Cripto-1 expression in patients with clear cell renal cell carcinoma is associated with poor disease outcome.

BACKGROUND: Cripto-1 (CR-1) has been reported to be involved in the development of several human cancers. The potential role of CR-1 in clear cell renal cell carcinoma (ccRCC) is still not clear. METHODS: CR-1 expression was evaluated in ccRCC tissues by Real-time quantitative PCR, Western blot and immunohistochemistry. Serum levels of CR-1 were tested by enzyme-linked immunosorbent assay (ELISA). The clinical significance of CR-1 was analyzed. The effects of CR-1 on cell proliferation, migration, invasion and angiogenesis were investigated in ccRCC cell lines in vitro and in vivo, and markers of the epithelial -mesenchymal transition (EMT) were analyzed. The impact of CR-1 on Wnt/ß-catenin signaling pathway was also evaluated in vitro and in vivo. RESULTS: CR-1 expression was elevated in ccRCC tumor tissues and serum samples. CR-1 expression was correlated with aggressive tumor phenotype and poor survival. Ectopic expression of CR-1 significantly promoted cell proliferation, migration, invasion and angiogenesis whereas knockdown of CR-1 inhibited these activities both in vitro and in vivo. Moreover, we found that CR-1 induced EMT and activated Wnt/ß-catenin signaling pathway both in vitro and in vivo. CONCLUSIONS: These results suggest that CR-1 is likely to play important roles in ccRCC development and progression, and that CR-1 is a prognostic biomarker and a promising therapeutic target for ccRCC.

Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma.

BACKGROUND: Fork head box M1 (FoxM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC). Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models. METHODS: Real-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA) in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed. RESULTS: FoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P <0.001), lymph node metastasis (P = 0.01), distant metastasis (P = 0.01), TNM stage (P < 0.001) and histological grade (P = 0.003). The Kaplan-Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P < 0.001). FoxM1 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis (P = 0.008). Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF), resulting in the inhibition of migration, invasion, and angiogenesis. CONCLUSIONS: These results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a promising therapeutic target for ccRCC.

[Sperm retrieval and the predictive parameter of non-obstructive azoospermia: a meta-analysis of literatures 1990 to 2008].

OBJECTIVE: To investigate which sperm retrieval technique is suitable for the non-obstructive azoospermia (NOA) patient, and to identify the relevant predictive parameters. METHODS: Literatures on NOA patients who had undergone sperm retrieval and pathological examination of testis were identified from Cochrane Library, CNKI and Medline (1990 to 2008) and analyzed. RESULTS: Twenty-five articles were enrolled. When testicular fine needle aspiration (TEFNA) was compared with testicular sperm extraction (TESE), the sperm retrieval rate of the former was 23.0%, significantly lower than that of the latter (52.2%, RR: 0.49, 95%CI: 0.41 - 0.60, P < 0.05); and when TESE was compared with micro-surgical testicular sperm extraction (mTESE), the sperm retrieval rate of the former was 35.7%, significantly lower than that of the latter (54.6%, RR: 0.70, 95%CI: 0.50 - 0.98, P < 0.05). Sperm retrieval rate was closely correlated with the testicular pathological category of the NOA patients. The sperm retrieval rates of the patients with hypospermatogenesis (HS), maturation arrest (MA), and Sertoli cell only syndrome (SCOS) were 76.7%, 46.2%, and 32.8% respectively (RR: 1.65, 2.40, 1.50; 95%CI: 1.21 - 2.91, 1.85 - 6.90, 1.02 - 2.26, P < 0.05). CONCLUSION: mTESE is the best sperm retrieval technique. A better to choice before deciding the treatment program of NOA patients is to identify the testicular pathological category in the NOA patients, and then to predict the outcome of TESE before assisted reproduction technology.