Transcriptional Reprogramming Regulates Tumor Cell Survival in Response to Ionizing Radiation: a Role of p53.

Senexin B, a non-toxic selective inhibitor of cyclin-dependent protein kinases 8 and 19 (CDK8 and CDK19), in combination with γ-photon irradiation in doses of 2-10 Gy increased the death of colon adenocarcinoma cell line HCT116 (intact p53) in a logarithmically growing culture, which was accompanied by the prevention of cell cycle arrest and a decrease of "senescence" phenotype. The effect of senexin B in cells with intact p53 is similar to that of Tp53 gene knockout: irradiated HCT116p53KO cells passed through the interphase and died independently of senexin B. The inhibitor reduced the ability of cells to colony formation in response to irradiation; p53 status did not affect the effectiveness of the combination of radiation and senexin B. Thus, the CDK8/19 inhibitor senexin B increased cell sensitivity to radiotherapy by mechanisms dependent and independent of p53 status.

[The p53 Tumor Suppressor and Copper Metabolism: An Unrevealed but Important Link].

The balance of redox reactions and the fate of the tumor cell are closely related to the regulation of intracellular homeostasis of transition metals, among which copper and its compounds play a key role. Elevated levels of intracellular copper may be a cause and/or consequence of malignancy, since the metabolism of this metal affects the functioning of the electron transport chain, transcription regulation, cell growth, and migration. This wide range of actions is used in antitumor therapy: ROS generation and apoptosis mediated by copper addition, copper deprivation by chelators, and targeted inhibition of specific participants in the copper metabolism chain effectively reduce the survival of tumor cells. However, the exact mechanisms of influence on the cell cycle and cell death behind the activity of copper-associated drugs are still largely unexplored. Numerous attempts to identify them led to the identification of the induction of oxidative stress and the activation of apoptotic cascades via the p53 tumor suppressor, an integral attribute of the action of such compounds. At the same time, the influence of p53, apparently also extends onto the activity of copper metabolism proteins, mediating the processes of antioxidant protection and survival. More and more research data confirm that the interaction of copper and p53 is multifaceted and is not limited solely to ROS. The purpose of this review is to describe how p53 regulation is related to copper metabolic pathways and how this interaction can be used to improve the effectiveness of oncotherapy.

The p53 Protein Family in the Response of Tumor Cells to Ionizing Radiation: Problem Development.

Survival mechanisms are activated in tumor cells in response to therapeutic ionizing radiation. This reduces a treatment's effectiveness. The p53, p63, and p73 proteins belonging to the family of proteins that regulate the numerous pathways of intracellular signal transduction play a key role in the development of radioresistance. This review analyzes the p53-dependent and p53-independent mechanisms involved in overcoming the resistance of tumor cells to radiation exposure.

Metal-derived nanoparticles in tumor theranostics: Potential and limitations.

Initially, metal derived nanoparticles have been used exclusively as contrasting agents in magnetic resonance imaging. Today, green routes of chemical synthesis together with numerous modifications of the core and surface gave rise to a plethora of biomedical applications of metal derived nanoparticles including tumor imaging, diagnostics, and therapy. These materials are an emerging class of tools for tumor theranostics. Nevertheless, the spectrum of clinically approved metal nanoparticles remains narrow, as the safety, specificity and efficiency still have to be improved. In this review we summarize the major directions for development and biomedical applications of metal based nanoparticles and analyze their effects on tumor cells and microenvironment. We discuss the advantages and possible limitations of metal nanoparticle-based tumor theranostics, as well as the potential strategies to improve the in vivo performance of these unique materials.

Effect of Sol-Gel Alumina Biocomposite on the Viability and Morphology of Dermal Human Fibroblast Cells.

This paper is the continuation of our previous work on the ability of biocomposites based on sol-gel alumina (boehmite) to promote skin recovery from burns and atrophic scars. The present study describes the increasing of the cytoplasma volume and the number of filopodias of HDF cells, which for the first time indicates their proliferation on the alumina itself and on alumina-based biocomposite. Studies in vivo confirm the efficiency of the composite in the treatment of atrophic scars.

SAFETY AND IMMUNOGENICITY OF COLD-ADAPTED RECOMBINANT INFLUENZA VECTOR EXPRESSING ESAT-6 AND AG85А ANTIGENS OF M. TUBERCULOSIS.

Recombinant viral vectors represent one of the most promising platforms for creating a new generation of vaccines against tuberculosis. We constructed a vaccine candidate based on a cold-adapted influenza vector with a truncated NS1 protein containing an insert of tuberculosis ESAT-6 and Ag85A antigens. The recombinant virus possessed a cold-adapted and temperature-sensitive phenotype and was attenuated for mice when administered intranasally. Immunofluorescent staining and Western blot showed the expression of ESAT-6 protein in MDCK cells infected by recombinant virus. After intranasal administration to mice, the recombinant virus stimulated a specific anti-tuberculosis CD4 + Th1-type response with the formation of polyfunctional antigen-specific T cells.