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Development of therapeutic agent targeting desmoplasia in pancreatic cancer and novel drug delivery system

Research Project

Project/Area Number 15K10189
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKyushu University

Principal Investigator

SHIRAHANE Kengo  九州大学, 医学研究院, 共同研究員 (10529803)

Co-Investigator(Kenkyū-buntansha) 難波江 俊永  九州大学, 大学病院, 助教 (10467889)
鬼丸 学  九州大学, 医学研究院, 共同研究員 (80529876)
大内田 研宙  九州大学, 大学病院, 講師 (20452708)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords膵癌 / desmoplasia / オートファジー / 化合物ライブラリー / 治療抵抗性 / drug delivery system / カルパイン
Outline of Final Research Achievements

We have reported that activation of pancreatic stellate cells(PSCs) is associated with autophagy and inhibiting autophagy results in suppression of pancreatic cancer progression and metastasis. Thus, autophagy in PSCs is a possible therapeutic target in pancreatic cancer.
Furthermore, we have developed a high-throughput screening system, based on a phenomenon that lipid droplets inside PSCs decrease during activation, to find PSCs suppressive compounds. In detail, candidate agents selected from compound library were administered to PSC, followed by lipid droplets dye with BODIPY, a fluorescent lipid dye. Then quantified the intensity of BODIPY fluorescence and found compounds which suppressed PSCs activation. Using this method we have found some compounds which may lead PSCs into quiescent state.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results)

  • [Journal Article] Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo1802018

    • Author(s)
      Koikawa K, Ohuchida K, Takesue S, Ando Y, Kibe S, Nakayama H, Endo S, Abe T, Okumura T, Horioka K, Sada M, Iwamoto C, Moriyama T, Nakata K, Miyasaka Y, Ohuchida R, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Hashizume M, Nakamura M.
    • Journal Title

      Cancer Letters

      Volume: 412 Pages: 143-154

    • DOI

      10.1016/j.canlet.2017.10.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells2017

    • Author(s)
      Endo Sho、Nakata Kohei、Sagara Akiko、Koikawa Kazuhiro、Ando Yohei、Kibe Shin、Takesue Shin、Nakayama Hiromichi、Abe Toshiya、Okumura Takashi、Moriyama Taiki、Miyasaka Yoshihiro、Ohuchida Kenoki、Ohtsuka Takao、Mizumoto Kazuhiro、Nakamura Masafumi
    • Journal Title

      Pancreatology

      Volume: 17 Issue: 6 Pages: 990-996

    • DOI

      10.1016/j.pan.2017.08.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy is required for activation of pancreatic sstellate cells, associated with pancreatic cancer progression and promotes growth of pancreatic tumors in mice.2017

    • Author(s)
      Endo S, Nakata K, Ohuchida K, Takesue S, Nakayama H, Abe T, Koikawa K, Okumura T, Sada M, Horioka K, Zheng B, Mizuuchi Y, Iwamoto C, Murata M, Moriyama T, Miyasaka Y, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
    • Journal Title

      Gastroenterology

      Volume: 印刷中 Issue: 6 Pages: 1492-1506

    • DOI

      10.1053/j.gastro.2017.01.010

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] オートファジーは膵星細胞の活性化に関与しており、その抑制は膵癌の進展を制御する2017

    • Author(s)
      仲田興平、遠藤翔、大内田研宙、水元一博、小田義直、橋爪誠、中村雅史
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵星細胞が誘導する新たな膵癌局所微小浸潤機序の解明2017

    • Author(s)
      肥川和寛、大内田研宙、森山大樹、仲田興平、宮坂義浩、真鍋達也、大塚隆生、永井英司、水元一博、中村雅史
    • Organizer
      第25回日本消化器関連学会週間 第15回日本消化器外科学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵癌局所浸潤を先導するleading cell -膵星細胞がつくる膵癌局所微少環境の機序解明-2017

    • Author(s)
      肥川和寛、大内田研宙、安藤陽平、岐部晋、中山宏道、武居晋、森山大樹、仲田興平、宮坂義浩、真鍋達也、大塚隆生、永井英司、水元一博、中村雅史
    • Organizer
      第38回癌免疫外科研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵癌の癌関連線維芽細胞におけるオートファジーの役割2016

    • Author(s)
      遠藤翔、仲田興平、佐田政史、大内田研宙、阿部俊也、肥川和寛、奥村隆志、佐田政史、堀岡宏平、水内祐介、大塚隆生、植木隆、永井英司、水元一博、小田義直、中村雅史
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      リーガロイヤルホテル大阪(大阪市)
    • Year and Date
      2016-04-16
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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