Induction of autophagic cell death via microRNA-mediated gene regulatory network

• Project/Area Number: 22791310
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: Okayama University
• Principal Investigator: TAZAWA Hiroshi 岡山大学, 岡山大学病院, 助教 (90415513)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌 / マイクロRNA / アデノウイルス / テロメラーゼ / オートファジー

Research Abstract

Tumor-specific replication-competent oncolytic adenovirus is a promising antitumor agent. However, the mechanism on the virus-mediated cell death remains unclear. Here we show that telomerase-specific replication-competent oncolytic adenovirus Telomelysin induces autophagic cell death through microRNA-mediated gene regulatory network.

Research Products

• [Journal Article] Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells (2013)
  • Author(s): Hasei J, Sasaki T, Tazawa H, Osaki S, Yamakawa Y, Kunisada T, Yoshida A, Hashimoto Y, Onishi T, Uno F, Kagawa S, Urata Y, Ozaki T, Fujiwara T
  • Journal Title: Mol Cancer Ther Volume: 12: 314-325
  • NAID: 120005324798
  • Peer Reviewed
• [Journal Article] A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus (2013)
  • Author(s): Sasaki T, Tazawa H, Hasei J, Osaki S, Kunisada T, Yoshida A, Hashimoto Y, Yano S, Yoshida R, Kagawa S, Uno F, Urata Y, Ozaki T, Fujiwara T
  • Journal Title: Gene Ther Volume: 20: 112-118
  • Peer Reviewed
• [Journal Article] Dual programmed cell death pathways induced by p53 transactivation overcome resistance to oncolytic adenovirus in human osteosarcoma cells. (2013)
  • Author(s): Hasei, J.
  • Journal Title: Molecular Cancer Therapeutics Volume: 12 Issue: 3 Pages: 314-325
  • DOI: 10.1158/1535-7163.mct-12-0869
  • Peer Reviewed
• [Journal Article] The hTERT promoter enhances the antitumor activity of an oncolytic adenovirus under a hypoxic microenvironment (2012)
  • Author(s): Hashimoto Y, Tazawa H, Teraishi F, Kojima T, Watanabe Y, Uno F, Yano S, Urata Y, Kagawa S, Fujiwara T
  • Journal Title: PLoS One Volume: 7: e39292
  • NAID: 120005232484
  • Peer Reviewed
• [Journal Article] Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells (2012)
  • Author(s): Yoshida R, Tazawa H, Hashimoto Y, Yano S, Onishi T, Sasaki T, Shirakawa Y, Kishimoto H, Uno F, Nishizaki M, Kagawa S, Fujiwara T
  • Journal Title: Cancer Immunol Immunother Volume: 61: 1905-1916
  • NAID: 120005232490
  • Peer Reviewed
• [Journal Article] Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis (2012)
  • Author(s): Tazawa H, Yano S, Yoshida R, Yamasaki Y, Sasaki T, Hashimoto Y, Kuroda S, Ouchi M, Onishi T, Uno F, Kagawa S, Urata Y, Fujiwara T
  • Journal Title: Int J Cancer Volume: 131: 2939-2950
  • NAID: 130004505785
  • Peer Reviewed
• [Journal Article] A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression (2012)
  • Author(s): Yamasaki Y, Tazawa H, Hashimoto Y, Kojima T, Kuroda S, Yano S, Yoshida R, Uno F, Mizuguchi H, Ohtsuru A, Urata Y, Kagawa S, Fujiwara T
  • Journal Title: Eur J Cancer Volume: 48: 2282-2291
  • Peer Reviewed
• [Journal Article] Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis (2012)
  • Author(s): Tazawa, H.
  • Journal Title: International Journal of Cancer Volume: (Epub ahead of print) Issue: 12 Pages: 2939-2950
  • DOI: 10.1002/ijc.27589
  • Peer Reviewed
• [Journal Article] A Novel Apoptotic Mechanism of Genetically Engineered Adenovirus-mediated Tumor-specific p53 Overexpression through E1A-dependent p21 and MDM2 suppression. (2012)
  • Author(s): Yasumoto Yamasaki
  • Journal Title: European Journal of Cancer Volume: 48 Pages: 282-291
  • Peer Reviewed
• [Journal Article] Mechanism of resistance to trastuzumab and molecular sensitization via ADCC activation by exogenous expression of HER2-extracellular domain in human cancer cells. (2012)
  • Author(s): Yoshida, R.
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 61 Issue: 11 Pages: 1905-1916
  • DOI: 10.1007/s00262-012-1249-x
  • Peer Reviewed
• [Journal Article] The hTERT Promoter Enhances the Antitumor Activity of an Oncolytic Adenovirus under a Hypoxic Microenvironment. (2012)
  • Author(s): Yuuri Hashimoto
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus (2012)
  • Author(s): Sasaki, T.
  • Journal Title: Gene Therapy Volume: (Epub ahead of print) Issue: 1 Pages: 112-118
  • DOI: 10.1038/gt.2011.213
  • Peer Reviewed
• [Journal Article] Synergistic Interaction of Telomerase-specific Oncolytic Virotherapy and Chemotherapeutic Agents for Human Cancer. (2012)
  • Author(s): Toshiyoshi Fujiwara
  • Journal Title: Current Pharmaceutical Biotechnology Volume: 13 Pages: 1809-1819
  • Peer Reviewed
• [Journal Article] A novel apoptotic mechanism of genetically engineered adenovirus-mediated tumour-specific p53 overexpression through E1A-dependent p21 and MDM2 suppression (2012)
  • Author(s): Yamasaki, Y.
  • Journal Title: European Journal of Cancer Volume: (Epub ahead of print) Issue: 14 Pages: 2282-2291
  • DOI: 10.1016/j.ejca.2011.12.020
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas (2011)
  • Author(s): Sasaki T, Tazawa H, Hasei J, Kunisada T, Yoshida A, Hashimoto Y, Yano S, Yoshida R, Uno F, Kagawa S, Morimoto Y, Urata Y, Ozaki T, Fujiwara T
  • Journal Title: Clin Cancer Res Volume: 17: 1828-1838
  • NAID: 40019397235
  • Peer Reviewed
• [Journal Article] Preclinical evaluation of telomerase-specific oncolytic virotherapy for human bone and soft tissue sarcomas (2011)
  • Author(s): Sasaki T, et al
  • Journal Title: Clinical Cancer Research Volume: 17 Issue: 7 Pages: 1828-1838
  • DOI: 10.1158/1078-0432.ccr-10-2066
  • Peer Reviewed
• [Journal Article] MicroRNAs as potential target gene in cancer gene therapy of gastrointestinal tumors. (2011)
  • Author(s): Hiroshi Tazawa
  • Journal Title: Expert Opinion on Biological Therapy Volume: 11 Pages: 145-155
  • Peer Reviewed
• [Journal Article] Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery (2010)
  • Author(s): Kuroda S, Fujiwara T, Shirakawa Y, Yamasaki Y, Yano S, Uno F, Tazawa H, Hashimoto Y, Watanabe Y, Noma K, Urata Y, Kagawa S, Fujiwara T
  • Journal Title: Cancer Res Volume: 70: 9339-9348
  • Peer Reviewed
• [Journal Article] In vivo biological purging for lymph node metastasis of human colorectal cancer by telomerase-specific oncolytic virotherapy (2010)
  • Author(s): Kojima T, Watanabe Y, Hashimoto Y, Kuroda S, Yamasaki Y, Yano S, Ouchi M, Tazawa H, Uno F, Kagawa S, Kyo S, Mizuguchi H, Urata Y, Tanaka N, Fujiwara T
  • Journal Title: Ann Surg Volume: 251: 1079-1086
  • Peer Reviewed
• [Journal Article] In vivo biological purging for lymph node metastasis of human colorectal cancer by telomerase-specific oncolytic virotherapy. (2010)
  • Author(s): Toru Kojima
  • Journal Title: Annals of Surgery Volume: 251 Pages: 1079-1086
  • Peer Reviewed
• [Journal Article] Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery. (2010)
  • Author(s): Shinji Kuroda
  • Journal Title: Cancer Research Volume: 70 Pages: 9339-9348
  • Peer Reviewed
• [Presentation] p53 関連アポトーシス経路の誘導はヒト骨肉腫細胞における腫瘍融解アデノウイルスに対する抵抗性を減弱する (2012)
  • Author(s): 長谷井 嬢、佐々木 剛、田澤 大、橋本悠里、国定俊之、浦田泰生、尾崎敏文、藤原俊義
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] Telomerase-specific oncolytic adenovirus suppresses the stem-like properties of CD133+ human gastric cancer MKN45 cells through microRNA modulation (2012)
  • Author(s): Onishi T, Tazawa H, Yano S, Hashimoto Y, Kikuchi S, Shigeyasu K, Osaki S, Kagawa S, Fujiwara T
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
  • Year and Date: 2012-06-28
• [Presentation] A simple detection system for viable circulating tumor cells using genetically bioengineered adenovirus (2012)
  • Author(s): Tazawa H
  • Organizer: 4th World Circulating Tumor Cell Summit
  • Place of Presentation: Berlin (Germany)
  • Year and Date: 2012-04-25
• [Presentation] Preclinical evaluation of cytotoxic effect of photosensitive fluorescent protein in human cancer cells (2012)
  • Author(s): Tazawa H, Sasaki T, Hashimoto Y, Kikuchi S, Kishimoto H, Mizuguchi H, Fujiwara T
  • Organizer: 103rd Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Chicago (USA)
  • Year and Date: 2012-04-04
• [Presentation] Oncolytic adenovirus inhibits the cancer-stem cell properties through microRNA modulation (2011)
  • Author(s): Tazawa H, Onishi T, Yano S, Urata Y, Fujiwara T
  • Organizer: 8th International Symposium on Minimal Residual Cancer
  • Place of Presentation: 大阪
  • Year and Date: 2011-09-22
• [Presentation] Oncolytic adenovirus inhibits the cancer stem cell properties through microRNA modulation (2011)
  • Author(s): Hiroshi Tazawa
  • Organizer: 8th International Symposium on Minimal Residual Cancer
  • Place of Presentation: 大阪
  • Year and Date: 2011-09-22
• [Presentation] ヒト癌細胞におけるマイクロRNAを介したオートファジー細胞死の誘導分子機構 (2011)
  • Author(s): 田澤 大、矢野修也、吉田亮介、浦田泰生、藤原俊義
  • Organizer: 第29回日本ヒト細胞学会
  • Place of Presentation: 富山
  • Year and Date: 2011-08-20
• [Presentation] Oncolytic adenovirus induces autophagic cell death through microRNA-7-mediated suppression of EGFR in human cancer cells (2011)
  • Author(s): Tazawa H, Yano S, Yoshida R, Urata Y, Fujiwara T
  • Organizer: 第16回日本遺伝子治療学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-07-03
• [Presentation] Bioengineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis (2011)
  • Author(s): Tazawa H, Yano S, Yoshida R, Urata Y, Fujiwara T
  • Organizer: 102nd Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Orlando (USA)
  • Year and Date: 2011-04-05
• [Presentation] Bioengineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis (2011)
  • Author(s): Hiroshi Tazawa
  • Organizer: 102nd Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Orlando
  • Year and Date: 2011-04-05
• [Presentation] アデノウイルス感染に伴うE2F1 の活性化によるマイクロRNA-7 の発現誘導とオートファジー細胞死の制御機構 (2010)
  • Author(s): 田澤 大、矢野修也、吉田亮介、浦田泰生、藤原俊義
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] E2F1-mediated microRNA-7 upregulation induces autophagic cell death-through EGFR suppression during adenovirus infection. (2010)
  • Author(s): Hiroshi Tazawa
  • Organizer: 第69回日本癌学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] Oncolytic adenovirus induces autophagic cell death through microRNA-7-mediated suppression of EGFR in human cancer cells. (2010)
  • Author(s): Hiroshi Tazawa
  • Organizer: 第16回日本遺伝子治療学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2010-07-03
• [Presentation] Preclinical Evaluation of Cytotoxic Effect of Photosensitive Fluorescent Protein in Human Cancer Cells.
  • Author(s): Hiroshi Tazawa
  • Organizer: 103rd Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: Chicago, USA
• [Presentation] A Simple Detection System for Viable Circulating Tumor Cells Using Genetically Bioengineered Adenovirus.
  • Author(s): Hiroshi Tazawa
  • Organizer: 4th World Circulating Tumor Cell Summit
  • Place of Presentation: Berlin, Germany
• [Presentation] Telomerase-specific Oncolytic Adenovirus Suppresses the Stem-like Properties of CD133+ Human Gastric Cancer MKN45 Cells through MicroRNA Modulation.
  • Author(s): Teppei Onishi
  • Organizer: 第18回日本遺伝子治療学会
  • Place of Presentation: 熊本
• [Presentation] p53関連アポトーシス経路の誘導はヒト骨肉腫細胞における腫瘍融解アデノウイルスに対する抵抗性を減弱する
  • Author(s): 長谷井 嬢
  • Organizer: 第71回日本癌学会
  • Place of Presentation: 札幌
• [Remarks] 山陽新聞朝刊掲載記事(2011年9月22日)「独自開発ウイルス製剤使用時 がん細胞死仕組み解明」