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2011 Fiscal Year Final Research Report

Development of novel molecular-targeted medicine against aminopeptidase

Research Project

  • PDF
Project/Area Number 21390373
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionThe University of Tokyo

Principal Investigator

KARAKO Takashi (TANG Wei)  東京大学, 医学部附属病院, 助教 (00313213)

Co-Investigator(Kenkyū-buntansha) KOKUDO Norihiro  東京大学, 医学部附属病院, 教授 (00205361)
SEKIMIZU Kazuhisa  東京大学, 薬学系研究科, 教授 (90126095)
NAKATA Munehiro  東海大学, 工学部, 教授 (00266371)
Project Period (FY) 2009 – 2011
Keywords分子標的治療薬 / 肝細胞癌 / 浸潤 / APN / 血管新生
Research Abstract

This study was aimed to develop novel inhibitors of aminopeptidase N(APN) overexpressed on cancer cell membrane and to evaluate the suppressive effect on cancer cell growth and angiogenesis. A newly-synthesized compound 24F, one of hydroxamic acid derivatives, inhibited the activity of aminopeptidases expressed on HL60 cell membrane. This compound inhibited the growth and invasion of hepatoma cell lines. In addition, incubation of vascular endothelial cells with 24F was found to be effective for the suppression of the angiogenic phenomena such as migration and tube formation. Furthermore, a newly-synthesized bestatin derivative LYP also had the ability to inhibit cancer cell growth as well as migration and tube formation of vascular endothelial cells. These results suggest that newly-synthesized aminopeptidase inhibitors are effective as an anti-cancer agent for hepatoma via inhibition of cancer cell invasion and angiogenesis surrounding cancer tissue.

  • Research Products

    (23 results)

All 2012 2011 2010 2009 Other

All Journal Article (16 results) (of which Peer Reviewed: 16 results) Presentation (7 results)

  • [Journal Article] Targeting c-Met as apromising strategy for the treatmentof hepatocellular carcinoma2012

    • Author(s)
      Gao J, Inagaki Y, Song P, Qu X, Kokudo N, Tang W.
    • Journal Title

      Pharmacol Res

      Volume: 65(1) Pages: 23-30

    • DOI

      DOI;j.phrs.2011.11.011

    • Peer Reviewed
  • [Journal Article] Evidence-based research ontraditional Japanese medicine, Kampo, in treatment of gastrointestinalcancer in Japan2012

    • Author(s)
      Gao JJ, Song PP, Qi FH, Kokudo N, Qu XJ, Tang W.
    • Journal Title

      Drug Discov Ther

      Volume: 6(1) Pages: 1-8

    • DOI

      DOI;10.5582/ddt.2012.v6.1.1

    • Peer Reviewed
  • [Journal Article] LYP, a bestatindimethylaminoethyl ester, inhibitedcancer angiogenesis both in vitro and in vivo2011

    • Author(s)
      Gao JJ, Xue X, Gao ZH, Cui SX, Cheng YN, Xu WF, Tang W, Qu XJ.
    • Journal Title

      Microvasc Res

      Volume: 82(2) Pages: 122-130

    • DOI

      DOI;j.mvr.2011.05.008

    • Peer Reviewed
  • [Journal Article] Caffeoylpyrrolidine derivative LY52 inhibitshepatocellular carcinoma invasion viasuppressing matrixmetalloproteinase-22011

    • Author(s)
      Zhao X, Xu HL, Inagaki Y, Kokudo N, Xu WF, Dong JH, Tang W.
    • Journal Title

      Hepatol Int

      Volume: 5(2) Pages: 716-721

    • DOI

      Doi;10.1007/s12072-010-9234-y

    • Peer Reviewed
  • [Journal Article] Effect of c-Met inhibitor SU11274 onhepatocellular carcinoma cell growth2011

    • Author(s)
      Inagaki Y, Qi FH, Gao JJ, Qu XJ, Hasegawa K, Sugawara Y, Tang W, Kokudo N.
    • Journal Title

      Biosci Trends

      Volume: 5(2) Pages: 52-56

    • DOI

      DOI;10.5582/bst.2011.v5.2.52

    • Peer Reviewed
  • [Journal Article] LYP, a novel bestatin derivative, inhibits cell growth and suppressesAPN/CD13 activity in human ovariancarcinoma cells more potently thanbestatin2011

    • Author(s)
      Gao JJ, Gao ZH, Zhao CR, Yuan Y, Cui SX, Zhang XF, Cheng YN, Xu WF, Tang W, Qu XJ.
    • Journal Title

      Invest New Drugs

      Volume: 29(4) Pages: 574-582

    • DOI

      DOI;10.1007/s10637-010-9391-9

    • Peer Reviewed
  • [Journal Article] Antitumor activityof extracts and compounds from the skinof the toad Bufo bufo gargarizans Cantor2011

    • Author(s)
      Qi F, Li A, Inagaki Y, Kokudo N, Tamura S, Nakata M, Tang W.
    • Journal Title

      Int Immunopharmacol

      Volume: 11(3) Pages: 342-349

    • DOI

      DOI;10.1016/j.intimp.2010.12.007

    • Peer Reviewed
  • [Journal Article] Clinical andmolecular insights into thehepatocellular carcinoma tumourmarker des-γ-carboxyprothrombin2011

    • Author(s)
      Inagaki Y, Tang W, Makuuchi M, Hasegawa K, Sugawara Y, Kokudo N.
    • Journal Title

      Liver Int

      Volume: 31(1) Pages: 22-35

    • DOI

      DOI;10.1111/j.1478-3231.2010.02348.x10.1111/j.1478-3231.2010.02348.x

    • Peer Reviewed
  • [Journal Article] Novel aminopeptidase N(APN/CD13) inhibitor 24F can suppressinvasion of hepatocellular carcinomacells as well as angiogenesis2010

    • Author(s)
      Inagaki Y, Tang W, Zhang L, Du G, Xu W, Kokudo N.
    • Journal Title

      Biosci Trends

      Volume: 4(2) Pages: 56-60

    • URL

      http://www.biosciencetrends.com/action/downloaddoc.php?docid=292

    • Peer Reviewed
  • [Journal Article] Chinese herbalmedicines as adjuvant treatment duringchemo-or radio-therapy for cancer2010

    • Author(s)
      Qi F, Li A, Inagaki Y, Gao J, Li J, Kokudo N, Li XK, Tang W.
    • Journal Title

      Biosci Trends

      Volume: 4(6) Pages: 297-307

    • URL

      http://www.biosciencetrends.com/action/downloaddoc.php?docid=369

    • Peer Reviewed
  • [Journal Article] Anti-hepatitis B virus activities ofcinobufacini and its active componentsbufalin and cinobufagin in HepG2. 2. 15cells2010

    • Author(s)
      Cui X, Inagaki Y, Xu H, Wang D, Qi F, Kokudo N, Fang D, Tang W.
    • Journal Title

      Biol Pharm Bull

      Volume: 33(10) Pages: 1728-1732

    • DOI

      DOI;10.1248/bpb.33.1728

    • Peer Reviewed
  • [Journal Article] Apoptosis-inducingactivity of compounds screened andcharacterized from cinobufacini bybioassay-guided isolation2010

    • Author(s)
      Wang DL, Qi FH, Xu HL, Inagaki Y, Orihara Y, Sekimizu K, Kokudo N, Wang FS, Tang W.
    • Journal Title

      Mol Med Rep

      Volume: 3(4) Pages: 717-722

    • DOI

      DOI;10.3892/mmr_00000323

    • Peer Reviewed
  • [Journal Article] Expression of KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma and its potential involvement in tumor cell adhesion and invasion2009

    • Author(s)
      Xu HL, Inagaki Y, Seyama Y, Sugawara Y, Kokudo N, Nakata M, Wang FS, Tang W.
    • Journal Title

      Life Sci

      Volume: 85(9-10) Pages: 395-400

    • DOI

      DOI;10.1016/j.lfs.2009.07.004

    • Peer Reviewed
  • [Journal Article] KL-6mucin in metastatic liver cancertissues from primary colorectalcarcinoma2009

    • Author(s)
      Zhang K, Tang W, Qu X, Guo Q, InagakiY, Seyama Y, Abe H, Gai R, Kokudo N, Sugawara Y, Nakata M, Makuuchi M. Y, Seyama Y, Abe H, Gai R, Kokudo N, Sugawara Y, Nakata M
    • Journal Title

      KL-6mucin in metastatic liver cancertissues from primary colorectalcarcinoma.

      Volume: 56(93) Pages: 960-963

    • Peer Reviewed
  • [Journal Article] Clinicopathology of sialomucin : MUC1, particularly KL-6 mucin, ingastrointestinal, hepatic andpancreatic cancers2009

    • Author(s)
      Inagaki Y, Xu H, Nakata M, Seyama Y, Hasegawa K, Sugawara Y, Tang W, KokudoN.
    • Journal Title

      Biosci Trends

      Volume: 3(6) Pages: 220-232

    • URL

      http://www.biosciencetrends.com/action/downloaddoc.php?docid=258

    • Peer Reviewed
  • [Journal Article] Sustained abberant localization of KL-6 mucin andβ-catenin at theinvasion front of human gastric cancercells

    • Author(s)
      Inagaki Y, Tang W, Xu H, Nakata M, Mafune K, Konishi T, Seto Y, Kokudo N.
    • Journal Title

      Anticancer Res

      Volume: 31(2) Pages: 535-542

    • URL

      http://ar.iiarjournals.org/content/31/2/535.long

    • Peer Reviewed
  • [Presentation] 肝胆膵領域の癌におけるKL-6ムチンの臨床病理学的有用性2011

    • Author(s)
      稲垣善則
    • Organizer
      第52回日本組織細胞化学会総会・学術集会
    • Place of Presentation
      金沢,日本
    • Year and Date
      2011-09-25
  • [Presentation] Biochemical effects ofdes-gamma-carboxy prothrombin on theprogression of hepatocellularcarcinoma2010

    • Author(s)
      Inagaki Y
    • Organizer
      20th World Congress of theInternational Association of Surgeons, Gastroenterologists and Oncologists
    • Place of Presentation
      Cairo, Egypt
    • Year and Date
      2010-10-23
  • [Presentation] Cinobufacini hasanti-hepatitis B virus activities viathe inhibition of RNA transcription invirus-transfected cells2010

    • Author(s)
      Tang W
    • Organizer
      20th World Congress of the InternationalAssociation of Surgeons, Gastroenterologists and Oncologists
    • Place of Presentation
      Cairo, Egypt
    • Year and Date
      2010-10-23
  • [Presentation] アミノペプチダーゼに着目した肝細胞癌再発抑制を目的とする新規分子標的治療薬の開発2010

    • Author(s)
      稲垣善則
    • Organizer
      第15回日本病態プロテアーゼ学会学術集会
    • Place of Presentation
      大阪,日本
    • Year and Date
      2010-08-20
  • [Presentation] Evaluation of KL-6 mucin, atype of MUC1 mucin, as a potentialtarget for diagnosis and therapy ofintrahepatic cholangiocarcinoma2010

    • Author(s)
      Tang W
    • Organizer
      第110回日本外科学会定期学術集会
    • Place of Presentation
      名古屋,日本
    • Year and Date
      2010-04-10
  • [Presentation] LY52, a caffeoylpyrrolidine derivative, suppressinvasion of both HepG2 and HepG2. 2. 15cells via blocking MMP-2 activity2009

    • Author(s)
      Xu HL, Zhao X, Inagaki Y, Kokudo N, Wang FS, Tang W.
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸,日本
    • Year and Date
      2009-10-24
  • [Presentation] Des-gamma-carboxy prothrombinenhances the production of angiogenicfactors in hepatocellular carcinomacells2009

    • Author(s)
      Inagaki Y, Qu XJ, Xu HL, Tang W, Kokudo N.
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸,日本
    • Year and Date
      2009-10-24

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Published: 2013-07-31   Modified: 2015-12-10  

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