Establishment of novel therapeutic strategies for castration-resistant prostate cancer by elucidation of molecular mechanism including endocrine FGFs

• Project/Area Number: 15K10591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Hiroshima University
• Principal Investigator: Teishima Jun 広島大学, 医歯薬保健学研究科(医), 准教授 (20397962)
• Co-Investigator(Kenkyū-buntansha): 松原 昭郎 広島大学, 医歯薬保健学研究科(医), 教授 (10239064) ; 神明 俊輔 広島大学, 病院(医), 助教 (70749936) ; 井上 省吾 広島大学, 病院(医), 講師 (90457177) ; 正路 晃一 独立行政法人国立病院機構東広島医療センター(臨床研究部), 診療部, 泌尿器科医師 (90565805)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 前立腺癌

Outline of Final Research Achievements

Enhanced expression of both FGF19 and FGF21 were detected in biopsy specimens derived from CRPC. The serum FGF19 and FGF21 level were significantly higher than those in cases with HSPC and other urological cancers. Increased level of serum FGF19 was associated with disease progression of CRPC. During these experiments, novel molecular mechanism of drug-resistance through non-coding RNA was elucidated. The data from the present study indicate that serum eFGFs might be a candidate of a novel biomarker of CRPC.

Research Products

• [Journal Article] Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. (2017)
  • Author(s): Sekino Y, Sakamoto N, Goto K, Honma R, Shigematsu Y, Sentani K, Oue N, Teishima J, Matsubara A and Yasui W
  • Journal Title: Oncotarget Volume: 8 Issue: 55 Pages: 94259-94270
  • DOI: 10.18632/oncotarget.21688
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Body mass index as a classifier to predict biochemical recurrence after radical prostatectomy in patients with lower prostate-specific antigen levels. (2017)
  • Author(s): Goto K, Nagamatsu H, Teishima J, Kohada Y, Fujii S, Kurimura Y, Mita K, Shigeta M, Maruyama S, Inoue Y, Nakahara M, Matsubara A.
  • Journal Title: Mol Clin Oncol. Volume: May;6(5) Issue: 5 Pages: 748-752
  • DOI: 10.3892/mco.2017.1223
  • Peer Reviewed
• [Journal Article] The effect of kinetics of C-reactive protein in the prediction of overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor. (2017)
  • Author(s): Teishima J, Kobatake K, Shinmei S, Inoue S, Hayashi T, Ohara S, Mita K, Hasegawa Y, Maruyama S, Kajiwara M, Shigeta M, Mochizuki H, Moriyama H, Fujiwara S, Matsubara A.
  • Journal Title: Urol Oncol. Volume: Nov;35(11) Issue: 11 Pages: 662.e1-662.e7
  • DOI: 10.1016/j.urolonc.2017.07.008
  • Peer Reviewed
• [Journal Article] Combination therapy using molecular-targeted drugs modulates tumor microenvironment and impairs tumor growth in renal cell carcinoma. (2017)
  • Author(s): Kitano H, Kitadai Y, Teishima J, Yuge R, Shinmei S, Goto K, Inoue S, Hayashi T, Sentani K, Yasui W, Matsubara A.
  • Journal Title: Cancer Med Volume: 6 Issue: 10 Pages: 2308-2320
  • DOI: 10.1002/cam4.1124
  • Peer Reviewed / Open Access
• [Journal Article] Impact of neutrophil-to-lymphocyte ratio on effects of targeted therapy for metastatic renal cell carcinoma patients with extrapulmonary metastasis. (2017)
  • Author(s): Teishima J, Ohara S, Sadahide K, Fujii S, Kitano H, Kobatake K, Shinmei S, Hieda K, Inoue S, Hayashi T, Mita K, Matsubara A.
  • Journal Title: Can Urol Assoc J. Volume: May;11(5) Issue: 5 Pages: 207-207
  • DOI: 10.5489/cuaj.4106
  • Peer Reviewed
• [Journal Article] Mechanism of development and progression in prostate cancer: Overview. (2016)
  • Author(s): Teishima J, Matsubara A.
  • Journal Title: Nihon Rinsho. Volume: 74 Pages: 80-86
• [Journal Article] The impact of change in serum C-reactive protein level on the prediction of effects of molecular targeted therapy in patients with metastatic renal cell carcinoma. (2016)
  • Author(s): Teishima J, Kobatake K, Kitano H, Nagamatsu H, Sadahide K, Hieda K, Shinmei S, Shoji K, Inoue S, Hayashi T, Inoue Y, Ohara S, Mita K, Matsubara A.
  • Journal Title: BJU Int. Volume: 117 Issue: 6B
  • DOI: 10.1111/bju.13260
  • Peer Reviewed
• [Journal Article] Prostate cancer and metabolic syndrome (2016)
  • Author(s): Nagamatsu H, Teishima J, Inoue S, Hayashi T, Matsubara A.
  • Journal Title: Nihon Rinsho Volume: 74 (1) Pages: 149-54
  • NAID: 40020694027
• [Journal Article] FGF19 promotes progression of prostate cancer. (2015)
  • Author(s): Nagamatsu H, Teishima J, Goto K, Shikuma H, Kitano H, Shoji K, Inoue S, Matsubara A.
  • Journal Title: The Prostate Volume: Apr 8 Issue: 10 Pages: 1092-101
  • DOI: 10.1002/pros.22994
  • Peer Reviewed / Open Access
• [Journal Article] Pin1 Inhibitor Juglone Exerts Anti-Oncogenic Effects on LNCaP and DU145 Cells despite the Patterns of Gene Regulation by Pin1 Differing between These Cell Lines. (2015)
  • Author(s): Kanaoka R, Kushiyama A, Seno Y, Nakatsu Y, Matsunaga Y, Fukushima T, Tsuchiya Y, Sakoda H, Fujishiro M, Yamamotoya T, Kamata H, Matsubara A, Asano T.
  • Journal Title: PLoS One. Volume: 10 (6) Issue: 6 Pages: e0127467-e0127467
  • DOI: 10.1371/journal.pone.0127467
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer. (2018)
  • Author(s): Sekino Y., Sakamoto N., Goto K., Honma R., Shigematsu Y., Sentani K., Oue N., Teishima J., Yasui W., Matsubara A.
  • Organizer: 33rd Annual EAU Congress
  • Int'l Joint Research
• [Presentation] The impact of endocrine fibroblast growth factor subfamily as serum biomarkers in castration-resistant prostate cancer (2017)
  • Author(s): Jun Teishima, Yuka Yamaguchi, Hirotaka Nagamatsu, Shinsuke Fujii, Naoya Yabumoto, Keisuke Goto, Shunsuke Shinmei, Shogo Inoue, Tetsutaro Hayashi, Akio Matsubara
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] The impact of kinetics of biomarkers on the prediction of overall survival in patients with metastatic renal cell carcinoma treated with a tyrosine kinase inhibitor. (2017)
  • Author(s): Jun Teishima, Shinya Ohara, Kousuke Sadahide, Shinsuke Fujii, Hiroyuki Kitano, Shunsuke Shinmei, Keisuke Hieda, Shogo Inoue, Tetsutaro Hayashi, Koji Mita, Akio Matsubara.
  • Organizer: AUA 2017 Annual Meeting
  • Int'l Joint Research
• [Presentation] 転移性腎細胞癌に対するcytoreductive nephrectomy前後のCRP変動の意義. (2017)
  • Author(s): 亭島淳、大原慎也、神明俊輔、井上省吾、林哲太郎、望月英樹、三田耕司、松原昭郎.
  • Organizer: 第3回日本泌尿器腫瘍学会
• [Presentation] 去勢抵抗性前立腺癌患者における治療前NSE値およびpro-GRP値の意義. (2017)
  • Author(s): 福岡憲一郎、栗村嘉昌、上野剛志、稗田景介、神明俊輔、井上省吾、林哲太郎、亭島淳、松原昭郎.
  • Organizer: 第3回日本泌尿器腫瘍学会
• [Presentation] The impact regerarating islet-derived related protein 4 as candidate of a novel biomarker in castration-resistant prostate cancer. (2016)
  • Author(s): Jun Teishima, Shisuke Fujii, Nagamatsu Hirotaka, Ryoken Yamanaka, Kohei Kobatake, Hiroyuki Kitano, Keisuke Goto, Shunsuke Shimei, Tetsutaro Hayashi, Norihide Oue, Wataru Yasui, Akio Matsubara.
  • Organizer: The 33th japan-Korea Urological Congress
  • Place of Presentation: Aomori
  • Year and Date: 2016-10-08
  • Int'l Joint Research
• [Presentation] Regenerating islet-derived related protein 4 as a candidate of a novel biomarker in castration-resistant prostate cancer patients. (2016)
  • Author(s): J.Teishima, H. Nagamatsu, K.Shoji, R.Yamanaka, K.Kobatake, H.Kitano, K.Goto, T.Hayashi, N.Oue, W.Yasui, A.Matsubara.
  • Organizer: AUA2016
  • Place of Presentation: San Diego(米国)
  • Year and Date: 2016-05-09
  • Int'l Joint Research
• [Presentation] Regenerating islet-derived related protein 4 as candidate of a novel biomarker in castration-resistant prostate cancer patients. (2016)
  • Author(s): Jun Teishima, Hirotaka Nagamatsu, Koichi Shoji, Ryoken Yamanaka, Tatsuya Hirano, Kohei Kobatake, Hiroyuki Kitano, Keisuke Goto, Tetsutaro Hayashi, Norihide Oue, Wataru Yasui, Akio Matsubara
  • Organizer: 31th EAU Congress
  • Place of Presentation: Germany,Munch(Internationales Congress Center Munchen)
  • Year and Date: 2016-03-11
  • Int'l Joint Research
• [Presentation] 去勢抵抗性前立腺癌におけるReg IV の役割. (2015)
  • Author(s): 亭島 淳、永松 弘孝、正路 晃一、山中 亮憲、平野 達也、小畠 浩平、北野 弘之、後藤 景介、林 哲太郎、大上 直秀、安井 弥、松原 昭郎.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08