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Development of a new postoperative recurrence control method for hepatocellular carcinoma targeting intestinal flora

Research Project

Project/Area Number 19K18137
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionAsahikawa Medical College (2023-2024)
Hokkaido University (2019-2020, 2022)

Principal Investigator

Shimada Shingo  旭川医科大学, 医学部, 助教 (40755576)

Project Period (FY) 2021-11-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脂肪肝 / 肝癌 / 虚血再灌流障害 / ストレス / 肝癌細胞 / イメージング質量分析 / イメージング質量分析法 / 肝細胞癌 / 腸内細菌叢 / 糖尿病
Outline of Research at the Start

脂肪肝を背景とした肝癌切除後における予後因子を探索し、予後改善策を見出す。
脂肪肝を背景とした肝癌モデルを作成し、肝切除モデル、probioticsおよびprebiotics治療のモデルを作成し、a) 肝障害、b) 肝再生、c) 線維化、d) 発癌を評価する。残肝を質量分析イメージング゛法(IMS)で解析し、予測マーカーを見出す。probioticsとして、①Lactobacillus、②Bifidobacterium、③Akkermansiaの投与を行う。prebioticsとしてオリゴ糖の投与を併用する。メトホルミン投与による相互作用も検証する。肝切除前後での腸内細菌叢の変化を検討する。

Outline of Final Research Achievements

1.A 70% partial warm ischemia-reperfusion model was established in fatty liver rats, with ischemia times set at 45 and 75 minutes. Liver and blood samples were collected at the end of ischemia and at 1 and 6 hours after reperfusion.
2.A 70% hepatectomy model was established in rats.
3.Using a hepatocellular carcinoma cell line, the effects of stress caused by steatosis and ischemia-reperfusion on the proliferation and metastasis of hepatocellular carcinoma were investigated in vitro through changes in the microenvironment.

Academic Significance and Societal Importance of the Research Achievements

肝癌細胞株を用いて、脂肪変性や虚血再灌流に伴うストレスが、微小環境の変化を介して肝細胞がんの増殖、転移に与える影響を解析したことにより肝癌と脂肪肝、ストレスが与える影響を解明する一助になった。

Report

(6 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • 2020 Annual Research Report
  • 2019 Research-status Report
  • Research Products

    (24 results)

All 2024 2023 2022 2020 2019

All Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Important Constituents of Heavy Water-containing Solution for Cold Storage and Subsequent Reperfusion on an Isolated Perfused Rat Liver2024

    • Author(s)
      Fukai Moto、Sakamoto Sodai、Shibata Kengo、Ishikawa Takahisa、Kawamura Norio、Fujiyoshi Masato、Fujiyoshi Sunao、Nakamura Kosei、Bochimoto Hiroki、Shimada Shingo、Shimamura Tsuyoshi、Taketomi Akinobu
    • Journal Title

      Transplantation Proceedings

      Volume: 56 Issue: 1 Pages: 223-227

    • DOI

      10.1016/j.transproceed.2023.10.005

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Post‐transplant outcomes and financial burden of donation after circulatory death donor liver transplant after the implementation of acuity circle policy2023

    • Author(s)
      Shimada Shingo、Yoshida Atsushi、Abouljoud Marwan、Miyake Katsunori、Ivanics Tommy、Shamaa Tayseer、Venkat Deepak、Moonka Dilip、Trudeau Sheri、Reed Elizabeth、Nagai Shunji
    • Journal Title

      Clinical Transplantation

      Volume: 38 Issue: 1

    • DOI

      10.1111/ctr.15190

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of the implementation of acuity circle policy on waitlist and post‐transplant outcomes of liver re‐transplantation2023

    • Author(s)
      Shimada Shingo、Shamaa Tayseer、Ivanics Tommy、Miyake Katsunori、Kitajima Toshihiro、Rizzari Michael、Yoshida Atsushi、Abouljoud Marwan、Moonka Dilip、Nagai Shunji
    • Journal Title

      Clinical Transplantation

      Volume: 37 Issue: 6

    • DOI

      10.1111/ctr.14977

    • Related Report
      2023 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Multiple Pretransplant Treatments for Patients Without Pathological Complete Response may Worsen Posttransplant Outcomes in Patients with Hepatocellular Carcinoma.2023

    • Author(s)
      Shimada S, Shamaa T, Ivanics T, Kitajima T, Adhnan M, Collins K, Rizzari M, Yoshida A, Abouljoud M, Salgia R, Nagai S.
    • Journal Title

      Ann Surg Oncol.

      Volume: 30(3) Issue: 3 Pages: 1408-1419

    • DOI

      10.1245/s10434-022-12789-2

    • Related Report
      2023 Research-status Report 2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Combination of Cold Storage in a Heavy Water-Containing Solution and Post-Reperfusion Hydrogen Gas Treatment Reduces Ischemia-Reperfusion Injury in Rat Livers2023

    • Author(s)
      Fukai Moto、Sakamoto Sodai、Shibata Kengo、Fujiyoshi Masato、Fujiyoshi Sunao、Bochimoto Hiroki、Ishikawa Takahisa、Shimada Shingo、Nakamura Kosei、Kawamura Norio、Shimamura Tsuyoshi、Taketomi Akinobu
    • Journal Title

      Transplantation Proceedings

      Volume: 55 Issue: 4 Pages: 1027-1031

    • DOI

      10.1016/j.transproceed.2023.03.061

    • Related Report
      2023 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improvements in liver transplant outcomes in patients with HCV/HIV coinfection after the introduction of direct-acting antiviral therapies.2022

    • Author(s)
      Shimada S, Ivanics T, Kitajima T, Shamaa T, Rizzari M, Collins K, Yoshida A, Abouljoud M, Moonka D, Zhang J, Lu M, Nagai S.
    • Journal Title

      Transpl Infect Dis.

      Volume: 24(2) Issue: 2

    • DOI

      10.1111/tid.13808

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impact on Waitlist Outcomes from Changes in the Medical Eligibility of Candidates for Simultaneous Liver-Kidney Transplantation Following Implementation of the 2017 Organ Procurement and Transplantation Network/United Network for Organ Sharing Policy in the United States.2022

    • Author(s)
      Shimada S, Kitajima T, Suzuki Y, Kuno Y, Shamaa T, Ivanics T, Collins K, Rizzari M, Yoshida A, Abouljoud M, Moonka D, Nagai S.
    • Journal Title

      Ann Transplant.

      Volume: 27

    • DOI

      10.12659/aot.934850

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Liver Transplant Recipient Characteristics Associated With Worse Post-Transplant Outcomes in Using Elderly Donors.2022

    • Author(s)
      Shimada S, Shamaa T, Ivanics T, Kitajima T, Collins K, Rizzari M, Yoshida A, Abouljoud M, Moonka D, Lu M, Nagai S.
    • Journal Title

      Transpl Int.

      Volume: 35 Pages: 10489-10489

    • DOI

      10.3389/ti.2022.10489

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long-term prognostic factors of patients with hepatocellular carcinoma who survive over 10 years after hepatectomy2020

    • Author(s)
      Shimada Shingo、Kamiyama Toshiya、Orimo Tatsuya、Nagatsu Akihisa、Asahi Yoh、Sakamoto Yuzuru、Kamachi Hirofumi、Taketomi Akinobu
    • Journal Title

      Journal of Surgical Oncology

      Volume: - Issue: 8 Pages: 1209-1217

    • DOI

      10.1002/jso.25910

    • NAID

      120007053064

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognoses, outcomes, and clinicopathological characteristics of very elderly patients with hepatocellular carcinoma who underwent hepatectomy2020

    • Author(s)
      Shimada Shingo、Kamiyama Toshiya、Orimo Tatsuya、Nagatsu Akihisa、Asahi Yoh、Sakamoto Yuzuru、Kamachi Hirofumi、Taketomi Akinobu
    • Journal Title

      World Journal of Surgical Oncology

      Volume: 18 Issue: 1 Pages: 122-122

    • DOI

      10.1186/s12957-020-01899-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High HbA1c is a risk factor for complications after hepatectomy and influences for hepatocellular carcinoma without HBV and HCV infection2020

    • Author(s)
      Shimada Shingo、Kamiyama Toshiya、Orimo Tatsuya、Nagatsu Akihisa、Kamachi Hirofumi、Taketomi Akinobu
    • Journal Title

      HepatoBiliary Surgery and Nutrition

      Volume: -

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Heavy Water (D2O) Containing Preservation Solution Reduces Hepatic Cold Preservation and Reperfusion Injury in an Isolated Perfused Rat Liver (IPRL) Model2019

    • Author(s)
      Shimada Shingo、Fukai Moto、Shibata Kengo、Sakamoto Sodai、Wakayama Kenji、Ishikawa Takahisa、Kawamura Norio、Fujiyoshi Masato、Shimamura Tsuyoshi、Taketomi Akinobu
    • Journal Title

      Journal of Clinical Medicine

      Volume: 8 Issue: 11 Pages: 1818-1829

    • DOI

      10.3390/jcm8111818

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 多職種合同チームによる新規生体腎移植プログラム体制の構築2024

    • Author(s)
      島田慎吾、松野直徒、髙橋裕之、内田大貴、菊池信介、和田直樹、佐野麻衣、今井浩二、柿崎秀宏、東信良、横尾英樹
    • Organizer
      第57回日本臨床腎移植学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 脳死および心停止ドナー肝移植における常温機械灌流法の使用成績2023

    • Author(s)
      Shingo Shimada, Katsunori Miyake, Lucy Chau, Michael Rizzari, Atsushi Yoshida, Marwan Abouljoud, Shunji Nagai
    • Organizer
      第49回日本臓器保存生物医学会学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] Clinical Characteristics of New-Onset Diabetes After Liver Transplantation and Outcomes2023

    • Author(s)
      Shingo Shimada, Katsunori Miyake, Deepak Venkat, Humberto Gonzalez, Dilip Moonka, Michael Rizzari, Atsushi Yoshida, Marwan Abouljoud, Shunji Nagai
    • Organizer
      第78回日本消化器外科学会総会
    • Related Report
      2023 Research-status Report
  • [Presentation] 高齢ドナーからの肝移植における考慮すべきレシピエント因子2023

    • Author(s)
      Shingo Shimada, Toshihiro Kitajima, Katsunori Miyake, Tayseer Shamaa, Tommy Ivanics, Michael Rizzari, Atsushi Yoshida, Marwan Abouljoud, Shunji Nagai
    • Organizer
      第123回日本外科学会学術集会
    • Related Report
      2023 Research-status Report
  • [Presentation] Post-transplant outcomes and financial burden in donation after cardiac death donor liver transplant after the implementation of acuity circle allocation policy.2022

    • Author(s)
      Shimada S, Shamaa T, Ivanics T, Kitajima T, Adhnan M, Collins K, Rizzari M, Yoshida A, Abouljoud M, Nagai S.
    • Organizer
      American Transplant Congress 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肝細胞癌に対する肝移植の至適タイミング-移植前治療からみた検討.2022

    • Author(s)
      島田慎吾, 北嶋俊寛, Shamaa T, Ivanics T, Collins K, Rizzari M, Yoshida A, Abouljoud M, 長井俊志.
    • Organizer
      第122回日本外科学会定期学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Post-transplant outcomes and financial burden in donation after cardiac death donor liver transplant compared to brain-death donor.2022

    • Author(s)
      Shimada S, Shamaa T, Ivanics T, Kitajima T, Adhnan M, Collins K, Rizzari M, Yoshida A, Abouljoud M, Nagai S.
    • Organizer
      第34回日本肝胆膵外科学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 肝細胞癌に対する肝移植における移植前治療の移植後予後への影響.2022

    • Author(s)
      島田慎吾, 北嶋俊寛, Shamaa T, Ivanics T, Adhnan M, Collins K, Rizzari M, Yoshida A, Abouljoud M, 長井俊志.
    • Organizer
      第77回日本消化器外科学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 亜区域切除以上の肝切除を施行した80歳以上高齢者肝細胞癌の切除成績と予後因子2020

    • Author(s)
      島田 慎吾、神山 俊哉、折茂 達也、長津 明久、旭 火華、坂本 譲、 蒲池 浩文、武冨 紹信
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Long-term prognostic factors in ten-year survivors after resection of hepatocellular carcinoma2019

    • Author(s)
      Shingo Shimada, Toshiya Kamiyama, Hideki Yokoo, Tatsuya Orimo, Akihisa Nagatsu, Hirofumi Kamachi, and Akinobu Taketomi
    • Organizer
      第31回日本肝胆膵外科学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 肝細胞癌切除後10年生存例における長期予後因子2019

    • Author(s)
      島田慎吾、神山俊哉、横尾 英樹、折茂達也、若山顕治、長津明久、蒲池浩文、武冨紹信
    • Organizer
      第55回日本肝癌研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] 肝細胞癌切除症例における術前HbA1cと予後および術後合併症2019

    • Author(s)
      島田慎吾、神山俊哉、折茂達也、長津明久、旭火華、坂本譲、蒲池浩文、武冨紹信
    • Organizer
      第81回日本臨床外科学会総会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2026-01-16  

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