Anti-tumor effects for solid tumors in digestive tracts were produced by a chimeric type of oncolytic adenoviruses and the carrier cells

• Project/Area Number: 21590879
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: KAWAMURA Kiyoko 千葉県がんセンター(研究所), がん治療開発グループ, 上席研究員 (80260248)
• Co-Investigator(Kenkyū-buntansha): TAGAWA Masatoshi 千葉県がんセンター, がん治療開発グループ, 部長 (20171572) ; YAMAGUCHI Taketo 千葉県がんセンター, 医療局, 診療部長 (00241969)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 膵臓癌 / アデノウイルス / 細胞死 / がん治療 / 膵がん / 遺伝子医薬 / アポトーシス / オートファジー / cytopathic effect / p53 / アデノイルス / G2/M期 / 細胞周期 / 転写調節 / 抗がん剤 / 塩酸ゲムシタビン / ペメトレキセド / Geldanamycin

Research Abstract

It is difficult to effectively treat patients with an extended tumor in the digestive tract in particular those who become refractory to standard chemotherapy. We thereby examined a possible anti-tumor effects produced by replication-competent adenoviruses that preferentially proliferate within the target tumors. We also modified the receptor-binding portion to facilitate the infectivity. The anti-tumor effects were also achieved with the adenovirally transduced cells.

Research Products

• [Journal Article] Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed (2012)
  • Author(s): Li, Q., Kawamura, K., Okamoto, S., Yamanaka, M., Yang, S., Yamauchi, S., Fukamachi, T., Kobayashi, H., Tada, Y., Takiguchi, Y., Tatsumi, K., Shimada, H., Hiroshima, K. and Tagawa, M.
  • Journal Title: Cancer Gene Ther Volume: 19 Issue: 3 Pages: 218-228
  • DOI: 10.1038/cgt.2011.86
  • Peer Reviewed
• [Journal Article] A possible anti-cancer agent, type III interferon, activates cell death pathways and produces anti-tumor effects (2011)
  • Author(s): Tagawa, M., Kawamura, K., Li, Q., Tada, Y., Hiroshima, K. and Shimada, H.
  • Journal Title: Clin. Dev. Immunol Volume: 2011 Pages: 1-6
  • DOI: 10.1155/2011/479013
  • Peer Reviewed
• [Journal Article] Adenoviruses-mediated transduction of human esophageal carcinoma cells with the interferon-lambda genes produced anti-tumor effects (2011)
  • Author(s): Li, Q., Kawamura, K., Okamoto, S., Fujie, H., Numasaki, M., Namba, M., Nagata, M., Shimada, H., Kobayashi, H. and Tagawa, M.
  • Journal Title: Br. J. Cancer Volume: 105 Issue: 9 Pages: 1302-1312
  • DOI: 10.1038/bjc.2011.379
  • Peer Reviewed
• [Journal Article] Tumor specific low pH environment enhance the cytotoxicity of lovastatin and cantharidin (2010)
  • Author(s): Fukamachi, T., Chiba, Y., Wang, X., Saito, H., Tagawa, M. and Kobayashi, H.
  • Journal Title: Cancer Lett Volume: 297 Issue: 2 Pages: 182-189
  • DOI: 10.1016/j.canlet.2010.05.010
  • Peer Reviewed
• [Journal Article] Combinatory cytotoxic effects produced by E1B-55kDa-deleted adenoviruses and chemotherapeutic agents are dependent on the agents in esophageal carcinoma (2010)
  • Author(s): Ma, G., Kawamura, K., Li, Q., Okamoto, S., Suzuki, N., Kobayashi, H., Liang, M., Tada, Y., Tatsumi, K., Hiroshima, K., Shimada, H. and Tagawa, M.
  • Journal Title: Cancer Gene Ther Volume: 17 Issue: 11 Pages: 803-813
  • DOI: 10.1038/cgt.2010.37
  • Peer Reviewed
• [Journal Article] Combinatory cytotoxic effects produced by E1B-55kDa-deleted adenoviruses and chemotherapeutic agents are dependent on the agents in esophageal carcinoma. (2010)
  • Author(s): Ma, G., et al.
  • Journal Title: Cancer Gene Ther. Volume: 17 Pages: 803-813
  • Peer Reviewed
• [Journal Article] Tumor specific low pH environment enhance the cytotoxicity of lovastatin and cantharidin. (2010)
  • Author(s): Fukamachi, T., et al.
  • Journal Title: Cancer Lett. Volume: 297 Pages: 182-189
  • Peer Reviewed
• [Journal Article] Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status (2009)
  • Author(s): Ma, G., Kawamura, K., Li, Q., Suzuki, N., Liang, M., Namba, M., Shimada, H. and Tagawa, M.
  • Journal Title: Cancer Gene Ther Volume: 16 Issue: 11 Pages: 832-840
  • DOI: 10.1038/cgt.2009.21
  • Peer Reviewed
• [Journal Article] Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status (2009)
  • Author(s): Ma, G., et al.
  • Journal Title: Cancer Gene Ther 16 Pages: 832-840
  • Peer Reviewed
• [Presentation] 制限増殖型アデノウイルスは、膵がん細胞においてアポトーシス、オートファジー非依存的な細胞死を誘導する (2011)
  • Author(s): 山内駿、川村希代子、岡本慎也、楊珊、江媛媛、深町利彦、小林弘、多田裕司、巽浩一郎、島田英昭、廣島健三、田川雅敏
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-03
• [Presentation] 制限増殖型アデノウイルスは、膵がん細胞においてアポトーシス、オートファジー非依存的な細胞死を誘導する (2011)
  • Author(s): 山内駿、川村希代子, その他
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2011-10-03
• [Presentation] 悪性中皮腫における細胞融解性アデノウイルス感受性の検討 (2010)
  • Author(s): 川村希代子、岡本慎也、深町利彦、小林弘、楊珊、久保秀司、山中満佳子、多田裕司、巽浩一郎、島田英昭、廣島健三、田川雅敏
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-23
• [Presentation] 制限増殖型アデノウイルスに対する腫瘍細胞の感受性を決定する因子の検討 (2009)
  • Author(s): 川村希代子、李全海、武井優輝、山口直人、藤森浩中、多田裕司、山中満佳子、滝口裕一、巽浩一郎、廣島健三、島田英昭、田川雅敏
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2009-10-01