Targeted therapy for anti-cancer drug resistance mediated by several kinase pathways activation

• Project/Area Number: 21590180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tokai University
• Principal Investigator: KOBAYASHI Hiroyuki 東海大学, 医学部, 教授 (60195807)
• Research Collaborator: MACE Rothenberg L. Vanderbilt大学, 癌センター, 教授 ; YU Shyr Vanderbilt大学, 癌センター, 教授
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 癌 / 薬剤反応性 / 酵素 / シグナル伝達 / 核酸

Research Abstract

Idarubicin is one of the standard treatments for patients with acute myeloid leukemia. We have developed human acute leukemia cell line resistant to idarubucin. Several kinase pathways were activated in the resistant cell line. Small interfering RNA-mediated gene silencing of the activated kinases resulted in the partial reversal of drug resistance. The magnitude of reversal depended on the effectiveness of gene silencing. The resistance for idarubucin was also partially overcome by means of molecular targeted drugs or inhibitors that inhibit the activated kinases. The magnitude of reversal depended on the effectiveness of kinase inhibition.

Research Products

• [Journal Article] VEGF signaling is disrupted in the hearts of mice lacking estrogen receptor alpha (2011)
  • Author(s): Jesmin S
  • Journal Title: European Journal of Pharmacology Volume: 641 Pages: 168-178
  • Peer Reviewed
• [Journal Article] One-year cardiovascular event rates in Japanese outpatients with myocardial infarction, stroke, and atrial fibrillation. -Results From the Japan Thrombosis Registry for Atrial Fibrillation, Coronary, or Cerebrovascular Events (J-TRACE)- (2011)
  • Author(s): Goto S
  • Journal Title: Circulation Journal Volume: 75 Pages: 2598-2604
  • Peer Reviewed
• [Journal Article] Significant relationship between platelet activation and apnea-hypopnea index in patients with obstructive sleep apnea syndrome (2011)
  • Author(s): Kondo Y
  • Journal Title: Tokai Journal of Experimental and clinical Medicine Volume: 36 Pages: 79-83
  • Peer Reviewed
• [Journal Article] Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. (2011)
  • Author(s): Takatoshi Kakuta
  • Journal Title: American Journal of Kidney Disease Volume: 57 Pages: 422-431
  • Peer Reviewed
• [Journal Article] Dioxins in ascites and serum of women with endometriosis (2011)
  • Author(s): L.Y.Cai
  • Journal Title: Human Reproduction Volume: 26 Pages: 117-126
  • Peer Reviewed
• [Journal Article] Cysteinyl leukotriene receptor antagonists inhibit tumor metastasis by inhibiting capillary permeability (2010)
  • Author(s): Nozaki M, Yoshikawa M, Ishitani K, Kobayashi H, Houkin K, Imai K, Ito Y, Muraki T
  • Journal Title: Keio Journal of Medicine Volume: 59 Pages: 10-18
  • NAID: 10026203480
  • Peer Reviewed
• [Journal Article] Cysteinyl leukotriene receptor antagonists inhibit tumor metastasis by inhibiting capillary permeability. (2010)
  • Author(s): Masako Nozaki
  • Journal Title: Keio Journal of Medicine Volume: 59 Pages: 10-18
  • Peer Reviewed
• [Journal Article] Beneficial effects of medical advice provided to elderly persons under the anti-aging health check-up system at Tokai University Tokyo Hospital (2009)
  • Author(s): Yasuhiro NISHIZAKI
  • Journal Title: Tokai J.Exp.Clin.Med. 34 Pages: 142-151
  • Peer Reviewed
• [Presentation] S-1 enhances radiosensitivity in a mouse xenograft model of human colon cancer (2009)
  • Author(s): MURAYAMA C
  • Organizer: Joint ECCO 15-34th ESMO Multidisciplinary Congress
  • Place of Presentation: Berlin
  • Year and Date: 2009-09-23
• [Presentation] S-1 enhances radiosensitivity in a mouse xenograft model of human colon cancer. (2009)
  • Author(s): Chieko MURAYAMA
  • Organizer: Joint ECCO 15- 34th ESMO Multidisciplinary Congress
  • Place of Presentation: Berlin
  • Year and Date: 2009-09-23
• [Remarks]
  • URL: http://www.cp-tokai.com/