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Development of indocyanine green-binding anti-cancer drug with specific accumulation in hepatocellular carcinoma

Research Project

Project/Area Number 17H03595
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor therapeutics
Research InstitutionThe University of Tokyo

Principal Investigator

Hasegawa Kiyoshi  東京大学, 医学部附属病院, 教授 (20292906)

Co-Investigator(Kenkyū-buntansha) 國土 典宏  国立研究開発法人国立国際医療研究センター, その他部局等, 理事長 (00205361)
浦野 泰照  東京大学, 大学院薬学系研究科(薬学部), 教授 (20292956)
稲垣 善則  東京大学, 医学部附属病院, 助教 (40733390)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords肝細胞癌 / 抗癌剤 / ドラッグデリバリーシステム / 物質代謝
Outline of Final Research Achievements

The present study aimed to develop the new anti-cancer drug for hepatocellular carcinoma (HCC) by utilizing indocyanine green (ICG) that has the characteristics of accumulating in HCC. The newly synthesized ICG-Gemcitabine (ICG-Gem) accumulated in HCC tissue as well as ICG. The cytotoxicity of ICG-Gem to normal cells was weaker than that of gemcitabine (Gem) while the cytotoxicity to HCC cells was comparable. The direct injection of ICG-Gem to mouse tumor xenograft had the effect to inhibit the tumor growth compared with that of Gem. These results suggest that ICG-Gem may be available for the new anti-cancer drug of hepatic arterial infusion chemotherapy.

Academic Significance and Societal Importance of the Research Achievements

本研究では、肝細胞癌(HCC)組織におけるインドシアニングリーン(ICG)の特異的滞留性がHCCへの抗癌剤の送達に有用であることを示唆した。この成果は、非特異的な毒性の発生という課題を抱えており、開発が立ち遅れているHCCに対する新規抗癌剤の開発に貢献するものと期待される。また、ICGの特異的滞留性機構の解明は、HCC細胞における特有の代謝機構の存在を立証することにつながり、学術的に意義深い。

Report

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

    (26 results)

All 2019 2018 2017

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (18 results) (of which Int'l Joint Research: 10 results,  Invited: 4 results)

  • [Journal Article] Albumin?Indocyanine Green Evaluation (ALICE) grade combined with portal hypertension to predict post‐hepatectomy liver failure2019

    • Author(s)
      Shirata Chikara、Kokudo Takashi、Arita Junichi、Akamatsu Nobuhisa、Kaneko Junichi、Sakamoto Yoshihiro、Kokudo Norihiro、Hasegawa Kiyoshi
    • Journal Title

      Hepatology Research

      Volume: 印刷中 Issue: 8 Pages: 942-949

    • DOI

      10.1111/hepr.13327

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Albumin-indocyanine green evaluation model in Western population.2019

    • Author(s)
      Shirata C, Hasegawa K.
    • Journal Title

      Journal of Hepatobiliary Pancreatic Science.

      Volume: 26 Issue: 9

    • DOI

      10.1002/jhbp.651

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of Preoperative Liver Function for Surgical Decision Making in Patients with Hepatocellular Carcinoma2019

    • Author(s)
      Kokudo Takashi、Hasegawa Kiyoshi、Shirata Chikara、Tanimoto Meguri、Ishizawa Takeaki、Kaneko Junichi、Akamatsu Nobuhisa、Arita Junichi、Demartines Nicolas、Uldry Emilie、Kokudo Norihiro、Halkic Nermin
    • Journal Title

      Liver Cancer

      Volume: 8 Issue: 6 Pages: 447-456

    • DOI

      10.1159/000501368

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] Usefulness of indocyanine green-fluorescence imaging for real-time visualization of pancreas neuroendocrine tumor and cystic neoplasm2018

    • Author(s)
      Shirata Chikara、Kawaguchi Yoshikuni、Kobayashi Kosuke、Kobayashi Yuta、Arita Junichi、Akamatsu Nobuhisa、Kaneko Junichi、Sakamoto Yoshihiro、Kokudo Norihiro、Hasegawa Kiyoshi
    • Journal Title

      Journal of Surgical Oncology

      Volume: 118 Issue: 6 Pages: 1012-1020

    • DOI

      10.1002/jso.25231

    • 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] 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Portal vein territory identification using indocyanine green fluorescence imaging: Technical details and short-term outcomes2017

    • Author(s)
      Kobayashi Yuta、Kawaguchi Yoshikuni、Kobayashi Kosuke、Mori Kazuhiro、Arita Junichi、Sakamoto Yoshihiro、Hasegawa Kiyoshi、Kokudo Norihiro
    • Journal Title

      Journal of Surgical Oncology

      Volume: 116 Issue: 7 Pages: 921-931

    • DOI

      10.1002/jso.24752

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Mutation analysis of OATP1B3 in cases with indocyanine green excretory defect.2019

    • Author(s)
      Tanimoto M, Kokudo T, Arita J, Ishizawa T, Akamatsu N, Kaneko J, Hasegawa K.
    • Organizer
      第31回日本肝胆膵外科学会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Wide applications of intraoperative fluorescence imaging for prevention of complications after laparoscopic hepato-biliary-pancreatic surgery.2019

    • Author(s)
      Watanabe G, Ishizawa T, Hayasaka M, Morito M, Ito D, Kokudo T, Akamatsu N, Kaneko J, Arita J, Hasegawa K.
    • Organizer
      第31回日本肝胆膵外科学会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Roles of Indocyanine Green in Surgical Treatments for Hepatocellular Carcinoma.2019

    • Author(s)
      Ishizawa T, Ichida A, Akamatsu N, Kaneko J, Arita J, Hasegawa K.
    • Organizer
      APPLE2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Near-Infrared Photothermal/Photodynamic Therapy with Indocyanine Green for Hepatocellular Carcinoma Cells.2019

    • Author(s)
      Shirata C, Kaneko J, Inagaki Y, Kokudo T, Ishizawa T, Akamatsu N, Arita J, Kokudo N.
    • Organizer
      APPLE2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 肝細胞癌に対するICG蛍光法を用いた系統的肝切除術2019

    • Author(s)
      國土 貴嗣, 石沢 武彰, 渡邉 元己, 真木 治文, 市田 晃彦, 金子 順一, 赤松 延久, 有田 淳一, 長谷川 潔
    • Organizer
      第81回日本臨床外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝癌蛍光イメージング:肝切除への臨床応用と光線力学的治療の可能性2019

    • Author(s)
      石沢 武彰, 白田 力, 稲垣 善則, 國土 貴嗣, 廣吉 淳子, 市田 晃彦, 赤松 延久, 有田 淳一, 金子 順一, 神谷 真子, 浦野 泰照, 長谷川 潔
    • Organizer
      第81回日本臨床外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝胆膵外科における術中蛍光イメージングの現況と展望2019

    • Author(s)
      石沢 武彰, 有田 淳一, 長谷川 潔
    • Organizer
      JDDW2019KOBE
    • Related Report
      2019 Annual Research Report
  • [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] 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] Low Expression of OATP1B3 Causes Delay in Indocyanine Green Clearance2018

    • Author(s)
      Tanimoto M, Kokudo T, Arita J, Inagaki Y, Akamatsu N, Kaneko 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] Clearance / Retention / Metabolism tests including ICG2018

    • Author(s)
      Hasegawa K
    • Organizer
      13th IHPBA World Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ICGを中心とした肝細胞癌の新規術前肝機能評価指標の開発2018

    • Author(s)
      國土貴嗣、谷本芽弘理、白田力、有田淳一、金子順一、赤松延久、阪本良弘、長谷川潔
    • Organizer
      第54回日本肝癌研究会
    • 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
  • [Presentation] ICG Navigation in HPB Surgery2018

    • Author(s)
      Hasegawa K
    • Organizer
      IHPBA India 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Surgical resection for HCC with macroscopic vascular invasion2017

    • Author(s)
      Hasegawa K
    • Organizer
      IASGO 2017 (27th World Congress of the International Association of Surgeons)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Assessment of preoperative liver function in patients with hepatocellular carcinoma - The ALICE Grade2017

    • Author(s)
      Kokudo T, Shirata C, Miyazaki Y, Amikura K, Yamaguchi T, Arita J, Kaneko J, Akamatsu N, Sakamoto Y, Takahashi A, Sakamoto H, Kokudo N, Hasegawa K
    • Organizer
      IASGO 2017 (27th World Congress of the International Association of Surgeons)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ICG-guided hepatectomy2017

    • Author(s)
      Hasegawa K, Kawaguchi Y, Yamashita S, Kokudo T, Togashi J, Arita J, Kaneko J, Akamatsu N, Sakamoto Y, Kokudo N.
    • Organizer
      11th International Minimal Invasive Surgery Symposium and 7th CME Course of IASGO
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Intraoperative use ICG in liver surgery2017

    • Author(s)
      Hasegawa K
    • Organizer
      APDW2017 (Asian Pacific Digestive Week)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited

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

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