Aim: To determine frequency of tumors with immunohistochemical markers of cancer stem cells (CSC) CD44+/CD24− in patients with breast cancer (BC) of different molecular subtype and to evaluate their prognostic value. Object: Surgical material of 132 patients with BC stage I–II, age from 23 to 75 years, mean age — 50.2 ± 3.1 years was studied. Methods: Clinical, immunohistochemical (expression CD44+/CD24−), morphological, statistical. Results: BC is characterized by heterogeneity of molecular subtypes and expression of markers (CD44+/CD24−). Immunohistochemical study of expression of CSC markers in surgical material has detected their expression in 34 (25.4%) patients with BC of different molecular subtypes. The highest frequency of cells with expression of CSC marker was observed in patients with basal molecular subtype (44.8% patients). Most of BC patients with phenotype CD44+/CD24 had stage I of tumor process (34.3%). Statistical processing of data has showen that Yule colligation coefficient equaled 0.28 (р > 0.05) that argues poor correlation between stage of tumor process and number of tumors with positive expression of CSC markers. Statistical processing of data has showen high correlation between presence of cells with expression of CSC markers and metastases of BC in regional lymph nodes (Yule colligation coefficient equals 0.943; р < 0.5). Difference in overall survival of patients with BC of basal molecular subtype depending on expression of CSC CD44+/CD24− markers was detected. Survival of patients with basal BC was reliably higher at lack in tumors of cells with CSC markers CD44+/CD24− and, correspondingly, lower at presence of such cells (р < 0.05). In patients with BC of luminal (A and B), HER-2-positive subtypes, significant change in survival of patients depending on expression of CSC markers was not determined (р > 0.05). Conclusion: Significance of tumor cells with markers CD44+/CD24− within the limits of molecular subtype of BC may be additional criterion for advanced biological characteristic of BC, and in patients with BC of basal molecular subtype — for predictive evaluation of individual potential of tumor to aggressive clinical course.

Aim: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin — Dox; cisplatin — DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. Materials and Methods: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Results: Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Conclusions: Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment.

Summary. Aim: to determine at the optical level the role of the fibrillar organization of the collagen-containing connective tissue component of the primary tumor focus in prostate cancer (PCa) progression. Objects and methods: the morphological study is based on the analysis of the histological material of the primary tumor foci of 55 PCa patients without tumor progression in the postoperative period and bone metastases. The tumors were graded Gleason 6–9 at surgery. The features of the architecture of collagen-containing connective tissue in tumors were determined in histological slides stained by Van-Gieson. Results: the remodeling of the collagen-containing stromal component located both around the glandular structures (increase in the percentage of straight and aligned collagen fibers compared to the curved ones) and in the stroma itself has been found. Such remodeling is manifested by an increase in the total mass of fibrous structures, an increase in the width of collagen fibrils, their compaction in relation to the density of their location, peculiarities of desmoplasia, alignment and elongation. The specified features are consistent with the Gleason score and the postoperative disease course, namely, the occurrence of metastases. Conclusions: the desmoplastically changed collagen-containing connective tissue component of the PCa creates favorable conditions for the unimpeded migration and realization of the invasive potential of cancer cells, in particular those expressing bone tissue remodeling proteins.