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in vivo Mechanisms of Novel Selective Fluorescent Leukemia Stem Cell Inhibitor

Research Project

Project/Area Number 15K15051
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionMie University

Principal Investigator

Tanaka Toshio  三重大学, 医学(系)研究科(研究院), 教授 (00135443)

Co-Investigator(Kenkyū-buntansha) Nishimura Yuhei  三重大学, 大学院医学系研究科, 准教授 (30303720)
Kawase Reiko  三重大学, 大学院医学系研究科, 助教 (50746740)
Project Period (FY) 2015-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywordsヒトがん幹細胞阻害薬 / ZM-B708 / 悪性腫瘍治療抵抗性 / ヒトがん幹細胞治療薬 / ゼブラフィッシュ / 免疫不全マウス / 蛍光試薬 / がん幹細胞選択性
Outline of Final Research Achievements

Elimination of leukemia stem cells is necessary for the destruction of malignant cell populations. Using the LSC-xenograft zebrafish screening method we previously developed, we found that the fluorescent compound DiOC5(3) selectively marked LSCs and suppressed their proliferation in vivo and in vitro. DiOC5(3) had no obvious toxicity to human umbilical cord blood CD34+ progenitor cells and normal zebrafish. It accumulated in mitochondria through organic anion transporter polypeptides that are overexpressed in the plasma membrane of LSCs, and induced apoptosis via ROS overproduction. DiOC5(3) also inhibited the nuclear translocation of NF-κB through the downregulation of LSC-selective pathways, as indicated from DNA microarray analysis. In summary, DiOC5(3) is a new type of anti-LSC compound available for diagnostic imaging and therapeutics that has the advantage of being a single fluorescent chemical.

Report

(2 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (16 results)

All 2016 2015

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results)

  • [Journal Article] Using zebrafish in systems toxicology for developmental toxicity testing.2016

    • Author(s)
      Nishimura Y, Inoue A, Sasagawa S, Koiwa J, Kawaguchi K, Kawase R, Maruyama T, Kim S, Tanaka T.
    • Journal Title

      Congenit Anom (Kyoto).

      Volume: 56 Issue: 1 Pages: 18-27

    • DOI

      10.1111/cga.12142

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vivo Detection of Mitochondrial Dysfunction Induced by Clinical Drugs and Disease-Associated Genes Using a Novel Dye ZMJ214 in Zebrafish.2016

    • Author(s)
      Sasagawa S, Nishimura Y, Koiwa J, Nomoto T, Shintou T, Murakami S, Yuge M, Kawaguchi K, Kawase R, Miyazaki T, Tanaka T.
    • Journal Title

      ACS Chem Biol.

      Volume: 11 Issue: 2 Pages: 381-388

    • DOI

      10.1021/acschembio.5b00751

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina2016

    • Author(s)
      Shota Sasagawa, Yuhei Nishimura, Tetsuo Kon, Yukiko Yamanaka, Soichiro Murakami, Yoshifumi Ashikawa, Mizuki Yuge, Shiko Okabe, Koki Kawaguchi, Reiko Kawase and Toshio Tanaka
    • Journal Title

      Front. Pharmacol.

      Volume: 7

    • DOI

      10.3389/fphar.2016.00057

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel immunologic tolerance of human cancer cell xenotransplants in zebrafish.2016

    • Author(s)
      Zhang B, Shimada Y, Hirota T, Ariyoshi M, Kuroyanagi J, Nishimura Y, Tanaka T.
    • Journal Title

      Transl Res.

      Volume: 170 Pages: 89-98

    • DOI

      10.1016/j.trsl.2015.12.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative study of the zebrafish embryonic toxicity test and mouse embryonic stem cell test to screen developmental toxicity of human pharmaceutical drugs2016

    • Author(s)
      Atsuto Inoue, Yuhei Nishimura, Norihito Matsumoto, Noriko Umemoto , Yasuhito Shimada, Toru Maruyama, Kana Kayasuga, Motohiko Morihara, Jun Katagi, Tsutomu Shiroya, Yasushi Hirota, Soonih Kim , Toshio Tanaka
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 3 Pages: 79-87

    • NAID

      130005140185

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systems pharmacology of adiposity reveals inhibition of EP300 as a common therapeutic mechanism of caloric restriction and resveratrol for obesity.2015

    • Author(s)
      Nishimura Y, Sasagawa S, Ariyoshi M, Ichikawa S, Shimada Y, Kawaguchi K, Kawase R, Yamamoto R, Uehara T, Yanai T, Takata R, Tanaka T.
    • Journal Title

      Front Pharmacol.

      Volume: 6

    • DOI

      10.3389/fphar.2015.00199

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacological profiling of zebrafish behavior using chemical and genetic classification of sleep-wake modifiers2015

    • Author(s)
      Nishimura Y, Okabe S, Sasagawa S, Murakami S, Ashikawa Y, Yuge M, Kawaguchi K, Kawase R,Tanaka T.
    • Journal Title

      Front Pharmacol.

      Volume: 6

    • DOI

      10.3389/fphar.2015.00257

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Zebrafish-Based Drug Discovery and Systems Pharmacology2016

    • Author(s)
      田中利男
    • Organizer
      International Meeting on Aquatic Model Organisms for Human Disease and Toxicology Research
    • Place of Presentation
      岡崎コンファレンスセンター(愛知県・岡崎市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] トランスレーショナル薬理学とゼブラフィッシュ創薬2016

    • Author(s)
      田中利男
    • Organizer
      第89回日本薬理学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] ゼブラフィッシュ創薬の新しい展開2015

    • Author(s)
      田中利男
    • Organizer
      第1回ゼブラフィッシュ創薬研究会
    • Place of Presentation
      三重大学(三重県・津市)
    • Year and Date
      2015-11-06
    • Related Report
      2015 Annual Research Report
  • [Presentation] 分子標的薬の心毒性に関するシステムズ薬理学2015

    • Author(s)
      田中利男
    • Organizer
      第2回Onco-Cardiology Meeting
    • Place of Presentation
      ソラシティカンファレンスセンター(東京都・千代田区)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] システムズ薬理学とゼブラフィッシュ創薬2015

    • Author(s)
      田中利男
    • Organizer
      第21回小型魚類研究会
    • Place of Presentation
      大阪大学銀杏会館(大阪府・吹田市)
    • Year and Date
      2015-09-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] High Throughput Forward and Reverse Screen for Cardiotoxicology of Anticancer Drugs in Zebrafish2015

    • Author(s)
      田中利男
    • Organizer
      ZDM8
    • Place of Presentation
      Boston(アメリカ合衆国)
    • Year and Date
      2015-08-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ゼブラフィッシュ創薬の国際的展開2015

    • Author(s)
      田中利男
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      石川県立音楽堂(石川県・金沢市)
    • Year and Date
      2015-06-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] ゼブラフィッシュ創薬と個別化医療の新展開2015

    • Author(s)
      田中利男
    • Organizer
      第62回日本実験動物学会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ゼブラフィッシュによるシステムズ栄養学のグローバル展開2015

    • Author(s)
      田中利男
    • Organizer
      第69回日本栄養・食糧学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
    • Invited

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Published: 2015-04-16   Modified: 2017-05-10  

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