Antioxidant treatment for oligoasthenoteratozoospermia and varicocele: a DBPC trial to evaluate the impact of age and body mass index.

ABSTRACT: Oxidative stress is one of the main mechanisms responsible for male infertility. Various conditions such as varicocele, obesity, advanced age, and lifestyle can lead to an increase in reactive oxygen species, causing an oxidative imbalance in the reproductive environment. Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizing the egg. Excessive reactive oxygen species can affect sperm metabolism, leading to immobility, impaired acrosome reaction, and cell death, thereby impairing reproductive success. This double-blind randomized study evaluated the effect of supplementation with L-carnitine, acetyl-L-carnitine, vitamins, and other nutrients on semen quality in 104 infertile patients with or without varicocele, while also investigating the impact of factors such as obesity and advanced age on treatment. Sperm concentration significantly increased in the supplemented group compared to the placebo group (P = 0.0186). Total sperm count also significantly increased in the supplemented group (P = 0.0117), as did sperm motility (P = 0.0120). The treatment had a positive effect on patients up to 35 years of age in terms of sperm concentration (P = 0.0352), while a body mass index (BMI) above 25 kg m-2 had a negative effect on sperm concentration (P = 0.0110). Results were not showing a net benefit in stratifying patients in accordance with their BMI since sperm quality increase was not affected by this parameter. In conclusion, antioxidant supplementation may be beneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

Clinical Effects of Oral Supplementation of Gamma-Cyclodextrin Curcumin Complex in Male Patients with Moderate-To-Severe Benign Prostatic Hyperplasia-Related Lower Urinary Tract Symptoms.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTSs) in males. Curcumin exhibits anti-inflammatory and anti-tumor properties which may be effective for BPH. This multi-arm observational study evaluated the real-world efficacy of QURMIN® (Gamma-cyclodextrin-curcumin Complex-CAVACURMIN®) as single or combination therapy for BPH. METHODS: Men with moderate-severe LUTS/BPH, receiving a 6-month supplementation with QURMIN® alone or in combination with BPH-specific medication were propensity score matched with patients not taking curcumin and then divided into subgroups based on concomitant baseline treatment. Cohorts were compared in the 6-month variation of IPSS, quality of life (IPSS-QoL), Benign Prostatic Hyperplasia Impact Index (BII) and uroflowmetry parameters. Curcumin tolerability was evaluated in terms of discontinuations and adverse effects. RESULTS: The 1:1 propensity score matching resulted in a treatment-naïve (n = 152), an alpha-blocker only (AB) (n = 138) and AB + 5-alpha reductase inhibitors (5-ARIs) (n = 78) subgroup. After 6 months, drug-naïve patients taking curcumin reported significant improvement in IPSS-storage (-3.9, p < 0.001), IPSS-voiding (-2.0, p = 0.011), IPSS-total (-5.9, p < 0.001), IPSS-QoL (-3.9, p < 0.001), BII (-2.0, p < 0.001), Qmax (+3.1 mL/s, p < 0.001), Qmean (+1.9 mL/s, p = 0.005), post-void residual volume (-7.7 mL, p < 0.001), and PSA (-0.3 ng/mL, p = 0.003), compared to controls. Patients taking ABs and curcumin showed improvement in IPSS-storage (-2.7, p < 0.001), IPSS-voiding (-1.3, p = 0.033), IPSS-total (-3.5, p < 0.001), IPSS-QoL (-1.1, p = 0.004), BII (-1.7, p = 0.006), Qmax (+1.0 mL/s, p = 0.006), and PSA (-0.2 ng/mL, p = 0.01). Patients taking curcumin and AB + 5-ARI showed improvement in IPSS-storage (-1.3, p = 0.007), IPSS-total (-1.6, p = 0.034), IPSS-QoL (-1.1, p < 0.001), and BII (-2.0, p < 0.001). No adverse reactions were reported for curcumin supplementation. CONCLUSION: QURMIN® (CAVACURMIN®) led to significant improvements in symptom burden, uroflow parameters, and QoL, without significant additional side effects, thus proving to be a potential new treatment for BPH, either as a single therapy or in addition to standard treatment.

Novel Key Ingredients in Urinary Tract Health-The Role of D-mannose, Chondroitin Sulphate, Hyaluronic Acid, and N-acetylcysteine in Urinary Tract Infections (Uroial PLUS®).

Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N-acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections.

n-3 PUFA-Enriched Diet Preserves Skeletal Muscle Mitochondrial Function and Redox State and Prevents Muscle Mass Loss in Mice with Chronic Heart Failure.

Rationale and Methods: Skeletal muscle derangements, potentially including mitochondrial dysfunction with altered mitochondrial dynamics and high reactive oxygen species (ROS) generation, may lead to protein catabolism and muscle wasting, resulting in low exercise capacity and reduced survival in chronic heart failure (CHF). We hypothesized that 8-week n-3-PUFA isocaloric partial dietary replacement (Fat = 5.5% total cal; EPA + DHA = 27% total fat) normalizes gastrocnemius muscle (GM) mitochondrial dynamics regulators, mitochondrial and tissue pro-oxidative changes, and catabolic derangements, resulting in preserved GM mass in rodent CHF [Myocardial infarction (MI)-induced CHF by coronary artery ligation, left-ventricular ejection fraction <50%]. Results: Compared to control animals (Sham), CHF had a higher GM mitochondrial fission-fusion protein ratio, with low ATP and high ROS production, pro-inflammatory changes, and low insulin signalling. n-3-PUFA normalized all mitochondrial derangements and the pro-oxidative state (oxidized to total glutathione ratio), associated with normalized GM cytokine profile, and enhanced muscle-anabolic insulin signalling and prevention of CHF-induced GM weight loss (all p < 0.05 vs. CHF and p = NS vs. S). Conclusions:n-3-PUFA isocaloric partial dietary replacement for 8 weeks normalizes CHF-induced derangements of muscle mitochondrial dynamics regulators, ROS production and function. n-3-PUFA mitochondrial effects result in preserved skeletal muscle mass, with potential to improve major patient outcomes in clinical settings.

Thermal ablation for small renal masses: Identifying the most appropriate tumor size cut-off for predicting perioperative and oncological outcomes.

OBJECTIVES: To test TRIFECTA achievement [1) absence of CLAVIEN-DINDO ≥3 complications; 2) complete ablation; 3) absence of ≥30% decrease in eGFR] and local recurrence rates, according to tumor size, in patients treated with thermal ablation (TA: radiofrequency [RFA] and microwave ablation [MWA]) for small renal masses. METHODS: Retrospective analysis (2008-2020) of 432 patients treated with TA (RFA: 162 vs. MWA: 270). Tumor size was evaluated as: 1) continuously coded variable (cm); 2) tumor size strata (0.1-2 vs. 2.1-3 vs. 3.1-4 vs. >4 cm). Multivariable logistic regression models and a minimum P-value approach were used for testing TRIFECTA achievement. Kaplan-Meier plots depicted local recurrence rates over time. RESULTS: Overall, 162 (37.5%) vs. 140 (32.4%) vs. 82 (19.0%) vs. 48 (11.1%) patients harboured, respectively, 0.1 to 2 vs. 2.1 to 3 vs. 3.1 to 4 vs. >4 cm tumors. In multivariable logistic regression models, increasing tumor size was associated with higher rates of no TRIFECTA achievement (OR:1.11; P< 0.001). Using a minimum P-value approach, an optimal tumor size cut-off of 3.2 cm was identified (P< 0.001). In multivariable logistic regression models, 3.1 to 4 cm tumors (OR:1.27; P< 0.001) and >4 cm tumors (OR:1.49; P< 0.001), but not 2.1 to 3 cm tumors (OR:1.05; P= 0.3) were associated with higher rates of no TRIFECTA achievement, relative to 0.1 to 2 cm tumors. The same results were observed in separate analyses of RFA vs. MWA patients. After a median (IQR) follow-up time of 22 (12-44) months, 8 (4.9%), 8 (5.7%), 11 (13.4%), and 5 (10.4%) local recurrences were observed in tumors sized 0.1 to 2 vs. 2.1 to 3 vs. 3.1 to 4 vs. >4 cm, respectively (P= 0.01). CONCLUSION: A tumor size cut-off value of ≤3 cm is associated with higher rates of TRIFECTA achievement and lower rates of local recurrence over time in patients treated with TA for small renal masses.

Current management of radiation cystitis after pelvic radiotherapy: a systematic review.

INTRODUCTION: We aimed to summarize current literature about radiation cystitis treatments, providing physician of a summary of current management options. EVIDENCE ACQUISITION: A systematic literature review searching on PubMed (Medline), Scopus, and Web of Science databases was performed in March 2021. PRISMA guidelines were followed. Population consisted of patients with a diagnosis of radiation cystitis after pelvic radiotherapy (P). We focused our attention on different treatments, such as conservative or surgical one (I). Single or multiple arms studies were deemed eligible with no mandatory comparison (C). Main outcomes of interest were symptoms control and adverse events rates (O). EVIDENCE SYNTHESIS: The search identified 1194 records. Of all, four studies focused on the use of hyperbaric oxygen therapy showing complete response rates ranging from 52% to 87% approximately. Oral administration of cranberry compounds was investigated in one study showing no superiority to placebo. Intravesical instillation of different compounds were investigated in five studies showing the highest complete response rates after alum (60%) and formalin administration (75%). Endoscopic conservative surgical treatments (fibrin glue or vaporization) also showed 75% complete response rates. In patients who did not respond to conservative treatments robotic cystectomy is feasible with overall complication rates of about 59.3% at 90 days. CONCLUSIONS: Radiotherapy induced cystitis is an under-reported condition after pelvic radiotherapy. Several treatments have been proposed, but in up to 10% of cases salvage cystectomy is necessary. A stepwise approach, with progressive treatment aggressiveness is recommended.

Perioperative Outcomes of Holmium Laser Enucleation of the Prostate: A Systematic Review.

INTRODUCTION: The aim of the study was to systematically review the literature and describe perioperative complications of holmium laser enucleation of the prostate (HoLEP), including the Clavien-Dindo classification of surgical complications. METHODS: All English language publications on HoLEP were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines to evaluate PubMed®, Scopus®, and Web of Science™ databases from January 1, 1998, to June 1, 2020. RESULTS: Fifty-seven studies were included, for a total of 10,371 procedures. We distinguished between intra-, peri-, and postoperative complications. Overall, the rate of complications is 0-7%. Intraoperative complications include incomplete morcellation (2.3%), capsular perforation (2.2%), bladder (2.4%), and ureteric orifice (0.4%) injuries. Perioperative complications include postoperative urinary retention (0.2%), hematuria and clot retention (2.6%), and cystoscopy for clot evacuation (0.7%). Postoperative complications include dysuria (7.5%), stress (4.0%), urge (1.8%), transient (7%) and permanent (1.3%) urinary incontinence, urethral stricture (2%) and bladder neck contracture (1%). CONCLUSIONS: HoLEP is a safe procedure, with a satisfactory low complication rate. The most common reported perioperative complications are not severe (Clavien-Dindo classification grades 1-2). Further randomized studies are certainly warranted to fully determine the predictor of surgical complications in order to prevent them and improve this technique.

Impact of Perioperative Immunonutrition on Complications in Patients Undergoing Radical Cystectomy: A Retrospective Analysis.

INTRODUCTION: Radical cystectomy (RC) is the gold standard treatment for patients with muscle-invasive or refractory non-muscle invasive bladder cancer. It is estimated that approximately 64% and 13% of RC patients experience any complication and major complications, respectively. Specialized immunonutrition (SIM) aims to reduce the rates of complications after RC. We reported surgical complication rates in RC patients who received (SIM group) versus who did not receive (no-SIM group) perioperative SIM. Moreover, we investigated factors associated with complications after RC. MATERIAL AND METHODS: This is a retrospective cohort study of 52 patients who underwent RC between April 2016 and December 2017. Overall, 26 (50%) patients received perioperative SIM. We recorded age, gender, Charlson Comorbidity Index (CCI), body mass index (BMI), Malnutrition Universal Screening Tool (MUST) score, unintentional weight loss (UWL), SIM drinks consume, surgical approach, urinary diversion, neoadjuvant chemotherapy (NAC), use of total parenteral nutrition (TPN), final pathology, length of stay (LOS), and complications. RESULTS: SIM was associated with higher rates of documented infections (P = .03). Conversely, post-operative ileus was associated with higher rates of overall infections (P = .03). Median LOS was comparable within the 2 groups. Overall, 4 (15.38%) versus 0 (0%) patients in SIM versus no-SIM group were readmitted to hospital (P = .03). Age, CCI, NAC, and TPN were not associated with complication rates. CONCLUSIONS: SIM is not associated with lower rates of post-operative complications in RC candidates. Moreover, higher rates of documented infections were observed in the SIM group. Patients with post-operative ileus experienced more infections. Age, CCI, NAC, and TPN were not predictive of complications.

A biofeedback-guided programme or pelvic floor muscle electric stimulation can improve early recovery of urinary continence after radical prostatectomy: A meta-analysis and systematic review.

PURPOSE: Urinary incontinence (UI) after radical prostatectomy (RP) is an early side effect after catheter removal. This systematic review and meta-analysis were conducted to compare different forms of non-invasive treatments for post-RP UI and to analyse whether the addition of biofeedback (BF) and/or pelvic floor muscle electric stimulation (PFES) to PF muscle exercise (PFME) alone can improve results in terms of continence recovery rate. MATERIALS AND METHODS: A literature search was performed following the PRISMA guidelines. We performed a cumulative meta-analysis to explore the trend in the effect sizes across subgroups during a 12-months follow-up. RESULTS: Twenty-six articles were selected. At baseline after RP and catheter removal, mean pad weight varied extremely. At 1- and 3-months intervals, mean difference in pad weight recovery from baseline was significantly higher using guided programs (BF, PFES or both) than using PFME alone (3-months: PFME 111.09 g (95%CI 77.59-144.59), BF 213.81 g (95%CI -80.51-508-13), PFES 306.88 g (95%CI 158.11-455.66), BF + PFES 266.31 g (95%CI 22.69-302.93); P < .01), while at 6- and 12-months differences were similar (P > .04). At 1- and 3-months intervals, event rate (ER) of continence recovery was significantly higher using guided programs than using PFME alone (3-months: PFME 0.40 (95%CI 0.30-0.49), BF 0.49 (95%CI 0.31-0.67), PFES 0.57 (95%CI 0.46-0.69), BF + PFES 0.75 (95%CI 0.60-0.91); P < .01), while at 6- and 12-months ERs were similar. CONCLUSIONS: Regarding non-invasive treatment of UI secondary to RP, the addition of guided programs using BF or/and PFES demonstrated to improve continence recovery rate, particularly in the first 3-month interval, when compared with the use of PFME alone.

Safety and Feasibility of Outpatient Surgery in Benign Prostatic Hyperplasia: a Systematic Review and Meta-Analysis.

Purpose: Most of the endourologic procedures along the urinary tract have been widely practiced as outpatient operations, including surgery for benign prostatic hyperplasia (BPH). This systematic review and meta-analysis was conducted to assess safety and feasibility of outpatient surgery for patients suffering from symptomatic BPH candidate for endoscopic disobstruction. Materials and Methods: PubMed, Web of Science, Cochrane, and Embase were searched up until March 30, 2020. Methodological index for nonrandomized studies (MINORS) tool was utilized to assess the quality of included studies, and a pooled measure of failure rate (FR) or event rate (ER) estimate was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate contribution of moderators to heterogeneity. Results: Twenty studies with a total of 1626 patients treated according to outpatient criteria for endoscopic BPH surgery were included. In total, 18 studies reporting data on immediate hospital readmission and/or inability to discharge after endoscopic procedure presented FR estimates ranging from 1.7% to 51.1%. Pooled FR estimate was 7.8% (95% confidence interval [CI]: 5.2-10.3); Heterogeneity: Q = 76.85; degree of freedom = 17, p < 0.001; I2 = 75.12%. Subgroup analysis according to surgical technique revealed difference among the three approaches with pooled FR of 3% (95% CI: 1-4.9), 7.1% (95% CI: 3.9-10.4), and 11.8% (95% CI: 7-16.7) for transurethral resection of the prostate, Green-light, and holmium laser vaporesection, respectively (p < 0.001). At meta-regression analysis, none of the retrieved covariates was able to significantly influence the cumulative outcomes reported. ER for postoperative complications and early outpatient visit showed a pooled estimate of 18.6% (95% CI: 13.2-23.9) and 7.7% (95% CI: 4.3-11), respectively. Conclusions: Our analysis revealed how transurethral procedures for BPH on an outpatient setting are overall reliable and safe. Of note, there were significant outcome differences between groups with regard to type of surgical procedure, perioperative prostate volume, and discharge protocol suggesting the need for further prospective analysis to better elucidate the best strategy in such outpatient conduct.

Management of nonischemic-dilated cardiomyopathies in clinical practice: a position paper of the working group on myocardial and pericardial diseases of Italian Society of Cardiology.

: Nonischemic-dilated cardiomyopathy (NIDCM) is an entity that gathers extremely heterogeneous diseases. This awareness, although leading to continuous improvement in survival, has increased the complexity of NIDCM patients' management. Even though the endorsed 'red-flags' approach helps clinicians in pursuing an accurate etiological definition in clinical practice, it is not clear when and how peripheral centers should interact with referral centers with specific expertise in challenging scenarios (e.g. postmyocarditis and genetically determined dilated cardiomyopathy) and with easier access to second-line diagnostic tools and therapies. This position paper will summarize each step in NIDCM management, highlighting the multiple interactions between peripheral and referral centers, from first-line diagnostic workup and therapy to advanced heart failure management and long-term follow-up.

Body mass index and age correlate with antioxidant supplementation effects on sperm quality: Post hoc analyses from a double-blind placebo-controlled trial.

Spermatozoa are vulnerable to lack of energy and oxidative stress as a result of elevated levels of reactive oxygen species. Therefore, it is essential that appropriate nutrients are available during maturation. This randomised, double-blind, placebo-controlled trial investigated the effect of 6-month supplementation with carnitines and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele. Semen analyses were done at the beginning and end of the treatment. In addition to main analyses, post hoc analyses for age and body mass index (BMI) were carried out. Results were interpreted by dividing the population into two age and BMI classes. In 94 patients who completed the study, all sperm parameters increased in supplemented patients compared to the placebo group. A significant (p = .0272) difference in supplementation efficacy was observed for total motility on patients with varicocele and BMI < 25. In the same group, also the progressive motility was significantly superior (p = .0159). For Responder analysis, total motility results were confirmed in both the cited group (p = .0066) and in the varicocele group with BMI < 25 and age < 35 (p = .0078). This study suggests that supplementation is more effective in subjects with varicocele younger than 35 years with BMI < 25.

New Cross-Talk Layer between Ultraconserved Non-Coding RNAs, MicroRNAs and Polycomb Protein YY1 in Bladder Cancer.

MicroRNAs (miRNAs) are highly conserved elements in mammals, and exert key regulatory functions. Growing evidence shows that miRNAs can interact with another class of non-coding RNAs, so-called transcribed ultraconserved regions (T-UCRs), which take part in transcriptional, post-transcriptional and epigenetic regulation processes. We report here the interaction of miRNAs and T-UCRs as a network modulating the availability of these non-coding RNAs in bladder cancer cells. In our cell system, antagomiR-596 increased the expression of T-UCR 201+. Moreover, T-UCR 8+ silencing increased miR-596 expression, which in turn reduced total T-UCR 283+, showing that the perturbation of one element in this network changes the expression of other interactors. In addition, we identify the polycomb protein Yin Yang 1 (YY1) as mediator of binding between miR-596 and T-UCR 8+. These new findings describe for the first time a network between T-UCRs, miRNAs and YY1 protein, highlighting the existence of an additional layer of gene expression regulation.

Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®).

BACKGROUND: Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. METHODS: 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. RESULTS: Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram - (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. CONCLUSIONS: Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. TRIAL REGISTRATION: NCT02130713. Date of trial Registration: 30/04/2014.

Inhibitory effect of standardized cannabis sativa extract and its ingredient cannabidiol on rat and human bladder contractility.

OBJECTIVES: To evaluate the effect of a Cannabis sativa extract enriched in cannabidiol (CBD) botanic drug substance (BDS) and pure CBD, on bladder contractility in vitro. Cannabis based-medicines, including CBD-enriched extracts, have been shown to reduce urinary urgency, incontinence episodes, frequency, and nocturia in patients with multiple sclerosis. METHODS: Strips were cut from male Wistar rats and the human bladder body and placed in organ baths containing Krebs solution. Contractions were induced by electrical field stimulation, acetylcholine, KCl, and α,ß-methylene adenosine triphosphate. RESULTS: CBD BDS significantly reduced the contractions induced by acetylcholine, but not those induced with electrical field stimulation, KCl, or α,ß-methylene adenosine triphosphate in the isolated rat bladder. The inhibitory effect of CBD BDS was not significantly modified by the cannabinoid or opioid receptor antagonists or by modulators of calcium levels, but it was increased by ruthenium red and capsazepine, 2 transient receptor potential vanilloid type-1 blockers. In humans, CBD BDS and pure CBD significantly reduced acetylcholine-induced contractions, an effect that was not changed by the transient receptor potential vanilloid type-1 blockers. CONCLUSIONS: Our data have suggested that CBD BDS reduces cholinergic-mediated contractility and that this effect is modulated by transient receptor potential vanilloid type-1 in rats but not in humans. CBD is the chemical ingredient of CBD BDS responsible for such activity. If confirmed in vivo, such results could provide a pharmacologic basis to explain, at least in part, the efficacy of Cannabis medicines in reducing incontinence episodes in patients with multiple sclerosis.

Effects of the ErbB1/ErbB2 kinase inhibitor GW2974 on androgen-independent prostate cancer PC-3 cell line growth and NSE, chromogranin A and osteopontin content.

Prostate cancer is one of the most frequently diagnosed cancer in men. Treatment by radical prostatectomy, radiotherapy and anti-androgen drugs is successful in patients with localized cancer. However, prolonged androgen deprivation often leads to hormone refractory condition, associated with disease relapse. ErbB1 and ErbB2 activity has been correlated with androgen-independence. We determined the effects of GW2974, a dual inhibitor of ErbB-1 and ErbB-2 tyrosine kinase activity, on growth, NSE, chromogranin A and osteopontin cytosol content in the androgen-independent prostate cancer cell line PC-3. We found that PC-3 cell growth was inhibited by GW2974, whereas NSE and chromogranin A cell contents were stimulated and osteopontin cytosol level was not affected. The present data may have clinical implications for the treatment of advanced prostate cancer.