Castration resistant prostate cancer with drug resistance and tumor microenvironment

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• 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 / 薬剤耐性 / 5α還元酵素 / 去勢抵抗性

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) Issue: 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) Issue: 1 Pages: 227-34
  • DOI: 10.1016/j.juro.2013.07.101
  • Peer Reviewed
• [Journal Article] Identification of drug candidate against prostate cancer from the aspect of somatic cell reprogramming. (2014)
  • Author(s): Kosaka T, Nagamatsu G, Saito S, Oya M, Suda T, Horimoto K
  • Journal Title: Cancer Sci Volume: 104 Issue: 8 Pages: 1017-1026
  • DOI: 10.1111/cas.12183
  • Peer Reviewed
• [Journal Article] Invasion and metastasis of renal cell carcinoma. (2014)
  • Author(s): Mikami S, Oya M, Mizuno R, Kosaka T, Katsube KI, Okada Y.
  • Journal Title: Med Mol Morphol. Volume: in press
  • 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] Prognostic significance of Bcl-xL expression and efficacy of Bcl-xL targeting therapy in urothelialcarcinoma. (2013)
  • Author(s): Shunsuke Yoshimine, Eiji Kikuchi, Takeo Kosaka, Shuji Mikami, Akira Miyajima, Yasunori Okada, Mototsugu Oya.
  • Journal Title: British Journal of Cancer (2013) Volume: 108 Issue: 11 Pages: 1-9
  • 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 Issue: 10 Pages: 2123-2129
  • DOI: 10.1038/bjc.2013.169
  • Peer Reviewed
• [Journal Article] Human castrationresistant 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 Volume: 3 Issue: 1 Pages: 1268-1268
  • 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): K. Suzuki, R. Mizuno, K. Suenaga, T. Teruya, N. Tanaka, T. Kosaka, M. Oya
  • Journal Title: Cancer Medicine Volume: 2 Issue: 1 Pages: 32-39
  • DOI: 10.1002/cam4.53
  • Peer Reviewed
• [Journal Article] Patient characteristics and outcomes in metastatic upper tract urothelial carcinoma after radical nephroureterectomy: the experience of Japanese multi-institutions (2013)
  • Author(s): Nobuyuki Tanaka, Eiji Kikuchi, Kent Kanao, Kazuhiro Matsumoto, Hiroaki Kobayashi, Yasumasa Miyazaki, Hiroki Ide, Jun Obata, Katsura Hoshino, Suguru Shirotake, Nozomi Hayakawa, Takeo Kosaka, Akira Miyajima, Tetsuo Momma, Ken Nakagawa, Shintaro Hasegawa, Yosuke Nakajima, Mototsugu Oya
  • Journal Title: British Journal of Urology Volume: 112 Issue: 2 Pages: 741-747
  • DOI: 10.1111/bju.12133
  • Peer Reviewed
• [Journal Article] The prognostic significance of vasohibin-1 expression in patients with prostate cancer (2013)
  • Author(s): Takeo Kosaka
  • Journal Title: Br J Cancer Volume: 未定
  • 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おける5α還元酵素活性の解析 (2013)
  • Author(s): 小坂 威雄
  • Organizer: 第22回 泌尿器科分子細胞研究会
  • Place of Presentation: 高知
• [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
  • Organizer: 第101回 日本泌尿器科学会総会
  • Place of Presentation: 北海道
• [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
• [Presentation] 進行前立腺癌におけるアンドロゲン産生系の解析 (2012)
  • Author(s): 小坂 威雄
  • Organizer: 前立腺シンポジウム
  • Place of Presentation: 東京
  • Invited
• [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
  • Author(s): 小坂 威雄、宮嶋 哲、長田 浩彦、前田 高宏、安水 洋太、服部 盛也、菊地 栄次、中川 健、大家 基嗣
  • Organizer: 第101回 日本泌尿器科学会総会
  • Place of Presentation: ロイトン札幌（北海道）
• [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
  • 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: グランキュ－ブ大阪（大阪）
  • Invited
• [Presentation] 前立腺癌における新規血管新生関連マーカーの発現の検討
  • 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、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: 品川コンベンションセンター（東京）
  • Invited
• [Presentation] 前立腺癌のがん幹細胞性遺伝子ネットワークを標的とした革新的新規治療戦略の確立
  • Author(s): 小坂 威雄、永松 剛、宮嶋 哲、三上 修治、斎藤 秀、宮崎 保匡、安水 洋太、水野 隆一、菊地 栄次、中川 健、堀本 勝久、岡田 保典、須田 年生、大家 基嗣
  • Organizer: 第23回 泌尿器科分子細胞研究会
  • Place of Presentation: ホテルメトロポリタン（山形）
• [Presentation] 抗がん剤耐性前立腺癌における、がん幹細胞関連遺伝子ネットワークを標的とした新規治療戦略
  • Author(s): 小坂 威雄、永松 剛、宮嶋 哲、三上 修治、斎藤 秀、宮崎 保匡、安水 洋太、水野 隆一、菊地 栄次、中川 健、堀本 勝久、岡田 保典、須田 年生、大家 基嗣
  • Organizer: 第102回 日本泌尿器科学会総会
  • Place of Presentation: 神戸国際展示場（神戸）
• [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
  • 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
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] Intracrine dynamics of CYP17A1 activities in human castration resistant prostate cancer
  • Author(s): Kosaka T, Miyajima A, Nagata H, Maeda T, Kikuchi E, Oya M.
  • Organizer: American Urological Asociation Annual Meeting
  • Place of Presentation: Sandiego (USA)
• [Presentation] A new strategy for castration resistant prostate cancer with targeting to feedback mechanism of PI3K/AKT/mTOR pathway
  • Author(s): Yasumizu Y, Kosaka T, Miyajima A,Kikuchi E, Oya M.
  • Organizer: American Urological Asociation Annual Meeting
  • Place of Presentation: Sandiego (USA)
• [Remarks]
  • URL: http://www.keio-urology.jp/
• [Remarks] 慶應大学医学部泌尿器科教室からの論文紹介 NO.32
  • URL: http://www.keio-urology.jp/
• [Remarks] 慶應大学医学部泌尿器科教室からの論文紹介 NO.31
  • URL: http://www.keio-urology.jp/