Increased DNA strand breaks and neoplastic transformation in human bladder cells treated with pioglitazone.

Pioglitazone (PIO), an oral hypoglycemic agent, is used in the treatment of type 2 diabetes. Some studies have suggested that an increased risk of bladder cancer with PIO exposure, while the others reported there is no such relationship. Therefore, it is doubtful whether PIO can increase the risk of bladder cancer.

Circadian coordination of ATP release in the urothelium via connexin43 hemichannels.

Day-night changes in the storage capacity of the urinary bladder are indispensable for sound sleep. Connexin 43 (Cx43), a major gap junction protein, forms hemichannels as a pathway of ATP in other cell types, and the urinary bladder utilizes ATP as a mechanotransduction signals to modulate its capacity. Here, we demonstrate that the circadian clock of the urothelium regulates diurnal ATP release through Cx43 hemichannels.

The Cytotoxicity and Genotoxicity of Particulate and Soluble Cobalt in Human Urothelial Cells.

Cobalt use is increasing particularly due to its use as one of the primary metals in cobalt-chromium-molybdenum (CoCrMo) metal-on-metal prosthetics. CoCrMo is a high-strength, wear-resistant alloy with reduced risk for prosthetic loosening and device fracture. More than 500,000 people receive hip implants each year in the USA which puts them at potential risk for exposure to metal ions and particles released by the prosthetic implants.

Intravital imaging of mouse urothelium reveals activation of extracellular signal-regulated kinase by stretch-induced intravesical release of ATP.

To better understand the roles played by signaling molecules in the bladder, we established a protocol of intravital imaging of the bladder of mice expressing a Förster/fluorescence resonance energy transfer (FRET) biosensor for extracellular signal-regulated kinase (ERK), which plays critical roles not only in cell growth but also stress responses. With an upright two-photon excitation microscope and a vacuum-stabilized imaging window, cellular ERK activity was visualized in the whole bladder wall, from adventitia to urothelium. We found that bladder distention caused by elevated intravesical pressure (IVP) activated ERK in the urothelium, but not in the detrusor smooth muscle.

Hexavalent chromium induces chromosome instability in human urothelial cells.

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants.

Pannexin 1 channels play essential roles in urothelial mechanotransduction and intercellular signaling.

Urothelial cells respond to bladder distension with ATP release, and ATP signaling within the bladder and from the bladder to the CNS is essential for proper bladder function. In other cell types, pannexin 1 (Panx1) channels provide a pathway for mechanically-induced ATP efflux and for ATP-induced ATP release through interaction with P2X7 receptors (P2X7Rs). We report that Panx1 and P2X7R are functionally expressed in the bladder mucosa and in immortalized human urothelial cells (TRT-HU1), and participate in urothelial ATP release and signaling.

Pannexin 1 involvement in bladder dysfunction in a multiple sclerosis model.

Bladder dysfunction is common in Multiple Sclerosis (MS) but little is known of its pathophysiology. We show that mice with experimental autoimmune encephalomyelitis (EAE), a MS model, have micturition dysfunction and altered expression of genes associated with bladder mechanosensory, transduction and signaling systems including pannexin 1 (Panx1) and Gja1 (encoding connexin43, referred to here as Cx43). EAE mice with Panx1 depletion (Panx1(-/-)) displayed similar neurological deficits but lesser micturition dysfunction compared to Panx1(+/+) EAE.

An hTERT-immortalized human urothelial cell line that responds to anti-proliferative factor.

Studies of the urothelium, the specialized epithelial lining of the urinary bladder, are critical for understanding diseases affecting the lower urinary tract, including interstitial cystitis, urinary tract infections and cancer. However, our understanding of urothelial pathophysiology has been hampered by a lack of appropriate model systems. Here, we describe the isolation and characterization of a non-transformed urothelial cell line (TRT-HU1), originally explanted from normal tissue and immortalized with hTERT, the catalytic subunit of telomerase.

Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma.

Background: MicroRNA regulate mRNA levels in a tissue specific way, either by inducing degradation of the transcript or by inhibiting translation or transcription. Putative mRNA targets of microRNA identified from seed sequence matches are available in many databases. However, such matches have a high false positive rate and cannot identify tissue specificity of regulation.

Identification of a microRNA panel for clear-cell kidney cancer.

Objectives: To identify a robust panel of microRNA signatures that can classify tumor from normal kidney using microRNA expression levels. Mounting evidence suggests that microRNAs are key players in essential cellular processes and that their expression pattern can serve as diagnostic biomarkers for cancerous tissues.

Methods: We selected 28 clear-cell type human renal cell carcinoma (ccRCC), samples from patient-matched specimens to perform high-throughput, quantitative real-time polymerase chain reaction analysis of microRNA expression levels.

Identification of novel epigenetic markers for clear cell renal cell carcinoma.

Purpose: We identified significantly hypermethylated genes in clear cell renal cell carcinoma.

Materials And Methods: We previously identified a set of under expressed genes in renal cell carcinoma tissue through transcriptional profiling and a robust computational screen. We selected 19 of these genes for hypermethylation analysis using a rigorous search for the best candidate regions, considering CpG islands and transcription factor binding sites.

Giant organ confined prostatic adenocarcinoma: a case report.

Introduction: Giant prostatic adenocarcinoma represents a rare and challenging treatment dilemma.

Case Presentation: We describe a case of an otherwise healthy 71-year-old African male who presented with a PSA of 5800 ng/ml and a prostate volume of over 1000cc. Unique aspects of this case include the size of the prostate, the apparent absence of distant metastases, and the safe usage of transabdominal biopsy of this mass.

Reflex UroVysion testing of bladder cancer surveillance patients with equivocal or negative urine cytology: a prospective study with focus on the natural history of anticipatory positive findings.

A proportion of patients under surveillance for recurrent bladder carcinoma with no immediate evidence of bladder tumor recurrence have positive multitarget fluorescence in situ hybridization (FISH; UroVysion, Vysis, Downers Grove, IL) results. The course of these "anticipatory positive" cases and the time to bladder tumor recurrence remains unknown. We followed up 250 patients with urine cytologic results, concurrent multitarget FISH, and cystoscopic examination for recurrent urothelial carcinoma.

Identification and characterization of renal cell carcinoma gene markers.

Microarray gene expression profiling has been used to distinguish histological subtypes of renal cell carcinoma (RCC), and consequently to identify specific tumor markers. The analytical procedures currently in use find sets of genes whose average differential expression across the two categories differ significantly. In general each of the markers thus identified does not distinguish tumor from normal with 100% accuracy, although the group as a whole might be able to do so.

Urothelial cancer biomarkers for detection and surveillance.

Cancer is a complex process, and the US cancer-specific death rate has not changed in the last 50 years. Cure of the disease usually results from early diagnosis and treatment. Urothelial carcinoma (UC) has the highest recurrence rate of any cancer and is the second most common cancer of the genitourinary tract.

Sling may hasten return of continence after radical prostatectomy.

Objectives: To place absorbable slings in 15 men at radical retropubic prostatectomy in an attempt to hasten recovery of continence.

Methods: Fifteen men underwent placement of a sling immediately after prostatectomy by a single surgeon. A strip of either porcine small intestine submucosa (SIS) or polyglactin mesh was placed beneath the anastomosis.

Effects of resveratrol on gene expression in renal cell carcinoma.

Studies have shown that Resveratrol (RE) can inhibit cancer initiation, promotion, and progression. However the gene expression profile in renal cell carcinoma (RCC) in response to RE treatment has never been reported. To understand the potential anticancer effect of RE on RCC at molecular level, we profiled and analyzed the expression of 2059 cancer-related genes in a RCC cell line RCC54 treated with RE.

Microarray gene expression profiling and analysis in renal cell carcinoma.

Background: Renal cell carcinoma (RCC) is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays.

Differential protein profiling in renal-cell carcinoma.

Characterizing the alterations of protein expression in cancer cells can be very useful in providing insight into the changes in the functional pathways and thus the fundamental mechanisms of cancer development at the molecular level. In this study, we profiled protein expressions in eleven pairs of primary cell cultures derived from renal-cell carcinoma (RCC) tissues and patient-matched normal kidney tissues utilizing two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Together with the immunoblot analysis of proteins from the RCC tissues, the study also demonstrated that the alterations of protein expression observed in RCC primary cell cultures reflected those observed in the original RCC tissues.

Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data.

Background: Renal cell carcinoma is a common malignancy that often presents as a metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal cell carcinogenesis, a number of genome-wide expression profiling studies have been performed. Surprisingly, there is very poor agreement among these studies as to which genes are differentially regulated.

Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology.

Purpose: The multitarget fluorescence in situ hybridization (FISH) probe set UroVysion (Vysis, Downers Grove, Illinois), containing probes to chromosomes 3, 7 and 17, and to the 9p21 band, has been recently shown to have high sensitivity and specificity for detecting transitional cell carcinoma. In this study we retrospectively tested 120 urine samples from patients with atypical, suspicious and negative cytology for whom concurrent and followup bladder biopsy data were available. We evaluated the ability of FISH to identify malignant cells in cytologically equivocal or negative cases.

Prognostic importance of resection margin width after nephron-sparing surgery for renal cell carcinoma.

Objectives: To examine the relationship between the width of the resection margin and disease progression in renal cell carcinoma (RCC) after nephron-sparing surgery (NSS). During NSS for RCC, it is standard practice to excise the tumor along with a surrounding margin of normal parenchyma (margin of resection) to ensure complete resection of the neoplasm. However, no agreement has been reached on how wide the margin of resection should be.