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The construction of a means to overcome cancerous multidrug resistance by mediating the post-translational regulators of drug-efflux transporters

Research Project

Project/Area Number 24590667
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionTakasaki University of Health and Welfare

Principal Investigator

OGIHARA Takuo  高崎健康福祉大学, 薬学部, 教授 (80448886)

Co-Investigator(Kenkyū-buntansha) KAORI Morimoto  高崎健康福祉大学, 薬学部, 講師 (90401009)
MASAHIRO Kajita  高崎健康福祉大学, 薬学部, 准教授 (40591871)
YOKO Idota  高崎健康福祉大学, 薬学部, 研究員 (90629594)
KENTARO Yano  高崎健康福祉大学, 薬学部, 助手 (40644290)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsP-糖タンパク / がん多剤耐性 / 裏打ちタンパク / 膜上発現 / 調節因子 / ERMタンパク / 組織選択性 / radixin / 多剤耐性 / 排出組織 / がん細胞 / 正常組織 / 輸送活性 / ラディキシン / 消化管吸収 / トランスポーター / 脳組織移行性 / シルニジピン / 脳保護作用
Outline of Final Research Achievements

P-glycoprotein (P-gp) excretes many therapeutic drugs from the cytoplasm to outside the cells. Therefore, it is well known as a major factor in multidrug resistance of cancer cells. Our previous study demonstrated that radixin among ezrin, radixin and moesin (ERM proteins) regulated P-gp transport activity and membrane localization. In this study, we investigated the relationship between P-gp and ERM proteins in cancer cells from other organs. The transport activity of intestinal P-gp was regulated by radixin in both normal and cancer cells. On the other hand, it was suggested that none of the ERM proteins affected the renal P-gp in either normal or cancer cells. Thus, we hypothesize that the functional regulation mechanism of P-gp via ERM proteins varies between different organs, such as the intestine and kidney, but not between normal and cancer cells in the same organ.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012 Other

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 1 results) Presentation (15 results) (of which Invited: 2 results) Book (5 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Multiple linear regression analysis indicates association of P-glycoprotein substrate or inhibitor character with bitterness intensity, measured with a sensor2015

    • Author(s)
      Kentaro Yano, Suzune Mita, Kaori Morimoto, Tamami Haraguchi, Hiroshi Arakawa, Miyako Yoshida, Fumiyoshi Yamashita, Takahiro Uchida, Takuo Ogihara
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 104 Issue: 9 Pages: 2789-2794

    • DOI

      10.1002/jps.24232

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of radixin to P-glycoprotein expression and transport activity in mouse small intestine in vivo2013

    • Author(s)
      Yano K, Tomono T, Sakai R, Kano T, Morimoto K, Kato Y, Ogihara T.
    • Journal Title

      J Pharm Sci.

      Volume: 102(8) Issue: 8 Pages: 2875-81

    • DOI

      10.1002/jps.23637

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Alginate enhances excretion and reduces absorption of strontium and cesium in rats2013

    • Author(s)
      dota Y, Harada H, Tomono T, Kobayashi S, Kaminuma C, Miyajima C, Kasahara F, Ogihara T
    • Journal Title

      Biol.Pharm.Bull.

      Volume: 36 Pages: 485-491

    • NAID

      130003382090

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The role of inter-segmental differences in P-glycoprotein expression and activity along the rat small intestine in causing the double-peak phenomenon of substrate plasma concentration2013

    • Author(s)
      S. Wada, T. Kano, S. Mita, Y. Idota, K. Morimoto, F. Yamashita, T. Ogihara
    • Journal Title

      Drug Metab.Pharmacokinet .

      Volume: 28 Pages: 98-103

    • NAID

      130004933523

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Challenges of drug delivery Systems that contribute to cancer chemotherapy2013

    • Author(s)
      T. Ogihara
    • Journal Title

      Biol.Pharm.Bull.

      Volume: 36 Pages: 691-691

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical impact and evidence of pharmacokinetic change by genetic polymorphism2013

    • Author(s)
      T. Ogihara
    • Journal Title

      Drug Metab. Pharmacokinet,

      Volume: 28 Pages: 3-3

    • NAID

      130005435330

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A new high-throughput analysis for drug metabolism profiling using liquid chromatography coupled with tandem mass spectrometry,2013

    • Author(s)
      K. Kusumoto, T. Nagao, T. Ogihara
    • Journal Title

      Drug Res.

      Volume: 63 Issue: 04 Pages: 1-6

    • DOI

      10.1055/s-0033-1333782

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Role of Inter-segmental Differences in P-glycoprotein Expression and Activity along the Rat Small Intestine in Causing the Double-peak Phenomenon of Substrate Plasma Concentration2013

    • Author(s)
      Sho Wada, Takashi Kano,Suzune Mita, Yoko Idota, Kaori Morimoto, Fumiyoshi Yamashita, Takuo Ogihara
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 28 Issue: 2 Pages: 98-103

    • DOI

      10.2133/dmpk.DMPK-12-RG-005

    • NAID

      130004933523

    • ISSN
      1347-4367, 1880-0920
    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 消化管P-糖タンパク質の輸送機能に対するゴマリグナンの影響2015

    • Author(s)
      大塚杏磨, 伴野拓巳, 矢野健太郎, 金川雅彦, 荒川 大, 荻原琢男
    • Organizer
      第135回日本薬学会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] P-glycoprotein Plays a Key Role in the Contractionary Effects against Brain Infarction of2014

    • Author(s)
      Takumi Tomono, Kentaro Yano, Toshimitsu Motegi, Shinobu Takimoto, Mihoko Hagiwara, Yoko Idota, Takashi Kano, Hiroshi Arakawa, Kaori Morimoto, Chihaya Kakinuma, Akira Takahara, Takuo Ogihara
    • Organizer
      19th North American ISSX/29th JSSX Meeting
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2014-10-19 – 2014-10-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] RadixinによるP-gp機能調節の臓器差2014

    • Author(s)
      大塚杏磨, 矢野健太郎, 川端秀明, 金井祐樹, 伴野拓巳, 荒川 大, 荻原琢男
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Year and Date
      2014-10-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト癌細胞のP-gp輸送活性に対するradixinの関与2014

    • Author(s)
      川端秀明, 矢野健太郎, 大塚杏磨, 金井祐樹, 伴野拓巳, 荒川 大, 荻原琢男
    • Organizer
      第9回トランスポーター研究会年会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-06-14 – 2014-06-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 薬物の苦味によるP-糖タンパクの基質認識性の予測2014

    • Author(s)
      三田鈴音, 矢野健太郎, 荒川 大, 原口珠実, 吉田 都, 内田享弘, 荻原琢男
    • Organizer
      日本薬剤学会 第29回年会
    • Place of Presentation
      大宮
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Contribution of radixin to P-glycoprotein expression and transport activity2013

    • Author(s)
      Yano K, Tomono T, Kawabata H, Idota Y, Morimoto K, Arakawa H, Ogihara T
    • Organizer
      28th JSSX Annual Meeting,
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Research-status Report
  • [Presentation] In vitroによる薬物代謝スクリーニングの現状と留意点,2013

    • Author(s)
      荻原琢男, 井戸田陽子
    • Organizer
      第40回日本毒性学会学術年会
    • Place of Presentation
      千葉
    • Related Report
      2013 Research-status Report
  • [Presentation] Contribution of radixin to P-glycoprotein expression and transport activity in mouse small intestine in vivo,2013

    • Author(s)
      伴野拓巳, 矢野健太郎, 川端秀明, 荒川 大, 荻原琢男
    • Organizer
      第8回トランスポーター研究会年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] Double-peak phenomena caused by intestinal segmental difference of P-glycoprotein activity,2013

    • Author(s)
      Wada S, Ogihara T, Nakanishi T, Tamai
    • Organizer
      4th ISSX/CSSX Joint Workshop
    • Place of Presentation
      Henan, China
    • Related Report
      2013 Research-status Report
  • [Presentation] Radixin is involved in P-glycoprotein expression in small intestine2012

    • Author(s)
      酒井 理予、叶 隆、和田 翔、森本 かおり、荻原 琢男
    • Organizer
      日本薬剤学会第27年会
    • Place of Presentation
      神戸(神戸国際会議場)
    • Related Report
      2012 Research-status Report
  • [Presentation] Contribution of radixin in segmental difference of P-glycoprotein expression in small intestine2012

    • Author(s)
      伴野 拓巳、酒井 理予、矢野 健太郎、叶 隆、森本 かおり、加藤 将夫、荻原 琢男
    • Organizer
      日本薬物動態学会第27年会
    • Place of Presentation
      千葉(タワーホール船堀)
    • Related Report
      2012 Research-status Report
  • [Presentation] P-糖タンパク機能発現におけるRadixinの役割

    • Author(s)
      川端秀明, 矢野健太郎, 伴野拓巳, 荒川 大, 荻原琢男
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 苦味センサーを用いたP-糖タンパクの基質認識性の解析

    • Author(s)
      三田鈴音, 矢野健太郎, 荒川 大, 原口珠実, 吉田 都, 内田享弘, 荻原琢男
    • Organizer
      第57回日本薬学会関東支部大会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] トランスポーター科学と薬物動態学の最前線,

    • Author(s)
      出口芳春, 荻原琢男
    • Organizer
      第57回日本薬学会関東支部大会,
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 薬の運び屋トランスポーターその働きを培養細胞で観察しよう

    • Author(s)
      荻原琢男
    • Organizer
      日本学術振興会ひらめき☆ときめきサイエンス
    • Place of Presentation
      高崎
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] 2 試料の調製および分析法, 薬剤学実験法必携マニュアル Pharmaceutical Scientistのために Ⅱ 生物薬剤学2014

    • Author(s)
      荻原琢男, 井戸田陽子
    • Total Pages
      14
    • Publisher
      南江堂
    • Related Report
      2014 Annual Research Report
  • [Book] 第1章 総論, わかりやすい生物薬剤学 第5版2014

    • Author(s)
      荻原琢男
    • Total Pages
      10
    • Publisher
      廣川書店
    • Related Report
      2014 Annual Research Report
  • [Book] 薬剤学実験法必携マニュアル 生物薬剤学2013

    • Author(s)
      荻原琢男,井戸田陽子
    • Total Pages
      423
    • Publisher
      日本薬剤学会出版委員会(南江堂)
    • Related Report
      2013 Research-status Report
  • [Book] DDS製剤の開発・評価と実用化手法,2013

    • Author(s)
      荻原琢男, 井戸田陽子
    • Publisher
      技術情報協会
    • Related Report
      2013 Research-status Report
  • [Book] DDS製剤の開発・評価と実用化手法2013

    • Author(s)
      荻原琢男,井戸田陽子
    • Total Pages
      680
    • Publisher
      技術情報協会
    • Related Report
      2012 Research-status Report
  • [Remarks] 高崎健康福祉大学薬学部生物薬剤学研究室

    • URL

      http://www.takasaki-u.ac.jp/p_yaku_labo/yaku-03-05/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 高崎健康福祉大学薬学部生物薬剤学研究室 研究業績

    • URL

      http://www.takasaki-u.ac.jp/p_yaku_labo/yaku-03-05/

    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] セシウム排泄剤,有機金属排泄剤,飲食品,飼料および医薬品2013

    • Inventor(s)
      笠原文善,宮島千尋,荻原琢男
    • Industrial Property Rights Holder
      笠原文善,宮島千尋,荻原琢男
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-09-05
    • Related Report
      2013 Research-status Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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