Focal Adhesion Kinase Suppresses Apoptosis by Binding to the Death Domain of Receptor-Interacting Protein

Tumor cells resist the apoptotic stimuli associated with invasion and metastasis by activating survival signals that suppress apoptosis. Focal adhesion kinase (FAK), a tyrosine kinase that is overexpressed in a variety of human tumors, mediates one of these survival signals. Attenuation of FAK expression in tumor cells results in apoptosis that is mediated by caspase 8- and FADD-dependent pathways, suggesting that death receptor pathways are involved in the process. Here, we report a functional link between FAK and death receptors. We have demonstrated that FAK binds to the death domain kinase receptor-interacting protein (RIP). RIP is a major component of the death receptor complex and has been shown to interact with Fas and tumor necrosis factor receptor 1 through its binding to adapter proteins. We have shown that RIP provides proapoptotic signals that are suppressed by its binding to FAK. We thus propose that FAK overexpression in human tumors provides a survival signal function by binding to RIP and inhibiting its interaction with the death receptor complex

Combination of RGD Compound and Low-Dose Paclitaxel Induces Apoptosis in Human Glioblastoma Cells

) peptide, to human glioblastoma U87MG cells with combination of low dose Paclitaxel (PTX) pre-treatment to augment therapeutic activity for RGD peptide-induced apoptosis. peptide induced U87MG programmed cell death. The increased expression of PTX-induced integrin-αvβ3 was correlated with the enhanced apoptosis in U87MG cells.This study provides a novel concept of targeting integrin-αvβ3 with RGD peptides in combination with low-dose PTX pre-treatment to improve efficiency in human glioblastoma treatment

Investigation of industrial contamination of protective clothing at oil industry sector

The article presents the research results of the interaction of the protective clothes surface with polluting components of production facilities of the oil and oil refining industry. The development direction of an oil-resistant clothing segment is proved. The aggressive components of the production environment of the oil sector are substantiated with respect to the protective functions of special clothes. Oil and petroleum products lead to a change in the properties of textile materials. This depends on the concentration of aggressive components in the structure of textile materials. The research results of the interaction of petroleum products with a textile composition of a woven structure with protective properties are presented. Based on the study of 50 suits that have passed the operational cycle of one season, restrictions are established on the areas of the clothing surface of uneven protection. Clothing zones risk-affected loss of protective effect is established. The results of experimental studies of the concentration of petroleum products in textile materials after chemical purification based on the method of gas capillary chromatography are presented. It was found that the main component with a high concentration of pollutants is hydrocarbons from C14H30 Tetradecane to C36H74 Hexatriacontane. The average values of the concentration of hydrocarbons on the purified samples for the main parts of the clothing surface were established. Using the methods of acoustic emission, the experimental level of contact activity of the permeability of the liquid phase of crude oil in the structure of woven textiles at the boundary of media is established. The effect of the saturation of protective clothing by the petroleum fractions on its strength has been experimentally evaluated. The chemical compositions of the active phases were identified on the basis of experimental data. This is the contact materials of industrial pollution at oil refining facilities. Recommendations have been developed to improve the system of individual protection of man during interaction with a polluting environment taking into account chemically aggressive components

CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts

Recent evidence suggests that breast cancer and other solid tumors possess a rare population of cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. We report here the development of a strategy to target these breast cancer stem cells (CSCs) through blockade of the IL-8 receptor CXCR1. CXCR1 blockade using either a CXCR1-specific blocking antibody or repertaxin, a small-molecule CXCR1 inhibitor, selectively depleted the CSC population in 2 human breast cancer cell lines in vitro. Furthermore, this was followed by the induction of massive apoptosis in the bulk tumor population via FASL/FAS signaling. The effects of CXCR1 blockade on CSC viability and on FASL production were mediated by the FAK/AKT/FOXO3A pathway. In addition, repertaxin was able to specifically target the CSC population in human breast cancer xenografts, retarding tumor growth and reducing metastasis. Our data therefore suggest that CXCR1 blockade may provide a novel means of targeting and eliminating breast CSCs