Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Manganese antagonizes iron blocking mitochondrial aconitase expression in human prostate carcinoma cells

Aim： To investigate the possible role of manganese in the regulation of mitochondrial aconitase （mACON） activity human prostate carcinoma cell line PC-3 cells. Methods： The mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dinucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the mACON. The putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays. Results： In vitro study revealed that manganese chloride （MnCI2） treatment for 16 h inhibited the enzymatic activity of mACON, which induced the inhibition of citrate utility and cell proliferation of PC- 3 cells. Although results from transient gene expression assays showed that MnCI2 treatment upregulated gene translation by approximately 5-fold through the iron response element pathway, immunoblot and reporter assays showed that MnCl2 treatments inhibited protein and gene expression of mACON. This effect was reversed by cotreatment with ferric ammonium citrate. Additional reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays suggested that a putative metal response element in the promoter of the mACON gene was involved in the regulation of MnCh on the gene expression of mACON. Conclusion： These findings suggest that manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.

Manganese antagonizes iron blocking mitochondrial aconitase expression in human prostate carcinoma cells

Aim:To investigate the possible role of manganese in the regulation of mitochondrial aconitase(mACON)activity human prostate carcinoma cell line PC-3 cells.Methods:The mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dmucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the mACON.The putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electro- phoretic mobility-shift assays.Results:In vitro study revealed that manganese chloride(MnCl2)treatment for 16h inhibited the enzymatic activity of mACON,which induced the inhibition of citrate utility and cell proliferation of PC- 3 cells.Although results from transient gene expression assays showed that MnCl_2,treatment upregulated gene translation by approximately 5-fold through the iron response element pathway,immunoblot and reporter assays showed that MnCl_2 treatments inhibited protein and gene expression of mACON.This effect was reversed by co- treatment with fenic ammonium citrate.Additional reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays suggested that a putative metal response element in the promoter of the mACON gene was involved in the regulation of MnCl_2 on the gene expression of mACON.Conclusion:These findings suggest that manganese acts as an antagonist of iron,disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.