GPNMB overexpression is associated with extensive bone metastasis and poor prognosis in renal cell carcinoma.

Glycoprotein non-metastatic protein B (GPNMB) promotes bone metastasis (BM) in various types of cancer. However, GPNMB expression and its function in patients with renal cell carcinoma (RCC) and BM is still unknown. Therefore, the clinical significance of GPNMB and its biological function in RCC with BM was investigated in the present study. A total of 31 patients with RCC and BM were retrospectively collected. The association between GPNMB protein expression level on the primary tumor and the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier analysis was used to investigate the association between GPNMB expression and the prognosis of the patients. The effects of GPNMB inhibition on cell proliferation, migration and invasion in RCC cells were investigated using short hairpin (sh)RNA. High GPNMB expression level was significantly associated with the number (P=0.001) and the extent of BM (P=0.001), Fuhrman grade (P=0.037), and ERK expression level (P=0.003) of the primary tumor. In addition, GPNMB overexpression was significantly associated with poor prognosis with respect to overall survival time (P=0.001). Furthermore, a specific shRNA sequence targeting the GPNMB gene was constructed and transduced into the ACHN cell line, using a lentivirus vector to obtain a stable cell line with low mRNA expression level of GPNMB. Low GPNMB expression level inhibited RCC cell proliferation, which was measured using a Cell Counting Kit-8 assay. Cell migration and invasion ability was significantly decreased in GPNMB knockdown RCC cells compared with that in cells transduced with the negative control shRNA. In addition, the protein expression levels of phosphorylated ERK were lower in the GPNMB shRNA-transduced ACHN cells compared with those in the control cells. Therefore, these results suggested that GPNMB plays an important role in tumor progression in RCC with BM. Furthermore, it might serve as a predictive marker for BM and as a poor prognostic factor in RCC with BM. GPNMB downregulation suppressed the proliferation, migration and invasion of the RCC cells, which may be mediated through the inhibition of the ERK signaling pathway.

[Management of female urethral obliteration with the rotary excision appliance].

OBJECTIVE: To describe a new technique using the rotary excision appliance for the treatment of female urethral obliteration and to evaluate the effect of the management. METHODS: Between October 2000 and July 2013, 5 cases of female urethral obstruction (age from 23 to 65 years, time to treatment from 3 to 60 months, obliteraion length from 0.5 to 1.8 cm) were managed using the rotary excision appliance and the patients had been followed up. RESULTS: After a mean of 32.4 months (range: 5 to 75 months) of follow-up, normal micturation had been achieved in all the patients. The maximal urinary flow rate (MFR) ranged from 15 to 28 mL/s (mean 20.6 mL/s). Three patients were continent and 2 patients had slight incontinence. CONCLUSION: The rotary excision appliance is a useful instrument for the management of female urethral obliteration. Our Long-term follow-up provides further support for use of this technique by demonstrating that urethral continuity can be established without increased incidence of stricture formation or incontinence.

[Association between HPV DNA and disease specific survival in patients with penile cancer].

OBJECTIVE: To examine the prevalence of human papilloma virus (HPV) in penile squamous-cell carcinomas (SCCs), explore the relationship between HPV and clinicopathological variables and determine its value for predicting disease-specific survival. METHODS: We retrospectively collected clinicopathological data of 28 patients with penile squamous cell carcinomas from 2000 to 2009 at Beijing Cancer Hospital, Beijing Hospital and Peking University People's Hospital. Polymerase chain reaction (PCR) was used to detect the presence of HPV DNA in tumor specimens. Regular follow-ups were conducted. Disease-specific survival plots were drawn with the Kaplan-Meier method and compared with the Log-Rank test. Cox proportional hazard analysis was applied to assess the independent effects of several prognostic factors on survival. RESULTS: HPV DNA was detected in 7/28 samples. After sequencing, all 7 samples were confirmed to be HPV-16 type. The median follow-up period was 60 (6-150) months. By the time of analysis, 8/28 patients died. HPV DNA was not significantly associated with age, pathological grading, pathologic T stage or lymph node metastasis (P = 0.191, 0.165, 1.000, 0.639 respectively). Cox multivariate regression analysis indicated that lymph node status (HR = 5.5, P = 0.023) was an independent predictive factor of disease specific survival, followed by pathological T classification (HR = 11.0, P = 0.035) . The 5-year disease-specific survival in patients with HPV DNA positive was higher than that in those with HPV DNA negative (67% vs 58%) . But survival had no significant differences (P = 0.431). CONCLUSIONS: Higher pathologic T stage and lymph node metastasis are independent prognostic factors for worse survival. And mortality does not increase markedly in penile cancer patients with HPV DNA positive.

[Penile cancer and human papillomavirus infection].

Human papillomavirus (HPV) infection is one of the major risk factors for penile cancer. This article presents an overview on the biological characteristics of HPVs, HPV infection in penile cancer, possible carcinogenic mechanisms of HPV, prognostic value of HPV in penile cancer, and HPV vaccine.

[Correlation of CD82 and hTERT expressions and HPV infection with penile cancer].

OBJECTIVE: To study the correlation of the expressions of CD82 and hTERT and HPV infection with the clinical pathological features of penile cancer and identify their prognostic significance in the lymphatic metastasis of the disease. METHODS: A total of 44 patients underwent partial or radical penectomy and lymph node dissection. The expressions of CD82 and hTERT were determined by immunohistochemistry, and HPV infection was detected by PCR. RESULTS: The positive rates of CD82, hTERT, and HPV DNA in penile carcinoma were 47.7%, 38.6% and 25.9%, respectively. The amplified HPV DNA was HPV-16. The pathological stage and hTERT expression were positively correlated with inguinal lymph node metastasis of penile cancer (P = 0.032, P = 0.041), and so was the pathological stage with the expression of CD82 (P = 0.045), but neither the pathological stage, nor the expression of CD82 or the positive rate of HPV DNA showed any correlation with lymph node metastasis (P = 0.627, P = 0.094, P = 0.633). CONCLUSION: The pathological grade and hTERT expression are independent prognostic factors for lymph node metastasis in penile carcinoma. These features help the prognosis and identification of the patient at the risk of nodal metastasis.