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Development of biomarkers target on exosomes which derived from stromal cells in premalignant microenvironment.

Research Project

Project/Area Number 16K10601
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

MIYASAKA Yoshihiro  九州大学, 大学病院, 助教 (40507795)

Co-Investigator(Kenkyū-buntansha) 白羽根 健吾  九州大学, 医学研究院, 共同研究員 (10529803)
当間 宏樹  九州大学, 医学研究院, 共同研究員 (80437780)
大内田 研宙  九州大学, 大学病院, 講師 (20452708)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsPDAC / ADM / exosome / micro RNA / biomarker / 膵癌 / バイオマーカー / エクソゾーム / miRNA / 膵液 / 膵星細胞 / 膵前癌病変 / 早期診断
Outline of Final Research Achievements

Most PDAC patients are diagnosed with advanced stage. Identification of biomarkers for early and definitive PDAC diagnosis is crucial. ADM known as morphological change of acinar cells, occurs during pancreatitis and pancreatic cancer progression etc. It has been suggested that ADM may lead to precancerous lesion that precedes pancreatic cancer. We revealed characterization of the ADM phenotype associated with different pathological conditions by RNA sequencing of tissues which captured by laser capture microdissection.
To investigate whether exosomal microRNAs (ex-miRs) could be used as biomarkers for PDAC, we isolated exosomes from pancreatic juice from patients with PDAC and chronic pancreatitis (CP). Relative expression levels of exosomal miR-21 and miR-155, which were reported to overexpress in PDAC tissue and pancreatic juice, were significantly higher in PDAC patients compared with CP patients. Ex-miRs, including ex-miR-21 and ex-miR-155, may represent novel biomarkers of PDAC.

Academic Significance and Societal Importance of the Research Achievements

膵癌の唯一の根治的治療は外科切除であるが、ほとんどの症例が切除不能の状態で診断される。よって、膵臓癌の治療成績改善のためには、画期的な早期診断法によって切除可能な段階で診断することが重要である。本研究において膵癌ハイリスク患者を模したマウスモデルを用いて微小環境内の細胞から早期診断のバイオマーカーとなりうる遺伝子候補を検索し、ヒト膵液由来のexosomeに含まれるマイクロRNAが優れた膵癌診断のバイオマーカーとなりうる可能性を示した。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (6 results)

All 2019 2018 2017

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

  • [Journal Article] Pancreatic juice exosomal microRNAs as biomarkers for detection of pancreatic ductal adenocarcinoma2019

    • Author(s)
      Nakamura S, Sadakari Y, Ohtsuka T, Okayama T, Nakashima Y, Gotoh Y, Saeki K, Mori Y, Nakata K, Miyasaka Y, Onishi H, Oda Y, Goggins M, Nakamura M.
    • Journal Title

      Ann Surg Oncol

      Volume: 印刷中 Issue: 7 Pages: 2104-11

    • DOI

      10.1245/s10434-019-07269-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells.2017

    • Author(s)
      Okumura T, Ohuchida K, Sada M, Abe T, Endo S, Koikawa K, Iwamoto C, Miura D, Mizuuchi Y, Moriyama T, Nakata K, Miyasaka Y, Manabe T, Ohtsuka T, Nagai E, Mizumoto K, Oda Y, Hashizume M, Nakamura M.
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 11 Pages: 18280-18295

    • DOI

      10.18632/oncotarget.15430

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 当科における膵上皮内癌の臨床病理学的検討と膵癌早期発見への展望2017

    • Author(s)
      後藤佳登、森泰寿、大塚隆生、中村聡、中島陽平、伊達健治朗、藤本崇聡、貞苅良彦、仲田興平、宮坂義浩、大内田研宙、永井英司、中村雅史
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵癌における膵周囲脂肪組織線維化と脂肪組織由来幹細胞の役割2017

    • Author(s)
      奥村隆志、大内田研宙、安藤陽平、岐部晋、武居晋、中山宏道、阿部俊也、遠藤翔、肥川和寛、厳子龍、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117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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