• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of new therapy for liver disease by regulating cellular senescence

Research Project

Project/Area Number 18K06985
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionKanazawa University

Principal Investigator

Sasaki Motoko  金沢大学, 医学系, 准教授 (70225895)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords病理学 / 原発性胆汁性胆管炎 / 自己免疫性疾患 / 細胞老化
Outline of Final Research Achievements

The hypothesis: “Removing senescent cells (senolysis) may be a novel effective therapy for primary biliary cholangitis (PBC)” was verified in this study. This study revealed that cellular senescence was frequently observed in biliary epithelial cells in small bile ducts and bile ductules in PBC and that the degree of cellular senescence was associated with the stage and activity of PBC and inadequate response to UDCA. Furthermore, cell culture study disclosed that senescence-associated molecules upregulated in biliary epithelial cells in PBC, such as Bcl-xL and IFIT3, could be novel therapeutic targets by senolytic drugs and siRNA.

Academic Significance and Societal Importance of the Research Achievements

PBCの国内患者数は5-6万人と推定されており,約30-40%のUDCA無効例に対する新しい治療薬の開発基盤の確立は意義がある。本研究では, PBCにおける胆管細胞老化は, 病期, 活動性, UDCA治療不応性に関連することを明らかにした。また, 細胞老化関連分子Bcl-xLやIFIT3などは,老化細胞除去薬やsiRNAなどを用いた老化細胞除去の有効な標的となった。本研究は, PBCの新しい治療法として老化細胞除去療法が有望である可能性を示した。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (47 results)

All 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (20 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 4 results) Presentation (22 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Book (2 results)

  • [Int'l Joint Research] Department of Pathology/University of Washington/School of Medicine(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Department of Pathology/Kaohsiung Chang Gung Memorial Hospital/Chang Gung University(その他の国・地域: 台湾)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Dept. of Liver and GI Diseases/Biodonostia Health Research Institute/University of the Basque Country(スペイン)

    • Related Report
      2018 Research-status Report
  • [Journal Article] The cyclin-dependent kinase pathway involving CDK1 is a potential therapeutic target for cholangiocarcinoma.2020

    • Author(s)
      Yamamura M, Sato Y, Takahashi K, Sasaki M, Harada K.
    • Journal Title

      Oncol Rep.

      Volume: 43 Pages: 306-317

    • DOI

      10.3892/or.2019.7405

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] MET amplification results in heterogeneous responses to osimertinib in EGFR ‐mutant lung cancer treated with erlotinib2020

    • Author(s)
      Nishiyama Akihiro、Takeuchi Shinji、Adachi Yuta、Otani Sakiko、Tanimoto Azusa、Sasaki Motoko、Matsumoto Shingo、Goto Koichi、Yano Seiji
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 10 Pages: 3813-3823

    • DOI

      10.1111/cas.14593

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunosuppressive tumor microenvironment in occupational cholangiocarcinoma: Supportive evidence for the efficacy of immune checkpoint inhibitor therapy2020

    • Author(s)
      Sato Yasunori, Tanaka Shogo, Kinoshita Masahiko, Takemura Shigekazu, Shinkawa Hiroji, Kokudo Takashi, Hasegawa Kiyoshi, Tanaka Hiromu, Yoshimoto Hidero, Mori Akira, Yamamura Minako, Sasaki Motoko, Harada Kenichi, Kubo Shoji
    • Journal Title

      Journal of Hepato-Biliary-Pancreatic Sciences

      Volume: 27 Issue: 11 Pages: 860-869

    • DOI

      10.1002/jhbp.788

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical features and diagnostic imaging of cholangiolocellular carcinoma compared with other primary liver cancers: a surgical perspective2020

    • Author(s)
      Takamura Hiroyuki, Gabata Ryousuke, Obatake Yoshinao, Nakanuma Shinichi, Hayashi Hironori, Kozaka Kazuto, Sasaki Motoko, et al.
    • Journal Title

      Technology in Cancer Research & Treatment

      Volume: 19

    • DOI

      10.1177/1533033820948141

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fulminant myocarditis and pulmonary cavity lesion induced by disseminated mucormycosis in a chronic hemodialysis patient: Report of an autopsied case.2020

    • Author(s)
      Fujisawa Y, Hara S, Zoshima T, Maekawa N, Inoue D, Sasaki M, Gamou T, Nagata Y, Hayashi K, Takeji A, Ito K, Mizushima I, Fujii H, Kawano M.
    • Journal Title

      Pathol Int.

      Volume: Aug;70(8) Issue: 8 Pages: 557-562

    • DOI

      10.1111/pin.12943

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 画像診断と病理・肝内胆管癌の病理 ここがポイント!WHO分類第5版2020

    • Author(s)
      佐々木素子
    • Journal Title

      肝臓クリニカルアップデート

      Volume: 6 Pages: 101-104

    • NAID

      40022300939

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 【消化器腫瘍II 新WHO分類のポイント 肝胆膵編】混合型肝癌2020

    • Author(s)
      佐々木素子
    • Journal Title

      病理と臨床

      Volume: 38 Pages: 1088-1092

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 特集: 自己免疫性肝疾患. II. 基礎 胆管上皮細胞2020

    • Author(s)
      佐々木素子
    • Journal Title

      日本臨床

      Volume: 78 Pages: 27-33

    • Related Report
      2019 Research-status Report
  • [Journal Article] Increased p16INK4a-expressing senescent bile ductular cells are associated with inadequate response to ursodeoxycholic acid in primary biliary cholangitis.2019

    • Author(s)
      Sasaki M, Sato Y, Nakanuma Y.
    • Journal Title

      J Autoimmun.

      Volume: Epub ahead of print Pages: 102377-102377

    • DOI

      10.1016/j.jaut.2019.102377

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cholangiolocellular Carcinoma With "Ductal Plate Malformation" Pattern May Be Characterized by ARID1A Genetic Alterations.2019

    • Author(s)
      Sasaki M, Sato Y, Nakanuma Y.
    • Journal Title

      Am J Surg Pathol.

      Volume: 43 Issue: 3 Pages: 352-360

    • DOI

      10.1097/pas.0000000000001201

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Asymptomatic giant cell hepatitis: a subtype of post-infantile giant cell hepatitis?2019

    • Author(s)
      Zenda T, Araki I, Sasaki M.
    • Journal Title

      Clin J Gastroenterol

      Volume: 12 Issue: 4 Pages: 367-371

    • DOI

      10.1007/s12328-019-00950-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 特集 胆嚢癌診療の現況 2. 胆嚢癌の病理2019

    • Author(s)
      佐々木素子
    • Journal Title

      臨床消化器内科

      Volume: 34 Pages: 139-145

    • Related Report
      2019 Research-status Report
  • [Journal Article] 画像診断と病理・肝炎ウイルス消失後の画像診断と病理  病理2019

    • Author(s)
      佐々木素子
    • Journal Title

      肝臓クリニカルアップデート

      Volume: 5 Pages: 85-89

    • NAID

      40022088450

    • Related Report
      2019 Research-status Report
  • [Journal Article] Blockade of Hedgehog Signaling Attenuates Biliary Cystogenesis in the Polycystic Kidney (PCK) Rat.2018

    • Author(s)
      Sato Y, Yamamura M, Sasaki M, Harada K
    • Journal Title

      Am J Pathol.

      Volume: 188 Issue: 10 Pages: 2251-2263

    • DOI

      10.1016/j.ajpath.2018.06.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amiodarone-induced reversible and irreversible hepatotoxicity: two case reports2018

    • Author(s)
      Tsuda Toyonobu、Tada Hayato、Tanaka Yoshihiro、Nishida Naoto、Yoshida Taiji、Sawada Takeshi、Sakata Kenji、Hayashi Kenshi、Kawashiri Masa-aki、Oyama Takeru、Sasaki Motoko、Kurose Nozomu、Yamagishi Masakazu
    • Journal Title

      Journal of Medical Case Reports

      Volume: 12 Issue: 1 Pages: 95-95

    • DOI

      10.1186/s13256-018-1629-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An impaired biliary bicarbonate umbrella may be involved in dysregulated autophagy in primary biliary cholangitis2018

    • Author(s)
      Sasaki Motoko, Sato Yasunori, Nakanuma Yasuni
    • Journal Title

      Laboratory Investigation

      Volume: (in press) Issue: 6 Pages: 745-754

    • DOI

      10.1038/s41374-018-0045-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased expression of senescence-associated cell cycle regulators in the progression of biliary atresia: an immunohistochemical study2018

    • Author(s)
      Sasaki Motoko, Kuo Fang-Ying, Huang Chao-Cheng, Swanson Paul E, Chen Chao-Long, Chuang Jiin-Haur, Yeh Matthew M
    • Journal Title

      Histopathology

      Volume: (in press) Issue: 7 Pages: 1164-1171

    • DOI

      10.1111/his.13476

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 胆道疾患におけるオートファジーの関与2018

    • Author(s)
      佐々木素子
    • Journal Title

      胆と膵

      Volume: 39 Pages: 165-171

    • Related Report
      2018 Research-status Report
  • [Journal Article] 誌上デイベート 「IPNB」は胆管癌の前癌病変か」 ①前癌病変であるとする立場から2018

    • Author(s)
      佐々木素子
    • Journal Title

      膵・胆道FRONTIER

      Volume: 7 Pages: 14-17

    • Related Report
      2018 Research-status Report
  • [Journal Article] 画像診断と病理・C 型肝炎ウイルス消失後の肝線維化の評価 病理2018

    • Author(s)
      佐々木素子
    • Journal Title

      肝臓クリニカルアップデート

      Volume: 4 Pages: 85-89

    • NAID

      40021605831

    • Related Report
      2018 Research-status Report
  • [Presentation] Increased expression of interferon- induced protein with tetratricopeptide repeats 3 (Ifit3) in senescent biliary epithelial cells may play a role in the pathogenesis of primary biliary cholangitis2020

    • Author(s)
      Motoko Sasaki, Yasunori Sato and Yasuni Nakanuma
    • Organizer
      AASLD The Liver Meeting Digital Experience; 2020.
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 特別講演 胆道腫瘍アップデート -WHO分類2019と新規約のポイント-2020

    • Author(s)
      佐々木 素子
    • Organizer
      第24回日本病理学会中部支部スライドセミナー (2021年 3月 6日 愛知県がんセンター (WEB))
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 胆管生検の良悪性診断に有用なバイオマーカーの探索2020

    • Author(s)
      佐々木 素子, 佐藤 保則
    • Organizer
      第109回日本病理学会総会(会期4/16-18; 福岡国際会議場;WEB開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胆管腺腫は小型胆管型(small duct type)肝内胆管癌の前癌病変か?2020

    • Author(s)
      佐々木素子 佐藤保則 中沼安二
    • Organizer
      第56回日本肝臓学会総会 (8/28, 29 大阪国際会議場/WEB)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 原発性肝癌におけるNestin発現と臨床病理学的意義の検討2020

    • Author(s)
      佐々木素子 佐藤保則 中沼安二
    • Organizer
      第56回肝癌研究会2020 (会期12/22-23; WEB開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 胆道癌におけるLong interspersed nucleotide factor-1 (LINE-1)ORF1p発現とその臨床病理学的意義の検討2020

    • Author(s)
      佐々木素子 佐藤保則
    • Organizer
      第56回胆道学会総会 (会期10/1-2; WEB開催)
    • Related Report
      2020 Annual Research Report
  • [Presentation] Altered expression of various inflammation and immune-related genes in senescent biliary epithelial cells relating to primary biliary cholangitis2019

    • Author(s)
      Motoko Sasaki, Yasunori Sato
    • Organizer
      Asian Pacific Association for the Study of the Liver Single Topic Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Increased p16INK4a-expressing senescent biliary epithelial cells in ductular reactions is associated with inadequate response to ursodeoxycholic acid and could be a target of senolytic elimination in primary biliary cholangitis2019

    • Author(s)
      Motoko Sasaki, Yasunori Sato and Yasuni Nakanuma
    • Organizer
      AASLD The Liver Meeting 2019 (Boston, November 8-12)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 末梢型-肝内胆管癌の前癌病変の探索2019

    • Author(s)
      佐々木 素子, 佐藤 保則
    • Organizer
      第108回日本病理学会総会(会期5/9-11; 東京国際フォーラム)
    • Related Report
      2019 Research-status Report
  • [Presentation] 原発性胆汁性胆管炎における胆管細胞老化と臨床病理学的特徴の関連2019

    • Author(s)
      佐々木素子 佐藤保則
    • Organizer
      第55回日本肝臓学会総会(会期5/30-31; 京王プラザホテル)
    • Related Report
      2019 Research-status Report
  • [Presentation] パネルディスカッション4「混合型肝癌の亜分類」  混合型肝癌・細胆管癌の組織学的分類と遺伝子異常2019

    • Author(s)
      佐々木素子
    • Organizer
      第55回肝癌研究会 (2019年7月4, 5日 東京)
    • Related Report
      2019 Research-status Report
  • [Presentation] 肝癌の背景肝における胆管腺腫, 胆管微小過誤腫/von Meyenburg complexの発生状況と臨床病理学的意義の検討2019

    • Author(s)
      佐々木素子 佐藤保則 中沼安二
    • Organizer
      第55回肝癌研究会 (2019年7月4, 5日 東京)
    • Related Report
      2019 Research-status Report
  • [Presentation] 胆管検体の病理診断におけるInsulin-like growth factor II mRNA-binding protein 3 (IMP3) 免疫染色の有用性2019

    • Author(s)
      佐々木素子 佐藤保則
    • Organizer
      第55回胆道学会 (2019年10月3, 4日 名古屋)
    • Related Report
      2019 Research-status Report
  • [Presentation] ARID1A alterations may be related to “ductal plate malformation” pattern in cholangiolocellular carcinoma and combined hepatocellular carcinoma-cholangiocarcinoma2018

    • Author(s)
      Motoko Sasaki, Yasunori Sato and Yasuni Nakanuma
    • Organizer
      AASLD The Liver Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Biliary epithelial senescence may play a critical role in the pathogenesis and could be a target of senolytic therapy in primary biliary cholangitis2018

    • Author(s)
      Motoko Sasaki, Yasunori Sato and Yasuni Nakanuma
    • Organizer
      AASLD The Liver Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 混合型肝癌・細胆管癌の遺伝子異常と臨床病理学的特徴との関連2018

    • Author(s)
      佐々木素子 佐藤保則 中沼安二
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 自己免疫性肝疾患の診断と治療の進歩」 原発性胆汁性胆管炎の病態における胆管細胞老化の意義と治療標的としての可能性2018

    • Author(s)
      佐々木素子
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 混合型肝癌・細胆管癌におけるSWI/SNFクロマチンリモデリング遺伝子群異常の臨床病理学的意義2018

    • Author(s)
      佐々木素子 佐藤保則 中沼安二
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 遺伝子異常を基盤とした胆管系分化を伴う肝癌の組織亜分類2018

    • Author(s)
      佐々木素子 佐藤保則 中沼安二
    • Organizer
      第54回肝癌研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] AT-rich interactive domain-containing protein 1A (ARID1A)発現消失を示す胆管性結節は肝内胆管癌の前癌病変か?2018

    • Author(s)
      佐々木素子 佐藤保則
    • Organizer
      第54回日本胆道学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 低分子デキストラン製剤が骨髄に沈着し貧血の原因と考えられた維持透析症例の解析2018

    • Author(s)
      杉森 尚美, 中村 万理, 原田 憲一, 佐々木 素子, 経田 克則, 中川 詩織, 原 章規, 古市 賢吾
    • Organizer
      第 80 回日本血液学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 若年男性に発症したbeta-catenin活性化型肝細胞腺腫の1例2018

    • Author(s)
      米田 憲秀, 北尾 梓, 小坂 一斗, 出雲崎 晃, 小森 隆弘, 井上 大, 蒲田 敏文, 小林 聡, 山口 貴久, 高村 博之, 太田 哲生, 大坪公士郎, 中村律子, 佐々木素子
    • Organizer
      第 32 回日本腹部放射線学会
    • Related Report
      2018 Research-status Report
  • [Book] 膵臓を診る医師のための膵臓病理テキスト (中沼安二, 古川 徹, 福村由紀 編)III章 腫瘍性疾患の病理. 1. 嚢胞性腫瘍.2020

    • Author(s)
      佐々木素子
    • Total Pages
      6
    • Publisher
      南江堂
    • Related Report
      2020 Annual Research Report
  • [Book] 腫瘍病理鑑別診断アトラス 肝癌第2版 (坂元享宇, 原田憲一 編) 第2部 組織型と診断の実際 II. 胆管細胞系腫瘍 6. 胆管腺腫および類似病変.2020

    • Author(s)
      佐々木素子
    • Total Pages
      5
    • Publisher
      文光堂
    • Related Report
      2020 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-08-18  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi