The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and its activation correlates with tyrosine phosphorylation of the RNAbinding protein Sam68. Herein, we have investigated the expression and function of Sam68 in human prostate cancer cells. Analysis of specimens obtained from 20 patients revealed that Sam68 is upregulated at the protein level in 35% of the samples. Real-time polymerase chain reaction confirmed the results at the mRNA level in most patients. Downregulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression and reduced the proliferation rate. Moreover, depletion of Sam68 sensitized cells to apoptosis induced by DNAdamaging agents. Similarly, stable cell lines expressing a truncated GFP-Sam68 GSG protein displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Our results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents.

SummaryBackground The rationale for combining anticancer drugs has not been applied consistently to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. We aimed to do a prospective, randomised comparison of BCG alone with that of sequential BCG and electromotive mitomycin in patients with stage pT1 bladder cancer.Methods After transurethral resection and multiple biopsies, 212 patients with stage pT1 bladder cancer were randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks (n=105); or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. This trial has been submitted for registration at the US National Cancer Institute website http://clinicaltrials.gov. Findings

Purpose: In laboratory studies electromotive mitomycin C (MMC) demonstrated markedly increased transport rates compared with passive transport. We performed a prospective study in patients with high risk superficial bladder cancer to assess the efficacy of intravesical electromotive vs passive MMC using bacillus Calmette-Guerin (BCG) as a comparative treatment.Materials and Methods: Following transurethral resection and multiple biopsies 108 patients with multifocal Tis, including 98 with T1 tumors, were randomized into 3 equal groups of 36 each who underwent 40 mg electromotive MMC instillation with 20 mA electric current for 30 minutes, 40 mg passive MMC with a dwell time of 60 minutes or 81 mg BCG with a dwell time of 120 minutes. Patients were scheduled for an initial 6 weekly treatments, a further 6 weekly treatments for nonresponders and a followup 10 monthly treatments for responders. Primary end points were the complete response rate at 3 and 6 months. MMC pharmacokinetics were assessed.Results: The complete response for electromotive vs passive MMC at 3 and 6 months was 53% versus 28% (p ϭ 0.036) and 58% versus 31% (p ϭ 0.012). For BCG the responses were 56% and 64%. Median time to recurrence was 35 vs 19.5 months (p ϭ 0.013) and for BCG it was 26 months. Peak plasma MMC was significantly higher following electromotive MMC than after MMC ((43 vs 8 ng/ml), consistent with bladder content absorption.Conclusions: Intravesical electromotive administration increases bladder uptake of MMC, resulting in an improved response rate in cases of high risk superficial bladder cancer. Intravesical anticancer therapy is appropriate treatment for high risk superficial bladder cancer even if the ultimate long-term benefits are in doubt. 4 Investigators have described superior results with intravesical bacillus CalmetteGuerin (BCG) compared with chemotherapeutic drugs and they also attributed more numerous and more severe side effects to BCG. 5A chemotherapeutic agent that has withstood the test of time is mitomycin C (MMC) but evaluation of its clinical efficacy is difficult because so many investigators have used widely varying MMC doses, concentrations, instillation volumes and residence times, usually in heterogeneous patient populations. However, as early as 1993 Wientjes et al combined data from laboratory, animal and human studies with computer simulations to describe a compelling MMC regimen primarily based on optimizing diffusion down concentration gradients (Fick's first law). 6 The same group followed up with a study showing the advantages of increased concentration gradients in animals and humans 7 and then reported a phase III trial, in which the optimized regimen proved superior to a standard MMC regimen in patients with Ta grade I/II bladder cancers.8 However, results in subgroups with Tis, grade III and T1 disease were less definitive, although trends toward improvement were discernible. Therefore, it must be assumed that there are several reasons for the many failures that occur using intravesica...

Objective: Diet interventions may reduce the risk of urinary stone formation and its recurrence, but there is no conclusive consensus in the literature regarding the effectiveness of dietary interventions and recommendations about specific diets for patients with urinary calculi. The aim of this study was to review the studies reporting the effects of different dietary interventions for the modification of urinary risk factors in patients with urinary stone disease. Materials and Methods: A systematic search of the Pubmed database literature up to July 1, 2014 for studies on dietary treatment of urinary risk factors for urinary stone formation was conducted according to a methodology developed a priori. Studies were screened by titles and abstracts for eligibility. Data were extracted using a standardized form and the quality of evidence was assessed. Results: Evidence from the selected studies were used to form evidencebased guideline statements. In the absence of sufficient evidence, additional statements were developed as expert opinions. Conclusions: General measures: Each patient with nephrolithiasis should undertake appropriate evaluation according to the knowledge of the calculus composition. Regardless of the underlying cause of the stone disease, a mainstay of conservative management is the forced increase in fluid intake to achieve a daily urine output of 2 liters. Hypercalciuria: Dietary calcium restriction is not recommended for stone formers with nephrolithiasis. Diets with a calcium content ≥ 1 g/day (and low protein-low sodium) could be protective against the risk of stone formation in hypercalciuric stone forming adults. Moderate dietary salt restriction is useful in limiting urinary calcium excretion and thus may be helpful for primary and secondary prevention of nephrolithiasis. A low-normal protein intake decrease calciuria and could be useful in stone prevention and preservation of bone mass. Omega-3 fatty acids and bran of different origin decreases calciuria, but their impact on the urinary stone risk profile is uncertain. Sports beverage do not affect the urinary stone risk profile. Hyperoxaluria: A diet low in oxalate and/or a calcium intake normal to high (800-1200 mg/day for adults) reduce the urinary excretion of oxalate, conversely a diet rich in oxalates and/or a diet low in calcium increase urinary oxalate. A restriction in protein intake may reduce the urinary excretion of oxalate although a vegetarian diet may lead to an increase in urinary oxalate. Adding bran to a diet low in oxalate cancels its effect of reducing urinary oxalate. Conversely, the addition of supplements of fruit and vegetables to a mixed diet does not involve an increased excretion of oxalate in the urine. The intake of pyridoxine reduces the excretion of oxalate. Hyperuricosuria: In patients with renal calcium stones SummaryNo conflict of interest declared. DOI: 10.4081/aiua.2015.2.105the decrease of the urinary excretion of uric acid after restriction of dietary protein and purine is suggested although not cle...