Changes in erythrocyte membrane permeability induced by verapamil, chlorpromazine, and their combinations with amphotericin BHemolysis induced by 2 amphipathic agents, verapamil and chlorpromazine, was investigated in various incubation conditions. Changes in absorbance of erythrocyte suspension were monitored by absorption spectrophotometry at a wavelength of 590 nm. The hemolysis induced by verapamil or chlorpromazine is of the permeability type. The resistance of erythrocytes to verapamil is much higher than their resistance to chlorpromazine. No evident difference is found between human and pig erythrocytes in their resistance to verapamil. Only a small decrease in the rate of hemolysis induced by verapamil is observed in isotonic CaCl2, MgCl2or K2SO4solutions, compared to 160 mM KCl (the standard incubation medium). The changes in hemolytic activity of chlorpromazine in the presence of the divalent cations and anions are less evident. No decrease in hemolytic activity of chlorpromazine and verapamil is observed in the sucrose medium. The hemolytic activity of both the agents increases when they act in combination with polyene antibiotic amphotericin B. The results indicate a strong synergy between amphotericin B and verapamil or chlorpromazine. By contrast, a combined effect of verapamil and chlorpromazine on erythrocytes leads to a decrease in their hemolytic activity. This indicates antagonism between verapamil and chlorpromazine.

Summary A few years ago, a so far unknown type of intercellular connections, involved in communication was discovered. Due to their specific nano-architecture, these connections were named membrane nanotubes or tunneling nanotubes. Nanotubes ensure the transfer of both membrane and cytosolic cellular components, including organelles. Nanotubes also participate in calcium signal transduction and apoptosis signal. The length of the distance at which cells contact via nanotubes reaches several hundred micrometers. The published data suggest that nanotubes have heterogeneous structure. Among them, there are nanotubes which provide direct contact of the cytoplasm in connected cells (open-ended structure), and those, in which the transport requires overcoming a barrier, which is the cell membrane (close-ended structure). An important finding in the study of membrane nanotubes was demonstrating the ability of these connections of the intercellular transfer of pathogens, such as HIV, or abnormal form of PrP prion protein. In addition, nanotubes mediate a transport of MDR protein, involved in resistance of cancer cells to chemotherapy. It means that this type of cell connection may play an important role in the pathomechanism of AIDS, prion as well as cancer diseases.

Summary: Blood vessel formation in tumor is defined as tumor angiogenesis. So far, the most known its mechanism is sprouting, which means formation of blood vessels from existing ones, as a result of the proliferation and migration of endothelial cells. The main mitogenic factor of these cells is vascular endothelial growth factor VEGF, acting by VEGFR-2 receptors. Recent studies have provided knowledge about the ability of tumors to form vessel-like structures. The phenomenon was called vascular mimicry. Tumor cells show a high plasticity and they can undergo differentiation to the ones with phenotype similar to endothelial cells. Each of the known tumor angiogenesis mechanisms is a result of many different factors and cell cooperation in tumor microenvironment. Tumor ability to the heterogeneous vascularization forces developing of complex, anti-angiogenic therapy directed to different molecular and cellular targets. Therapies, used so far, often lead to drug-induced hypoxia, which increases tumor cell aggressiveness and metastasis.Keywords: tumor angiogenesis, vasculogenic mimicry, anti-angiogenic strategies, resistance to anti-angiogenic therapy Sprouting angiogenesis -formation via endothelial cells proliferation and migration towards avascular tumor area of new branches of blood vessels Intussusception -formation of blood vessels as a result of intussusception (septum) inside existing blood vessels Co-option -oxygen and nutrients acquire as a result of tumor cells migration along existing blood vessels Vasculogenic mimicry -formation by tumor cells of vessel-like structures, without endothelial cells participation Vasculogenesis -formation of tumor blood vessels de novo, as a result of endothelial progenitor cells recruitment

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Since their initial identification three decades ago, there has been extensive research regarding cancer stem cells (CSCs). It is important to consider the biology of cancer stem cells with a particular focus on their phenotypic and metabolic plasticity, the most important signaling pathways, and non-coding RNAs (ncRNAs) regulating these cellular entities. Furthermore, the current status of therapeutic approaches against CSCs is an important consideration regarding employing the technology to improve human health. Cancer stem cells have claimed to be one of the most important group of cells for the development of several common cancers as they dictate features, such as resistance to radio- and chemotherapy, metastasis, and secondary tumor formation. Therapies which could target these cells may develop into an effective strategy for tumor eradication and a hope for patients for whom this disease remains uncurable.