Anti-PERP (C-terminal) polyclonal antibody

The ability of breast cancer cells to resist anoikis, apoptosis caused by detachment of the non-malignant epithelial cells from the extracellular matrix (ECM), is thought to be critical for breast tumor growth, invasion and metastasis. ErbB2, an oncoprotein that is often overproduced in breast tumors, can block breast cancer cell anoikis via mechanisms that are understood only in part. In an effort to understand them better we found that detachment of the non-malignant human breast epithelial cells from the ECM upregulates a protein Perp in these cells. Perp is a component of the desmosomes, multiprotein complexes involved in cell-to-cell adhesion. Perp can cause apoptosis via unknown mechanisms. We demonstrated that Perp upregulation by cell detachment is driven by detachment-induced loss of epidermal growth factor receptor (EGFR). We also found that Perp knockdown by RNA interference (RNAi) rescues detached cells from death which indicates that Perp contributes to their anoikis. We observed that ErbB2, when overexpressed in detached breast epithelial cells, causes Perp downregulation. Furthermore, ErbB2-directed RNAi or treatment with lapatinib, an ErbB2/EGFR small-molecule inhibitor used for breast cancer therapy, upregulated Perp in ErbB2positive human breast and ovarian carcinoma cells. We established that ErbB2 downregulates Perp by activating an ErbB2 effector protein kinase Mek that blocks detachment-induced EGFR loss in a manner that requires the presence of a signaling protein Sprouty-2. Finally, we observed that restoration of the wild-type Perp levels in ErbB2-overproducing breast epithelial cells increases their anoikis susceptibility and blocks their clonogenicity in the absence of adhesion to the ECM. In summary, we have identified a novel mechanism of ErbB2-mediated mechanism of anoikis resistance of ErbB2-overproducing breast epithelial cells. This mechanism allows such cells to grow without adhesion to the ECM and is driven by ErbB2-induced activation of Mek, subsequent EGFR upregulation and further EGFR-dependent Perp loss.

Background and aim: Peter Cerny Ambulance Service - Premature Eye Rescue Program (PCA-PERP) uses digital retinal imaging (DRI) with remote interpretation in bedside ROP screening, which has advantages over binocular indirect ophthalmoscopy (BIO) in screening of premature newborns. We aimed to demonstrate that PCA-PERP provides good value for the money and to model the cost ramifications of a similar newly launched system. Methods: As DRI was demonstrated to have high diagnostic performance, only the costs of bedside DRI-based screening were compared to those of traditional transport and BID-based screening (cost-minimization analysis). The total costs of investment and maintenance were analyzed with micro-costing method. A ten-year analysis time-horizon and service provider's perspective were applied. Results: From the launch of PCA-PERP up to the end of 2014, 3722 bedside examinations were performed in the PCA covered central region of Hungary. From 2009 to 2014, PCA-PERP saved 92,248 km and 3633 staff working hours, with an annual nominal cost-savings ranging from 17,435 to 35,140 Euro. The net present value was 127,847 Euro at the end of 2014, with a payback period of 4.1 years and an internal rate of return of 20.8%. Our model presented the NPVs of different scenarios with different initial investments, annual number of transports and average transport distances. Conclusions: PCA-PERP as bedside screening with remote interpretation, when compared to a transport-based screening with BIO, produced better cost-savings from the perspective of the service provider and provided a return on initial investment within five years after the project initiation. (C) 2017 Elsevier Ireland Ltd. All rights reserved.