CD147 overexpression is a prognostic factor and a potential therapeutic target in bladder cancer.

CD147, also named extracellular matrix metalloproteinase inducer (EMMPRIN), has been shown to be involved in the progression of malignancy by regulating expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). The goal of this study was to evaluate the role of CD147 in the biology of bladder cancer and to determine its potential as a therapeutic target. CD147 protein expression was detected by immunohistochemistry in 108 bladder cancers using a tissue microarray annotated with patient follow-up. In immunohistochemistry, CD147 protein expression was associated with poor prognosis (P<0.001), lymph node status (P<0.001), tumor stage (P=0.003), histologic grade (P=0.011). Multivariate analysis showed that CD147 overexpression was an independent prognostic factor (P=0.019). Infection of T24 bladder cancer cells with an adenovirus that expressed a small interfering RNA (siRNA) against CD147 efficiently inhibited CD147 protein and mRNA expression. This resulted in decreased proliferation, soft agar colony formation, migration, and invasion of T24 cells in vitro. Moreover, downregulation of CD147 reduced secretion of MMP-2 and MMP-9 and expression of VEGF in these cells. Our findings suggest that CD147 overexpression plays an important role in progression of bladder cancer, and CD147 could be a potential target of bladder cancer therapy.

[The clinical study for reducing bladder cancer recurrence after surgical treatment for renal pelvic carcinoma].

OBJECTIVE: To investigate the clinical methods for reducing bladder cancer recurrence after surgical treatment for renal pelvic carcinoma. METHODS: From October 1997 to December 2007, the data of 227 patients undergoing total nephroureterectomy for clinically localized transitional cell carcinoma of the renal pelvis with follow-up results were analyzed retrospectively, including 126 cases of male and 101 cases of female, and the age was 34 to 78 years old. There were 2 kinds of technique used in the dissection of bladder wall circumferentially around the ureteral orifice. Technique A was dissection along the ipsilateral ureter to the bladder wall. Technique B was dissection along the vas deferens to the bladder wall circumferentially around the ipsilateral ureteral orifice and division of the lateral vesical ligament to reach the seminal vesicle. Prophylactic intravesical chemotherapy included 3 method. Method 1 was intraoperative intravesical chemotherapy and then administrated once a week, 10 times in total. Method 2 was intraoperative intravesical chemotherapy and then administrated once a week from the 4(th) week after operation, 10 times in total. Method 3 was intravesical chemotherapy was given once a week from the 4(th) week after operation, 10 times in total. The time of follow-up was 1 to 10 years with regular cystoscopy. Chi-square test and Logistic regression were used to analyzed the recurrence rate of bladder cancer. RESULTS: Recurrence rate of bladder cancer was 27.8% (63/227). The recurrence rates of bladder cancer in patients using technique A and B were 18.0% (7/39) and 12.5% (3/24), respectively (P < 0.05). The postoperative recurrence rates of bladder cancer in patients using 3 kinds of intravesical chemotherapy regimen were 17.9% (11/67), 20.8% (10/48) and 33.3% (17/51), respectively. There was significant difference between the recurrence rates of patients using method 1 and method 3 intravesical chemotherapy (P < 0.05). CONCLUSION: Complete removal of the bladder mucosa circumferentially around the ureteral orifice, administration of the intraoperative intravesical chemotherapy instillation and instillation once a week may be a useful approach to reduce the recurrence of bladder cancer after operation for renal pelvic carcinoma.

[The clinical analysis of 62 cases of the urothelial inverted papilloma].

OBJECTIVE: To investigate the clinical manifestation, biological behavior, diagnosis and treatment of the urothelial inverted papilloma. METHODS: Sixty-two cases of urothelial inverted papilloma were analyzed retrospectively from January 1990 to August 2008. Of the 62 patients, 51 were men and 11 were women. The average age at presentation was 56.4 years old. Fifty-six cases were solitary tumors and 6 were multiple. The most common compliant was macroscopic hematuria. The tumor located at the ureter in 5 cases. Of these cases, 4 were treated by local excision, 1 by nephroureterectomy. One case of multiple ureteral inverted papilloma with coexistent bladder inverted papilloma was treated by total cystectomy. The tumor located at the bladder in 52 cases, with 44 treated by transurethral resection of bladder tumor, 6 by partial cystectomy, 2 by total cystectomy. Four cases had the tumor located at the urethra, with 1 treated by transurethral resection of tumor, 3 by tumorectomy. RESULTS: The postoperative pathological diagnosis of all the 62 cases was inverted papilloma, synchronous urothelial carcinoma in 7. Follow-up data were available in 49 cases. Two cases had a recurrence at 7 months and 79 months, respectively. Three case of subsequent transitional cell carcinoma developed 18 months, 2 years and 6 years later, respectively. CONCLUSIONS: Inverted urothelial papilloma is a kind of benign tumor. It should be differentiated from malignant urothelial tumors. Surgical operation is the main treatment choice. Cystoscopic surveillance and followup are necessary after the operation regularly.

Ability of alpha-lipoic acid to reverse the diabetic cystopathy in a rat model.

AIM: The present study was conducted to investigate whether alpha-lipoic acid (alpha-LA) is able to reverse impaired bladder function induced by diabetes in a rat model and to explore the possible mechanism mediating the effect. METHODS: Male Sprague-Dawley rats were divided randomly into 3 age-matched groups: control, diabetes mellitus (DM) treated with vehicle, and DM with alpha-LA treatment. The diabetic rats were induced by a single intraperitoneal (ip) injection of streptozotocin (60 mg/kg). Six weeks after the induction of DM, the two groups received another 6 weeks of treatment with vehicle or alpha-LA (100 mg/kg, i.p.). Body weight and blood glucose levels were measured weekly. The bladder function was evaluated by in vitro cystometry. The oxidative stress status was determined by biochemical methods, and the level of nerve growth factor was investigated by enzyme-linked immunosorbent assay. RESULTS: The streptozotocin-induced diabetic rats showed impaired bladder function characterized by increased bladder capacity, decreased bladder contractility (voiding efficiency), and an increase in residual urine. Treatment with alpha-LA significantly normalized the increased bladder capacity for inducing voiding, single-voided volume, and post-void residual volume. Alpha-LA treatment significantly reversed the increased level of malondialdehyde and reduced the activities of both superoxide dismutase and catalase. DM caused a decrease in the bladder nerve growth factor (NGF) level, and alpha-LA upregulated the level of NGF in the diabetic rat bladder. CONCLUSION: These results indicate that alpha-LA has a beneficial effect on diabetes-induced cystopathy by ameliorating oxidative stress and normalizing the NGF level in the bladder.

[RNA interference inhibits the expression of survivin and induces the apoptosis of PC-3 cells].

OBJECTIVE: To investigate the inhibitory effect of RNA interference (RNAi) on the expression of survivin mRNA and its inducibility of the apoptosis of PC-3 cells. METHODS: siRNA expression vectors were designed and constructed to be directed at survivin and transfected into PC-3 cells by Lipofectamine in 4 groups: plasmid A, plasmid B, negative sequence and control E. RT-PCR, Western blot and flow cytometry were used to detect the expression of survivin mRNA and the apoptosis of PC-3 cells. RESULTS: The expression rates of survivin protein were 18.94% +/- 0.63%, 16.35 +/- 0.23%, 46.41% +/- 0.76% and 46.20 +/- 1.47%, those of survivin mRNA were 27.94% +/- 1.43%, 24.51% +/- 1.37%, 49.46% +/- 0.71% and 48.49% +/- 1.32%, and the apoptosis rates of PC-3 cells were 12.80% +/- 1.33%, 16.48% +/- 1.00%, 3.03% +/- 0.62% and 2.96% +/- 0.41% respectively in different groups. CONCLUSION: RNAi can effectively inhibit the expression of survivin mRNA and induce the apoptosis of PC-3 cells.

[Study on multiple aldosterone-producing adenomas].

OBJECTIVE: To investigate the experience on diagnosis and treatment of multiple adrenal aldosterone-producing adenomas (APA). METHODS: Eighteen cases of multiple adrenal APA were analyzed retrospectively, which were admitted from October 1992 to April 2006. RESULTS: Adrenalectomy was performed for 4 cases of unilateral synchronous multiple APA, which were discovered with three adenomas by 3D-CT; bilateral tumor resection was performed for 6 cases of bilateral synchronous multiple APA. There were 8 cases of bilateral metachronous multiple APA, including 2 cases of ipsilateral recurrent adrenal APA after adrenal tumor removal, which underwent tumor resection. Another 6 cases were contralateral APA following adrenalectomy due to adrenal APA, and underwent tumor resection. After operation, the adrenal function seemed to be normal, and no recurrence had been found on follow-up. CONCLUSIONS: Unilateral multiple synchronous APA require adrenalectomy. Tumor resection should be performed for bilateral or asynchronous APA, and it is very important to preserve healthy adrenal tissue as much as possible. 3D-CT has much value on diagnosis of small APA, unilateral multiple synchronous APA and ipsilateral recurrent adrenal APA.

[Clinical analysis in diagnosis and treatment of 11 patients with hereditary renal cell carcinoma].

OBJECTIVE: To evaluate the diagnosis and treatment of hereditary renal cell carcinoma. METHODS: Clinical data of 11 patients with hereditary renal cell carcinoma were analyzed retrospectively. Eight patients were male and 3 were female, age ranged from 32 to 67 (mean: age 48 years). Four cases were bilateral renal cell carcinoma, and 4 were multiple renal cell carcinoma. Two cases were diagnosed as Von Hippel-Lindau syndrome, 6 as familial clear cell renal cell cancer, and 3 as hereditary papillary renal carcinoma. RESULTS: Ten patients performed nephron-sparing surgery and/or radical nephrectomy and 1 had no operation. The patients were followed up from 12 to 114 months. Tumor recurrence was observed in 4 patients, 1 patient died of tumor metastasis, and 2 died of other causes. Four patients survived free of tumor. CONCLUSIONS: Hereditary renal carcinoma appears in the youth, and it is predominantly multiple and bilateral. Nephron-sparing surgery is the standard method of treatment for the patients.

[The role of protein kinase C alpha in recurrence of superficial bladder carcinoma].

OBJECTIVE: To investigate the relationship of protein kinase C-alpha (PKCalpha) expression/activation with tumor differentiation and resistance to chemotherapy drugs in superficial bladder carcinoma. METHODS: Expression of PKCalpha was measured by Western-blot analysis in 76 samples including tumor and normal tissues, respectively. A human RT4 bladder cancer cell line stably expressing green fluorescent protein (GFP)-PKCalpha (RT4/PKCalpha) was established. The sensitivity of the RT4/PKCalpha and parental cells to adriamycin (ADM) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The change of sensitivity of the RT4/PKCalpha to ADM were observed under the conditions of PKC activation and inhibition, respectively. RESULTS: Total level of PKCalpha expression and the ratio of the amount of PKCalpha expression or PKC activity in membrane to that in cytosol (M/C) were all more higher in cancerous tissues than in normal tissues (P < 0.01); With the increase of tumor grade, the relative level of PKCalpha expression significantly increased in membrane (P < 0.01) and decreased in cytosol (P < 0.01), M/C of PKCalpha was significantly elevated (P < 0.01), and total relative level of PKCalpha expression significantly increased (P < 0.01). Thirty-eight cases recurred during the follow-up period in total seventy cases. Multivariate analysis showed that high M/C of PKCalpha was independent prognostic factor for tumor recurrence after standard ADM treatment in the 2-year follow-up (RR = 3.98, 95% CI 1.22-5.68, P = 0.03). Transfection of PKCalpha increased resistance of RT4 cells to ADM [resistance index (RI): 6.97, t = 3.24, P < 0.01]. PKCalpha activation further greatly promoted the resistance (RI: 148.11, t = 5.18, P < 0.001) while inhibition of PKCalpha did conversely (RI: 1.6, t = 1.29, P > 0.05). CONCLUSION: The abnormal activation and expression level of PKCalpha closely correlate with both tumor grade and intrinsic resistance to ADM in patients with superficial bladder carcinoma.

[Treatment of glandular cystitis].

OBJECTIVE: To improve the therapeutic results of patients with glandular cystitis. METHODS: One hundred and twenty-seven patients with glandular cystitis were treated according to their different etiological factors. The therapeutic methods included anti-infection, obstruction relief, bladder irrigation, transurethral resection, partial cystectomy, total cystectomy. RESULTS: The patients who were associated stones and foreign bodies (50%) were cured spontaneously with an effective rate of 94%. The effective rate in patients with low urinary tract obstruction was 84%. Patients with simple urinary tract infection (53%) were cured spontaneously after anti-infection therapy. The effective rate, recurrence rate and malignancy rate in patients without associated diseases were 71%, 46% and 21% respectively. CONCLUSIONS: Cystitis glandularis should be treated according to different etiological factors.

[The role of cell adhesion, multidrug resistance and cell proliferation in short-term recurrent cases with T1G3 superficial bladder cancer].

OBJECTIVE: To evaluate the roles of cell adhesion, multidrug resistance and cell proliferation in short-term recurrent cases with superficial bladder cancer, and the prognostic value of the three indexes. METHODS: Immunohistochemical staining for E-cad, P-gp and Ki-67 was performed on the tumors of 100 patients with stage T0-T1 transitional cell carcinoma of the bladder who had been included in a retrospective research by follow-up. RESULTS: E-cad and P-gp expression was positive in 51 (43.2%)and 17 (14.4%) of the tumors, respectively and mean proliferation index (PI) was 22.1%. The decrease in E-cad expression was accompanied with the increasing recurrent episodes (P < 0.05), while increase of P-gp expression and PI were accompanied with the increasing recurrence episodes (P < 0.05). There was significant difference according to E-cad, P-gp positivity and between T(1)G(3) patients and no-T(1)G(3) patients (P < 0.05). There was negative correlation of E-cad expression with P-gp expression and PI. CONCLUSIONS: Minimum adhesion, strong drug resistance and maximum proliferation are the main factors that promote short-term recurrence of superficial bladder cancer and also the inherent reasons for easy recurrence and high malignancy of T(1)G(3) tumors. During this course, the three aspects may interact.