Aim - to compare biological properties of primary tumor cells isolated from malignant effusion of cancer patients with the same cells of permanent lines established during their long-term cultivation in vitro and to assess the impact of phenotypic conversion that was caused by changes in their microenvironment on their behavioral characteristics. The study was performed on primary cell cultures from pleural effusion or ascites of breast and ovarian cancer and permanent cell lines derived from them, namely permanent ovarian cancer cell line I, permanent ovarian cancer cell line II and permanent breast cancer cell line I. Biological characteristics were studied using standard cell culture methods and immunocytochemical assays. Three new cell lines were established from breast and ovarian cancer and cell morphology, migration activity, the kinetics of growth, colony forming activity in semisolid agar and sensitivity to anticancer drug were examined. These characteristics were compared with those of the primary tumor cells. It has been shown that among the primary tumor cells from malignant effusion, cells with mesenchymal characteristics were the most prevalent. Cultivation of primary cancer cells in vitro leads to a phenotypic change of their population: it becomes more homogeneous in morphology with predominantly epithelial-like cells. Also, later after a number of cell doublings in vitro, the cell population changes to include cells primarily with immunophenotypic properties characteristic of epithelial cells. These changes include increase in number of E-cadherin-positive cells and a decrease in number of vimentin and alpha-smooth muscle actin-positive cells. It was found that significant changes in expression of epithelial-mesenchymal transition associated proteins in cells during their cultivation in vitro in new microenvironment are accompanied by a rapid change in their sensitivity to anticancer drugs. Conclusions: the new breast and ovarian cancer cell lines were established and characterized. The induction of phenotypic transdifferentiation in malignant cells from pleural effusion and ascites can be an important approach for suppressing the progression of neoplastic process.

Objective: to estimate the impact of the low-dose anticancer drugs (ACD) with the different mechanisms of action and human interferon (IFN) alpha 2b on the biological properties, immunophenotypic and cytogenetic characteristics of colon cancer cells in vitro. The study was performed on human colon cancer cell lines COLO 205, HT-29 and 3C-P treated with ACD and IFN in subtoxic concentrations. Expression of CD44, N-cadherin, vimentin, beta-catenin, ERCC1 and Slug was assessed by immunocytochemical method. Using cytogenetic analysis, the numbers of mitoses, cells with micronuclei, apoptotic cells and cells with nuclear protrusions were studied. The prolonged exposure (up to 30 days) of colon cancer cells to low-dose ACD (0,2 - 0,5 mu g/ml cisplatin and 0,1 - 0,2 mu g/ml irinotecan) in combination with IFN (500 - 1000 IU/ml) led to 37-fold decreased colony-forming activity of these cell and 10-fold reduction of the number of cells expressing mesenchymal protein markers (N-cadherin, vimentin). Also, in COLO 205 cells treated with ACD and IFN the number of SLUG- and CD44-positive cells decreased by 92 and by 85 %, respectively. Long-term cultivation of HT-29 cells in the presence of cisplatin and IFN resulted in 5-fold suppression of ERCC1 expression. The cytogenetic analysis has shown that the ACD, IFN and their combinations in subtoxic concentrations caused significant genotoxic effect, suppression of cell proliferation and accumulation of cells with micronuclei. The sensitivity of colon cancer cells to ACD in standard cytotoxic concentrations did not change after prolonged low-dose exposure. Conclusion: the data showed that the prolonged action of the low doses of ACD on human colon cancer cells resulted in the suppression of cell proliferation, colony-forming activity in soft agar, expression of epithelial-mesenchymal transition-associated markers and significant cytogenetic changes.

Індекс рубрикатора НБУВ: Р569.133.1

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Пухлини молочних (грудних) залоз

Шифр НБУВ: Ж14160 Пошук видання у каталогах НБУВ 

The article is devoted to the comprehensive analysis of scientific, practical and legal issues of personalized medicine that is a rapidly developing science-driven approach to healthcare. It is concluded that there is lack of general legal framework for the encouragement of scientific researches and practical implementation in this field. The article shows foreign experience and prospects for the introduction of personalized medicine as a key concept of healthcare system, which is based on a selection of diagnostic, therapeutic and preventive measures that would be the most effective for a particular person in view of individual characteristics. The conclusions and proposals to improve the current legislation and development of personalized medicine in Ukraine are suggested.