We investigated whether inhibiting phosphorylated p70S6K （p-p70S6K） suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma （LG-URCa） in vitro and whether p-p70S6K can serve as a pred...We investigated whether inhibiting phosphorylated p70S6K （p-p70S6K） suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma （LG-URCa） in vitro and whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray （TMA） for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group （P 〈 0.05; hazard ratio （HR）, 2.415） and the high p-p70S6K staining group （P 〈 0.05; HR, 2.249） were independent factors for predicting recurrence. Rapamycin inhibited RT4 and 253J cell proliferation in a dose-dependent manner （r = -0.850, P 〈 0.001 in RT4 cells; r = -0.835, P 〈 0.001 in 253J cells）. RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively （P 〈 0.05）. Transfection of p70S6K siRNA resulted in inhibitory effects on cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder.展开更多
The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen （PSA） levels in healthy men with serum PSA level below 4 ng mL-1. The men included ...The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen （PSA） levels in healthy men with serum PSA level below 4 ng mL-1. The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment （HOMA [fasting glucose × fasting insulin]/22.5） and quantitative insulin sensitivity check index （QUICK/; 1/[log （fasting insulin） ＋ log （fasting glucose）]）. Age-adjusted body mass index （BMI） was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance （ANOVA） test and Duncan＇s multiple comparison test （P 〈 0.001）, but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICK/（P 〈 0.001）. Age, BMI, insulin resistance by HOMA or QUICK/were significantly independent variables to serum PSA level in a multivariate linear regression analysis （P 〈 0.001）. Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.展开更多
文摘We investigated whether inhibiting phosphorylated p70S6K （p-p70S6K） suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma （LG-URCa） in vitro and whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray （TMA） for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group （P 〈 0.05; hazard ratio （HR）, 2.415） and the high p-p70S6K staining group （P 〈 0.05; HR, 2.249） were independent factors for predicting recurrence. Rapamycin inhibited RT4 and 253J cell proliferation in a dose-dependent manner （r = -0.850, P 〈 0.001 in RT4 cells; r = -0.835, P 〈 0.001 in 253J cells）. RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively （P 〈 0.05）. Transfection of p70S6K siRNA resulted in inhibitory effects on cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder.
文摘The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen （PSA） levels in healthy men with serum PSA level below 4 ng mL-1. The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment （HOMA [fasting glucose × fasting insulin]/22.5） and quantitative insulin sensitivity check index （QUICK/; 1/[log （fasting insulin） ＋ log （fasting glucose）]）. Age-adjusted body mass index （BMI） was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance （ANOVA） test and Duncan＇s multiple comparison test （P 〈 0.001）, but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICK/（P 〈 0.001）. Age, BMI, insulin resistance by HOMA or QUICK/were significantly independent variables to serum PSA level in a multivariate linear regression analysis （P 〈 0.001）. Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.
