In summary, depending on which criterion is used for interpretation, polysomy 17 is a crucial cause of misinterpretation of HER2 FISH results. Using the 2013 ASCO/CAP scoring criteria evaluate HER2 status resulted in a significantly higher number of HER2-amplified cases being identified, especially IHC 2+ cases, which identifies more patients appropriate for targeted treatment. However,
as there are no methods to determine Dinaciclib cell line chromosome 17 status precisely, determining what CEP17 amplification means in terms of response to trastuzumab and anthracycline treatment requires further study. “
“Protease-activated receptors (PAR) comprise a family of transmembrane G-coupled receptors (PAR-1, PAR-2, PAR-3 and PAR-4) that are uniquely activated by proteolytic cleavage of their extracellular portion. This cleavage “unmasks” a new N-terminus, which serves as a “tethered ligand” that binds to the second extracellular domain of the protein, resulting in a variety of cellular responses [1]. PAR-1, the prototypic receptor of the family, is activated by thrombin, as well as PARP inhibitor other proteases, being associated with several physiological and pathological processes [2]. Physiologically, PAR-1 is expressed by different tissues including vascular cells, neurons, fibroblasts, epithelial cells and others [2]. On the other hand, PAR-1 has been recognized
as an oncogene, promoting transformation in NIH 3T3 cells [3]. PAR-1 has been shown to be overexpressed in various human cancers types including breast [4], melanoma [5] and [6], colon [7], prostate [8], ovarian [9],
esophagus [10] and others. Moreover, studies employing cultured cells have demonstrated strong correlation between PAR-1 expression and aggressive behavior [4] and [11]. Thus, PAR-1 has been associated with several pro-tumoral responses in solid tumors including primary growth, invasion, metastasis and angiogenesis [4], [8], [11], [12], [13] and [14]. Previous studies employing human leukemic cell lines have demonstrated expression of PAR-1. Activation of PAR-1 elicits cell signaling responses which have been associated with increased production of interleukin 2 in Jurkat T cells [15]. In addition, PAR-1 is found in HL-60 cells [16] Enzalutamide order and its activation stimulates proliferation and decreases idarubicin-induced cell death in vitro [17]. Based on these data authors suggested that PAR-1 could play a role in the leukemic process. However the status of PAR-1 expression in human leukemic patients has not been fully evaluated. The aim of this study was to evaluate the expression pattern of PAR-1 receptor in patients with the four main types of leukemia – chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML).