Specific Biomarkers of Prostate Cancer-Associated Ischemic Stroke: A Case-Control Study.

BACKGROUND Ischemic stroke in cancer patients is associated with poor prognosis. However, the specific biomarkers of cancer-associated ischemic stroke (CaIS) have not been well defined. MATERIAL AND METHODS A retrospective study was conducted on PCaIS patients. Clinical data and laboratory and imaging findings were collected. Multivariable logistic regression analysis was used to analyze the independent risk factors for PCaIS. A multiple model combining the independent risk factors of PCaIS was developed using the receiver operating characteristic (ROC) and area under the ROC curve (AUC). RESULTS A total of 83 PCaIS patients and 83 prostate cancer (PCa) patients were included. PCaIS patients had higher levels of D-dimer, neutrophil-to-lymphocyte ratio (NLR), and total prostate-specific antigen (T-PSA). In the multivariate analysis, D-dimer [OR=1.001, 95% CI: 1.00,1.00, P=0.002], NLR [OR=1.12, 95% CI: 1.04,1.22, P=0.005], and T-PSA [OR=6.275, 95% CI: 2.57,15.31, P<0.001] were independent risk factors of PCaIS. Additionally, the AUC of the multiple model of PCaIS was 0.815 (95% CI, 0.750-0.869), with sensitivity of 81.71% and specificity of 70.21%. CONCLUSIONS Elevated levels of D-dimer and T-PSA and increased NLR are independent risk factors of PCaIS. The multiple model of PCaIS can be a specific biomarker and is a reliable predictor of development of PCaIS.

Overexpression of 14-3-3 protein protects pheochromocytoma cells against 1-methyl-4-phenylpyridinium toxicity.

Objective To investigate the effects of 14-3-3 protein overexpression on the 1-methyl-4-phenylpyridinium (MPP(+)) induced pheochromocytoma (PC12) cell death and the potential mechanisms. Methods pcDNA3.1(+)-14-3-3 plasmids, which could be expressed in mammalian cell, were constructed and transfected into PC12 cells with Lipofectamine 2000. The expression of 14-3-3 protein, Bcl-2 protein, and BAD protein were determined by western blot. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, microplate reader, and flow cytometric analysis were used to measure cell viability, the caspase activity, and apoptotic ratio respectively. Results (1) The expression of 14-3-3 protein increased significantly three weeks after pcDNA3.1 (+)-14-3-3 plasmids transfected into PC12 cells. (2) MPP(+) caused a decrease of cell viability in a dose-dependent manner. At 100 mu mol/L MPP(+), cell viability reduced approximately 50%. (3) The caspase activity increased along with the MPP(+) concentrations rising and reached its maximum value (0.34 mu mol/mg protein) at 100 mu mol/L MPP(+). However caspase activity decreased significantly when the MPP(+) concentration exceeded 100 mu mol/L. (4) Overexpression of 14-3-3 protein decreased the apoptosis ratio of PC12 cells treated with 100 mu mol/L MPP(+) from 26.5% to 8.6%. (5) Bcl-2 protein tended to decrease but BAD protein tended to increase after treatment of PC12 cells with 100 mu mol/L MPP(+). Overexpression of 14-3-3 protein significantly increased the cellular level of Bcl-2 protein and decreased that of BAD protein. Conclusion Overexpression of 14-3-3 protein may reduce MPP(+)-induced apoptotic cell death in PC12 cells by up-regulating the Bcl-2 expression and down-regulating the BAD expression. These results may provide a promising target for treatment of Parkinson' s disease.