Androgen-mediated resistance to apoptosis.

BACKGROUND: Previous studies demonstrate that androgen is capable of exerting a protective effect in the androgen-sensitive human prostate cancer cell line LNCaP. Limited studies, however, have addressed the underlying mechanisms involved, in particular the effects of androgen on both pro- and anti-apoptotic gene expression. METHODS: We investigated the effects of androgen on apoptotic sensitivity and the expression of the caspases and specific members of the Bcl-2 family in the LNCaP cell line. The effects of androgen on NF-kappaB activation were also investigated by using a gel mobility shift assay. RESULTS: 5alpha-Dihydrotestosterone (5-alphaDHT) conferred resistance to radiation (5 Gy) and etoposide-induced apoptosis in the LNCaP cell line. This finding was associated with a time-dependent decrease in the expression of the caspases and pro-apoptotic Bcl-2 family members. 5-alphaDHT did not confer protection against apoptosis in the LNCaP line transfected with the IkappaB super repressor of NF-kappaB, nor in the androgen insensitive PC-3 and DU-145 cell lines. CONCLUSION: The ability of 5-alphaDHT to raise the apoptotic threshold in the LNCaP cell line by altering specific pro-apoptotic gene expression suggests that androgen may serve as a general survival signal against diverse pathways that ultimately signal for apoptosis. We hypothesize that NF-kappaB serves as an important mediator in androgen survival signaling.

Extracorporeal shock wave therapy in the treatment of Peyronie's disease: experience with standard lithotriptor (siemens-multiline).

OBJECTIVES: To assess in a prospective study whether extracorporeal shock wave therapy (ESWT) using a standard radioscopic location lithotriptor is effective in the treatment of Peyronie's disease. METHODS: Fifty-four patients were included in this prospective study. Before and after treatment, the angulation was calculated by auto-photography. Pain severity was assessed by a visual analog pain scale. A self-evaluation questionnaire (International Index of Erectile Function) was used. All patients had symptoms (35 had pain during erection and 51 angulation greater than 20 degrees ). The mean disease duration was 16 months. The mean angulation before treatment was 48 degrees (range 10 degrees to 100 degrees ). Twenty-four patients had erectile dysfunction (questionnaire score less than 18). The Multiline Siemens lithotriptor was used. The plaque was located by palpation, and 1 mL of contrast agent was injected. Scopic visualization was used. Each patient received a minimum of one session of ESWT (3000 shock waves, 7 kJ) applied to a flaccid penis. RESULTS: All patients completed the protocol. The tolerance and safety were excellent. Of the 35 patients with pain on erection, 31 (91%) noticed relief immediately after ESWT (mean reduction 2.9 on the visual analog pain scale) (P <0.00001). For 29 patients (53.7%), an improvement in angulation (greater than 10 degrees ) was observed, with a mean reduction of 31 degrees (P <0.001). For patients with erectile dysfunction, only 6 (25%) had an increased questionnaire score (greater than 4). Twenty-five patients thought the plaque was smoother. CONCLUSIONS: ESWT with a standard lithotriptor (without the mobile arm) in Peyronie's disease is a feasible, safe, and effective treatment for pain on erection and significantly improves the penile angle.