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New therapeutic strategy for non-small cell lung cancer by REIC gene therapy

Research Project

Project/Area Number 26670627
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Respiratory surgery
Research InstitutionOkayama University

Principal Investigator

Toyooka Shinichi  岡山大学, 医歯薬学総合研究科, 教授 (30397880)

Co-Investigator(Kenkyū-buntansha) 宗 淳一  岡山大学, 大学病院, 講師 (90559890)
山本 寛斉  岡山大学, 大学病院, 助教 (40467733)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsREIC遺伝子 / 非小細胞肺癌 / 遺伝子治療 / REIC / 肺癌 / 悪性胸膜中皮腫 / NK細胞 / MHC Class I / GRP78 / MHC Class-I / MHC Class1
Outline of Final Research Achievements

REIC is down-regulated in many human cancer cells and is considered to function as a tumor suppressor. REIC-expressing adenovirus vector (Ad-REIC) induces endoplasmic reticulum (ER) stress and cancer-specific apoptosis in human cancers. We examined the therapeutic impact of Ad-REIC on non-small cell lung cancer and malignant pleural mesothelioma. We examined the direct anti-tumor effect of Ad-REIC gene therapy on non-small cell lung cancer and malignant pleural mesothelioma cell lines in vitro, and the distant bystander effect using immunocompetent mouse allograft models with bilateral flank tumors. Ad-REIC treatment showed antitumor effect in many lung cancer and malignant pleural mesothelioma cell lines in vitro. In an in vivo model, Ad-REIC treatment inhibited the growth not only of directly treated tumors but also distant untreated tumors. Ad-REIC treatment not only had a direct antitumor effect but also an indirect bystander effect through stimulation of the immune system.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2017 2016 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Distant Bystander Effect of REIC/DKK3 Gene Therapy Through Immune System Stimulation in Thoracic Malignancies.2017

    • Author(s)
      Suzawa K, Shien K, Peng H, Sakaguchi M, Watanabe M, Hashida S, Maki Y, Yamamoto H, Tomida S, Soh J, Asano H, Tsukuda K, Nasu Y, Kumon H, Miyoshi S, Toyooka S.
    • Journal Title

      Anticancer Research

      Volume: 37 Pages: 301-307

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Anti-Cancer Effects of REIC/Dkk-3-encoding Adenoviral Vector for the Treatment of Non-small Cell Lung Cancer2014

    • Author(s)
      Shien K, Tanaka N, Watanabe M, Soh J, Sakaguchi M, Matsuo K, Yamamoto H, Furukawa M, Asano H, Tsukuda K, Nasu Y, Huh NH, Miyoshi S, Kumon H, Toyooka S
    • Journal Title

      PLoS ONE

      Volume: 9 Issue: 2 Pages: e87900-e87900

    • DOI

      10.1371/journal.pone.0087900

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 悪性胸膜中皮腫に対するREIC/Dkk-3遺伝子治療2016

    • Author(s)
      山本寛斉、諏澤憲、枝園和彦、宗淳一、三好健太郎、大谷真二、杉本誠一郎、山根正修、大藤剛宏、三好新一郎、豊岡伸一
    • Organizer
      第69回日本胸部外科学会定期学術集会
    • Place of Presentation
      岡山
    • Year and Date
      2016-09-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胸部悪性腫瘍に対するREIC遺伝子治療2016

    • Author(s)
      豊岡伸一、諏澤憲、枝園和彦、牧佑歩、山本寛斉、宗淳一、山根正修、大藤剛宏、公文裕巳、三好新一郎
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2016-04-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] The proof of concept of REIC/Dkk-3 gene therapy for thoracic malignancies.2016

    • Author(s)
      Shinichi Toyooka, Ken Suzawa, Kazuhiko Shien, Masakiyo Sakaguchi, Masami Watanabe, Peng Huang, Kei Namba, Hidejiro Torigoe, Hiroki Sato, Junichi Soh, Hiromasa Yamamoto, Yuho Maki, Kazunori Tsukuda, Shuta Tomida, Yasutomo Nasu, Hiromi Kumon, Shinichiro Miyoshi
    • Organizer
      10th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: From Biology to Therapeutics
    • Place of Presentation
      米国
    • Year and Date
      2016-02-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 悪性胸膜中皮腫に対するREIC/Dkk-3遺伝子治療2015

    • Author(s)
      山本寛斉、枝園和彦、牧佑歩、宗淳一、大谷真二、三好健太郎、杉本誠一郎、山根正修、大藤剛宏、渡部昌実、那須保友、公文裕巳、三好新一郎、豊岡伸一
    • Organizer
      第56回日本肺癌学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2015-11-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Adenovirus-mediated REIC/Dkk-3 gene therapy shows indirect antitumor effects on thoracic malignancies through immune system stimulation2015

    • Author(s)
      Ken Suzawa, Kazuhiko Shien, Masakiyo Sakaguchi, Masami Watanabe, Shinsuke Hashida, Junichi Soh, Hiromasa Yamamoto, Yuho Maki, Kazunori Tsukuda, Yasutomo Nasu, Hiromi Kumon, Shinichiro Miyoshi, Shinichi Toyooka
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      米国
    • Year and Date
      2015-10-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Distant bystander effect of REIC/Dkk-3 gene therapy through immune system stimulation in a murine model of thoracic malignancies2015

    • Author(s)
      Ken Suzawa, Kazuhiko Shien, Pen Huang, Masakiyo Sakaguchi, Mototsugu Watanabe, Shinsuke Hashida, Junichi Soh, Hiromasa Yamamoto, Yuho Maki, Hiroaki Asano, Kazunori Tsukuda, Yasutomo Nasu, Hiromi Kumon, Shinichiro Miyoshi, Shinichi Toyooka
    • Organizer
      16th World Conference on Lung Cancer
    • Place of Presentation
      名古屋
    • Year and Date
      2015-09-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2014-04-04   Modified: 2018-03-22  

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