Elucidation of characteristic alterations of spermatogonial stem cells in testicular cancer and application to genome-based drug discovery using novel cell line

• Project/Area Number: 26462421
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: MIZUNO Kentaro 名古屋市立大学, 大学院医学研究科, 講師 (70448710)
• Co-Investigator(Kenkyū-buntansha): 神沢 英幸 名古屋市立大学, 大学院医学研究科, 研究員 (00551277) ; 西尾 英紀 名古屋市立大学, 大学院医学研究科, 助教 (10621063) ; 郡 健二郎 名古屋市立大学, その他部局等, 学長 (30122047) ; 林 祐太郎 名古屋市立大学, 大学院医学研究科, 准教授 (40238134) ; 黒川 覚史 名古屋市立大学, 大学院医学研究科, 研究員 (50468253)
• 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 精子幹細胞 / 精巣がん / 細胞分化

Outline of Final Research Achievements

Spermatogonial stem cells (SSCs), which is the stem cells of testicular tissue, undergo self-renewal with preserving pluripotency and act as the source of spermatozoa after puberty throughout life. Recently, it is suggested that phenotypic alteration of SSCs is involved in the onset of testicular cancer. We investigated the phenotypic alteration of SSCs using animal model of cryptorchidism, which is one of the etiology of testicular cancer. Subsequently, we elucidated that the expressions of histone modifying enzyme Kdm5a and microRNA miR-135a were significantly changed in the cryptorchid testes, via androgen action.

Research Products

• [Journal Article] Robot assisted laparoscopic pyeloplasty for ureteropelvic junction obstruction: Comparison between pediatric and adult patient - Japanese series. (2016)
  • Author(s): Mizuno K, Kojima Y, Kurokawa S, Kamisawa H, Nishio H, Moritoki Y, Nakane A, Maruyama T, Okada A, Kawai N, Tozawa K, Kohri K, Yasui T, Hayashi Y.
  • Journal Title: Journal of Robotic Surgery Volume: 印刷中 Issue: 2 Pages: 151-157
  • DOI: 10.1007/s11701-016-0633-5
  • Peer Reviewed
• [Journal Article] Treatment strategy for pediatric paratesticular rhabdomyosarcoma based on chimeric gene assessment. (2016)
  • Author(s): Unno R, Mizuno K, Ito Y, Etani T, Okada A, Kawai N, Yasui T, Saitoh S, Hayashi Y.
  • Journal Title: Urology Volume: 95 Pages: 187-189
  • DOI: 10.1016/j.urology.2016.03.024
  • Peer Reviewed
• [Journal Article] Hemiscrotal agenesis: Pathogenesis and management strategies. (2015)
  • Author(s): Nishio Hidenori, Mizuno Kentaro, Moritoki Yoshinobu, Kamisawa Hideyuki, Naiki Taku, Kurokawa Satoshi, Nakane Akihiro, Okada Atsushi, Yasui Takahiro, Hayashi Yutaro
  • Journal Title: International Journal of Urology Volume: 69(10) Issue: 6 Pages: 824-831
  • DOI: 10.1111/iju.13079
  • Peer Reviewed
• [Journal Article] Clear cell sarcoma of the kidney distinguished from synovial sarcoma of the kidney by genetic analysis (2015)
  • Author(s): Hirose M, Mizuno K, Kamisawa H, Nishio H, Moritoki Y, Kohri K, Hayashi Y.
  • Journal Title: BMC Research Notes Volume: 8 Issue: 1 Pages: 129-133
  • DOI: 10.1186/s13104-015-1100-5
  • Peer Reviewed / Open Access
• [Journal Article] Novel splice site mutation in MAMLD1 in a patient with hypospadias. (2015)
  • Author(s): 10.1038/ejhg.2015.13
  • Journal Title: Sex Dev Volume: 3 Issue: 3 Pages: 1-1
  • DOI: 10.1159/000380842
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Truncating mutation in NFIA causes brain malformation and urinary tract defects (2015)
  • Author(s): Negishi Y, Miya F, Hattori A, Mizuno K, Hori I, Ando N, Okamoto N, Kato M, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K. Saitoh S.
  • Journal Title: Human Genome Variation Volume: 2 Pages: 15007-15010
  • Peer Reviewed / Open Access
• [Journal Article] Proinflammatory and Metabolic Changes Facilitate Renal Crystal Deposition in an Obese Mouse Model of Metabolic Syndrome. (2015)
  • Author(s): Taguchi K, Okada A, Hamamoto S, Iwatsuki S, Naiki T, Ando R, Mizuno K, Tozawa K, Kohri K, Yasui T.
  • Journal Title: J Urol. Volume: 194 Issue: 6 Pages: 1787-96
  • DOI: 10.1016/j.juro.2015.07.083
  • Peer Reviewed / Open Access
• [Journal Article] First case report of staghorn calculi successfully removed by mini-endoscopic combined intrarenal surgery in a 2-year-old boy. (2015)
  • Author(s): Taguchi Kazumi, Hamamoto Shuzo, Okada Atsushi, Mizuno Kentaro, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro, Yasui Takahiro
  • Journal Title: International Journal of Urology Volume: 22 Issue: 10 Pages: 978-80
  • DOI: 10.1111/iju.12860
  • Peer Reviewed
• [Journal Article] Elucidation of distinctive genomic DNA structures in patients with 46, XX testicular disorders of sex development using genome-wide analyses (2014)
  • Author(s): Mizuno K, Kojima Y, Kamisawa H, Moritoki Y, Nishio H, Nakane A, Kurokawa S, Kohri K, Hayashi Y
  • Journal Title: J Urol Volume: (in press) Issue: 2 Pages: 1-7
  • DOI: 10.1016/j.juro.2014.02.044
  • Peer Reviewed / Open Access
• [Journal Article] Distinctive changes in histone H3K4 modification mediated via Kdm5a expression in spermatogonial stem cells of cryptorchid testes (2014)
  • Author(s): Nishio H, Hayashi Y, Moritoki Y, Kamisawa H, Mizuno K, Kojima Y, Kohri K
  • Journal Title: J Urol Volume: 191 Issue: 5S Pages: 1564-72
  • DOI: 10.1016/j.juro.2013.10.071
  • Peer Reviewed
• [Journal Article] Expression profiling of microRNAs in cryptorchid testes : miR-135a contributes to the maintenance of spermatogonial stem cells by regulating FoxO1 (2014)
  • Author(s): Moritoki Y, Hayashi Y, Mizuno K, Kamisawa H, Nishio H, Kurokawa S, Ugawa S, Kojima Y, Kohri K
  • Journal Title: J Urol Volume: 191 Issue: 4 Pages: 1174-80
  • DOI: 10.1016/j.juro.2013.10.137
  • Peer Reviewed / Open Access
• [Presentation] パネルディスカッション 小児腹腔内精巣－どう扱うか？ 「腹腔鏡下精巣固定術 ～精巣血管の温存をめざして～」 (2016)
  • Author(s): 水野健太郎、西尾英紀、守時良演、加藤大貴、林祐太郎、安井孝周
  • Organizer: 第30回日本泌尿器内視鏡学会総会
  • Place of Presentation: イベントラボ・グランフロント大阪（大阪府大阪市）
  • Year and Date: 2016-11-17
• [Presentation] 精子幹細胞の分化過程におけるアンドロゲンの関与～初代培養系を用いた精子形成細胞マーカーの発現解析～ (2016)
  • Author(s): 水野健太郎、守時良演、加藤大貴、林祐太郎、安井孝周
  • Organizer: 第25回日本小児泌尿器科学会総会
  • Place of Presentation: ホテルグランヴィア京都（京都府京都市）
  • Year and Date: 2016-06-28
• [Presentation] Involvement of BMP-SMAD signaling pathway in the etiology of congenital anomalies of kidney and urinary tract accompanied by cryptorchidism using whole exsome sequencing. (2016)
  • Author(s): Mizuno K, Hayashi Y, Kamisawa H, Moritoki Y, Nishio H, Kurokawa S, Nakane A, Maruyama T, Yasui T.
  • Organizer: Society for Pediatric Urology’s 64st Annual Meeting
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2016-05-06
  • Int'l Joint Research
• [Presentation] Elucidation of regulatory mechanisms during differentiation of spermatogonial stem cell via androgen action (2015)
  • Author(s): Mizuno K, Hayashi Y, Kamisawa H, Moritoki Y, Nishio H, Kurokawa S, Nakane A, Maruyama T, Yasui T
  • Organizer: 26th European Society of Pediatric Urology Congress
  • Place of Presentation: プラハ市、チェコ共和国
  • Year and Date: 2015-10-14
  • Int'l Joint Research
• [Presentation] Feasibility of laparoscopic orchiopexy for intracanalicular testes in comparative study of surgical outcome with open transinguinal orchiopexy (2015)
  • Author(s): Mizuno K, Hayashi Y, Kamisawa H, Moritoki Y, Nishio H, Kurokawa S, Nakane A, Maruyama T, Yasui T
  • Organizer: 26th European Society of Pediatric Urology Congress
  • Place of Presentation: プラハ市、チェコ共和国
  • Year and Date: 2015-10-14
  • Int'l Joint Research
• [Presentation] 停留精巣を合併したCAKUT症例における遺伝子多型の全エクソーム解析 (2015)
  • Author(s): 水野健太郎、守時良演、林祐太郎、安井孝周
  • Organizer: 第24回 日本小児泌尿器科学会総会
  • Place of Presentation: 御茶ノ水ソラシティカンファレンスセンター(東京都千代田区)
  • Year and Date: 2015-07-01
• [Presentation] シンポジウム2「小児泌尿器科学における基礎研究の意義と面白さ」 (2015)
  • Author(s): 水野健太郎
  • Organizer: 第24回 日本小児泌尿器科学会総会
  • Place of Presentation: 御茶ノ水ソラシティカンファレンスセンター(東京都千代田区)
  • Year and Date: 2015-07-01
• [Presentation] 全エクソーム解析を用いた先天性腎尿路奇形症候群における遺伝子多型の網羅的検索 (2015)
  • Author(s): 水野健太郎、西尾英紀、守時良演、岩月正一郎、神沢英幸、黒川覚史、中根明宏、丸山哲史、梅本幸裕、佐々木昌一、林祐太郎
  • Organizer: 第 103回 日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂、ANAクラウンプラザホテル他(金沢市)
  • Year and Date: 2015-04-18
• [Presentation] 精子幹細胞の分化過程におけるアンドロゲン作用機序の解明 (2014)
  • Author(s): 水野健太郎、神沢英幸、守時良演、黒川覚史、中根明宏、梅本幸裕、佐々木昌一、林祐太郎、郡健二郎
  • Organizer: 第102回 日本泌尿器科学会総会
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2014-04-24 – 2014-04-27