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Elucidation of hypoxia-responsive genes that control recurrence after hepatic artery embolization and development of siRNA-loaded embolization preparations

Research Project

Project/Area Number 20K08010
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionHyogo Medical University

Principal Investigator

Takaki Haruyuki  兵庫医科大学, 医学部, 准教授 (30378377)

Co-Investigator(Kenkyū-buntansha) 平田 豊  兵庫医科大学, 医学部, 講師 (10441247)
山門 亨一郎  兵庫医科大学, 医学部, 教授 (20263022)
児玉 大志  兵庫医科大学, 医学部, 助教 (20422834)
鈴木 亮佑  神戸学院大学, 薬学部, 講師 (80611540)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肝癌 / 肝動脈塞栓術 / 低酸素誘導因子 / マイクロ粒子 / siRNA / 塞栓物質 / HIF-1 / PD-L1
Outline of Research at the Start

肝動脈塞栓術による腫瘍の低酸素状態は、低酸素誘導因子依存的に複数の遺伝子を活性化し、ガン細胞を増悪させる主要な因子として注目されている。 そこで、”肝動脈塞栓術の際にHIF-1の蓄積や低酸素応答遺伝子を阻害すれば、抗腫瘍効果を高めることができる” という仮説を立案した。 そして、肝動脈塞栓術の際に用いる塞栓物質に低酸素応答遺伝子を標的としたsiRNAを搭載した新しい塞栓製剤を開発すれば、効果の高い治療ができるのではないかという着想に至った。
本研究の最終目標は、HIF-1の蓄積や低酸素応答遺伝子を制御するsiRNAを搭載した新しい塞栓製剤を開発し、肝動脈塞栓術の治療成績向上を目指すことである。

Outline of Final Research Achievements

In this study, using a biodegradable polymer, we attempted to develop a new vascular embolization material that can be applied to prevent recurrence after hepatic artery embolization. By adjusting the ratio of the polymer solvent and the stabilizing water, the flow rate during preparation, etc., it became possible to freely adjust the particle size. Furthermore, it led to the development of new vascular embolization substances that can inhibit hypoxia-inducible factors involved in liver cancer recurrence.

Academic Significance and Societal Importance of the Research Achievements

肝動脈塞栓術後の再発抑制に応用可能な、新しい血管塞栓物質の開発基盤を確立した。更に、肝癌再発に関与する低酸素誘導因子を標的とする新しい塞栓物質のプロトタイプも作成することができた。今後、臨床への応用が期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (38 results)

All 2023 2022 2021 2020

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 8 results) Presentation (25 results) (of which Int'l Joint Research: 10 results,  Invited: 19 results) Book (1 results)

  • [Journal Article] Impact of the Ablative Margin on Local?Tumor Progression after Radiofrequency Ablation for Lung Metastases from Colorectal Carcinoma: Supplementary Analysis of a Phase II Trial (MLCSG-0802)2023

    • Author(s)
      Hasegawa Takaaki、Takaki Haruyuki、Kodama Hiroshi、Matsuo Keitaro、Yamanaka Takashi、Nakatsuka Atsuhiro、Takao Motoshi、Gobara Hideo、Hayashi Sadao、Inaba Yoshitaka、Yamakado Koichiro
    • Journal Title

      Journal of Vascular and Interventional Radiology

      Volume: 34 Issue: 1 Pages: 31-37.e1

    • DOI

      10.1016/j.jvir.2022.08.032

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Optimal threshold of a control parameter for tomotherapy respiratory tracking: A phantom study2023

    • Author(s)
      Sano Keisuke、Fujiwara Masayuki、Okada Wataru、Tanooka Masao、Takaki Haruyuki、Shibata Mayuri、Nakamura Kenji、Sakai Yusuke、Suzuki Hitomi、Takahashi Kanae、Tanaka Masahiro、Yamakado Koichiro
    • Journal Title

      Journal of Applied Clinical Medical Physics

      Volume: - Issue: 5

    • DOI

      10.1002/acm2.13901

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver regeneration after portal vein embolization: comparison between absolute ethanol and N-butyl-cyanoacrylate in an in vivo rat model2023

    • Author(s)
      Mitsunari Maruyama, Haruyuki Takaki, Naoko Yamada, Yutaka Hirata, Koichiro Yamakado, Hajime Kitagaki
    • Journal Title

      Diagn Interv Radiol

      Volume: Online ahead of print Issue: 4 Pages: 621-627

    • DOI

      10.4274/dir.2022.211144

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Experience of Percutaneous Radiofrequency Ablation Using an arfa RF ABLATION SYSTEM<sup>®</sup> in Various Organs2022

    • Author(s)
      Kinota Naoya、Takaki Haruyuki、Kobayashi Kaoru、Kako Yasukazu、Kodama Hiroshi、Ogasawara Atsushi、Maruyama Mitsunari、Takahagi Motonori、Taniguchi Junichi、Moriyama Taiki、Yokoyama Hiroyuki、Komoto Hisashi、Kunimoto Ryo、Yoshimura Nahomi、Yamakado Koichiro
    • Journal Title

      Interventional Radiology

      Volume: 7 Issue: 3 Pages: 93-99

    • DOI

      10.22575/interventionalradiology.2022-0012

    • ISSN
      2432-0935
    • Year and Date
      2022-11-04
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective Effect of Polaprezinc and Hyperbaric Oxygen Therapy on Radiation-induced Small Intestinal Damage in Mice2022

    • Author(s)
      SUZUKI HITOMI、FUJIWARA MASAYUKI、KODAMA HIROSHI、KAMIKONYA NORIHIKO、NIWA YASUE、YOSHIMURA NAHOMI、KUNIMOTO RYO、TAKAKI HARUYUKI、YAMAKADO KOICHIRO
    • Journal Title

      In Vivo

      Volume: 36 Issue: 5 Pages: 2218-2223

    • DOI

      10.21873/invivo.12948

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation of Angiomyolipoma With Minimal Fat from Clear Cell Renal Cell Carcinoma Using Non-contrast Multiparametric Magnetic Resonance Imaging2022

    • Author(s)
      JOMOTO WATARU、TAKAKI HARUYUKI、YAMAMOTO SHINGO、KANEMATSU AKIHIRO、IGETA MASATAKA、HIROTA SEIICHI、YAMAKADO KOICHIRO
    • Journal Title

      In Vivo

      Volume: 36 Issue: 6 Pages: 2790-2799

    • DOI

      10.21873/invivo.13016

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fogarty Balloon Catheter for Performing Ipsilateral Portal Vein Embolization with Absolute Ethanol2021

    • Author(s)
      Cornelis Francois H.、Barral Matthias、Razakamanantsoa Leo、Takaki Haruyuki、Paye Francois、El-Mouhadi Sanaa
    • Journal Title

      Journal of Vascular and Interventional Radiology

      Volume: 32 Issue: 5 Pages: 775-778

    • DOI

      10.1016/j.jvir.2021.02.007

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Adrenal pheochromocytoma treated by combination of adrenal arterial embolization and radiofrequency ablation2021

    • Author(s)
      Kako Yasukazu、Ueki Ryusuke、Yamamoto Shingo、Takaki Haruyuki、Aoki Yoshitaka、Yokoyama Osamu、Yamakado Koichiro
    • Journal Title

      Clinical Case Reports

      Volume: 9 Issue: 3 Pages: 1261-1265

    • DOI

      10.1002/ccr3.3745

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development and Accuracy Evaluation of Augmented Reality-based Patient Positioning System in Radiotherapy: A Phantom Study2021

    • Author(s)
      TARUTANI KAZUO、TAKAKI HARUYUKI、IGETA MASATAKA、FUJIWARA MASAYUKI、OKAMURA AYAKO、HORIO FUTO、TOUDOU YUKI、NAKAJIMA SATOSHI、KAGAWA KAZUFUMI、TANOOKA MASAO、YAMAKADO KOICHIRO
    • Journal Title

      In Vivo

      Volume: 35 Issue: 4 Pages: 2081-2087

    • DOI

      10.21873/invivo.12477

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term survival following radiofrequency ablation of lung metastases in an elderly patient with calcaneal osteosarcoma2021

    • Author(s)
      Futani Hiroyuki、Takaki Haruyuki、Sawai Tatsuo、Taniguchi Junichi、Kako Yasukazu、Ide Yoshi-Hiro、Yamakado Koichiro、Tachibana Toshiya
    • Journal Title

      Medicine

      Volume: 100 Issue: 34 Pages: e26681-e26681

    • DOI

      10.1097/md.0000000000026681

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatic Artery Embolization Enhances Expression of Programmed Cell Death 1 Ligand 1 in an Orthotopic Rat Hepatocellular Carcinoma Model: In?Vivo and in?Vitro Experimentation2020

    • Author(s)
      Takaki Haruyuki、Hirata Yutaka、Ueshima Eisuke、Kodama Hiroshi、Matsumoto Seiji、Wada Reona、Suzuki Hitomi、Nakasho Keiji、Yamakado Koichiro
    • Journal Title

      Journal of Vascular and Interventional Radiology

      Volume: 31 Issue: 9 Pages: 1475-1482.e2

    • DOI

      10.1016/j.jvir.2020.03.023

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radiofrequency Ablation by a 21-Gauge Internally Cooled Electrode: Ex Vivo and In Vivo Evaluation by Rat Liver2020

    • Author(s)
      Takaki Haruyuki、Kodama Yuki、Miyamoto Hisao、Iijima Yuto、Kikuchi Yoshinari、Kodama Hiroshi、Ueshima Eisuke、Nakasho Keiji、Wada Reona、Yamakado Koichiro
    • Journal Title

      CardioVascular and Interventional Radiology

      Volume: 44 Issue: 1 Pages: 150-155

    • DOI

      10.1007/s00270-020-02660-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 腫瘍アブレーション2023

    • Author(s)
      高木治行
    • Organizer
      日本医学放射線学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 21G細径ラジオ波電極針の開発2023

    • Author(s)
      高木治行
    • Organizer
      日本アブレーション研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 骨軟部腫瘍に対する凍結治療2023

    • Author(s)
      高木治行
    • Organizer
      日本アブレーション研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Combination of Tumor Ablation and Immunotherapy2023

    • Author(s)
      Haruyuki Takaki
    • Organizer
      ISVIR 2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cool-tip進化論―適応拡大が切り拓く新たな地平2022

    • Author(s)
      高木治行
    • Organizer
      日本IVR学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] がん診療とIVR-RFAの適応拡大を含めて2022

    • Author(s)
      高木治行
    • Organizer
      日本IVR学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 大腸癌肝転移に対する動脈塞栓術併用RFA2022

    • Author(s)
      高木治行
    • Organizer
      日本肝癌研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 肺ラジオ波治療2022

    • Author(s)
      高木治行
    • Organizer
      日本IVR学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] リピオドールの細胞内取り込みについての検討2022

    • Author(s)
      高木治行、平田豊、上嶋英介、児玉大志、山門亨一郎
    • Organizer
      第71回関西IVR研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 21G電極針を用いたRFA:抗腫瘍効果の検討2022

    • Author(s)
      高木治行、平田豊、上嶋英介、児玉大志、山門亨一郎
    • Organizer
      第71回関西IVR研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 腎癌RFA後に上行結腸-腎盂瘻をきたした一例2022

    • Author(s)
      加古泰一、高木治行ほか
    • Organizer
      第71回関西IVR研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胸水および肺結節を契機に発見された肺類上皮血管内皮腫の1例2022

    • Author(s)
      波多野倫子、高木治行ほか
    • Organizer
      日本医学放射線学会関西地方会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Translational research for the development of next-generation hepatic embolotherapy2022

    • Author(s)
      Haruyuki Takaki
    • Organizer
      JSIR/APSCVIR 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 次世代TACEの開発2021

    • Author(s)
      高木治行
    • Organizer
      日本肝臓学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 副腎腫瘍のアブレーション2021

    • Author(s)
      高木治行
    • Organizer
      泌尿器画像診断・治療技術研究会 (JSURT)
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Ablation for Bone and Soft Tissue Tumor2021

    • Author(s)
      高木治行
    • Organizer
      RFA凍結療法研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 光イメージングで視認可能な担癌ラットモデルの開発(第2報)2021

    • Author(s)
      高木治行
    • Organizer
      第69回関西IVR研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] IO in 20302021

    • Author(s)
      高木治行
    • Organizer
      ECIO 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Inciting an Immune Response: Ablation2021

    • Author(s)
      高木治行
    • Organizer
      GEST 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Radiofrequency Ablation by Japan Life line2021

    • Author(s)
      高木治行
    • Organizer
      ACTA 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Ablation and Immunomodulation2021

    • Author(s)
      高木治行
    • Organizer
      ACTA 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Hepatic Artery Embolization and Immunomodulation2021

    • Author(s)
      Haruyuki Takaki
    • Organizer
      APSCVIR 2021
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Ablation for Bone and Soft Tissue Tumor2021

    • Author(s)
      Haruyuki Takaki
    • Organizer
      AOCR 2021
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] IO in 20302021

    • Author(s)
      Haruyuki Takaki
    • Organizer
      ECIO 2021
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cancer Neoantigen Presentation Following Interventional Oncology2020

    • Author(s)
      Haruyuki Takaki
    • Organizer
      SIR 2021
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] IVRのすべて2021

    • Author(s)
      吉川 公彦、荒井 保明、山門亨一郎、高木治行ほか
    • Total Pages
      624
    • Publisher
      メジカルビュー社
    • ISBN
      9784758321006
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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