Organizer
      日本脳神経外科学会 第72回学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Salvage immuno-chemotherapy with a combination of rituximab and high-dose methotrexate for patients with primary CNS lymphoma2012

    • Author(s)
      Mishima K, Suzuki T, Adachi J, Koga T, Fukuoka K, Yanagisawa T, Fujimaki T, Matsutani M, Nishikawa R.
    • Organizer
      The 19th International Brain Tumor Research and Therapy Conference
    • Place of Presentation
      Niagara Falls, Canada
    • Related Report
      2012 Research-status Report
  • [Presentation] Salvage immuno-chemotherapy with a combination of rituximab and high-dose methotrexate for patients with primary CNS lymphoma2012

    • Author(s)
      Mishima K, Suzuki T, Adachi J, Koga T, Fukuoka K, Yanagisawa T, Fujimaki T, Nishikawa R
    • Organizer
      10th Congress of European Association of NeuroOncology
    • Place of Presentation
      Marseille, France
    • Related Report
      2012 Research-status Report
  • [Presentation] 高齢者初発中枢神経系原発悪性リンパ腫に対する照射を回避した免疫化学療法の治療成績

    • Author(s)
      三島一彦、甲賀智之、鈴木智也, 安達淳一、柳澤隆昭, 藤巻高光、西川 亮
    • Organizer
      第71回日本脳神経外科学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 悪性脳腫瘍の標準 最新治療

    • Author(s)
      三島一彦
    • Organizer
      奈良脳腫瘍カンファレンス
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 高齢者初発中枢神経系原発悪性リンパ腫に対する照射を回避免疫化学療法の治療成績

    • Author(s)
      三島一彦、甲賀智之、白畑充章、鈴木智也, 安達淳一、福岡講平、柳澤隆昭, 藤巻高光、西川 亮
    • Organizer
      第30回日本脳腫瘍学会学術集会
    • Place of Presentation
      広島
    • Related Report
      2012 Research-status Report
  • [Presentation] 高齢者初発中枢神経系原発悪性リンパ腫に対する照射を回避した免疫化学療法の治療成績

    • Author(s)
      三島一彦、甲賀智之、白畑充章、安達淳一、鈴木智也,福岡講平、渡辺祐子、柳澤隆昭、西川 亮
    • Organizer
      第26回日本老年脳神経外科学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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