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Development of cancer cell-selective necrosis-inducing agents for cancer treatment

Research Project

Project/Area Number 15K14983
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionSojo University

Principal Investigator

KUNIYASU Akihiko  崇城大学, 薬学部, 教授 (90241348)

Co-Investigator(Kenkyū-buntansha) 村田 和義  生理学研究所, 脳機能計測・支援センター, 准教授 (20311201)
牧瀬 正樹  崇城大学, 薬学部, 准教授 (80433001)
Research Collaborator ARAP Wadih  米国ニューメキシコ大学, 医学部, 教授
PASQUALINI Renata  米国ニューメキシコ大学, 医学部, 教授
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsネクローシス / ペプチドミメティクス / がん / 細胞死 / 肺がん / 癌 / 細胞膜透過性ペプチド / ペプチドミメティックス / 乳がん
Outline of Final Research Achievements

To assess therapeutical implications of the necrosis-inducing agents for cancer treatment, we developed a neuropilin-1 (NRP-1)-targeted hybrid peptide, which induces non-apoptotic cell death against lung and breast cancer cells. We determined that the mode of cell death induced with the peptide is similar to necrosis. siRNA knockdown of NRP-1 on A549 cells significantly reduced cytotoxicity of the hybrid peptide. Also, treatment of the hybrid peptide on A549 cells lead to the extracellular release of a necrotic marker protein high mobility group B-1. The peptides will be a useful tool for development of novel concept-based anti-tumor agents such as a necrosis-inducer.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (10 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] ニューメキシコ大学(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] ニューメキシコ大学(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] The role of vimentin in the tumor marker Nup88-dependent multinucleated phenotype2018

    • Author(s)
      Makise Masaki、Nakamura Hideaki、Kuniyasu Akihiko
    • Journal Title

      BMC Cancer

      Volume: 18 Issue: 1

    • DOI

      10.1186/s12885-018-4454-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery2018

    • Author(s)
      Ichimizu Shota、Watanabe Hiroshi、Maeda Hitoshi、Hamasaki Keisuke、Nakamura Yuka、Chuang Victor Tuan Giam、Kinoshita Ryo、Nishida Kento、Tanaka Ryota、Enoki Yuki、Ishima Yu、Kuniyasu Akihiko、Kobashigawa Yoshihiro、Morioka Hiroshi、Futaki Shiro、Otagiri Masaki、Maruyama Toru
    • Journal Title

      Journal of Controlled Release

      Volume: 277 Pages: 23-34

    • DOI

      10.1016/j.jconrel.2018.02.037

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic targeting of membrane-associated GRP78 in leukemia and lymphoma: preclinical efficacy in vitro and formal toxicity study of BMTP-78 in rodents and primates2017

    • Author(s)
      Staquicini D I、D'Angelo S、Ferrara F、Karjalainen K、Sharma G、Smith T L、Tarleton C A、Jaalouk D E、Kuniyasu A、Baze W B、Chaffee B K、Hanley P W、Barnhart K F、Koivunen E、Marchio S、Sidman R L、Cortes J E、Kantarjian H M、Arap W、Pasqualini R
    • Journal Title

      The Pharmacogenomics Journal

      Volume: - Issue: 3 Pages: 1-8

    • DOI

      10.1038/tpj.2017.46

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The novel monoclonal antibody 9F5 reveals expression of a fragment of GPNMB/osteoactivin processed by furin-like protease(s) in a subpopulation of microglia in neonatal rat brain.2016

    • Author(s)
      Kawahara K, Hirata H, Ohbuchi K, Nishi K, Maeda A, Kuniyasu A, Yamada D, Maeda T, Tsuji A, Sawada M, Nakayama H.
    • Journal Title

      Glia

      Volume: 64 Issue: 11 Pages: 1938-1961

    • DOI

      10.1002/glia.23034

    • NAID

      120006510950

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens.2015

    • Author(s)
      Karjalainen K, Jaalouk DE, Bueso-Ramos C, Bover L, Sun Y, Kuniyasu A, Driessen WH, Cardo-Vila M, Rietz C, Zurita AJ, O'Brien S, Kantarjian HM, Cortes JE, Calin GA, Koivunen E, Arap W, Pasqualini R.
    • Journal Title

      Clin. Cancer Res.

      Volume: 21(13) Issue: 13 Pages: 3041-3051

    • DOI

      10.1158/1078-0432.ccr-13-3059

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 腫瘍マーカーNup88の過剰発現はヘッジホッグシグナル経路の活性化を導く2018

    • Author(s)
      牧瀬正樹、安藤早織、國安明彦
    • Organizer
      日本薬学会 第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ミクログリア選択的結合ペプチドの受容体分子解析2018

    • Author(s)
      國安 明彦, 牧瀬 正樹, 髙妻 咲慧, 友永 遥香, 香月 博志, 川原 浩一, Fernanda-I. Staquicini, Wadih Arap, Renata Pasqualini
    • Organizer
      日本薬学会 第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Notch-1断片ペプチドが誘導する白血病細胞選択的ネクローシスとPTEN発現2017

    • Author(s)
      國安明彦、牧瀬正樹
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 核膜孔因子Nup88の過剰発現が誘導する細胞多核化に対するビメンチンの関与2017

    • Author(s)
      牧瀬正樹、秀徳優美、白石梨花子、白川裕貴、和田 耀、國安明彦
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 腫瘍マーカーNup88はKif7の発現抑制を介してヘッジホッグ経路の活性化に寄与する2017

    • Author(s)
      牧瀬正樹、安藤早織、國安明彦
    • Organizer
      2017年度 生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The structural basis for the leukemia-specific necrosis induction by the Notch-1-derived peptide fragment2016

    • Author(s)
      Akihiko Kuniyasu, Masaki Makise
    • Organizer
      欧州がん学会EACR24
    • Place of Presentation
      イギリス・マンチェスター
    • Year and Date
      2016-07-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞選択的膜透過性ペプチドのレトロインバーソ体の合成と活性評価2016

    • Author(s)
      國安明彦、今泉友里、牧瀬正樹
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 核膜孔因子Nup88とビメンチンの相互作用とその細胞運動性への役割2016

    • Author(s)
      牧瀬正樹、秀徳優美、白石梨花子、白川裕貴、和田曜、國安明彦
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] The structural basis for the leukemia-specific necrosis induction by the Notch-1-derived peptide fragment2016

    • Author(s)
      A. Kuniyasu, M. Makise.
    • Organizer
      EACR Conference Series 2016 "Matter of Life or Death"
    • Place of Presentation
      オランダ・アムステルダム
    • Year and Date
      2016-01-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Nucleoporin Nup88 facilitates cancer cell motility through interacting with vimentin.2015

    • Author(s)
      牧瀬正樹、秀徳優美、白石梨花子、白川裕貴、和田曜、國安明彦
    • Organizer
      BMB 2015
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-06-07  

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