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2013 Fiscal Year Final Research Report

Development of novel lead compounds with enhancing effect on ALA-based photodynamic therapy

Research Project

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Project/Area Number 23501305
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Clinical oncology
Research InstitutionKanazawa University

Principal Investigator

ENDO YOSHIO  金沢大学, がん進展制御研究所, 准教授 (30211783)

Co-Investigator(Renkei-kenkyūsha) UTO Yoshihiro  徳島大学, 工学部, 准教授 (20304553)
Project Period (FY) 2011 – 2013
Keywords光線力学的療法 / PDT / 5-アミノレブリン酸 / 5-ALA / トランスポーター / 効果増強剤
Research Abstract

Protoporphyrin IX (PpIX)-dependent photodynamic diagnosis (PDD) and therapy (PDT) using 5-aminolevulinic acid (ALA-PDD and ALA-PDT) are widely recognized novel therapeutic strategies for the treatment of various cancers.Previously, we demonstrated that the balance between the influx of ALA through the transporter PEPT1 and the efflux of intracellular PpIX through the ABC transporter ABCG2 determines the sensitivity of cancer cells to ALA-PDT. Recently, we found that the Schiff base derivative TX-816 could significantly increase the effect of ALA-PDT. The ability of TX-816 to enhance the efficacy of ALA-PDT was markedly stronger than that of dipyridamole, which inhibits ABCG2 and equilibrative nucleoside transporters. Furthermore, TX-816 could recover the sensitivity to ALA-PDT in cancer cells with acquired resistance. These results indicate TX-816 is a potent lead compound to develop an ALA-PDT sensitizer.

  • Research Products

    (18 results)

All 2014 2013 2012 2011

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (13 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Photodynamic detection and management of intraperitoneal spreading of primary peritoneal papillary serous carcinoma in a man : report of a case2014

    • Author(s)
      Canbay E, Ishibashi H, Sako S, Kitai T, Nishino E, Hirano M, Mizumoto A, Endo Y, Ogura S, Yonemura Y
    • Journal Title

      Surg Today

      Volume: 44(2) Pages: 373-377

    • DOI

      10.1007/s00595-013-0500-1

    • Peer Reviewed
  • [Journal Article] Expression levels of PEPT1 and ABCG2 play key roles in 5-aminolevulinic acid (ALA)-induced tumor-specific protoporphyrin IX (PpIX) accumulation in bladder cancer2013

    • Author(s)
      Hagiya Y, Fukuhara H, Matsumoto K, Endo Y, Nakajima M, Tanaka T, Okura I, Kurabayashi A, Furihata M, Inoue K, Shuin T, Ogura S
    • Journal Title

      Photodiagnosis Photodyn Ther

      Volume: 10(3) Pages: 288-295

    • DOI

      10.1016/j.pdpdt.2013.02.001

    • Peer Reviewed
  • [Journal Article] Tumor Suppressor Protein p53-dependent Cell Death Induced by 5-Aminolevulinic Acid (ALA)-based Photodynamic Sensitization of Cancer cells in Vitro2012

    • Author(s)
      Hagiya Y, Endo Y (equal contribution), Yonemura Y, Okura I, Ogura S
    • Journal Title

      ALA-Porphyrin Science

      Volume: 1(1) Pages: 23-31

    • URL

      http://porphyrin-ala.com/wp-content/uploads/21_31.pdf

    • Peer Reviewed
  • [Journal Article] Pivotal roles of peptide transporter PEPT1 and ATP-binding cassette (ABC) transporter ABCG2 in 5-aminolevulinic acid (ALA)-based photocytotoxicity of gastric cancer cells in vitro2012

    • Author(s)
      Hagiya Y, Endo Y, Yonemura Y, Takahashi K, Ishizuka M, Abe F, Tanaka T, Okura I, Nakajima M, Ishikawa T, Ogura S
    • Journal Title

      Photodiagnosis Photodyn Ther

      Volume: 9(3) Pages: 204-214

    • DOI

      10.1016/j.pdpdt.2011.12.004

    • Peer Reviewed
  • [Presentation] ABCG2阻害剤による5-アミノレブリン酸を用いるがん光線力学的療法の効果増強2014

    • Author(s)
      遠藤良夫、小倉俊一郎、米村 豊
    • Organizer
      日本薬学会第134 年会
    • Place of Presentation
      熊本県、熊本市総合体育館
    • Year and Date
      20140327-30
  • [Presentation] 腫瘍移植鶏卵モデルを用いた5-aminolevulinic acid およびTin chlorin e6 の超音波増感活性の評価2014

    • Author(s)
      玉谷 大、宇都義浩、水木佑輔、國安翔太、野口智帆、遠藤良夫、中西郁夫、大久保敬、石塚昌宏、田中 徹、口池大輔、久保健太郎、乾 利夫、堀 均
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本県、熊本市総合体育館
    • Year and Date
      20140327-30
  • [Presentation] Enhanced effect of ALA-PDT using dipyridamole2013

    • Author(s)
      Yoshio Endo, Shun-ichiro Ogura, Yutaka Yonemura, Kimura Masashi
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      神奈川県、パシフィコ横浜
    • Year and Date
      20131003-05
  • [Presentation] Development of antimetastatic hypoxic cytotoxin TX-2137 targeting for Akt/protein kinase B2013

    • Author(s)
      Yoshihiro Uto, Yoshio Endo, Hiroshi Sato, Hitoshi Hori
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      神奈川県、パシフィコ横浜
    • Year and Date
      20131003-05
  • [Presentation] 5-ALAを用いるがんの光線力学的療法における耐性化機序の解析2013

    • Author(s)
      遠藤良夫, 小倉俊一郎, 米村 豊
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      神奈川県、パシフィコ横浜
    • Year and Date
      20130327-30
  • [Presentation] 発育鶏卵を用いた5-aminolevulinic acid およびTin Chlorin e6 の超音波増感活性と薬物動態の評価2013

    • Author(s)
      宇都義浩,玉谷 大,河井智仁,遠藤良夫,大久保敬,中西郁夫,石塚昌宏,田中 徹,口池大輔,久保健太郎,乾 利夫, 堀 均
    • Organizer
      第17回バイオ治療法研究会
    • Place of Presentation
      福岡県、福岡大学病院 福大メディカルホール
    • Year and Date
      2013-12-07
  • [Presentation] 発育鶏卵を用いた5-ALA の超音波増感活性の評価2013

    • Author(s)
      宇都義浩, 玉谷 大, 遠藤良夫, 石塚昌宏, 田中 徹, 堀 均
    • Organizer
      第3回ポルフィリン-ALA 学会年会
    • Place of Presentation
      神奈川県、東京工業大学 すずかけ台キャンパス すずかけホール
    • Year and Date
      2013-04-27
  • [Presentation] Molecular mechanism underlying ALA-PDT resistance in human cancer cells2012

    • Author(s)
      Yoshio Endo, Shun-ichiro Ogura, Yutaka Yonemura, Masahiro Ishizuka, Katsushi Inoue, Kiwamu Takahashi, Motowo Nakajima, Masashi Kimura
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      北海道、ロイトン札幌、札幌市教育文化会館
    • Year and Date
      20120919-21
  • [Presentation] Visualization and detection small PC by 5-aminolevulinic acid (5-ALA)2012

    • Author(s)
      Yutaka Yonemura, Yoshio Endo, Shun-ichiro Ogura, Akiyoshi Mizumoto, Haruki Ishibashi, Candy Emel
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      北海道、ロイトン札幌、札幌市教育文化会館
    • Year and Date
      20120919-21
  • [Presentation] 5-アミノレブリン酸を用いるがんの光線力学的療法感受性と膜輸送系の関連性2012

    • Author(s)
      遠藤良夫, 小倉俊一郎, 萩谷祐一郎, 米村 豊, 石塚昌宏, 井上克司, 高橋究, 中島元夫
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道、北海道大学
    • Year and Date
      20120328-31
  • [Presentation] Significance of membrane transporters in determining the ALA-PDT sensitivity in human cancer cells2011

    • Author(s)
      Yoshio Endo, Shun-ichiro Ogura, Yuichiro Hagiya, Yutaka Yonemura, Masahiro Ishizuka, Tohru Tanaka, Katsushi inoue, Kiwamu Takahashi, Motowo Nakajima, Masashi Kimura
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      愛知県、国際会議場
    • Year and Date
      20111003-05
  • [Presentation] Pivotal Role of PEPT1 and ABCG2 on 5-Aminolevulinic Acid (ALA)-based Photodynamic Sensitization of Gastric Cancer Cells in Vitro2011

    • Author(s)
      Yuichiro Hagiya, Yoshio Endo, Yutaka Yonemura, Kiwamu Takahashi, Masahiro Ishizuka, Fuminori Abe, Motowo Nakajima, Toshihisa Ishikawa, Shun-ichiro Ogura
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      愛知県、国際会議場
    • Year and Date
      20111003-05
  • [Presentation] Role of membrane transporters in determining ALA-PDT sensitivity in human cancer cells2011

    • Author(s)
      Yoshio Endo, Shun-ichiro Ogura, Yuichiro Hagiya, Yutaka Yonemura, Masahiro Ishizuka, Tohru Tanaka, Katsushi inoue, Kiwamu Takahashi, Motowo Nakajima
    • Organizer
      日本分子生物学会第11回春季シンポジウム
    • Place of Presentation
      石川県、金沢、石川県立音楽堂
    • Year and Date
      2011-05-25
  • [Patent(Industrial Property Rights)] PDT 効果増強剤WO/2013/1870692013

    • Inventor(s)
      遠藤良夫、宇都義浩、堀均、田中徹、石塚昌宏、高橋究
    • Industrial Property Rights Holder
      国立大学法人金沢大学、国立大学法人徳島大学、SBIファーマ株式会社(共同出願)
    • Industrial Property Rights Type
      国際出願 A61K 31/197
    • Industrial Property Number
      PCT/JP2013/003728
    • Filing Date
      2013-06-13
    • Overseas

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Published: 2015-07-16  

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