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Induction and course of programmed cell death in cancer cells after taxane application."
Kábelová, Adéla ; Jelínek, Michael (advisor) ; Gemperle, Jakub (referee)
The taxanes are a class of commonly used anticancer agents, which are very effective in treatment of breast, ovarian, prostate or lung cancer. Taxanes bind to the β-tubulin subunit of microtubules and lead to their stabilization and inhibition of depolymerization. Such microtubules lose their function to form mitotic spindle, thus arresting cells in G2/M phase and resulting in apoptosis. Unfortunately some cells are able to escape from taxanes-induced apoptosis by developing various mechanisms of resistance including alteration in taxanes target microtubules or upregulation of specific transporters that pump the drug out of cells. Other types of resistance are connected with process of programmed cell death (PCD), especially with proteins that after taxane application participate in its successful progress. Taxanes can directly or indirectly modify the activity of Bcl-2-family proteins that control mitochondrial and endoplasmic reticulum integrity, thus regulating the initiation of PCD. Caspases are executioners of PCD and caspase-2 activated by cytoskeletal disruption seems to be especially important in taxanes- induced apoptosis. In some cases can taxane treatment also result in caspase-independent cell death. Special role has protein p53 that seems to be involved only in apoptosis caused by low taxanes...
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Low carbohydrate diet in type 2 diabetes mellitus therapy
Kábelová, Adéla ; Krejčí, Hana (advisor) ; Šeda, Ondřej (referee)
Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder, which substantially affects quality of patients' lives and simultaneously increases the risk of early death due to development of its specific complications. Current T2D therapy comprises mainly pharmacotherapy, however, lifestyle changes, particularly modification of dietary habits, also assume an important role in the process. While conventional dietotherapy of T2D primarily concerns reduction of dietary fat intake aiming to achieve caloric restriction, the low carbohydrate diet (LCD), recently often discussed in relation to T2D therapy, is based on the reduction of dietary carbohydrates, whereas fats and/or proteins are increased. The positive effects of LCD in T2D therapy and its comorbidities are summarized in the theoretical part of this thesis. The aim of the practical part of the bachelor thesis was to asses the effect of LCD on health parameters associated with T2D as well as the subjective sense of respondents' satisfaction with this diet together with their adherence and compliance. The results of the survey showed that LCD led to weight loss, decreased waist circumference, glycaemia and levels of glycated haemoglobin and led, in a number of cases, to medication reduction. The level of satisfaction with LCD in the...
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Molecular mechanisms of carcinogenic effects of alcohol
Vepřková, Jana ; Kábelová, Adéla (advisor) ; Novotná, Božena (referee)
Alcohol (ethanol) enters the human body mainly through ingestion of alcoholic beverages and its chronic consumption is considered a worldwide socio-economic problem. Besides others, alcohol consumption increases the risk of development of breast, liver, colorectal and upper aerodigestive tract cancer. In the liver, ethanol is metabolised into toxic acetaldehyde which is the main cause of DNA damage leading to cancer development. Acetaldehyde covalently interacts with nucleotides in the DNA forming DNA adducts such as N2 -ethylidene-2'-deoxyguanosine or S- and R-α-methyl-γ-hydroxy-1,N2 - propano-2′-deoxyguanosine. Acetaldehyde can also interact with proteins and disrupt their function. Ethanol metabolism by cytochrome P450 2E1 leads to production of reactive oxygen species, that subsequently damage cellular molecules such as lipides and DNA. Ethanol also initiates carcinogenesis through aberant DNA methylation or interference with retinoic acid metabolism. In cancer development, alcohol interacts with other environmental and genetic factors, which can increase the risk of developing cancer in predisposed individuals.
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Remission of type 2 diabetes in patients on various dietary regimens
Kábelová, Adéla ; Krejčí, Hana (advisor) ; Šeda, Ondřej (referee)
Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder linked with the development of specific complications and comorbidities that negatively affect life quality and greatly increase the risk of an early death. The main goal of T2D treatment, which in common clinical practice comprises lifestyle changes and pharmacotherapy, is to delay onset of these complications. Evidence from many recent studies shows the ability of some interventional methods to induce remission of T2D, meaning a major improvement or complete disappearance of T2D symptoms. Besides bariatric surgery procedures, some dietary regimens such as low-energy diet, low-carbohydrate diet and intermittent fasting, can also lead to T2D remission. Attributes of these dietary regimens, especially their effect in T2D treatment, is summarized in the theoretical part of this theses. The aim of the practical part of this thesis was to assess the effect of the dietary regimens mentioned above on morphometric and biochemical parameters associated with T2D by clinical and survey research. In most of the subjects with T2D, the individual dietary regimens, more precisely low-energy diet and low-carbohydrate diet, decreased body weight, where the weight loss induced by low-carbohydrate diet was caused by major decrease in the amount...
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The effect of curcumin on carcinogenesis and metastasis development
Kašík, Petr ; Kábelová, Adéla (advisor) ; Vališ, Karel (referee)
Curcumin is a polyphenol from the roots of plant Curcuma longa. Highly pleiotropic effect of curcumin has presently application not only in prevention, but also in treatment of various diseases including cancer. Therefore, this bachelor thesis aims to summarize the current knowledge concerning the effect of curcumin on carcinogenesis and metastasis development. Considering the inhibition of cancer cells proliferation, curcumin stops the progression of cell cycle, primarily via regulating the activity of cyclins and cyclin-dependent kinases, their inhibitory proteins or tumor suppressor protein p53. Additionally, p53 also seems to have an important role in the initiation of intrinsic apoptotic pathway, which was observed in many cancer cell lines after curcumin administration. Apoptotic proteins involved in apoptosis induction after curcumin application also comprise Bcl-2 family proteins and, caspases. Other mechanisms exerted by which curcumin prevent cancer development include suppression of angiogenesis, increase of oxidative stress or modulation of inflammatory response. Finally, curcumin also suppress cancer cells invasion and migration by enhancing the transcription of E- cadherin and decreasing of the transcription of matrix metalloproteinases. Because the application of curcumin in clinical...
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Low carbohydrate diet in type 2 diabetes mellitus therapy
Kábelová, Adéla ; Krejčí, Hana (advisor) ; Šeda, Ondřej (referee)
Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder, which substantially affects quality of patients' lives and simultaneously increases the risk of early death due to development of its specific complications. Current T2D therapy comprises mainly pharmacotherapy, however, lifestyle changes, particularly modification of dietary habits, also assume an important role in the process. While conventional dietotherapy of T2D primarily concerns reduction of dietary fat intake aiming to achieve caloric restriction, the low carbohydrate diet (LCD), recently often discussed in relation to T2D therapy, is based on the reduction of dietary carbohydrates, whereas fats and/or proteins are increased. The positive effects of LCD in T2D therapy and its comorbidities are summarized in the theoretical part of this thesis. The aim of the practical part of the bachelor thesis was to asses the effect of LCD on health parameters associated with T2D as well as the subjective sense of respondents' satisfaction with this diet together with their adherence and compliance. The results of the survey showed that LCD led to weight loss, decreased waist circumference, glycaemia and levels of glycated haemoglobin and led, in a number of cases, to medication reduction. The level of satisfaction with LCD in the...
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The role of autophagy and selected beta-tubulin isotypes in taxane resistance in breast cancer cells
Kábelová, Adéla ; Jelínek, Michael (advisor) ; Truksa, Jaroslav (referee)
Drug resistance in cancer cells is a frequent cause of breast cancer therapy failure. The aim of this thesis was to elucidate mechanisms of resistance to taxanes, that are used in therapy of various types of cancer, including breast cancer. We particularly assessed the role of autophagy and changes in βII- and βIII isotype gene expression in development of taxane resistance. As model of breast cancer we used human sensitive cell lines SK-BR-3, MCF-7 a T47-D and resistant sublines SK-BR-3-PAC/REZ a MCF-7- PAC/REZ which grow in paclitaxel concentration lethal for sensitive sublines. In cell lines SK-BR-3 and MCF-7, taxane application decreased the level of autophagy, however in cell line T47-D led to its activation. We detected no difference between basal levels of autophagy in sensitive subline SK-BR-3 compared to resistant subline SK-BR-3-PAC/REZ, but we observed increased basal level of autophagy in sensitive subline MCF-7 compared to the resistant subline. Increase or decrease level of autophagy did not affect taxane resistance, except activation of autophagy in resistant subline SK-BR-3-PAC/REZ, that further increased the resistance to paclitaxel. Taxane application in cell line T47-D increased the levels of βII- and βIII-tubuline expression, however we did not find any similar effect in other tested...
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Induction and course of programmed cell death in cancer cells after taxane application."
Kábelová, Adéla ; Jelínek, Michael (advisor) ; Gemperle, Jakub (referee)
The taxanes are a class of commonly used anticancer agents, which are very effective in treatment of breast, ovarian, prostate or lung cancer. Taxanes bind to the β-tubulin subunit of microtubules and lead to their stabilization and inhibition of depolymerization. Such microtubules lose their function to form mitotic spindle, thus arresting cells in G2/M phase and resulting in apoptosis. Unfortunately some cells are able to escape from taxanes-induced apoptosis by developing various mechanisms of resistance including alteration in taxanes target microtubules or upregulation of specific transporters that pump the drug out of cells. Other types of resistance are connected with process of programmed cell death (PCD), especially with proteins that after taxane application participate in its successful progress. Taxanes can directly or indirectly modify the activity of Bcl-2-family proteins that control mitochondrial and endoplasmic reticulum integrity, thus regulating the initiation of PCD. Caspases are executioners of PCD and caspase-2 activated by cytoskeletal disruption seems to be especially important in taxanes- induced apoptosis. In some cases can taxane treatment also result in caspase-independent cell death. Special role has protein p53 that seems to be involved only in apoptosis caused by low taxanes...
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