Interactional expression of netrin-1 and its dependence receptor UNC5B in prostate carcinoma.

Acting via its receptor UNC5B, netrin-1, one of the major neuronal guidance cues, plays an important role in angiogenesis, neurogenesis, tissue morphogenesis, embryonic development, cancer, inflammation, and various pathologies. However, its role has not been reported in prostate carcinoma. To investigate the association of netrin-1 and UNC5B expression with prostate carcinoma, several human prostate carcinoma cell lines were cultured and the expression levels of netrin-1 and UNC5B were determined by real-time PCR and Western blot. Calphostin C, (the inhibitor of PKC α) and phorbol-12-myristate 13-acetate-PMA (the agonist of PKC α) were used to treat the prostate carcinoma cells, and the cell proliferation and invasion abilities were measured by CCK-8 and wound-healing assays. Proliferation of DU145 cells was affected by the recruitment of PMA and calphostin C in a dose-dependent manner. By immunofluorescence, we identified the localization of netrin-1 and UNC5B in prostate carcinoma cell lines (DU145, 22RV1, PC3, PC3M, and RWEP) and found that netrin-1 was highly expressed in the nucleolus but there was no expression of UNC5B. The co-localization expression of PKC α and UNC5B was confirmed by the confocal immunofluorescence. Higher netrin-1 and lower UNC5B expression in all prostate carcinoma cell lines indicated that netrin-1 and UNC5B could be used to predict metastasis.

Variation of urinary and serum trace elements (Ca, Zn, Cu, Se) in bladder carcinoma in China.

BACKGROUNDS: Deficiency or excess of trace elements can induce body metabolic disorders and cellular growth disturbance, even mutation and cancerization. Since there are few studies of the effect of trace elements in bladder carcinoma in China, the aim of this study was thus to assess variation using a case control approach. METHODS: To determine this, 81 patients with bladder carcinoma chosen as a study group and 130 healthy persons chosen as a control group were all assayed for urinary and serum trace elements (calcium [Ca], zinc [Zn], copper [Cu], selenium [Se]) using an atomic absorption spectrophotometer, and the results were analyzed by independent sample t tests. The correlative factors on questionnaires answered by all persons were analyzed by logistic regression. RESULTS: The results showed urinary Ca, Zn and serum Cu levels of the study group to be significantly higher (P<0.05) than those of he control group. Serum Ca and Se levels of study group were significantly lower (P<0.05) than those of control group. CONCLUSION: There were higher urinary Zn and serum Cu concentrations in bladder carcinoma cases. Bladder carcinoma may be associated with Ca metabolic disorder, leading to higher urinary Ca and lower serum Ca. Low serum Se and smoking appear to be other risk factors for bladder carcinoma in China.

Knockdown of Cdc25B in renal cell carcinoma is associated with decreased malignant features.

Cdc25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of Cdc25B in renal cell carcinomas remains unknown. To shed light on influence on renal cell carcinogenesis and subsequent progression, Cdc25B expression was examined by real-time RT-PCR and western blotting in renal cell carcinoma and normal tissues. 65 kDa Cdc25B expression was higher in carcinomas than in the adjacent normal tissues (P<0.05), positive correlations being noted with clinical stage and histopathologic grade (P<0.05). To additionally investigate the role of Cdc25B alteration in the development of renal cell carcinoma, Cdc25B siRNA was used to knockdown the expression of Cdc25B. Down-regulation resulted in slower growth, more G2/M cells, weaker capacity for migration and invasion, and induction of apoptosis in 769-P transfectants. Reduction of 14-3-3 protein expression appeared related to Cdc25B knockdown. These findings suggest an important role of Cdc25B in renal cell carcinoma development and provide a rationale for investigation of Cdc2B-based gene therapy.

Low microsomal epoxide hydrolase expression is associated with bladder carcinogenesis and recurrence.

Microsomal epoxide hydrolase (mEH) plays a significant role in the metabolism of numerous xenobiotics and is associated with several forms of cancer. Here, we investigated the role of mEH expression in bladder carcinogenesis, subsequent progression and recurrence. The expression of mEH was analyzed by Western blot in 50 bladder urothelial carcinoma and 20 normal epithelial tissues. There was a significantly higher mEH expression in the normal epithelium (P<0.05) and mEH expression was lower in high stage than in low stage tumors (P<0.05). Further, immunohistochmistry in 106 bladder urothelial carcinoma demonstrated mEH expression to be negatively correlated with histological grade, pT stage and recurrence (P<0.05). These findings suggest the important role of mEH in bladder carcinogenesis, cancer development and recurrence, providing support for efforts to develop mEH-based gene therapy.

Aberrant FHIT expression is linked to bladder carcinogenesis and apoptosis.

The fragile histidine triad gene (FHIT) functions as tumor suppressor in many epithelial cell types. Although the exact mechanisms remain unclear, it is apparent that in its absence, cell cycle homeostasis is often perturbed resulting in the development of soft tissue tumors. Here, we investigated the role of FHIT expression in bladder carcinogenesis and progression using immunohistochemistry. Bladder carcinoma tissue and the 5637 cell line were also studied for FHIT expression by RT-PCR and Western blotting, respectively. FHIT was found to be expressed in carcinoma and adjacent normal tissues at both mRNA and protein levels, but the 17 kDa FHIT was lower in tumors (P<0.05), this being confirmed immunohistochemically. There was a negative correlation between FHIT expression and histological grade of bladder transitional cell carcinoma (P<0.05), but no clear relationship with clinical stage or relapse (P>0.05). Overexpression of FHIT could induce apoptosis in bladder carcinoma 5637 cells, which could be enhanced by adding adriamycin (ADR). These findings suggest important roles of FHIT in bladder cancer development and provide support for the feasibility of FHIT-based gene therapy.

[The effect of simvastatin on the regeneration of sciatic nerve with crush injury in rats].

AIM: To explore the effect of Simvastatin on the regeneration of sciatic nerve with crush injury in rats. METHODS: Animals were randomized into the following experimental groups: Simvastatin-treated, vehicle and sham-operated groups. Sciatic nerves with crush injury were performed. After surgery, the functional evaluation of nerve recovery, electrophysiologic assessment, histological assessment, serum IL-6 and lipid were performed. RESULTS: The toe spread index of Simvastatin-treated rats after operation was higher significantly than vehicle rats at 5 d and 8 d (P<0.05). CMAP was higher and NCV was faster (P < 0.05). The serum IL-6 at 5 d of post-operation was significant lower (P < 0.05). Total serum cholesterol of Simvastatin-treated animals was higher than that of other animals (P < 0.05) at 2 weeks of post-operation. The histological analysis showed that the numbers of myelinated axons and the thickness of myelin sheath of Simvastatin-treated crush injury animals at 4 weeks of post-operation were more than that of vehicle animals. CONCLUSION: The present study showed that Simvastatin could promote the regeneration of the sciatic nerve after crush injury in rats, partly through inhibiting immune and inflammatory responses and making the balance of serum cholesterol during these processes.