Basic research to realize personalized medicine based on pharmacogenomics and drug discovery in benign prostatic hyperplasia

• Project/Area Number: 26462448
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Fukushima Medical University
• Principal Investigator: Kojima Yoshiyuki 福島県立医科大学, 医学部, 教授 (60305539)
• Co-Investigator(Kenkyū-buntansha): 柳田 知彦 福島県立医科大学, 医学部, 講師 (20363765) ; 櫛田 信博 福島県立医科大学, 医学部, 講師 (30381396) ; 羽賀 宣博 福島県立医科大学, 医学部, 助教 (50586617) ; 相川 健 福島県立医科大学, 医学部, 准教授 (80295419) ; 石橋 啓 福島県立医科大学, 医学部, 准教授 (90347211)
• Research Collaborator: KATAOKA Masao 福島県立医科大学, 医学部 泌尿器科学講座, 学内講師 (90554204) ; OGAWA Soichiro 福島県立医科大学, 医学部 泌尿器科学講座, 学内講師 (50554200) ; AKAIHATA Hidenori 福島県立医科大学, 医学部 泌尿器科学講座, 助教 (70644178) ; SATO Yuichi 福島県立医科大学, 医学部 泌尿器科学講座, 助手 (00706848) ; YABE Michihiro 福島県立医科大学, 医学部 泌尿器科学講座, 博士研究員 (30745782) ; HATA Junya 福島県立医科大学, 医学部 泌尿器科学講座, 助教 (00769606)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 前立腺肥大症 / 細胞増殖 / 一塩基遺伝子多型 / オーダーメード医療 / ゲノム薬理学 / 筋線維芽細胞 / サイトカイン / 増殖因子 / 網羅的遺伝子解析 / 繊維芽細胞 / TGF-β / IGFBP3 / 創薬 / モデル動物 / ケモカイン

Outline of Final Research Achievements

Recently, a rat model of BPH produced by implanting fetal urogenital sinus (UGS) into adult rat ventral prostate was developed. Using this model, we found that genes associated with growth factors, cytokines and chemokines were up-regulated in the BPH specimens compared with those in normal prostate, suggesting that their multiple families act through paracrine signaling to stimulate prostate proliferation. In addition, we found that myofibroblasts differntiation played a significant role in prostate growth in BPH.
Genome-wide association studies can link multiple SNPs to drug response. More limited genetic variant studies have been performed within alpha1-AR subtypes SNPs within a biologic pathway implicated in BPH could improve predictive ability. We have found 9 potential candidate SNPs associated with the efficacy of alpha1-AR antagonists, although further study will be needed.

Research Products

• [Journal Article] Molecular classification of benign prostatic hyperplasia: A gene expression profiling study in a rat model. (2016)
  • Author(s): Hata Junya, Satoh Yuichi, Akaihata Hidenori, Hiraki Hiroyuki, Ogawa Soichiro, Haga Nobuhiro, Ishibashi Kei, Aikawa Ken, Kojima Yoshiyuki.
  • Journal Title: International Journal of Urology. Volume: 23. 7. Issue: 7 Pages: 599-612
  • DOI: 10.1111/iju.13106
• [Journal Article] Elucidation of the pattern of the onset of male lower urinary tract symptoms using cluster analysis:Efficacy of tamsulosin in each symptom group. (2015)
  • Author(s): Aikawa K, Kataoka M, Ogawa S, Akaihata H, Sato Y, Yabe M, Hata J, Koguchi T, Kojima Y, Shiragasawa C, Kobayashi T, Yamaguchi O.
  • Journal Title: Urology Volume: 86 Pages: 849-853
  • Peer Reviewed / Open Access
• [Journal Article] Pelvic arterial occlusive disease affects the Rho-A/Rho-kinase pathway in bladder smooth muscle. (2015)
  • Author(s): Akaihata H, Nomiya M, Hata J, Yabe M, Takahashi N, Haga N, Kushida N, Ishibashi K, Aikawa K, Yamaguchi O, Kojima Y.
  • Journal Title: The Journal of Urology Volume: 194 Issue: 2 Pages: 706-713
  • DOI: 10.1016/j.juro.2014.09.102
  • Peer Reviewed / Open Access
• [Presentation] 前立腺筋線維芽細胞の経時的変化からみた前立腺肥大症発症のメカニズムの解明. (2016)
  • Author(s): 秦淳也, 松岡香菜子, 胡口智之, 佐藤雄一, 赤井畑秀則, 小川総一郎, 片岡政雄, 羽賀宣博, 櫛田信博, 栁田知彦, 石橋啓, 相川健, 小島祥敬.
  • Organizer: 第23回日本排尿機能学会
  • Place of Presentation: 東京
• [Presentation] 前立腺肥大症学-ゲノム薬理学と前立腺細胞増殖機構の解明に向けた基礎的研究- (2016)
  • Author(s): 小島祥敬
  • Organizer: 第26回高知泌尿器科セミナー
  • Place of Presentation: 高知
• [Presentation] 前立腺疾患と下部尿路機能-疾患制御とQOL- (2016)
  • Author(s): 小島祥敬
  • Organizer: 第159回広島地方会学術集会
  • Place of Presentation: 広島
• [Presentation] 前立腺肥大症に対する薬物治療におけるトランスレーショナルリサーチ (2016)
  • Author(s): 小島祥敬
  • Organizer: 第11回鹿児島泌尿器科セミナー
  • Place of Presentation: 鹿児島
• [Presentation] 男性下部尿路症状に対する治療戦略 (2016)
  • Author(s): 小島祥敬
  • Organizer: 第203回宮崎県泌尿器科医会
  • Place of Presentation: 宮崎
• [Presentation] Translational pharmacology in benign prostatic hyperplasia/lower urinary tract symptoms (2014)
  • Author(s): Yoshiyuki Kojima
  • Organizer: 16th Annual Congress of Urology
  • Place of Presentation: Kish Island
  • Year and Date: 2014-12-05
  • Invited
• [Presentation] 前立腺肥大症モデルラットを用いた遺伝子ネットワーク解析ー前立腺肥大症特異発現遺伝子の同定と発症機序解明及び治療開発への展開 (2014)
  • Author(s): 秦淳也、矢部通弘、佐藤雄一、赤井畑秀則、小川総一郎、片岡政雄、熊谷伸、熊谷研、羽賀宣博、櫛田信博、栁田知彦、石橋啓、相川健、小島祥敬
  • Organizer: 第21回日本排尿機能学会
  • Place of Presentation: 岡山
  • Year and Date: 2014-09-17 – 2014-09-20
• [Presentation] Future prospects for personalized medicine in the treatment of BPH (2014)
  • Author(s): Yoshiyuki Kojima
  • Organizer: American Urological Association annual meeting 2014
  • Place of Presentation: Orland, USA
  • Year and Date: 2014-05-18
  • Invited