Browsing by Author "Erenpreisa, Jekaterina"
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Item Role of the Circadian Clock “Death-Loop” in the DNA Damage Response Underpinning Cancer Treatment Resistance(2022-03-01) Vainshelbaum, Ninel Miriam; Salmina, Kristine; Gerashchenko, Bogdan I.; Lazovska, Marija; Zayakin, Pawel; Cragg, Mark Steven; Pjanova, Dace; Erenpreisa, JekaterinaHere, we review the role of the circadian clock (CC) in the resistance of cancer cells to genotoxic treatments in relation to whole-genome duplication (WGD) and telomere-length regulation. The CC drives the normal cell cycle, tissue differentiation, and reciprocally regulates telomere elongation. However, it is deregulated in embryonic stem cells (ESCs), the early embryo, and cancer. Here, we review the DNA damage response of cancer cells and a similar impact on the cell cycle to that found in ESCs—overcoming G1/S, adapting DNA damage checkpoints, tolerating DNA damage, coupling telomere erosion to accelerated cell senescence, and favouring transition by mitotic slippage into the ploidy cycle (reversible polyploidy). Polyploidy decelerates the CC. We report an intriguing positive correlation between cancer WGD and the deregulation of the CC assessed by bioinformatics on 11 primary cancer datasets (rho = 0.83; p < 0.01). As previously shown, the cancer cells undergoing mitotic slippage cast off telomere fragments with TERT, restore the telomeres by ALT-recombination, and return their depolyploidised offspring to telomerase-dependent regulation. By reversing this polyploidy and the CC “death loop”, the mitotic cycle and Hayflick limit count are thus again renewed. Our review and proposed mechanism support a life-cycle concept of cancer and highlight the perspective of cancer treatment by differentiation.Item Toluidine Blue Test for Sperm DNA Integrity and Elaboration of Image Cytometry Algorithm(2003-03) Erenpreisa, Jekaterina; Erenpreiss, Juris; Freivalds, Talivaldis; Slaidina, Maija; Krampe, Rasma; Butikova, Jelena; Ivanov, Andrey; Pjanova, DaceBackground: Sperm DNA integrity is of paramount importance in the prognosis of fertility. We applied image cytometry to a toluidine blue (TB) test we recently proposed. Methods: Sperm samples from 33 men were assayed for standard sperm parameters and classified as normal or abnormal. Sperm smears were subjected to the TB test, DNA denaturation testing with acridine orange (AO), and terminal deoxyuridine triphosphate biotin nick end labeling (TUNEL). In CCD image analysis, TB-stained sperm cell heads were microscopically assigned to one of four color groups (dark, blue, light violet, and light blue). The optical densities of 6,600 cells in green and red CCD images were used to elaborate an algorithm for discrimination of these groups. Results: The proportions of sperm in TB color groups, as estimated with the developed image cytometry algorithm, correlated with microscopic features. The number of TB dark cells correlated with the number of AO-red and TUNEL+ cells. The proportion of TB dark cells in normal samples did not exceed 35%. Light-blue sperm cell heads prevailed in normal samples, whereas dark and blue sperm cell heads dominated in abnormal samples. Conclusions: The TB test was suitable for the assessment of sperm cell DNA integrity. The elaborated image cytometry algorithm can be used for this purpose and for finer determination of sperm nucleus status.Item When Three Isn't a Crowd : A Digyny Concept for Treatment-Resistant, Near-Triploid Human Cancers(2019-07) Salmina, Kristine; Gerashchenko, Bogdan, I; Hausmann, Michael; Vainshelbaum, Ninel M.; Zayakin, Pawel; Erenpreiss, Juris; Freivalds, Talivaldis; Cragg, Mark S.; Erenpreisa, Jekaterina; Rīga Stradiņš University