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Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents approximately 15-30% of all invasive breast cancers. Despite the recent advances in therapeutic practices of HER2 subtype, drug resistance and tumor recurrence still have remained as major problems. Drug discovery is a long and difficult process, so the aim of this study is to find potential new application for existing therapeutic agents. Gene expression data for breast invasive carcinoma were retrieved from The Cancer Genome Atlas (TCGA) database. The normal and tumor samples were analyzed using Linear Models for Microarray Data (LIMMA) R package in order to find the differentially expressed genes (DEGs). These genes were used as entry for the library of integrated network-based cellular signatures (LINCS) L1000CDS 2 software and suggested 24 repurposed drugs. According to the obtained results, some of these drugs including vorinostat, mocetinostat, alvocidib, CGP-60474, BMS-387032, AT-7519, and curcumin have significant functional similarity and structural correlation with FDA-approved breast cancer drugs. Based on the drug-target network, which consisted of the repurposed drugs and their target genes, the aforementioned drugs had the highest degrees. Moreover, the experimental approach verified curcumin as an effective therapeutic agent for HER2 positive breast cancer. Hence, our work suggested that some repurposed drugs based on gene expression data can be noticed as potential drugs for the treatment of HER2-positive breast cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Endothelial cell (EC) dysfunction contributes to atherosclerosis, which is associated with arterial stiffening and fibronectin (FN) deposition, by ECs and smooth muscle cells (SMCs). The effect of stiffness on the EC/FN interaction and fibrillar adhesion formation has been poorly studied. An in vitro model was prepared that included FN-coated polydimethylsiloxane (PDMS) films with similar hydrophobicity and roughness but distinct Young's modulus values, mimicking healthy (1.0 MPa) and atherosclerotic (2.8 MPa) arteries. Human aortic abdominal endothelial cells (HAAECs) seeded on 1.0 MPa PDMS films spread over time and reached their maximum surface area faster than on 2.8 MPa PDMS films. In addition, HAAECs appeared to organize focal adhesion more rapidly on 1.0 MPa PDMS films, despite the similar cell binding domain accessibility to adsorbed FN. Interestingly, we also observed up to a ~5-fold increase in the percentage of HAAECs that had a well-developed fibrillar adhesion on 1.0 MPa compared to 2.8 MPa PDMS films as verified by integrin α 5 subunits, tensin, and FN staining. This variation did not affect EC migration. These results suggest that there are favourable conditions for FN matrix assembly by ECs in early atherosclerosis rather than at advanced stages. Our in vitro model will therefore be helpful to understand the influence of bulk stiffness on cells involved in atherosclerosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of this cross-sectional study was to assess the health status and quality of life (QOL) of paid unrelated versus related living kidney donors postdonation at Shiraz Transplant Center in Iran. We invited all donors (n = 580, 347 paid unrelated, 233 related) who underwent donor nephrectomy at our center from 2004 to 2010 to participate in a health survey and physical examination. Of 580 donors, 144 consented to participate; participation of paid unrelated donors was significantly lower than related (52/347 vs. 92/233; p < 0.001). Participants underwent a complete physical examination, QOL assessment (using a 36-item short form health survey [SF-36] questionnaire) and laboratory work-up. The paid unrelated donors compared with related donors were younger (34.2 ± 7.2 vs. 40.7 ± 9.7 years, p < 0.001), had shorter time since donation (2.9 ± 1.6 vs. 3.8 ± 2 years, p = 0.004), had higher estimated GFR (72.6 ± 22 vs. 63.8 ± 15.3 mL/min/1.73 m(2), p = 0.006) and had a higher percentage of patients with microalbuminuria (35% vs. 0%, p < 0.001). Additionally, general health and social functioning scores among paid unrelated donors were significantly lower (p < 0.001 and p = 0.02, respectively) than related donors. Other SF-36 scores, although lower in paid unrelated donors, did not reach statistical significance. Iranian paid unrelated donors have lower QOL and higher incidence of microalbuminuria compared with related donors., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)