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

• Project/Area Number: 15K10330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Shiga 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: ¥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.

Research Products

• [Journal Article] Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification. (2016)
  • 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: 1195-1202
  • DOI: 10.1016/j.jacl.2015.12.027
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men. (2016)
  • 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: 29 Issue: 9
  • DOI: 10.1161/jaha.116.003738
  • NAID: 120006334825
  • 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 hypercholesterolemia. (2016)
  • 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: 172-80
  • DOI: 10.1016/j.jacl.2015.10.010
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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