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1.
BMC Endocr Disord ; 23(1): 30, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36732722

RESUMEN

PURPOSE: Metabolic syndrome is a risk factor for several diseases. The relationship between metabolic syndrome and hypogonadism is well known. Our objetive is to assess whether a low carbohydrate diet can increase total serum testosterone and improve erectile function in hypogonadal men with metabolic syndrome. METHODS: An open label randomized clinical trial was conducted comparing a low carbohydrate diet and controls, during three months, in hypogonadal men with metabolic syndrome. Anthropometric measurements were evaluated as well as total serum testosterone levels, and symptoms of hypogonadism, using the ADAM and AMS scores, and sexual function using IIEF-5 score. RESULTS: Eighteen men were evaluated. Anthropometric measures were improved only in low carbohydrate diet group. The intervention group also had a statistically increase in IIEF-5 score and a significant reduction in AMS and ADAM scores (p < 0.001). The increase in serum total testosterone levels was statistically significant in the low carbohydrate group compared to the control group as well as calculated free testosterone (p < 0.001). CONCLUSIONS: Low carbohydrate diet may increase serum levels of testosterone and improve erectile function in hypogonadal men with metabolic syndrome. However, larger studies are necessary to strongly prove the effectiveness of low carbohydrate diet in treating male hypogonadism.


Asunto(s)
Disfunción Eréctil , Hipogonadismo , Síndrome Metabólico , Masculino , Humanos , Disfunción Eréctil/etiología , Síndrome Metabólico/complicaciones , Testosterona , Hipogonadismo/complicaciones , Dieta Baja en Carbohidratos
2.
World J Urol ; 40(12): 2925-2930, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36284002

RESUMEN

PURPOSE: To evaluate the neurovascular bundle preservation grades during robotic-assisted radical prostatectomy and compared to the trifecta combined outcome (oncologic control, continence, and sexual function) twelve months after the surgery. METHODS: Cohort of patients who underwent nerve-sparing robotic-assisted radical prostatectomy had the neurovascular bundle preservation retrospectively graded from 0 to 8 according to the Hopkins subjective visual classification. Patients then were divided into two groups, according to the median of nerve-sparing grading: those with score six or high and those with score less than six. Main outcome was the trifecta combined outcome and secondary outcomes was the individual trifecta criteria (prospective analysis). A secondary analysis with groups divided according to pre-operatory SHIM score was made. RESULTS: One hundred robotic-assisted nerve-sparing radical prostatectomy were performed, of which 83 were included. There were 53 patients with grading greater than or equal to six (group 1) and 30 patients less than six (group 2). 66.6% patients (35/53) in group 1 had a trifecta combined outcome of compared to 33.3% (10/30) in group 2 (p = 0.017). Individually, the erectile function was higher in group 1 (73.6%) compared to group 2 (46.7%) (p = 0.014). Both the results of the combined endpoint trifecta and erection were also maintained in the group with preoperative SHIM ≥ 17. CONCLUSIONS: The grading of preservation of the neurovascular bundle in radical prostatectomy is related to a better combined trifecta outcome one year after surgery.


Asunto(s)
Disfunción Eréctil , Procedimientos Quirúrgicos Robotizados , Robótica , Masculino , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Disfunción Eréctil/etiología , Disfunción Eréctil/prevención & control , Estudios Retrospectivos , Prostatectomía/métodos , Resultado del Tratamiento
3.
Urol Case Rep ; 44: 102112, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35692631

RESUMEN

Renal oncocytoma (RO) represents about 7% of kidney tumors. They usually behave in a benign fashion, with a slow-growth rate. Patients are often asymptomatic and the tumour is found incidentally on imaging. Due to its wide variation of presentations and multiple radiological findings it is difficult to differentiate RO from renal-cell carcinomas. Interpretation of the images in the appropriate clinical context is crucial and supports the surgeon to avoid aggressive surgical procedures in favor of a nephron-sparing approach, whenever possible. We report a case of a 71-year-old female patient with a large calcified RO which was resected laparoscopically.

4.
J Surg Educ ; 78(5): 1725-1734, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33849788

RESUMEN

BACKGROUND: Partial nephrectomy (PN) is the preferred modality of treatment for small renal masses. Laparoscopic partial nephrectomy (LPN) has been adopted worldwide and a fundamental role is played by surgical skills. The need for skill instruction outside the operating room is well recognized in the modern models of surgery residency training. We aim to investigate the impact of residents' laparoscopic surgical skills training on the successful implementation of LPN in a reference public teaching hospital in southern Brazil. METHODS: We accessed all patients undergoing LPN by senior's urology residents at Hospital de Clínicas de Porto Alegre. Patients were stratified in 2 periods of time named 'LPN eras' 1 and 2, to report the training impact on the outcome. LPN era 1 was from October 2012 to February 2017 and LPN era 2 from March 2017 to June 2019. All the senior residents of LPN era 2 followed a simulation training divided into 4 years with a total training time of 244 hours before performing the LPN. Residents from LPN era 1 did not have simulation training. RESULTS: 124 patients underwent LPN during the study period, 53 (42.7%) of those were performed in LPN era 1 and 71 (57.3%) in LPN era 2. Baseline characteristics of the patients in the two groups were similar. The training performed by LPN era 2 residents was able to significantly reduce estimated blood loss, ischemia time and LOS with p value respectively 0.007, 0.001 and 0.001. LPN era 2 group also reached Trifecta in 77.5% of patients, being significantly more than in the LPN era 1 (p = 0.007). CONCLUSIONS: Simulation in residents surgical training was able to improve clinical outcomes in LPN. These data reinforce the fundamental importance of adequate residents training before performing surgery on a patient.


Asunto(s)
Neoplasias Renales , Laparoscopía , Entrenamiento Simulado , Urología , Humanos , Neoplasias Renales/cirugía , Nefrectomía , Resultado del Tratamiento
5.
World J Urol ; 39(2): 365-376, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32314009

RESUMEN

PURPOSE: This study aims to evaluate the impact of 5-alpha-reductase inhibitors (5ARI) for prostate cancer (PCa) primary prevention on specific and overall mortality (primary outcomes), the incidence of PCa diagnosis and disease aggressiveness (secondary outcomes). METHODS: We searched MEDLINE, EMBASE, Cochrane, ClinicalTrials and BVS through April 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement to identify randomized clinical trials (RCT) and cohort studies (CS). We included articles with data on mortality or PCa incidence for men using 5ARI previously to PCa diagnosis. RESULTS: Regarding the included studies, nine had data on mortality, 16 on PCa incidence and 12 on Gleason scores (GS). We found that the use of 5ARI had no impact on overall mortality (RR 0.93 95% CI 0.78-1.11) and PCa-related mortality (RR 1.35 95% CI 0.50-3.94), nor on high-grade PCa diagnosis (RR 1.06 95% CI 0.72-1.56). We identified a relative risk reduction of 24% in moderate-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.98) and low-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.97) Also, a reduction of 26% in overall PCa diagnosis was observed in the RCT subgroup analysis (RR 0.74 95% CI 0.65-0.84). CONCLUSION: 5ARI significantly reduced the risk of being diagnosed with PCa, not increasing high-grade disease, overall or cancer-specific mortality. Due to the relatively short mean follow-up of most studies, the mortality analysis is limited.


Asunto(s)
Inhibidores de 5-alfa-Reductasa/uso terapéutico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/prevención & control , Quimioprevención , Humanos , Masculino
7.
Neurourol Urodyn ; 38(1): 278-284, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30350876

RESUMEN

AIMS: To evaluate the accuracy of dynamic ultrasonography (DUS), as a feasible alternative diagnostic method to identify detrusor overactivity (DO) in patients with neurogenic bladder. METHODS: We performed concurrent analysis of 81 pairs of urodynamic study (UDS) and DUS, in 63 patients with myelomeningocele (MMC), from June 2014 to February 2017. The assessment focused on bladder behavior during the filling phase, DO evaluation, DO with leakage, compliance, and maximum cystometric capacity (MCC). RESULTS: Patient age ranged from 3 months to 34 years (median, 84 months); 47.6% were male. Overall, 9.5% of patients had chronic kidney disease, 20.6% had recurrent urinary tract infection, 19.05% had vesicoureteral reflux, and 69.8% had constipation. Anticholinergic therapy was used by 41.3% of patients. DO was observed in 45.67% of patients and DO with leakage in 42.6%. Mean bladder compliance was 10.39 mL/cmH2 O and normal MCC was 56.79%. DUS had 91.89% sensitivity in identifying DO, 88.64% specificity, 87.18% positive predictive value, 92.86% negative predictive value, and 90.12% accuracy, with a kappa coefficient of 0.8 (P < 0.001). CONCLUSION: MMC follow-up is essential because urinary parameters can change during patient growth. The standard examination is invasive and has related complications, making noninvasive evaluation a desirable alternative, like DUS. Our data suggest that DO and MCC can be evaluated using DUS in patients with MMC. UDS should be performed in patients with abnormal findings on ultrasound evaluation or those with worsening of urinary tract function.


Asunto(s)
Meningomielocele/diagnóstico por imagen , Vejiga Urinaria Neurogénica/diagnóstico por imagen , Vejiga Urinaria Hiperactiva/diagnóstico por imagen , Urodinámica/fisiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Meningomielocele/fisiopatología , Estudios Prospectivos , Sensibilidad y Especificidad , Ultrasonografía , Vejiga Urinaria Neurogénica/fisiopatología , Vejiga Urinaria Hiperactiva/fisiopatología
8.
PLoS One ; 13(7): e0200613, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30028845

RESUMEN

The role of molecular changes in the androgen receptor (AR) as AR variants (AR-Vs) is not clear in the pathophysiology of benign prostatic hyperplasia (BPH) and hormone-naïve PCa. The aim of the current work was to identify the presence of AR isoforms in benign tissue and primary PCa, and to evaluate the possible association with tumor aggressiveness and biochemical recurrence in primary PCa. The mRNA levels of full length AR (AR-FL) and AR-Vs (AR-V1, AR-V4 and AR-V7) were measured using RT-qPCR. The protein expression of AR-FL (AR-CTD and AR-NTD) and AR-V7 were evaluated by the H-Score in immunohistochemistry (IHC). All investigated mRNA targets were expressed both in BPH and PCa. AR-FL mRNA levels were similar in both groups. AR-V4 mRNA expression showed higher levels in BPH, and AR-V1 and AR-V7 mRNA expression were higher in PCa. The AR-V7 protein showed a similar H-Score in both groups, while AR-CTD and AR-NTD were higher in nuclei of epithelial cells from BPH. These results support the assumption that these constitutively active isoforms of AR are involved in the pathophysiology of primary PCa and BPH. The role of AR-Vs and their possible modulation by steroid tissue levels in distinct types of prostate tumors needs to be elucidated to help guide the best clinical management of these diseases.


Asunto(s)
Recurrencia Local de Neoplasia/patología , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Anciano , Núcleo Celular/patología , Células Epiteliales/citología , Células Epiteliales/patología , Perfilación de la Expresión Génica , Humanos , Calicreínas/sangre , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Próstata/citología , Próstata/patología , Próstata/cirugía , Antígeno Prostático Específico/sangre , Prostatectomía , Hiperplasia Prostática/cirugía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/cirugía , Isoformas de Proteínas/metabolismo , ARN Mensajero/metabolismo , Receptores Androgénicos/genética
9.
Urology ; 120: 253-257, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29958971

RESUMEN

OBJECTIVE: To present the results of technique of continent urinary diversion, described by Macedo, that allows the configuration of a tunnel with a flap of the ileal tube at the same segment created for the reservoir. METHODS: From January 2006 to November 2016, 29 patients were underwent a urinary diversion by Macedo's technique. Patients' demographics, hospitalization time, surgical time, follow up, continence rate, reservoir capacity, and postoperative complications were evaluated. RESULTS: Sixty-nine percent were male and the median age was 16.9 years. The main etiology was meningomyelocele (69.1%). The mean surgical time was 4.2 hours (standard deviation [SD] 0.9 range 2.9-6.3). The median length of hospital stay was 10 days (interquartile range: 11.3 range 5-51). The mean follow up was 3.3 years (SD 2.2 range 0.3-9.8). Procedure in the bladder neck was performed in 12 patients (41.3%). A continence rate of the catheterizable conduit was 82.8%.The reservoir capacity increased from 134.4 to 364.4 ml (P <.0001). The continence rate improved significantly (20 vs 74%, P <.0001). There was no change in glomerular filtration rates in the long term (143.1 vs 147, P = .45). Morbidity rate was 58% (25 complications in 17 patients), 72% occurred within the first 60 days and 60% were classified as Clavien-Dindo I or II. CONCLUSION: Except for publications from the original author, this is the first series described. The outcomes are similar, adding important data with respect to this technique. They show that the ileal reservoir is feasible, reproducible, and with good results.


Asunto(s)
Derivación Urinaria/métodos , Reservorios Urinarios Continentes , Adolescente , Adulto , Niño , Preescolar , Colon Sigmoide/cirugía , Femenino , Estudios de Seguimiento , Humanos , Íleon/cirugía , Tiempo de Internación/estadística & datos numéricos , Masculino , Meningomielocele/cirugía , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias , Estudios Retrospectivos , Adulto Joven
10.
J Surg Educ ; 75(4): 1075-1081, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29191757

RESUMEN

OBJECTIVE: Studies addressing the effect of laparoscopic experience on robotic skills have produced conflicting results. This study aimed to compare simulated robotic surgical tasks using the virtual reality simulator dV-Trainer between laparoscopically experienced surgeons and first-year surgical residents. DESIGN: A cross-sectional study. Participants completed 4 trials of the following tasks on the dV-Trainer: Peg Board 2, Ring and Rail 1, and Suture Sponge 1. Performance was recorded using a computerized built-in scoring algorithm. Scores and metrics were compared between groups 1 and 2 and between the first and subsequent trials. SETTING: Hospital de Clínicas, Porto Alegre, Brazil, a tertiary care teaching hospital. PARTICIPANTS: Twenty laparoscopically experienced surgeons (group 1) and 20 first-year surgical residents (group 2). All participants completed the study. RESULTS: The overall scores for Peg Board 2 (738.04 ± 267.83 vs 730.39 ± 225.31; p = 0.57), Ring and Rail 1 (919.03 ± 242.69 vs 965.84 ± 222.96; p = 0.13), and Suture Sponge 1 (563.62 ± 185.50 vs 560.99 ± 152.71; p = 0.67) did not differ significantly between groups 1 and 2. Group 1 had better results for master workspace range in Peg Board 2 and Ring and Rail 1. Group 2 had higher scores for economy of motion in Peg Board 2 and Ring and Rail 1 and for excessive instrument force in Ring and Rail 1. In both groups, the overall scores in the third and fourth trials were significantly higher than those in the first trial. CONCLUSIONS: There are no significant differences in the performance of simulated robotic surgical tasks between laparoscopically experienced surgeons and laparoscopically naïve surgical residents. Some slight differences were observed in specific metrics, but these differences were not sufficient to change the final results. We may assume that laparoscopic experience should not be an essential step in the initial learning curve of robotic surgery.


Asunto(s)
Competencia Clínica , Educación Médica Continua/organización & administración , Educación de Postgrado en Medicina/organización & administración , Laparoscopía/educación , Procedimientos Quirúrgicos Robotizados/educación , Entrenamiento Simulado , Adulto , Brasil , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad
11.
Int Braz J Urol ; 43(2): 304-310, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28128915

RESUMEN

OBJECTIVES: To assess patient satisfaction and quality of life after urethroplasty using two different self-reported outcome measures and to compare it with objective clinical data. MATERIALS AND METHODS: We prospectively collected data from 35 consecutive patients who underwent urethroplasty from January 2013 to September 2014. Patient demographics, International Prostate Symptom Score (IPSS), quality of life score, urethral stricture surgery patient-reported outcome measure (USS-PROM), maximum flow rate (Qmax) and post-void residual urine were collected before, two and eight months after surgery. Failure occurred when any postoperative instrumentation was performed. General estimation equation was used to compare the results and linear regression analysis to correlate both questionnaires with objective data. RESULTS: Mean age was 61 years. Urethroplasties were equally divided between anastomotic and buccal mucosa grafts and 19 patients (59.3%) had a previous urethral procedure. Overall success rate was 87.5%. IPSS improved from a mean 19 at baseline to 5.32 at 8 months (p < 0.001). The mean USS-PROM score also improved from 13.21 preoperatively to 3.36 after surgery (p< 0.001) and 84.3% of patients were satisfied or very satisfied with surgical results. Mean Qmax increased from 4.64mL/s to 11mL/s (p< 0.001). Strong negative correlation was found respectively between flow rate and USS-PROM (r=-0.531, p< 0.001) and with IPSS (r=-0.512, p < 0.001). CONCLUSIONS: Significant improvements in urinary symptoms and in quality of life are expected after urethroplasty and they are correlated with objective measures.


Asunto(s)
Satisfacción del Paciente/estadística & datos numéricos , Procedimientos de Cirugía Plástica/estadística & datos numéricos , Calidad de Vida , Autoinforme/normas , Uretra/cirugía , Estrechez Uretral/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Análisis Costo-Beneficio , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Periodo Posoperatorio , Estudios Prospectivos , Resultado del Tratamiento , Micción/fisiología , Adulto Joven
12.
BMC Health Serv Res ; 16: 227, 2016 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-27387752

RESUMEN

BACKGROUND: Many Brazilian patients with complex diseases who are treated in tertiary referral clinics have been stable for long periods. The main needs of these patients involve monitoring of risk factors and review of drug prescriptions, which could be satisfactorily done in primary care facilities. The goal of this protocol is to evaluate the safety and effectiveness of telemedicine services to support the transition of patients with stable chronic coronary artery disease from the tertiary to the primary level of care. METHODS/DESIGN: We designed a randomized non-inferiority protocol that will include 280 patients with stable coronary artery disease (for at least 12 months). Patients will be selected from the Ischemic Heart Disease Clinic in a tertiary care hospital in southern Brazil. Enrolled participants will be randomized into one of two groups: 12 months of follow-up at the same clinic; or 12 months of follow-up at a primary care facility with clinical support from a telemedicine platform including a toll-free line for physicians (intervention group). In the intervention group, decisions to refer patients to tertiary care during follow-up will be made jointly by primary physicians and medical teleconsultants. The groups will be compared in terms of the primary outcome-maintenance of baseline functional class 1 or 2 after 12 months. Secondary outcomes include control of risk factors and instability of the disease. DISCUSSION: We intend to determine the effectiveness of using telemedicine to qualify the transition of patients with chronic coronary disease from the tertiary to the primary level of care. This should facilitate the access of patients to the healthcare system, since care will be provided closer to their homes, and provide more opportunities for treatment of severe cases at tertiary care hospitals that are often overcrowded. TRIAL REGISTRATION: ClinicalTrials.gov # NCT02489565 - trial registration date May 13, 2015.


Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Atención Primaria de Salud , Telemedicina , Centros de Atención Terciaria , Brasil , Enfermedad Crónica , Femenino , Humanos , Masculino , Derivación y Consulta , Proyectos de Investigación , Factores de Riesgo , Telemedicina/métodos , Cuidado de Transición
13.
J Pediatr Urol ; 9(2): e99-101, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23287647

RESUMEN

Non-ischemic priapism in children is an uncommon entity usually related to blunt trauma in the perineal region and subsequent fistula formation into the corpus cavernosum. In this report we present the case of a 7-year-old boy who had undergone perineal trauma and developed non-ischemic priapism confirmed radiologically. He was treated by conservative measures along with ultrasonographic monitoring. We discuss the diagnostic approach, the radiologic findings and the mainly conservative management of this infrequent pathology.


Asunto(s)
Traumatismos en Atletas/complicaciones , Vendajes , Priapismo , Patinación/lesiones , Heridas no Penetrantes/complicaciones , Niño , Humanos , Masculino , Pene/irrigación sanguínea , Pene/lesiones , Priapismo/diagnóstico por imagen , Priapismo/etiología , Priapismo/terapia , Ultrasonografía
14.
Mol Biol Rep ; 40(4): 2955-62, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23269617

RESUMEN

Selection of reference genes to normalize mRNA levels between samples is critical for gene expression studies because their expression can vary depending on the tissues or cells used and the experimental conditions. We performed ten cell cultures from samples of prostate cancer. Cells were divided into three groups: control (with no transfection protocol), cells transfected with siRNA specific to knockdown the androgen receptor and cells transfected with inespecific siRNAs. After 24 h, mRNA was extracted and gene expression was analyzed by Real-time qPCR. Nine candidates to reference genes for gene expression studies in this model were analyzed (aminolevulinate, delta-, synthase 1 (ALAS1); beta-actin (ACTB); beta-2-microglobulin (B2M); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); hypoxanthine phosphoribosyltransferase 1 (HPRT1); succinate dehydrogenase complex, subunit A, flavoprotein (Fp) (SDHA); TATA box binding protein (TBP); ubiquitin C (UBC); tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ)). Expression stability was calculated NormFinder algorithm to find the most stable genes. NormFinder calculated SDHA as the most stable gene and the gene with the lowest intergroup and intragroup variation, and indicated GAPDH and SDHA as the best combination of two genes for the purpose of normalization. Androgen receptor mRNA expression was evaluated after normalization by each candidate gene and showed statistical difference in the transfected group compared to control group only when normalized by combination of GAPDH and SDHA. Based on the algorithm analysis, the combination of SDHA and GAPDH should be used to normalize target genes mRNA levels in primary culture of prostate cancer cells submitted to transfection with siRNAs.


Asunto(s)
Cultivo Primario de Células , Neoplasias de la Próstata/metabolismo , ARN Mensajero/genética , Expresión Génica , Humanos , Masculino , Neoplasias de la Próstata/genética , Estándares de Referencia
15.
BJU Int ; 107(4): 656-63, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20735391

RESUMEN

UNLABELLED: What's known on the subject? and What does the study add? Epithelial-mesenchymal transition (EMT) is involved in tumor progression where the underlying cellular changes associated with EMT have been identified in in vitro models and confirmed in a limited number of in vivo studies. ZEB1, which targets E-cadherin repression, is a transcriptional regulator that has been implicated in EMT, and is associated with uterine and colorectal cancers. Regulation of ZEB1 expression has been shown to involve different microRNAs (miRNAs), identifying a potential role for miRNA in EMT. In the present study we have identified novel expression of ZEB1 in bladder tumours and shown a role for ZEB1 in enhanced migration and invasion potential in in vitro assays. Confirmation of ZEB1 expression in bladder tumours was shown in tissue microarrays (TMAs). OBJECTIVE: To evaluate ZEB1 expression in bladder tumorigenesis and define a possible role for this transcription factor in urothelial carcinomas of the bladder (UCBs). MATERIALS AND METHODS: Five hundred and fifty-eight samples were assembled in 10 tissue microarrays (TMAs; 263 non-muscle-invasive Ta/T1/Tis, 295 muscle-invasive T2-T4). All tumours were transitional cell carcinomas (TCCs) and processed for immunohistochemistry to assess nuclear ZEB1 expression. Expression levels of ZEB1 were modulated in bladder carcinoma cell lines CUBIII or UM-UC-3 after forced expression or shRNA knockdown, respectively. Protein expression levels were determined using western blot analysis and transfectants were assessed for migration and invasion potential in standard in vitro assays. RESULTS: Nuclear ZEB1 expression was recorded in 22.8% of non-muscle-invasive UCBs and 21.7% of muscle-invasive UCBs, including 24.1% grade I/II and 21.1% grade III tumours, and absent in normal bladder mucosa. No significant correlation was observed for tumour stage and grade, nodal involvement, vascular invasion, metastasis and overall or cancer-specific survival. The introduction or knockdown of ZEB1 expression in bladder carcinoma cell lines showed enhanced or reduced migration and invasive potential, respectively. Changes in ZEB1 expression were accompanied by altered microRNA (miRNA) expression underlying events linked to epithelial-mesenchymal transition (EMT). CONCLUSION: The results in the present study showed novel expression of ZEB1 in bladder cancer in the absence of a link to clinical variables of change, including metastasis and survival. However, in vitro assays showed enhanced or reduced migration and invasion after the introduction or reduction of ZEB1, respectively, in transfected bladder cell lines. Modulation in expression of ZEB1 was closely linked to changes in the miR-200 family along with alternative known prognostic indicators of bladder tumour progression.


Asunto(s)
Proteínas de Homeodominio/metabolismo , Proteínas de Neoplasias/metabolismo , Factores de Transcripción/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Western Blotting , Línea Celular Tumoral , Movimiento Celular , Humanos , Inmunohistoquímica , Invasividad Neoplásica/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Matrices Tisulares , Neoplasias de la Vejiga Urinaria/patología , Homeobox 1 de Unión a la E-Box con Dedos de Zinc
16.
Urol Oncol ; 28(1): 39-48, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-18799331

RESUMEN

OBJECTIVE: The goal of this study was to identify a microRNA (miRNA) signature in bladder cancer capable of differentiating superficial from invasive disease. METHODS: Expression profiling of 343 miRNAs was performed in a microarray format using noninvasive and invasive bladder carcinoma cell lines with differential expression confirmed using a single molecule detection platform assay. miR-21 and miR-205 expression levels were determined in 53 bladder tumors (28 superficial and 25 invasive). Sensitivity, specificity, and a ROC curve were calculated to determine the discriminatory power of the miRNA ratio to predict invasion. Knockdown and forced expression of miRNAs was performed to evaluate their role in invasion. RESULTS: Expression profiling of 343 miRNAs, using noninvasive and invasive bladder cell lines, revealed significant differential expression of 9 miRNAs. Cell lines characterized as invasive showed a miR-21:miR-205 ratio at least 10-fold higher than the quantitative ratio obtained from non-invasive cell lines. The same expression ratio was determined in 53 bladder tumors. From these results, we recorded a sensitivity and specificity of 100% and 78%, respectively, using a cutoff of 1.79 to predict an invasive lesion. The area under the receiver operator characteristic curve was 0.89. Using in vitro invasion assays, we have demonstrated a role for miR-21 in establishing the invasive phenotype of bladder carcinoma cells. CONCLUSION: In this study, we identified a miR-21:miR-205 expression ratio that has the ability to distinguish between invasive and noninvasive bladder tumors with high sensitivity and specificity, with the potential to identify superficial lesions at high risk to progress.


Asunto(s)
MicroARNs/biosíntesis , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Anciano , Línea Celular Tumoral , Femenino , Humanos , Masculino , Invasividad Neoplásica , Fenotipo , Células Tumorales Cultivadas
17.
Int Urol Nephrol ; 41(2): 313-8, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-18800236

RESUMEN

OBJECTIVE: To assess the hormone secretion and viability of subcutaneous autotransplanted testicles in Wistar rats. STUDY DESIGN: Wistar rats were randomly divided into four groups: sham (group I, n = 4), bilateral orchiectomy (group II, n = 4), sliced autotransplantation group (group III, n = 4), and whole-testicle autotransplantation group (group IV, n = 4). Sexual behavior (genital sniffing, thrusting intromissions, mounts with pelvic thrusting frequency), serum testosterone levels, and body weight were measured eight weeks after the procedure. RESULTS: Subcutaneous autotransplantation elicited an increased number of mounts (P < 0.007) and intromissions (P < 0.009) and a significant reduction in the latency of these two behaviors (P < 0.034) compared with castrated animals. The frequency of sniffing of the bodies of sexually receptive females was not affected by castration (P = 0.326). Serum testosterone in whole autotransplantation group (219.23; 184.02-229.23) was higher than for the sliced autotransplantation group (0.74; 0.54-0.91) and bilateral orchiectomy group (0.59; 0.4-0.82; P < 0.05). We demonstrated that testicles transplanted without vascular anastomosis maintain their hormone secretion and exert neuroendocrine function on sexual behavior in rats. Autotransplantation could be an important alternative means of gonadal preservation for oncological patients considered for oncological therapies.


Asunto(s)
Tejido Subcutáneo/cirugía , Testículo/trasplante , Trasplante Autólogo/métodos , Anastomosis Quirúrgica , Animales , Supervivencia de Injerto , Masculino , Orquiectomía , Ratas , Ratas Wistar , Conducta Sexual Animal , Testículo/metabolismo , Testículo/patología , Testosterona/sangre
18.
J Urol ; 178(4 Pt 1): 1510-4, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17707060

RESUMEN

PURPOSE: We established the frequency of mutation of the epidermal growth factor receptor in bladder cancer and determined whether the activation status of epidermal growth factor receptor confers sensitivity to erlotinib. MATERIALS AND METHODS: The identification of mutations in the kinase domain (exons 18-21) of epidermal growth factor receptor was performed using single strand conformation polymorphism. The action of erlotinib was established within a bladder carcinoma cell panel using clonogenic assays and Western blot analysis. RESULTS: In 112 invasive bladder tumors a total of 6 mutations in 4 patients (3.6%) were identified in exon 21. Erlotinib demonstrated concentration dependent inhibition of growth where three cell lines showed high and 2 showed low sensitivity to the drug. Erlotinib inhibited activation of epidermal growth factor receptor, mitogen activated protein kinase, Akt and STAT3. However, the activation status of Akt was maintained in cell lines that were insensitive to the inhibitory action of erlotinib and were characterized as having undergone epithelial-to-mesenchymal transition. CONCLUSIONS: Although mutations in the coding region of epidermal growth factor receptor are rare in invasive bladder tumors, differential sensitivity to erlotinib was recorded within a panel of cell lines. Maintenance of the phosphorylation status of Akt in the presence of erlotinib along with epithelial-to-mesenchymal transition correlates with insensitivity to growth inhibition in bladder carcinoma cell lines. Even in the absence of epidermal growth factor receptor mutations erlotinib shows potential as a therapeutic agent for the treatment of bladder cancer.


Asunto(s)
Carcinoma de Células Transicionales/genética , División Celular/genética , Receptores ErbB/antagonistas & inhibidores , Quinazolinas/farmacología , Neoplasias de la Vejiga Urinaria/genética , Western Blotting , Carcinoma de Células Transicionales/patología , División Celular/efectos de los fármacos , Línea Celular Tumoral , Análisis Mutacional de ADN , Relación Dosis-Respuesta a Droga , Receptores ErbB/genética , Clorhidrato de Erlotinib , Exones/genética , Humanos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Factor de Transcripción STAT3/antagonistas & inhibidores , Ensayo de Tumor de Célula Madre , Neoplasias de la Vejiga Urinaria/patología
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