The impact of steroid receptors in chemohormone resistant prostate cancer

• Project/Area Number: 16K10992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Akita University
• Principal Investigator: Narita Shintaro 秋田大学, 医学部附属病院, 准教授 (40396552)
• Co-Investigator(Kenkyū-buntansha): 井上 高光 秋田大学, 医学系研究科, 准教授 (60375243) ; 黄 明国 秋田大学, 医学系研究科, 助教 (60448503)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 前立腺癌 / ステロイド受容体 / 生化学的再発 / 化学療法 / アンドロゲン受容体 / プロゲステロン受容体 / Hippo経路 / 抗癌剤耐性 / ステロイドホルモン受容体

Outline of Final Research Achievements

We assessed the impact of tissue biomarkers in patient with prostate cancer who underwent surgery after different neoadjuvant setting using tissue microarray analyses. We found that a high nuclear androgen receptor and a high nuclear YAP1 in residual cancer cells had a poor biochemical recurrence-free survival. Furthermore, The nuclear YAP1 expression was markedly higher in docetaxel resistant prostate cancer cells than that in parental cells.

Academic Significance and Societal Importance of the Research Achievements

これまで報告されているアンドロゲン受容体発現と前立腺癌化学内分泌療法抵抗性の関係のみならず、近年腫瘍の治療抵抗性やステロイド受容体との関連が示唆されるHippo経路の中心的転写因子の発現が前立腺癌化学内分泌療法抵抗性に関連する可能性を見出した。本分子は術前化学内分泌療法後前立腺全摘を行った症例の組織バイオマーカーとなる可能性のみならず化学内分泌療法抵抗性機序解明の足がかりや新規治療の標的となる可能性がある。

Research Products

• [Journal Article] Radical Prostatectomy With and Without Neoadjuvant Chemohormonal Pretreatment for High-Risk Localized Prostate Cancer: A Comparative Propensity Score Matched Analysis (2019)
  • Author(s): Narita Shintaro、Nara Taketoshi、Kanda Sohei、Numakura Kazuyuki、Saito Mitsuru、Inoue Takamitsu、Satoh Shigeru、Nanjo Hiroshi、Tsuchiya Norihiko、Mitsuzuka Koji、Koie Takuya、Kawamura Sadafumi、Ohyama Chikara、Tochigi Tatsuo、Arai Yoichi、Habuchi Tomonori
  • Journal Title: Clinical Genitourinary Cancer Volume: 17 Issue: 1 Pages: e113-e122
  • DOI: 10.1016/j.clgc.2018.09.019
  • Peer Reviewed
• [Journal Article] Impact of early changes in serum biomarkers following androgen deprivation therapy on clinical outcomes in metastatic hormone-sensitive prostate cancer (2018)
  • Author(s): Sato Hiromi、Narita Shintaro、Tsuchiya Norihiko、Koizumi Atsushi、Nara Taketoshi、Kanda Sohei、Numakura Kazuyuki、Tsuruta Hiroshi、Maeno Atsushi、Saito Mitsuru、Inoue Takamitsu、Satoh Shigeru、Nomura Kyoko、Habuchi Tomonori
  • Journal Title: BMC Urology Volume: 18 Issue: 1 Pages: 32-32
  • DOI: 10.1186/s12894-018-0353-4
  • Peer Reviewed / Open Access
• [Journal Article] Incidence and location of positive surgical margin among open, laparoscopic and robot-assisted radical prostatectomy in prostate cancer patients: a single institutional analysis (2018)
  • Author(s): Koizumi A, Narita S, Nara T, Takayama K, Kanda S, Numakura K, Tsuruta H, Maeno A, Huang M, Saito M, Inoue T, Tsuchiya N, Satoh S, Nanjo H, Habuchi T.
  • Journal Title: Jpn J Clin Oncol. Volume: 48 Issue: 8 Pages: 765-770
  • DOI: 10.1093/jjco/hyy092
  • Peer Reviewed
• [Journal Article] The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the "obesity paradox". (2017)
  • Author(s): Ito R, Narita S, Huang M, Nara T, Numakura K, Takayama K, Tsuruta H, Maeno A, Saito M, Inoue T, Tsuchiya N, Satoh S, Habuchi T
  • Journal Title: PLoS One Volume: 12 Issue: 2 Pages: e0171615-e0171615
  • DOI: 10.1371/journal.pone.0171615
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Host-related Risk Factors for Adherent Perinephric Fat in Healthy Individuals Undergoing Laparoscopic Living-donor Nephrectomy. (2017)
  • Author(s): Narita, S., Kumazawa, T., Tsuchiya, N., Mingguo, H., Saito, M., Inoue, T., Tsuruta, H.,Numakura, K., Maeno, A., Nanjo, H., Satoh, S., Habuchi, T.
  • Journal Title: Surg Laparosc Endosc Percutan Tech. Volume: 27 Issue: 4 Pages: e69-e73
  • DOI: 10.1097/sle.0000000000000433
  • Peer Reviewed
• [Journal Article] Altered miRNA expression in high-fat diet-induced prostate cancer progression. (2016)
  • Author(s): Nara T, Narita S, Mingguo H, Yoshioka T, Koizumi A, Numakura K, Tsuruta H, Maeno A, Saito M, Inoue T, Tsuchiya N, Satoh S, Habuchi T
  • Journal Title: Carcinogenesis Volume: 37 Pages: 1129-1137
  • DOI: 10.1093/carcin/bgw108
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Neoadjuvant chemohormonal therapy followed by radical prostatectomy in patients with high-risk prostate cancer. (2018)
  • Author(s): Narita. S., Tochigi. T., Ohyama. C., Arai. Y.,Habuchi. T.
  • Organizer: 2018 East Asia Urologic Oncology Group Symposium, April, Seoul, Korea
  • Int'l Joint Research
• [Presentation] The expression profile of phosphatidylinositol phosphates in pre-clinical and clinical prostate cancer. (2018)
  • Author(s): Narita,S., Koizumi. A., Nakanishi. H., Takehiko. Sasaki., Habuchi, T.
  • Organizer: Urological Research Society Annual Meeting 2018, Oct, Seoul
  • Int'l Joint Research
• [Presentation] Tissue biomarkers in patients with high-risk prostate cancer treated with neoadjuvant chemohormonal therapy. (2018)
  • Author(s): Narita. S., Nara. T., Chiba. S., Kanda. S., Numakura. K., Saito. M., Inoue. T., Huang. M., Nanjo. H., Habuchi. T.
  • Organizer: 第77回日本癌学会総会, 9月, 大阪
• [Presentation] Pure host-related risk factors for adherent perinephric fat in healthy individuals during laparoscopic renal surgery (2017)
  • Author(s): Narita, S., Nara, T., Takayama, K., Numakura, K., Tsuruta, H., Maeno, A., Saito, M., Inoue, T., Satoh, S., Habuchi, T.
  • Organizer: The 112th Annual Meeting of the American Urological Association, May, Boston, USA.
  • Int'l Joint Research
• [Presentation] Impact of Hippo pathway protein expression in residual cancer after neoadjuvant chemohormonal therapy with docetaxel for high-risk localized prostate cancer. (2017)
  • Author(s): Narita, S., Nara, T., Huang, M., Numakura, K., Tsuruta, H., Maeno, A., Saito, M., Inoue, T., Satoh, S., Habuchi, T.
  • Organizer: The 112th Annual Meeting of the American Urological Association, May, Boston, USA.
  • Int'l Joint Research
• [Presentation] MiR-130a modulates high-fat diet-induced prostate cancer progression through the activation of MET. (2017)
  • Author(s): Narita,S., Nara, T., Habuchi, T.
  • Organizer: Urological Research Society Annual Meeting 2017, Oct, Quebec
  • Int'l Joint Research
• [Presentation] ハイリスク前立腺癌に対する術前化学内分泌療法併用前立腺全摘の治療成績と組織バイオマーカーの探索 (2017)
  • Author(s): 成田伸太郎, 奈良健平、高山孝一朗、黄明国、鶴田大、沼倉一幸、前野淳、齋藤満、井上高光、南條博、羽渕友則.
  • Organizer: 第105回日本泌尿器科学会総会
• [Presentation] ロボット支援腹腔鏡下前立腺全摘除術における断端陽性の検討～多施設共同後ろ向き試験の成績から. (2017)
  • Author(s): 成田伸太郎、大久保、三塚浩二、古家琢也、荒井陽一、大山力、羽渕友則.
  • Organizer: 第30回日本内視鏡外科学会総会
• [Presentation] ハイリスク前立腺癌に対する術前化学内分泌療法併用前立腺全摘の治療成績～手術単独療法とのpropensity score-matched analysis. (2017)
  • Author(s): 成田伸太郎, 奈良健平, 神田壮平, 鶴田大, 沼倉一幸, 齋藤満, 井上高光, 羽渕友則, 三塚浩二, 古家琢也, 川村貞文, 栃木達夫, 大山力, 荒井陽一.
  • Organizer: 第55会日本癌治療学会学術総会
• [Presentation] Expression of steroid hormone receptors in residual cancer and stromal cells after neoadjuvant chemohormonal therapy with docetaxal for high-risk localized prostate cancer. (2016)
  • Author(s): Narita, S., Nara, T., Huang, M., Numakura, K., Tsuruta, H., Maeno, A., Saito,M., Inoue, T., Tsuchiya, N., Nanjo, H., Satoh,S., Habuchi, T.
  • Organizer: The 111th annual meeting of the American Urological Association
  • Place of Presentation: San diego
  • Year and Date: 2016-05-08
  • Int'l Joint Research
• [Presentation] 進行前立腺癌患者に生活で気をつけることがありますかと聞かれたら, フロンティアシンポジウム「進行前立腺癌のunmet needsに答える」 (2016)
  • Author(s): 成田伸太郎
  • Organizer: 第104回日本泌尿器科学会総会
  • Place of Presentation: Munich
  • Year and Date: 2016-04-25
• [Book] Hormone therapy and castration resistance of prostate cancer (2018)
  • Author(s): Narita, S, Habuchi, T.
  • Total Pages: 12
  • Publisher: Springer
• [Book] 月刊腎臓内科・泌尿器科 (2017)
  • Author(s): 成田伸太郎, 井上高光, 羽渕友則.
  • Total Pages: 7
  • Publisher: 科学評論社
• [Book] ハイリスク限局性前立腺癌に対する治療戦略 (2016)
  • Author(s): 成田伸太郎, 井上高光, 羽渕友則.
  • Total Pages: 8
  • Publisher: 日本臨床社
• [Remarks] 秋田大学大学院医学系研究科腎泌尿器科学講座
  • URL: http://www.med.akita-u.ac.jp/~hinyoki/