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Mitochondria as a target of anticancer therapy.
Dvořák, Aleš
RK se podílí a prolifera i ádorový h u ěk ve stíže ý h zkrá e é Kre sově klu v tváří reverz í reak í z OG itrát, který ůže ýt e portová do tosolu, kde slouží jako prekurzor ast ý h k seli a další h olekul. )ároveň IDH při RK spotře ovává stej ě tak i při s téze HG NADPH. RK se tak z výzku u zdá ještě zají avější, e oť ůže ovliv it produk i ROS a íru o idač ího stresu. HG ůže ýt s tetizová a IDH i ěkolik další h e z ů. HG regulač í olekul součas é do ě je v užívá Bývá oz ačová jako ož ý i hi itor α DD , jež se pod í a růz ý h epige eti ký h z ě á h a zv šují alig itu rakovi ého fe ot pu spoje ou se z ě ou prolifera e u ěč ý h li ií h kar i o u prsu a další h uňká h, včet ě pri ár í h potka í h fi ro lastů a aktivitě respira e. de o strují, že HG ádorový h uňká h, a aví že ve zdravý h uňká h z ě hladi ovlivňují prolifera i. elkově jeví jako vhod ý íl proti ádorové terapie, zej é a ve světle edáv ý h o jevů, ve který h se ukázalo, že utova á íře s tézu α Klíčová slova: MS, uňk prs ího 6, fi ro last , HG/ OG po ěr, C izotopi ké z ače í, prolifera e fi ro lastů, h po ie
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The effect of carbon nanostructures on human cell behavior and the role of fetal bovine serum in cell adhesion
Jannová, Martina
Graphene (G) and nanocrystalline diamond (NCD) are carbon allotropes and promising nanomaterials with an excellent combination of their properties, such as high mechanical strength, electrical and thermal conductivity, possibility of functionalization and very high surface area to volume ratio. For these reasons, G and NCD are employed next to electronics in biomedical applications, including implant coating, drug and gene delivery and biosensing. For a fundamental characterization of cell behavior on G and NCD, we studied osteoblast adhesion and proliferation on differently treated G and NCD. Generally, both G and NCD exhibited better properties for osteoblast cultivation than control tissue culture polystyrene. Better cell adhesion but lower cell proliferation were observed on NCD compared to G. The most surprising finding was that hydrophobic G with nanowrinkled topography enhanced cell proliferation extensively, in comparison to hydrophilic and flat G and both NCDs (hydrophobic and hydrophilic) with slightly higher roughness. Promoted cell proliferation enables faster cell colonization of G and NCD substrates, meaning faster new tissue formation which is beneficial in biomedical applications. Furthermore, it was shown that osteoblast adhesion was promoted in the initial absence of fetal bovine...
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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....
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Adhesion, growth and differentiation of skin cells on nanofibrous polymer membranes
Pajorová, Júlia ; Bačáková, Lucie (advisor) ; Eckhardt, Adam (referee)
Our study contributes to the tissue engineering, mainly to the construction of appropriate scaffolds for regeneration of damaged skin. Simultaneously, it brings valuable insights for basic research in the field of molecular mechanisms of adhesion, proliferation and phenotypic maturation of cells and the control of the cell behavior through the cell extracellular matrix (ECM), represented by synthetic nanofibrous material. Nanofibrous polylactic-co-glycolic acid (PLGA) membranes were prepared by needle-less electrospinning technology. These membranes were further modified with cell adhesion-mediating biomolecules, e.g. collagen, fibronectin and fibrin in order to increase their affinity to colonizing cells. Adhesion, growth and differentiation of keratinocytes (HaCaT) and fibroblasts, i.e. major cell types of epidermis and dermis, were evaluated on these nanofibrous membranes. The results show that the membrane modification using fibrin structures improved adhesion and proliferation of human dermal fibroblasts. The collagen structure on the surface of membranes improved the adhesion and proliferation of human HaCaT keratinocytes. Furthermore, fibrin structure stimulated fibroblasts to produce collagen, which is a major component of ECM in the natural skin dermis. Fibronectin enhanced cell attachment...
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The effect of carbon nanostructures on human cell behavior and the role of fetal bovine serum in cell adhesion
Verdánová, Martina ; Hubálek Kalbáčová, Marie (advisor) ; Brábek, Jan (referee) ; Smetana, Karel (referee)
Graphene (G) and nanocrystalline diamond (NCD) are carbon allotropes and promising nanomaterials with an excellent combination of their properties, such as high mechanical strength, electrical and thermal conductivity, possibility of functionalization and very high surface area to volume ratio. For these reasons, G and NCD are employed next to electronics in biomedical applications, including implant coating, drug and gene delivery and biosensing. For a fundamental characterization of cell behavior on G and NCD, we studied osteoblast adhesion and proliferation on differently treated G and NCD. Generally, both G and NCD exhibited better properties for osteoblast cultivation than control tissue culture polystyrene. Better cell adhesion but lower cell proliferation were observed on NCD compared to G. The most surprising finding was that hydrophobic G with nanowrinkled topography enhanced cell proliferation extensively, in comparison to hydrophilic and flat G and both NCDs (hydrophobic and hydrophilic) with slightly higher roughness. Promoted cell proliferation enables faster cell colonization of G and NCD substrates, meaning faster new tissue formation which is beneficial in biomedical applications. Furthermore, it was shown that osteoblast adhesion was promoted in the initial absence of fetal bovine...
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The Role of the Tumour Microenvironment on Melanoma Cell Invasiveness
Jobe, Njainday ; Rösel, Daniel (advisor) ; Kořínek, Vladimír (referee) ; Bušek, Petr (referee)
Cancer cell invasion and metastasis are hallmarks of cancer. It is becoming apparent that the interaction between cancer cells and the surrounding microenvironment are involved in their ability to invade and metastasise. In general, cancer cells can either migrate individually, in an amoeboid or mesenchymal manner, or collectively. The first aim of this thesis was to analyse the role of NG2 in amoeboid to mesenchymal transition (AMT) and Rho/ROCK signalling. We found that NG2 promotes an amoeboid morphology, and increased invasiveness, in a Rho-dependent manner. Secondly, we analysed the role of the major tumour microenvironment (TME) component, cancer-associated fibroblasts (CAFs), on melanoma cell invasiveness. We found the CAF interaction with melanoma cells leads to increased levels of interleukin-6 (IL-6) and IL-8, and this leads to increased invasiveness. Simultaneous blocking of IL-6 and IL-8, using neutralising antibodies, inhibits CAF-dependent invasion. Further analysis of another major component in the melanoma TME, keratinocytes, has highlighted the importance of the tumour cell niche in invasion. Our results indicate that cancer cells have the ability to change morphology, and that the TME plays an important role in melanoma cell invasiveness. Metastatic melanoma treatment has proven...
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