Clinical application of inhibition of Nuclear Factor-kappa B: oncogenic proliferation and surgical stress

• Project/Area Number: 24591870
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OCHIAI Takanori 東京医科歯科大学, 医学部附属病院, 助教 (20447486)
• Co-Investigator(Kenkyū-buntansha): INOUE Yoshinori 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (70280964) ; SAITO Yasunori 東京医科歯科大学, 医歯(薬)学総合研究科, 助教 (00516312) ; YAMAOKA Shoji (TANABE Minoru) 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (50197513) ; TANAKA Shinji 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (30253420) ; 山岡 昇司 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (90263160)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: NF-κB / 癌 / 手術 / シグナル伝達

Outline of Final Research Achievements

Nuclear Factor-kappa B is activated by carcinogens, tumor promoters, inflammatory cytokines, and chemotherapeutic agents. We focused on anti-tumorigenesis and anti-inflammation effects by means of inhibition of NF-κB activity. ①We revealed that (1)molecular target agent (IMD-0354) suppressed constitutive NF-κB activity, (2)gemcitabine stimulated NF-κB activity, and (3)combined therapy of IMD-0354 and gemcitabine revealed enhanced anti-tumor effects. ②We investigated a swine model to assess the invasiveness of surgical stress. In this model, inferior vena cava, aorta, the trunks of celiac artery and superior mesenteric artery were exposed. Intraoperative hemodynamics were monitored at the stable points after clamping each vessels, respectively. Inhibition of NF-κB activity in this model is still ongoing.

Research Products

• [Journal Article] High resectability of colorectal liver metastases with aggressive chemotherapy in the era of molecular target-based agents. (2013)
  • Author(s): Ochiai T, Ohta K, Iida M, Kumagai Y, Mitsunori Y, Aihara A, Noguchi N, Tanaka S, Arii S, Yamazaki S.
  • Journal Title: Hepatogastroenterology Volume: 60 Pages: 955-60
  • Peer Reviewed
• [Journal Article] High resectability of colorectal liver metastases with aggressive chemotherapy in the era of molecular target-based agents. (2013)
  • Author(s): Ochiai T, Ohta K, Iida M, Kumagai Y, Mitsunori M, Aihara A, Noguchi N, Tanaka S, Arii S, Yamazaki S.
  • Journal Title: Hepatogastroenterology Volume: 60
  • Peer Reviewed
• [Presentation] Combination Treatment of IκB Kinase β Inhibitor IMD-0354 and Gemcitabine Suppresses Oncogenic Proliferation of Pancreatic Cancer Cells。 (2014)
  • Author(s): Takanori Ochiai, Ayumi Shioya, Hiromi Honma, Yasunori Saito, Satoshi Matsumura, Daisuke Ban, Takumi Irie, Atsuhi Kudo, Noriaki Nakamura, Tomoyuki Fujikawa, Akiko Itai, Shinji Tanaka, Shigeki Arii, Shoji Yamaoka, and Minoru Tanabe
  • Organizer: Academic Surgical Congress 2014
  • Place of Presentation: San Diego, USA
• [Presentation] GemcitabineとIκB kinase β抑制による膵癌増殖抑制効果 (2013)
  • Author(s): 落合 高徳, 塩谷 歩美, 本間 宏美, 斎藤 愛記, 松村 聡, 伴 大輔, 入江 工, 工藤 篤, 中村 典明, 武藤 進, 板井 昭子, 山岡 昇司, 田中 真二
  • Organizer: 第113回日本外科学会
  • Place of Presentation: 福岡
• [Presentation] 下大静脈遮断下手術における大動脈遮断併用の限界と上腸間膜動脈遮断の有効性 (2013)
  • Author(s): 落合 高徳, 松村 聡, 伴 大輔, 入江 工, 工藤 篤, 中村 典明, 工藤 敏文, 地引 政利, 井上 芳徳, 田中 真二
  • Organizer: 第25回日本肝胆膵外科学会
  • Place of Presentation: 宇都宮
• [Presentation] Gemcitabine とIκB kinaseβ抑制による膵癌増殖抑制効果 (2013)
  • Author(s): 落合高徳、塩谷歩美、本間宏美、齋藤愛記、武藤進、松村聡、伴大輔、入江工、工藤篤、中村典明、板井昭子、山岡昇司、田中真二
  • Organizer: 第113回日本外科学会
  • Place of Presentation: 福岡
• [Presentation] 下大静脈遮断下手術における大動脈遮断併用の限界と上腸間膜動脈遮断の有効性 (2013)
  • Author(s): 落合高徳、松村聡、伴大輔、入江工、工藤篤、中村典明、工藤敏文、地引政利、井上芳徳、田中真二
  • Organizer: 第25回肝胆膵外科学会
  • Place of Presentation: 宇都宮