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Tumor-Inhibition Effect of Levetiracetam in Combination with Temozolomide in Glioblastoma Cells

Research Project

Project/Area Number 26462188
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionNara Medical University

Principal Investigator

Nakase Hiroyuki  奈良県立医科大学, 医学部, 教授 (10217739)

Co-Investigator(Kenkyū-buntansha) 本山 靖  奈良県立医科大学, 医学部, 准教授 (30405386)
松田 良介  奈良県立医科大学, 医学部, 助教 (60453164)
田村 健太郎  奈良県立医科大学, 医学部, 助教 (00423913)
竹島 靖浩  奈良県立医科大学, 医学部, 助教 (60510203)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsglioblastoma / levetiracetam / temozolomide / premature senescence / levetiracetam / γδT cell
Outline of Final Research Achievements

Glioblastoma (GBM) is a malignant brain tumor with a poor prognosis. The standard postoperative chemotherapy is temozolomide (TMZ), which does not greatly improve survival. Antiepileptic drug levetiracetam (LEV) is commonly prescribed, but the therapeutic advantages of the LEV and TMZ combination remain poorly understood.
We evaluated cell proliferation and premature senescence after single and combined treatments of TMZ and LEV in several GBM cell lines that differ in TMZ sensitivity. Both LEV and TMZ reduced cell proliferation in a dose-dependent manner in A172 cells. A senescent-like phenotype was induced by both TMZ and LEV. Overall, there was a greater effect following combined treatment compared to the monotherapy groups. Thus, LEV appears to have a tumor-suppressive effect and induces cellular senescence, and combined treatment of LEV and TMZ enhanced these effects. LEV use in GBM treatment may allow for reduction of the TMZ dose to enhance the clinical efficacy of TMZ.

Report

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

    (29 results)

All 2016 2015 2014

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 6 results) Book (5 results)

  • [Journal Article] Current Topics of Implantation of BCNU Wafers for the Treatment of Malignant Glioma2016

    • Author(s)
      松田良介,田中祥貴,尾本幸治,西村文彦,中川一郎,本山靖,朴永銖,中瀬裕之
    • Journal Title

      Japanese Journal of Neurosurgery

      Volume: 25 Issue: 11 Pages: 889-894

    • DOI

      10.7887/jcns.25.889

    • NAID

      130005284632

    • ISSN
      0917-950X, 2187-3100
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antitumor effects of minodronate, a third-generation nitrogen-containing bisphosphonate, in synergy with γδT cells in human glioblastoma in vitro and in vivo.2016

    • Author(s)
      Nakazawa T, Nakamura M, Matsuda R, Nishimura F, Park YS, Motoyama Y, Hironaka Y, Nakagawa I, Yokota H, Yamada S, Tamura K, Takeshima Y, Omoto K, Tanaka Y, Ouji Y, Yoshikawa M, Tsujimura T, Nakase H.
    • Journal Title

      J Neurooncol

      Volume: 129 Issue: 2 Pages: 231-241

    • DOI

      10.1007/s11060-016-2186-x

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor-Inhibition Effect of Levetiracetam in Combination with Temozolomide in Glioblastoma Cells2016

    • Author(s)
      Marutani A., Nakamura M., Nishimura F., Nakazawa T., Matsuda R., Hironaka Y., Nakagawa I., Tamura K., Takeshima Y., Motoyama Y., Park Y-S, Ouji Y., Yoshikawa M., Nakase H.
    • Journal Title

      Neurochemical Journal

      Volume: Volume10, No4 Issue: 1 Pages: 333-339

    • DOI

      10.1134/s1819712416040073

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abscess in the splenium of the corpus callosum treated with direct drainage via an occipital interhemispheric approach.2015

    • Author(s)
      Motoyama Y., Kawai H., Kogeichi Y., Gurung P., Park Y-S, Nakase H.
    • Journal Title

      Open Journal of Modern Neurosurgery

      Volume: 5 Issue: 01 Pages: 34-40

    • DOI

      10.4236/ojmn.2015.51006

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Magnetic Resonance Imaging Technique to Evaluate Tumor-Brain Adhesion in Meningioma: Brain-Surface Motion Imaging2015

    • Author(s)
      Yamada S, Taoka T, Nakagawa I, Nishimura F, Motoyama Y, Park YS, Nakase H, Kichikawa K
    • Journal Title

      World Neurosurg

      Volume: 83 Issue: 1 Pages: 102-107

    • DOI

      10.1016/j.wneu.2013.02.015

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glioblastoma multiforme in the pineal region with leptomeningeal dissemination and lumbar metastasis.2015

    • Author(s)
      Matsuda R., Hironaka Y., Sugimoto T., Nakase H.
    • Journal Title

      J Korean Neurosurg Soc

      Volume: 58 Issue: 5 Pages: 479-482

    • DOI

      10.3340/jkns.2015.58.5.479

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intracranial capillary hemangioma in an elderly patient.2015

    • Author(s)
      Okamoto A., Nakagawa I., Matsuda R., Nishimura F., Motoyama Y., Park Y-S, Nakamura M., Nakase H.
    • Journal Title

      Surg Neurol Int

      Volume: 6 Issue: 22 Pages: 539-539

    • DOI

      10.4103/2152-7806.168066

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 症候性嚢胞形成を来しBCNU wafer除去を施行した膠芽腫の1例.2015

    • Author(s)
      中瀬健太, 松田良介, 西村文彦, 中村光利, 本山靖, 朴永銖, 中瀬裕之
    • Journal Title

      脳神経外科

      Volume: 43 Pages: 747-752

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intracranial Meningioma as Initial Clinical Manifestation of Occult Lung Carcinoma: Case Report2014

    • Author(s)
      Chatani M., Nakagawa I., Yamada S., Sugimoto T., Hironaka Y., Nakamura M., Nakase H.
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 54 Issue: 8 Pages: 670-672

    • DOI

      10.2176/nmc.cr2013-0061

    • NAID

      130003383276

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] A guide to the safe and successful neurosurgical management to deep-seated AVMs2016

    • Author(s)
      中瀬裕之
    • Organizer
      The 13th Japan-Korea Joint Conference on Surgery for Cerebral Stroke (JKJC 2016)
    • Place of Presentation
      釜山
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comprehensive neurosurgical management for hemangioblastomas in the posterior fossa2016

    • Author(s)
      中瀬裕之
    • Organizer
      The 7th Japan-india Neurosurgical Conference
    • Place of Presentation
      大阪
    • Year and Date
      2016-06-18
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Surgical strategy to the cranio-vertebral junction (CVJ) tumors2016

    • Author(s)
      中瀬裕之
    • Organizer
      7th International Congress of Skull Base Societies
    • Place of Presentation
      大阪
    • Year and Date
      2016-06-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 頭蓋頸椎移行部病変に対する外科的治療(特別)2016

    • Author(s)
      中瀬裕之
    • Organizer
      第10回Skill-building Neurosurgical Conference
    • Place of Presentation
      札幌
    • Year and Date
      2016-06-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Neurosurgical management and outcomes of the craniovertebral junction(CVJ) turmors2016

    • Author(s)
      中瀬裕之
    • Organizer
      12th Congress of the European Skull Base Society
    • Place of Presentation
      Berlin
    • Year and Date
      2016-05-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neurosurgical Phlebology -Basic and Clinical Studies.2015

    • Author(s)
      Nakase H.
    • Organizer
      2015 SMC Neurosurgical Symposium
    • Place of Presentation
      Seou
    • Year and Date
      2015-12-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 脳神経外科手術における脳静脈還流障害:基礎と臨床2015

    • Author(s)
      中瀬裕之
    • Organizer
      第12回信州脳神経外科研究会
    • Place of Presentation
      松本
    • Year and Date
      2015-10-23
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 頭蓋頸椎移行部病変に対する外科治療2015

    • Author(s)
      中瀬裕之
    • Organizer
      第9回杉田記念フォーラム
    • Place of Presentation
      新潟
    • Year and Date
      2015-08-21
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 脳卒中の予防と治療 -ガイドライン2015をふまえて.2015

    • Author(s)
      中瀬裕之
    • Organizer
      第20回福島脳血管障害治療研究会
    • Place of Presentation
      福島
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 脳神経外科における術中モニタリングの応用2015

    • Author(s)
      中瀬裕之
    • Organizer
      第10回山梨脳・血管セミナー
    • Place of Presentation
      甲府
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 膠芽腫細胞株におけるミノドロン酸の抗腫瘍効果の検討2014

    • Author(s)
      中村光利, 中澤務, 松田良介, 朴永銖, 本山靖, 新靖史, 弘中康雄, 中川一郎, 西村文彦, 田村健太郎, 竹島靖浩, 丸谷明子, 中瀬裕之
    • Organizer
      第32回日本脳腫瘍学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-30 – 2014-12-02
    • Related Report
      2014 Research-status Report
  • [Presentation] 末梢血由来細胞傷害性γδT細胞による膠芽腫治療法の開発.2014

    • Author(s)
      丸谷明子, 中村光利, 中澤務, 朴永銖, 本山靖, 新靖史, 弘中康雄, 中川一郎, 西村文彦, 松田良介, 田村健太郎, 竹島靖浩, 辻村貴弘, 中瀬裕之
    • Organizer
      第73回日本脳神経外科学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] 後頭蓋窩血管芽腫の手術-リスク予測と合併症回避.2014

    • Author(s)
      中瀬裕之, 弘中康雄, 松田良介, 中川一郎, 西村文彦, 新靖史, 本山靖, 朴永銖
    • Organizer
      第19回日本脳腫瘍の外科学会
    • Place of Presentation
      東京
    • Year and Date
      2014-09-12 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 悪性神経膠腫に対するギリアデル留置術. -合併症例から学んだこと-2014

    • Author(s)
      松田良介, 西村文彦, 中村光利, 田村健太郎, 弘中康雄, 中川一郎, 新靖史, 本山靖, 朴永銖, 中瀬裕之
    • Organizer
      第19回日本脳腫瘍の外科学会
    • Place of Presentation
      東京
    • Year and Date
      2014-09-12 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] ギリアデル留置後の病理学的変化. -再手術症例の検討から-2014

    • Author(s)
      松田良介, 中村光利, 西村文彦, 小谷有希子, 本山靖, 朴永銖, 中瀬裕之
    • Organizer
      第32回日本脳腫瘍病理学会
    • Place of Presentation
      徳島
    • Year and Date
      2014-05-23 – 2014-05-24
    • Related Report
      2014 Research-status Report
  • [Book] EBMに基づく脳神経疾患の基本治療指針2016

    • Author(s)
      中川一郎,中瀬裕之
    • Total Pages
      3
    • Publisher
      株式会社メディカルビュー社
    • Related Report
      2016 Annual Research Report
  • [Book] 脳静脈エッセンス 脳静脈の歩き方2016

    • Author(s)
      中川一郎,中瀬裕之
    • Total Pages
      7
    • Publisher
      株式会社中外医学社(東京)
    • Related Report
      2016 Annual Research Report
  • [Book] 日本臨床2016

    • Author(s)
      中瀬裕之,本山靖,山田修一
    • Total Pages
      6
    • Publisher
      日本臨牀社
    • Related Report
      2016 Annual Research Report
  • [Book] Clinical Neuroscience2016

    • Author(s)
      中瀬裕之
    • Total Pages
      2
    • Publisher
      中外医学社
    • Related Report
      2016 Annual Research Report
  • [Book] 研修医のための外科の周術期管理,2015

    • Author(s)
      中瀬裕之
    • Total Pages
      7
    • Publisher
      羊土社(東京)
    • Related Report
      2015 Research-status Report

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

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