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2008 Fiscal Year Annual Research Report

HSP32を標的とする高分子型制癌剤PEG化亜鉛プロトポルフィリン(ZnP)

Research Project

Project/Area Number 20015045
Research InstitutionSojo University

Principal Investigator

前田 浩  Sojo University, 薬学部, 教授 (90004613)

Co-Investigator(Kenkyū-buntansha) 方 軍  崇城大学, 薬学部, 講師 (20412736)
中村 秀明  崇城大学, 薬学部, 助手 (30435151)
KeywordsHSP32阻害剤 / HO-1阻害剤 / 高分子型制癌剤 / DDS / 腫瘍ターゲティング / Znプロトポルフィリン / 新しい光化学療法 / PEG化制癌剤
Research Abstract

本研究の目的は、毒性がなく、腫瘍に集中し、多くの癌腫にユビキタスに有効な画期的制癌剤を開発することである。そのため、HSP-32(HO-1、ヘムオキシゲナーゼ)阻害剤のZn化プロトポルフィリン(ZnPP)をPEG化して行うことである。本年度は所定のPEG化ZnPPの合成法の最適化を行い、Key stepとして98%程度のprotoporphyrin-bis(ethylene-diamine)の作成に成功した。
また、内視鏡光源(xenon光)の照射とPEG-ZnPPとの併用によるDMBAによるラットの化学発がん(乳がん)モデルを用い、より詳細な治療効果を検討した。その結果、PEG-5000と同様、PEG-2000からもT/B比5〜10%の高い腫瘍集積能力を示すPEG-ZnPPを得た。また、腫瘍細胞(腫瘍化リンパ球(K562)および乳がん細胞SW480)へのuptakeをin vitroで、PEG-ZnPPおよびZnPPのもつ自家蛍光をもとに定量した。PEG-ZnPPの細胞へのuptakeはコンフォーカル顕微鏡を使用し、タイムプラス法により解析を行った。同時に比較のためにSMA-ZnPPのとり込みを比べた。

  • Research Products

    (20 results)

All 2009 2008

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (12 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Styrene maleic acid-pirarubicin disrupts tumor microcirculation and enhances the permeability of colorectal Liver Metastases2009

    • Author(s)
      J. Daruwalla, 他
    • Journal Title

      Journal of Vascular Research 46

      Pages: 218-228

    • Peer Reviewed
  • [Journal Article] Polymeric drugs and nanomedicines for efficient tumor targeted drug delivery based on EPR-effect2009

    • Author(s)
      H. Maeda, 他
    • Journal Title

      Eur. J. of Pharmaceutics and Biopharmaceutics 77

      Pages: 409-419

    • Peer Reviewed
  • [Journal Article] Therapeutic strategies by modulating oxygen stress in cancer and inflammation2009

    • Author(s)
      J.Fang, 他
    • Journal Title

      Adv. Drug Delivery Reviews 61

      Pages: 290-302

    • Peer Reviewed
  • [Journal Article] Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia : a novel approach to overcome resistance against imatinib2008

    • Author(s)
      M. Mayerhofer, 他
    • Journal Title

      Blood 111

      Pages: 2200-2210

    • Peer Reviewed
  • [Journal Article] Oxystress inducing antitumor therapeutics via tumor-targeted delivery of PEG-conjugated D-amino acid oxidase2008

    • Author(s)
      J. Fang, 他
    • Journal Title

      International Journal of Cancer 122

      Pages: 1135-1144

    • Peer Reviewed
  • [Journal Article] Targeting of heat-shock protein32/heme oxygenase-1 in canine mastocytoma cells is associated with reduced growth and induction of apoptosis2008

    • Author(s)
      E. Hadzijusufovic, 他
    • Journal Title

      Experimental Hematology 36

      Pages: 1461-1470

    • Peer Reviewed
  • [Presentation] Enhanced permeability and retention (EPR) effect of Solid tumor-The universal mechanism for tumor selective delivery using macromolecular therapeutics and beyond2008

    • Author(s)
      前田浩
    • Organizer
      Seminar at City of Hope
    • Place of Presentation
      City of Hope, Los Angeles, USA
    • Year and Date
      2008-12-12
  • [Presentation] Enhanced permeability and retention (EPR) effect of Solid tumor-The universal mechanism for tumor selective delivery using macromolecular therapeutics and beyond2008

    • Author(s)
      前田浩
    • Organizer
      Seminar at Thomas Jefferson University
    • Place of Presentation
      Thomas Jefferson Univ., Philadelphia, USA
    • Year and Date
      2008-12-08
  • [Presentation] Identification of heat shock protein32(Hsp32)as a novel target in acute lymphoblastic leukemia(ALL)2008

    • Author(s)
      P. Valent, 他
    • Organizer
      American Society of Hematology
    • Place of Presentation
      San Francisco、USA
    • Year and Date
      2008-12-06
  • [Presentation] Oxystress-induced antitumor therapeutics via targeted-inhibiting heme oxygenase-1(HSP32)in tumor2008

    • Author(s)
      方軍他
    • Organizer
      Ehrlich II 2nd World conference on Magic Bullets
    • Place of Presentation
      Nuremberg, Germany
    • Year and Date
      2008-11-28
  • [Presentation] たん白化学/SMANCS/高分子制癌剤からEPR効果の発見まで2008

    • Author(s)
      前田浩
    • Organizer
      The 4th Sojo Frontier Seminar in Pharmaceutical Sciences
    • Place of Presentation
      崇城大学
    • Year and Date
      2008-11-28
  • [Presentation] ミセル化ヘムオキシゲナーゼ-1(熱ショック蛋白質32)阻害剤PZPの抗腫瘍効果と前臨床研究2008

    • Author(s)
      方軍他
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-29
  • [Presentation] ニトログリセリンの局所塗布による表層がんへの高分子制がん剤のデリバリーと治療効果の増強2008

    • Author(s)
      前田浩, 他
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-29
  • [Presentation] クマイ笹高温高圧抽出物の前投与による化学発がんおよび移植がんの抑制効果2008

    • Author(s)
      関孝弘, 他
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-10-29
  • [Presentation] Enhanced antitumor drug-delivery by topical applications of nitroglycerin on superficial tumors2008

    • Author(s)
      前田浩, 他
    • Organizer
      NO 5th International conference
    • Place of Presentation
      Bregenz, Austlia
    • Year and Date
      2008-08-26
  • [Presentation] Highly immunopotentiating and cancer suppressing effect of"Vigorous"extract of Kumaizasa bamboo leaves2008

    • Author(s)
      前田浩, 他
    • Organizer
      Italian-Japanese Joint Symposium
    • Place of Presentation
      Salerno, Italy
    • Year and Date
      2008-06-28
  • [Presentation] Liver cancer in Egypt and an experience of collaboration in cancer treatment2008

    • Author(s)
      前田浩
    • Organizer
      Egypt-Japan Intemational symposium on science&technology
    • Place of Presentation
      早稲田大学
    • Year and Date
      2008-06-09
  • [Presentation] Tumor targeted delivery of PEG*conjugated D-amino acid oxidase for antitumor therapy via enzymatic generation of hydrogen peroxide2008

    • Author(s)
      前田浩
    • Organizer
      International Symposium on Polymer Therapeutics
    • Place of Presentation
      Valencia, Spain
    • Year and Date
      2008-05-27
  • [Book] Pharmaceutical Perspectives of Cancer Therapeutics2009

    • Author(s)
      T. Seki, 他
    • Total Pages
      45
    • Publisher
      AAPS-Springer
  • [Patent(Industrial Property Rights)] Antitumor agents2009

    • Inventor(s)
      H. Maeda
    • Industrial Property Rights Holder
      H. Maeda
    • Industrial Property Number
      US 7514076 B2
    • Filing Date
      20090400
    • Overseas

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Published: 2010-06-11   Modified: 2016-04-21  

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