National Repository of Grey Literature 3 records found  Search took 0.00 seconds. 
Mitochondria as a target of anticancer therapy.
Dvořák, Aleš ; Ježek, Petr (advisor) ; Poučková, Pavla (referee) ; Vecka, Marek (referee)
Mitochondrial isocitrate dehydrogenase 2 (IDH2) catalyzes reductive carboxylation (RC, reverse Krebs cycle pathway) and 2HG synthesis (2HG) - metabolite of which many scientists are interested. 2HG may be concurrently synthetized in cytosol by IDH1. RC is involved in anabolic reactions necessary for cell proliferation - produces citrate, fatty acid precursor - especially in hypoxia. IDH2 and IDH1 are not the only enzymes that are involved in 2HG synthesis. Recently, several enzymes, which participate in 2HG production, have been discovered. 2HG is useful in cancer diagnostics due to its overproduction by transformed cells. Moreover, 2HG may cause epigenetic changes via inhibition of 2-oxoglutarate dependent dioxygenase. In this work, the importance of RC and 2HG synthesis in cancer and healthy cells was investigated by gas chromatography with mass spectrometry detection as well as IDH2 influence. We found that IDH2 significantly participates in reverse RC and 2HG synthesis in breast cancer cell lines and uses glutaminolysis as a supplementary anaplerotic pathway. RC is increased by hypoxia, inhibition of respiration, and decreased by activation of respiration or hypocapnia. We confirmed 2HG synthesis and RC in healthy cells (fibroblasts, breast epithelial cells etc.) as well as in cancer cells....
The significance of the analysis of noncholesterol sterols and profile of fatty acids in various pathophysiological states
Vecka, Marek ; Tvrzická, Eva (advisor) ; Zadák, Zdeněk (referee) ; Kazdová, Ludmila (referee)
At present time, there is growing interest in two classes of lipids - sterols and fatty acids, which posses many different roles in living organisms. The concentrations of cholesterol biosynthetic precursors (lathosterol, desmosterol) reflect level of cholesterol biosynthesis, whereas the plasma phytosterol (campesterol, β-sitosterol) concentrations can be used for estimation of fractional absorption of dietary cholesterol. These groups are sometimes called together as noncholesterol sterols. The dissertation thesis dealt with the significance of analysis of noncholesterol sterols and fatty acid profile in various pathophysiological states. The methodology part of the thesis covered some aspects of analysis of these compounds with capillary gas chromatography. We found that for the minor fatty acid analysis, both the type of the column and the software used play an important role. The gas chromatography step contributes by the least part to the total error of the procedure, whereas the effect of other steps (extraction, thin-layer chromatography and methylation process) is more pronounced. The comparison of fatty acid profiles in lipoprotein particles with low and very low density revealed differences, but these differences were highly interindividual. We also found that it is possible to replace the...

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