To identify biomarkers that discriminate the aggressive forms of prostate cancer, we performed gene expression profiling of prostate tumors using a genetically engineered mouse model that recapitulates the stages of human prostate cancer, namely Nkx3.1; Pten mutant mice. We observed a significant deregulation of the epidermal growth factor and mitogen-activated protein kinase (MAPK) signaling pathways, as well as their major downstream effectors-the activator protein-1 transcription factors c-Fos and c-Jun. Forced expression of c-Fos and c-Jun in prostate cancer cells promotes tumorigenicity and results in activation of extracellular signal-regulated kinase (Erk) MAPK signaling. In human prostate cancer, up-regulation of c-Fos and c-Jun proteins occurs in advanced disease and is correlated with Erk MAPK pathway activation, whereas high levels of c-Jun expression are associated with disease recurrence. Our analyses reveal a hitherto unappreciated role for AP-1 transcription factors in prostate cancer progression and identify c-Jun as a marker of high-risk prostate cancer. This study provides a striking example of how accurate mouse models can provide insights on molecular processes involved in progression and recurrence of human cancer. [Cancer Res 2008;68(7):2132-44]

The roles of endothelial nitric oxide synthase gene polymorphisms in coronary artery disease have been intensively analyzed, with inconsistent results. Therefore, we performed this study to better assess the relationship between endothelial nitric oxide synthase genetic variations and the risk of coronary artery disease. Eligible studies were searched in PubMed, Medline, Embase, and Web of Science. Odds ratios with 95% confidence intervals were used to evaluate associations between endothelial nitric oxide synthase polymorphisms and coronary artery disease. A total of 132 genetic association studies were finally included. Significant associations with the risk of coronary artery disease were detected for the rs891512, rs1799983, rs2070744, rs11771443 and rs869109213 polymorphisms. Further subgroup analyses according to ethnicity of participants revealed that the rs1799983 and rs2070744 polymorphisms were significantly associated with the risk of coronary artery disease in both Caucasians and Asians, whereas the rs869109213 polymorphism was only associated with the risk of coronary artery disease in Caucasians. When we stratified data based on type of disease, we found that the rs1799983, rs2070744 and rs869109213 polymorphisms were all significantly correlated with the risk of myocardial infarction or acute coronary syndrome in certain genetic models. In conclusion, our findings indicate that the rs891512, rs1799983, rs2070744, rs11771443 and rs869109213 polymorphisms may serve as genetic biomarkers of coronary artery disease.

Objectives The relationship between inflammatory cytokines and postoperative delirium (POD) remains to be further investigated, especially in patients undergoing acute type A aortic dissection (AAD). Interleukin-6 (IL-6) is involved in the inflammatory process and has recently been identified as a biomarker of cerebral dysfunction. We explored the hypothesis that IL-6 was one of the critical causes of POD after surgical repair of AAD. Methods Plasma IL-6 was measured using electrochemiluminescence technology in patients preoperatively and 24 h, 48 h, and 72 h after surgical repair of acute type A aortic dissection. After the first three postoperative days, delirium was evaluated twice daily using the Confusion Assessment Method. ROC curves were used to evaluate the ability of IL-6 measurements to distinguish POD. Results The incidence of POD was 14.03% (31 of 221 patients). The patients in the POD group were significantly older than the patients in the non-POD group (56.48 ± 11.68 years vs 52.22 ± 10.50 years, P = 0.040). Plasma IL-6 concentrations were significantly higher in the POD group than in the non-POD group at three time points: preoperatively, after 24 h, and after 48 h. The AUC values corresponding to IL-6 preoperatively and 24 h after surgery were 0.73 and 0.72, respectively. Conclusions Cerebral dysfunction after the surgical repair of AAD shows elevated stress levels and inflammatory responses. Plasma IL-6 is a potential biomarker to predict the onset of POD in acute type A aortic dissection patients following surgical repair.