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Establishment of a new gene therapy strategy for prostate cancer stem cells

Research Project

Project/Area Number 17K11138
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionOkayama University

Principal Investigator

HUANG PENG  岡山大学, 医歯薬学総合研究科, 研究准教授 (00610841)

Co-Investigator(Kenkyū-buntansha) 那須 保友  岡山大学, 医歯薬学総合研究科, 教授 (20237572)
定平 卓也  岡山大学, 大学病院, 助教 (20733322)
植木 英雄  岡山大学, 医学部, 技術専門職員 (90537218)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords前立腺がん / 癌幹細胞 / 遺伝子治療 / 前立腺癌 / REIC/DKK-3 / ips細胞 / iPS細胞 / 標的治療
Outline of Final Research Achievements

In this study, using an independently developed REIC gene vector and prostate cancer cancer stem cells, we clarified what kind of intracellular signal during autophagy induction is involved in the construction of the stationary phase maintenance of cancer stem cells, and elucidated the molecular basis for targeting cancer stem cells. The results of this study are to strengthen the foundation for the creation of cancer stem cell-targeted therapies based on REIC / Dkk-3 gene seeds in Japan, and to correspond to endoplasmic reticulum stress responses not only to urological cancer but also to many refractory solid tumors. We determined that this would be the basis for the development of a new autophagy-induced gene therapy.

Academic Significance and Societal Importance of the Research Achievements

今回の申請研究による成果は、REIC/Dkk-3遺伝子を基盤シーズとする日本発の癌幹細胞標的治療の創出基盤を強化し、泌尿器科領域の癌のみならず、多くの難治固形癌に対する、小胞体ストレス応答より新規オートファジー誘導遺伝子治療の展開基盤になるものと判断された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (24 results)

All 2019 2018 2017 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (11 results) (of which Int'l Joint Research: 9 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] National Institutes of Health (NIH)/Virginia Commonwealth University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Southern Medical University/Shanxi Medical University/Peking university(中国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] National Cancer Centre Singapore(シンガポール)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Proteomics and single-cell RNA analysis of Akap4-knockout mice model confirm indispensable role of Akap4 in spermatogenesis2019

    • Author(s)
      Fang Xiang、Huang Ling-Long、Xu Jian、Ma Cai-Qi、Chen Zhi-Heng、Zhang Zhan、Liao Cai-Hua、Zheng Shu-Xin、Huang Peng、Xu Wen-Ming、Li Na、Sun Ling
    • Journal Title

      Developmental Biology

      Volume: 454 Issue: 2 Pages: 118-127

    • DOI

      10.1016/j.ydbio.2019.06.017

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Role of outer dense fiber in multiple morphological abnormalities of the sperm flagella in Akap4 gene defect mice2019

    • Author(s)
      Huang L, Huang P.
    • Journal Title

      Zhong Nan Da Xue Xue Bao Yi Xue Ban

      Volume: 44 Pages: 1367-1375

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Novel Combination of Nitroxoline and PD-1 Blockade, Exerts a Potent Antitumor Effect in a Mouse Model of Prostate Cancer2019

    • Author(s)
      Naijin Xu, Linglong Huang, Xiezhao Li, Masami Watanabe, Chaoming Li, Abai Xu, Chunxiao Liu, Qiang Li, Motoo Araki, Koichiro Wada, Yasutomo Nasu, Peng Huang
    • Journal Title

      International Journal of Biological Sciences

      Volume: 15 Issue: 5 Pages: 919-928

    • DOI

      10.7150/ijbs.32259

    • Related Report
      2018 Research-status Report
  • [Journal Article] Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway2018

    • Author(s)
      Xie Jinlin、Lin Wenfeng、Huang Linglong、Xu Naijin、Xu Abai、Chen Binshen、Watanabe Masami、Liu Chunxiao、Huang Peng
    • Journal Title

      Oncology Letters

      Volume: 16 Pages: 3867-3873

    • DOI

      10.3892/ol.2018.9111

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Induction of cells with prostate cancer stem-like properties from mouse induced pluripotent stem cells via conditioned medium2018

    • Author(s)
      Xu N, Li X, Watanabe M, Ueki H, Hu H, Li N, Araki M, Wada K, Xu A, Liu C, Nasu Y, Huang P
    • Journal Title

      Am J Cancer Res

      Volume: 8 Pages: 1624-1632

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glaucocalyxin A induces G2/M cell cycle arrest and apoptosis through the PI3K/Akt pathway in human bladder cancer cells2018

    • Author(s)
      Lin Wenfeng、Xie Jinlin、Xu Naijin、Huang Linglong、Xu Abai、Li Hulin、Li Chaoming、Gao Yubo、Watanabe Masami、Liu Chunxiao、Huang Peng
    • Journal Title

      International Journal of Biological Sciences

      Volume: 14 Issue: 4 Pages: 418-426

    • DOI

      10.7150/ijbs.23602

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synergistic effects of the immune checkpoint inhibitor CTLA-4 combined with the growth inhibitor lycorine in a mouse model of renal cell carcinoma2017

    • Author(s)
      Li Xiezhao、Xu Peng、Wang Chongshan、Xu Naijin、Xu Abai、Xu Yawen、Sadahira Takuya、Araki Motoo、Wada Koichiro、Matsuura Eiji、Watanabe Masami、Zheng Junxia、Sun Pinghua、Huang Peng、Nasu Yasutomo、Liu Chunxiao
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 13 Pages: 21177-21186

    • DOI

      10.18632/oncotarget.15505

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exogenous DKK-3/REIC inhibits Wnt/β-catenin signaling and cell proliferation in human kidney cancer KPK12017

    • Author(s)
      Xu Jiaqi、Sadahira Takuya、Kinoshita Rie、Li ShunAi、Huang Peng、Wada Koichiro、Araki Motoo、Ochiai Kazuhiko、Noguchi Hirofumi、Sakaguchi Masakiyo、Nasu Yasutomo、Watanabe Masami
    • Journal Title

      Oncology Letters

      Volume: 14 Pages: 5638-5642

    • DOI

      10.3892/ol.2017.6833

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Programmed death ligand 1 expression in bladder rhabdomyosarcoma and its association with clinicopathological features2017

    • Author(s)
      Peng Zhou、Qiongren Wang、Chongshan Wang、 Xiezhao Li、Wei Du、Chunxiao Liu、Masami Watanabe、Peng Huang、Abai Xu
    • Journal Title

      Int J Clin Exp Pathol

      Volume: 10 Pages: 10565-10570

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Nitroxoline inhibits bladder cancer progression by reversing epithelial-to-mesenchymal transition process2019

    • Author(s)
      Wenfeng Lin, Naijin Xu, Chunxiao Liu, Yasutomo Nasu, Peng Huang
    • Organizer
      Best-ASCO 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Glaucocalyxin A, a potential anti-cancer agent, inhibits bladder cancer progression in vitro and in vivo via the PI3K/Akt pathway2019

    • Author(s)
      Naijin Xu, Wenfeng Lin,Yasutomo Nasu, Peng Huang
    • Organizer
      Best-ASCO 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Monitoring preclinical cancer models: Multilateral evaluation of innovating the discovery of therapeutics2018

    • Author(s)
      Peng Huang, Peng Xu, Naijin Xu, Xiezhao Li, Masami Watanabe, Chunxiao Liu and Yasutomo Nasu
    • Organizer
      Third AACR-SNMMI Joint Conference 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel nitroxoline treatment, targeting the PI3K pathway, in combination with PD-1 blockage, exerts a potent prostate cancer anti-tumor effect2018

    • Author(s)
      Naijin Xu , Chaoming Li , Abai Xu , Chunxiao Liu , Qiang Li , Masami Watanabe , Motoo Araki , Koichiro Wada Yasutomo Nasu, Peng Huang
    • Organizer
      AUA2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Programmed death ligand 1 expression in bladder RMS (rhabdomyosarcoma) and its association with clinicopathological features2018

    • Author(s)
      Peng Huang, Peng Xu, Naijin Xu, Xiezhao Li, Masami Watanabe, Chunxiao Liu and Yasutomo Nasu
    • Organizer
      AUA2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Induction of prostate cancer stem cell properties in mouse induced pluripotent stem cells via conditioned medium and tracking drug response2018

    • Author(s)
      Peng Huang, Naijin Xu, Masami Watanabe, Yasutomo Nasu
    • Organizer
      JSGT2018
    • Related Report
      2018 Research-status Report
  • [Presentation] Prostate cancer precision immunotherapy2018

    • Author(s)
      peng huang, Motoo Araki, Ichiro Tsuboi, Tomohiro Hongo, yasutomo Nasu
    • Organizer
      2018 Pearl River Urology Hi-Tec Forum
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Oral nitroxoline in combination with intravesical Bacille Calmette-Guerin shows synergistic antitumor efficacy in mouse bladder cancer orthotopic xenograft2017

    • Author(s)
      Peng Huang、Xiezhao Li、Naijin Xu、Qiang Li、and Kevin Pan
    • Organizer
      AACR2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] INDUCTION OF PROSTATE CANCER STEM CELL PROPERTIES IN MOUSE INDUCED PLURIPOTENT STEM CELLS VIA DEFINED CARCINOMA NICHE AND TRACKING DRUG RESPONSE IN PRECLINICAL RESEARCH2017

    • Author(s)
      Naijin Xu、Xiezhao Li、Abai Xu、Masami Watanabe、Peng Huang、Yasutomo Nasu、Chunxiao Liu
    • Organizer
      AUA2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] IMMUNE CHECKPOINT INHIBITOR COMBINED WITH THE GROWTH INHIBITOR LYCORINE SYNERGISTICALLY FUNCTION TO MEDIATE ANTI-TUMOR EFFECTS IN A MOUSE MODEL OF RENAL CELL CARCINOMA2017

    • Author(s)
      Xiezhao Li、Naijin Xu、Abai Xu、Masami Watanabe、Peng Huang、Yasutomo Nasu、Chunxiao Liu
    • Organizer
      AUA2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] REAL-TIME MONITORING OF TUMOR PROGRESSION AND DRUG RESPONSES IN A PRECLINICAL MOUSE MODEL OF PROSTATE CANCER2017

    • Author(s)
      Peng Huang、Naijin Xu、Xiezhao Li、Abai Xu、Masami Watanabe、Yasutomo Nasu、Chunxiao Liu
    • Organizer
      AUA2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] Combinational Use of Nitroxoline and Its Analogues with Chemotherapies and Immunotherapies in the Treatment of Cancer2018

    • Inventor(s)
      Peng Huang, Ke Pan, Qiang Li
    • Industrial Property Rights Holder
      Peng Huang, Ke Pan, Qiang Li
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report
    • Overseas

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Published: 2017-04-28   Modified: 2021-02-19  

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