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2019 Fiscal Year Annual Research Report

肝臓特異的ハイドロダイナミック法による核酸医薬送達と肝癌遺伝子治療法への応用

Research Project

Project/Area Number 17K09408
Research InstitutionNiigata University

Principal Investigator

上村 顕也  新潟大学, 医歯学総合病院, 講師 (00579146)

Co-Investigator(Kenkyū-buntansha) 寺井 崇二  新潟大学, 医歯学系, 教授 (00332809)
坂牧 僚  新潟大学, 医歯学系, 助教 (40792289)
横尾 健  新潟大学, 医歯学総合研究科, 特任助教 (80750629)
Project Period (FY) 2017-04-01 – 2021-03-31
Keywords遺伝子治療 / ハイドロダイナミック遺伝子導入法 / 肝癌 / 核酸医薬 / ジフテリアトキシン
Outline of Annual Research Achievements

本研究は、ハイドロダイナミック遺伝子導入法(HGD)を肝癌治療に応用するための方法論、抗腫瘍効果を学術的に検証するためのステップと位置づけ、HGDパラメーターの確立、治療遺伝子の選択、効果と安全性の検証、肝癌モデル動物に対する治療効果の検証を行うことを目的とした。

今年度は前二年度に肝癌の増殖制御に有用であることを明らかにした、ジフテリアトキシンA遺伝子を用いた肝癌に対する遺伝子治療確立のためのマウス肝癌モデルに対する遺伝子治療効果を検証した。
これまでに、in vitroでは、ジフテリアトキシンA発現遺伝子が肝細胞癌に対して抗腫瘍効果を有することを明らかにし、同遺伝子を肝癌で発現するAFPのプロモーター制御下に発現するコンストラクトを作成した。今年度は、発がん遺伝子をハイドロダイナミック遺伝子導入法でマウス肝に遺伝子導入して作製したマウス肝癌モデルに対する、ジフテリアトキシン遺伝子Aの遺伝子治療効果を検討した。また、プロモーター選択性による遺伝子治療の安全性も検証した。
具体的には、肝癌マウスモデルに対して、腫瘍発生の各段階において、ジフテリアトキシンA遺伝子発現コンストラクトによる遺伝子治療を行い、腫瘍数、腫瘍径、腫瘍マーカー、などにより治療効果を、血液生化学的評価による安全性の検討を行った。
その結果、肝癌モデルマウスにおいても肝発癌率の抑制、腫瘍マーカーの低下を認め、ジフテリアトキシンA遺伝子による肝癌遺伝子治療の効果を実証することができた。またプロモーター選択性により、肝障害の観点からも安全な遺伝子治療が可能であった。本研究の成果により、プロモータ選択性によりジフテリアトキシンA遺伝子を用いた種々の悪性疾患治療が可能であることが示唆された。

  • Research Products

    (40 results)

All 2020 2019 Other

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (12 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Ghrelin‐insulin‐like growth factor‐1 axis is activated via autonomic neural circuits in the non‐alcoholic fatty liver disease2020

    • Author(s)
      Nagoya Takuro、Kamimura Kenya、Inoue Ryosuke、Ko Masayoshi、Owaki Takashi、Niwa Yusuke、Sakai Norihiro、Setsu Toru、Sakamaki Akira、Yokoo Takeshi、Kamimura Hiroteru、Nakamura Yuka、Ueno Masaki、Terai Shuji
    • Journal Title

      Neurogastroenterology & Motility

      Volume: 32 Pages: e13799.

    • DOI

      10.1111/nmo.13799

    • Peer Reviewed
  • [Journal Article] Prostaglandin E 2 and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition2020

    • Author(s)
      Ishihara Erika、Nagaoka Yuya、Okuno Toshiaki、Kofuji Satoshi、Ishigami‐Yuasa Mari、Kagechika Hiroyuki、Kamimura Kenya、Terai Shuji、Yokomizo Takehiko、Sugimoto Yukihiko、Fujita Yasuyuki、Suzuki Akira、Nishina Hiroshi
    • Journal Title

      Genes to Cells

      Volume: 25 Pages: 197~214

    • DOI

      10.1111/gtc.12750

    • Peer Reviewed
  • [Journal Article] Rare Brain Metastasis From a Pancreatobiliary Subtype of Intraductal Papillary Mucinous Neoplasm2020

    • Author(s)
      Arao Yoshihisa、Kamimura Kenya、Ikemi Masatoshi、Hayashi Kazunao、Takaki Masayuki、Takahashi Shunsaku、Seino Satoshi、Abe Hiroyuki、Tsuboguchi Shintaro、Otsu Yutaka、Sanpei Kazuhiro、Kohisa Junji、Kondo Shuhei、Tani Yusuke、Ito Junko、Toyoshima Yasuko、Kakita Akiyoshi、Ajioka Yoichi、Terai Shuji
    • Journal Title

      Pancreas

      Volume: 49 Pages: e8~e11

    • DOI

      10.1097/MPA.0000000000001450

    • Peer Reviewed
  • [Journal Article] Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma2020

    • Author(s)
      Kamimura Kenya、Yokoo Takeshi、Abe Hiroyuki、Sakai Norihiro、Nagoya Takuro、Kobayashi Yuji、Ohtsuka Masato、Miura Hiromi、Sakamaki Akira、Kamimura Hiroteru、Miyamura Norio、Nishina Hiroshi、Terai Shuji
    • Journal Title

      Cancers

      Volume: 12 Pages: 472~472

    • DOI

      10.3390/cancers12020472

    • Peer Reviewed
  • [Journal Article] Huge liver tumor in young man2020

    • Author(s)
      Shibata Osamu、Kamimura Kenya、Azumi Rie、Shibuya Kei、Shiba Shintaro、Ohno Tatsuya、Terai Shuji
    • Journal Title

      JGH Open

      Volume: 4 Pages: 301~302

    • DOI

      10.1002/jgh3.12234

    • Peer Reviewed
  • [Journal Article] Antiprogrammed Cell Death‐1 Immunotherapy‐Related Secondary Sclerosing Cholangitis2019

    • Author(s)
      Ogawa Kohei、Kamimura Kenya、Terai Shuji
    • Journal Title

      Hepatology

      Volume: 69 Pages: 914~916

    • DOI

      10.1002/hep.30189

    • Peer Reviewed
  • [Journal Article] Usefulness of Capsule Endoscopy and Double-balloon Enteroscopy for the Diagnosis of Multiple Carcinoid Tumors in the Small Intestine: Case Reports and a Literature Review2019

    • Author(s)
      Tominaga Kentaro、Kamimura Kenya、Yokoyama Junji、Terai Shuji
    • Journal Title

      Internal Medicine

      Volume: 58 Pages: 655~659

    • DOI

      10.2169/internalmedicine.1700-18

    • Peer Reviewed
  • [Journal Article] A Rare Duodenal Carcinosarcoma: A Case Report and Literature Review2019

    • Author(s)
      Arao Yoshihisa、Kamimura Kenya、Ikemi Masatoshi、Takaki Masayuki、Takahashi Shunsaku、Seino Satoshi、Abe Hiroyuki、Kohisa Junji、Kato Takashi、Ajioka Yoichi、Terai Shuji
    • Journal Title

      Internal Medicine

      Volume: 58 Pages: 1273~1278

    • DOI

      10.2169/internalmedicine.2094-18

    • Peer Reviewed
  • [Journal Article] Esophageal Stenosis by Prostate Cancer Metastasis2019

    • Author(s)
      Kamimura Kenya、Shinagawa-Kobayashi Yoko、Mizuno Kenichi、Terai Shuji
    • Journal Title

      The American Journal of Gastroenterology

      Volume: 114 Pages: 685~687

    • DOI

      10.14309/ajg.0000000000000185

    • Peer Reviewed
  • [Journal Article] Identification of molecular transition of hepatocellular carcinoma: a novel method to predict the initiation of metastasis2019

    • Author(s)
      Kamimura Kenya
    • Journal Title

      Stem Cell Investigation

      Volume: 6 Pages: 5~5

    • DOI

      10.21037/sci.2019.02.02

    • Peer Reviewed
  • [Journal Article] Inhibition of sodium glucose cotransporter 2 ( SGLT 2) delays liver fibrosis in a medaka model of nonalcoholic steatohepatitis ( NASH )2019

    • Author(s)
      Goto Ryo、Kamimura Kenya、Shinagawa‐Kobayashi Yoko、Sakai Norihiro、Nagoya Takuro、Niwa Yusuke、Ko Masayoshi、Ogawa Kohei、Inoue Ryosuke、Yokoo Takeshi、Sakamaki Akira、Kamimura Hiroteru、Abe Satoshi、Nishina Hiroshi、Terai Shuji
    • Journal Title

      FEBS Open Bio

      Volume: 9 Pages: 643~652

    • DOI

      10.1002/2211-5463.12598

    • Peer Reviewed
  • [Journal Article] Considerations of elderly factors to manage the complication of liver cirrhosis in elderly patients2019

    • Author(s)
      Kamimura Kenya、Sakamaki Akira、Kamimura Hiroteru、Setsu Toru、Yokoo Takeshi、Takamura Masaaki、Terai Shuji
    • Journal Title

      World Journal of Gastroenterology

      Volume: 25 Pages: 1817~1827

    • DOI

      10.3748/wjg.v25.i15.1817

    • Peer Reviewed
  • [Journal Article] Efficacy and safety of ribavirin therapy for chronic hepatitis E after kidney transplantation2019

    • Author(s)
      Yoshida Tomoaki、Takamura Masaaki、Goto Ryo、Takeuchi Suguru、Tsuchiya Atsunori、Kamimura Kenya、Tasaki Masayuki、Nakagawa Yuki、Saito Kazuhide、Tomita Yoshihiko、Terai Shuji
    • Journal Title

      Hepatology Research

      Volume: 49 Pages: 1244~1248

    • DOI

      10.1111/hepr.13363

    • Peer Reviewed
  • [Journal Article] Multiple Endocrine Neoplasia Type 1?Related Acute Pancreatitis2019

    • Author(s)
      Takahashi Shunsaku、Kamimura Kenya、Abe Hiroyuki、Watanabe Yukari、Hayashi Kazunao、Mizuno Kenichi、Yamamoto Takashi、Takeuchi Manabu、Natsui Masaaki、Terai Shuji
    • Journal Title

      Pancreas

      Volume: 48 Pages: e35~e38

    • DOI

      10.1097/MPA.0000000000001267

    • Peer Reviewed
  • [Journal Article] Rational arrangement of measuring shear wave speed in the liver2019

    • Author(s)
      Yokoo Takeshi、Kanefuji Tsutomu、Suda Takeshi、Nagayama Itsuo、Hoshi Takahiro、Abe Satoshi、Morita Shinichi、Kamimura Hiroteru、Kamimura Kenya、Tsuchiya Atsunori、Takamura Masaaki、Yagi Kazuyoshi、Terai Shuji
    • Journal Title

      World Journal of Gastroenterology

      Volume: 25 Pages: 2503~2513

    • DOI

      10.3748/wjg.v25.i20.2503

    • Peer Reviewed
  • [Journal Article] <p>Effective prevention of sorafenib-related vascular damage induced adverse events and maintenance of hepatic function by dried bonito broth and histidine</p>2019

    • Author(s)
      Sakai Norihiro、Kamimura Kenya、Shinagawa-Kobayashi Yoko、Nagoya Takuro、Niwa Yusuke、Ko Masayoshi、Setsu Toru、Sakamaki Akira、Yokoo Takeshi、Abe Satoshi、Kamimura Hiroteru、Sugitani Soichi、Yanagi Masahiko、Terai Shuji
    • Journal Title

      Cancer Management and Research

      Volume: Volume 11 Pages: 4437~4448

    • DOI

      10.2147/CMAR.S201424

    • Peer Reviewed
  • [Journal Article] Efficacy of gelatin hydrogels incorporating triamcinolone acetonide for prevention of fibrosis in a mouse model2019

    • Author(s)
      Nakajima Nao、Hashimoto Satoru、Sato Hiroki、Takahashi Kazuya、Nagoya Takuro、Kamimura Kenya、Tsuchiya Atsunori、Yokoyama Junji、Sato Yuichi、Wakatsuki Hanako、Miyata Masayuki、Akashi Yusuke、Tanaka Ryusuke、Matsuda Ken、Tabata Yasuhiko、Terai Shuji
    • Journal Title

      Regenerative Therapy

      Volume: 11 Pages: 41~46

    • DOI

      10.1016/j.reth.2019.04.001

    • Peer Reviewed
  • [Journal Article] A case report of psychiatric symptoms following direct-acting antiviral and ribavirin combination therapy for chronic hepatitis C in a patient with innate anxiety2019

    • Author(s)
      Sakamaki Akira、Kamimura Kenya、Fukui Naoki、Watanabe Haruka、Sakai Norihiro、Tominaga Kentaro、Mizuno Kenichi、Takamura Masaaki、Kawai Hirokazu、Sugai Takuro、Yamagiwa Satoshi、Someya Toshiyuki、Terai Shuji
    • Journal Title

      BMC Gastroenterology

      Volume: 19 Pages: 85

    • DOI

      10.1186/s12876-019-1013-1

    • Peer Reviewed
  • [Journal Article] Colorectal neuroendocrine carcinoma: A case report and review of the literature2019

    • Author(s)
      Yoshida Tomoaki、Kamimura Kenya、Hosaka Kazunori、Doumori Koji、Oka Hiromitsu、Sato Akito、Fukuhara Yasuo、Watanabe Shoji、Sato Tomomi、Yoshikawa Akira、Tomidokoro Takashi、Terai Shuji
    • Journal Title

      World Journal of Clinical Cases

      Volume: 7 Pages: 1865~1875

    • DOI

      10.12998/wjcc.v7.i14.1865

    • Peer Reviewed
  • [Journal Article] Rare Mesenteric Arterial Diseases: Fibromuscular Dysplasia and Segmental Arterial Mediolysis and Literature Review2019

    • Author(s)
      Ko Masayoshi、Kamimura Kenya、Sakamaki Akira、Niwa Yusuke、Tominaga Kentaro、Mizuno Kenichi、Terai Shuji
    • Journal Title

      Internal Medicine

      Volume: 58 Pages: 3393~3400

    • DOI

      10.2169/internalmedicine.3094-19

    • Peer Reviewed
  • [Journal Article] Change in body composition in patients with achalasia before and after peroral endoscopic myotomy2019

    • Author(s)
      Mizusawa Takeshi、Sato Hiroki、Kamimura Kenya、Hashimoto Satoru、Mizuno Ken‐ichi、Kamimura Hiroteru、Ikarashi Satoshi、Hayashi Kazunao、Takamura Masaaki、Yokoyama Junji、Terai Shuji
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: 35 Pages: 601~608

    • DOI

      10.1111/jgh.14847

    • Peer Reviewed
  • [Journal Article] Inhibition of sodium‐glucose cotransporter 2 ameliorates renal injury in a novel medaka model of nonalcoholic steatohepatitis‐related kidney disease2019

    • Author(s)
      Nagoya Takuro、Kamimura Kenya、Goto Ryo、Shinagawa‐Kobayashi Yoko、Niwa Yusuke、Kimura Atsushi、Sakai Norihiro、Ko Masayoshi、Nishina Hiroshi、Terai Shuji
    • Journal Title

      FEBS Open Bio

      Volume: 9 Pages: 2016~2024

    • DOI

      10.1002/2211-5463.12734

    • Peer Reviewed
  • [Journal Article] Methotrexate-related lymphoproliferative disorders in the liver: Case presentation and mini-review2019

    • Author(s)
      Mizusawa Takeshi、Kamimura Kenya、Sato Hiroki、Suda Takeshi、Fukunari Hiroyuki、Hasegawa Go、Shibata Osamu、Morita Shinichi、Sakamaki Akira、Yokoyama Junji、Saito Yu、Hori Yoshihisa、Maruyama Yuduru、Yoshimine Fumitoshi、Hoshi Takahiro、Morita Shinichi、Kanefuji Tsutomu、Kobayashi Masaaki、Terai Shuji
    • Journal Title

      World Journal of Clinical Cases

      Volume: 7 Pages: 3553~3561

    • DOI

      10.12998/wjcc.v7.i21.3553

    • Peer Reviewed
  • [Journal Article] Gene Therapy for Liver Cancers: Current Status from Basic to Clinics2019

    • Author(s)
      Kamimura Kenya、Yokoo Takeshi、Abe Hiroyuki、Terai Shuji
    • Journal Title

      Cancers

      Volume: 11 Pages: 1865~1865

    • DOI

      10.3390/cancers11121865

    • Peer Reviewed
  • [Journal Article] Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature2019

    • Author(s)
      Morita Shinichi、Kamimura Kenya、Abe Hiroyuki、Watanabe-Mori Yukari、Oda Chiyumi、Kobayashi Takamasa、Arao Yoshihisa、Tani Yusuke、Ohashi Riuko、Ajioka Yoichi、Terai Shuji
    • Journal Title

      World Journal of Gastroenterology

      Volume: 25 Pages: 6949~6958

    • DOI

      10.3748/wjg.v25.i48.6949

    • Peer Reviewed
  • [Presentation] Development of Hydrodynamic Gene Therapy; Assessment of Liver-targeted Hydrodynamic Gene Delivery in Large Animal Disease Model2019

    • Author(s)
      Kenya Kamimura, et al.
    • Organizer
      JAPAN SOCIETY OF GENE AND CELL THERAPY 2019
    • Int'l Joint Research
  • [Presentation] 肝癌に対する分子標的薬の有害事象の発症予測2019

    • Author(s)
      上村顕也、他。
    • Organizer
      第55回日本肝臓学会総会
  • [Presentation] 肝癌に対する分子標的治療中のヒスチジンによる肝予備能維持効果と副作用予防2019

    • Author(s)
      上村顕也 他。
    • Organizer
      第23回 日本肝臓学会大会
  • [Presentation] Effective Prevention of Sorafenib-Related Adverse Events and Maintenance of Hepatic Function by Histidine2019

    • Author(s)
      Kenya Kamimura, et al.
    • Organizer
      The American Association for the Study of Liver Diseases 2019
    • Int'l Joint Research
  • [Presentation] NASH/NAFLDの病態における自律神経を介した消化管ホルモンの関与2019

    • Author(s)
      上村顕也、他。
    • Organizer
      第55回日本肝臓学会総会
  • [Presentation] Effect of gastrointestinal hormone on liver regeneration via neuronal relay2019

    • Author(s)
      Kenya Kamimura, et al.
    • Organizer
      GUTS FORUM 2019
  • [Presentation] SGLT2阻害薬によるNASH進展抑制効果の検証:メダカNASHモデルを用いて2019

    • Author(s)
      上村顕也、他。
    • Organizer
      第105回日本消化器病学会総会
  • [Presentation] マウス肝線維化進展予防薬の探索及びレトロゾールによる線維化進展予防効果の検証2019

    • Author(s)
      上村顕也、他。
    • Organizer
      第105回日本消化器病学会総会
  • [Presentation] 肝癌に対する放射線治療の検討2019

    • Author(s)
      上村顕也、他。
    • Organizer
      第55回日本肝臓学会総会
  • [Presentation] 肝原発悪性腫瘍に対する放射線治療への期待-内科医の立場から2019

    • Author(s)
      上村顕也
    • Organizer
      第28回日本定位放射線治療学会
  • [Presentation] 肝癌の局所制御及び集学的治療法としての放射線治療の検討2019

    • Author(s)
      上村顕也、他。
    • Organizer
      第43回日本肝臓学会西部会
  • [Presentation] 遺伝子治療の現況と新規遺伝子治療法開発に向けた基礎及び前臨床研究2019

    • Author(s)
      上村顕也
    • Organizer
      東海医学会
    • Invited
  • [Book] Nucleic acid-based therapy: Development of a non-viral-based delivery approach in In Vivo and Ex Vivo Gene Therapy for Inherited and Non-Inherited Disorders2019

    • Author(s)
      Takeshi Yokoo, Kenya Kamimura, Tsutomu Kanefuji, Takeshi Suda and Shuji Terai
    • Total Pages
      18
    • Publisher
      IntechOpen Limited
  • [Book] The Management of Constipation: Current Status and Future Prospects in Constipation2019

    • Author(s)
      Maruyama M, Kamimura K, Sugita M, Nakajima N, Takahashi Y, Isokawa O, Terai S
    • Total Pages
      16
    • Publisher
      IntechOpen Limited
  • [Remarks] 肝がんに対する遺伝子治療法を開発 -肝がん細胞に毒素遺伝子を発現し、治療効果と安全性を明らかに-

    • URL

      https://www.med.niigata-u.ac.jp/contents/info/news_topics/121_index.html

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Published: 2021-01-27  

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