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Correlation between molecularly targeted therapy and circadian clock in hepatocellular carcinoma

Research Project

Project/Area Number 20K08312
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionSapporo Medical University

Principal Investigator

akutsu noriyuki  札幌医科大学, 医学部, 講師 (50531191)

Co-Investigator(Kenkyū-buntansha) 佐々木 茂  札幌医科大学, 医学部, 准教授 (10305229)
仲瀬 裕志  札幌医科大学, 医学部, 教授 (60362498)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords分子標的治療 / 時計遺伝子 / 肝細胞癌
Outline of Research at the Start

切除不能肝細胞癌に対しては、全身化学療法が行われており、ここ数年で使用可能な薬剤が4剤となった。多数の薬剤を使いこなすためには、症例個々の特 徴を把握した上で、治療薬を選択する個別化治療が肝細胞癌における今後の課題である。本 申請研究では、概日時計に着目し、概日時計の変化による抗癌剤治療効果および副作用の変 化について検討し、その相互関係を明らかにすることで、肝癌治療選択の個別化に結びつけることを目的とした研究を行いたい。

Outline of Final Research Achievements

The cDNA was prepared using cancerous tissue and normal tissue surrounding the cancer in cases of hepatocellular carcinoma. The expression of PER1 and PER2 was significantly lower in non-cancers compared to cancers. We analyzed the expression of Clock, Bmal1, Per1, Per2, and Cry1 using cDNA from several hepatocellular carcinoma cell lines. Cytokines were added to hepatocellular carcinoma cell lines to examine changes in the clock genes. IL6 and TNFα expression was higher in cell lines of low Per2 expression compared to those of high Per2 expression. Hep3B was mixed with 1 micro M of lenvatinib and incubated at 37°C for 48 hours. We found that the expression of clock genes was altered in several genes.

Academic Significance and Societal Importance of the Research Achievements

肝細胞癌において、癌部と非癌部で時計遺伝子に差があることがわかり、さらにいくつかのサイトカインが影響を受けることが分かった。また、分子標的治療薬で時計遺伝子の変化があることがわかった。これらのことは、肝細胞癌においても時計遺伝子の発現解析を用いることで、治療薬剤の選択や有効な投与方法に関わる可能性があり、今後さらに検討を進めていく。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (35 results)

All 2024 2023 2022 2021 2020

All Journal Article (18 results) (of which Peer Reviewed: 12 results,  Open Access: 2 results) Presentation (17 results)

  • [Journal Article] Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma2024

    • Author(s)
      Numata Yuto、Akutsu Noriyuki、Idogawa Masashi、Wagatsuma Kohei、Numata Yasunao、Ishigami Keisuike、Nakamura Tomoya、Hirano Takehiro、Kawakami Yujiro、Masaki Yoshiharu、Murota Ayako、Sasaki Shigeru、Nakase Hiroshi
    • Journal Title

      Hepatology Research

      Volume: Online ahead of print. Issue: 9 Pages: 859-865

    • DOI

      10.1111/hepr.14034

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Generalized crystal-storing histiocytosis with noncirrhotic portal hypertension: an autopsy case report2023

    • Author(s)
      Numata Yasunao、Sasaki Shigeru、Magara Kazufumi、Takasawa Akira、Sugawara Taro、Ohara Naruki、Akutsu Noriyuki、Hasegawa Tadashi、Osanai Makoto、Nakase Hiroshi
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 16 Issue: 3 Pages: 450-456

    • DOI

      10.1007/s12328-023-01782-1

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome Precedes the Development of Hepatocellular Carcinoma2022

    • Author(s)
      Sae Ohwada 1 , Noriyuki Akutsu 1 , Yoshiharu Masaki 1 , Shigeru Sasaki 1 , Minoru Nagayama 2 , Yasutoshi Kimura 2 , Ichiro Takemasa 2 , Hiroki Takahashi 3 , Hiroshi Nakase 1
    • Journal Title

      JMA Journal

      Volume: 5 Issue: 3 Pages: 393-397

    • DOI

      10.31662/jmaj.2022-0066

    • ISSN
      2433-328X, 2433-3298
    • Year and Date
      2022-07-15
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Positive Pattern Recognition System Using Alanine Aminotransferase, Type IV Collagen 7s, and E Value (Liver Stiffness) for the Diagnosis of Nonalcoholic Steatohepatitis Based on Natural History2022

    • Author(s)
      Masayuki Tsujisaki 1 , Shigeru Sasaki 2 , Noriyuki Akutsu 2 , Takenori Takamura 1 , Tetsuyuki Igarashi 3 , Mitsuru Yoshimoto 1 , Hideto Itoh 1 , Yoshio Kurihara 4 , Hiroshi Nakase 2
    • Journal Title

      JMA Journal

      Volume: 5 Issue: 2 Pages: 230-239

    • DOI

      10.31662/jmaj.2021-0199

    • ISSN
      2433-328X, 2433-3298
    • Year and Date
      2022-04-15
    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum Soluble Fas Levels and Incidence of Liver Cancer in Nested Case?Control Study2022

    • Author(s)
      Adachi Yasushi、Nojima Masanori、Mori Mitsuru、Kubo Toshiyuki、Akutsu Noriyuki、Sasaki Yasushi、Nakase Hiroshi、Lin Yingsong、Kurozawa Youichi、Wakai Kenji、Tamakoshi Akiko、for the Japan Collaborative Cohort Study
    • Journal Title

      Cancer Epidemiology, Biomarkers & Prevention

      Volume: 32 Issue: 2 Pages: 260-265

    • DOI

      10.1158/1055-9965.epi-22-0902

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacological Treatments Available for Immune-Checkpoint-Inhibitor-Induced Colitis2022

    • Author(s)
      Ohwada Sae、Ishigami Keisuke、Akutsu Noriyuki、Nakase Hiroshi
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 6 Pages: 1334-1334

    • DOI

      10.3390/biomedicines10061334

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synergistic effect of IFN-γ and IL-1β on PD-L1 expression in hepatocellular carcinoma2022

    • Author(s)
      Numata Yasunao、Akutsu Noriyuki、Ishigami Keisuke、Koide Hideyuki、Wagatsuma Kohei、Motoya Masayo、Sasaki Shigeru、Nakase Hiroshi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 30 Pages: 101270-101270

    • DOI

      10.1016/j.bbrep.2022.101270

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Calibrating Hepatitis E Virus Serological Assays Using Asymptomatic Specimens Obtained in Japan2022

    • Author(s)
      Terahara Kazutaka、Li Tian-Cheng、Matsubayashi Keiji、Sakata Hidekatsu、Kato Takanobu、Naganuma Atsushi、Ogawa Koji、Honda Koichi、Itakura Jun、Akutsu Noriyuki、Tobita Hiroshi、Korenaga Masaaki、Kanto Tatsuya、Sugiyama Ryuichi、Suzuki Ryosuke、Hamaguchi Isao、Isogawa Masanori、Takahashi Yoshimasa
    • Journal Title

      Microbiology Spectrum

      Volume: 10 Issue: 5

    • DOI

      10.1128/spectrum.02146-22

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genomic analysis of an aggressive case with metastatic intrahepatic mucinous cholangiocarcinoma.2022

    • Author(s)
      Yoshiharu Masaki
    • Journal Title

      Clin J Gastroenterol.

      Volume: 15 Issue: 4 Pages: 809-817

    • DOI

      10.1007/s12328-022-01649-x

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of hepatocellular carcinoma with long-term survival by multidisciplinary treatment for cranial and skeletal muscle metastases2022

    • Author(s)
      Akutsu Noriyuki、Kawakami Yujiro、Numata Yasunao、Hirano Takehiro、Wagatsuma Kohei、Ishigami Keisuke、Sasaki Shigeru、Nakase Hiroshi
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 15 Issue: 5 Pages: 960-967

    • DOI

      10.1007/s12328-022-01669-7

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment2021

    • Author(s)
      Akutsu Noriyuki、Sasaki Shigeru、Matsui Takeshi、Akashi Hirofumi、Yonezawa Kazuhiko、Ishigami Keisuke、Tsujisaki Masayuki、Isshiki Hiroyuki、Yawata Atsushi、Yamaoka Satoshi、Ban Toshihiro、Adachi Takeya、Nakahara Seiya、Takagi Hideyasu、Nakachi Kohei、Tanaka Katsunori、Hirano Takehiro、Nakase Hiroshi
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 21 Pages: 3369-3376

    • DOI

      10.2169/internalmedicine.7098-21

    • NAID

      130008110304

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-11-01
    • Related Report
      2021 Research-status Report
  • [Journal Article] A case of hepatitis B virus and hepatitis C virus co-infection that achieved sustained virological response 12 following treatment with glecaprevir hydrate/pibrentasvir for 3 days2021

    • Author(s)
      Numata Yasunao、Sasaki Shigeru、Akutsu Noriyuki、Hirano Takehiro、Wagatsuma Kohei、Kawakami Yujiro、Ishigami Keisuke、Nakase Hiroshi
    • Journal Title

      Kanzo

      Volume: 62 Issue: 9 Pages: 578-584

    • DOI

      10.2957/kanzo.62.578

    • NAID

      130008086356

    • ISSN
      0451-4203, 1881-3593
    • Year and Date
      2021-09-01
    • Related Report
      2021 Research-status Report
  • [Journal Article] Mixed neuroendocrine non-neuroendocrine neoplasm of the gallbladder complicated by a pancreaticobiliary maljunction of a non-dilated biliary duct2021

    • Author(s)
      Wagatsuma Kohei、Akita Kotaro、Motoya Masayo、Kimura Yasutoshi、Sugita Shintaro、Hirano Takehiro、Kawakami Yujiro、Numata Yasunao、Ishigami Keisuke、Masaki Yoshiharu、Murota Ayako、Shitani Masahiro、Akutsu Noriyuki、Sasaki Shigeru、Nakase Hiroshi
    • Journal Title

      Medicine

      Volume: 100 Issue: 39 Pages: e27336-e27336

    • DOI

      10.1097/md.0000000000027336

    • Related Report
      2021 Research-status Report
  • [Journal Article] Insulin-Like Growth Factor 2 and Incidence of Liver Cancer in a Nested Case?Control Study2021

    • Author(s)
      Adachi Yasushi、Nojima Masanori、Mori Mitsuru、Himori Ryogo、Kubo Toshiyuki、Akutsu Noriyuki、Lin Yingsong、Kurozawa Youichi、Wakai Kenji、Tamakoshi Akiko
    • Journal Title

      Cancer Epidemiology, Biomarkers & Prevention

      Volume: 30 Issue: 11 Pages: 2130-2135

    • DOI

      10.1158/1055-9965.epi-21-0481

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunoglobulin G4-related autoimmune hepatitis simultaneously concomitant with autoimmune pancreatitis: a case report2021

    • Author(s)
      Yokoyama Yoshihiro、Akutsu Noriyuki、Numata Yasunao、Okuda Keiko、Morita Rena、Masaki Yoshiharu、Sasaki Hajime、Suzuki Ryo、Yabana Takashi、Arimura Yoshiaki、Kondo Yoshihiro、Nakase Hiroshi
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 14 Issue: 6 Pages: 1740-1745

    • DOI

      10.1007/s12328-021-01509-0

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sustained hyperbilirubinemia following clarithromycin administration2021

    • Author(s)
      Yamamoto Tomoka、Ishigami Keisuke、Ueno Akari、Akutsu Noriyuki、Numata Yasunao、Wagatsuma Kohei、Sasaki Shigeru、Nakase Hiroshi
    • Journal Title

      Medicine: Case Reports and Study Protocols

      Volume: 2 Issue: 2 Pages: e0057-e0057

    • DOI

      10.1097/md9.0000000000000057

    • Related Report
      2021 Research-status Report
  • [Journal Article] Author’s reply: acute serologic autoimmune hepatitis in the post-partum period2020

    • Author(s)
      Akutsu Noriyuki、Ishigami Keisuke、Nakase Hiroshi
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 13 Issue: 4 Pages: 634-634

    • DOI

      10.1007/s12328-020-01120-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of anti-centromere antibody-positive autoimmune hepatitis after childbirth2020

    • Author(s)
      Saito Mitsunobu、Akutsu Noriyuki、Numata Yasunao、Ishigami Keisuke、Sasaki Shigeru、Nakase Hiroshi
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 13 Issue: 5 Pages: 855-859

    • DOI

      10.1007/s12328-020-01092-w

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 切除不能肝細胞癌に対する分子標的治療症例の複数レジメン治療の有用性2023

    • Author(s)
      阿久津 典之, 沼田 泰尚, 平野 雄大, 我妻 康平, 川上 裕次郎, 柾木 喜晴, 石上 敬介, 室田 文子, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 高齢者肝細胞癌に対する経皮的ラジオ波焼灼療法の検討2023

    • Author(s)
      沼田 泰尚, 阿久津 典之, 我妻 康平, 平野 雄大, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本高齢消化器病学
    • Related Report
      2023 Annual Research Report
  • [Presentation] 肝硬変の成因と病態の推移 2018年以降に当科で加療した肝硬変症例の検討2023

    • Author(s)
      阿久津 典之, 沼田 泰尚, 石上 敬介, 我妻 康平, 平野 雄大, 川上 裕次郎, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本肝臓学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 当科の核酸アナログ治療20年の検討2023

    • Author(s)
      阿久津 典之, 佐々木 茂, 沼田 泰尚, 平野 雄大, 我妻 康平, 石上 敬介, 川上 裕次郎, 柾木 喜晴, 室田 文子, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 当科における原発性硬化性胆管炎(PSC)症例の検討2023

    • Author(s)
      沼田 泰尚, 阿久津 典之, 世戸 凌太, 中村 隼人, 浪岡 万由子, 廣部 洋輔, 三浦 克与志, 平野 雄大, 我妻 康平, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 術前に肝細胞癌との鑑別が困難であった肝血管筋脂肪腫の2切除例2022

    • Author(s)
      加藤 透, 永山 稔, 木村 康利, 今村 将史, 久木田 和晴, 村上 武志, 水口 徹, 阿久津 典之, 佐々木 茂, 仲瀬 裕志, 竹政 伊知朗
    • Organizer
      日本臨床外科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 陰茎転移をきたした膵尾部癌の1例2022

    • Author(s)
      井澤 朋, 川上 裕次郎, 世戸 凌太, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 本谷 雅代, 舛森 直哉, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 小腸原発Gastrointestinal stromal tumor(GIST)に対するイマチニブ投与中に肝転移破裂、腹腔内出血をきたした1例2022

    • Author(s)
      山本 智香, 室田 文子, 沼田 泰尚, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 阿久津 典之, 本谷 雅代, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 5年の経過で消失した多発肝炎症性偽腫瘍の1例2022

    • Author(s)
      浪岡 万由子, 阿久津 典之, 石上 敬介, 三浦 克予志, 平野 雄大, 我妻 康平, 沼田 泰尚, 佐々木 茂, 永山 稔, 菅原 太郎, 長谷川 匡, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 当院における悪性肝門部胆管狭窄に対するドレナージの成績2022

    • Author(s)
      室田 文子, 我妻 康平, 川上 裕次郎, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 阿久津 典之, 本谷 雅代, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本胆道学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 胆膵癌におけるEUS-FNA検体を用いたMSI検査2022

    • Author(s)
      川上 裕次郎, 本谷 雅代, 仲瀬 裕志, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之
    • Organizer
      日本消化器内視鏡学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 胆道鏡下生検検体で遺伝パネル検査を施行しえた切除不能胆嚢管癌の1例2022

    • Author(s)
      越前 栄次朗, 川上 裕次郎, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 本谷 雅代, 佐々木 茂, 杉田 真太郎, 櫻井 晃洋, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2022 Research-status Report
  • [Presentation] FDG-PETを契機に診断に至ったIgG4関連消化管病変の1例2022

    • Author(s)
      沼田 有斗, 川上 裕次郎, 越前 栄次郎, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 本谷 雅代, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 難治性腹水を呈した全身性結晶蓄積性組織球症の1例2022

    • Author(s)
      大原 成喜, 沼田 泰尚, 沼田 有斗, 谷口 正浩, 越前 栄次朗, 平野 雄大, 我妻 康平, 川上 裕次郎, 柾木 喜晴, 石上 敬介, 室田 文子, 阿久津 典之, 本谷 雅代, 佐々木 茂, 真柄 和史, 菅原 太郎, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 転移性肺腫瘍に対するEUS-FNAにて診断した後腹膜原発の絨毛癌の1例2022

    • Author(s)
      廣部 洋輔, 川上 裕次郎, 越前 栄次朗, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 本谷 雅代, 佐々木 茂, 辻脇 光洋, 舛森 直哉, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 治療困難肝内結石に対するSpyGlass DSを用いた胆道鏡下治療の検討2022

    • Author(s)
      越前 栄次朗, 川上 裕次郎, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 本谷 雅代, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本消化器病学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 高齢者切除不能膵癌患者に対するGEM+nabPTX療法の有効性と安全性2022

    • Author(s)
      大和田 紗恵, 室田 文子, 本谷 雅代, 我妻 康平, 沼田 泰尚, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 阿久津 典之, 佐々木 茂, 仲瀬 裕志
    • Organizer
      日本高齢消化器病学会
    • Related Report
      2022 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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