Project description:Inverted papilloma (IP) of the urinary bladder is a relatively rare neoplasm that accounts for < 1% of bladder tumor. Although generally accepted as a benign lesion, occasional reports of IP admixed with urothelial carcinoma (UC) or IP patients with synchronous or metachronous UC have raised a concern in the biologic potential of IP.
Project description:Purpose: The goals of this study are to compare 1. The transcription profile in KDM6A wildtype and KDM6A mutated urothelial bladder carcinoma. 2. The transcriptional changes in KDM6A mutated urothelial bladder carcinoma upon EZH2 inhibitor treatment.
Project description:Metastatic urothelial carcinoma (UC) of the bladder is associated with multiple somatic copy number alterations (SCNAs). We evaluated SCNAs to identify predictors of poor survival in patients with metastatic UC treated with platinum chemotherapy.
Project description:Metastatic urothelial carcinoma (UC) of the bladder is associated with multiple somatic copy number alterations (SCNAs). We evaluated SCNAs to identify predictors of poor survival in patients with metastatic UC treated with platinum chemotherapy.
Project description:PURPOSE: Despite over 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluate the role of Aurora A, identified as an upregulated candidate molecule in bladder cancer, in regulating bladder tumor growth. EXPERIMENTAL DESIGN: Gene expression in human bladder cancer samples was evaluated using RNA microarray and reverse-transcriptase PCR. The specific Aurora kinase A inhibitor MLN8237 (Millennium) was used to determine effects on bladder cancer cell growth using in vitro and in vivo models using malignant T24 and UM-UC-3 and papilloma-derived RT4 bladder cells. RESULTS: Urothelial carcinoma upregulates a set of 13 mitotic spindle associated transcripts, as compared to normal urothelium, including MAD2L1 (7.6-fold), BUB1B (8.8-fold), Aurora kinases A (5.6-fold) and Aurora kinase B (6.2-fold). Application of MLN8237 (10nM-1µM) to the human bladder tumor cell lines T24 and UM-UC-3 induced dose-dependent G2 cell cycle arrest, aneuploidy, mitotic spindle abnormalities, and apoptosis. MLN8237 arrested tumor growth when administered orally over 4 weeks in a mouse bladder cancer xenograft model (p<0.05). Finally, in vitro combination of MLN8237 with either paclitaxel or gemcitabine produced schedule-dependent synergistic antiproliferative effects in T24 cells when administered sequentially. CONCLUSIONS: Mitotic spindle checkpoint dysfunction is a common characteristic of human urothelial carcinoma, and can be exploited with pharmacologic Aurora A inhibition. Future studies that explore the mechanisms of spindle checkpoint failure in bladder cancer and evaluate the therapeutic role of Aurora kinases for bladder cancer patients would be of value. Tissue samples with urothelial cell carcinoma from bladder as well as normal references were collected and the gene expression profiles were compared. No technical replicates.
Project description:We are using circRNA expression profiling to identify novel circular RNA regulating EMT progression in urothelial carcinoma of the bladder.
Project description:Urothelial carcinoma of the bladder is characterized by significant variability in clinical outcomes depending on stage and grade. The addition of molecular information may improve our understanding of such heterogeneity and enhance prognostic prediction. The purpose of this study was to validate and improve published prognostic signatures for high-risk bladder cancer. We evaluated microarray data from 93 bladder cancer patients managed by radical cystectomy to determine gene expression patterns associated with clinical and prognostic variables.
Project description:Expression profiling by arrays Urothelial carcinoma (UC) can arise at any location along the urothelial tract, including the urethra, bladder, ureter or renal pelvis. Although tumors arising in these various locations demonstrate similar morphology, it is unclear whether the gene expression profiles are similar in the upper tract (ureter and renal pelvis) or in the lower tract (bladder and urethra) carcinomas, especially given their different embryologic origins. As differences may facilitate potentially different screening and treatment modalities, we sought to examine the relationship between urothelial carcinoma of the renal pelvis (rUC) and urothelial carcinoma of the bladder (bUC). Fresh tumor tissue was collected from patients with bUC (n=10) and benign mucosa from the bladder (n=7) was collected from individuals undergoing resection for non-UC conditions for comparison. Gene expression profiles from these samples were determined using high-throughput Affymetrix gene expression microarray chips. Bioinformatic approaches were used to compare gene expression profiles of these samples and those of rUC (n= 14) and normal kidney (n=14) that were mostly used in our previous publication. Using unsupervised analytic approaches, rUC and bUC were indistinguishable. When supervised analytic approach was used, a very small number of potentially differentially expressed genes was identified; these differences were most likely to be limited to a single pathway - the chloride ion binding activity pathway -which was more frequently activated in rUC than in bUC. We found that the gene expression profiles of UCs from the upper and lower tract were extremely similar, suggesting that similar pathogenic mechanisms likely function in the development of these tumors. The differential expression of genes in the identified pathway may represent a potential new avenue for detection of upper tract tumors. Tissue samples with urothelial cell carcinoma from lower tract (bladder) as well as normal references were collected and the gene expression profiles were compared with gene expression profiles of samples in our previously published data set . No technical replicates.
