Role of p63 in metastasis and therapeutic resistance of bladder cancer

• Project/Area Number: 23501266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KOGA Fumitaka 東京医科歯科大学, 医歯(薬)学総合研究科, 非常勤講師 (10285851)
• Project Period (FY): 2011-04-28 – 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 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2011: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 膀胱癌 / 転移 / 治療抵抗性 / ｐ６３ / 化学放射線治療抵抗性 / リスク因子 / 癌幹細胞 / p63

Outline of Final Research Achievements

The following findings were obtained in the present study series and reported in international medical journals. (1) Bladder cancer stem cells are resistant to cisplatin and they lose expression of p63 protein, suggesting that loss of p63 is associated with cisplatin resistance. (2) No significant association was obtained between chemoradiation resistance and p63 expression profile in muscle-invasive bladder cancer. (3)Overexpression of erbB2 in bladder cancer is significantly associated with resistance to chemoradiation and bladder cancer death.

Research Products

• [Journal Article] Significance of ERBB2 overexpression in therapeutic resistance and cancer-specific survival in muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach (2014)
  • Author(s): Inoue M, Koga F, Yoshida S, Tamura T, Fujii Y, Ito E, Kihara K.
  • Journal Title: Int J Radiat Oncol Biol Phys Volume: 90 Issue: 2 Pages: 303-311
  • DOI: 10.1016/j.ijrobp.2014.05.043
  • Peer Reviewed / Open Access
• [Journal Article] Potential role of Hsp90 inhibitors in overcoming cisplatin resistance of bladder cancer-initiating cells (2012)
  • Author(s): Tatokoro M, Koga F, Yoshida S, Kawakami S, Fujii Y, Neckers L, Kihara K
  • Journal Title: Int J Cancer Volume: 131 Issue: 4 Pages: 987-96
  • DOI: 10.1002/ijc.26475
  • Peer Reviewed
• [Journal Article] Role of diffusion-weighted magnetic resonance imaging in predicting sensitivity to chemoradiotherapy in muscle-invasive bladder cancer (2012)
  • Author(s): Yoshida S, Koga F, Kobayashi S, Ishii C, Tanaka H, Tanaka H, Komai Y, Saito K, Masuda H, Fujii Y, Kawakami S, Kihara K
  • Journal Title: Int J Radiat Oncol Biol Phys Volume: 83
  • Peer Reviewed
• [Journal Article] ErbB2 and NFκB overexpression as predictors of chemoradiation resistance and putative targets to overcome resistance in muscle-invasive bladder cancer (2011)
  • Author(s): Koga F, Yoshida S, Tatokoro M, Kawakami S, Fujii Y, Kumagai J, Neckers L, Kihara K
  • Journal Title: PLoS one Volume: 6
  • Peer Reviewed
• [Journal Article] Low-dose Hsp 90 inhibitors tumor-selectively sensitize bladder cancer cells to chemoradiotherapy (2011)
  • Author(s): Yoshida S, Koga F, Tatokoro M, Kawakami S, Fujii Y, Kumagai J, Neckers L, Kihara K
  • Journal Title: Cell Cycle Volume: 10 Pages: 4291-4299
  • Peer Reviewed
• [Presentation] Pre-therapeutic risk stratification of muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach (2014)
  • Author(s): Koga F, Inoue M, Kijima T, Yoshida S, Ishioka J, Matsuoka Y, Numao N, Saito K, Masuda H, Fujii Y, Kihara K
  • Organizer: 29th annual EAU congress
  • Place of Presentation: Stockholm
  • Year and Date: 2014-04-14
• [Presentation] Hsp90 阻害剤による膀胱癌幹細胞のシスプラチン抵抗性克服の可能性 (2012)
  • Author(s): 古賀文隆
  • Organizer: 第7回 Basic Urology Research Seminar
  • Place of Presentation: 大分市
  • Invited
• [Presentation] Diffusion-weighted MRI predicts sensitivity to chemoradiation in muscle-invasive bladder cancer (2012)
  • Author(s): Koga F, Yoshida S, Kobayashi S, Ishii C, Tanaka Hiroshi, Fujii Y, Tanaka Hajime, Masuda H, Saito K, Komai Y, Kawakami S, Kihara K
  • Organizer: 27th annual EAU congress
  • Place of Presentation: Paris
• [Presentation] ErbB2 overexpression predicts chemoradiotherapy resistance and worse prognosis in muscle-invasive bladder cancer patients treated with induction chemoradiotherapy followed by partial or radical cystectomy
  • Author(s): 井上雅晴、古賀文隆
  • Organizer: 29th European Association of Urology annual meeting
  • Place of Presentation: ストックホルム（スウェ－デン）
• [Presentation] Pre-therapeutic risk stratification of muscle-invasive bladder cancer patients treated with chemoradiation-based selective bladder-sparing approach
  • Author(s): 古賀文隆
  • Organizer: 29th European Association of Urology annual meeting
  • Place of Presentation: ストックホルム（スウェ－デン）