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high-throughput screening for tumor endothelial cell specific inhibitors

Research Project

Project/Area Number 18H02891
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55040:Respiratory surgery-related
Research InstitutionHokkaido University

Principal Investigator

Hida Yasuhiro  北海道大学, 大学病院, 准教授 (30399919)

Co-Investigator(Kenkyū-buntansha) 菊地 奈湖 (間石奈湖)  北海道大学, 歯学研究院, 助教 (00632423)
樋田 京子  北海道大学, 歯学研究院, 教授 (40399952)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords血管新生 / 肺腫瘍 / 肺癌
Outline of Final Research Achievements

Tumor endothelial cells from human clinical tumors and normal endothelial cells from non-cancerous portions were isolated and cultured. FACS analysis and RT-PCR confirmed the establishment of highly pure primary cultured cells. The hTERT gene was transfected into these primary cultured cells, and more than 50 generations of passages were possible. The transgenic cells maintained a endothelial cell phenotype. The transgenic cells retained the phenotype of endothelial cells and the characteristic differences in gene expression observed in primary cultured cells were also retained, and it was confirmed that the cells met the conditions for use in cell-based high through-put assays. We are validating the inhibitors found by screening and verifying in the preclinical models.

Academic Significance and Societal Importance of the Research Achievements

血管新生阻害剤はさまざまな固形癌の治療に使用されているが,分子標的であるVEGFやVEGF受容体は正常血管内皮細胞の保持に必須な分子であるために,高血圧,出血,創傷治癒遅延などの副作用が不可避である点が課題として残っている.本研究では正常血管内皮細胞と腫瘍血管内皮細胞の違いを利用してhigh-through put screeningで腫瘍血管内皮細胞特異的な阻害剤を探索する手法を確立出来た.今後理想的な次世代腫瘍血管新生阻害の開発に寄与することが期待している.

Report

(3 results)
  • 2021 Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (7 results)

All 2021 2020

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 5 results)

  • [Journal Article] miRNA-1246 in extracellular vesicles secreted from metastatic tumor induces drug resistance in tumor endothelial cells2021

    • Author(s)
      Torii Chisaho、Maishi Nako、Kawamoto Taisuke、Morimoto Masahiro、Akiyama Kosuke、Yoshioka Yusuke、Minami Takashi、Tsumita Takuya、Alam Mohammad Towfik、Ochiya Takahiro、Hida Yasuhiro、Hida Kyoko
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 13502-13502

    • DOI

      10.1038/s41598-021-92879-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correlation between endothelial CXCR7 expression and clinicopathological factors in oral squamous cell carcinoma2021

    • Author(s)
      Yanagiya Misa、Dawood Randa I. H.、Maishi Nako、Hida Yasuhiro、Torii Chisaho、Annan Dorcas A.、Kikuchi Hiroshi、Yanagawa Matsuda Aya、Kitamura Tetsuya、Ohiro Yoichi、Shindoh Masanobu、Tanaka Shinya、Kitagawa Yoshimasa、Hida Kyoko
    • Journal Title

      Pathology International

      Volume: - Issue: 6 Pages: 1-9

    • DOI

      10.1111/pin.13094

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of stromal biglycan promotes normalization of the tumor microenvironment and enhances chemotherapeutic efficacy2021

    • Author(s)
      Cong Li、Maishi Nako、Annan Dorcas A.、Young Marian F.、Morimoto Hirofumi、Morimoto Masahiro、Nam Jin-Min、Hida Yasuhiro、Hida Kyoko
    • Journal Title

      Breast Cancer Research

      Volume: 23 Issue: 1 Pages: 51-51

    • DOI

      10.1186/s13058-021-01423-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Biglycan, tumor endothelial cell secreting proteoglycan, as possible biomarker for lung cancer2021

    • Author(s)
      Morimoto Hirofumi、Hida Yasuhiro、Maishi Nako、Nishihara Hiroshi、Hatanaka Yutaka、Li Cong、Matsuno Yoshihiro、Nakamura Toru、Hirano Satoshi、Hida Kyoko
    • Journal Title

      Thoracic Cancer

      Volume: - Issue: 9 Pages: 1-11

    • DOI

      10.1111/1759-7714.13907

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemotherapy-Induced IL8 Upregulates MDR1/ABCB1 in Tumor Blood Vessels and Results in Unfavorable Outcome2020

    • Author(s)
      Kikuchi H, Maishi N, Annan DA, Alam MT, Dawood RIH, Sato M, Morimoto M, Takeda R, Ishizuka K, Matsumoto R, Akino T, Tsuchiya K, Abe T, Osawa T, Miyajima N, Maruyama S, Harabayashi T, Azuma M, Yamashiro K, Ameda K, Kashiwagi A, Matsuno Y, Hida Y, Shinohara N, Hida K.
    • Journal Title

      Cancer Res

      Volume: 80 Pages: 2996-3008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemotherapy-induced IL-8 upregulates MDR1/ABCB1 in tumor blood vessels and results in unfavorable outcome2020

    • Author(s)
      Kikuchi Hiroshi、Maishi Nako、Annan Dorcas A.、Towfik Alam Mohammad、Sato Masumi、Morimoto Masahiro、Takeda Ryo、Ishizuka Keita、Matsumoto Ryuji、Akino Tomoshige、Matsuno Yoshihiro、Hida Yasuhiro、Shinohara Nobu、Hida Kyoko
    • Journal Title

      Cancer Research

      Volume: 80 Issue: 14 Pages: 2996-3008

    • DOI

      10.1158/0008-5472.can-19-3791

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor Endothelial Cell-A Biological Tool for Translational Cancer Research2020

    • Author(s)
      Annan Dorcas Akuba-Muhyia、Kikuchi Hiroshi、Maishi Nako、Hida Yasuhiro、Hida Kyoko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 9 Pages: 3238-3238

    • DOI

      10.3390/ijms21093238

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access

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Published: 2018-04-23   Modified: 2024-12-25  

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