Differential mechanisms of bicalutamide-induced apoptosis in prostate cell lines.

Bicalutamide is a non-steroidal antiandrogen used in the treatment of prostate cancer. Although widely accepted as an androgen receptor antagonist, the mechanism by which it induces apoptosis remains unclear. Defining exact pathways by which bicalutamide induces its apoptotic effects would help to advance its clinical applications. We aimed to (a) examine the apoptotic effects of bicalutamide at 24 h and (b) comment on the role of the caspases and calpains in mediating bicalutamide-induced apoptosis in androgen-dependent and androgen-independent cells. PWR-1E, PC-3 and DU-145 cells were treated with bicalutamide and assessed for apoptosis by flow cytometry at 24 h. DU-145 cells were used to compare differences between two different metastatic receptor-negative cells and to verify apoptotic induction at 48 h. To delineate a specific pathway of action for bicalutamide, PC-3 and PWR-1E cells were pretreated with specific inhibitors of caspase-dependent (zVAD-FMK) and caspase-independent pathways (calpain 2 inhibitor). Bicalutamide induced apoptosis in androgen-dependent PWR-1E cells via a caspase-dependent and calpain-independent mechanism. In androgen-independent PC-3 cells, bicalutamide also induced apoptosis by mechanisms that were partially inhibited by pan-caspase inhibition but were partially calpain dependent. Understanding into how bicalutamide exerts its effects in androgen-independent cells will yield further insights into the treatment of hormone-refractory disease.

Is digital rectal examination still necessary in the early detection of prostate cancer?

BACKGROUND: PSA measurement is important in prostate cancer detection. However, applying cut-off values of >4 ng/ml as indication for biopsy misses 20-30% of tumours. AIMS: To determine the number of patients with prostate cancer and normal age-related PSA, referred for TRUS biopsy due to abnormal DRE alone. METHODS: We reviewed patients referred for biopsy over 12 months. Indication for biopsy included abnormal PSA, abnormal DRE, or both. RESULTS: Four-hundred and sixty-five (465) TRUS biopsies were performed, 209 were positive. Of the 183 (183/209) positive on whom complete data were available, 4 (2.2%) had a normal age-related PSA but an abnormal DRE. CONCLUSIONS: Metastatic prostate cancer remains incurable. Therefore detection of organ-confined and potentially curable disease, is crucial. Though PSA has led to earlier detection, this study emphasises the importance of clinical examination, illustrating a normal PSA cannot eliminate the possibility of cancer. DRE and PSA should be interpreted as being collaborative, not competitive.

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines.

Epidemiologic studies have demonstrated an inverse association between flavonoid intake and prostate cancer (PCa) risk. The East Asian diet is very high in flavonoids and, correspondingly, men in China and Japan have the lowest incidence of PCa worldwide. There are thousands of different naturally occurring and synthetic flavonoids. However, only a few have been studied in PCa. Our aim was to identify novel flavonoids with antiproliferative effect in PCa cell lines, as well as determine their effects on cell cycle. We have screened a representative subgroup of 26 flavonoids for antiproliferative effect on the human PCa (LNCaP and PC3), breast cancer (MCF-7), and normal prostate stromal cell lines (PrSC). Using a fluorescence-based cell proliferation assay (Cyquant), we have identified five flavonoids, including the novel compounds 2,2'-dihydroxychalcone and fisetin, with antiproliferative and cell cycle arresting properties in human PCa in vitro. Most of the flavonoids tested exerted antiproliferative effect at lower doses in the PCa cell lines compared to the non-PCa cells. Flow cytometry was used as a means to determine the effects on cell cycle. PC3 cells were arrested in G2/M phase by flavonoids. LNCaP cells demonstrated different cell cycle profiles. Further studies are warranted to determine the molecular mechanism of action of 2,2'-DHC and fisetin in PCa, and to establish their effectiveness in vivo.

Medical and minimally invasive treatment of urinary incontinence.

Newer agents and procedures give urologists more options in treating patients who have urinary incontinence related to such etiologies as an ineffective sphincter, detrusor hypersensitivity, obstruction, or a combination of these. Abolition of the involuntary contractions characteristic of detrusor instability can be accomplished pharmacologically or surgically. First-line anticholinergic agents are tolterodine and oxybutynin XL, given orally. Alternatively, intravesical administration provides a high concentration of drug, such as capsaicin or resiniferatoxin, at the detrusor muscle level. However, this commits the patient to intermittent self-catheterization. Surgery is reserved for those who have failed prolonged trials of conservative therapies. For patients with intractable urge incontinence, urologists have the new technique of sacral nerve stimulation.

The role of orchiectomy in the management of postpubertal cryptorchidism.

PURPOSE: Owing to the risk of future malignancy, many postpubertal male subjects presenting with unilateral cryptorchidism undergo orchiectomy rather than orchiopexy. We examined the incidence of spermatogenesis and carcinogenesis in whole orchiectomy specimens removed from postpubertal cryptorchid male subjects. We review the concept that orchiectomy is justifiable in these patients. MATERIALS AND METHODS: A total of 52 patients with postpubertal cryptorchidism (unilateral in 48, bilateral in 4) were retrospectively analyzed from 1984. Patient age ranged from 15 to 66 years (mean 26). Six patients presented with primary infertility (unilateral in 3, bilateral in 3). The undescended testicles were palpable in 32 cases (62%). All patients underwent unilateral orchiectomy and whole specimens were examined histologically. RESULTS: Histology showed normal spermatogenesis in only 1 orchiectomy specimen, while 15 had maturation arrest, 6 testicular agenesis and 30 seminiferous tubular atrophy and/or Sertoli-cell-only syndrome with no spermatogenesis. The location of the undescended testis was the superficial inguinal pouch in 32 cases, inguinal canal in 6 and inside the deep ring in 8. Absent spermatogenesis was significantly associated with a high level of maldescent and with increasing age. Two patients (4%) had carcinoma in situ of the testicle. Torsion of an undescended testicle occurred in 1 patient (2%). CONCLUSIONS: This analysis of cryptorchid testes in postpubertal male subjects confirms that the majority cannot contribute to fertility, have significant malignant potential and may undergo torsion. Therefore, orchiectomy remains the treatment of choice for the majority of postpubertal male subjects presenting with unilateral cryptorchidism.