Horbay R. Morphofunctional characteristics of giant murine Nemeth-Kellner lymphoma cells and it sensitiveness to drugtreatment

In the thesis the pathways of formation of giant cancer cell, mechanisms of their functional regulation and elimination have been studied. An effective method to obtain giant cell-enriched ascites was designed. Several cytomorphological changes of the giant cancer cells were found (such as chromatine condensation, inner vacuolization and plasma membrane blebbing) comparing to parental ones. Giant cells posses a 2.8x higher atomaric oxygen release after plasma membrane permaebilization. Oligomycin inhibited the respiration rate of giant cells by 46%, whereas of the parental - by 12 %. This results in tighter coupling of mitochondrial respiration and oxidative phosphorylation. Doxorubicin and cisplatine reduced the number of parental cell, whereas the giant ones were drug resistant. Vinblastine induced apoptosis in giant cancer cells via p53- and AIF-dependent pathways. The higher the dose was, the higher the level of these proteins occurred. After a single injection of vinblastine conjugated with nanosized carriers VEP-GMA-PEG the number of giant cells increased up to 85 %, whereas a pure drug had similar effect after a third injection (83 %).