RESUMEN
OBJECTIVE: To evaluate archival tissue specimens from bladder tumours and seek molecular changes in samples collected over seven decades previously, as although the frequencies of some cancer types have remained stable during the last 50 years, the incidence of others, including bladder tumours, has increased significantly, and molecular analyses of bladder cancer over periods with an increasing incidence are of interest as the findings might reflect varying external influences. MATERIALS AND METHODS: Immunohistochemical staining with the biological markers p53 protein, p16 protein, epidermal growth factor receptor (EGFR), cytokeratin 7 and high molecular weight 34betaE12 cytokeratin (HMW-cytokeratin, characteristic of basal cells) was used on archival, paraffin wax-embedded autopsy/biopsy tissue material collected from 144 patients with invasive bladder cancer (World Health Organisation grade II and III). The cases were selected from the periods 1932-48, 1950-59, 1960-70 and 1990-2004. Control immunohistochemistry was done on available normal tissue (i.e. connective and fatty tissue, heart, lungs and normal urinary bladder epithelium) obtained from the autopsies. RESULTS: The normal tissues were all largely negative for EGFR, had <1% positively stained nuclei for p53 and strong positive reactions for p16, and in epithelial tissues the two cytokeratins were detected. The positive scores for HMW-cytokeratin in the tumour tissue decreased significantly from approximately 90% to 30% over the 70 years. For p53 there was a higher fraction of positive scores (borderline significant) with time. The p16-positive tumours showed no significant variation, with the highest frequency of positive scores in recent years. Overexpression of EGFR in the tumours was significantly correlated with the occurrence of HMW-cytokeratin and decreased from approximately 85% to 65% (not significant), with the lowest frequency in the samples from 1990 to 2004. Autolysis after death or long storage periods did not compromise good quality in the histochemical analyses of the autopsy tissue. CONCLUSION: The higher frequency of HMW-cytokeratin, lower p53 accumulation and more EGFR expression in grade II and III urinary bladder carcinomas from the 1930s could indicate different phenotypes in bladder cancer during this 70-year period. The successful detection of these protein markers in old archival material allows larger retrospective studies that might increase the understanding of molecular carcinogenesis in bladder cancer.
Asunto(s)
Adhesión en Parafina , Conservación de Tejido , Neoplasias de la Vejiga Urinaria/química , Anciano , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Receptores ErbB/análisis , Humanos , Inmunohistoquímica/normas , Queratina-7/análisis , Factores de Tiempo , Bancos de Tejidos , Proteína p53 Supresora de Tumor/análisis , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVES: To assess the clinical efficacy of ProstaLund Feedback Treatment (PLFT) using the CoreTherm device versus transurethral resection of the prostate (TURP) and prostate enucleation surgery. METHODS: We performed a prospective, randomized, controlled, multicenter study of 120 patients with symptomatic benign prostatic hyperplasia and persistent urinary retention requiring an indwelling catheter or clean intermittent catheterization. The primary efficacy variables were success in catheter removal and symptom improvement. RESULTS: Of the 120 patients, 79% and 88% were catheter free after PLFT and surgery, respectively. The bother score (quality-of-life question) decreased from 4.6 in both groups before treatment to 1.4 in the PLFT group and 0.8 in the surgery group at 6 months of follow-up. The peak urinary flow rate was 13.4 mL/s after PLFT and 18.0 mL/s after surgery. The mean catheterization time was 34 days in the PLFT group and 5 days in the surgery group. CONCLUSIONS: PLFT is an effective alternative to surgical treatment in this group of catheterized patients. The risk of severe complications is reduced using PLFT, and an excellent treatment option can thereby be offered to this high-risk patient group who earlier could be treated only with lifelong catheterization.
Asunto(s)
Hiperplasia Prostática/cirugía , Resección Transuretral de la Próstata/métodos , Retención Urinaria/etiología , Anciano , Humanos , Masculino , Estudios Prospectivos , Hiperplasia Prostática/complicaciones , Resultado del Tratamiento , Cateterismo Urinario , Retención Urinaria/terapiaAsunto(s)
Publicidad , Industria Farmacéutica , Imidazoles , Inhibidores de Fosfodiesterasa , Piperazinas , Disfunción Eréctil/tratamiento farmacológico , Humanos , Imidazoles/uso terapéutico , Masculino , Erección Peniana/efectos de los fármacos , Inhibidores de Fosfodiesterasa/uso terapéutico , Piperazinas/uso terapéutico , Sulfonas/uso terapéutico , Triazinas/uso terapéutico , Diclorhidrato de VardenafilRESUMEN
As bladder cancer is potentially lethal, the development of effective and tolerable therapeutic options is vital. In the present assay, we examined the in vitro effect of paclitaxel (Taxol) on the transitional cell carcinoma (TCC) cell line Hu1703He. Our model has several advantages over other in vitro models. The microenvironment in vivo is mimicked, and the important interaction between benign and malignant cells is consequently preserved in vitro. In addition, the results are not influenced by humoral immune factors. LacZ transfection and exposure to X-gal resulted in blue staining of the tumour cells and made them easy to visualise in sections. Tumour cell aggregates were cultured with continuous paclitaxel exposure to examine the drug's effect on tumour cell migration in monolayer and spheroidal growth in suspension culture. Paclitaxel treatment inhibited both tumour cell migration and spheroidal growth. Invasion was studied by confronting paclitaxel-treated and untreated tumour spheroids with benign bladder fragments in suspension culture. The co-cultures were followed for 4 weeks. Growth of the tumour cells encircling the bladder fragment and cellular infiltration of the bladder stroma were both inhibited by paclitaxel treatment. The expression of MMP-1 in tumour cells was also negatively influenced.