Castration resistant prostate cancer with drug resistance and tumor microenvironment

2013 Fiscal Year Final Research Report

• Project/Area Number: 24890230
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Keio University
• Principal Investigator: TAKEO Kosaka 慶應義塾大学, 医学部, 助教 (30445407)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Keywords: 前立腺癌 / 血管新生 / アンドロゲン / 去勢抵抗性前立腺癌 / 微小環境 / VASH1 / C4-2AT6

Research Abstract

To reveal tumor microenvironment in Prostate Cancer (PCa), we focused on angiogenesis and androgen production. We examine the expression of VASH1 in PCa specimens. We found VASH1 density represents a clinically relevant predictor of patient prognosis and can be a new biomarker that would provide additional prognostic information in PCa (Kosaka T. et al. Br J Cancer 2013). To ascertain the potential SRD5A activity, we cultured two human CRPC cell lines: C4-2 and C4-2AT6 cells with steroid precursors: 13C-Adione, and analyzed the sequential biosynthesis of 13C-T and 13C-DHT by LC/MS/MS. 13C-DHT concentration in C4-2AT6 cells was significantly lower than C4-2. An increased concentration of DHT did not have a positive effect on cell proliferation. SRD5A inhibitors did not have any inhibitory effect, suggesting CRPC cells may have an unknown regulation system to protect themselves from androgenic suppressive effect mediated by SRD5A activity (Kosaka T. et al. Scientific Rep 2013).

Research Products

• [Journal Article] Prognostic value of preoperative multiparametric magnetic resonance imaging (MRI) for predicting biochemical recurrence after radical prostatectomy (2014)
  • Author(s): Hattori S, Kosaka T, Mizuno R, Kanao K, Miyajima A, Yasumizu Y, Yazawa S, Nagata H, Kikuchi E, Mikami S, Jinzaki M, Nakagawa K, Tanimoto A, Oya M
  • Journal Title: BJU Int Volume: 113(5) Pages: 741-7
  • DOI: 10.1111/bju.12329
  • Peer Reviewed
• [Journal Article] Dual PI3K/mTOR inhibitor NVP-BEZ235 sensitizes docetaxel in castration resistant prostate cancer (2014)
  • Author(s): Yasumizu Y, Miyajima A, Kosaka T, Miyazaki Y, Kikuchi E, Oya M
  • Journal Title: J Urol Volume: 191(1) Pages: 227-34
  • DOI: 10.1016/j.juro.2013.07.101
  • Peer Reviewed
• [Journal Article] Invasion and metastasis of renal cell carcinoma (2013)
  • Author(s): Mikami S, Oya M, Mizuno R, Kosaka T, Katsube KI, Okada Y
  • Journal Title: Med Mol Morphol
  • Peer Reviewed
• [Journal Article] Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming (2013)
  • Author(s): Kosaka T, Nagamatsu G, Saito S, Oya M, Suda T, Horimoto K
  • Journal Title: Cancer Sci Volume: 104(8) Pages: 1017-26
  • DOI: 10.1111/cas.12183
  • Peer Reviewed
• [Journal Article] Prognostic significance of Bcl-xL expression and efficacy of Bcl-xL targeting therapy in urothelial carcinoma (2013)
  • Author(s): Yoshimine S, Kikuchi E, Kosaka T, Mikami S, Miyajima A, Okada Y, Oya M
  • Journal Title: Br J Cancer Volume: 108(11) Pages: 2312-20
  • DOI: 10.1038/bjc.2013.216
  • Peer Reviewed
• [Journal Article] The prognostic significance of vasohibin-1 expression in patients with prostate cancer (2013)
  • Author(s): Kosaka T, Miyazaki Y, Miyajima A, Mikami S, Hayashi Y, Tanaka N, Nagata H, Kikuchi E, Nakagawa K, Okada Y, Sato Y, Oya M
  • Journal Title: Br J Cancer Volume: 108(10) Pages: 2123-9
  • DOI: 10.1038/bjc.2013.169
  • Peer Reviewed
• [Journal Article] Human castration resistant prostate cancer rather prefer to decreased 5α-reductase activity (2013)
  • Author(s): Kosaka T, Miyajima A, Nagata H, Maeda T, Kikuchi E, Oya M
  • Journal Title: Sci Rep Pages: 1268
  • DOI: 10.1038/srep01268
  • Peer Reviewed
• [Journal Article] Bisebromoamide, an extract from Lyngbya species, induces apoptosis through ERK and mTOR inhibitions in renal cancer cells (2013)
  • Author(s): 8: Suzuki K, Mizuno R, Suenaga K, Teruya T, Tanaka N, Kosaka T, Oya M
  • Journal Title: Cancer Med Volume: 2(1) Pages: 32-9
  • DOI: 10.1002/cam4.53
  • Peer Reviewed
• [Presentation] 前立腺癌における新規血管新生マーカーの発現の検討 (2013)
  • Author(s): 小坂威雄,宮崎保匡,宮嶋哲、三上修治,安水洋太,菊地栄次,田中川健,岡田保典,佐藤靖史,大家基嗣
  • Organizer: 第29回前立腺シンポジウム
  • Place of Presentation: 東京品川コンベンションセンター
  • Year and Date: 2013-12-14
• [Presentation] PI3K-mTORシグナル阻害剤は去勢抵抗性前立腺癌においてドセタキセルへの感受性を増大させる (2013)
  • Author(s): 安水洋太,宮嶋哲,小坂威雄,宮崎保匡、菊地栄次,大家基嗣
  • Organizer: 第72回日本癌学会総会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2013-10-05
• [Presentation] 上部尿路上皮癌における新規血管新生制御因子Vasohibin-1発現の臨床的意義 (2013)
  • Author(s): 宮崎保匡,小坂威雄,三上修治,菊地栄次,田中伸之,前田高宏,石田勝,宮嶋哲,中川健,岡田保典,佐藤靖史,大家基嗣
  • Organizer: 日本癌治療学会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2013-09-14
• [Presentation] 去勢抵抗性前立腺癌におけるアンドロゲン産生系の生化学的解析 (2013)
  • Author(s): 小坂威雄,宮嶋哲,安水洋太,菊地栄次,大家基嗣
  • Organizer: 第32回アンドロロジー学会
  • Place of Presentation: 大阪グランキューブ大阪
  • Year and Date: 2013-07-26
• [Presentation] A new strategy for castration resistant prostate cancer with targeting to feedback mechanisms of PI3K/AKT/mTOR pathway (2013)
  • Author(s): 5: Yasumizu Y, Miyajima A, Kosaka T, Kikuchi E, Oya M
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: Sandiego USA
  • Year and Date: 2013-05-06
• [Presentation] Intracrine dynamics of CYP17A1 activities in human castration resistant prostate cancer (2013)
  • Author(s): Kosaka T, Miyajima A, Nagata H, Maeda T,Kikuchi E, Oya M
  • Organizer: American Urological Association Annual Meeting
  • Place of Presentation: Sandiego USA
  • Year and Date: 2013-05-05
• [Presentation] アンドロゲン産生系に着目した去勢抵抗性前立腺癌の生化学的解析 (2013)
  • Author(s): 小坂威雄,宮嶋哲,長田浩彦、前田高宏、安水洋太,菊地栄次,大家基嗣
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: 札幌ロイトン札幌
  • Year and Date: 2013-04-25
• [Presentation] 去勢抵抗性前立腺癌に対するPI3K・mTORC1/2阻害剤とドセタキセル併用効果についての検討(Combination Therapy with PI3K-mTOR Pathway Inhibitor and Docetaxel in Castration Resistant Prostate Cancer) (2012)
  • Author(s): 安水洋太,宮嶋哲,小坂威雄,城武卓,菊地栄次,大家基嗣
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌ロイトン札幌
  • Year and Date: 2012-09-20
• [Presentation] 上部尿路上皮癌におけるVasohibin-1の発現に関する予後因子として検討(The prognostic significance of vasohibin-1 expression in patients with upper urinary tract urothelial carcinoma) (2012)
  • Author(s): 宮崎保匡,小坂威雄,三上修治,菊地栄次,田中伸之,前田高宏,石田勝,宮嶋哲,中川健,岡田保典,佐藤靖史,大家基嗣
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌ロイトン札幌
  • Year and Date: 2012-09-20
• [Presentation] 去勢抵抗性前立腺癌におけるCYP17A1活性(Direct evidence of dual CYP17A1 activities in human castration resistant prostate cancer) (2012)
  • Author(s): 小坂威雄,宮嶋哲,菊地栄次,大家基嗣
  • Organizer: 第71回日本癌学会総会
  • Place of Presentation: 札幌ロイトン札幌
  • Year and Date: 2012-09-20
• [Remarks]
  • URL: http://www.keio-urology.jp/