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Development of novel strategies for the chemoresistant pancreatic tumors using the patient-derived library

Research Project

Project/Area Number 17K09454
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

TAKAHARA NAMINATSU  東京大学, 医学部附属病院, 助教 (10750622)

Co-Investigator(Kenkyū-buntansha) 立石 敬介  東京大学, 医学部附属病院, 講師 (20396948)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords膵癌
Outline of Final Research Achievements

In this project, we established the library of patient-derived tumor xenografts (PDX) and Patient-derived organoids (PDO). Using the system, we performed the drug screening in epigenetic field for the pancreatic cancer cells. Especially, we tried to analyze the mechanism of drug resistance in pancreatic cancer cells. We found the effectiveness of BET inhibitor against the growth of pancreatic cancer PDOs and published the report. We are conducting in vivo validation of in vitro data. Additionally, we analyze the function of target genes in pancreatic cancer.

Academic Significance and Societal Importance of the Research Achievements

申請者らはこれまでに標準治療に抵抗性となった膵癌に対する腹腔内化学療法や新規化学療法regimen の開発に携わるとともに、遺伝子多型SNPや腫瘍マーカーを用いた治療効果予測の有用性を報告してきた。本研究では、患者由来ヒト膵癌異種移植腫瘍を用いることで、化学療法への耐性を改善する低分子化合物の探索とその機序の解明を試みた。ヒト膵癌細胞とマウスでの分子機序における相違点の有無についても解析を行い、新たな膵癌増殖抑制効果を持つエピゲノム分子としての意義を確立した。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (10 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 2 results)

  • [Journal Article] Long-term Risk of Malignancy in Branch-Duct Intraductal Papillary Mucinous Neoplasms.2020

    • Author(s)
      Oyama H, Tada M, Takagi K, Tateishi K, Hamada T, Nakai Y, Hakuta R, Ijichi H, Ishigaki K, Kanai S, Kogure H, Mizuno S, Saito K, Saito T, Sato T, Suzuki T, Takahara N, Morishita Y, Arita J, Hasegawa K, Tanaka M, Fukayama M, Koike K.
    • Journal Title

      Gastroenterology.

      Volume: 158 Issue: 1 Pages: 226-237

    • DOI

      10.1053/j.gastro.2019.08.032

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of age and comorbidity in advanced or recurrent biliary tract cancer receiving palliative chemotherapy.2020

    • Author(s)
      Takahara N, Nakai Y, Saito K, Sasaki T, Suzuki Y, Inokuma A, Oyama H, Kanai S, Suzuki T, Sato T, Hakuta R, Ishigaki K, Saito T, Hamada T, Mizuno S, Kogure H, Tada M, Isayama H, Koike K.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 10 Issue: 10 Pages: 15066-15066

    • DOI

      10.1111/jgh.15066

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation2019

    • Author(s)
      Fujiwara H、Tateishi K、Misumi K、Hayashi A、Igarashi K、Kato H、Nakatsuka T、Suzuki N、Yamamoto K、Kudo Y、Hayakawa Y、Nakagawa 、Tanaka Y、Ijichi H、Kogure H、Nakai Y、Isayama H、Hasegawa K、Fukayama M、Soga T、Koike K
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 18859-18859

    • DOI

      10.1038/s41598-019-55211-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Blocking CXCLs?CXCR2 axis in tumor?stromal interactions contributes to survival in a mouse model of pancreatic ductal adenocarcinoma through reduced cell invasion/migration and a shift of immune-inflammatory microenvironment2019

    • Author(s)
      Sano Makoto、Ijichi Hideaki、Takahashi Ryota、Miyabayashi Koji、Fujiwara Hiroaki、Yamada Tomoharu、Kato Hiroyuki、Nakatsuka Takuma、Tanaka Yasuo、Tateishi Keisuke、Morishita Yasuyuki、Moses Harold L.、Isayama Hiroyuki、Koike Kazuhiko
    • Journal Title

      Oncogenesis

      Volume: 8 Issue: 2 Pages: 8-8

    • DOI

      10.1038/s41389-018-0117-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A feasibility study of gemcitabine, S-1 and leucovorin combination therapy (GSL) for advanced biliary tract cancer2019

    • Author(s)
      Takahara Naminatsu、Isayama Hiroyuki、Nakai Yousuke、Sasaki Takashi、Saito Kei、Sato Tatsuya、Hakuta Ryunosuke、Ishigaki Kazunaga、Saito Tomotaka、Hamada Tsuyoshi、Mizuno Suguru、Kogure Hirofumi、Tada Minoru、Koike Kazuhiko
    • Journal Title

      Journal of Chemotherapy

      Volume: 31 Issue: 5 Pages: 284-289

    • DOI

      10.1080/1120009x.2019.1626088

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Second-line chemotherapy in patients with advanced or recurrent biliary tract cancer: a single center, retrospective analysis of 294 cases2018

    • Author(s)
      Takahara Naminatsu、Nakai Yousuke、Isayama Hiroyuki、Sasaki Takashi、Saito Kei、Oyama Hiroki、Kanai Sachiko、Suzuki Tatsunori、Sato Tatsuya、Hakuta Ryunosuke、Ishigaki Kazunaga、Takeda Tsuyoshi、Saito Tomotaka、Mizuno Suguru、Kogure Hirofumi、Tada Minoru、Koike Kazuhiko
    • Journal Title

      Investigational New Drugs

      Volume: 36 Issue: 6 Pages: 1093-1102

    • DOI

      10.1007/s10637-018-0670-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A phase II trial of gemcitabine, S-1 and LV combination (GSL) neoadjuvant chemotherapy for patients with borderline resectable and locally advanced pancreatic cancer2018

    • Author(s)
      Saito Kei、Isayama Hiroyuki、Sakamoto Yoshihiro、Nakai Yousuke、Ishigaki Kazunaga、Tanaka Mariko、Watadani Takeyuki、Arita Junichi、Takahara Naminatsu、Mizuno Suguru、Kogure Hirofumi、Ijichi Hideaki、Tateishi Keisuke、Tada Minoru、Hasegawa Kiyoshi、Fukayama Masashi、Kokudo Norihiro、Koike Kazuhiko
    • Journal Title

      Medical Oncology

      Volume: 35 Issue: 7 Pages: 100-100

    • DOI

      10.1007/s12032-018-1158-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gemcitabine and S-1 versus gemcitabine and cisplatin treatment in patients with advanced biliary tract cancer: a multicenter retrospective study.2017

    • Author(s)
      Takahara N, Isayama H, Nakai Y, Sasaki T, Ishigaki K, Saito K, Akiyama D, Uchino R, Mizuno S, Yagioka H, Kogure H, Togawa O, Matsubara S, Ito Y, Toda N, Tada M, Koike K.
    • Journal Title

      Invest New Drugs

      Volume: 35(3) Issue: 3 Pages: 269-276

    • DOI

      10.1007/s10637-017-0430-7

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Novel Partially Covered Self-Expandable Metallic Stent with Proximal Flare in Patients with Malignant Gastric Outlet Obstruction.2017

    • Author(s)
      Takahara N, Isayama H, Nakai Y, Yoshida S, Saito T, Mizuno S, Yagioka H, Kogure H, Togawa O, Matsubara S, Ito Y, Yamamoto N, Tada M, Koike K.
    • Journal Title

      Gut Liver.

      Volume: 11(4) Issue: 4 Pages: 481-488

    • DOI

      10.5009/gnl16259

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer.2017

    • Author(s)
      Takahara N, Nakai Y, Isayama H, Sasaki T, Saito K, Noguchi K, Suzuki T, Nakamura T, Sato T, Ishigaki K, Hakuta R, Takeda T, Uchino R, Mizuno S, Kogure H, Tada M, Koike K.
    • Journal Title

      Cancer Chemother Pharmacol.

      Volume: 80(6) Issue: 6 Pages: 1105-1112

    • DOI

      10.1007/s00280-017-3456-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed

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Published: 2017-04-28   Modified: 2021-02-19  

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