Changcheng Guo

Statin use and risk of kidney cancer: a meta‐analysis of observational studies and randomized trials

Clinical studies have shown that statin use may modify the risk of kidney cancer. However, these studies yielded different results. To quantify the association between statin use and risk of kidney cancer, we performed a detailed meta‐analysis of published studies regarding this subject.

Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials

The purpose of the present meta-analysis was to evaluate the efficacy and safety of testosterone replacement therapy in men with hypogonadism. A search was conducted for appropriate randomized controlled trials and the data from 16 trials were pooled. The intended primary outcome of the present study was to determine the efficacy and safety of testosterone replacement therapy. The current data demonstrated that scores for Aging Male Symptoms (AMS) were significantly reduced following testosterone replacement therapy, with a mean decrease in AMS score of 1.52 [95% confidence interval (CI), 0.72 to 2.32; P=0.0002]. Testosterone replacement therapy increased lean body mass [mean difference (MD), 1.22; 95% CI, 0.33 to 2.11; P=0.007], reduced fat mass in a non-significantly manner (MD, −0.85; 95% CI, −1.74 to 0.04; P=0.06) and significantly reduced total cholesterol (MD, −0.16; 95% CI, −0.29 to −0.03; P=0.01). No significant differences were identified in body weight (MD, 0.09; 95% CI, −1.13 to 1.31; P=0.89), body mass index (MD, 0.10; 95% CI, −0.62 to 0.82; P=0.78) or bone mineral density (MD, −0.01; 95% CI, −0.03 to 0.02; P=0.60). Average prostate volume increased (MD, 1.58; 95% CI, 0.6 to 2.56; P=0.002) following testosterone replacement therapy, but the levels of prostate-specific antigen (PSA) (MD, 0.10; 95% CI, −0.03 to 0.22; P=0.14) and the International Prostate Symptom Scores (MD, 0.01; 95% CI, −0.37 to 0.39; P=0.96) did not change. In conclusion, testosterone replacement therapy improves quality of life, increases lean body mass, significantly decreases total cholesterol, and is well-tolerated and safe for men with hypogonadism who are exhibiting PSA levels of <4 ng/ml.

Valproic acid upregulates NKG2D ligand expression and enhances susceptibility of human renal carcinoma cells to NK cell-mediated cytotoxicity

Introduction We aimed to investigate the effect of valproic acid (VPA) on NKG2D ligand expression in human renal carcinoma cell lines and to investigate the mechanisms. Material and methods Different concentrations of VPA from 0.5 mM to 8.0 mM were applied to 786-O and ACHN cell lines, respectively. Cell viability after treatment with VPA was determined by flow cytometry (FCM). Real-time PCR and FCM were used to detect the changes of mRNA and protein level of NKG2D ligands (MICA/B and ULBPs) in the two cell lines treated with 4 mM VPA. The cytotoxicity assay and CD107a mobilization assay were carried out to detect the cytotoxicity changes of NK cells against renal carcinoma cell lines after the same treatment. Results Valproic acid can efficiently upregulate MICA/B, ULBP1 and ULBP2 expression in the renal carcinoma cell lines at the mRNA and protein level (p < 0.05). 786-O and ACHN cells treated with VPA were more susceptible to killing by NK cells than untreated cells and the enhanced cytotoxicity of NK cells was blocked by the pretreatment of NK cells with anti-NKG2D monoclonal antibodies (p < 0.05). Conclusions Valproic acid can clearly induce the expression of NKG2D ligands of renal carcinoma cell lines, thereby enhancing the cytotoxicity of NK cells against renal carcinoma cell lines.

The effect of Pokemon on bladder cancer epithelial-mesenchymal transition.

OBJECTIVE This study aimed at detecting Pokemon expression in bladder cancer cell and investigating the relationship between Pokemon and epithelial-mesenchymal transition. Furthermore, we investigated the functions of Pokemon in the carcinogenesis and development of bladder cancer. This study was also designed to observe the inhibitory effects of siRNA expression vector on Pokemon in bladder cancer cell. METHODS The siRNA expression vectors which were constructed to express a short hairpin RNA against Pokemon were transfected to the bladder cancer cells T24 with a liposome. Levels of Pokemon, E-cadherin and β-catenin mRNA and protein were examined by real-time quantitative-fluorescent PCR and Western blot analysis, respectively. The effects of Pokemon silencing on epithelial-mesenchymal transition of T24 cells were evaluated with wound-healing assay. RESULTS Pokemon was strongly inhibited by siRNA treatment, especially siRNA3 treatment group, as it was reflected by Western blot and real-time PCR. The gene and protein of E-cadherin expression level showed increased markedly after Pokemon was inhibited by RNA interference. While there were no differences in the levels of gene and protein of β-catenin among five groups. The bladder cancer cell after Pokemon siRNA interference showed a significantly reduced wound-closing efficiency at 6, 12 and 24h. CONCLUSIONS Our findings suggest Pokemon may inhibit the expression of E-cadherin. The low expression of E-cadherin lead to increasing the phenotype and apical-base polarity of epithelial cells. These changes of cells may result in the recurrence and progression of bladder cancer at last.

Matrix metallopeptidase 2 (MMP2) media la eliminación de MHC class I polypeptide-related sequence A (MICA) en el cáncer de células renales

INTRODUCTION The MHC class i chain-related molecule A (MICA) is a ligand for the natural killer group 2, member D (NKG2D) immunoreceptor activation. The engagement of tumor cell surface MICA to NKG2D stimulates the NK and T cell antitumor immunity. Shedding of MICA by tumor cells facilitates tumor immune evasion, which might partially contribute to tumor progression. MATERIAL AND METHODS Inmunohistochemistry was performed on both normal and neoplastic renal tissue. Human renal carcinoma cell lines 786-0 and ACHIN were transfected and target sequences to silence human MMP2 by shRNA expression were established. The degree of MICA shedding was measured and quantitative real-time PCR and Western-blot analysis were performed. RESULTS The membrane type matrix metalloproteinase 2 (MMP2) mediated the MICA shedding, which was blocked by suppression of MMP2 expression. Concomitantly, MMP2 over-expression enhanced the MICA shedding, indicating that MMP2 was involved in the renal cell carcinoma-associated proteolytic release of soluble MICA (sMICA), which facilitated the tumor immune escape. CONCLUSIONS These findings suggested that MMP2 might be a new potential target for tumor immune therapy. Elucidation of the mechanisms by which tumors shed MICA could be of a great importance for cancer treatment in order to reinforce the NK and T cell antitumor immunity.

Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma

PURPOSE Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. MATERIALS AND METHODS The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. RESULTS The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p <0.001). A colony of circulating endothelial progenitor cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p <0.001). The culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p <0.001). The circulating endothelial progenitor cell level correlated positively with the number of patient colonies (r = 0.762, p <0.001). Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p <0.001). CONCLUSIONS Earlier emergence of circulating endothelial progenitor cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results indicate the important significance of VEGF-R2(+) circulating endothelial progenitors in patients with renal cell carcinoma.

The expression and clinical significance of ZBTB7 in transitional cell carcinoma of the bladder

Zinc finger and BTB domain containing 7A (ZBTB7) is a ZBTB protein family member of transcriptional repressors that serves a critical role in cell transformation and malignancy. However, the association between ZBTB7 expression in bladder cancer tissues and the prognosis of patients remains unclear. The aim of the current study was to detect the expression of ZBTB7 in transitional cell carcinoma (TCC) of the bladder and normal bladder mucous tissues to evaluate the diagnostic and prognostic value of ZBTB7 in TCC of the bladder. A total of 100 TCC specimens were analyzed and the expression of ZBTB7 mRNA was examined via reverse transcription-quantitative polymerase chain reaction. The expression of ZBTB7 protein was examined by western blotting and immunohistochemistry. The association between ZBTB7 expression and the clinical prognosis of patients from the TCGA database was analyzed. High expression of ZBTB7 mRNA and protein in TCC tissue was detected and TCC expression was significantly higher in TCC tissue than in normal bladder mucous tissues (P<0.05). Furthermore, ZBTB7 expression was associated with recurrence, a larger tumor size and higher tumor grade. In terms of overall and recurrence-free survival, the group expressing high levels of ZBTB7 exhibited lower overall and recurrence-free survival compared with the low ZBTB7 expression group, although these differences were not statistically significant. Therefore, ZBTB7 may be important in the initiation and progression of TCC.

Inhibitory effect of valproate on proliferation of human kidney carcinoma ACHN cells and its mechanism

Objective: To investigate the effects of VPA (valproate) on proliferation, cell cycle distribution and apoptosis of human kidney carcinoma ACHN cells and the possible underlying mechanisms. Methods: The effect of VPA on the proliferation of ACHN cells was examined by CCK-8 (cell counting kit-8) assay. Flow cytometry was used to analyze the cell cycle distribution and apoptosis of ACHN cells exposed to VPA. The mRNA expressions of cyclin E1, P21WAF1, Bcl-2 and Bax were detected by real-time fluorescence quantitative-PCR. Results: Incubation with various concentrations of VPA for 48 h resulted in a significant inhibition of proliferation of ACHN cells with an IC50 (50% inhibitory concentration) value of 4.21 mmol/L. After treatment with VPA, the cell cycle was arrested obviously at G0/G1 phase and the apoptotic rate was significantly increased as compared with the control group. After treatment with 4 mmol/L VPA for 48 h, the levels of P21WAF1 and Bax mRNAs were both significantly increased, and at the same time, the levels of cyclin E1 and Bcl-2 mRNAs were obviously decreased. Conclusion: VPA can inhibit the proliferation of kidney carcinoma ACHN cells by inducing cell-cycle arrest and apoptosis. DOI:10.3781/j.issn.1000-7431.2013.03.004