Development of novel therapies targeting esophageal cancer using Midkine inhibitors

• Project/Area Number: 23591950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kawasaki Medical School
• Principal Investigator: NAOMOTO YOSHIO 川崎医科大学, 医学部, 教授 (00237190)
• Co-Investigator(Kenkyū-buntansha): YAMATSUJI Tomoki 川崎医科大学, 医学部, 准教授 (40379730) ; FUKAZAWA Takuya 川崎医科大学, 医学部, 講師 (20379845) ; TAKAOKA Munenori 川崎医科大学, 医学部, 講師 (50548568) ; 繁光 薫 川崎医科大学, 医学部, 講師 (50585007)
• Co-Investigator(Renkei-kenkyūsha): NAKAJIMA Motowo 東京大学, 分子細胞生物学研究所, 客員教授 (90240738)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 食道癌 / 肺癌 / Midkine / 11 / 食道外科学 / 分子標的治療

Research Abstract

Midkine is a heparin-binding growth factor that is highly expressed in many malignant tumors. Therefore,the inhibition of Midkine is considered a potential strategy forcancer therapy. In the present study, we demonstrate a novel small molecule compound:MDK#3 that targets Midkine. MDK#3 suppressed the cell growth of Midkine-positive esophageal cancer cells and pulmonary adenocarcinoma cells. However, the inhibitor did not reduce the cell viability of normal human lung fibroblast cells.MDK#3 increased caspase-3 activity and apoptosis in MDK positive pulmonary adenocarcinoma cell. These results imply that inhibition of Midkine with MDK#3 provides a potential therapeutic approach for the treatment of esophageal cancer and lung cancer that are driven by Midkine.

Research Products

• [Journal Article] (2013)
  • Author(s): Hao H, Maeda Y, Fukazawa T, Yamatsuji T, Takaoka M, Bao XH, Matsuoka J, Okui T, Shimo T, Takigawa N, Tomono Y, Nakajima M, Fink-Baldauf IM, Nelson S, Seibel W, Papoian R, Whitsett JA, Naomoto Y.
  • Journal Title: PLoS One Volume: 8(8)
  • Peer Reviewed
• [Journal Article] Inhibition of the growth factor MDK/midkine by a novel small molecule compound to treat non-small cell lung cancer. (2013)
  • Author(s): Hao H, Maeda Y, Fukazawa T, Yamatsuji T, Takaoka M, Bao XH, Matsuoka J, Okui T, Shimo T, Takigawa N, Tomono Y, Nakajima M, Fink-Baldauf IM, Nelson S, Seibel W, Papoian R, Whitsett JA, Naomoto Y.
  • Journal Title: PLoS One. Volume: 16 Issue: 8 Pages: 8-8
  • DOI: 10.1371/journal.pone.0071093
  • Peer Reviewed
• [Presentation] Midkine阻害剤を用いた非小細胞肺癌に対する新規治療法開発. (2013)
  • Author(s): 深澤拓也、前田豊、山辻知樹、高岡宗徳、森田一郎、瀧川奈義夫、猶本良夫
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: 東京都千代田区
  • Year and Date: 2013-11-21
• [Presentation] 肺腺癌に対するMidkineを標的とした新規治療法の開発 (2013)
  • Author(s): 深澤拓也、山辻知樹、前田豊、瀧川奈義夫、高岡宗徳、森田一郎、中島元夫、ジェフリー・ウィトセット、猶本良夫
  • Organizer: 第113回日本外科学会学術集会
  • Place of Presentation: 福岡県博多
  • Year and Date: 2013-04-11
• [Presentation] Development of novel targeted therapies for non-small cell carcinoma by novel Midkine inhibitors (2013)
  • Author(s): Takuya Fukazawa, Yutaka Maeda, Huifang Hao, Tomoki Yamatsuji, Munenori Takaoka, Nagio Takigawa, and Yoshio Naomoto
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: 米国ワシントンDC
  • Year and Date: 2013-04-08
• [Presentation] Inhibition of Midkine by a novel small molecule compound to treat non-small cell lung cancer (2013)
  • Author(s): Takuya Fukazawa1, Huifang Hao1, Tomoki Yamatsuji1, Munenori Takaoka1, Nagio Takigawa2, Yutaka Maeda3, Junji Matsuoka4, Tatsuo Okui5, Tsuyoshi Shimo5, Yasuko Tomono6, Motowo Nakajima7, Jeffrey A. Whitsett2 and Yoshio Naomoto
  • Organizer: 第72回日本癌学会 学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Remarks]
  • URL: http://www.kawasaki-m.ac.jp/med/index.html