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Identification and clinical application of colon cancer-specific gamma-secretase-targeting molecules

Research Project

Project/Area Number 20390361
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

YAMAGUCHI Kouji  Kyushu University, 大学院・医学研究院, 共同研究員 (50191226)

Co-Investigator(Kenkyū-buntansha) KATANO Mitsuo  九州大学, 大学院・医学研究院, 教授 (10145203)
NAKAMURA Masafumi  九州大学, 大学病院, 講師 (30372741)
MORISAKI Takashi  九州大学, 大学院・医学研究院, 共同研究員 (90291517)
ONISHI Hideya  九州大学, 大学院・医学研究院, 准教授 (30553276)
SATOH Norihiro  九州大学, 大学院・医学研究院, 助教 (20423527)
KOJIMA Masayuki  九州大学, 大学病院, 助教 (90380394)
KUBO Makoto  九州大学, 大学病院, 助教 (60403961)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2009: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Keywords大腸癌 / 膵癌 / gamma secretase (GS)複合体 / GS 阻害剤 / Taxane / アポトーシス / 分子標的治療 / 細胞周期 / ガンマセクレターゼ複合体 / Presenilin-1 / Presenilin-2 / Nicastrin / 細胞増殖 / g-secretase / Notch / G2 / M集積 / γ-secretase / 特異的 / 薬剤耐性
Research Abstract

We showed for the first time that gamma secretase (GS) complexes regulate the response of colon and pancreatic cancer cells to taxanes through GS-dependent and GS-independent mechanisms. GS-dependent pathway is independent of Notch signaling. Interestingly, it was strongly indicated that GS complexes regulate the cell cycle progression of these cells in a GS-independent manner. Data suggest that GS complexes could be a new therapeutic target for overcoming resistance to taxanes in these cancers.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (25 results)

All 2010 2009 2008 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (12 results) Remarks (3 results)

  • [Journal Article] Gamma-secretase complexes regulate the response of human pancreatic ductal adenocarcinoma cells to taxanes.2010

    • Author(s)
      Tasaka T, Akiyoshi T, Yamaguchi K, Tanaka M, Onishi H, Katano M
    • Journal Title

      Anticancer Res 30

      Pages: 4999-5010

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Wnt signaling pathway decreases chemotherapy-resistant side-population colon cancer cells.2010

    • Author(s)
      Chikazawa N, Tanaka H, Tasaka T, Nakamura M, Tanaka M, Onishi H, Katano M
    • Journal Title

      Anticancer Res 30

      Pages: 2041-2048

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gamma-secretase complexes regulate the responses of human pancreatic ductal adenocarcinoma cells to taxanes2010

    • Author(s)
      Tasaka T, Yamaguchi K, et al.
    • Journal Title

      Anticancer Research

      Volume: 30 Pages: 4999-5010

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A protein-bound polysaccharide, PSK, enhances tumor suppression induced by docetaxel in a gastric cancer xenograft model.2009

    • Author(s)
      Yamasaki A, Shoda M, Iijima H, Nagai S, Wada J, Suzuki H, Chikazawa N, Tasaka T, Kameda C, Tanaka H, Ikebe M, Jo E, Sato N, Nakamura M, Sekine F, Morisaki T, Katano M
    • Journal Title

      Anticancer Res 29

      Pages: 843-850

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of paclitaxel-induced apoptosis by inhibition of mitogen-activated protein kinase pathway in colon cancer cells.2009

    • Author(s)
      Xu R, Sato N, Yanai K, Akiyoshi T, Nagai S, Wada J, Koga K, Mibu R, Nakamura M, Katano M
    • Journal Title

      Anticancer Res 29

      Pages: 261-270

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of paclitaxel-induced apoptosis by inhibition of mitogen-activated protein kinase pathway in colon cancer cells.2009

    • Author(s)
      Xu R, Sato N, Katano M, et al.
    • Journal Title

      Anticancer Research 29

      Pages: 261-270

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of paclitaxel-induced apoptosis by inhibition of mitogen-activated protein kinase pathway in colon cancer cells2009

    • Author(s)
      Xu R, et al.
    • Journal Title

      Anticancer Res 29

      Pages: 261-270

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gamma-secretase inhibitors enhance taxane-induced mitotic arrest and apoptosis in colon cancer cells.2008

    • Author(s)
      Akiyoshi T, Nakamura M, Yanai K, Nagai S, Wada J, Koga K, Nakashima H, Sato N, Tanaka M, Katano M
    • Journal Title

      Gastroenterology 134

      Pages: 131-144

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Gamma-secretase inhibitors enhance taxane-induced mitoticarrest and apoptosis in colon cancer cells2008

    • Author(s)
      Akiyoshi, et al.
    • Journal Title

      Gastroenterology 134

      Pages: 131-144

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual blockade of phosphatidylinositol 3'-kinase and mitogen-activated protein kinase pathways overcomes paclitaxel-resistance in colorectal cancer.

    • Author(s)
      Xu R, Nakano K, Iwasaki H, Kumagai M, Wakabayashi R, Yamasaki A, Suzuki H, Onishi H, Katano M
    • Journal Title

      Cancer Lett in press

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] 膵癌における新たな治療標的分子:Presenilin2010

    • Author(s)
      田坂健彦
    • Organizer
      第23回日本バイオセラピィ学会総会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-12-10
    • Related Report
      2010 Final Research Report
  • [Presentation] Wntシグナル阻害による大腸癌の抗癌剤耐性克服:siRNA療法の可能性2010

    • Author(s)
      近沢信人
    • Organizer
      第110回日本外科学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2010-04-10
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵癌に対する新たな治療戦略:Paclitaxel/g-secretase阻害剤併用療法の可能性と機序解析2010

    • Author(s)
      田坂健彦
    • Organizer
      第110回日本外科学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2010-04-09
    • Related Report
      2010 Final Research Report
  • [Presentation] g-secretase阻害剤の膵がん治療への応用の可能2009

    • Author(s)
      田坂健彦
    • Organizer
      第22回日本バイオセラピィ学会総会
    • Place of Presentation
      スイスホテル南海大阪
    • Year and Date
      2009-11-27
    • Related Report
      2010 Final Research Report
  • [Presentation] WntシグナルによるABCトランスポーター発現制御:大腸がんの薬剤耐性克服への応用2009

    • Author(s)
      近沢信人
    • Organizer
      第22回日本バイオセラピィ学会総会
    • Place of Presentation
      スイスホテル南海大阪
    • Year and Date
      2009-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] PI(3)キナーゼ経路阻害による大腸癌細胞のPaclitaxel感受性亢進2009

    • Author(s)
      徐睿
    • Organizer
      第22回日本バイオセラピィ学会総会
    • Place of Presentation
      スイスホテル南海大阪
    • Year and Date
      2009-11-26
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵癌における新たな治療標的分子:g-secretase2009

    • Author(s)
      田坂健彦
    • Organizer
      第109回日本外科学会総会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2009-04-04
    • Related Report
      2010 Final Research Report
  • [Presentation] 膵癌における新たな治療標的分子 : g-secretase2009

    • Author(s)
      田坂健彦、片野光男, 他
    • Organizer
      第109回日本外科学会定期学術集会
    • Place of Presentation
      福岡・福岡国際会議場
    • Year and Date
      2009-04-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] g-secretaseを標的とした新たな膵癌治療法の開発2008

    • Author(s)
      田坂健彦
    • Organizer
      第21回日本バイオセラピィ学会総会
    • Place of Presentation
      東京ドームホテル
    • Year and Date
      2008-11-19
    • Related Report
      2010 Final Research Report
  • [Presentation] MAP, PI(3)経路阻害による大腸癌Taxol感受性亢進2008

    • Author(s)
      徐睿
    • Organizer
      第21回日本バイオセラピィ学会総会
    • Place of Presentation
      東京ドームホテル
    • Year and Date
      2008-11-19
    • Related Report
      2010 Final Research Report
  • [Presentation] Wntシグナルを標的とした薬剤抵抗性大腸癌治療法の可能性2008

    • Author(s)
      近沢信人
    • Organizer
      第21回日本バイオセラピィ学会総会
    • Place of Presentation
      東京ドームホテル
    • Year and Date
      2008-11-19
    • Related Report
      2010 Final Research Report
  • [Presentation] γ-secretaseを標的とした新たな膵癌治療法の開発2008

    • Author(s)
      田坂健彦, 他
    • Organizer
      第21回日本バイオセラピィ学会学術集会総会
    • Place of Presentation
      東京ドームホテル
    • Year and Date
      2008-11-19
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      http://WWW.tumor.med.kyushu-u.ac.jp/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.tumor.med.kyushu-u.ac.jp/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.tumor.med.kyushu-u.ac.jp/

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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