Ribonucleases (RNases) are a non-mutagenic alternative to harmful DNA-damaging anticancer drugs. Targeting of RNases with antibodies to surface antigens that are selectively expressed on tumor cells endows specificity to the cytotoxic actions of RNases. Barnase, a ribonuclease from Bacillus amyloliquefaciens, is a promising candidate for targeted delivery to cancer cells because of its insusceptibility to the ubiquitous cytoplasmic ribonuclease inhibitor, and its high stability and catalytic activity. Here, we characterized in vitro and in vivo an immunoRNase, scFv 4D5-dibarnase, which consists of two barnase molecules that are fused serially to the single-chain variable fragment (scFv) of humanized 4D5 antibody. The latter is directed against the extracellular domain of human epidermal growth factor receptor 2 (HER2), a cancer marker that is overexpressed in many human carcinomas. The scFv 4D5-dibarnase exerted a specific cytotoxic effect on HER2-overexpressing SKBR-3 and BT-474 human breast carcinoma cells (IC(50) = 4.1 and 2.4 nM, respectively) via induction of apoptosis. Ten doses of 0.7 mg/kg scFv 4D5-dibarnase to BALB/c nude mice that bore SKBR-3 human breast cancer xenografts resulted in a 76% reduction in tumor growth. A single injection of scFv 4D5-dibarnase at a total course dose of 7 mg/kg did not cause severe side effects in BALB/c nude or BDF1 mice. The cytotoxicity and selectivity of scFv 4D5-dibarnase merit consideration of this immunoRNase as a potent anticancer agent.
The developed technique of PTX sustained delivery from PHB-microparticles has therapeutic potential as prolong anticancer drug formulation.
Introduction: the main purpose of this paper is to present the theoretical and practical aspects of professional and personal self-development of future professionals, the construction of the structural model and the determination of levels of self-development. The study of personal and professional self-development attributes of future professionals is of special interest to modern researchers, as well as for practicing psychologists studying the problem of self-realization and self-improvement in their professional fields. This article discusses the theoretical approaches to the study of the model and structure of personal and professional self-development. It analyses the results of the comparative empirical study of the features of students self-development with various levels of formation of motivational-semantic sphere. The authors carried out the detailed theoretical analysis of the problem of personal and professional self-development. They offer the structural model of the process, including the set of interrelated value-semantic, reflexive and regulatory components. The study revealed that the personal and professional self-development is a comprehensive system based on the active personal transformation being carried out in the course of behavior and activities self-regulation of their behavior, designed to achieve personal and professional goals. Materials and Methods: diagnostic methods were used to identify the level of self-development and personal qualities of students. Processing of the data was carried out by means of correlation, factor and cluster analysis. Results: this article considers the results of the empirical study conducted with the help of psycho-diagnostic methods aimed at identifying the level of self-development of future professionals, its structure and features. The scientifically valid results are obtained, allowing to identify the levels of self-development of students as well as to identify factors affecting the process of self-development of future social sphere specialists. Discussion and Conclusions: the structural model of the personal-professional self-development includes a set of interconnected components: value-semantic, reflexive and regulative. The main factor influencing the process of personal and professional self-development of future professionals is the indicator of the meaningfulness of life, which is significantly associated with readiness to self-knowledge and selfdevelopment and affect the level of self-development. The desire for self-development can be considered as one of the personal and professional values, which give future professionals the opportunity to feel the meaningfulness of life, satisfaction with the process and its results, and achieve their personal and professional goals. The results of this study have several important implication for practicing psychologists who can broaden the scope of research of self-development and self-identity processes and determine the basic ways of self-realization of the young people potential in their profes...
We studied the effect of combination treatment with T-activin and vitamin E on acute toxicity and antitumor activity of cyclophosphamide in mice. Combined administration of these preparations 1.37-fold increased the maximum permissible dose of cyclophosphamide without affecting its LD(50)and delayed mouse death from cyclophosphamide toxicity. Most mice died only 3 days after combination treatment with the test preparations and cyclophosphamide in doses of LD(16)-LD(84). The second peak of death from hematologic toxicity of cyclophosphamide was absent under these conditions. T-activin and vitamin E did not abolish the antitumor effect of cyclophosphamide on mice with subcutaneously implanted P-388 lympholeukemia. Tumor growth was suppressed by 100%.
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