MicroRNA-23b and microRNA-27b plus flutamide treatment enhances apoptosis rate and decreases CCNG1 expression in a castration-resistant prostate cancer cell line.

The acquisition of a castration-resistant prostate cancer phenotype by prostate cancer cells is the alteration that has the worst prognosis for patients. The aim of this study was to evaluate the role of the microRNAs-23b/-27b as well as the possible CCNG1 target gene in tissue samples from patients with localized prostate cancer that progressed to castration-resistant prostate cancer and in a castration-resistant prostate cancer cell line (PC-3). The microRNAs and target gene expression levels of the surgical specimens were analyzed by quantitative real-time polymerase chain reaction. The prostate cancer cell line, PC-3, was transfected with pre-miR-23b, pre-miR-27b, and their respective controls using Lipofectamine RNAiMAX and exposed or not to flutamide. After transfections, expression levels of both the microRNAs and the gene, CCNG1, were analyzed by quantitative real-time polymerase chain reaction. The apoptosis and cell cycle assays were performed on the mini MUSE cytometer. MicroRNAs-23b/-27b were underexpressed in surgical specimens of prostate cancer; however, their target gene, CCNG1, was overexpressed in 69% of the cases. After transfection with the microRNAs-23b/-27b and flutamide, we observed a reduction in gene expression compared with cells that were treated only with microRNAs or only with flutamide. In the apoptosis assay, we demonstrated cell sensitization following transfection with microRNAs-23b/-27b and potentiation when co-administered with flutamide. The number of cells in apoptosis was almost three times higher with the simultaneous treatments (miR + flutamide) compared with the control (p < 0.05). In the cell cycle assay, only flutamide treatment showed better results; a higher number of cells were found in the G0-G1 phase, and a lower percentage of cells completed the final phase of the cycle (p < 0.05). We conclude that microRNAs-23b/-27b are downexpressed in prostate cancer, and their target gene, CCNG1, is overexpressed. We postulated that microRNAs-23b/-27b sensitize the PC-3 cell line and that after the addition of flutamide in the apoptosis assay, we would observe synergism in the treatments between miR and flutamide. In the cell cycle assay, the use of flutamide was sufficient to decrease the number of cells in mitosis. Therefore, we postulate that microRNAs, along with other drugs, may become very useful therapeutic tools in the treatment of castration-resistant prostate cancer.

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer.

OBJECTIVE: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. METHOD: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. RESULTS: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). CONCLUSION: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer / Baixa testosterona sérica é prognóstica de doença de alto grau em pacientes com câncer de próstata

Summary Objective: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. Method: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. Results: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). Conclusion: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.

Resumo Objetivo: Avaliar a relação entre testosterona sérica total (TT) e grau do câncer de próstata (CP) e o efeito da raça e de características demográficas sobre essa associação. Método: Foram analisados 695 pacientes submetidos a prostatectomia radical (PR), dos quais 423 tinham medidas dos níveis séricos de TT. Os pacientes foram classificados como portadores de hipogonadismo ou eugonadismo com base em dois limites de testosterona: limite 1 (300 ng/dL) e limite 2 (250 ng/dL). Avaliou-se a relação entre nível de TT e escore Gleason (GS) ≥ 7 em amostras de PR. Os resultados foram avaliados por análises univariada e multivariada, com ajuste para raça e outros fatores prognósticos demográficos. Resultados: Do total de 423 pacientes, 37,8% apresentavam hipogonadismo com base no limite 1, e 23,9% com base no limite 2. Os pacientes com hipogonadismo, independentemente do limite de referência, tiveram uma chance maior de GS ≥ 7 (OR 1,79, p=0,02 e OR 2,08, p=0,012, respectivamente). Na análise multivariada, após ajuste para idade, TT, índice de massa corporal (IMC) e raça, baixo TT (p=0,023) e idade (p=0,002) foram considerados fatores de risco independentes para GS ≥ 7. Entre os indivíduos negros, baixo TT sérico foi mais preditivo de doença de alto grau em comparação com os brancos (p=0,02). Conclusão: O hipogonadismo é independentemente associado a escores mais altos de GS no CP localizado. O efeito dessa associação é significativamente mais pronunciado entre homens negros, o que poderia explicar, em parte, as características agressivas do CP observadas nessa população.

Retroperitoneoscopic pyelolithotomy: a good alternative treatment for renal pelvic calculi in children.

INTRODUCTION: Nephrolitiasis, once considered an adult disease, has become increasingly prevalent in children, with na increase from 6% to 10 % annually in past 25 years. Kidney stones in pediatric population can result from metabolic diseases in up to 50% of children affected. Other factors associated with litiasis are infection, dietary factors, and anatomic malformations of urinary tract. Standard treatment procedures for pediatric population are similar to adult population. Extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy (URS), percutaneous nepfrolithotomy (PCNL), as well as laparoscopic and retroperitoneoscopic approaches can be indicated in selected cases. The advantages of laparoscopic or retroperitoneoscopic approaches are shorter mean operation time, no trauma of renal parenchyma, lower bleeding risk, and higher stone-free rates, especially in pelvic calculi with extrarenal pelvis, where the stone is removed intact. PATIENT AND METHODS: A 10 year-old girl presented with right abdominal flank pain, macroscopic hematuria,with previous history of urinary infections.. Further investigation showed an 1,5 centimeter calculi in right kidney pelvis. A previous ureterorenoscopy was tried with no success, and a double J catheter was placed. After discussing options, a retroperitoneoscopic pielolithotomy was performed. RESULTS: The procedure occurred with no complications, and the calculi was completely removed. The foley catheter was removed in first postoperative day and she was discharged 2 days after surgery. Double J stent was removed after 2 weeks. CONCLUSIONS: Retroperitoneoscopic pielolithotomy is a feasible and safe procedure in children, with same outcomes of the procedure for adult population.