Targeting of mechanochemically activated doxorubicin (MA DOXO) nanoparticles, conventional doxorubicin, and electromagnetic irradiation (EMI) at A-549 lung carcinoma cells in vitro was investigated. Conventional DOXO was micronized using an input energy of 20 W/g for 5 min resulting in positively charged MA DOXO particles 10 times smaller than conventional DOXO. Mechanochemical activation gives rise to additional free quinone radicals. High performance liquid chromatograph analyses demonstrate that conventional and MA DOXO are quantitatively similar. Tumor cells were exposed to 40 MHz electromagnetic irradiation at a power density of 2 W/cm2. The lethal dose LD50 values of MA DOXO were 5 times greater than conventional doxorubicin. MA DOXO in combination with EMI at 37 degrees C demonstrates improved drug delivery to A-549 human lung carcinoma and greater cell kill than does conventional DOXO.

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. Materials and Methods: 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. Results: 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 α- 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.

Breast cancer provides a typical example of an inflammation-linked malignant disease. The inflammatory components present in the tumor microenvironment contribute to the further progression of the disease. The present study was conducted to evaluate the correlation between levels of proinflammation cytokines tumor necrosis factor α, interleukin 1β, interleukin 6, C-reactive protein and tumor recurrence in breast cancer patients. Seventy two breast cancer patients with histologically proven diagnosis and 15 healthy donors were enrolled into study. Thirty one patients with progression of the disease and 41 patients with clinical stabilization (conditional remission) were included to "progression" and "remission" groups respectively. This division of breast cancer patients was made during the 3 years study. The levels of proinflammation cytokinestumor necrosis factor α, interleukin 1β, interleukin 6 and C-reactive protein were revealed. This cytokines in bone marrow and peripheral blood act as a specific microenvironment and was found that the elevated levels of this cytokines were strongly associated with progression of breast cancer. The data showed that most prominent predictive markers of tumor recurrence are high levels of indicated cytokines in combination with other markers (C-reactive protein; disseminated tumor cells in bone marrow). Determination of the high levels of tumor necrosis factor, interleukin 1β, interleukin 6 in bone marrow and peripheral blood of breast cancer patients are important to establish the features of bone marrow microenvironment for prediction of metastasis and correction antitumor therapy.

The aim of this study was to investigate an inhibitory effect of baculovirus-mediated transduction of the murine interferon-beta gene on mouse melanoma in vitro and in vivo. Methods. Studies were performed on B16 mouse melanoma (MM-4 cell line). Transduction, immunocytochemical and tumor cell biology approaches have been used in this study. Results. Transduction of MM-4 cells by the recombinant baculovirus with IFN-beta gene is accompanied by morphological changes of tumor cells, suppression of cell proliferation, significant inhibition of platting efficiency of cells and their colonies formation in semisolid agar. Moreover, transduction of melanoma MM-4 cells by the baculovirus IFN-transgene leads to inhibition of tumorigenicity and metastatic ability of the cells in vivo.The intravenous administration of recombinant baculovirus vector with IFN gene inhibits growth of metastases induced in the lungs of mice by intravenously injected tumor cells. Conclusions. Transduction of mouse melanoma cells by the recombinant baculovirus with murine IFN-beta gene inhibits their proliferative potential, tumorigenicity and metastatic activity.

The mutational events that take place in mammalian somatic cells influenced with different endogenous and exogenous factors are presented in this review. The nonchromosomal method of research allows taking into account the complex cell characteristics without time-consuming analysis of the chromosomes as such. As a result, the information can be obtained about the mitotic (phases of mitosis, the number of nuclei per cell, micronuclei, pathology of mitosis) and vital (mitotic index, apoptosis) cell statuses, as well as about the state of chromosomal integrity (the presence of nucleoplasmic bridges, nucleus protrusions, chromosome fragmentation, micronuclei). Depending on the material studied (erythrocytes and lymphocytes of peripheral blood, buccal cells, permanent cell lines etc.), a complex of cytogenetic characteristics can be selected for each case which is the most informative for determination of the mutational spectra in mammalian somatic cells