Garmanchouk L. Cellular model systems to identify and evaluate the effects of biologically active substances

Obect: biological mechanisms of action on cells of synthetic and natural compounds - of potential therapeutic agents with anticarcinogenic and immunomodulatory actions. Aim: To develop, characterize, and test cell model systems for screening of anticarcinogenic and immunomodulating agents. Methods: The methods of cell biology, biochemical, immunological, cytofluorimetric, HRP methods of studying cells, Methods of Experimental Oncology, evaluation of adhesive properties of cells, generate spheroid, Western blot analysis, spectroscopic, colorimetric analysis, statistical methods. Results: Of the models involving contact and contactless cocultivation tumor, endothelial and immunocompetent cells for the first time shown the significant role of intercellular communication in tumor angiogenesis that is mediated system proangiogenic growth factors and their receptors. In various models of experimental carcinogenesis, sets of samples of surgically resected tumors and autologous serum from patients with breast cancer, and in cultured epithelial cell functional role of erbB/EGF-R family receptors in cell proliferation, angiogenesis and tumor metastasis have been uncovered. Futhermore, correlations between the patient survival and levels of erB/EGF-R like receptor in tumors and antibodies to the erbB/EGF-R in the circulating immune complexes of serum have been registered. A multilevel system for the screening of the neuro-immunomodulating effects of drugs with neuroprotective action was developed based on the use of cell lines, primary cultures and the experimental model for the induced hemorrhagic insult in rats. Novelty: With applying of the cell model systems, in the thesis were developed the principles for efficiency assessment of potential carcinogenic and immunomodulating pharmaceuticals. Introduced into scientific research of the ESC "Institute of Biology" of Taras Shevchenko National University of Kiev and the two NASU research institutes. Scope: cell biology, biochemistry, molecular biology, pharmacology, medical diagnostics.