Purpose: Minimally invasive methods of predicting the risk of muscle-invasive urothelial bladder carcinoma may expedite appropriate therapy and reduce morbidity and cost. Experimental Design: Here, capillary electrophoresis coupled mass spectrometry was used to identify urinary polypeptide bladder cancer biomarkers in 127 patients. These markers were used to construct a panel discriminating muscle-invasive from noninvasive disease, which was refined in 297 additional samples from healthy volunteers, patients with malignant and nonmalignant genitourinary conditions. Sequencing of panel polypeptides was then done. Finally, the ability of the panel to predict muscle-invasive disease was evaluated prospectively in 130 bladder carcinoma patients. Four sequenced polypeptides formed a panel predictive of muscle-invasive disease. Conclusions: Use of urinary peptides seems promising in estimating the probability a patient harbors muscle-invasive urothelial bladder cancer. These peptides may also shed novel insights into the biology of bladder tumor progression not obtainable by other methods. Clinical trials seem warranted to evaluate the effect of this approach on practice.
Cell line models aid in understanding cancer aggressiveness. The aim of this study was the establishment of a metastatic variant (T24M) of the T24 bladder cancer cell line and its initial characterization at chromosomal and proteomic levels. T24M were spontaneously developed in mice from T24 cells, following cycles of subcutaneous injections and culture in vitro. Transwell migration assays and injections in mice revealed increased migration and tumorigenic properties of T24M compared to the T24 cells. Cytogenetic analysis demonstrated that T24M retained several karyotypic characteristics of the parental cells and also acquired novel chromosomal aberrations related to aggressive bladder cancer. Proteomic analysis of the T24 and T24M cells by 2-DE and MS led to the generation of their 2-DE proteomic map and revealed differences in multiple proteins. These include proteases of the lysosomal and proteasome degradation pathways, mitochondrial and cytoskeletal proteins. The 2-DE findings were confirmed by immunoblotting of cell lysates and immunohistochemistry of bladder cancer tissue sections for cathepsin D and activity assays for proteasome. Collectively, our results suggest that the T24M cells reflect many known chromosomal and proteomic aberrations encountered in aggressive bladder cancers but also provide access to novel findings with potentially clinical applications.
The protein components of urine are useful indicators of renal function and human health in general. Urine samples are easily attainable making them ideal substrates for biomarker research. Analysis of the urine proteome however, has been hindered by the great variability of the urine specimens, and the presence of various proteins in low abundance or modified forms. To alleviate some of these problems urine samples from five different individuals were pooled, concentrated and the proteome characterized by a combination of preparative electrophoresis and 2-DE, followed by PMF. A total of 778 protein spots corresponding to 141 different gene products were identified. In comparison, 171 spots corresponding to 44 unique proteins were identified in the unfractionated starting material. Among the proteins identified from the preparative electrophoresis were many of low abundance such as proteins involved in signal transduction. Furthermore, the median molecular mass of the identified proteins from the preparative electrophoresis was significantly lower in comparison to the proteins identified from the unfractionated starting material (39 886 Da versus 71 317 Da, respectively). Concluding, application of this methodology provides a coherent analysis of the urine proteome and contributes to the generation of the urine protein map in health and disease.
TRUS is more accurate than transabdominal ultrasound in predicting adenoma volume in patients with BPH and its standard use might lead to fewer open approaches, with consequent less morbidity and hospitalization.
The evolution of tumor characteristics at presentation in a single institution is apparent within the last 25 years. Major changes were noticed within organ-confined and small tumors and call for familiarization of urologists with nephron-sparing techniques and novel ablation technologies.
Segmental testicular infarction is a rare cause of acute scrotum and only a few cases have been reported. Torsion of the testis, testicular tumor and infection are important differential diagnoses. The present case report describes a 61-year-old man with left-sided testicular pain increasing over 24 h. The diagnosis of segmental testicular infarction was considered after color Doppler ultrasound of the left scrotum and it was confirmed by surgical exploration and pathological examination. Although it is uncommon, segmental testicular infarction should be taken into consideration when acute scrotal pain is encountered, especially for younger patients, since a testis-sparing treatment strategy can be performed.
A 62-year old male patient presented complaining of intermittent macroscopic hematuria. The ultrasonographic investigation revealed a hydronephrosis of remarkable degree with indiscrete renal parenchyma. The abdominal computed tomography scan identified a ureteral lesion with proximal dilatation, hydronephrosis and a functionless ipsilateral renal unit. The retrograde urography showed a 4-cm lesion with multiple filling defects and a smooth contour. The endoscopic examination showed an exophytic lesion, highly suspicious for malignancy. Urine cytology revealed atypia. Right nephroureterectomy was performed and the pathology revealed a ureteral inverted papilloma (UIP). Polymerase chain reaction examination for the presence of human papilloma virus, using GP5+/6+ consensus primers, was negative. The presence UIP should be considered in patients with urotheleal lesions in the ureter when the diagnostic workup for malignancy is inconclusive. The clinical course of the disease seems to be favorable.
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