Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance. 相似文献
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
This article begins with an overview of the knowledge translation (KT) process, introduces commonly used KT terms and the Aware-Adopt-Adapt (A3) KT map. The A3 was created by a nurse practitioner (NP) for practitioners and NP students to provide a map for those who wish to move existing knowledge to practice, yet do not know where to start or do not have the time to take a deeper dive into specific KT theories. 相似文献
ObjectiveThe objective of this study was to investigate the association between morphological variation and postsurgical pulmonary vein (PV) stenosis (PPVS) in patients with cardiac total anomalous pulmonary venous connection (TAPVC).MethodsThis single-center, retrospective study included 168 pediatric patients who underwent surgical repair of cardiac TAPVC from 2013 to 2019 (connection to the coronary sinus [CS], n = 136; connection directly to the right atrium [RA], n = 32). Three-dimensional computed tomography modeling and geometric analysis were performed to investigate the morphological features; their relevance to the PPVS was examined.ResultsThe connection type had no association with PPVS (CS type: 18% vs right atrial type: 19%; P = .89) but there was a higher incidence of PPVS in patients with a single PV orifice than > 1 orifice (P < .001). Confluence-to-total PV area ratio (hazard ratio, 4.78, 95% CI, 1.86-12.32; P = .001) and length of drainage route (hazard ratio, 1.22; 95% CI, 1.14-1.31; P < .001) had a 4- and 1-fold increase in the risk for PPVS in the CS type after adjustment for age and preoperative pulmonary venous obstruction. In the right atrial type, those with anomalous PV return to the RA roof were more likely to develop PPVS than to the posterior wall of the RA (P < .001).ConclusionsThe number of inter-junction PV orifice correlated with PPVS development in cardiac TAPVC. The confluence-to-total PV ratio, length of drainage route, and anomalous PV return to the RA roof are important predictors for PPVS. Morphological subcategorization in this clinical setting can potentially assist in surgical decision-making. 相似文献
1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.
2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.
3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos. 相似文献