Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research Into Interstitial Cystitis / 대한배뇨장애요실금학회지

PURPOSE: We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder. METHODS: Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis. RESULTS: In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups. CONCLUSIONS: Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.

Atypical Epidermoid Cyst in Renal Pelvis and Histogenetic Implications / 대한배뇨장애요실금학회지

Since the renal epidermoid cyst is too rare, the mechanisms of squamous morphogenesis have not well characterized. A 73-year-old female was referred with an incidentally detected renal pelvis mass. Abdominopelvic computed tomography scan revealed a noncalcified soft tissue mass in the renal pelvis. Total nephroureterectomy was performed under the impression of a renal pelvis malignancy. The patient was discharged without postoperative complication. The outer surface of mass lesion was lined with urothelia and squamous epithelia, containing keratinous materials. The urothelia were positively stained against uroplakin II and cytokeratin 7, whereas almost of the squamous epithelia were negative with uroplakin II. The two different epithelia were generally sharply demarcated. Interestingly, some part of squamous epithelia contained uroplakin-positive and many more cytokeratin 7-positive cells. The atypical clinical features in our case can reconsider the diagnostic clues of renal epidermoid cysts that have been reported before, and the unique immunohistochemical results may understand the histogenetic implications of the lesion.

A Experimental Model of Bladder Cancer Using Nonviral Vector Expressing Uroplakin II Promoter and SV40 T Antigen / 대한비뇨기과학회지

PURPOSE: The goal of this study was to constructing a nonviral vector, expressing the chimeric gene of the SV40 T antigen and mouse uroplakin II promoter (UPII promotor), which was uniquely expressed in the urothelium, to aid in the treatment of bladder cancer by the creation of a tumor that will express itself in the bladder only, but that will have no effect on the other urothelium. MATERIALS AND METHODS: 36 female C3H/He mice, weighing 20-25grams, were used in this study. A UPII-GFP-liposome complex was installed into the bladder, with Enhanced Green Fluorescent Protein (EGFP), expressing the bladder mucosa, and analyzed via fluorescent microscopy. A UPII- SV40T-liposome complex was then administered into the bladders of the mice, and the bladder and ureter examined, grossly and microscopically, at 1, 2, 3 and 4 weeks, to find transitional cell carcinomas specific to the bladder, the degree of bladder cancer development, and whether the development was from superficial to deep tumors, as well as tumor metastasis. RESULTS: The expression of EGFP was found in all four mice after 2 days. No development of tumors was evident in any mice. However, of the 6 mice sacrificed 28 days after bladder instillation, urothelial dysplasia was evident in 4. There was no evidence of transient cell carcinomas in the ureter or renal pelvis in any of the mice, or of distant metastasis during the term of the study. CONCLUSIONS: This model of bladder cancer seems to take longer than other models for cancer formation as the carcinogen affects the DNA of urothelial cell for the formation of bladder cancer. However, our bladder cancer model was better than others due to its similarity for the processes of normal bladder cancer formation.

Effect of mouse uroplakin II promoter on human bladder cancer cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of gene expression of mouse uroplakin II (UPII) promoter on human bladder cell cancer cell line.</p><p><b>METHODS</b>The mRNA expression of different cell lines was quantified by RT-PCR. Green fluorescent protein (GFP) and luciferase (Luc) were used as reporter genes. The plasmids carrying UPII or GFP were constructed and transfected into human cell lines of bladder transitional cell cancer (BIU-87), kindey cancer (GRC-1), vascular endothelium (EC), lung cancer cell line (A549) and skin fibroblast cell line (Hs27). GFP activity of cells was detected by confocual microscopy and flow cytometry (FCM). Luciferase value was measured by luminometer (microplate) and luciferase to beta-galactosidase ratios (L/G values) were used for evaluating transfection efficiency.</p><p><b>RESULTS</b>RT-PCR showed high expression level of UPII mRNA in bladder cancer cell line BIU-87, whereas low level or no expression in nonbladder cancer cell lines. The activity of GFP in bladder cancer (BIU-87) cell was higher than that in the other cell lines (5 - 10/HP versus 0 - 2/HP), with 4.34% positive cells in BIU-87 detected by FCM, but no positive cell was found in the other cell lines. L/G values indicated that the luciferase expression in human bladder cancer cells transfected with mouse UPII promoter was 1.8 - 8.2-fold as high as that in the nonbladder cell lines.</p><p><b>CONCLUSION</b>Mouse UPII promoter gene can be expressed in a tissue-specific fashion in human urinary bladder cancer. It is capable of initiating transcription of reporter genes in human bladder cancer cell line.</p>