Therefore, bone markers are increasingly being recognized as a potential surrogate endpoints. Although prostate cancer is not the most recent recommendations of the Working Group included bone markers as validated endpoint for clinical trials of CRPC interpret CCT239065 various data, the bone biomarkers important information on the impact of available treatment of bone metastases. In particular, the correlation between bone markers and outcomes in patients in trials of beating BP, show that Ver changes In biomarker levels k Able to treatment failure and / or the need for a more aggressive treatment. In addition, recent studies suggest non-specific cytotoxic effects on bone and other clinical benefits k Can independently Ngig occur apart from Ver Level.
However changes in the PSA, the suggestion that bone biomarkers additionally Useful Information to deliver on pr predictive phone start-up traditional estimates requires further investigation and validation in prospective studies. It should also be noted that diurnal and are daily fluctuations in the H Height of bone biomarkers occurs, and analytical results vary considerably BMS-387032 between laboratories, even if they use the same method, which means that a strict standardization necessary before the assessment is integrated into clinical practice. Overall, the available evidence indicates that bone biomarkers hold promise for future monitoring and optimization of targeted therapies for bone microenvironment.
Background of the endothelin system endothelin system consists of four peptide ligands of endothelin, and 1, 2, 3, and discovered recently and 4, the two G protein-coupled receptors, ETAR and EtBr and enzymes conversion of endothelin, the production of biologically active ETs catalyze. ETs are derived from precursor Shore proteins After cleavage by membranebound metalloproteinase and EPA are known for their total vasoconstrictor known. Among them, 1 is the ligand st Is expressed in endothelial cells and widely distributed strongest. The endothelin peptides exert their function by binding to its receptors A and B, where they have different intracellular Re effects to engender, Through the activation of many downstream signaling pathways. The members of the endothelin system have in the neural tissues, kidney, vascular And have been identified, and their involvement was also in a number of physiological processes such as embryonic development, reproduction, angiogenesis, and the Horn Homeostasis documented cardiovascular .
R The endothelin system in the disease, the r The endothelin system was also kardiovaskul Ren and kidney diseases characterized. And 1 from endothelial cells exerts autocrine and paracrine functions by binding to ETAR on vascular and EtBr Pericytes and endothelial cells produced Ren. Balanced activation of both receptors, vascular tone and regulates unterh lt proliferation of endothelial cells, w while the imbalance in this system tr gt to the development of GE Antr for reprints: George Coukos, University of Pennsylvania 421 Curie Boulevard CRRWH, 1316 BRB II / III, Philadelphia, PA 19104th Phone: 215 746 5137, Disclosure of m Resembled no conflicts of interest, conflicts of interest were disclosed. NIH Public Access Author Manuscript Clin Cancer Res Author manuscript, increases available in PMC 2010 5 July. Ver published in its final form: Clin Cancer Res 2009 July 15 15: 4521 4528th doi: 10.1158/1078 0432.CCR 08 0543rd NIH Author Manuscri PA