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Development of molecular targeted anticancer drug using peptide probe for glioblastoma multiforme

Research Project

Project/Area Number 15K10330
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurosurgery
Research InstitutionShiga University of Medical Science

Principal Investigator

Shiino Akihiko  滋賀医科大学, 神経難病研究センター, 准教授 (50215935)

Co-Investigator(Kenkyū-buntansha) 谷垣 健二  滋賀県立成人病センター(研究所), 神経病態研究部門, 専門研究員 (70362473)
Zhao Li  滋賀医科大学, 医学部, 客員研究員 (40636156)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords悪性神経膠腫 / 分子標的薬 / 血液脳関門 / ファージディスプレイ / DDS / がん幹細胞 / エンドゾーム / MRI / 抗癌剤 / 癌幹細胞 / 抗がん剤 / 磁気共鳴画像 / ゲルダナマイシン
Outline of Final Research Achievements

We try to develop a molecular targeted anti-cancer drug for glioblastoma, which is the most malignant and difficult for treatment. In the brain, tumor cells are protected by blood brain barrier (BBB) that inhibiting transmission of anti-cancer drugs. First, we developed a peptide probe by a method of phage display, which selectively entered into tumor cells and could pass-through BBB in vivo. The proto-type of anti-cancer agent of ours was made by simply conjugated an anticancer drug to the peptide probe, which did not show any effect to the cancer cells. Possible mechanism of this would be that the tumor cells must discharge or break down the agent via endocytosis-endosome mechanism. To overcome, we added pH-dependent membrane active peptide (PMAPs) to the molecular targeted anti-cancer drug and confirmed the effect of tumor shrinkage in PDX model mouse on MRI.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (10 results)

All 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (6 results)

  • [Journal Article] Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification2016

    • Author(s)
      Zaid M, Miura K, Fujiyoshi A, Abbott RD, Hisamatsu T, Kadota A, Arima H, Kadowaki S, Torii S, Miyagawa N, Suzuki S, Takashima N, Ohkubo T, Sekikawa A, Maegawa H, Horie M, Nakamura Y, Okamura T, Ueshima H; SESSA Research Group.
    • Journal Title

      J Clin Lipidol.

      Volume: 10 Issue: 5 Pages: 1195

    • DOI

      10.1016/j.jacl.2015.12.027

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men2016

    • Author(s)
      Hisamatsu T, Miura K, Arima H, Kadota A, Kadowaki S, Torii S, Suzuki S, Miyagawa N, Sato A, Yamazoe M, Fujiyoshi A, Ohkubo T, Yamamoto T, Murata K, Abbott RD, Sekikawa A, Horie M, Ueshima H; Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) Research Group
    • Journal Title

      J Am Heart Assoc.

      Volume: 5 Issue: 9

    • DOI

      10.1161/jaha.116.003738

    • NAID

      120005952637

    • URL

      https://pure.teikyo.jp/en/publications/3b250448-a793-472a-ba32-23047c9906a7

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Serum level of LOX-1 ligand containing ApoB is associated with increased carotid intima-media thickness in Japanese community-dwelling men, especially those with hypercholesterolemiaLOX-1 ligand and IMT in Japanese2016

    • Author(s)
      Okamura T, Miura K, Sawamura T, Kadota A, Hisamatsu T, Fujiyoshi A, Miyamatsu N, Takashima N, Miyagawa N, Kadowaki T, Ohkubo T, Murakami Y, Nakamura Y, Ueshima H.
    • Journal Title

      J Clin Lipidol.

      Volume: 10 Issue: 1 Pages: 172

    • DOI

      10.1016/j.jacl.2015.10.010

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Correction: Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor.2016

    • Author(s)
      Yoshimura Y, Shiino A, Muraki K, Fukami T, Yamada S, Satow T, Fukuda M, Saiki M, Hojo M, Miyamoto S, Onishi N, Saya H, Inubushi T, Nozaki K, Tanigaki K.
    • Journal Title

      PLoS One

      Volume: 16;11(2): Issue: 2 Pages: e0149826-e0149826

    • DOI

      10.1371/journal.pone.0149826

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 悪性神経膠腫特異的抗がん剤の開発-endosomal escapeの効果2017

    • Author(s)
      椎野顯彦
    • Organizer
      第16回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 人工知能を用いた脳形状画像解析2016

    • Author(s)
      椎野顯彦
    • Organizer
      第35回日本認知症学会学術集会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
  • [Presentation] アルツハイマーの画像診断―VBMと人工知能によるADSの有用性2016

    • Author(s)
      椎野顯彦
    • Organizer
      第59回日本脳循環代謝学会学術集会
    • Place of Presentation
      徳島市あわぎんホール
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
  • [Presentation] 発症前アルツハイマー病の画像バイオマーカー2016

    • Author(s)
      椎野顯彦
    • Organizer
      一般社団法人日本脳神経外科学会第75回学術総会
    • Place of Presentation
      福岡サンパレス・マリンメッセ福岡
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] 人工知能を用いた脳形状画像解析:Alzheimer's disease scoreの開発2016

    • Author(s)
      椎野顯彦
    • Organizer
      第44回日本電気共鳴医学会大会
    • Place of Presentation
      大宮ソニックシティ
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] BAADソフトウェアによる脳形態解析2016

    • Author(s)
      椎野顯彦
    • Organizer
      第57回日本神経学会学術大会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2016-05-18
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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