Search

The aim of the current study was to assess the prognostic value of circulating tumor cells (CTCs) and their related markers at different points of chemotherapy regimens in metastatic breast cancer (MBC) patients. The impact of CTCs on progression free survival (PFS) and overall survival (OS) rates were also assessed. Peripheral blood samples were obtained from 66 female patients with MBC at different time intervals for evaluation of CTCs by flow cytometry (FC). cytokeratin 19 (CK19), mammaglobin, prolactin inducible peptide (PIP), aldehyde dehydrogenase 1 (ALDH1) and human chorionic gonadotropin (hCG) were also assessed by qRT-PCR. Analysis of different CTC levels (at 4, 5, and 6 cells/7 ml), showed statistically significant values at 4 cells/7 ml blood. The presence of baseline CTCs < 4 cells/7 ml, associated significantly with higher PFS (P value = 0.03). Patients showing a decrease in the CTCs level after treatment had significantly prolonged median PFS and OS rates compared to those whose CTCs level increased (P = 0.007 and P = 0.014; respectively). Mammaglobin, CK19, PIP, ALDH1 and hCG expression did not affect PFS or OS. However, patients with CTCs ≥ 4 at diagnosis had higher rates of progression compared to those with CTCs < 4 (1.9 times, P = 0.07), and who metastasized before 4 years showed a worse decrease outcomes (they were 2.4 time more progressed than those who metastasized after 4 years; P = 0.029). CTCs could be an independent prognostic and predictive biomarker for MBC patients' outcomes. Although none of the assessed genes (mammaglobin, CK19, PIP, ALDH1 and hCG) showed correlation with PFS or OS rates, further studies on a larger number of patients are required to validate the current results.

The human pathogen Staphylococcus aureus encodes the ESAT6-like Secretion System (ESS). The ESS pathway secretes pathogenic substrates such as EsxA, EsxB, EsxC, EsxD and EssD that mediate staphylococcal establishment in persistent abscess lesions. The biochemical behavior of these substrates is not fully understood. EsxC is species-specific lysine-rich homodimer that lacks recognizable topogenic sequence. Studies have shown that EsxC is required for the secretion of other substrates, thereby revealing its biomedical importance. Here, EsxC self-association was investigated in the presence of several metal ion chelators. Results show that EsxC homodimerization is abolished in the presence of EDTA and EGTA, suggesting a role for calcium in mediating EsxC self-association. Complementation experiments confirm that EsxC homodimerization is calcium-dependent. N- and C-terminal truncations of EsxC were constructed, followed by bacterial two-hybrid screening. Results show that EsxC self-association is mediated by its C-terminal domain. Affinity purification of recombinant EsxC to apparent homogeneity, followed by chemical crosslinking and SDS-PAGE led to the detection of the monomeric and dimeric forms of the protein. In contrast and when a purified EsxC variant lacking the C-terminus was subjected to similar conditions, only the monomeric form was observed. These in vivo and in vitro data highlight the contribution of the C-terminus of the virulence factor EsxC to self-association, and document a previously unreported role for calcium in mediating protein-protein interactions in this pathogenic secretion system., (Copyright © 2018 Elsevier Ltd. All rights reserved.)