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Glycolytic enzymes and their inhibition in cancer cell invasiveness
Martinková, Eliška ; Peltanová, Barbora (advisor) ; Raudenská, Martina (referee)
Glycolysis, an essential metabolic pathway, serves to obtain energy from glucose. All ten enzymes, which are part of the glycolytic pathway, may be involved in processes that influence migration and the ability of tumor cells to invade surrounding tissues, which is closely related to the formation of metastases. Since the majority of patients with diagnosed solid tumors die because of complications associated with primary tumor metastases, studying this phenomenon is of great interest. The purpose of this thesis is to summarize the findings on the relationship between glycolytic enzymes and tumor cell invasion. Diverse roles of enzymes related to invasion, migration and metastases are described herein, ranging from influencing angiogenesis, cytoskeleton formation and mRNA and protein stabilization to affecting various signal cascades. Room is devoted not only to the relevant mechanisms at the molecular level but also to the results of research focused on therapy to date. The thesis also provides an overview of selected inhibitors of glycolytic enzymes that affect tumor cells invasion. Key words: invasion, migration, metastasis, glycolytic enzymes, inhibition, EMT, Warburg effect
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Mitochondrial dysfunction in brain tumors
Rollerová, Kateřina ; Vaňátko, Ondřej (advisor) ; Zobalová, Renata (referee)
Brain tumors are one of the most serious pathologies of the central nervous system. Brain tumors are aggressive and very hard to treat due to the fragile nature of the nervous system, presence of blood-brain barrier and high recurrence rate. One of the hallmarks of brain tumors is mitochondrial dysfunction. Mitochondria are organelles involved in essential cellular processes, such as energy production, redox and calcium signaling, or the regulation of cell death. Structural and functional abnormalities, mutations in the mitochondrial genome and other mitochondrial dysregulations may cause disruptions in various cellular processes, such as production of reactive oxygen species, migration, proliferation, or regulation of cell death, promoting the development and/or maintenance of brain tumors. The goal of this thesis is to summarize current knowledge about mitochondrial dysfunction in brain tumors. Key words: brain tumors; mitochondria; mitochondrial dysfunction; Warburg effect; apoptosis; reactive oxygen species; isocitrate dehydrogenase
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Metabolic alterations in cancer cells and their implications in the therapy of acute leukemias
Harárová, Alžbeta ; Starková, Júlia (advisor) ; Mrvová, Silvia (referee)
Cancer metabolism differs from that of the healthy cells in several aspects. Aerobic glycolysis (e.g. converting pyruvate to lactate under normoxic conditions) was the first described metabolic alteration of cancer cells. Metabolic alterations have since been described in the tricarboxylic acid cycle, oxidative phosphorylation, in the metabolism of amino acids (especially glutamine, asparagine and serine) and also in the metabolism of fatty acids and cholesterol. The common feature of these changes is the tendency to prefer anabolic pathways, thus enabling fast proliferation of cancer cells. The study of cancer metabolism is particularly important in the case of cancer cells that show resistance to treatment, as their aberrant metabolism is not only a potential diagnostic marker but also a potential therapeutic target. The majority of metabolic alterations have been described for the first time in solid tumors, whereas only recently has the metabolism of acute leukamias gained more attention. Asparaginase is an example of a chemotherapeutic agent that targets a metabolic alteration of leukemic cells. Distinct metabolic profile is also associated with the glucocorticoid resistance. Detailled study of the metabolic alterations of leukemic cells has elucitated the mechanisms of the asparaginase and...
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The role of mitochondrial respiratory chain in invasiveness and metastasis of cancer cells and possible therapeutic interventions
Legátová, Anna ; Brábek, Jan (advisor) ; Truksa, Jaroslav (referee)
The mitochondrial respiratory chain, also called the electron transport chain (ETC), has a pivotal role in key features of cancer cells e.g., proliferation, the metabolic shift from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, or the ability to form metastases. This review summarizes current knowledge about ETC and its relationship to cancer, especially to invasiveness and metastases formation. Firstly, it deals with a process called the Warburg effect and with metabolic complexity in the tumor microenvironment. Then it shows how OXPHOS activity affects invasiveness of cancer cells and metastases formation, and it points out the connection between invasiveness and increased levels of ETC-generated reactive oxygen species. At the end, the review deals with possible use of ETC inhibitors in anticancer therapy.
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Metabolic alterations in cancer cells and their implications in the therapy of acute leukemias
Harárová, Alžbeta ; Starková, Júlia (advisor) ; Mrvová, Silvia (referee)
Cancer metabolism differs from that of the healthy cells in several aspects. Aerobic glycolysis (e.g. converting pyruvate to lactate under normoxic conditions) was the first described metabolic alteration of cancer cells. Metabolic alterations have since been described in the tricarboxylic acid cycle, oxidative phosphorylation, in the metabolism of amino acids (especially glutamine, asparagine and serine) and also in the metabolism of fatty acids and cholesterol. The common feature of these changes is the tendency to prefer anabolic pathways, thus enabling fast proliferation of cancer cells. The study of cancer metabolism is particularly important in the case of cancer cells that show resistance to treatment, as their aberrant metabolism is not only a potential diagnostic marker but also a potential therapeutic target. The majority of metabolic alterations have been described for the first time in solid tumors, whereas only recently has the metabolism of acute leukamias gained more attention. Asparaginase is an example of a chemotherapeutic agent that targets a metabolic alteration of leukemic cells. Distinct metabolic profile is also associated with the glucocorticoid resistance. Detailled study of the metabolic alterations of leukemic cells has elucitated the mechanisms of the asparaginase and...
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