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2013 Fiscal Year Final Research Report

The basic study of molecular targeted therapy via pancreatic duct tight junctions by using a novel culture system of human pancreatic duct epithelial cells

Research Project

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Project/Area Number 23590404
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human pathology
Research InstitutionSapporo Medical University

Principal Investigator

KOJIMA Takashi  札幌医科大学, 医学部, 教授 (30260764)

Co-Investigator(Renkei-kenkyūsha) MURATA Masaki  札幌医科大学, 医学部, 講師 (10404592)
TAKASAWA Akira  札幌医科大学, 医学部, 助教 (00593021)
Project Period (FY) 2011 – 2013
Keywordsヒト正常膵管上皮細胞 / 膵癌 / 分子標的治療 / PKC / claudin
Research Abstract

In the present study, using normal human pancreatic duct epithelial cells and cancer cell lines. we investigated the basic study targeting tight junction molecules claudin-4, -18 and a signal molecule PKC that highly expressed in pancreatic cancer. Claudin-4 and -18 were regulated via a PKCalpha signal transduction pathway in both human pancreatic duct epithelial cells and cancer cells. The cytotoxic effects of CPE via claudin-4 are thought to be useful as a novel therapeutic tool for pancreatic cancer. The cytotoxicity was not observed at any concentration of CPE, whereas in pancreatic cancer cells, CPE had a dose-dependent cytotoxic effect. PKCalpha inhibitors represent potential therapeutic agents against human pancreatic cancer cells by the use of CPE cytotoxicity via claudin-4.

  • Research Products

    (32 results)

All 2013 2012 2011

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (6 results) Book (1 results)

  • [Journal Article] Expression of tricellulin in epithelail cells and non-epithelial cells2013

    • Author(s)
      Kojima T, Ninomiya T, Konno T, Kohno T, Taniguchi M, Sawada N
    • Journal Title

      Histol Histopathol

      Volume: 28 Pages: 1383-1392

    • URL

      http://www.hh.um.es/Abstracts/Vol_28/28_11/28_11_1383.htm

    • Peer Reviewed
  • [Journal Article]2013

    • Author(s)
      Kojima T, Yamaguchi H, Ito T, Kyuno D, Kono T, Konno T, Sawada N
    • Journal Title

      Tissue Barriers

      Volume: 1 Pages: e24894

    • DOI

      10.4161/tisb.24894

    • Peer Reviewed
  • [Journal Article] Protein kinase Cαinhibitor protects against downregulation of claudin-1 during epithelial-mesenchymal transition of pancreatic cancer2013

    • Author(s)
      Kyuno D, Kojima T, Yamaguchi H, Ito T, Kimura Y, Imamura M, Takasawa A, Murata M, Tanaka S, Hirata K, Sawada N
    • Journal Title

      Carcinogenesis

      Volume: 34 Pages: 1232-43

    • DOI

      10.1093/carcin/bgt057

    • Peer Reviewed
  • [Journal Article] Behavior of tricellulin during destruction and formation of tight junctions under various extracellular calcium conditions2013

    • Author(s)
      Takasawa A, Kojima T, Ninomiya T, Tsujiwaki M, Murata M, Tanaka S, Sawada N
    • Journal Title

      Cell Tissue Res. 2013

      Volume: 351 Pages: 73-84

    • DOI

      10.1007/s00441-012-1512-7

    • Peer Reviewed
  • [Journal Article] Regulation of Tight Junctions in Upper Airway Epithelium2013

    • Author(s)
      Kojima T, Go M, Takano K, Kurose M, Ohkuni T, Koizumi J, Kamekura R, Ogasawara N, Masaki T, Fuchimoto J, Obata K, Hirakawa S, Nomura K, Keira T, Miyata R, Fujii N, Tsutsumi H, Himi T, Sawada N
    • Journal Title

      BioMed Research International

      Volume: 2013 Pages: 947072

    • DOI

      10.1155/2013/947072

    • Peer Reviewed
  • [Journal Article] Curcumin prevents replication of respiratory syncytial virus and the epithelial responses to it in human nasal epithelial cells2013

    • Author(s)
      Obata K, Kojima T, Masaki T, Okabayashi T, Yokota S, Hirakawa S, Nomura K, Takasawa A, Murata M, Tanaka S, Fuchimoto J, Fujii N, Tsutsumi H, Himi T, Sawada N
    • Journal Title

      PloS One

      Volume: 8 Pages: e70225

    • DOI

      10.1371/journal.pone.0070225

    • Peer Reviewed
  • [Journal Article] Marked induction of matrix metalloproteinase-10 by respiratory syncytial virus infection in human nasal epithelial cells2013

    • Author(s)
      Hirakawa S, Kojima T, Obata K, Okabayashi T, Yokota SI, Nomura K, Obonai T, Fuchimoto J, Himi T, Tsutsumi H, Sawada N
    • Journal Title

      J Med Virol

      Volume: 85 Pages: 2141-2150

    • DOI

      10.1002/jmv.23718

    • Peer Reviewed
  • [Journal Article] Humulone suppresses replication of respiratory syncytial virus and release of IL-8 and RANTES in normal human nasal epithelial cells2013

    • Author(s)
      Fuchimoto J, Kojima T, Okabayashi T, Masaki T, Ogasawara N, Obata K, Nomura K, Hirakawa S, Kobayashi N, Shigyo T, Yokota SI, Fujii N, Tsutsumi H, Himi T, Sawada N
    • Journal Title

      Med Mol Morphol

      Volume: 46 Pages: 203-209

    • DOI

      10.1007/s00795-013-0024-1

    • Peer Reviewed
  • [Journal Article] Targeting claudin-4 in human pancreatic cancerRegulation of tight junctions by sex hormones in normal human endometrial epithelial cells and uterus cancer cell line Sawano2013

    • Author(s)
      Someya M, Kojima T, Ogawa M, Ninomiya T, Nomura K, Takasawa A, Murata M, Tanaka S, Saito T, Sawada N
    • Journal Title

      Cell Tissue Res. 2013

      Volume: 354 Pages: 481-494

    • DOI

      10.1007/s00441-013-1676-

    • Peer Reviewed
  • [Journal Article] Targeting claudin-4 in human pancreatic cancer2012

    • Author(s)
      Kojima T, Kyuno D, Sawada N
    • Journal Title

      Expert Opinion on Therapeutic Targets

      Volume: 16 Pages: 881-887

    • DOI

      10.1517/14728222.2012.708340

    • Peer Reviewed
  • [Journal Article] Regulation of tight junctions in human normal pancreatic duct epithelial cells and cancer cells2012

    • Author(s)
      Kojima T, Sawada N
    • Journal Title

      Ann N Y Acad Sci

      Volume: 1257 Pages: 85-92

    • DOI

      10.1111/j.1749-6632.2012.06579.x

    • Peer Reviewed
  • [Journal Article] Hop water extract inhibits double-stranded RNA-induced thymic stromal lymphopoietin release from human nasal epithelial cells2012

    • Author(s)
      Fuchimoto J, Kojima T, Kobayashi N, Ohkuni T, Ogasawara N, Masaki T, Obata K, Nomura K, Kondoh A, Shigyo T, Himi T, Sawada N
    • Journal Title

      Am J Rhinol Allergy

      Volume: 26 Pages: 433-438

    • DOI

      10.2500/ajra.2012.26.3814

    • Peer Reviewed
  • [Journal Article] Effects of atelocollagen formulation containing oligonucleotide on endothelial permeability2012

    • Author(s)
      Hanai K, Kojima T, Ota M, Onodera J, Sawada N.
    • Journal Title

      J Drug Deliv

      Volume: 2012 Pages: 245835

    • DOI

      10.1155/2012/245835

    • Peer Reviewed
  • [Journal Article] Regulation of IL-33 and TSLP in human nasal fibroblasts by proinflammatory cytokines2012

    • Author(s)
      Nomura K, Kojima T, Fuchimoto J, Obata K, Keira T, Himi T, Sawada N
    • Journal Title

      Laryngoscope

      Volume: 122 Pages: 1185-1192

    • DOI

      10.1002/lary.23261

    • Peer Reviewed
  • [Journal Article] Expression of claudins 7 and 18 in pancreatic ductal adenocarcinoma : association with features of differentiation2012

    • Author(s)
      Soini Y, Takasawa A, Eskelinen M, Juvonen P, Ka¨rja¨ V, Hasegawa T, Murata M, Tanaka S, Kojima T, Sawada N
    • Journal Title

      J Clin Pathol

      Volume: 65 Pages: 431-436

    • DOI

      10.1136/jclinpath-2011-200400

    • Peer Reviewed
  • [Journal Article] The role of IL-33 and its receptor ST2 in human nasal epithelium with allergic rhinitis2012

    • Author(s)
      Kamekura R, Kojima T, Takano K, Go M, Sawada N, Himi T.
    • Journal Title

      Clinical & Experimental Allergy

      Volume: 42 Pages: 218-228

    • DOI

      10.1111/j.1365-2222.2011.03867.x

    • Peer Reviewed
  • [Journal Article] Claudin-4-targeted therapy using Clostridium perfringens enterotoxin for prostate cancer2012

    • Author(s)
      Maeda T, Murata M, Chiba H, Takasawa A, Tanaka S, Kojima T, Masumori N, Tsukamoto T, Sawada N
    • Journal Title

      Prostate

      Volume: 72 Pages: 351-360

    • DOI

      10.1002/pros.21436

    • Peer Reviewed
  • [Journal Article] Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells2012

    • Author(s)
      Kojima T, Takasawa A, Kyuno, Tatsuya Ito T, Yamaguchi H, Hirata K, Tsujiwaki, Murata M, Tanaka S, Sawada N
    • Journal Title

      Exp Cell Res

      Volume: 317 Pages: 2288-2298

    • DOI

      10.1016/j.yexcr.2011.06.020

    • Peer Reviewed
  • [Journal Article] An NF-κB signaling pathway via PKCδregulates replication of respiratory syncytial virus in polarized normal human nasal epithelial cells2011

    • Author(s)
      Masaki T, Kojima T, Okabayashi T, Ogasawara N, Ohkuni T, Obata K, Takasawa A, Murata M, Tanaka S, Hirakawa S, Fuchimoto J, Ninomiya T, Fujii N, Tsutsumi H, Himi T, Sawada N
    • Journal Title

      Mol Biol Cell

      Volume: 22 Pages: 2144-2156

    • DOI

      10.1091/mbc.E10-11-0875

    • Peer Reviewed
  • [Journal Article] Effects of Clostridium perfringens enterotoxin via claudin-4 on normal human pancreatic duct epithelial cells and cancer cells2011

    • Author(s)
      Yamaguchi H, Kojima T, Ito T, Kyuno D, Kimura Y, Imamura M, Hirata K, Sawada N
    • Journal Title

      Cell Mol Biol Lett

      Volume: 16 Pages: 385-397

    • DOI

      10.2478/s11658-011-0014-z

    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of claudin-18 via specific protein kinase C signaling pathways and modification of DNA-methylation in human pancreatic cancer cells2011

    • Author(s)
      Ito T, Kojima T, Yamaguchi H, Kyuno D, Kimura Y, Imamura M, Takasawa A, Murata M, Tanaka S, Hirata K, Sawada N
    • Journal Title

      J Cell Biochem

      Volume: 112 Pages: 1761-1772

    • DOI

      10.1002/jcb.23095

    • Peer Reviewed
  • [Journal Article] Altered expression of claudin-1, claudin-7, and tricellulin regardless of human papilloma virus infection in human tonsillar squamous cell carcinoma2011

    • Author(s)
      Kondoh A, Takano K, Kojima T, Ohkuni T, Kamekura R, Ogasawara N, Go M, Sawada N, Himi T
    • Journal Title

      Acta-Otolaryngol

      Volume: 131 Pages: 861-868

    • DOI

      10.3109/00016489.2011.562537

    • Peer Reviewed
  • [Journal Article] Poly(I : C) reduces expression of JAM-A and induces secretion of IL-8 and TNF-αvia distinct NF-κB pathways in human nasal epithelial cells2011

    • Author(s)
      Ohkuni T, Kojima T, Ogasawara N, Masaki T, Fuchimoto J, Kamekura R, Koizumi JI, Ichimiya S, Murata M, Tanaka S, Himi T, Sawada N
    • Journal Title

      Toxicol Appl Pharmacol

      Volume: 205 Pages: 29–38

    • DOI

      10.1016/j.taap.2010.09.023

    • Peer Reviewed
  • [Journal Article] Expression and function of claudins in hepatocytes. CLAUDINS : METHODS AND PROTOCOLS2011

    • Author(s)
      Kojima T, Sawada N
    • Journal Title

      Methods Mol Biol

      Volume: 762 Pages: 233-24

    • DOI

      10.1007/978-1-61779-185-7_16

    • Peer Reviewed
  • [Journal Article] Epithelial barrier and antigen uptake in lymphoepithelium of human adenoids2011

    • Author(s)
      Ogasawara N, Kojima T, Go M, Takano KI, Kamekura R, Ohkuni T, Koizumi JI, Masaki T, Fuchimoto J, Obata K, Kurose M, Shintani T, Sawada N, Himi T
    • Journal Title

      Acta Otolaryngol

      Volume: 131 Pages: 116-123

    • DOI

      10.3109/00016489.2010.520022

    • Peer Reviewed
  • [Presentation] ヒト膵管上皮細胞株におけるJun N-terminal kinase (JNK)阻害剤によるバリア機能および細胞の高さの亢進2013

    • Author(s)
      小島隆
    • Organizer
      第65回日本細胞生物学会
    • Place of Presentation
      名古屋
    • Year and Date
      20130619-21
  • [Presentation] PKCα阻害剤は膵癌細胞のEMTにおけるタイト結合分子claudin-1の低下を抑制する2013

    • Author(s)
      及能大輔, 小島隆
    • Organizer
      第114回日本外科学会
    • Place of Presentation
      京都
    • Year and Date
      20130403-05
  • [Presentation] ヒト膵管上皮細胞株におけるJun N-terminal kinase (JNK)阻害剤によるバリア機能および細胞の高さの亢進2012

    • Author(s)
      小島隆,金野匠,及能大輔,澤田典均
    • Organizer
      第44回日本臨床分子形態学会
    • Place of Presentation
      高知
    • Year and Date
      20120928-29
  • [Presentation] 正常ヒト膵菅上皮細胞および膵癌細胞におけるclaudinの発現調節機構の解明2012

    • Author(s)
      小島隆,澤田典均
    • Organizer
      第45回日本臨床分子形態学会,第62回日本顕微鏡学会
    • Place of Presentation
      福岡
    • Year and Date
      20120913-14
  • [Presentation] Regulation of tight junctions in normal human pancreatic duct epithelial cells and cancer cells2011

    • Author(s)
      Kojima T
    • Organizer
      International conference, Berlin 2011
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      20110922-24
  • [Presentation] シンポジウムヒト膵菅上皮細胞におけるタイト結合の調節機構2011

    • Author(s)
      小島隆
    • Organizer
      第62回日本顕微鏡学会
    • Place of Presentation
      福岡
    • Year and Date
      20110516-18
  • [Book] 細胞間結合装置.病気の分子形態学.日本臨床分子形態学会編2011

    • Author(s)
      小島隆,村田雅樹,高澤啓,田中敏,澤田典均
    • Publisher
      学際企画

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Published: 2015-07-16  

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