Clarify the molecular mechanisms of the induction of apoptosis by the highly active nucleosides

• Project/Area Number: 20590533
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Tohoku University
• Principal Investigator: SATO Takeya Tohoku University, 大学院・医学系研究科, 助教 (10312696)
• Co-Investigator(Kenkyū-buntansha): YANAGISAWA Teruyuki 東北大学, 大学院・医学系研究科, 教授 (90133941) ; SUKEGAWA Jun 東北大学, 大学院・医学系研究科, 准教授 (30187687)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 遺伝子 / 癌 / 生体機能利用 / トランスレーショナルリサーチ / 薬剤反応性

Research Abstract

Bystander effect was observed in the non-gene modified cells adjacent to the gene modified cells expressing tmpk-variants treated with nontoxic dose of AZT against the normal cells. GJIC formed between these cells are crucial to exhibit the effect. These results suggest that our tmpk/AZT approach is feasible to use for the anti-cancer gene therapy.

Research Products

• [Journal Article] Vezatin, a potential target for ADP-ribosylation factor 6, regulates the dendritic formation of hippocampal neurons. (2010)
  • Author(s): Sanda M, Ohara N, Kamata A, Hara Y, Tamaki H, Sukegawa J, Yanagisawa T, Fukunaga K, Kondo H, Sakagami H.
  • Journal Title: Neurosci Res. Volume: 67 Pages: 126-136
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor broadens lentivector distribution in the heart after neonatal injection. (2009)
  • Author(s): Sato T, Ramsubir S, Higuchi K, Yanagisawa T, Medin JA.
  • Journal Title: J Cardiol 54(2) Pages: 245-254
  • NAID: 10025583300
  • Peer Reviewed
• [Journal Article] Direct injection of kit ligand-2 lentivirus improves cardiac repair and rescues mice post-myocardial infarction. (2009)
  • Author(s): Higuchi K, Ayach B, Sato T, Chen M, Devine SP, Rasaiah VI, Dawood F, Yanagisawa T, Tei C, Takenaka T, Liu PP, Medin JA.
  • Journal Title: Mol Ther. 17(2) Pages: 262-268
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor broadens lentivector distribution in the heart after neonatal injection (2009)
  • Author(s): Sato, Takeya, Ramsubir, Shobha, Higuchi, Koji Yanagisawa, Teruyuki Medin, Jeffrey A
  • Journal Title: J Cardiol 54 Pages: 245-254
  • NAID: 10025583300
  • Peer Reviewed
• [Journal Article] Direct Injection of Kit Ligand-2 Lentivirus Improves Cardiac Repair and Rescues Mice Post-myocardial Infarction (2009)
  • Author(s): Higuchi K, Ayach B, Sato T, Chen M, Devine SP, Rasaiah VI, Dawood F, Yanagisawa T, Tei C, Takenaka T, Liu PP, Medin JA
  • Journal Title: Molecular Theapy 17(2) Pages: 262-268
  • Peer Reviewed
• [Journal Article] CLIC4 interacts with histamine H3 receptor and enhances the receptor cell surface expression. (2008)
  • Author(s): Maeda K, Haraguchi M, Kuramasu A, Sato T, Ariake K, Sakagami H, Kondo H, Yanai K, Fukunaga K, Yanagisawa T, Sukegawa J.
  • Journal Title: Biochem Biophys Res Commun. 369(2) Pages: 603-608
  • Peer Reviewed
• [Journal Article] Potentiation of potassium currents by beta-adrenoceptor agonists in human urinary bladder smooth muscle cells : a possible electrical mechanism of relaxation. (2008)
  • Author(s): Takemoto J, Masumiya H, Nunoki K, Sato T, Nakagawa H, Ikeda Y, Arai Y, Yanagisawa T.
  • Journal Title: Pharmacology. 81(3) Pages: 251-258
  • Peer Reviewed
• [Journal Article] CLIC4 interacts with histamine H3 receptor and enhances the receptor cell surface expression (2008)
  • Author(s): Maeda K, Haraguchi M, Kuramasu A, Sato T, Ariake K, Sakagami H, Kondo H, Yanai K, Fukunaga K, Yanagisawa T, Sukegawa J
  • Journal Title: Biochem Biophys Res Commun 369(2) Pages: 603-608
  • Peer Reviewed
• [Presentation] 抗ガン治療法としてのTmpk/AZT系におけるBystander効果発現の分子機構 (2010)
  • Author(s): 佐藤岳哉
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-10
• [Presentation] 抗ガン治療法としてのTmpk/AZT系におけるBystander効果発現の分子機構 (2010)
  • Author(s): 佐藤岳哉、鈴木夕起、伊東萌、助川淳、柳澤輝行
  • Organizer: 第61回日本薬理学会北部会
  • Place of Presentation: 札幌市
  • Year and Date: 2010-09-10
• [Presentation] Mechanism of the tmpk/AZT-system bystander effect ; cell fate control gene therapy for anti-cancer treatment. (2010)
  • Author(s): Takeya Sato
  • Organizer: 第13回アメリカ遺伝子細胞治療学会ジウム
  • Place of Presentation: ワシントンDCアメリカ
• [Presentation] 新生マウスに対するVEGF前投与は遺伝子治療効果を改善する (2010)
  • Author(s): 佐藤岳哉
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] Mechanism of the tmpk/AZT-system bystander effect ; cell fate control gene therapy for anti-cancer treatment. (2010)
  • Author(s): Takeya Sato, Anton Neschaaim, Jun Sukegawa, Teruyuki Yanagisawa, Jeffrey A.Medin.
  • Organizer: 第13回アメリカ遺伝子・細胞治療学学会年会
  • Place of Presentation: アメリカ、ワシントンDC
• [Presentation] Next generation lentiviral cell fate control gene therapy based on engineered variants of human deoxycytidine kinase. (2010)
  • Author(s): Anton Neschadim, Arnon Lavie, Takeya Sato, Daniel H.Fowler, Vlodimir Ponomarev, Jeffrey A.Medin.
  • Organizer: 第13回アメリカ遺伝子・細胞治療学学会年会
  • Place of Presentation: アメリカ、ワシントンDC
• [Presentation] 新生マウスに対するVEGF前投与は遺伝子治療効果を改善する (2010)
  • Author(s): 佐藤岳哉, Shobha Ramsbir, 樋口公嗣, Jeffrey Medin, 柳澤輝行
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] ヒスタミンH3受容体に結合する細胞内タンパク質の機能解析 (2010)
  • Author(s): 木下和樹、廣田佳那、佐藤岳哉、前田恵、原口満也、福永浩司、柳澤輝行、助川淳
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] 新規遺伝子治療法tmpk/AZT系の抗ガン治療法としての有効性の検証(In vivo Bystander効果の確認) (2009)
  • Author(s): 佐藤岳哉
  • Organizer: 第60回日本薬理学会北部会
  • Place of Presentation: 富山
  • Year and Date: 2009-09-26
• [Presentation] Gap junction-mediated bystander killing highlights the utility of the TmpkF105Y/AZT system for cancer suicide gene therapy. (2009)
  • Author(s): Takeya Sato
  • Organizer: 第15回日本遺伝子治療学会年会
  • Place of Presentation: 大阪
• [Presentation] Cell surface expression of histamine H3 receptor is regulated by proteins interacting with the carboxy-terminus of the receptor (2009)
  • Author(s): Kinoshita K., Takayanagi S., Sato T., Maeda., Haraguchi M., Yanai K., Fukunaga K., Yanagisawa T., Sukegawa J.
  • Organizer: 10th MOVD 2009
  • Place of Presentation: 宮城県、松島
• [Presentation] Gap junction-mediated bystander killing highlights the utility of the TmpkF105Y/AZT system for cancer suicide gene therapy (2009)
  • Author(s): 佐藤岳哉, Anton Neschadim, Jeffrey A.Medin, 柳澤輝行
  • Organizer: 第15回日本遺伝子治療学会年会
  • Place of Presentation: 大阪
• [Presentation] 抗レトロウィルス薬代謝物のミトコンドリア機能に対する影響の評価 (2009)
  • Author(s): 佐藤岳哉、助川淳、柳澤輝行
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] ヒスタミンH3受容体の細胞表面発現調節 (2009)
  • Author(s): 助川淳、木下和樹、高柳詩織、佐藤岳哉、前田恵、原口満也、谷内一彦、福永浩司、柳澤輝行
  • Organizer: 82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] ヒスタミンH3受容体に結合し発現量を制御するタンパク質の新たな同定 (2009)
  • Author(s): 高柳詩織、木下和樹、佐藤岳哉、前田恵、原口満也、谷内一彦、福永浩司、柳澤輝行、助川淳
  • Organizer: 第82回日本薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] 抗ウィルス薬の副作用に関する分子薬理学研究 (2008)
  • Author(s): 佐藤友香、助川淳、柳澤輝行、佐藤岳哉
  • Organizer: 第59回日本薬理学会北部会
  • Place of Presentation: 仙台
  • Year and Date: 2008-09-27
• [Presentation] ヒスタミンH3受容体の細胞表面発現調節 (2008)
  • Author(s): 木下和樹、高柳詩織、前田恵、原口満也、佐藤岳哉、谷内一彦、福永浩司、柳澤輝行、助川淳
  • Organizer: 第59回日本薬理学会北部会
  • Place of Presentation: 仙台
  • Year and Date: 2008-09-27
• [Presentation] Bystander killing highlights the utility of the tmpkF105Y/AZT system for suicide gene therapy of cancer (2008)
  • Author(s): Takeya Sato, Anton Neschadim, Jun Sukegawa, Teruyuki Yanagisawa, Jeffrey A. Medin
  • Organizer: 第11回アメリカ遺伝子治療学会年会
  • Place of Presentation: Boston, USA
• [Presentation] Thymidylate kinase over-expressing cells showed the mitochondrial myopathy by anti-HIV drug (2008)
  • Author(s): Teruyuki Yanagisawa and Takeya Sato
  • Organizer: 第12回日本心不全学会学術集会
  • Place of Presentation: 東京
• [Presentation] Apoptosis induction by the anti-retrovirus drug through mitochondrial dysfunction (2008)
  • Author(s): Yuka Sato, Jun Sukegawa, Teruyuki Yanagisawa, Takeya Sato
  • Organizer: XI Workshop on apoptosis in biology and medicine
  • Place of Presentation: 仙台
• [Remarks] ホームページ等