Volodko N. Role of some cell-molecular factors microenvironment in progression of malignant tumours of the female reproductive system

Thesis is devoted to the topical issue of oncology - investigation of the pathogenetic role of some cell-molecular factors of tumor microenvironment in the progression of breast cancer (BC) and ovarian cancer (OC), the definition of their predictive value, the development of therapeutic approaches, abrogating their negative effects. In particular, the concentrations of TNFand TGF-beta in primary culture conditional media, the expression level of lamіnіn, CD44s and its CD44v5, CD44v6 isoforms, quantity and functional activity of tumor-associated macrophages, tumor microvessels density in the local and advanced stages of tumour growth and in OC and BC patients were evaluated. It has been revealed, that proven indicators of adverse prognosis and aggressive clinical course BC are the high degree of tumour-associated macrophage infiltration, the increased expression level of the TNF in tumour microenvironment, the high degree of microvesseles density in tumours, high expression ofCD44v5 isoform, the reduced expression of laminin and the reduced level of TGF-beta, which were associated with metastatic spreading in the regional lymph nodes and the worst survival. The new criteria for determining the aggressive outcome of OC were proposed. They included the high concentration of TNF (> 0.7 ng/ml) in the supernatants of primary tumor cultures, the reduced level of TGF-beta, a high degree of microvessels density. Chemoresistance of recurrent OC is accompanied by proinflamatory reactions in tumour microenvironment, which included the growth of TNF expression, reducing the TGF-beta expression, high and moderate degree of TAM infiltration, high microvessels density, and expression of the mutant p53. The application of modulators activity of cytokines tumour microenvironment in treatment of recurrent chemoresistant OC has been substantiated. The method of metronomic usage of tamoxifen, nimesulid, laferon had been developed and its efficacy was evaluated. It allowed to improve the overall survival and quality of life of recurrent chemoresistant OC patients.