br Introduction Cancer related inflammation
Introduction Cancer related inflammation is associated with poor prognosis and reduced survival in numerous human malignancies. Expansion of myeloid derived immune Superoxide Dismutase (SOD) Activity Assay Kit in response to tumor-secreted factors largely contributes to the heightened systemic and intra-tumoral inflammatory milieu observed in cancer patients. While the pattern of infiltrating immune cells is heterogeneous between different cancers, granulocytic myeloid cells are amongst the most predominant immune cell types that confer adverse clinical outcomes. This was most strikingly demonstrated by a recent transcriptomic analysis of 18,000 tumors, encompassing 39 distinct human cancers. The authors reported that a cancer-wide granulocytic gene signature was most significantly correlated with poor prognosis, thereby implicating infiltrating granulocytes and neutrophils as central and potentially targetable regulators of tumor growth . In accordance with this major finding, a large number of preclinical animal studies confirm myeloid skewing, particularly towards the granulocytic lineage, as a characteristic phenomenon in the setting of most cancers , , . Moreover, high neutrophil to lymphocyte ratios (NLR), which are likely peripheral manifestations of myeloid skewing, have prognostic value for human cancer patients , . We recently reported that infiltrating myeloid cells exert pro-tumorigenic actions via neutrophil elastase in prostate cancer . The contribution of granulocytic myeloid cells and neutrophils to cancer progression is multifaceted and has been extensively reviewed elsewhere , ; however, accumulating literature on the role of neutrophil elastase in cancer warrants further consideration. In this review, we examine the mechanisms by which neutrophil elastase may facilitate primary tumor growth and secondary organ metastasis. Importantly, we conclude with a brief discussion of neutrophil elastase as a novel therapeutic target in cancer.
Conclusions Infiltrating and circulating myeloid cells exert important actions at both the primary tumor and metastatic sites. The pro-tumorigenic actions of these cells may be mediated in part by enhanced production and activity of neutrophil elastase. In one potential model, MDSCs may be drawn from the blood vessels to tumor sites, where they then secrete neutrophil elastase. This enzyme in turn promotes tumor proliferation, EMT, migration, and invasion, which ultimately leads to metastasis (Fig. 1). As evidenced by numerous preclinical studies highlighted in this review, neutrophil elastase may therefore serve as a novel cancer biomarker or therapeutic target. That said, the recent development and safe utilization of more potent and bioavailable neutrophil elastase inhibitors in human patients is promising and warrants further investigation in the cancer field.
Introduction Nanocellulose-based materials have widespread interest for their renewable, sustainable, nontoxic, biodegradable, thermal and chemical stability (Habibi, Lucia, & Rojas, 2010; Wang, Lu, & Zhang, 2016). Moreover, the applications of nanocellulose in the biomedical area are growing rapidly (Jorfi & Foster, 2015). In this regard, the actual application of cellulose and nanocellulose to the development of biosensor transducer surfaces has received increased attention in recent years (Edwards, Prevost, Sethumadhavan, Ullah, & Condon, 2013). This is especially the case with protease sensors where the goal is point of care diagnostics interfaced with wound care treatment of chronic wounds, and a timely topic for clinical translation research as relates to protease modulating dressings to chronic wound treatment (Edwards, Fontenot, Prevost et al., 2016; Romanelli, Miteva, Romanelli, Barbanera, & Dini, 2013; Serena et al., 2016). Although, some approaches to point of care protease diagnostics and treatment have been adopted internationally as a clinical point of care tool, the use of protease sensors as guides to chronic wound treatment have not been completely realized worldwide. This in part is due to an incomplete understanding of the complexity of chronic wound types where variable protease levels have demonstrated less than a predictable certainty correlating to a trajectory to wound healing in different wound types and thus a choice of appropriate dressings to treat pathological protease levels (Dabiri, Damstetter, & Phillips, 2016). Nonetheless, as research in this area strengthens the paradigm of monitoring protease activity, basic to protease sensor design and development is the balance of protease sensor detection sensitivity and selectivity with optimization of dressing treatment. Thus, fundamental questions regarding approaches to protease detection and treatment are currently based on the surface chemistry of dressing/sensor interface design and transducer surfaces consisting of nanocellulosic materials, which provides a platform for adopting point of care protease sensors for chronic wound treatment, and other inflammatory diseases where proteases biomarker are central to disease diagnostics or theranostics. (Edwards, Fontenot, Prevost et al., 2016; Salas, Nypelö, Rodriguez-Abreu, Carrillo, & Rojas, 2014).