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Novel therapeutic strategy by combination of histone deacetylase inhibitors and death signal activators for malignant brain tumors

Research Project

Project/Area Number 18591607
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKyorin University

Principal Investigator

SHIOKAWAYOSHIAKI Shiokawa Yoshiaki  Kyorin University, 医学部, 教授 (20245450)

Co-Investigator(Kenkyū-buntansha) 永根 基雄  杏林大学, 医学部, 准教授 (60327468)
Co-Investigator(Renkei-kenkyūsha) NAGANE Motoo  杏林大学, 医学部, 准教授 (60327468)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordshistone / glioma / HDAC / apoptosis / inhibitor / FLIP / siRNA / proteasome
Research Abstract

腫瘍細胞に特異的な細胞死を誘導しうるHDAC阻害剤とTRAILによるアポトーシス誘導療法の併用により, 相乗的治療効果が得られることが期待される.HDAC 阻害剤であるSAHA とTRAIL 受容体に特異的ヒトモノクローナル抗体(抗DR5 抗体)の併用療法は, ヒトglioma 細胞株の多くに相乗的細胞死を誘導し, 細胞死抑制因子c-FLIP の関与が示唆された.ヌードマウス担癌動物モデルにおいても本併用療法により相乗的腫瘍増殖抑制効果が認められ, 悪性神経膠腫に対する新規治療法としての可能性が示唆された.

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (45 results)

All 2009 2008 2007 2006

All Journal Article (25 results) (of which Peer Reviewed: 9 results) Presentation (16 results) Book (4 results)

  • [Journal Article] Prolonged and severe thrombocytopenia with pancytopenia induced by radiation-combined temozolomide therapy in a patient with newly-diagnosed glioblastoma---analysis of O^6-methylguanine-DNA methyltransferase status2009

    • Author(s)
      Nagane M, Nozue K, Shimizu S, Waha A, Miyazaki H, Kurita H, Homori M, Fujioka Y, Shiokawa Y
    • Journal Title

      J Neuro-Oncol 92

      Pages: 227-232

    • Related Report
      2008 Annual Research Report 2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] MGMT とtemozolomide (in Japanese)2009

    • Author(s)
      永根基雄
    • Journal Title

      脳21 12(1)

      Pages: 38-43

    • Related Report
      2008 Final Research Report
  • [Journal Article] 遺伝性脳腫瘍(神経皮膚症候群含む)2009

    • Author(s)
      永根基雄
    • Journal Title

      In III. 脳・脊髄系の疾患・脳腫瘍, 月刊ナーシング(学習研究社, 東京) vol 29 (5)

      Pages: 88-91

    • Related Report
      2008 Final Research Report
  • [Journal Article] 転移性脳腫瘍2009

    • Author(s)
      小林啓一, 永根基雄
    • Journal Title

      In Clinical Neuroscience Vol 27 (6)

    • Related Report
      2008 Final Research Report
  • [Journal Article] 再発悪性神経膠腫に対するcarboplatin/etoposide併用療法2009

    • Author(s)
      横矢重臣, 永根基雄, 小林啓一, 塩川芳昭
    • Journal Title

      Neuro-Oncology(Tokyo) (In press)

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 中枢神経系リンパ腫に対する大量MTX療法単独による初期治療の検討2009

    • Author(s)
      小林啓一, 永根基雄, 塩川芳昭
    • Journal Title

      Neuro-Oncology(Tokyo) (In press)

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 悪性グリオーマ治療における薬剤耐性機構の最近の知見---temozolomide耐性・分子標的薬・脳腫瘍幹細胞---2009

    • Author(s)
      永根基雄
    • Journal Title

      癌と化学療法 35

      Pages: 918-925

    • Related Report
      2008 Annual Research Report
  • [Journal Article] MGMTとtemozolomide2009

    • Author(s)
      永根基雄
    • Journal Title

      脳21 12

      Pages: 38-43

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells2008

    • Author(s)
      Kobayashi K, Ohnishi A, Promsuk J, Shimizu S, Kanai Y, Shiokawa Y, Nagane M
    • Journal Title

      Neurosurgery 62 (2)

      Pages: 493-504

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 悪性グリオーマ治療における薬剤耐性機構の最近の知見---temozolomide 耐性・分子標的薬・脳腫瘍幹細胞---2008

    • Author(s)
      永根基雄
    • Journal Title

      Jpn J Cancer chemother 35(6)

      Pages: 918-925

    • Related Report
      2008 Final Research Report
  • [Journal Article] Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells2008

    • Author(s)
      Kobayashi K, Ohnishi A, Promsuk J, Shimizu S, Kanai Y, Shiokawa Y, Nagane M
    • Journal Title

      Neurosurgery 62

      Pages: 493-504

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic cytotoxicity through the activation of multiple apoptosis pathways in human glioma cells induced by combined treatment with ionizing irradiation and tumor necrosis factor-related apoptosis-inducing ligand2007

    • Author(s)
      Nagane M, Cavenee WK, Shiokawa Y
    • Journal Title

      J Neurosurg 106

      Pages: 407-416

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide2007

    • Author(s)
      Nagane M, Kobayashi K, Ohnishi A, Shimizu S, Shiokawa Y
    • Journal Title

      Jpn J Clin Oncol 37(12)

      Pages: 897-906

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 初発悪性神経膠腫に対する術後放射線併用 PAV 変法療法2007

    • Author(s)
      小林啓一, 永根基雄, 塩川芳昭
    • Journal Title

      Neuro-Oncology (Tokyo) 17(1)

      Pages: 33-35

    • Related Report
      2008 Final Research Report
  • [Journal Article] 悪性神経膠腫の化学療法2007

    • Author(s)
      永根基雄
    • Journal Title

      No Shinkei Geka 35(5)

      Pages: 433-450

    • Related Report
      2008 Final Research Report
  • [Journal Article] A randomized controlled trial of hydrocortisone against hyponatremia in patients with aneurismal subarachnoid hemorrhage2007

    • Author(s)
      Katayama Y, Shiokawa Y, et. al.
    • Journal Title

      Stroke 38

      Pages: 2373-2375

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic cytotoxicity through the activation of multiple apoptosis pathways in human glioma cells induced by combined treatment with ionizing irradiation and tumor necrosis factor-related apoptosis inducing ligand2007

    • Author(s)
      Nagane M, et. al.
    • Journal Title

      J Neurosurg 106

      Pages: 407-416

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prognostic significance of O°-methylguanine-DNA methyltransferase protein expres sion in patients with recurrent glioblastoma treated with temozolomide2007

    • Author(s)
      Nagane M, et. al.
    • Journal Title

      Jpn J Clin Oncol 37

      Pages: 897-906

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪性神経膠腫の化学療法2007

    • Author(s)
      永根 基雄
    • Journal Title

      No Shinkei Geka 35

      Pages: 433-450

    • Related Report
      2007 Annual Research Report
  • [Journal Article] 再発悪性神経膠腫に対するCarboplatin/高圧酸素併用療法の治療経験palliation療法の可能性2006

    • Author(s)
      小林啓一, 永根基雄, 藤井芳樹, 塩川芳昭
    • Journal Title

      日本臨床高気圧酸素・潜水病学会誌 3

      Pages: 37-41

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 再発悪性神経膠腫に対するtemozolomide 単独療法の治療成績2006

    • Author(s)
      永根基雄, 小林啓一, 塩川芳昭
    • Journal Title

      Neuro-Oncology (Tokyo) 16(2)

      Pages: 26-29

    • Related Report
      2008 Final Research Report
  • [Journal Article] 再発中枢神経系リンパ腫に対するsecond line PAV療法2006

    • Author(s)
      小林啓一, 永根基雄, 塩川芳昭
    • Journal Title

      Neuro-Oncology (Tokyo) 16(2)

      Pages: 74-77

    • Related Report
      2008 Final Research Report
  • [Journal Article] 特集 脳内出血のUp To Daate2006

    • Author(s)
      塩川芳昭
    • Journal Title

      分子脳血管病 5

      Pages: 161-162

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 急性期破裂脳動脈瘤に対する治療選択2006

    • Author(s)
      塩川芳昭
    • Journal Title

      脳外誌 15

      Pages: 185-188

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 再発悪性神経膠腫に対するCarboplatin/高圧酸素併用療法の治療経験-palliation療法の可能性2006

    • Author(s)
      小林啓一, 永根基雄ら
    • Journal Title

      日本臨床高気圧酸素・潜水病学会誌 3

      Pages: 37-41

    • Related Report
      2006 Annual Research Report
  • [Presentation] 再発膠芽腫に対するtemozolomide療法効果とMGMT解析法の検討2009

    • Author(s)
      永根基雄, 小林啓一, 清水早紀, Andreas Waha, 塩川芳昭
    • Organizer
      第4回 脳腫瘍の基礎シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2009-01-31
    • Related Report
      2008 Annual Research Report
  • [Presentation] MGMT解析によるtemozolomide療法効果の検討2008

    • Author(s)
      永根基雄, 小林啓一, 清水早紀, 水谷徹, Andreas Waha, 塩川芳昭
    • Organizer
      第26回 日本脳腫瘍学会
    • Place of Presentation
      松山
    • Year and Date
      2008-12-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] 低悪性度乏突起膠腫系腫瘍に対する化学療法単独による初期治療の検討2008

    • Author(s)
      永根基雄, 小林啓一, 清水早紀, 塩川芳昭
    • Organizer
      第26回 日本脳腫瘍学会
    • Place of Presentation
      松山
    • Year and Date
      2008-12-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Combined treatment with histone deacetylase inhibitors enhances cytotoxic activity of anti-DR5/TRAIL-R2 monoclonal antibodies in human glioma cells2008

    • Author(s)
      Motoo Nagane, Saki Shimizu, Eiji Mori, Shiro Kataoka, Yoshiaki Shiokawa
    • Organizer
      The 13th Annual Meeting of the Society for Neuro-Oncology
    • Place of Presentation
      Las Vegas, Nevada, U.S.A.
    • Year and Date
      2008-11-22
    • Related Report
      2008 Final Research Report
  • [Presentation] Combined treatment with histone deacetylase inhibitors enhances cytotoxic activity of anti-DR5/TRAIL-R2 monoclonal antibodies in human glioma cells2008

    • Author(s)
      Motoo Nagane, Saki Shimizu, Eiji Mori, Shiro Kataoka, Yoshiaki Shiokawa.
    • Organizer
      The13th Annual Meeting of the Society for Neuro-Oncology.
    • Place of Presentation
      Las Vegas, Nevada, U.S.A.
    • Year and Date
      2008-11-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] 膠芽腫に対するtemozolomide療法における予測因子MGMT statusの解析法の検討2008

    • Author(s)
      永根基雄, 小林啓一, 清水早紀, 水谷徹, 塩川芳昭
    • Organizer
      第67回 日本脳神経外科学会総会
    • Place of Presentation
      盛岡
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] ヒストン脱アセチル化酵素阻害剤併用によるTRAIL-R2モノクローナル抗体誘導glioma細胞傷害の相乗的増強効果2008

    • Author(s)
      永根基雄, 清水早紀, 森英治, 片岡之郎, 塩川芳昭
    • Organizer
      第9回日本分子脳神経外科学会
    • Place of Presentation
      京都
    • Year and Date
      2008-08-30
    • Related Report
      2008 Final Research Report
  • [Presentation] ヒストン脱アセチル化酵素阻害剤併用によるTRAIL-R2モノクローナル抗体誘導glioma細胞傷害の相乗的増強効果2008

    • Author(s)
      永根基雄, 清水早紀, 森英治, 片岡之郎, 塩川芳昭
    • Organizer
      第9回 日本分子脳神経外科学会
    • Place of Presentation
      京都
    • Year and Date
      2008-08-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] 悪性脳腫瘍の病態・治療の現状と展望2008

    • Author(s)
      永根基雄
    • Organizer
      第7回埼玉医科大学国際医療センター包括的がんセンター教育カンファランス
    • Place of Presentation
      日高市, 埼玉県
    • Year and Date
      2008-06-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells2008

    • Author(s)
      Motoo Nagane, Keiichi Kobayashi, Akiko Ohnishi, Katsuyoshi Kanai, Yoshiaki Shiokawa
    • Organizer
      The 17th International Conference on Brain Tumor Research and Therapy
    • Place of Presentation
      Hakodate, Hokkaido, Japan
    • Year and Date
      2008-06-10
    • Related Report
      2008 Final Research Report
  • [Presentation] Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells. The 17th International Conference on Brain Tumor Research and Therapy2008

    • Author(s)
      Motoo Nagane, Keiichi Kobayashi, Akiko Ohnishi, Katsuyoshi Kanai, Yoshiaki Shiokawa
    • Organizer
      The 17th International Conference on Brain Tumor Research and Therapy
    • Place of Presentation
      Hakodate, Hokkaido
    • Year and Date
      2008-06-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] 膠芽腫に対するtemozolomide療法におけるMGMT解析法の検討2008

    • Author(s)
      永根基雄, 小林啓一, 清水早紀, 水谷徹, 塩川芳昭
    • Organizer
      第26回 日本脳腫瘍病理学会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] Combined treatment with histone deacetylase inhibitors enhances cytotoxic activity of anti-DR5/TRAIL-R2 monoclonal antibodies in human glioma cells2008

    • Author(s)
      Motoo Nagane, Saki Shimizu, Eiji Mori, Shiro Kataoka, Yoshiaki Shiokawa
    • Organizer
      Annual Meeting of the American Association for Cancer Research 2008
    • Place of Presentation
      San Diego, CA
    • Year and Date
      2008-04-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Combined treatment with histone deacetylase inhibitors enhances cytotoxic activity of anti-DR5/TRAIL-R2 monoclonal antibodies in human glioma cells.2008

    • Author(s)
      Motoo Nagane, Saki Shimizu, Eiji Mori, Shiro Kataoka, Yoshiaki Shiokawa.
    • Organizer
      Annual Meeting of the American Association for Cancer Research 2008
    • Place of Presentation
      San Diego, CA, U.S.A.
    • Year and Date
      2008-04-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] 悪性神経膠腫おける完全ヒト抗TRAIL 受容体モノクローナル抗体の感受性規定因子2007

    • Author(s)
      永根基雄, 清水早紀, 森英治, 片岡之郎, 塩川芳昭
    • Organizer
      第8回日本分子脳神経外科学会
    • Place of Presentation
      兵庫
    • Year and Date
      2007-09-01
    • Related Report
      2008 Final Research Report
  • [Presentation] Predominant antitumor effect by fully human anti-DR5/TRAIL-R2 monoclonal antibodies in human glioma cells2007

    • Author(s)
      Nagane M, Kobayashi K, Shimizu S, Mori E, Kataoka S, Shiokawa Y
    • Organizer
      The 100th Annual Meeting of the American Association for Cancer Research
    • Place of Presentation
      Los Angeles, CA
    • Year and Date
      2007-04-16
    • Related Report
      2008 Final Research Report
  • [Book] 臨床研修医のための画像医学教室-脳神経領域2008

    • Author(s)
      永根 基雄
    • Publisher
      医療科学社
    • Related Report
      2007 Annual Research Report
  • [Book] 脳腫瘍実践ケーススタディ第1巻2008

    • Author(s)
      永根 基雄
    • Publisher
      エサップ
    • Related Report
      2007 Annual Research Report
  • [Book] 脳腫瘍.がん看護 実践シリーズ12007

    • Author(s)
      永根 基雄
    • Publisher
      メジカルフレンド社
    • Related Report
      2007 Annual Research Report
  • [Book] グリオーマ--病態と治療2006

    • Author(s)
      永根基雄ら
    • Total Pages
      274
    • Publisher
      Springer-Verlag
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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