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Purpose Despite several therapeutic options renal cell carcinoma is associated with a poor clinical outcome. Therefore, we investigated whether combining 5-fluorouracil with the histone deacetylase inhibitor belinostat would exert a synergistic effect on renal cell carcinoma cells in vitro and in vivo. Materials and Methods We used SN12C cells treated with 5-fluorouracil and/or belinostat in vitro and in xenograft experiments in vivo. Cell viability and death mechanisms were assessed by MTS assay and Western blot. To investigate the role of reactive oxygen species we used H 2 DCF-DA, reactive oxygen species scavengers and the roGFP2 construct. Results Belinostat potentiated the anticancer effect of 5-fluorouracil. It synergistically induced apoptosis by activating caspases and increasing the subG1 cell population. Effects on reactive oxygen species mediated DNA damage included decreased thioredoxin expression and increased levels of TBP-2, γ-H2AX and Ac-H3. Furthermore, belinostat attenuated the 5-fluorouracil mediated induction of thymidylate synthase via HSP90 hyperacetylation. Co-administration of 5-fluorouracil with belinostat similarly reduced tumor volume and weight, and increased γ-H2AX and Ac-H3 levels in the SN12C xenograft model. Conclusions In combination with 5-fluorouracil the targeted inhibitor of histone deacetylase synergistically inhibited renal cancer cell growth by the blockade of thymidylate synthase induction and the induction of reactive oxygen species mediated DNA damage in vitro and in vivo. Our results suggest that combined treatment with belinostat and 5-fluorouracil may represent a promising new approach to renal cancer. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the effectiveness of photodynamic therapy using Radachlorin® in patients with high grade, nonmuscle invasive bladder cancer refractory or intolerant to bacillus Calmette-Guérin therapy who refused radical cystectomy. Materials and Methods: Between July 2009 and December 2011 photodynamic therapy was performed in 22 men and 12 women. Radachlorin (0.5 to 0.6 mg/kg) was injected intravenously 2 to 3 hours before photodynamic therapy. After complete transurethral resection, a diffuser using a 22Fr cystoscope was placed in the bladder for irradiation with a 662 nm laser. Output beam power was adjusted to 1.8 W and the light dose was 15 J/cm2. Photodynamic therapy was performed for 16 to 30 minutes. Recurrence after photodynamic therapy was followed by regular cystoscopy at 1, 2 and 3 months, and at 3-month intervals thereafter for up to 2.8 years. Efficacy was assessed by cystoscopy, cytology and histology, and defined as the number of patients who were tumor free after initial photodynamic therapy. Results: Mean ± SD patient age was 62.94 ± 8.71 years. Average followup was 26.74 ± 6.34 months (median 28.12). As the primary efficacy outcome, the recurrence-free rate was 90.9% at 12 months, 64.4% at 24 months and 60.1% at 30 months. As the secondary efficacy outcome, there was no statistical difference in mass size, carcinoma in situ, number of previous bacillus Calmette-Guérin administrations, number of transurethral bladder resections or tumor multiplicity on Kaplan-Meier analysis (each p >0.05). No evidence of severe adverse effects was detected after photodynamic therapy. Conclusions: Photodynamic therapy with Radachlorin is a safe, effective treatment for nonmuscle invasive bladder cancer refractory or intolerant to bacillus Calmette-Guérin therapy in select patients. [ABSTRACT FROM AUTHOR]

Purpose: We compared postoperative outcomes in patients treated with laparoendoscopic single site varicocele ligation with or without testicular artery and lymphatic preservation. Materials and Methods: A total of 80 patients with left varicocele were randomly divided into 2 groups and treated with laparoendoscopic single site varicocele ligation with preservation of the testicular artery and lymphatics (40 in group 1) or complete ligation of the testicular vessels and lymphatics (40 in group 2). Operative time, hospital stay, return to normal activity, postoperative visual analog scale pain scores and complications were analyzed. In patients with subfertility preoperative and 3-month postoperative semen analyses were performed. In patients with scrotal pain preoperative and 12-month postoperative visual analog scale pain scores were analyzed. Results: A total of 35 patients per group completed the study. Hospital stay, return to normal activity and postoperative pain scores did not differ between the groups. No major complications were observed. Mean ± SD operative time was 60.7 ± 10.7 and 48.6 ± 6.0 minutes in groups 1 and 2, respectively (p <0.001). Patients with subfertility, including 22 in group 1 and 21 in group 2, showed improved semen parameters 3 months postoperatively but postoperative values did not differ between the groups. The 17 patients in each group with scrotal pain showed decreased pain scores 12 months postoperatively with no difference between the groups. Conclusions: Laparoendoscopic single site varicocele ligation is feasible. No differences in postoperative outcomes and complications were observed when preserving or not preserving the testicular artery and lymphatics. [ABSTRACT FROM AUTHOR]