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
Objective: Transurethral resection of the prostate (TURP) is the current optimal therapy for the relief of bladder outflow obstruction, with subjective and objective success rate of 85 to 90%. Aim of this study was to evaluate efficacy and safety of Plasmakinetic energy (Gyrus electro surgical system), which produces vaporization of tissue immersed in isotonic saline against standard monopolar transurethral resection of the prostate. Results: Comparative data on IPSS symptom score, IIEF-5, Qol, PSA, peak urinary flow rate and post-void residual urine volume were similar in the two groups but showed a significant improvement respect to baseline values. The postoperative haemoglobin levels, postoperative catheterization time, hospital stay and 3-year overall surgical re-treatment-free rate were significantly better in the bipolar group. Conclusions: Bipolar TURP has a comparable outcome to standard monopolar TURP at short and medium term regard to subjective and objective outcome measurements. Its impact on bladder outlet function is also similar to that of monopolar TURP. Improvement in IPSS, Qol index, IIEF-5, Q max and post-void residual urine volume were comparable in both group denoting similar efficacy of the techniques.
This study demonstrates that the use of Holmium laser lithotripsy is a safe and effective means of treating ureteral stones regardless of sex, age, stone location, or stone size. The instrumentation we used was extremely limited, in order to reduce costs related to the procedure to an absolute minimum whilst maintaining the two quality indicators for the procedure, namely success rate and length of hospitalisation (86.1% and 34 hours).
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