Development of treatment and prevention for pancreatic neuroendocrine tumor using glucagon gene knock-out mouse

• Project/Area Number: 15K10049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Nagoya University
• Principal Investigator: Kikumori Toyone 名古屋大学, 医学部附属病院, 講師 (90402635)
• Co-Investigator(Renkei-kenkyūsha): Hayashi Yoshitaka 名古屋大学, 環境医学研究所, 准教授 (80420363)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 膵内分泌腫瘍 / グルカゴン / mTOR阻害剤 / EMT

Outline of Final Research Achievements

We explored treatment / prevention methods by clarifying pathologically and molecular biologically the biological properties of tumor developed in glucagon gene knockout mouse in which pancreatic tumors arose spontaneously. We reported that the pancreatic tumor developed in this mouse closely resembles histological and biological attitudes to human pancreatic neuroendocrine tumor (pNET). Expression of cellular growth factors and angiogenic factors (AKT, mTOR, VEGF, etc.) in pancreatic islet cells at each stage of the process of malignant transformation were examined by immunostaining of excised tissue specimens. Everolimus, an mTOR inhibitor which has clinical indication for pNET, was continued to be administered to these mice shortly after birth, and it was confirmed that pancreatic tumor development was suppressed.

Research Products

• [Journal Article] Pancreatic Neuroendocrine Tumors in Mice Deficient in Proglucagon-Derived Peptides. (2015)
  • Author(s): Takano Y, Kasai K, Takagishi Y, Kikumori T, Imai T, Murata Y, Hayashi Y.
  • Journal Title: PLoS One Volume: 10 Issue: 7 Pages: e0133812-e0133812
  • DOI: 10.1371/journal.pone.0133812
  • Peer Reviewed / Open Access
• [Presentation] 副腎悪性腫瘍39例の術後長期予後 (2017)
  • Author(s): 今井 常夫, 武内 大, 安立 弥生, 稲石 貴弘, 高野 悠子, 中西 賢一, 野田 純代, 宮嶋 則行, 菊森 豊根
  • Organizer: 第29回日本内分泌外科学会総会
• [Presentation] 褐色細胞腫・パラガングリオーマに対する集学的治療 当院における褐色細胞腫・パラガングリオーマの集学的治療 (2017)
  • Author(s): 宮嶋 則行, 稲石 貴弘, 安立 弥生, 高野 悠子, 中西 賢一, 野田 純代, 武内 大, 菊森 豊根
  • Organizer: 第29回日本内分泌外科学会総会
• [Presentation] 多発性内分泌腫瘍症の診断と治療 当院のMEN1に随伴する腫瘍の検討 (2016)
  • Author(s): 武内 大, 稲石 貴弘, 宮嶋 則行, 安立 弥生, 大西 英二, 柴田 雅央, 高野 悠子, 中西 賢一, 野田 純代, 林 裕倫, 角田 伸行, 菊森 豊根, 今井 常夫
  • Organizer: 第28回日本内分泌外科学会総会
  • Place of Presentation: 神奈川県横浜市 ロイヤルホールヨコハマ
  • Year and Date: 2016-05-26
• [Presentation] The efficacy and safety of total parathyroidectomy and autotransplantation for the treatment of hyperparathyroidism in multiple endocrine neoplasia type 1 (2015)
  • Author(s): Dai Takeuchi, Toyone Kikumori, Hironori Hayashi,Tsuneo Imai
  • Organizer: World Congress of Surgery
  • Place of Presentation: バンコック（タイ）
  • Year and Date: 2015-08-24
  • Int'l Joint Research