The newly discovered target Fas ligand, resulting in altered host cell apoptosis and innate immunity. Thus, the production of OMVs by Y. pestis may provide an explanation for how a pathogen with a significant array of anti-inflammatory virulence factors is able to induce a highly pro-inflammatory state during disease. Y. pestis infection of mammals is generally extracellular in nature, and the only bacterial products thought to be delivered to the host cell cytoplasm are those injected by the T3SS. It has been repeatedly demonstrated, however, that OMVs released by other bacterial pathogens are capable of fusing with or are internalized by host cells. Thus, OMV production by Y. pestis could potentially result in the delivery of otherwise extracellular or cell surface-associated bacterial factors directly to the eukaryotic cell cytosol. If Y. pestis-produced OMVs are capable of fusing with the host cell during infection, this raises the possibility that extracellular virulence factors of the plague bacillus may also have intracellular activities. For instance, if Pla is internalized via OMV fusion or endocytosis, the Pla protease could alter host cell function by cleaving or degrading intracellular proteins. If these targeted proteins contribute to pathogen sensing, signaling, or basic biological processes, this could explain the diverse roles of Pla during pneumonic plague beyond its effects on fibrinolysis and apoptosis. While the release of OMVs by Y. pestis may be playing a natural role during host infections, it is also tempting to speculate on the use of purified OMVs as a tool to determine the specific roles of outer membrane virulence factors in the host independent of replicating, metabolically active, or secretion-competent bacteria. This could be particularly useful for the study of proteins that are otherwise intransigent to purification due to their structure or requirement for bacterial co-factors for full activity, such as Pla. Biomarkers able to characterize and predict multifactorial diseases, such as cancer, are still one of the most important targets for all the “omics” investigations. These clinically oriented studies have also been successfully performed in the peripheral fluids, taking advantage of non- or very low-invasive collection methods. In particular, the urinary low-molecular-weight proteome, also LY2109761 termed urinary peptidome, represents an important source of information for biomarker discovery. The analysis of the urinary peptidome should be most applicable to renal diseases, given that urine should contain a higher amount of molecules, including these naturally occurring polypeptides, with an altered concentration deriving directly from kidney. In particular, Renal cell carcinoma needs markers for detection, prognosis and therapeutic targeting. Whereas RCC includes an heterogeneous group of tumours with variable clinical outcomes, that range from indolent to explicitly malignant.