Novel resveratrol derivatives induce apoptosis and cause cell cycle arrest in prostate cancer cell lines.

BACKGROUND: Resveratrol (RV), a naturally occurring phytoalexin, exerts manifold biological effects against a variety of human tumor cell lines. In this study, the cytotoxic and biological effects of novel RV derivatives were investigated in prostate cancer cells. MATERIALS AND METHODS: Cytotoxicity of the compounds was assessed by clonogenic assays in PC-3, LNCaP and DU-145 human prostate cancer cell lines. Induction of apoptosis was studied by Hoechst-propidium-iodide double staining. Cell cycle phase distribution of prostate cancer cells was analyzed using flow cytometry. RESULTS: Methoxy- and hydroxy-substituted RV derivatives exerted cytotoxic effects against all three cell lines. The most potent compounds, 3,3',4,4',5,5'-hexahydroxy-stilbene and 3,4,4',5-tetramethoxystilbene, induced apoptosis at concentrations lower than RV and caused cell cycle arrest in the cell lines investigated. CONCLUSION: Introducing additional hydroxy- and methoxymoieties to the stilbene ring of RV is capable of enhancing its cytotoxic and pro-apoptotic effects in hormone-responsive and non-responsive prostate cancer cells.

Progression delay in men with mild symptoms of bladder outlet obstruction: a comparative study of phytotherapy and watchful waiting.

To determine the effect of phytotherapy (Serona repens) on the clinical progression in men with mild symptoms of bladder outlet obstruction (BOO). A total of 189 patients with mild symptoms of BOO, recruited from four different European clinics, were included in the analysis. Age, prostate specific antigen (PSA), international prostate symptom score (IPSS), quality of life (QOL), maximum urinary flow rate (Qmax) and total prostate and transitional zone volume were recorded. Clinical progression was defined as change from the mild-IPSS group into the moderate or severe group or the occurrence of urinary retention and need of surgery. Cumulative progression rate was 1, 7, 9 and 16% at 6, 12, 18 and 24 month, respectively, for the active group (Serona repens) as compared to 6, 13, 15 and 24% for the watchful waiting group. (P=0.03) significant improvements in the Qmax, IPSS and QOL were seen in the group receiving Serona repens. Serona repens significantly reduced the clinical progression rates in men with mild symptoms of BOO. It also led to improvements in urinary symptoms, QOL scores and urinary flow rates.

The Vienna nomogram: validation of a novel biopsy strategy defining the optimal number of cores based on patient age and total prostate volume.

PURPOSE: We conducted a trial in patients with prostate specific antigen (PSA) levels from 2 to 10 ng/ml to validate a newly developed nomogram that defines the optimal number of biopsy cores required for prostate cancer (PCa) detection based on patient age and total prostate volume (Vienna nomogram). MATERIALS AND METHODS: A total of 502 patients underwent transrectal ultrasound guided prostate biopsy using the Vienna nomogram. These results were compared with those of a previous group of 1,051 patients who had standard octant biopsies followed by systematic repeat biopsies after 6 to 8 weeks if the initial biopsy result was negative for PCa. RESULTS: The overall PCa detection rate using the Vienna nomogram was 36.7% compared with 22% on first and 10% on repeat biopsy in the control group. The PCa detection rate using the Vienna nomogram was superior (p=0.002) to the octant biopsy technique, and comparable to a combination of first and repeat biopsy in the control group. Multivariate analysis of the Vienna nomogram showed that only PSA and the number of cores were independent predictors of PCa detection (chi-square = 49, p <0.001). Total prostate volume, transition zone volume and age were not independent predictors of PCa detection. CONCLUSIONS: The Vienna nomogram offers an easy tool to select the optimal number of prostate biopsy cores based on patient age and total prostate volume in PSA range 2 to 10 ng/ml. Cancer detection is significantly improved (66.4%) compared to the control group. The bias factor of larger prostate volume is eliminated by using the Vienna nomogram. Moreover, the Vienna nomogram is advantageous not only in terms of the improved PCa detection rate but also economically makes systematic repeat biopsies unnecessary.

Dutasteride: a review of current data on a novel dual inhibitor of 5alpha reductase.

Dutasteride is used in the treatment of benign prostatic hyperplasia. Like finasteride, it reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% in 2 years. It differs from finasteride in that it inhibits both isoenzymes of 5alpha reductase and results in near-complete suppression of serum dihydrotestosterone. Randomized placebo-controlled trials over 2 years have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate, and reduction of acute urinary retention events and need for surgery. Side effects occurring in therapy with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia. However, when dutasteride treatment is compared with placebo, these sexual adverse events are only modestly elevated. Long-term use over 4 years did not increase side effects. An efficient treatment of side effects is the combination of dutasteride and tamsulosin, especially for patients with large prostate volumes. Finally, the anticancer properties of dutasteride have been shown in placebo-controlled trials and are being investigated in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

Longitudinal study of men with mild symptoms of bladder outlet obstruction treated with watchful waiting for four years.

OBJECTIVES: To determine the risk of clinical progressions in men with mild lower urinary tract symptoms of bladder outlet obstruction and identify the predictors for progression in this group of men. METHODS: A total of 397 men who presented to the urology clinics with mild symptoms of bladder outlet obstruction (International Prostate Symptom Score less than 8) were analyzed in this longitudinal study conducted during a 4-year period. They began with the watchful waiting protocol and were followed up every 3 months for 48 months. Age, International Prostate Symptom Score (IPSS), divided into obstructive symptom score and irritative symptom score, serum prostate-specific antigen level, total prostate volume, transitional zone volume, urinary flow rates, and postvoid residual urine volume were documented. RESULTS: The cumulative incidence of clinical progression, defined as worsening of the IPSS with migration to the moderate symptom group (IPSS 8 to 18) or severe symptom group (IPSS 19 to 35) and an increase in IPSS of more than 2 points, was 6%, 13%, 15%, 24%, 28%, and 31% at 6, 12, 18, 24, 36, and 48 months, respectively. Nineteen patients (4.9%) developed acute urinary retention within the 48-month follow-up period. Of these 19 patients, only 2 (0.6%) required transurethral resection of the prostate. The variables of importance for disease progression in the artificial neural network analysis were, in order of statistical significance, prostate-specific antigen level, obstructive symptom score, and transitional zone volume. CONCLUSIONS: The risk for men with mild symptoms of bladder outlet obstruction to progress clinically and develop complications such as acute retention of urine is moderate. Prostate-specific antigen, obstructive symptom score, and transitional zone volume were identified as important risk factors.

Preventing progression in men with mild symptoms of benign prostatic hyperplasia: a potential role for phytotherapy.

Prevalence of benign prostate hyperplasia (BPH) is increasing with the aging population worldwide. Throughout the 20th century, men with minimally symptomatic BPH were generally advised to defer treatment. Treatment deferral or watchful waiting has always appeared reasonable because mild lower urinary tract symptoms suggestive of bladder outlet obstruction are not bothersome and are often regarded as part of the aging process, progression is usually slow, and symptoms often regress spontaneously. This review examines the evidence of the natural history of BPH, highlighting the group of patients with mild symptoms, the risk factors for progression, and the potential role of phytotherapy in this group of men.