Androgen, acting via the androgen receptor (AR), is associated with the development and progression of prostate cancer. Anti-androgen therapy is widely used to manage prostate cancer. However, the conversion of the tumor from a hormone-sensitive to a hormone-insensitive status causes such therapy to fail. Several mechanisms have now been put forward for this conversion, including neuroendocrine (NE) differentiation of the tumor cells. In this study, we evaluated the prognostic significance of tumor-cell proliferation activity, NE differentiation and AR expression. Formalin-fixed, paraffin-embedded sections were prepared from 42 patients with adenocarcinoma of the prostate. Using antibodies to AR, the Ki-67 antigen (MIB-1), chromogranin A and synaptophysin, immunohistochemical expression of AR, tumor proliferation activity and NE differentiation were analyzed. Our study revealed that AR expression was significantly lower in adenocarcinoma (52.2 +/- 27.1%) than in non-tumorous prostate tissue (68.3 +/- 18.3%; P < 0.001). NE differentiation was found in 50% of the tumors, which was correlated with the Gleason score (P < 0.05). An univariate analysis revealed a significant correlation between progression-free survival with both AR expression (P < 0.01) and proliferation activity (P < 0.001). NE differentiation was not a prognostic factor in this study.
Purpose
To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria.Materials and methodsThis multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume.Results and limitationsCompared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, −0.6 ± 0.9 in IM twice/day, and −0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged.ConclusionsA short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.
Background : Lack of androgen receptor (AR) expression or mutation on the AR gene creates the tendency for androgen independence and progression of prostate cancer. However, the association between the progression and AR expression or mutations is still controversial. In this study, we evaluated the prognostic significance of AR expression and mutations in prostate cancers. Methods : Forty-two prostate adenocarcinomas and three lymph node metastatic lesions sampled prior to hormonal therapy were included in this study; AR expression was analyzed immunohistochemically using an antibody against AR and the result was scored as the percentage of AR-positive tumor cells in the total tumor cells. Polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis and DNA sequencing were used to detect AR mutations. Results : Our study revealed the average AR expression in the prostate adenocarcinoma was 52.2 ± 27.1%, which was significantly lower than that in the adjacent non-tumorous prostate tissue (68.3 ± 18.3% in average) ( P < 0.001). A significant correlation was obtained between progressionfree survival and AR expression ( P < 0.01). By SSCP analysis, three silent mutations (T649T, E709E and E711E) were detected in three separate prostate carcinomas. Conclusion : We conclude that AR expression is a useful prognostic indicator for tumor progression. Androgen receptor mutation may be an uncommon molecular event in untreated prostate cancer in Japanese men.
This therapy is a new strategy for patients with locally advanced bladder cancer. It can be a curative treatment not only in patients for whom total cystectomy is indicated, but also in patients whose condition is not amenable to curative treatment and for whom merely palliative treatment would otherwise seem the only option.
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