Mechanisms of accumulation of G1-S phase cell cycle regulating protein in bladder carcinogenesis for the development of novel intarvesical treatment modalities to bladder cancer

• Project/Area Number: 19890113
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Kyoto University
• Principal Investigator: WATANABE Jun Kyoto University, 医学研究科, 助教 (10452335)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,294,000 (Direct Cost: ¥1,970,000、Indirect Cost: ¥324,000); Fiscal Year 2008: ¥1,404,000 (Direct Cost: ¥1,080,000、Indirect Cost: ¥324,000); Fiscal Year 2007: ¥890,000 (Direct Cost: ¥890,000)
• Keywords: triptolide / TBP-2 / urinary bladder / galectin-7 / CXCL1

Research Abstract

癌細胞に対するTriptolideの負荷により、p53の転写共役因子のひとつであるGSK-3βのリン酸化を介してp21発現の減少が生じ、シスプラチン誘導性細胞死が増強することを明らかにした。また、TBP2ノックアウトマウスにおいて、発癌物質BBNの経口摂取により、正常マウスに比較して早期より悪性度の高い尿路上皮癌が生ずることをあきらかにした。発癌に差異を与えたシグナル経路を解析し、発癌経路そのものに起因する抗癌剤耐性についても解析を進めることで、TBP2により細胞周期関連蛋白発現を介し抗癌剤誘導性細胞死感受性の低下が認められることを明らかにした。

Research Products

• [Journal Article] Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3beta with p53 (2008)
  • Author(s): Y Matsui, J Watanabe, M Ikegawa, T Kamoto, O Ogawa and H Nishiyama
  • Journal Title: Oncogene 27 Pages: 4603-4614
  • Peer Reviewed
• [Journal Article] Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder (2008)
  • Author(s): Holyoake A, O'Sullivan P, Pollock R, Best T, Watanabe J, Kajita Y, Matsui Y, Ito M, Nishiyama H, Kerr N, da Silva Tately F, Cambridge L, Toro T, Ogawa O, Guilford P.
  • Journal Title: Clinical Cancer Research 14(3) Pages: 742-74
  • Peer Reviewed
• [Journal Article] Secreted CXCL1 is a potential mediator and marker of the tumor invasion of bladder cancer (2008)
  • Author(s): Kawanishi H, Matsui Y, Ito M, Watanabe J, Takahashi T, Nishizawa K, Nishiyama H, Kamoto T, Mikami Y, Tanaka Y, Jung G, Akiyama H, Nobumasa H, Guilford P, Reeve A, Okuno Y, Tsujimoto G, Nakamura E, Ogawa O.
  • Journal Title: Clinical Cancer Research 14(9) Pages: 742-749
  • Peer Reviewed
• [Journal Article] Cancer-specific enhancement of cisplatin-induced cytotoxicity with triptolide through an interaction of inactivated glycogen synthase kinase-3beta with p53. (2008)
  • Author(s): Y Matsui, J Watanabe, M Ikegawa, T Kamoto, O Ogawa, H Nishiyama
  • Journal Title: Oncogene 27 Pages: 4603-4614
  • Peer Reviewed
• [Journal Article] Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder (2008)
  • Author(s): Holyoake A, O' Sullivan P, Pollock R, Best T, Watanabe J, Kajita Y, Matsui Y, Ito M, Nishiyama H, Kerr N, da Silva Tately F, Cambridge L, Toro T, Ogawa O, Guilford P.
  • Journal Title: Clinical Cancer Research 14(3) Pages: 742-749
  • Peer Reviewed
• [Journal Article] Secreted CXCL1 is a potential mediator and marker of the tumor invasion of bladder cancer. (2008)
  • Author(s): Kawanishi H, Matsui Y, Ito M, Watanabe J, Takahashi T, Nishizawa K, Nishiyama H, Kamoto T, Mikami Y, Tanaka Y, Jung G, Akiyama H, Nobumasa H, Guilford P, Reeve A, Okuno Y, Tsujimoto G, Nakamura E, Ogawa O.
  • Journal Title: Clinical Cancer Research 14(9) Pages: 2579-2587
  • Peer Reviewed
• [Journal Article] Genetic analysis of multifocal urothelial cancers by array-based comparative genomic hybridisation, (2007)
  • Author(s): kawanishi H, Takahashi T, Ito M, Matsui Y, Watanabe J, Ito N, Kamoto T, Kadowaki T, Tsujimoto G, Imoto I, Inazawa J, Nishiyama H, Ogawa O.
  • Journal Title: British Journal of cancer 97(2) Pages: 260-266
  • Peer Reviewed
• [Presentation] Thioredoxin-binding protein 2は膀胱癌におけるシスプラチン併用化学療法の耐性化因子である (2008)
  • Author(s): 西澤恒二、松井喜之、西山博之、渡部淳、梶田洋一郎、賀本敏行、小川修
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Thioredoxin-binding protein 2 as a predictive factor for response to cisplatinum-based chemotherapy in bladder cancer (2008)
  • Author(s): Koji Nishizawa, Yoshiyuki Matsui, Hiroyuki Nishiyama, Jun Watanabe, Yoichiro Kajita, Toshiyuki Kamoto, and Osamu Ogawa
  • Organizer: 9th Asian Congress of Urology
  • Place of Presentation: New Delhi, India
  • Year and Date: 2008-10-04
• [Presentation] Thioredxin-binding protein 2 as a predictive factor for response to cisplatinum-based chemotherapy in bladde rcancer. (2008)
  • Author(s): Koji Nishizawa, Yoshiyuki Matsui, Hiroyuki Nishiyama, Jun Watanabe, Yoichiro Kajita, Toshiyuki Kamoto, Osamu Ogawa
  • Organizer: 9th Asian Congress of Urology
  • Place of Presentation: New Delhi, India
  • Year and Date: 2008-10-04
• [Presentation] 尿路上皮癌におけるtriptolideを用いた癌特異的p21target therapyに関する検討 (2008)
  • Author(s): 松井喜之、西山博之、渡部 淳、西澤恒二、梶田洋一郎、賀本敏行、小川 修
  • Organizer: 第17回泌尿器科分子細胞研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-02-16
• [Remarks] ホームページ等