Establishment of human benign prostatic hyperplasia model in super-SCID mice and its pathological analysis

• Project/Area Number: 26670196
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: NOMURA Taisei 独立行政法人医薬基盤研究所, 難病・疾患資源研究部, プロジェクトリーダー (90089871)
• Co-Investigator(Kenkyū-buntansha): RYO Haruko 独立行政法人医薬基盤研究所, 難病・疾患資源研究部, サブプロジェクトリーダー (90301267) ; ADACHI Shigeki 独立行政法人医薬基盤研究所, 難病・疾患資源研究部, 特任研究員 (60379261)
• Research Collaborator: NONOMURA Norio
• Project Period (FY): 2014-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: ヒト前立腺肥大症 / ヒト疾患移植モデル / Super-SCIDマウス / 病態解析 / PSA / 機能測定 / ヒト前立腺肥大症PDX / 抑制効果

Outline of Final Research Achievements

Benign prostatic hyperplasia (BPH) is a very common disease over the age of 50. Since there is no suitable human model for BPH, however, we aimed to establish human model, using our super-SCID mouse system which can maintain human organs/tissues for long period. In this model, morphology and function of original BPH examined by H&E staining and immuno-histochemical staining (p63, CK8, AR, PSA, etc.) were well maintained in the biopsy tissues taken at 2, 6 and 12 month after BPH transplantation. In the mouse serum, furthermore, we can measure human PSA secreted from the xenograft by our micro-detection system.
To evaluate this human BPH model, Dutasteride was given to SCID mouse with BPH xenograft. It suppressed BPH volume and cell proliferation (Ki 63), and enhanced apoptosis (TUNEL).　Thus, our new human BPH-PDX model in Super-SCID mice is very useful and valuable for medical research and drug development.

Research Products

• [Journal Article] Histological Evaluation of Human Benign Prostatic Hyperplasia Treated by Dutasteride: A Study by Xenograft Model with Improved Severe Combined Immunodeficient (Super-SCID) Mice. (2015)
  • Author(s): Akira Tsujimura, Shinichiro Fukuhara, Tetsuji Soda, Kentaro Takezawa, Hiroshi Kiuchi, Tetsuya Takao, Yasushi Miyagawa, Norio Nonomura, Shigeki Adachi, Yoriko Tokita, Taisei Nomura.
  • Journal Title: Urology Volume: 85 Issue: 1 Pages: 274.e1-274.e8
  • DOI: 10.1016/j.urology.2014.09.024
  • Peer Reviewed
• [Journal Article] Absence of lactobacilli containing glycolipids with the α-galactose epitope and the enhanced fucosylation of a receptor glycolipid GA1 in the digestive tracts of immune-deficient scid mice. (2015)
  • Author(s): Iwamori M, Tanaka K, Adachi S, Aoki D, Nomura T.
  • Journal Title: J Biochem Volume: pii Issue: 1 Pages: 73-82
  • DOI: 10.1093/jb/mvv021
  • Peer Reviewed
• [Journal Article] ヒトがん組織等移植SCIDマウスを用いた重粒子線治療の有効性・安全性の研究 (2015)
  • Author(s): 野村大成、足立成基、梁 治子、坂巻 靖、鳥 正幸、吉留克英、野々村祝夫、古澤佳也、鵜澤玲子
  • Journal Title: 平成26年度放射線医学総合研究所 重粒子線がん治療装置等共同利用研究報告書 Volume: 26 Pages: 56-58
• [Journal Article] Altered Actions of Memantine and NMDA-Induced Currents in a New Grid2-Deleted Mouse Line. (2014)
  • Author(s): Ayako Kumagai, Akira Fujita, Tomoki Yokoyama, Yuki Nonobe, Yasuhiro Hasaba, Tsutomu Sasaki, Yumi Itoh, Minako Koura, Osamu Suzuki, Shigeki Adachi, Haruko Ryo, Arihiro Kohara, Lokesh P. Tripathi, Masato Sanosaka, Toshiki Fukushima, Taisei Nomura, Hiroshi Takemori, et al.
  • Journal Title: Genes Volume: 5 Issue: 4 Pages: 1095-1114
  • DOI: 10.3390/genes5041095
  • Peer Reviewed / Open Access
• [Journal Article] p53-Dependent suppression of genome instability in germ cells. (2014)
  • Author(s): Otozai S, Ishikawa-Fujiwara T, Oda S, Kamei Y, Ryo H, Sato A, Nomura T, Mitani H, Tsujimura T, Inohara H, Todo T.
  • Journal Title: Mutat Res, Volume: 760 Pages: 24-32
  • DOI: 10.1016/j.mrfmmm.2013.12.004
  • Peer Reviewed
• [Presentation] Establishment of Prostate Cancer and Benign Prostatic Hyperplasia PDX (Patient-Derived Xenograft) in Super-SCID Mice (2015)
  • Author(s): Ｔａｉｓｅｉ Nomura
  • Organizer: International Conference on Prostate Cancer
  • Place of Presentation: Hyatt Regency, Orlando, Florida, USA
  • Year and Date: 2015-06-22 – 2015-06-24
  • Invited
• [Presentation] Transgenerational Health Effects of Radiation in Mice and Humans. (2014)
  • Author(s): Nomura, T.
  • Organizer: XIII Annual Congress "New Technologies in Pediatria and Children's Surgery" Symposium on "Mechanism of Radiation-induced Health State in the Next Generations after radiation exposure"
  • Place of Presentation: Hotel "Cosmos", Moscow, Russia
  • Year and Date: 2014-10-21 – 2014-10-23
  • Invited
• [Presentation] Suppression of Mouse and Human Cancer by AHCC. (2014)
  • Author(s): Taisei Nomura, Shigeki Adachi, Haruko Ryo, Eiko Hatanaka, Momoyo Kaji, Koujun Yasuda
  • Organizer: 22nd ICNIM 2014
  • Place of Presentation: Hotel Royton Sapporo, Sapporo
  • Year and Date: 2014-07-27 – 2014-07-28
  • Invited
• [Presentation] 乳酸菌の腸内共生と免疫の役割 (2014)
  • Author(s): 岩森正男、足立成基、野村大成、田中京子、青木大輔
  • Organizer: 第56回日本脂質生化学会「ライフサイエンスにおける脂質生化学研究」
  • Place of Presentation: 近畿大学東大阪キャンパス、東大阪市
  • Year and Date: 2014-06-06 – 2014-06-07