We previously reported that combinations of antibodies directed at non-overlapping epitopes of HER2 are endowed with enhanced antitumor effects, probably due to accelerated receptor degradation. Here, we extend these observations to three-dimensional mammary cell models, and compare the effects of single mAbs with the effects
of antibody combinations. Collectively, our in vitro assays and computational BYL719 research buy image analyses indicate that combining mAbs against different epitopes of HER2 better inhibits invasive growth. Importantly, while growth factors are able to reduce intraluminal apoptosis and induce an invasive phenotype, combinations of mAbs better than single mAbs can reverse the growth factor-induced phenotypes of HER2-overexpressing spheroids. In conclusion, our studies propose that mAb combinations negate the biological effects of growth factors on invasive growth of HER2-overexpressing cells. Hence, combining mAbs offers a therapeutic strategy,
potentially able to enhance clinical efficacy of existing antireceptor immunotherapeutics. Oncogene (2011) 30, 1631-1642; doi:10.1038/onc.2010.547; published online 6 December 2010″
“Background: Both coronary artery disease (CAD) and diabetes mellitus (DM) are associated with inflammation. However, whether and which leukocytes can predict the presence and extent of CAD in patients with DM has not been investigated. The aim of the present Silmitasertib study was to examine the association of leukocyte and its subsets counts with the severity of CAD in patients with
DM.\n\nMethods and Findings: Three hundred and seventy-three diabetic patients who were scheduled for coronary angiography due to typical stable angina pectoris were enrolled in this study. They were classified into the three groups according to tertiles of Gensini score (GS, low group <8, n = 143; intermediate group 8 similar to 28, n = 109; high group >28, n = 121). The relationship between the leukocyte and its subsets counts with the severity of CAD were evaluated. The data indicated that there were significant correlations between leukocyte and neutrophil counts with Buparlisib purchase GS (r = 0.154 and 0.156, respectively, all P<0.003 for Pearson’s correlation). Similarly, area under the receivers operating characteristic curve of leukocyte and neutrophil counts were 0.61 and 0.60 respectively (95% CI: 0.55-0.67, all P = 0.001) for predicting high GS. Multivariate logistic regression analysis demonstrated that leukocyte count was an independent predictor for high GS patients with DM (OR = 1.20, 95% CI 1.03-1.39, P = 0.023) after adjusting for conventional risk factors of CAD.\n\nConclusions: Compared with its subsets, leukocyte count appeared to be an independent predictor for the severity of CAD and the optimal cut-off value for predicting high GS (>28 points) was 5.