Chemosensitization of human glioma cellt to chemotherapeutic agent temozolomide

• Project/Area Number: 20390391
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Fujita Health University
• Principal Investigator: HIROSE Yuichi Fujita Health University, 医学部, 教授 (60218849)
• Co-Investigator(Kenkyū-buntansha): SASAKI Hikaru 慶應義塾大学, 医学部, 講師 (70245512)
• Co-Investigator(Renkei-kenkyūsha): UGAWA Fujiko 藤田保健衛生大学, 医学部, 研究補助員 (80465517)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000); Fiscal Year 2010: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2009: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2008: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: 悪性神経膠腫 / temozolomide / G2チェックポイント / cancer stem cell / グリオーマ / flavopiridol / cyclin-dependent kinase / Aktキナーゼ / DNA二重鎖断裂 / 標的治療

Research Abstract

Using human glioma cell line U87MG, biological responses of glioma cells to chemotherapeutic agent temozlomide (TMZ) was investigated. Especially, linkage between G2 checkpoint activation and DNA repair mechanism was thoroughly investigated in order to develop novel TMZ-related therapeutic regime against chemotherapy-refractory gliomas.

Research Products

• [Journal Article] Single-copy gain of chromosome 1q is a negative prognostic marker in pediatric nonependymal, nonpilocytic gliomas. (2011)
  • Author(s): Miwa T, Hirose Y, Sasaki H, Ezalci T, Yoshida K, Kawase T.
  • Journal Title: Neurosurgery Volume: 68 Pages: 206-212
  • Peer Reviewed
• [Journal Article] Whole genome analysis from microdissected tissue revealed adult supratentorial grade II-III gliomas are divided into clinically relevant subgroups by genetic profile. (2011)
  • Author(s): Hirose Y, Sasaki H, Miwa T, Ohba S, Ikeda E, Abe M, Ikeda S, Kobayashi M, Kawase T, Hasegawa M, Yoshida K.
  • Journal Title: Neurosurgery Volume: (in press)
  • Peer Reviewed
• [Journal Article] 脳腫瘍の治療感受性 (2011)
  • Author(s): 廣瀬雄一
  • Journal Title: 日本臨牀 Volume: 68(増刊号10) Pages: 76-80
• [Journal Article] 悪性グリオーマの集学的治療に向けての生物学 (2011)
  • Author(s): 廣瀬雄一
  • Journal Title: 脳神経外科ジャーナル Volume: 19 Pages: 880-886
  • Peer Reviewed
• [Journal Article] Inhibition of 90-kD heat shock protein potentiates the cytotoxicity of chemotherapeutic agents in human glioma cells. (2010)
  • Author(s): Ohba S, Hirose Y, Yoshida K, Yazaki T, Kawase T.
  • Journal Title: Journal of Neurosurgery. 112 Pages: 33-42
  • Peer Reviewed
• [Journal Article] 脳腫瘍の治療感受性 (2010)
  • Author(s): 廣瀬雄一
  • Journal Title: 日本臨休 68(増刊号10) Pages: 76-80
• [Journal Article] 悪性グリオーマの集学的治療に向けての生物学 (2010)
  • Author(s): 廣瀬雄一
  • Journal Title: 脳神経外科ジャーナル 19 Pages: 880-886
  • Peer Reviewed
• [Journal Article] 脳腫瘍-診療・研究の最近の進歩- (2010)
  • Author(s): 廣瀬雄一
  • Journal Title: 現代医学 58(2) Pages: 231-238
• [Journal Article] Inhibition of 90-kD heat shock protein potentiates the cytotoxicity of chemotherapeutic agents in human glioma cells (2010)
  • Author(s): Ohba S, Hirose Y, Yoshida K, Yazaki T, Kawase T.
  • Journal Title: Journal of Neurosurgery 112 Pages: 33-42
  • Peer Reviewed
• [Journal Article] 細胞死:最近の知見 (2010)
  • Author(s): 廣瀬雄一, 佐野公俊
  • Journal Title: 脳神経外科速報 20 Pages: 72-79
• [Journal Article] Inhibition of c-Jun N-terminal kinase enhances temozolomide-induced totoxicity in human glioma cells. (2009)
  • Author(s): Ohba S, Hirose Y, Kawase T, Sano H.
  • Journal Title: Journal of Neuro-oncology 95(3) Pages: 307-316
  • Peer Reviewed
• [Journal Article] グリオーマの遺伝子異常 (2009)
  • Author(s): 廣瀬雄一
  • Journal Title: 脳21 12 Pages: 21-25
• [Journal Article] Inhibition of c-Jun N-terminal kinase enhances temozolomide-induced cytotoxicity in human glioma cells (2009)
  • Author(s): Ohba S, Hirose Y, Kawase T, Sano H.
  • Journal Title: Journal of Neuro-oncology 95 Pages: 307-316
  • Peer Reviewed
• [Journal Article] Inhibition of 90-kD heat shock protein potentiates the cyto-toxicity of chemotherapeutic agents in human glioma cells
  • Author(s): Ohba S, Hirose Y, Yoshida K, Yazaki T, Kawase T.
  • Journal Title: Journal of Neurosurgery in press
  • Peer Reviewed
• [Presentation] グリオーマの遺伝学的解析と化学療法 (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 日本脳神経外科学会中国四国地方会(招待講演)
  • Place of Presentation: 広島市
  • Year and Date: 2010-12-04
• [Presentation] グリオーマの遺伝学的解析と化学療法 (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 日本脳神経外科学会中国四国地方会
  • Place of Presentation: 広島市(招待講演)
  • Year and Date: 2010-12-04
• [Presentation] Chkl阻害剤UCN-OlによるTMZ耐性グリオーマ細胞のテモゾロミド感受性回復効果 (2010)
  • Author(s): 大場茂生、廣瀬雄一
  • Organizer: 第28回日本脳腫瘍学会
  • Place of Presentation: 軽井沢市
  • Year and Date: 2010-11-28
• [Presentation] Chkl阻害剤UCN-01によるTMZ耐性グリオーマ細胞のテモゾロミド感受性回復効果 (2010)
  • Author(s): 大場茂生、廣瀬雄一
  • Organizer: 第28回日本脳腫瘍学会
  • Place of Presentation: 軽井沢市
  • Year and Date: 2010-11-28
• [Presentation] グリオーマの遺伝学的解析と化学療法 (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第5回鹿児島脳腫瘍セミナー(招待講演)
  • Place of Presentation: 鹿児島市
  • Year and Date: 2010-11-09
• [Presentation] グリオーマの遺伝学的解析と化学療法 (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第5回鹿児島脳腫瘍セミナー
  • Place of Presentation: 鹿児島市(招待講演)
  • Year and Date: 2010-11-09
• [Presentation] 悪性グリオーマにおける化学療法抵抗性とその克服への戦略 (2010)
  • Author(s): 廣瀬雄一,佐々木光,長谷川光広, ほか
  • Organizer: 第69回日本脳神経外科学会学術総会
  • Place of Presentation: 福岡市
  • Year and Date: 2010-10-29
• [Presentation] グリオーマの化学療法耐性 (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第69回日本脳神経外科学会学術総会
  • Place of Presentation: 福岡市
  • Year and Date: 2010-10-27
• [Presentation] Chkl inhibitor UCN-01 and cdk inhibitor flavopiridol re-sensitize temozolomide-resistant human glioma cells to temozolomide by increasing DNA dameges. (2010)
  • Author(s): Ohba S, Sasaki H, Hirose Y
  • Organizer: Congress of Neurological Surgeons 2010 Annual Meeting
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2010-10-16
• [Presentation] Chkl inhibitor UCN-01 and cdk inhibitor flavopiridol re-sensitize temozolomide-resistant human glioma cells to temozolomide by increasing DNA dameges. (2010)
  • Author(s): Shigeo Ohba, Hikaru Sasaki, Yuichi Hirose
  • Organizer: Congress of Neurological Surgeons 2010 Annual Meeting
  • Place of Presentation: 米国、サンフランシスコ市
  • Year and Date: 2010-10-16
• [Presentation] Low-gradegliomaの遺伝子診断とneoadjuvant approach (2010)
  • Author(s): 佐々木光、廣瀬雄一戸田正博, ほか
  • Organizer: 第15回脳腫瘍の外科学会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-10-02
• [Presentation] Low-grade gliomaの遺伝子診断とneoadjuvant approach (2010)
  • Author(s): 佐々木光、廣瀬雄一、戸田正博、大平貴之、吉田一成
  • Organizer: 第15回脳腫瘍の外科学会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-10-02
• [Presentation] 既存の膠芽腫治療の限界、新規治療による突破口の可能性:化学療法について (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第11回日本分子脳神経外科学会(招待講演)
  • Place of Presentation: 仙台市
  • Year and Date: 2010-08-27
• [Presentation] 悪性グリオーマにおけるDNA修復機構の解析に基づいた新規化学療法開発の可能性 (2010)
  • Author(s): 廣瀬雄一、佐々木光、長谷川光広, ほか
  • Organizer: 第11回日本分子脳神経外科学会
  • Place of Presentation: 仙台市
  • Year and Date: 2010-08-27
• [Presentation] 既存の膠芽腫治療の限界、新規治療による突破口の可能性:化学療法について (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第11回日本分子脳神経外科学会
  • Place of Presentation: 仙台市(招待講演)
  • Year and Date: 2010-08-27
• [Presentation] Glioma cells can acquire temozolimide resistance through enhanced DNA repair linked with G2 checkpoint activation. (2010)
  • Author(s): Hirose Y, Ohba S, Sasaki H
  • Organizer: The 7^<th> Meeting of Asian Society for Neuro-oncology
  • Place of Presentation: 韓国、ソウル
  • Year and Date: 2010-06-12
• [Presentation] グリオーマのgenetic subgrouping (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第28回日本脳腫瘍病理学会(招待講演)
  • Place of Presentation: 大阪市
  • Year and Date: 2010-05-21
• [Presentation] グリオーマのgenefic subgrouping (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第28回日本脳腫瘍病理学会
  • Place of Presentation: 大阪市(招待講演)
  • Year and Date: 2010-05-21
• [Presentation] Cyclin-dependent kinase inhibitor enhances temozolomide-induced cytotoxixity in human glioma cells by suppressing DNA repair associated with G2 checkpoint. (2010)
  • Author(s): 廣瀬雄一
  • Organizer: The 18th International Conference on Brain Tumor Research and Therapy
  • Place of Presentation: ドイツ Travemunde
  • Year and Date: 2010-05-19
• [Presentation] Cyclin-dependent kinase inhibitor enhances temozolomide-induced cytotoxixity in human glioma cells by suppressing DNA repair associated with G2 checkpoint. (2010)
  • Author(s): Yuichi Hirose
  • Organizer: The 18th International Conference on Brain Tumor Research and Therapy
  • Place of Presentation: ドイツTravemunde
  • Year and Date: 2010-05-19
• [Presentation] 悪性グリオーマの集学的治療に向けての生物学 (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第30回日本脳神経外科コングレス総会(招待講演)
  • Place of Presentation: 横浜市
  • Year and Date: 2010-05-07
• [Presentation] 悪性グリオーマの集学的治療に向けての生物学 (2010)
  • Author(s): 廣瀬雄一
  • Organizer: 第30回日本脳神経外科コングレス総会
  • Place of Presentation: 横浜市(招待講演)
  • Year and Date: 2010-05-07
• [Presentation] Cdk inhibitor enhances DNA damage in human glioma cells treated with DNA-methylating agent temozolomide (2009)
  • Author(s): Hirose Y, Sano H
  • Organizer: American Association for Cancer Research special conference
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2009-12-14
• [Presentation] Temozolomide resistance of glioma cells could be overcome by Cdk inhibitor (2009)
  • Author(s): Hirose Y, Kanno T, Sano H.
  • Organizer: SNO-AANS/CNS Tumor Section Joint Meeting
  • Place of Presentation: New Orleans, LO, USA
  • Year and Date: 2009-10-23
• [Presentation] 細胞周期制御機構を標的としたグリオーマのtemozolomide増感法開発の可能性 (2009)
  • Author(s): 廣瀬雄一、川瀬司、吉田耕一郎, ほか
  • Organizer: 第68回日本脳神経外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-14
• [Presentation] 細胞周期制御機構を標的としたグリオーマの temozolomide 増感法開発の可能性 (2009)
  • Author(s): 広瀬雄一, 川瀬司, 吉田耕一郎, 他
  • Organizer: 第68回日本脳神経外科学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-10-14
• [Presentation] Biological responses of glioma cell to chemotherapeutic agent temozolomide (2009)
  • Author(s): Hirose Y, Sano H
  • Organizer: 第14回World Congress of Neurological Surgery
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2009-09-04
• [Presentation] Biological responses of glioma cell to chemotherapeutic agent temozolomide (2009)
  • Author(s): Hirose Y, Sano H
  • Organizer: 第14回 World Congress of Neurological Surgery
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2009-09-04
• [Presentation] Cdk inhibitor blocks DNA repair following G2 checkpoint activation in human glioma cells treated with temozolomide (2009)
  • Author(s): Hirose Y, Sano H
  • Organizer: 第3回World Federation of Neuro-oncology
  • Place of Presentation: 横浜市
  • Year and Date: 2009-05-14
• [Presentation] Cdk inhibitor blocks DNA repair following G2 checkpoint activation in human glioma cells treated with temozolomide (2009)
  • Author(s): Hirose Y, Sano H
  • Organizer: 第3回 World Federation of Neuro-oncology
  • Place of Presentation: 横浜市
  • Year and Date: 2009-05-14
• [Presentation] グリオーマにおける放射線学的特徴と遺伝学的特徴、その予後に関する関連性の解析 (2009)
  • Author(s): 西山悠也、廣瀬雄一、川瀬司, ほか
  • Organizer: 第27回日本脳腫瘍病理学会
  • Place of Presentation: 福岡市
  • Year and Date: 2009-05-09
• [Presentation] グリオーマにおける放射線学的特徴と遺伝学的特徴、その予後に関する関連性の解析 (2009)
  • Author(s): 西山悠也, 廣瀬雄一, 川瀬司, ほか
  • Organizer: 第27回脳腫瘍病理学会
  • Place of Presentation: 福岡市
  • Year and Date: 2009-05-09
• [Presentation] Cdk inhibitor blocks DNA repair following G2 checkpoint activation in human glioma cells treated with DNA-methylating agent temozolomide American Association for Cancer Research (2009)
  • Author(s): Hirose Y, Ugawa F, Ohba S, et al.
  • Organizer: the 100^<th> Annual Meeting
  • Place of Presentation: Denver, CO, USA
  • Year and Date: 2009-04-21
• [Presentation] Cdk inhibitor blocks DNA repair following G2 checkpoint activation in humanglioma cells treated with DNA-methylating agent temozolomide (2009)
  • Author(s): Hirose Y, Ugawa F, Ohba S, et al.
  • Organizer: American Association for Cancer Research, the 100h Annual Meeting
  • Place of Presentation: Denver, CO, USA
  • Year and Date: 2009-04-21
• [Presentation] 初発グリオーマ(G2)に対する治療法の検討 (2008)
  • Author(s): 廣瀬雄一
  • Organizer: 第3回東海脳腫瘍セミナ
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-12-02
• [Presentation] 初発グリオーマ(G2)に対する治療法の検討 (2008)
  • Author(s): 広瀬雄一
  • Organizer: 第3回東海脳腫瘍セミナー
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-12-02
• [Presentation] グリオーマのテモゾロミド耐性獲得機構と細胞周期制御機構との関連性 (2008)
  • Author(s): 廣瀬雄一、佐々木光、三輪点, ほか
  • Organizer: 第26回日本脳腫瘍学会
  • Place of Presentation: 松山市
  • Year and Date: 2008-11-30
• [Presentation] グリオーマのテモソロミド耐性獲得機構と細胞周期制御機構との関連性 (2008)
  • Author(s): 広瀬雄一, 佐々木光, 三輪点, 川瀬司, 長谷川光広, 佐野公俊
  • Organizer: 第26回日本脳腫瘍学会
  • Place of Presentation: 松山市
  • Year and Date: 2008-11-30
• [Presentation] DNA修復系の変化によるグリオーマ細胞のtemozomide耐性獲得 (2008)
  • Author(s): 廣瀬雄一、佐々木光
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-29
• [Presentation] DNA修復系の変化によるグリオーマ細胞のtemozomide耐性獲得 (2008)
  • Author(s): 広瀬雄一, 佐々木光
  • Organizer: 第67回 日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2008-10-29
• [Presentation] グリオーマにおけるDNA修復能の変化とtemozolomide耐性獲得機構 (2008)
  • Author(s): 廣瀬雄一、佐々木光、三輪点、安倍雅人、川瀬司、長谷川光広、佐野公俊
  • Organizer: 第67回日本脳神経外科学会総会
  • Place of Presentation: 盛岡市
  • Year and Date: 2008-10-03
• [Presentation] グリオーマにおけるDNA修復能の変化とtemozolomide耐性獲得機構 (2008)
  • Author(s): 広瀬雄一, 佐々木光, 三輪点, 安倍雅人, 川瀬司, 長谷川光広, 佐野公俊
  • Organizer: 第67回 日本脳神経外科学会総会
  • Place of Presentation: 盛岡市
  • Year and Date: 2008-10-03
• [Presentation] グリオーマのtemozolomide耐性獲得におけるDNA修復能変化の意義 (2008)
  • Author(s): 廣瀬雄一、佐々木光、三輪点、佐野公俊
  • Organizer: 第9回日本分子脳神経外科学会
  • Place of Presentation: 京都市
  • Year and Date: 2008-08-31
• [Presentation] グリオーマのtemozolomide耐性獲得におけるDNA修復能変化の意義 (2008)
  • Author(s): 広瀬雄一, 佐々木光, 三輪点, 佐野公俊
  • Organizer: 第9回 日本分子脳神経外科学会
  • Place of Presentation: 京都市
  • Year and Date: 2008-08-31
• [Presentation] Cdk inhibitor flavopiridol enhances cytotoxic action of DNA-damaging agents on human glioma cells. (2008)
  • Author(s): Hirose Y, Ohba S, Kawase T., et al.
  • Organizer: The 17^<th> International Conference on Brain Tumor Research and Therapy
  • Place of Presentation: 北海道青沼
  • Year and Date: 2008-06-10
• [Presentation] Cdkinhibitor flavopiridol enhances cytotoxic action of DNA-damaging agents on human glioma cell (2008)
  • Author(s): Hirose Y, Ohba S. Kawase T., et al.
  • Organizer: Intemational Conference on Brain Tumor Research and Therapy
  • Place of Presentation: 北海道 青沼
  • Year and Date: 2008-06-10
• [Presentation] Cdk inhibitor flavopiridol enhances cytotoxic action of DNA-damaging agents on human glioma cells. (2008)
  • Author(s): Hirose Y, Ugawa F, Ohba S, et al.
  • Organizer: American Association for Cancer Research, the 99^<th> Annual Meeting
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2008-04-13
• [Presentation] Cdkinhibitor flavopiridol enhances cytotoxic action of DNA-damaging agents on human glioma cells (2008)
  • Author(s): Hirose Y, Ueawa F, Ohba S, et al.
  • Organizer: American Association for Cancer Research, the 99th Annual Meeting
  • Place of Presentation: San Diego, CA
  • Year and Date: 2008-04-13
• [Book] 腫瘍内アポトーシス-グリオーマにおける細胞死(NS NOW No.5 グリオーマ) (2009)
  • Author(s): 廣瀬雄一
  • Publisher: メジカルビュー社
• [Book] NS NOW No. 5グリオーマ「腫瘍内アポトーシス - グリオーマにおける細胞死」 (2009)
  • Author(s): 広瀬雄一
  • Total Pages: 130
  • Publisher: メジカルビュー社