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2013 Fiscal Year Final Research Report

Combinatory use of replication-competent adenoviruses and chemotherapeutic agents produces anti-tumor effects on human esophageal carcinoma cells

Research Project

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Project/Area Number 23591951
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionChiba Cancer Center (Research Institute)

Principal Investigator

TAGAWA Masatoshi  千葉県がんセンター(研究所), がん治療開発グループ, 部長 (20171572)

Co-Investigator(Kenkyū-buntansha) SHIMADA Hideaki  東邦大学, 医学部, 教授 (20292691)
Project Period (FY) 2011 – 2013
Keywords遺伝子 / ウイルス / 癌 / 受容体 / 化学療法 / CD46 / 抗腫瘍効果
Research Abstract

We examined a novel therapeutic strategy for intractable cancer in particular esophageal carcinoma. We replaced a transcriptional regulatory region of the E1 region-encoded genes in adenoviruses (Ad) with a 5' region of a gene that was highly expressed in human tumors but not in normal tissues such as midkine, survivin and cyclooxygenase-2. We also changed the fiber region of conventional type 5 Ad, which played a key role in infecting target cells, with a type 35-derived fiber region. The modification increased the viral infectivity since an expression level of the CAR molecules, which were a cellular receptor of type 5 Ad, were often down-regulated in human tumors. In contract, the expression of CD46 molecules, which are the major receptor of type 35 Ad, is rather up-regulated in human tumors. The fiber replacement greatly enhanced Ad infectivity in CAR-low tumors and subsequently enhanced the Ad-mediated cytotoxicity, and produced combinatory effects with anti-cancer agents.

  • Research Products

    (27 results)

All 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (12 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Combination of adenoviruses expressing melanoma differentiation-associated gene-7 and chemotherapeutic agents produces enhanced cytotoxicity on esophageal carcinoma2014

    • Author(s)
      Ma, G., Kawamura, K., Yang, S., Okamoto, S., Li, Q., Namba, M., Shingyoji, M., Tada, Y., Tatsumi, K., Hiroshima, K., Shimada, H. and Tagawa, M.
    • Journal Title

      Cancer Gene Ther

      Volume: 21 Pages: 31-37

    • DOI

      10.1038/cgt.2013.79

    • Peer Reviewed
  • [Journal Article] Fiber-substituted conditionally replicating adenovirus Ad5F35 induces oncolysis of human bladder cancer cells in in vitro analysis2013

    • Author(s)
      Gotoh A, Nagaya H, Kanno T, Tagawa M, Nishizaki T.
    • Journal Title

      Urology

      Volume: 81 Pages: 920.e7-920.e11

    • DOI

      10.1016/j.urology.2012.12.023

    • Peer Reviewed
  • [Journal Article] Gene therapy for malignant mesothelioma : Current prospects and challenges2013

    • Author(s)
      Tagawa, M., Tada, Y., Shimada, H. and Hiroshima, K.
    • Journal Title

      Cancer Gene Ther

      Volume: 20 Pages: 150-156

    • DOI

      10.1038/cgt.2013.1

    • Peer Reviewed
  • [Journal Article] Enhanced antitumor efficacy of fiber-modified, midkine promoter-regulated oncolytic adenovirus in human malignant mesothelioma2013

    • Author(s)
      Takagi-Kimura, M., Yamano, T., Tamamoto, A., Okamura, N., Okamura, H., Hashimoto-Tamaoki, T., Tagawa, M., Kasahara, N. and Kubo, S.
    • Journal Title

      Cancer Sci.

      Volume: 104 Pages: 1433-1439

    • DOI

      10.1111/cas.12267

    • Peer Reviewed
  • [Journal Article] Antitumor effect of chromatin sulfate-coated ternary granulocyte macrophage-colony-stimulating factor plasmid complex for ovarian cancer2012

    • Author(s)
      Hamada, K., Yoshihara, C., Ito, T., Tani, K., Tagawa, M., Sakuragawa, N., Itoh, H. and Koyama, Y.
    • Journal Title

      J. Gene Med

      Volume: 14 Pages: 120-127

    • DOI

      10.1002/jgm.1647

    • Peer Reviewed
  • [Journal Article] Expression of a murine homologue of apoptosis-inducing human IL-24/MDA-7 in murine tumors fails to induce apoptosis or produce anti-tumor effects2012

    • Author(s)
      Nagakawa, H., Shimozato, O., Yu, L., Wada, A., Kawamura, K., Li, Q., Chada, S., Tada, Y., Takiguchi, Y., Tatsumi, K and Tagawa, M.
    • Journal Title

      Cell. Immunol.

      Volume: 275 Pages: 90-97

    • DOI

      10.1016/j.cellimm.2012.02.010

    • Peer Reviewed
  • [Journal Article] Impact of serum biomarkers on esophageal squamous cell carcinoma2012

    • Author(s)
      Shimada, H., Yajima, S., Oshima, Y., Hiwasa, T., Tagawa, M., Matsushita, K. and Nomura, F.
    • Journal Title

      Esophagus

      Volume: 9 Pages: 131-140

    • DOI

      10.1007/s10388-012-0332-x

    • Peer Reviewed
  • [Journal Article] Fiber-substituted conditionally replicating adenovirus for oncolysis of human renal carcinoma cells2012

    • Author(s)
      Nagaya, H., Tagawa, M., Hiwasa, K., Terao, S., Kanno, T., Nishizaki, T. and Gotoh, A.
    • Journal Title

      Anticancer Res.

      Volume: 32 Pages: 2985-2990

    • URL

      http://ar.iiarjournals.org/content/32/7/2985.abstract

    • Peer Reviewed
  • [Journal Article] Upregulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of cisplatin and pemetrexed2012

    • 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 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 (Article ID 479013)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] Antitumor activity of type III interferon alone or in combination with type I interferon against human non-small-cell lung cancer2011

    • Author(s)
      Fujie, H., Tanaka, T., Tagawa, M., Kaijun, N., Watanabe, M., Suzuki, T., Nakayama, K. and Numasaki, M.
    • Journal Title

      Cancer Sci.

      Volume: 102 Pages: 1977-1990

    • DOI

      10.1111/j.1349-7006.2011.02079

    • Peer Reviewed
  • [Journal Article] Adenoviruses-mediated transduction of human esophageal carcinoma cells with the interferon-genes produced anti-tumor effects2011

    • 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 Pages: 1302-1312

    • DOI

      10.1038/bjc.2011.379

    • Peer Reviewed
  • [Presentation] An HSP90 inhibitor, which blocks p53 degradation, suppresses adenoviruses-mediated p53 production and the apoptosis2013

    • Author(s)
      柴寛, その他
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜市
    • Year and Date
      2013-10-05
  • [Presentation] Updated gene therapy for malignant mesothelioma : Challenges for the intractable caner2013

    • Author(s)
      Masatoshi Tagawa, その他
    • Organizer
      19th annual meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Okayama
    • Year and Date
      2013-07-06
  • [Presentation] Midkine promoter-driven oncolytic adenovirus with Ad35 fiber modification achieves enhanced transduction of human osteosarcoma cells2013

    • Author(s)
      Shuji Kubo, その他
    • Organizer
      19th annual meeting of Japan Society of Gene Therapy
    • Place of Presentation
      Okayama
    • Year and Date
      2013-07-06
  • [Presentation] A Cancer-targeting ligand strongly enhances oncolytic activity of a conditionally replicative adenovirus2013

    • Author(s)
      Yuki Yamamoto, その他
    • Organizer
      16th annual meeting of American Society of Gene and Cell Therapy
    • Place of Presentation
      Salt Lake City, USA
    • Year and Date
      2013-05-18
  • [Presentation] Development of doubly regulated oncolytic adenovirus for human malignant mesothelioma2013

    • Author(s)
      Shuji Kubo, その他
    • Organizer
      16th annual meeting of American Society of Gene and Cell Therapy
    • Place of Presentation
      Salt Lake City, USA
    • Year and Date
      2013-05-18
  • [Presentation] Gene therapy for malignant mesothelioma with restored p53 functions2012

    • Author(s)
      Masatoshi Tagawa, その他
    • Organizer
      International Society for Cell and Gene Therapy of Cancer2012 Singapore Conference
    • Place of Presentation
      Singapore
    • Year and Date
      2012-10-05
  • [Presentation] Cytotoxicity of replication-competent adenoviruses in esophageal carcinoma was enhanced by forced p53 expression2012

    • Author(s)
      楊珊, その他
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
  • [Presentation] Development of doubly regulated oncolytic adenovirus for human malignant mesothelioma2012

    • Author(s)
      久保秀司, その他
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
  • [Presentation] Analysis of serum anti-galectin-1 antibody in stage I/II gastroenterological carcinomas2012

    • Author(s)
      島田英昭, その他
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
  • [Presentation] Bisphosphonates induce apoptosis through the suppression of Rab and produce combinatory effects with anti-cancer agents2012

    • Author(s)
      田川雅敏, その他
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌市
    • Year and Date
      2012-09-20
  • [Presentation] Up-regulated p53 expression activates apoptotic pathways in wild-type p53-bearing mesothelioma and enhances cytotoxicity of the first-line chemotherapeutic agents2011

    • Author(s)
      Masatoshi Tagawa, その他
    • Organizer
      19th Annual Congress of the European Society of Gene and Cell Therapy
    • Place of Presentation
      Brighton, UK
    • Year and Date
      20111027-31
  • [Presentation] Promoter-mediated replication of adenoviruses induces apoptosis-independent cell death in p53-null pancreatic carcinoma cells2011

    • Author(s)
      Masatoshi Tagawa, その他
    • Organizer
      14th annual meeting of American Society of Gene and Cell Therapy
    • Place of Presentation
      Seattle、USA
    • Year and Date
      2011-05-21
  • [Book] Type III interferon family-mediated anti-tumor responses through multiple mechanisms. In : Cellular and genetic practices for translational medicine. ed. by Jong-Young Kwak and Jin-Yeong Han2011

    • Author(s)
      Tagawa, M., Tada, Y., Hiroshima, K. and Shimada, H.
    • Total Pages
      247-260
    • Publisher
      Research Signpost
  • [Remarks]

    • URL

      http://www.pref.chiba.lg.jp/gan/kenkyujo/institute/organization/cell-therapy/index.html

  • [Remarks]

    • URL

      http://www.pref.chiba.lg.jp/gan/kenkyujo/institute/projects/007.html

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Published: 2015-07-16  

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