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KUBOTA Eiji

    Graduate School of Medical Sciences Core Laboratory　Associate Professor
Contact： ekubotamed.nagoya-cu.ac.jp
Last Updated :2024/06/11

Researcher Information

Research funding number

  • 30405188

J-Global ID

Research Interests

  • Gastroenterology   

Research Areas

  • Life sciences / Gastroenterology

Academic & Professional Experience

  • 2018/01 - Today  Nagoya City University Graduate School of Medical SciencesDepartment of Gastroenterology and MetabolismAssociate professor
  • 2015/05 - 2017/12  Nagoya City University Graduate School of Medical SciencesDepartment of Gastroenterology and MetabolismLecturer
  • 2014/07 - 2015/04  Nagoya City University Graduate School of Medical SciencesDepartment of Gastroenterology and MetabolismLecturer
  • 2013/04 - 2014/06  Nagoya City University Graduate School of Medical Sciences消化器代謝内科Research associate
  • 2010/07 - 2013  University of CalgaryDepartment of Biochemistry and Molecular Biology and OncologyPostdoctoral Fellow

Association Memberships

  • 日本神経消化器病学会   THE JAPANESE SOCIETY OF ULCER RESEARCH   日本消化器癌発生学会   THE JAPANESE CANCER ASSOCIATION   THE JAPANESE GASTROENTEROLOGICAL ASSOCIATION   JAPAN GASTROENTEROLOGICAL ENDOSCOPY SOCIETY   JAPANESE SOCIETY OF GASTROENTEROLOGY   THE JAPANESE SOCIETY OF INTERNAL MEDICINE   

Published Papers

Conference Activities & Talks

  • 大腸鋸歯状病変の遺伝子変異、メチル化の統合解析  [Not invited]
    中西 宏佳; 澤田 武; 海崎 泰治; 佐々木 泰史; 山本 英一郎; 青木 敬則; 永塚 真; 高橋 直樹; 波佐谷 兼慶; 久保田 英嗣; 片岡 洋望; 太田 亮介; 稲垣 聡子; 山田 真也; 源 利成; 鈴木 拓; 菅井 有
    日本消化器病学会雑誌  2018/10  (一財)日本消化器病学会
  • EVALUATION OF THE EFFICACY AND SAFETY OF HELICOBACTOR PYLORI ERADICATION WITH VONOPRAZAN, A NOVEL POTASSIUM-COMPETITIVE ACID BLOCKER  [Not invited]
    Hirotada Nishie; Keiji Ozeki; Hiromi Kataoka; Hiroshi Ichikawa; Yu Nojiri; Yusuke Inagaki; Satoshi Nomura; Noriyuki Hayashi; Takahito Katano; Yasuyuki Okamoto; Tsutomu Mizoshita; Takaya Shimura; Yoshinori Mori; Eiji Kubota; Satoshi Tanida; Takashi Joh
    GASTROENTEROLOGY  2017/04  W B SAUNDERS CO-ELSEVIER INC
  • Tomohisa Sakaue; Ayako Fujisaki; Hironao Nakayama; Masashi Maekawa; Hiromi Hiyoshi; Eiji Kubota; Takashi Joh; Hironori Izutani; Shigeki Higashiyama
    CANCER SCIENCE  2017/02  WILEY
     
    Vascular endothelial (VE)-cadherin, a major endothelial adhesion molecule, regulates vascular permeability, and increased vascular permeability has been observed in several cancers. The aim of this study was to elucidate the role of the NEDD8-Cullin E3 ligase, in maintaining barrier permeability. To this end, we investigated the effects of the inhibition of Cullin E3 ligases, by using inhibitors and knockdown techniques in HUVECs. Furthermore, we analyzed the mRNA and protein levels of the ligases by quantitative RT-PCR and Western blotting, respectively. The results revealed that NEDD8-conjugated Cullin 3 is required for VE-cadherin-mediated endothelial barrier functions. Treatment of HUVECs with MLN4924, a chemical inhibitor of the NEDD8-activating enzyme, led to high vascular permeability due to impaired cell-cell contact. Similar results were obtained when HUVECs were treated with siRNA directed against Cullin 3, one of the target substrates of NEDD8. Immunocytochemical staining showed that both treatments equally depleted VE-cadherin protein localized at the cell-cell borders. However, quantitative RT-PCR showed that there was no significant difference in the VE-cadherin mRNA levels between the treatment and control groups. In addition, cycloheximide chase assay revealed that the half-life of VE-cadherin protein was dramatically reduced by Cullin 3 depletion. Together, these findings suggest that neddylated Cullin 3 plays a crucial role in endothelial cell barrier function by regulating VE-cadherin.
  • Sakaue T; Fujisaki A; Nakayama H; Maekawa M; Hiyoshi H; Kubota E; Joh T; Izutani H; Higashiyama S
    Cancer science  2017/02
  • Glucagon Promotes Colon Cancer Cell Proliferation by Modulation of AMPK and MAPK/ERK  [Not invited]
    Takashi Yagi; Naotsuka Okayama; Mayo Hachiya; Satoshi Yasuda; Asami Hotta; Shunsuke Ito; Hideomi Oguchi; Kenro Imaeda; Eiji Kubota; Takashi Joh
    DIABETES  2016/06  AMER DIABETES ASSOC
  • Mechanisms of PTHrP-induced Suppression of Gastric Smooth Muscle Contractility in the Guinea Pig Stomach  [Not invited]
    Hideomi Ohguchi; Hikaru Hashitani; Kenro Imaeda; Mayo Hachiya; Eiji Kubota; Hiromi Kataoka; Takashi Joh
    GASTROENTEROLOGY  2016/04  W B SAUNDERS CO-ELSEVIER INC
  • Anti-Tumor Effect of Oncolytic Reovirus Against Gastrointestinal Stromal Tumor  [Not invited]
    Yusuke Inagaki; Eiji Kubota; Yoshinori Mori; Hirotada Nishie; Noriyuki Hayashi; Takahito Katano; Keiji Ozeki; Hiromi Kataoka; Randal N. Johnston; Takashi Joh
    GASTROENTEROLOGY  2016/04  W B SAUNDERS CO-ELSEVIER INC
  • Utility of reovirus as an inhibitor of metastasis in gastric cancer  [Not invited]
    E. Kubota; H. Kataoka; Y. Mori; T. Joh
    EUROPEAN JOURNAL OF CANCER  2015/09  ELSEVIER SCI LTD
  • New photodynamic therapy targeting tumor-associated macrophages and cancer cells  [Not invited]
    N. Hayashi; H. Kataoka; E. Kubota; S. Yano; Y. Sakai; T. Joh
    EUROPEAN JOURNAL OF CANCER  2015/09  ELSEVIER SCI LTD
  • Gastric Dysmotility and Its Relationship to Upper Gastrointestinal Symptoms in Patients With Long-Standing Diabetes Mellitus  [Not invited]
    Takeshi Kamiya; Michiko Shikano; Tsutomu Mizoshita; Yoshinori Mori; Eiji Kubota; Satoshi Tanida; Hiromi Kataoka; Kenro Imaeda; Naotsuka Okayama; Takashi Joh
    GASTROENTEROLOGY  2015/04  W B SAUNDERS CO-ELSEVIER INC
  • ATM and P53 Expression Level Correlate With Sensitivity to Olaparib in Gastric Cancer  [Not invited]
    Eiji Kubota; Chris T. Williamson; Susan P. Lees-Miller; Gwyn Bebb
    GASTROENTEROLOGY  2014/05  W B SAUNDERS CO-ELSEVIER INC
  • The Association Between Persistent Reflux Symptoms and Health-Related Quality of Life in Patients With Gastroesophageal Reflux Disease Under Treatment With Proton Pump Inhibitors  [Not invited]
    Takeshi Kamiya; Michiko Shikano; Eiji Kubota; Tsutomu Mizoshita; Yoshinori Mori; Satoshi Tanida; Hiromi Kataoka; Yoshihide Kimura; Kyoji Senoo; Takashi Joh
    GASTROENTEROLOGY  2014/05  W B SAUNDERS CO-ELSEVIER INC
  • ROLE OF ATM IN RESPONSE OF NON-SMALL CELL LUNG CANCER CELL LINES TO THERAPEUTIC AGENTS  [Not invited]
    Anifat A. Elegbede; D. G. Bebb; Lars F. Petersen; Eiji Kubota; Susan P. Lees-Miller
    JOURNAL OF THORACIC ONCOLOGY  2013/11  LIPPINCOTT WILLIAMS & WILKINS
  • Utility of Reovirus as an Inhibitor of Metastasis in Gastric Cancer  [Not invited]
    Eiji Kubota; Hiromi Kataoka; Yoshinori Mori; Takashi Joh
    DIGESTIVE DISEASES AND SCIENCES  2013/09  SPRINGER
  • Role of ES Cell-Expressed Ras, ERas in Tumorigenicity of Gastric Cancer  [Not invited]
    Eiji Kubota; Hiromi Kataoka; Takashi Joh
    DIGESTIVE DISEASES AND SCIENCES  2010/10  SPRINGER
  • 胃癌、大腸癌に対するグルコース結合クロリンによる新規光線力学的治療法(Novel photodynamic therapy with glucose conjugated chlorine for gastric and colon cancer)  [Not invited]
    田中 守; 片岡 洋望; 平田 慶和; 志村 貴也; 溝下 勤; 久保田 英嗣; 神谷 武; 森田 明理; 城 卓志
    日本癌学会総会記事  2010/08  日本癌学会
  • Rabeprazole vs. Itopride: A Randomized, Multicenter Trial in Nagoya to Determine Efficacy in Japanese Patients with Functional Dyspepsia  [Not invited]
    Takeshi Kamiya; Michiko Shikano; Makoto Hirako; Tsutomu Mizoshita; Eiji Kubota; Tsuneya Wada; Satoshi Tanida; Hiromi Kataoka; Makoto Sasaki; Takashi Mizushima; Yoshikazu Hirata; Takashi Joh
    GASTROENTEROLOGY  2009/05  W B SAUNDERS CO-ELSEVIER INC
  • Tumor Suppressor At Motif Binding Factor 1 (ATBF1) Negatively Regulates Cell Growth Through the Nuclear Translocation with Runt Domain Transcription Factor 3 (RUNx3) in Cooperation with TGF-beta Signal Transduction  [Not invited]
    Motoshi Mabuchi; Hiromi Kataoka; Tsutomu Mizoshita; Eiji Kubota; Tsuneya Wada; Satoshi Tanida; Makoto Sasaki; Takeshi Kamiya; Takashi Joh
    GASTROENTEROLOGY  2009/05  W B SAUNDERS CO-ELSEVIER INC
  • IL-8-Induced Colon Cancer Proliferation Through Trafficking of C-Terminal HB-EGF Into Nucleus As a New Mechanism  [Not invited]
    Satoshi Tanida; Hiromi Kataoka; Makoto Sasaki; Eiji Kubota; Tsuneya Wada; Tsutomu Mizoshita; Kenji Murakami; Yoshikazu Hirata; Takashi Mizushima; Masahide Ebi; Motoshi Mabuchi; Mamoru Tanaka; Takeshi Kamiya; Takashi Joh
    GASTROENTEROLOGY  2009/05  W B SAUNDERS CO-ELSEVIER INC
  • BCL6 Degradation Caused By the Interaction with the Carboxyl-Terminal Fragment of Pro-HB-EGF Induces Cyclin D2 Expression in Gastric Cancers  [Not invited]
    Yoshikazu Hirata; Naotaka Ogasawara; Makoto Sasaki; Tsutomu Mizoshita; Eiji Kubota; Tsuneya Wada; Takashi Mizushima; Satoshi Tanida; Hiromi Kataoka; Takeshi Kamiya; Takashi Joh
    GASTROENTEROLOGY  2009/05  W B SAUNDERS CO-ELSEVIER INC
  • IBD Prevention Using An Oligosaccharide Synthesize Enzyme via Improvement of Bowel Flora, TLR-2 and Claudin-4  [Not invited]
    Makoto Sasaki; Takashi Mizushima; Takeshi Kamiya; Hiromi Kataoka; Naotaka Ogasawara; Eiji Kubota; Tsuneya Wada; Tsutomu Mizoshita; Yoshikazu Hirata; Satoshi Noikeda; Takashi Joh
    GASTROENTEROLOGY  2009/05  W B SAUNDERS CO-ELSEVIER INC
  • The Blockage of Angiotensin II Type 1 Receptor Regulated Cytokine Induced MADCAM-1 Expression By Preventing the NF-kappa B Binding Activity in Nucleus and Ameliorates Colitis  [Not invited]
    Takashi Mizushima; Makoto Sasaki; Tomoaki Ando; Tsuneya Wada; Mamoru Tanaka; Masahide Ebi; Yoshikazu Hirata; Kenji Murakami; Tsutomu Mizoshita; Eiji Kubota; Naotaka Ogasawara; Satoshi Tanida; Hiromi Kataoka; Takeshi Kamiya; Steven J. Alexander; Takashi Joh
    GASTROENTEROLOGY  2009/05  W B SAUNDERS CO-ELSEVIER INC
  • The gastric and intestinal mucinous phenotypes of gastric cancers in human and Helicobacter pylori-infected and -eradicated mongolian gerbils  [Not invited]
    Tsutomu Mizoshita; Hiromi Kataoka; Makoto Sasaki; Takaya Shimura; Eiji Kubota; Tsuneya Wada; Takashi Joh
    GASTROENTEROLOGY  2008/04  W B SAUNDERS CO-ELSEVIER INC
  • ES cell specific RAS, eras in gastric cancer accelerates its liver metastasis  [Not invited]
    Eiji Kubota; Hiromi Kataoka; Makoto Sasaki; Tsuneya Wada; Takaya Shimura; Tsutomu Mizoshita; Takashi Joh
    GASTROENTEROLOGY  2008/04  W B SAUNDERS CO-ELSEVIER INC
  • Rabeprazole vs. itopride; a randomized multicenter trial to determine efficacy in functional dyspepsia in japan  [Not invited]
    Takeshi Kamiya; Makoto Hirako; Michiko Shikano; Tsutomu Mizoshita; Takaya Shimura; Eiji Kubota; Tsuneya Wada; Hiromi Kataoka; Makoto Sasaki; Takashi Joh
    GASTROENTEROLOGY  2008/04  W B SAUNDERS CO-ELSEVIER INC
  • Suppression of prohb-EGF carboxy terminal fragment nuclear translocation might be a new molecular targeting therapy for gastric cancer  [Not invited]
    Takaya Shimura; Hiromi Kataoka; Makoto Sasaki; Eiji Kubota; Tsuneya Wada; Tsutomu Mizoshita; Takashi Joh
    GASTROENTEROLOGY  2008/04  W B SAUNDERS CO-ELSEVIER INC
  • Gastric mucosa atrophy decreased the efficacy of proton pump inhibitor treatment on gastroesophageal reflux disease  [Not invited]
    Tsuneya Wada; Makoto Sasaki; Hiromi Kataoka; Naotaka Ogasawara; Eiji Kubota; Yoshinori Mori; Takaya Shimura; Tsutomu Mizoshita; Takashi Mizushima; Yasuyuki Okamoto; Takeshi Kamiya; Takashi Joh
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY  2007/10  BLACKWELL PUBLISHING
  • Yoshinori Mori; Hiromi Kataoka; Yutaka Miura; Makoto Kawaguchi; Eiji Kubota; Naotaka Ogasawara; Tadayuki Oshima; Satoshi Tanida; Makoto Sasaki; Hirotaka Ohara; Tsutomu Mizoshita; Masae Tatematsu; Kiyofumi Asai; Takashi Joh
    INTERNATIONAL JOURNAL OF CANCER  2007/07  WILEY-LISS
     
    Human gastric epithelium has a unique mucin gene expression pattern, which becomes markedly altered in gastrointestinal disorder. This alteration in mucin expression, including the mucin MUC5AC, may be related to the development and prognosis of gastric cancers, and MUC5AC-positive gastric cancer has been reported to be poor prognosis. However, the molecular mechanism of MUC5AC transcriptional regulation has not been fully elucidated. AT motif-binding factor 1 (ATBF1) is a homeotic transcriptional regulatory factor recently identified as a tumor suppressor gene, and its subcellular localization suggests a link to cell proliferation and differentiation. We investigated the mechanism of MUC5AC transcriptional regulation by ATBF1. In 123 gastric cancer lesions, ATBF1 expressed in the nucleus significantly suppressed MUC5AC expression, as determined by immunohistochemistry. In addition, analysis of the MUC5AC promoter region revealed an AT motif-like element. This element was found to be essential for ATBF1 suppression of MUC5AC promoter activity as shown in a dual luciferase-reporter assay. Over-expressed ATBF1 also significantly suppressed enclogenous MUC5AC protein expression in gastric cancer cells. Chromatin immunoprecipitation demonstrated that ATBF1 binds to the AT motif-like element in the MUC5AC promoter. These results indicate that ATBF1 in the nucleus negatively regulates the MUC5AC gene in gastric cancer by binding to an AT motif-like element in the MUC5AC promoter. (c) 2007 Wiley-Liss, Inc.
  • Takaya Shimura; Makoto Sasaki; Hiromi Kataoka; Satoshi Tanida; Tadayuki Oshima; Naotaka Ogasawara; Tsuneya Wada; Eiji Kubota; Tomonori Yamada; Yoshinori Mori; Fumitaka Fujita; Haruhisa Nakao; Hirotaka Ohara; Masami Inukai; Kunio Kasugai; Takashi Joh
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY  2007/06  BLACKWELL PUBLISHING
     
    Background: Endoscopic mucosal resection is an established method for treating intramucosal gastric neoplasms. Conventional endoscopic mucosal resection has predominantly been performed using strip biopsy, but local recurrence sometimes occurs due to such piecemeal resection. Endoscopic submucosal dissection has recently been performed in Japan using new devices such as an insulation-tip diathermic knife. The efficacy and problems associated with endoscopic submucosal dissection were evaluated by comparison with conventional endoscopic mucosal resection. Methods: Treatment consisted of conventional endoscopic mucosal resection for 48 lesions from January 1999 to October 2002, and endoscopic submucosal dissection for 59 lesions from November 2002 to June 2005. Endoscopic submucosal dissection was performed using an insulation-tip diathermic knife and flex and hook knives, as appropriate. Results: For lesions >= 11 mm in size, en bloc resection rates were significantly higher with endoscopic submucosal dissection than with conventional endoscopic mucosal resection, but treatment time was significantly longer. En bloc resection rates were higher with endoscopic submucosal dissection than with conventional endoscopic mucosal resection in all areas. Treatment of lesions in the upper one-third of the stomach took a long time using endoscopic submucosal dissection, and intraoperative bleeding was frequent. However, en bloc resection rates and intraoperative bleeding with endoscopic submucosal dissection were improved using various knives. Conclusions: Endoscopic submucosal dissection can take a long time, but is superior to conventional endoscopic mucosal resection for treating intramucosal gastric neoplasms.
  • Low acid secretion is a risk of resistant to proton pump inhibitor treatment on gastroesophageal reflux disease  [Not invited]
    Tsuneya Wada; Makoto Sasaki; Hiromi Kataoka; Naotaka Ogasawara; Eiji Kubota; Yoshinori Mori; Takaya Shimura; Tsutomu Mizoshita; Takashi Mizushima; Yasuyuki Okamoto; Takeshi Kamiya; Takashi Joh
    GASTROENTEROLOGY  2007/04  W B SAUNDERS CO-ELSEVIER INC
  • Amelioration of dextran sulfate sodium induced colitis in angiotensin II type 1 receptor knockout mice  [Not invited]
    Makoto Sasaki; Tsuneya Wada; Takashi Mizushima; Naotaka Ogasawara; Eiji Kubota; Yoshinori Mori; Takaya Shimura; Tsutomu Mizoshita; Yasuyuki Okamoto; Hiromi Kataoka; Takeshi Kamiya; Takashi Joh
    GASTROENTEROLOGY  2007/04  W B SAUNDERS CO-ELSEVIER INC
  • A novel strategy for oligosaccharide generation in the digestive tract using transglucosidase; Good heath promotion and disease prevention  [Not invited]
    Makoto Sasaki; Hiromi Kataoka; Naotaka Ogasawara; Eiji Kubota; Tsumeya Wada; Yoshinori Mori; Takaya Shimura; Tsutomu Mizoshita; Takashi Mizushima; Yasuyuki Okamoto; Takeshi Kamiya; Satoshi Koikeda; Takashi Joh
    GASTROENTEROLOGY  2007/04  W B SAUNDERS CO-ELSEVIER INC
  • At motif binding factor 1 (ATBF1) upregulates p21 transcription in cooperation with P53 and Runx3  [Not invited]
    Yoshinori Mori; Hiromi Kataoka; Tsuneya Wada; Eiji Kubota; Naotaka Ogasawara; Makoto Sasaki; Takeshi Kamiya; Yutaka Miura; Takashi Joh
    GASTROENTEROLOGY  2007/04  W B SAUNDERS CO-ELSEVIER INC
  • Role of es cell specific RAS, eras in gastric cancer  [Not invited]
    Eiji Kubota; Hirorm Kataoka; Makoto Sasaki; Kiyofumi Asai; Takashi Job
    GASTROENTEROLOGY  2007/04  W B SAUNDERS CO-ELSEVIER INC
  • Contribution of JAM-1 to gastric mucosal barrier function  [Not invited]
    T Oshima; T Joh; F Fujita; Y Mori; T Yamada; E Kubota; T Wada; S Togawa; N Ogasawara; K Itoh; S Tanida; H Kataoka; M Sasaki; M Itoh
    GASTROENTEROLOGY  2005/04  W B SAUNDERS CO
  • Diagnosis and treatment of laryngopharyngeal reflux disease  [Not invited]
    T Wada; T Joh; F Fujita; Y Mori; E Kubota; S Togawa; N Ogasawara; T Oshima; K Ito; T Yamada; S Tanida; H Kataoka; M Sasaki; M Ito
    GASTROINTESTINAL ENDOSCOPY  2005/04  MOSBY-ELSEVIER
  • Interstitial cells of Cajal increase with age in human colon of the elderly  [Not invited]
    N Takahashi; T Joh; M Kawade; S Takamatsu; K Ando; K Kobayashi; E Kubota; M Iida; M Itoh
    GASTROENTEROLOGY  2003/04  W B SAUNDERS CO

MISC

Awards & Honors

  • 2014 内視鏡医学研究振興財団 平成25年度研究助成
     
    受賞者: 久保田英嗣
  • 2010 United European Gastroenterology Travel Grant to UEGW for Basic scientist
     
    受賞者: 久保田英嗣

Research Grants & Projects

  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2025/03 
    Author : 澤田 武; 笠島 里美; 久保田 英嗣; 中村 慶史; 佐々木 泰史; 八尾 隆史
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2025/03 
    Author : 久保田 英嗣; 八木 崇志; 片岡 洋望
  • 日本学術振興会：科学研究費助成事業
    Date (from‐to) : 2022/04 -2025/03 
    Author : 森 義徳; 久保田 英嗣; 片岡 洋望; 青山 峰芳
  • 大腸癌における循環腫瘍DNAを用いた抗EGFR抗体薬耐性の検出と病状モニタリングの確立
    金沢大学：金沢大学がん進展制御研究所共同利用・共同研究費
    Date (from‐to) : 2020/04 -2022/04
  • 大腸がんにおけるグルコース輸送体の機能解析と治療標的として有用性の検討
    Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2019/04 -2022/03 
    Author : 久保田 英嗣; 八木 崇志; 片岡 洋望
     
    これまでに申請者らはグルコース輸送体、SGLT1、SGLT2が大腸がん細胞に発現していること、糖尿病薬として上市されているSGLT2阻害剤が大腸がん細胞、HCT116の増殖抑制効果を示すことを確認している。今年度は、複数のヒト大腸がん細胞（HCT116、SW480)を用い、SGLT2阻害剤による細胞内への当取り込み抑制作用および、SGLT2阻害剤による細胞内シグナル伝達系への影響を検討した。がん細胞内へのグルコース取り込みへの影響については、がん細胞をSGLT2阻害剤で処理した後に、グルコース類似体2-DGを用いたアッセイを用いて評価したところ、SW480では糖取り込みが抑制されたが、HCT-116では取り込みの抑制を認めなかった。グルコース輸送体のsiRNAを用いた検討でも同様の結果で、ともにSGLT2を発現しているものの、細胞により作用が異なることが示された。更に、阻害剤を用いてグルコース輸送体の機能を阻害した後に、大腸がん細胞から蛋白質を抽出し、Western blot法により細胞内シグナルの活性について検討した。SGLT2阻害剤は細胞内伝達経路のAMPKの活性を認め、SGLT2阻害剤による大腸がん細胞の増殖抑制にAMPK活性が関与している可能性が示された。このSGLT2阻害剤によるAMPK活性作用は、HCT116、SW480ともに認められ、SGLT2阻害剤による腫瘍細胞の増殖抑制には細胞内シグナル制御が関与していると考えられた。
  • 腫瘍溶解性ウイルスによる抗がん免疫応答の解析と新規消化管がん治療開発への応用
    Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2018/04 -2021/03 
    Author : 森 義徳; 久保田 英嗣; 片岡 洋望
     
    マウス大腸がん細胞、CT26を用いて、in vivoの研究を行った。マウス大腸がんモデルに腫瘍溶解性ウイルス、reovirusを投与し、腫瘍増殖抑制効果を評価した。さ らにSTING agoinst投与, reovirusとSTING agonistの併用効果を評価した。reovirus、STING agonistはともに腫瘍増殖抑制効果を示した。reovirus、STING agonistの併用投与では、より強い抗腫瘍効果が認められた。更に、それぞれの薬剤による抗腫瘍免疫誘導について、フローサイトメトリーを用いた腫瘍浸潤T細胞のプロファイル解析により評価した。reoviru単独投与では腫瘍浸潤T細胞の分画でCD8+細胞の誘導が認められた。STING agonistにおいても同様の結果が得られた。併用療法では、CD8+細胞の誘導に加えて、制御性T細胞の減少を認め、より強力な腫瘍免疫が誘導されている可能性が示された。なおreovirus、STING agonistおよび両者の併用による明らかな副作用は認めなかった。reovirus、STING agonistの投与のタイミングについては、reovirusを先行する投与方法、STING agonistをを先行する投与方法では抗腫瘍効果に有意差は認められなかった。薬剤投与後に摘出した腫瘍を用い、免疫染色で細胞障害について検討したところ、すべての投与方法で、アポトーシスの誘導が示された。
  • 胃がん細胞におけるPD-L1タンパク質膜輸送システムの解明と免疫療法への応用
    Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2017/04 -2021/03 
    Author : 城 卓志; 東山 繁樹; 久保田 英嗣; 日吉 裕美
     
    昨年度、申請者らは、CUL3発現と、PD-L1発現に関連を認めた細胞株、 NUGC-3、MKN28、NUGC-4、NCI-N87を用いて検討をすすめ、CUL3 siRNAによるPD-L1の細胞内局在変化を蛍光免疫染色を用い明らかとした。具体的には、NCI-N87ではCUL3 knockdownにより細胞膜に存在していたPD-L1が消失していた。NUGC-4ではCUL3 knockdownにより細胞膜でのPD-L1の発現が惹起された。このようにPD-L１発現へのCUL3 の関与は細胞株により異なる結果が得られた。一方で、細胞の形態や運動能、増殖能についてはCUL3 knockdownによる明らかな変化は認められなかった。 ヒト183種のBTBPに対するsiRNAを用いたPD-L1の発現制御におけるCUL3のパートナーとなるBTBPの網羅的な探索により明らかとなったPD-L1の発現制御への関与が推測される複数種のBTBPのsiRNAを作成し、細胞株への影響について検討した。これらのBTBPのknockdownでは、PD-L1の発現に変化のパターンがCUL3のknockdownとは異なり、またその一方で、CUL3 kncokdownとは異なり、細胞増殖能や細胞運動能の抑制が誘導される結果であった。また細胞増殖能や細胞運動能へのBTBP knockdownの影響についても、細胞株特異性が認められた。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2017/04 -2020/03 
    Author : Inagaki Satoko
     
    The aim of this study was to clarify the involvement of tumor-associated macrophages (TAM) in the microenvironment of colorectal cancer by analyzing these expression profiles. However, dissociation of TAM from colorectal cancer tissue was unsuccessful. Instead, protein expression study was performed in advanced colorectal cancer and colorectal premalignant lesions by immunohistochemistry. However, association between invasion of TAM and clinicopathological factors was not shown. Alternatively, the prevalence of abnormal nuclear β-catenin accumulation was shown to be significantly higher in traditional serrated adenomas (TSAs) than sessile serrated adenomas by immunohistochemistry, indicating the significance of Wnt signaling pathway activation in the carcinogenesis of TSAs.
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2014/04 -2018/03 
    Author : takemura masaya
     
    We prospectively recruited GER-associated chronic cough patirnts (n=37) and GER without cough (n=5). A PPI rabeprazole 20 mg qd and a prokinetic itopride 50 mg tid were given for 4 wks. We performed esophageal mucosal biopsy before the treatmet in all participants.Before and after this, we examined cough and reflux symptoms by scores of cough VAS, Japanese version of Leicester Cough Questionnaire (LCQ) and modified frequency scale for the symptoms of GERD (FSSG) sputum (s-) cells(%), and s- and plasma (p-) SP levels. Before the treatment, the expression of TRPV1 mRNA levels were significantly greater in GER-associated cough patients compared to GER without cough patients. Anti-reflux treatment significantly improved VAS, LCQ and FSSG scores for the 37 patients. The ΔVAS and ΔFSSG showed significant correlations. Δp-SP levels and Δs-neutrophils were significantly greater in the good responders than in the intractable , and these changes were intercorrelated (r=0.46, p<0.05).
  • DNA修復機構を標的とした新規消化器癌治療の開発
    日本学術振興会：科研費 基盤研究（C)
    Date (from‐to) : 2016 -2018 
    Author : 久保田英嗣
  • マスターモデュレーターとしてのCUL3システムを標的とした血管新生制御法の開発とがん治療応用
    日本医療研究開発機構：次世代がん医療創生研究事業
    Date (from‐to) : 2016 -2017 
    Author : 東山繁樹
  • 臨床応用のための新規光感受性糖鎖連結クロリンを用いた癌細胞超選択的次世代光線力学療法の開発
    文部科学省：橋渡し研究加速ネットワークプログラム・シーズB
    Date (from‐to) : 2014 -2016 
    Author : 片岡洋望
  • 消化器癌におけるATM発現とPARP阻害剤感受性の検討
    日本学術振興会：科研費 基盤研究（C)
    Date (from‐to) : 2013 -2015 
    Author : 久保田英嗣
  • 胃癌の新規診断，化学療法を目指したES細胞特異的Ras, ERasの機能解析
    日本学術振興会：科研費 挑戦的萌芽研究
    Date (from‐to) : 2008 -2009 
    Author : 久保田英嗣
  • ES細胞特異的Ras, ERasを標的とした新規胃癌治療の基礎的解析
    日本学術振興会：科研費 基盤研究（C)
    Author : 久保田英嗣

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