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Construction of the model for the prospective evaluation of intrahepatic metastasis in silico and its application for the drug discovery.

Research Project

Project/Area Number 17K15478
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Inagaki Yoshinori  東京大学, 医学部附属病院, 助教 (40733390)

Research Collaborator CHEN Yu  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords肝細胞癌 / 肝内転移 / 化学療法
Outline of Final Research Achievements

The construction of the model for the evaluation of intrahepatic metastasis is effective for the development of therapeutic method for hepatocellular carcinoma (HCC). The present study aimed to establish the in vivo and the in silico predictive model of evaluating the intrahepatic metastasis. As results, the mouse model of metastasis that shows metastatic foci in the liver by transplanting HCC cells into the spleen was established. In addition, the in vitro cell migration assay was also performed, and the data from those in vitro assay and in vivo model was accumulated in the in silico system. The predictive evaluation of cell migration and metastasis by the in silico system was correlated with those experimental data. However, the quantitative capability of the present in silico system was low because of the large variations in the experimental data. Accumulation of more experimental data is necessary for the accuracy enhancement of the in silico system.

Academic Significance and Societal Importance of the Research Achievements

本研究で構築したin vivo肝内転移モデルは、肝細胞癌細胞の転移を評価するのに有効であり、開発が立ち遅れている肝細胞癌に対する抗癌剤を開発する創薬研究などにおいて有用であると考えられる。また、肝細胞癌の肝内転移に関する分子メカニズムの解明はまだ不十分であり、本モデルは肝細胞癌細胞の転移に重要な分子種の解明に貢献できると考えられる。

Report

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

    (11 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] A novel liver-specific fluorescent anti-cancer drug delivery system using indocyanine green2019

    • Author(s)
      Inagaki Yoshinori、Kokudo Takashi、Kamiya Mako、Uno Shin-nosuke、Sato Masumitsu、Kaneko Junichi、Kokudo Norihiro、Urano Yasuteru、Hasegawa Kiyoshi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 3044-3044

    • DOI

      10.1038/s41598-019-39269-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Host MICA polymorphism as a potential predictive marker in response to chemotherapy for colorectal liver metastases2018

    • Author(s)
      Nishioka Yujiro, Shindoh Junichi, Inagaki Yoshinori
    • Journal Title

      Digestive Disease

      Volume: 36 Issue: 6 Pages: 437-445

    • DOI

      10.1159/000490411

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Innovative treatment for hepatocellular carcinoma (HCC)2018

    • Author(s)
      Kaneko Junichi、Kokudo Takashi、Inagaki Yoshinori、Hasegawa Kiyoshi
    • Journal Title

      Translational Gastroenterology and Hepatology

      Volume: 3 Pages: 78-78

    • DOI

      10.21037/tgh.2018.10.04

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shufeng Jiedu Capsule and its active ingredients induce apoptosis, inhibit migration and invasion, and enhances doxorubicin therapeutic efficacy in hepatocellular carcinoma2018

    • Author(s)
      Xia Jufeng、Rong Ling、Sawakami Tatsuo、Inagaki Yoshinori、Song Peipei、Hasegawa Kiyoshi、Sakamoto Yoshihiro、Tang Wei
    • Journal Title

      Biomedicine & Pharmacotherapy

      Volume: 99 Pages: 921-930

    • DOI

      10.1016/j.biopha.2018.01.163

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Near-infrared photothermal/photodynamic therapy with indocyanine green induces apoptosis of hepatocellular carcinoma cells through oxidative stress2017

    • Author(s)
      Shirata Chikara、Kaneko Junichi、Inagaki Yoshinori、Kokudo Takashi、Sato Masumitsu、Kiritani Sho、Akamatsu Nobuhisa、Arita Junichi、Sakamoto Yoshihiro、Hasegawa Kiyoshi、Kokudo Norihiro
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 13958-13958

    • DOI

      10.1038/s41598-017-14401-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination of Cinobufacini and Doxorubicin Increases Apoptosis of Hepatocellular Carcinoma Cells through the Fas- and Mitochondria-Mediated Pathways2017

    • Author(s)
      Xia Jufeng、Inagaki Yoshinori、Gao Jianjun、Qi Fanghua、Song Peipei、Han Guohua、Sawakami Tatsuo、Gao Bo、Luo Chuan、Kokudo Norihiro、Hasegawa Kiyoshi、Sakamoto Yoshihiro、Tang Wei
    • Journal Title

      Am J Chin Med.

      Volume: 45 Issue: 07 Pages: 1537-1556

    • DOI

      10.1142/s0192415x17500835

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Expression of OATP1B3 in Cases with Indocyanine Green Excretory Defect2018

    • Author(s)
      Tanimoto M, Kokudo T, Arita J, Inagaki Y, Akamatsu N, Kaneko J, Sakamoto Y, Hasegawa K
    • Organizer
      13th IHPBA World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Effect of C-Met Inhibitor on HCC Associated with Portal Vein Tumor Thrombosis2018

    • Author(s)
      Abe S, Kokudo T, Inagaki Y, Kaneko J, Akamatsu N, Arita J, Sakamoto Y, Hasegawa K
    • Organizer
      APASL(the Asian Pacific Association for the Study of the Liver) Single Topic Conference on HCC: Strategy in the New Era
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ICG不耐症を疑う症例におけるOATP1B3の発現解析2018

    • Author(s)
      谷本芽弘理、國土貴嗣、有田淳一、稲垣善則、赤松延久、金子順一、阪本良弘、長谷川潔
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 大腸癌肝転移に対する術前化学療法の奏功規定因子の探索2018

    • Author(s)
      西岡裕次郎、進藤潤一、稲垣善則、五ノ井渉、阿部浩幸、山下俊、有田淳一、赤松延久、金子順一、阪本良弘、國土典宏、長谷川潔
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝細胞癌に対する新規治療としてのIndocyanine greenを用いた光線力学療法の作用メカニズムの検討2018

    • Author(s)
      早阪誠、金子順一、白田力、稲垣善則、國土貴嗣、有田淳一、赤松延久、阪本良弘、長谷川潔
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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