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Effect on the carcinogenesis of male rat bladder cancer of antiandrogen and 5_<alpha>-reductase inhibitor

Research Project

Project/Area Number 05671298
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionUniversity of Tsukuba

Principal Investigator

AKAZA Hideyuki  Univ.Tsukuba Associ.Prof., 臨床医学系, 助教授 (70010486)

Co-Investigator(Kenkyū-buntansha) OOTANI Mikinobu  Univ.Tsukuba, 臨床医学系, 講師 (80133081)
MATSUKI Katsuyuki  Univ.Tsukuba, 臨床医学系, 講師 (40165791)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsbladder cancer / carcinogenesis / testosterone / 5_<alpha>-reductase inhibitor / anti-androgen / DHT / アンチアンドロゲン / 5α-reductase / 性ホルモン / Dihydrotestosterone
Research Abstract

It has been reported that blocking of androgen inhibits bladder carcinogenesis in male rats. However, the mechanism of action of androgen in bladder carcinogenesis is not known. To investigate this problem, we designed the following study using three antiandrogen drugs that have different mechanisms.
We administered 0.05% BBN orally to 117 Wistar rats for 10 weeks, and divided them into 7 treatment groups (control, surgical castration, finasteride, LH-RH agonist, flutamide, LH-RH agonist + finasteride and LH-RH agonist + flutamide). Rats were cystectomized in the 21st week and speciments were examined histopathologically. Results demonstrated that surgical castration and LH-RH agonist treatment (three groups) reduced the incidence of carcinoma significantly and that surgical castration had a greater inhibitory effect than the LH-RH agonist. These observations suggest that androgen acts directly on the bladder mucosa. On the other hand, LH-RH agonist + flutamide showed greater inhibition than LH-RH agonist + finasteride, suggesting that testosterone combines directly with androgen receptor without conversion to DHT.We also investigated the presence of androgen receptors in rat and mouse bladder mucosa using monclonal and polyclonal antibodies and western blotting after homogenation. Results confirmed the existence of monoclonal antibody overlapping nuclei in mouse and rat bladder mucosa, as in accessory sex organs, and recognition of a protein corresponding to the molecular weight of the androgen receptor.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Imada S,Akaza H: "Effects and mechanism of androgen in rat bladoler carcinegenesis" J.Urol. (発表予定).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akaza H,et al: "Bacillus Colmette-Guerin treatment of existing popillary bladder cancer and CIS of the bladder" Cancer. 75. 552-559 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Imada S,Akaza H et al.: "Effects and its mechanism of androgen in rat bladder carcinogenesis" J.Urol to be submitted.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Imada S,Akaza H: "Effects and mechanism of androgen in rat bladder carcinogenesis" J.Urol. (発表予定).

    • Related Report
      1994 Annual Research Report
  • [Publications] Akaza H.,et al: "Role of attachment and viability of BCG to bladder cancer cells" Cancer. 72. 558-563 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Akaza H.,et al: "A randomized phase II trial of flutarnide us chlormadinone acetate in previously untreated advanced prostatic cancer" Jpn J Clin Oncol. 23. 178-185 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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