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Mechanism of recurrence progression after hepatectomy in non-alcoholic steatohepatitis

Research Project

Project/Area Number 19K09095
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55010:General surgery and pediatric surgery-related
Research InstitutionThe University of Tokushima

Principal Investigator

YAMADA Shinichiro  徳島大学, 病院, 特任助教 (30579884)

Co-Investigator(Kenkyū-buntansha) 齋藤 裕  徳島大学, 病院, 講師 (50548675)
森根 裕二  徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60398021)
居村 暁  徳島大学, 病院, 特任教授 (90380021)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsNASH / 肝切除 / 転移性肝癌 / Western diet / 肝発癌 / 腫瘍微小環境 / 大建中湯(TU-100)
Outline of Research at the Start

ウイルス性肝炎由来の肝細胞癌(HCC)の治療に関しては切除が最も根治性が高いが、実臨床において、肝切除によるストレスが残肝再発を促進しうることは経験される。近年肝切除マウスモデルを用いた実験でその機序について検討されているが(Hepatology 2017, Gastroenterology 2018)、NASHにおける再発促進のメカニズムについては依然不明であり、HCCの治療に携わる外科医にとって、このメカニズムを解明することは喫緊の課題である。本研究では、NASH肝切除モデルにおける肝発癌促進の機序解明を目指し、現在NASHを抑制すると考えている薬剤により発癌制御が可能か否かを検討し、NASHにおける病態増悪の予防に繋げたい。

Outline of Final Research Achievements

The aim of this study was to investigate the mechanism of progressed hepatocarcinogenesis after hepatectomy in NASH. However, model of NASH carcinogenesis could not be established. So, colon cancer liver metastasis model after hepatectomy in NASH was investigated. Tumor diameter was significantly smaller in NASH liver than normal liver after hepatectomy. Furthermore, expressions of IL-6 and SAA1 mRNA were significantly lower in NASH liver compared with normal liver. From these findings, liver metastasis was suppressed after hepatectomy in NASH liver due to suppressed metastatic niche.

Academic Significance and Societal Importance of the Research Achievements

近年食生活の欧米化に伴い、非アルコール性脂肪肝炎(NASH)の罹患率は急激に増大している。大腸癌肝転移の根治は外科手術が第一選択となるが、肝転移形成におけるNASHの影響については未だ不明な点が多い。本研究によりそのメカニズムを解明することは、今後増加するであろうNASH肝の転移巣切除の可否等の決定に重要な役割を果たすと考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (8 results)

  • [Journal Article] Inhibition of the VEGF signaling pathway attenuates tumor associated macrophage activity in liver cancer.2022

    • Author(s)
      Shohei Okikawa, Yuji Morine, Yu Saito, Shinichiro Yamada, Kazunori Tokuda, Hiroki Teraoku, Katsuki Miyazaki, Shoko Yamashita, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada
    • Journal Title

      Oncology Reports

      Volume: 47 Pages: 71-71

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cancer associated fibroblast induced M2 polarized macrophages promote hepatocellular carcinoma progression via the plasminogen activator inhibitor 1 pathway.2021

    • Author(s)
      Shuhai Chen, Yuji Morine, Kazunori Tokuda, Shinichiro Yamada, Yu Saito, Masaaki Nishi, Tetsuya Ikemoto, Mitsuo Shimada
    • Journal Title

      International Journal of Oncology

      Volume: 59 Pages: 59-59

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.2021

    • Author(s)
      Luping Gao, Yuji Morine, Shinichiro Yamada, Yu Saito, Tetsuya Ikemoto, Kazunori Tokuda, Chie Takasu, Katsuki Miyazaki, Mitsuo Shimada
    • Journal Title

      PLoS One

      Volume: 16

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The BAFF/NFκB axis is crucial to interactions between sorafenib-resistant HCC cells and cancer-associated fibroblasts.2021

    • Author(s)
      Luping Gao, Yuji Morine, Shinichiro Yamada, Yu Saito, Tetsuya Ikemoto, Kazunori Tokuda, Katsuki Miyazaki, Shouhei Okikawa, Chie Takasu, Mitsuo Shimada
    • Journal Title

      Cancer Science

      Volume: 112 Pages: 3545-3554

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The interaction between cancer associated fibroblasts and tumor associated macrophages via the osteopontin pathway in the tumor microenvironment of hepatocellular carcinoma.2021

    • Author(s)
      Kazunori Tokuda, Yuji Morine, Katsuki Miyazaki, Shinichiro Yamada, Yu Saito, Masaaki Nishi, Takuya Tokunaga, Tetsuya Ikemoto, Satoru Imura, Mitsuo Shimada
    • Journal Title

      Oncotarget

      Volume: 12 Pages: 333-343

    • NAID

      120007188430

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] The role of PAI-1 expression in tumor microenvironment of HCC2021

    • Author(s)
      山田眞一郎, 陳 述海, 島田 光生, 森根 裕二, 居村 暁, 池本 哲也, 齋藤 裕, 徳田 和徳, 沖川 昌平, 岩橋 祥子, 宮崎 克己
    • Organizer
      第121回日本外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] The multifaceted effect of DKT on gastrointestinal disease focusing on microbiome and HSC2020

    • Author(s)
      山田眞一郎, 森根裕二, 居村暁, 池本哲也, 齋藤裕, 徳田和憲, 沖川昌平, 山下祥子, 宮崎克己, 島田光生
    • Organizer
      第82回臨床外科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Nrf2 signaling promotes cancer stemness, migration ability and expression of ABC transporters in sorafenib-resistant hepatocellular carcinoma cell2020

    • Author(s)
      山田眞一郎, 高露萍, 森根裕二, 居村暁, 池本哲也, 齋藤裕, 宮崎克己, 島田光生
    • Organizer
      第31回日本癌発生学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 腫瘍関連マクロファージを介した肝胆膵癌の悪性度獲得に関する検討2020

    • Author(s)
      山田眞一郎, 島田光生, 森根裕二, 居村暁, 池本哲也, 齋藤裕, 吉川雅登, 宮崎克己
    • Organizer
      第53回制癌剤適応研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 原発性肝癌の分子生物学的アプローチによる腫瘍悪性度評価2019

    • Author(s)
      森根裕二、山田眞一郎
    • Organizer
      第30回日本消化器癌発生学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腸管Microbiome解析を加えた大建中湯の消化器疾患に対する多面的効果の検討2019

    • Author(s)
      森根裕二、山田眞一郎
    • Organizer
      第81回日本臨床外科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 大建中湯(TU-100)のNASH発癌抑制効果に関する検討2019

    • Author(s)
      山田眞一郎, 島田光生, 森根裕二, 居村暁, 池本哲也, 岩橋衆一, 齋藤裕, 和田佑馬, 良元俊昭, 西山光恵, 五十嵐康
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 大建中湯(TU-100)のNASH発癌抑制効果に関する検討2019

    • Author(s)
      山田眞一郎, 島田光生, 森根裕二, 居村暁, 池本哲也, 岩橋衆一, 齋藤裕, 良元俊昭, 岩橋祥子, 西山光恵, 五十嵐康
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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