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1998 Fiscal Year Final Research Report Summary

Relationship between antiandrogen withdrawal syndrome and genetic alterations of the androgen receptor in prostate cancer

Research Project

Project/Area Number 09671603
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionChiba University

Principal Investigator

AKAKURA Koichiro  Scool of Medicine, Department of Urology, Lecturer, 医学部附属病院, 講師 (60261898)

Co-Investigator(Kenkyū-buntansha) ITO Haruo  Scool of Medicine, Department of Urology, Professor, 医学部, 教授 (20009583)
Project Period (FY) 1997 – 1998
KeywordsProstate cancer / Endocrine therapy / Antiandrogen withdrawal syndrome / Androgen receptor / Molecular biology
Research Abstract

In patients with progressive prostate cancer who have been treated with maximum androgen blockade (MAB) by surgical or medical castration plus an antiandrogen, antiandrogen withdrawal can result in a significant decline in serum prostate-specific antigen (PSA) and, in some cases, it was associated with clinical response. This phenomenon was named as antiandrogen withdrawal syndrome. In 1997, we investigated relationship between clinical outcome and mutations of the androgen receptor gene. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was carried out using prostate cancer tissue from untreated patients. No mutation was found in the androgen receptor gene of 17 cases irrespective of development of antiandrogen withdrawal syndrome. In 1998, the numbers of CAG and GGC repeats in the androgen receptor were examined in relation to antiandrogen withdrawal syndrome. Genomic DNA was extracted from prostate cancer tissue or peripheral blood and the numbers of CAG and GGC repeats were determined by PCR and polyacrylamide gel electrophoresis. The number of CAG repeat ranged 20-29 (mean : 22.3) in 7 of responders of endocrine therapy, 2 1-29 (mean : 24.2) in 5 of endocrine therapy-refractory patients who did not develop antiandrogen withdrawal syndrome, and 20-26 (mean : 22.5) in 6 of antiandrogen withdrawal syndrome cases, respectively. There was no close relationship between antiandrogen withdrawal syndrome and the number of CAG repeat of the androgen receptor gene. The number of GGC repeat was found to be 17 in most cases, and no significant difference was observed between the groups. Based on these results, at present it would be difficult to predict development of antiandrogen withdrawal syndrome by means of molecular biological examination of the androgen receptor gene.

  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Furuya, Y.et al: "Smcking and obesity in relation to the etiology and disease progression of prostate cancer in Japan." Int.J.Urol. 5. 134-137 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akimoto, S.et al: "Comparison of markers of bcne formation and resorption in prostate cancer patients to predict bone metastasis." Endocrine J.45. 97-104 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akakura, K.et al: "Incidence and characteristics of antiandrogen withdrawal syndrome in prostate cancer after treatment with chlormadinone acetate." Eur.Urol.33. 567-571 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akimoto, S.et al: "Prognestic value of the serum levels of bone formation and bone rescrption markers in prostate cancer patients with bone metastasis." Eur.Urol.34. 142-147 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Furuya, Y.et al: "Progncstic of patients with prostate carcinoma presenting as nonregional lymph node metastases." Urol.Int.61. 17-21 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akakura, K.et al: "The long-term results of a randomized trial for the treatment of stages B2 and C prostate cancer." Urology. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akimoto, S.et al.: "Prostate-specific antigen levels from a mass screening program using highly sensitive RIA kits." Int.J.Urol.4. 269-273 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akimoto, S.et al.: "Prognostic factors in patients with prostate cancer refractory to endocrine therapy : univariate and multivariate analysis including doubling times of prostate-specific antigen and prostatic acid phosphatase." Jpn.J.Clin.Oncol.27. 258-262 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akimoto, S.et al.: "Relationship between prostate-specific antigen, clinical stage, and degree of bone metastasis in patients with prostate cancer : comparison with prostatic acid phosphatase and alkaline Phosphatase." Int.J.Urol.4. 572-575 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akimoto, S.et al.: "Influence of osteoarthritis on serum marker levels of bone formation and resorption in patients with benign prostatic hypertrophy." Int.J.Urol.4. 580-582 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Bruchovsky, N.et al.: "Intermittent therapy for prostate cancer." Endocrine-Related Cancer. 4. 153-177 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furuya, Y.et al.: "Smoking and obesity in relation to the etiology and disease progression of prostate in Japan." Int.J.Urol.5. 134-137 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akimoto, S.et al.: "Comparison of markers of bone formation and resorption in prostate cancer patients to predict bone metastasis." Endocrine J.45. 97-104 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akakura, K.et al.: "Incidence and characteristics of antiandrogen withdrawal syndrome in prostate cancer after treatment with chlormadinone acetate." Eur.Urol.33. 567-572 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akimoto, S.et al.: "Prognostic value of the serum levels of bone formation and bone resorption markers in prostate cancer patients with bone metastasis." Eur.Urol.34. 142-147 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furuya, Y.et al.: "Prognosis of patients with prostate carcinoma presenting as nonregional lymph node metastases." Urol.Int.61. 17-21 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akakura, K.et al.: "The long-term results of a randomized trial for the treatment of stages B2 and C prostate cancer : radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities." Urology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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