Substantial evidence suggests that cancer stem cells (CSCs) are the main cause of the initiation, progression and recurrence of tumors. Benzidine has been identified as a risk factor for bladder cancer. The aim of the present study was to investigate the effects of benzidine on bladder CSCs (BCSCs) and the possible mechanism underlying its action. The bladder cancer cell lines UM-UC-3 and EJ were maintained in serum-free medium and cells forming three-dimensional spheres were characterized as BCSCs. The sphere-forming cells were exposed to different concentrations of benzidine and vismodegib, and western blotting was performed to evaluate the expression of markers associated with CSCs and the Sonic hedgehog (SHH) signaling pathway. Flow cytometry was used to detect the distribution of cells in different phases of the cell cycle, and immunofluorescence staining was used to detect the protein expression of CD44. The results revealed that the levels of BCSC markers, namely CD133, CD44, aldehyde dehydrogenase 1-A1, Nanog and octamer-binding transcription factor-4, in the cell spheres were markedly elevated compared with those in cells cultured in serum-supplemented medium. Furthermore, benzidine increased the expression of BCSC markers and promoted the sphere-forming ability of the cells. In addition, it was observed that benzidine activated the SHH pathway, while inhibition of the Shh pathway using vismodegib diminished the promoting effects of benzidine on BCSCs. The findings of the present study indicate that benzidine promoted the stemness of BCSCs via activation of the SHH pathway, which may support further exploration of the molecular basis of the association between benzidine exposure and bladder oncogenesis.
Background Asthenozoospermia is a troublesome disease experienced by men in their reproductive years, but its exact etiology remains unclear. To address this problem, this study aims to identify the hub genes and crucial pathways in asthenozoospermia. Methods We screened two Gene Expression Omnibus (GEO) datasets (GSE92578 and GSE22331) to extract the differentially expressed genes (DEGs) between normozoospermic and asthenozoospermic men using the “Limma” package. Gene enrichment analyses of the DEGs were conducted using the “clusterProfiler” R package. The protein-protein interaction (PPI) network was then established using the STRING database. A miRNA-transcription factor-gene network was constructed based on the predicted results of hub genes using the RegNetwork database. The expression of four hub genes in asthenozoospermia and normal samples were verified using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting. Results We identified 271 DEGs, which included 218 upregulated and 53 downregulated in two asthenozoospermia datasets. These DEGs were observed to be markedly enriched in pathways with cell growth and embryonic organ development, phospholipase D signaling pathway, cGMP-PKG signaling pathway, and Wnt signaling pathway. The most significant genes were identified, including COPS7A, CUL3, KLHL7, NEDD4. We then constructed regulatory networks of these genes, miRNAs, and transcription factors. Finally, we found that the COPS7A was significantly upregulated in patients with asthenozoospermia, but CUL3, KLHL7 and NEDD4 were significantly downregulated compared with normal samples. Conclusion We applied bioinformatics methods to analyze the DEGs of asthenozoospermia based on the GEO database and identified the novel crucial genes and pathways in this disease. Our findings may provide novel insights into asthenozoospermia and identify new clues for the potential treatment of this disease.
Cite as: Can Urol Assoc J 2014;8(1-2):e44-7. http://dx.doi.org/10.5489/cuaj.1491 Published online January 14, 2014. AbstractWe present the case of a 34-year-old female, complaining of frequent micturition and progressive dysuria. By cystoscopy and computerized tomography, we found that she had multiple submucosal protuberant lesions in the entire bladder. After surgical excision, she has thus far showed no further signs of the disease. The postoperative histopathologic examination revealed a ganglioneuroma and leiomyomatosis. Urinary bladder paraganglioma is an unusual tumour; when it is combined with leiomyomatosis, it is extremely rare. We describe the main clinical presentation, diagnostic procedures, and pathologic features. We also review the English literature.
Cite as: Can Urol Assoc J 2014;8(11-12):e859-61. http://dx.doi.org/10.5489/cuaj.2169 Published online November 24, 2014. AbstractProstate cancer is one of the most common male malignancies, but it rarely metastasizes to the proximal ureter. We report a case of a 76-year-old man who presented with flank pain and lower urinary tract symptoms. Abdominal computed tomography scan revealed multiple filling defects at the middle of the left ureter, enlarged retroperitoneal lymph nodes, and probable psoas invasion. The patient underwent nephroureterectomy with excision of a cuff of bladder, and was found to have an adhesion between the middle part of left ureter and psoas intraoperatively. The pathological examination displayed positive immunohistochemical staining with prostate-specific antigen and prostate acid phostate, supporting the diagnosis of metastatic ureteral tumour from prostate cancer. In this case, periureteral soft tissue and ureteral muscular layer were infiltrated by metastatic tumour, whereas the mucosa was spared. The periureteral lymphatic pathway played an important role in the metastatic procedure of prostate cancer to the proximal ureter.
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