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Development of Hydrodynamics-based Gene Therapy for the Pancreatic Cancer

Research Project

Project/Area Number 20K08379
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Kamimura Kenya  新潟大学, 医歯学系, 教授 (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, 特任准教授 (80750629)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Discontinued (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords遺伝子治療 / ハイドロダイナミック遺伝子導入法 / 膵臓癌 / 膵癌遺伝子治療 / 核酸医薬 / 膵癌
Outline of Research at the Start

本研究では、膵癌に対する新規治療法として、臓器選択的なハイドロダイナミック遺伝子導入法による遺伝子治療が応用可能か、検討することを目的とする。その目的を達成するために、膵癌モデル動物の確立、膵癌遺伝子治療のための治療遺伝子の選択、抗腫瘍効果、安全性を評価する。申請者らがこれまでに報告した、臓器選択的な遺伝子導入及びそのシステムを使用して、これまでに確立した治療遺伝子を応用する点でも実現性の高い、創造的な研究であると考える。

Outline of Final Research Achievements

In this project, in order to develop a novel therapeutic method for the pancreatic cancer, we applied pancreas-targeted HGD to establish a pancreatic cancer model, HGD parameters, and therapeutic target genes. Firstly, we performed HGD using various pancreatic cancer-related genes which are reported to be activated in human pancreatic cancer. We observed tumor formation in rat pancreas and found the tumor development efficiently in a short period of time. The histopathological analyses have shown the multistage pancreatic cancer model ranging from pancreatic ductal epithelial atypia to high-grade pancreatic cancer, and distant organ metastasis. Using this model, we analyzed parameters for pancreatic cancer gene therapy and gene and protein expression changes in tissues and serum to select therapeutic genes can be used for the gene therapy.
The above results revealed that pancreas-selective HGD can be applied as a useful methodology for pancreatic cancer treatment.

Academic Significance and Societal Importance of the Research Achievements

膵癌は化学療法の効果が十分でないことから、増加傾向にある予後不良な疾患である。その要因として、疾患モデル動物が確立されていないこと、そのため新規治療法が開発されていないことが原因で解決すべき課題である。そして、新規治療法については、疾患の進行速度を考慮すると、少ない治療回数で、より長期間の治療効果を示す方法論の必要性、重要度が高い。これらの点や社会的ニーズを鑑み、膵癌に対する治療法として遺伝子治療は有用であると考えられる。以上から、本研究成果による膵癌モデル動物作製と新規治療のための対象遺伝子選択は、臓器選択的なHGDによる新規膵癌遺伝子治療法の確立に向けた学術的基盤の確立に結びつくと考える。

Report

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

    (31 results)

All 2022 2021 2020

All Journal Article (26 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 26 results,  Open Access: 12 results) Presentation (3 results) (of which Int'l Joint Research: 3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Effects of Atezolizumab and Bevacizumab on Adrenal Gland Metastasis of Hepatocellular Carcinoma: A Case Report and Review of Literature2022

    • Author(s)
      Ishikawa Natsuki、Kamimura Kenya、Endo Saori、Ishii Soichi、Ogawa Kazuya、Sakai Norihiro、Abe Hiroyuki、Ko Masayoshi、Shibata Osamu、Koseki Youhei、Yokoyama Junji、Sakamaki Akira、Terai Shuji
    • Journal Title

      Internal Medicine

      Volume: 61 Issue: 21 Pages: 3233-3237

    • DOI

      10.2169/internalmedicine.9341-22

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2022-11-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a pancreatic cancer animal model using the pancreas-targeted hydrodynamic gene delivery method2022

    • Author(s)
      Shibata Osamu、Kamimura Kenya、Tanaka Yuto、Ogawa Kohei、Owaki Takashi、Oda Chiyumi、Morita Shinichi、Kimura Atsushi、Abe Hiroyuki、Ikarashi Satoshi、Hayashi Kazunao、Yokoo Takeshi、Terai Shuji
    • Journal Title

      Molecular Therapy - Nucleic Acids

      Volume: 28 Pages: 342-352

    • DOI

      10.1016/j.omtn.2022.03.019

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Longitudinal increase in albumin?bilirubin score is associated with non-malignancy-related mortality and quality of life in patients with liver cirrhosis2022

    • Author(s)
      Sakamaki A, Takamura M, Sakai N, Watanabe Y, Arao Y, Kimura N, Setsu T, Abe H, Yokoo T, Kamimura H, Tsubata S, Waguri N, Ishikawa T, Kawai H, Sugitani S, Sato T, Funakoshi K, Watanabe M, Igarashi K, Kamimura K, et al.
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 2 Pages: e0263464-e0263464

    • DOI

      10.1371/journal.pone.0263464

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of a novel selective PPARα modulator, statin, sodium-glucose cotransporter 2 inhibitor, and combinatorial therapy on the liver and vasculature of medaka nonalcoholic steatohepatitis model2022

    • Author(s)
      Kimura Atsushi、Kamimura Kenya、Ohkoshi-Yamada Marina、Shinagawa-Kobayashi Yoko、Goto Ryo、Owaki Takashi、Oda Chiyumi、Shibata Osamu、Morita Shinichi、Sakai Norihiro、Abe Hiroyuki、Yokoo Takeshi、Sakamaki Akira、Kamimura Hiroteru、Terai Shuji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 596 Pages: 76-82

    • DOI

      10.1016/j.bbrc.2022.01.086

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of the liver-gut peripheral neural axis in nonalcoholic fatty liver disease pathologies via hepatic HTR2A2022

    • Author(s)
      Owaki Takashi、Kamimura Kenya、Ko Masayoshi、Nagayama Itsuo、Nagoya Takuro、Shibata Osamu、Oda Chiyumi、Morita Shinichi、Kimura Atsushi、Sato Takeki、Setsu Toru、Sakamaki Akira、Kamimura Hiroteru、Yokoo Takeshi、Terai Shuji
    • Journal Title

      Disease Models & Mechanisms

      Volume: 15 Issue: 7

    • DOI

      10.1242/dmm.049612

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of a selective PPARα modulator, sodium-glucose cotransporter 2 inhibitor, and statin on the myocardial morphology of medaka nonalcoholic fatty liver disease model2022

    • Author(s)
      Ohkoshi-Yamada Marina、Kamimura Kenya、Kimura Atsushi、Tanaka Yuto、Nagayama Itsuo、Yakubo Shunta、Abe Hiroyuki、Yokoo Takeshi、Sakamaki Akira、Kamimura Hiroteru、Terai Shuji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 625 Pages: 116-121

    • DOI

      10.1016/j.bbrc.2022.07.117

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin D1 Binding Protein 1 Responds to DNA Damage through the ATM / CHK2 Pathway2022

    • Author(s)
      Niwa Yusuke、Kamimura Kenya、Ogawa K、Oda C、Tanaka Y、Horigome R、Ohtsuka M、Miura H、Fujisawa Koichi、Yamamoto Naoki、Takami Taro、Okuda Shujiro、Ko Masayoshi、Owaki Takashi、Kimura Atsushi、Shibata Osamu、Morita Shinichi、Sakai N、Abe H、Yokoo T、Sakamaki A、Kamimura H、Terai S
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 3 Pages: 851-851

    • DOI

      10.3390/jcm11030851

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of a Deep Learning Approach for the Sensitive Prediction of Hepatitis B Surface Antigen Levels in Inactive Carrier Patients2022

    • Author(s)
      Kamimura Hiroteru、Nonaka Hirofumi、Mori Masaya、Kobayashi Taichi、Setsu Toru、Kamimura Kenya、Tsuchiya Atsunori、Terai Shuji
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 2 Pages: 387-387

    • DOI

      10.3390/jcm11020387

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intestinal duplication diagnosed preoperatively with double-balloon enteroscopy: an extremely rare case report and literature review2022

    • Author(s)
      Niwa Yusuke、Tominaga Kentaro、Kawata Yuzo、Kobayashi Takamasa、Mizuwasa Takeshi、Takahashi Kazuya、Sato Hiroki、Kohisa Junji、Abe Satoshi、Kamimura Kenya、Yokoyama Junji、Kawai Hirokazu、Sugino Hideaki、Umezu Hajime、Hirai Yumiko、Nakano Masato、Shimada Yoshifumi、Kameyama Hitoshi、Wakai Toshifumi、Terai Shuji
    • Journal Title

      Clinical Journal of Gastroenterology

      Volume: 15 Issue: 2 Pages: 381-387

    • DOI

      10.1007/s12328-022-01596-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrogen-producing small intestinal bacterial overgrowth is associated with hepatic encephalopathy and liver function2022

    • Author(s)
      Yokoyama Kunihiko、Sakamaki Akira、Takahashi Kazuya、Naruse Takumi、Sato Chihiro、Kawata Yuzo、Tominaga Kentaro、Abe Hiroyuki、Sato Hiroki、Tsuchiya Atsunori、Kamimura Kenya、Takamura Masaaki、Yokoyama Junji、Terai Shuji
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 2 Pages: e0264459-e0264459

    • DOI

      10.1371/journal.pone.0264459

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Lenvatinib on a Hepatocellular Carcinoma with Fibroblast Growth Factor Receptor 4 Expression: A Case Report and Review of the Literature2021

    • Author(s)
      Shibata Osamu、Kamimura Kenya、Ko Masayoshi、Sakai Norihiro、Abe Hiroyuki、Morita Shinichi、Mizusawa Takeshi、Sato Hiroki、Sakamaki Akira、Terai Shuji
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 11 Pages: 1709-1715

    • DOI

      10.2169/internalmedicine.6580-20

    • NAID

      130008046766

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-06-01
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple Tumor-Like Fatty Changes in the Liver Disappeared After Hepatitis C Virus Eradication With Direct-Acting Antiviral Treatment2021

    • Author(s)
      Sakai Norihiro、Kamimura Kenya、Terai Shuji
    • Journal Title

      American Journal of Gastroenterology

      Volume: 116 Issue: 2 Pages: 237-237

    • DOI

      10.14309/ajg.0000000000000703

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between detection of hepatitis B virus in saliva and periodontal disease in hepatitis B virus carriers in Japan, Journal of Infection and Chemotherapy2021

    • Author(s)
      Kamimura Hiroteru, Jun Watanabe, Tomoyuki Sugano, Junji Kohisa, Hiroyuki Abe, Keny Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Shogo Okoshi, Yoshinari Tanabe, Ritsuo Takagi, Hirofumi Nonaka, Shuji Terai
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: Vol.27, No.3 Issue: 3 Pages: 492-496

    • DOI

      10.1016/j.jiac.2020.10.028

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers2021

    • Author(s)
      Kamimura Kenya、Suda Takeshi、Fukuhara Yasuo、Okuda Shujiro、Watanabe Yu、Yokoo Takeshi、Osaki Akihiko、Waguri Nobuo、Ishikawa Toru、Sato Toshihiro、Aoyagi Yutaka、Takamura Masaaki、Wakai Toshifumi、Terai Shuji
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 6255-6255

    • DOI

      10.1038/s41598-021-85498-7

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver2021

    • Author(s)
      Ko Masayoshi、Kamimura Kenya、Owaki Takashi、Nagoya Takuro、Sakai Norihiro、Nagayama Itsuo、Niwa Yusuke、Shibata Osamu、Oda Chiyumi、Morita Shinichi、Kimura Atsushi、Inoue Ryosuke、Setsu Toru、Sakamaki Akira、Yokoo Takeshi、Terai Shuji
    • Journal Title

      Disease Models & Mechanisms

      Volume: 14 Issue: 3

    • DOI

      10.1242/dmm.048922

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] The promise of radiotherapy for hepatocellular carcinoma2021

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

      Hepatology Research

      Volume: 51 Issue: 8 Pages: 837-838

    • DOI

      10.1111/hepr.13687

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors2021

    • Author(s)
      Sakamaki Akira、Kamimura Kenya、Yokoo Takeshi、Osaki Akihiko、Yoshikawa Seiichi、Arao Yoshihisa、Setsu Toru、Kamimura Hiroteru、Waguri Nobuo、Takeuchi Manabu、Funakoshi Kazuhiro、Terai Shuji
    • Journal Title

      Medicine

      Volume: 100 Issue: 32 Pages: e26902-e26902

    • DOI

      10.1097/md.0000000000026902

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rare complication of hepatocellular carcinoma in Wilson's disease2021

    • Author(s)
      Ohkoshi‐Yamada Marina、Kamimura Kenya、Kamimura Hiroteru、Terai Shuji
    • Journal Title

      JGH Open

      Volume: 5 Issue: 10 Pages: 1220-1222

    • DOI

      10.1002/jgh3.12648

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid progression of colonic mucinous adenocarcinoma with immunosuppressive condition: A case report and review of literature2021

    • Author(s)
      Koseki Youhei、Kamimura Kenya、Tanaka Yuto、Ohkoshi-Yamada Marina、Zhou Qiliang、Matsumoto Yoshifumi、Mizusawa Takeshi、Sato Hiroki、Sakamaki Akira、Umezu Hajime、Yokoyama Junji、Terai Shuji
    • Journal Title

      World Journal of Clinical Cases

      Volume: 9 Issue: 30 Pages: 9182-9191

    • DOI

      10.12998/wjcc.v9.i30.9182

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel Reporter Mouse Models Useful for Evaluating In Vivo Somatic Cell Gene Editing and for Optimization of Methods of Delivering Genome Editing Tools.2021

    • Author(s)
      Miura H., Imafuku J., Kurosaki A., Sato M., Ma Y., Zhang G., Mizutani A., Kamimura K., Gurumurthy CB., Liu D., Ohtsuka M.
    • Journal Title

      Molecular Therapy-Nucleic Acids.

      Volume: 24 Pages: 325-336

    • DOI

      10.1016/j.omtn.2021.03.003

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ghrelin-insulin-like growth factor-1 axis is activated via autonomic neural circuits in the non-alcoholic fatty liver disease.2020

    • Author(s)
      Nagoya T, Kamimura K, Inoue R, Ko M, Owaki T, Niwa Y, Sakai N, Setsu T, Sakamaki A, Yokoo T, Kamimura H, Nakamura Y, Ueno M, Terai S.
    • Journal Title

      Neurogastroenterol Motil

      Volume: 32 Issue: 5

    • DOI

      10.1111/nmo.13799

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition.2020

    • Author(s)
      Ishihara E, Nagaoka Y, Okuno T, Kofuji S, Ishigami-Yuasa M, Kagechika H, Kamimura K, Terai S, Yokomizo T, Sugimoto Y, Fujita Y, Suzuki A, Nishina H.
    • Journal Title

      Genes Cells.

      Volume: 25(3) Issue: 3 Pages: 197-214

    • DOI

      10.1111/gtc.12750

    • NAID

      120006873037

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Issue: 2 Pages: 472-472

    • DOI

      10.3390/cancers12020472

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy and Safety of the Radiotherapy for Liver Cancer: Assessment of Local Controllability and Its Role in Multidisciplinary Therapy2020

    • Author(s)
      Ohkoshi-Yamada M, Kamimura K, et al.
    • Journal Title

      Cancers

      Volume: 12 Issue: 10 Pages: 2955-2955

    • DOI

      10.3390/cancers12102955

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis2020

    • Author(s)
      Sakamaki Akira、Yokoyama Kunihiko、Koyama Kyutaro、Morita Shinichi、Abe Hiroyuki、Kamimura Kenya、Takamura Masaaki、Terai Shuji
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 11 Pages: e0242582-e0242582

    • DOI

      10.1371/journal.pone.0242582

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Esophageal High-Resolution Manometry for Diagnosing the Severity of the Chronic Intestinal Pseudo-Obstruction: A Case Series2020

    • Author(s)
      Sato Hiroki、Kamimura Kenya、Matsui Hideaki、Owaki Takashi、Morita Shinichi、Tanaka Yuto、Ishikawa Natsuki、Shimada Yoshifumi、Yokoyama Junji、Wakai Toshifumi、Terai Shuji
    • Journal Title

      Digestive Diseases and Sciences

      Volume: - Issue: 11 Pages: 3960-3967

    • DOI

      10.1007/s10620-020-06701-9

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Development of Hydrodynamics-Based Gene Therapy for Liver Cancer2021

    • Author(s)
      Kenya Kamimura
    • Organizer
      ASGCT 24TH ANNUAL MEETING
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Establishment of a Pancreatic Cancer Animal Model using the Pancreas-Targeted Hydrodynamic Gene Delivery Method2021

    • Author(s)
      Osamu Shibata, Kenya Kamimura, et al.
    • Organizer
      2021 第27回日本遺伝子治療学会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Assessment of Clinical Feasibility of Image-Guided Liver Specific Hydrodynamic Gene Transfer in Non-Human Primates2020

    • Author(s)
      Kamimura K, et al.
    • Organizer
      The American Society of Gene & Cell Therapy (ASGCT)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 膵臓癌治療システム2020

    • Inventor(s)
      上村顕也、寺井崇二
    • Industrial Property Rights Holder
      上村顕也、寺井崇二
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2021
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 野生型ラットの膵臓へのヒト膵癌関連遺伝子の導入による膵癌モデル動物の開発と利用2020

    • Inventor(s)
      上村顕也、寺井崇二、柴田理、五十嵐聡
    • Industrial Property Rights Holder
      上村顕也、寺井崇二、柴田理、五十嵐聡
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report

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

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