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Advanced lipidomics in selected clinical conditions
Staňková, Barbora ; Tvrzická, Eva (advisor) ; Hyánek, Josef (referee) ; Kazdová, Ludmila (referee)
Abnormalities of lipid metabolism are considered risk factors for cardiovascular, metabolic, nephrologic diseases amd some malignancies, as well. Nowadays, a lot of effort is devoted to study new risk factors and surrogate markers of conditions mentioned above to improve their prognosis and decrease mortality. The aim of this thesis was to provide a comprehensive survey of lipid metabolism, characteristics of different lipid compounds in health and diseases and of possibilities of utilization of selected lipid parameters in the diagnostics of pathological conditions listed above. Selected lioid parameters were observed in several studies, focused on specific pathological conditions. Besides conventional lipid analytes, the composition of fatty acids in plasma lipid pools was studied in healthy controls, and in the patients suffering from metabolic syndrome, chronic pancreatitis, and pancreatic cancer, as well. Markers of an oxidative stress (oxidatively modified LDL particles and conjugated dienes in precipitated LDL) were assessed in healthy controls, patients with metabolic syndrome, chronic pancreatitis, pancreatic cancer, and in the patients with different concentrations of plasma apoB-48, too. LDL particles subfraction were investigated in healthy controls, in the patients with different...
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Pathophysiology of chronic pancreatitis and pancreatic cancer.
Mačinga, Peter ; Hucl, Tomáš (advisor) ; Krechler, Tomáš (referee) ; Trna, Jan (referee)
Chronic pancreatitis is considered a risk factor for pancreatic cancer. An exact mechanism how chronic inflammation of the pancreas leads to pancreatic cancer is not yet understood; the possibility of a shared genetic predisposition for both diseases is also assumed. A similar association in patients with AIP has not yet been demonstrated. The aim of our work was to expand the knowledge about relationship between chronic pancreatitis and pancreatic cancer. We studied the association of the diseases in two synchronous projects. In the first one, we examined the occurrence of pancreatic cancer in patients with autoimmune pancreatitis. In the second project, we investigated the presence of genetics variants associated with chronic pancreatitis in patients with pancreatic cancer. In the retrospective study of our cohort of patients, we were one of the very first in the world to show occurrence of pancreatic cancer in patients with autoimmune pancreatitis, and as the only one, we have defined the characteristics of such patients. To assess the association of the diseases, we performed a systematic review where we identified all reported cases of coincidence of pancreatic cancer and autoimmune pancreatitis; the incidence of cancer in patients with autoimmune pancreatitis was similar to that of patients...
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Metabolomics Study of the Association between Pancreatic Cancer and Diabetes Mellitus.
Michálková, Lenka ; Horník, Štěpán ; Sýkora, Jan ; Habartová, L. ; Setnička, V.
In our study, 1H NMR metabolomics was employed to plasma samples of pancreatic cancer patients, individuals with long-term diabetes mellitus type 2 (lasting more than 5 years) and healthy controls. The NMR analyses were followed by establishing a statistical model based on principal component analysis and discriminant analysis. The aim was to discover differences between these groups and to define a potential biomarker panel. The statistical evaluation of metabolomics-based profiles provided high values of sensitivity and specificity. Subsequently, plasma samples of the risk group, specifically patients with recently diagnosed diabetes mellitus with a duration of <3 years (possible T3cDM), were analysed and the possibility of PC development was predicted. The achieved results showed strong potential of 1H NMR metabolomics to establish a biomarker panel that would facilitate the early diagnosis of PC and the possibility identify diabetic individuals, who are at risk of developing PC.
Fulltext: content.csg -  PDF
Plný tet: SKMBT_C22019041212340 - PDF
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NMR Metabolomics Study of the Association between Pancreatic Cancer and Diabetes Mellrtus.
Michálková, Lenka ; Horník, Štěpán ; Sýkora, Jan ; Habartová, L. ; Setnička, V.
In our study, 1H NMR metabolomics was employed to plasma samples of pancreatic cancer patients, individuals with long-term diabetes mellitus type 2 (lasting more than 5 years) and healthy controls. The NMR analyses were followed by establishing a statistical model based on principal component analysis and discriminant analysis. The aim was to discover differences between these groups and to define a potential biomarker panel. The statistical evaluation of metabolomics-based profiles provided high values of sensitivity and specificity. Subsequently, plasma samples of the risk group, specifically patients with recently diagnosed diabetes mellitus with a duration of <3 years (possible T3cDM), were analysed and the possibility of PC development was predicted. The achieved results showed strong potential of 1H NMR metabolomics to establish a biomarker panel that would facilitate the early diagnosis of PC and the possibility identify diabetic individuals, who are at risk of developing PC.
Fulltext: content.csg - PDF
Plný tet: SKMBT_C22019041208491 - PDF
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Optimization of miRNA analysis in fine-needle biopsy samples of pancreatic cancer tissue.
Čuperková, Romana ; Benešová, Lucie (advisor) ; Kuthan, Martin (referee)
Pancreatic cancer (PC) is extremely severe malignant disease with a five-year survival of less than 5%. Currently there is no reliable tool for the diagnosis of PC in its early stages. At the time of clinical symptoms most patients are in an advanced stage of the disease and the treatment does not usually have a significant effect. For these reasons emphasis is gradually shifting to the search for the suitable molecular markers for improvement of the diagnosis and assessment of the survival prognosis with respect to a possibility of surgical treatment. MiRNA represent one of the most promising markers, although, their examination in pancreatic tissue is a complicated process. One of the reasons is the very small amount of the source material coming from a fine needle biopsy. A second cause of problems is the subtle character of the pancreatic tissue resulting in significantly lower yields of molecular genetic analysis when compared to other epithelial tissues. An additional negative factor is heterogeneity of the tissue resulting in disproportionate representation of tumor cells within the sample. A suitable choice of procedures for isolation of nucleic acids (NA) and subsequent analysis including quantification of tumor cells is critical for accurate evaluation of the miRNA levels. This work is...
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Peritoneal lavage cytology and biochemistry in cases of upper GI tumours
Hoskovec, David ; Antoš, František (advisor) ; Lischke, Robert (referee) ; Aujeský, René (referee)
Introduction: Intraperitoneal tumor seeding is a common form of recurrence after surgery for GI tumours. Early diagnosis and treatment may influence the course of disease. Hypothesis and objectives of the work The finding of free tumor cells and / or elevation of tumor markers in peritoneal fluid predicts intraperitoneal tumor recurrence. The results of these tests can be used to indicate HIPEC. Aim of this work is to determine the sensitivity and specificity of cytology and tumor markers levels and importance of these tests for early diagnosis and prognosis of recurrence. Another objective was to confirm the applicability of RT PCR for identification of free tumor cells. Patients and methods . Materials are sourced both during initial surgery (220 patients) and by the dispensary controls (25 patients). The peritoneal fluid was examined cytologically and biochemically too. 50 samples was exemined by RT PCR. Results Elevation of tumor markers or finding of free intraperitoneal tumor cells predicts recurrence. The prognosis of these patients corresponds to stage IV TNM classification, regardless of other parameters TNM. Low sensitivity of these tests (34% for cytology, 53% for tumor markers) does not allow its use as an indicator of HIPEC. Due to degradation of RNA we did not confirm the value of RT...
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Glutathion a glutathion dependentní enzymy za různých patofyziologických stavů.
Kodydková, Jana ; Tvrzická, Eva (advisor) ; Kazdová, Ludmila (referee) ; Vejražka, Martin (referee)
Backround: Oxidative stress (OS) has been implicated in pathogenesis of human disorders such as depressive disorder, sepsis, cardiovascular disease, acute and chronic pancreatitis, and cancer. Increased OS is result of imbalance between increased reactive oxygen and nitrogen species (RONS) production and / or insufficient activity of antioxidant defence system. Antioxidant system, which is composed of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidases (GPX), glutathione reductase (GR) and non- enzymatic antioxidant reduced glutathione (GSH) plays an important role in the protection of cells against enhanced OS. The aim of this study was to assess the OS markers and antioxidant enzymes in different pathophysiological states. Materials and methods: Activities of erythrocyte glutathione peroxidase (GPX1), GR and concentration of GSH as well as levels of OS markers were analysed in six different pathophysiologic states. These parameters were measured in 35 women with depressive disorder (DD), 40 patients with metabolic syndrome (MetS), 30 septic patients (S) followed up in the course of sepsis; 15 non-septic critically ill patients (NC), 13 patients with acute pancreatitis (AP), 50 with chronic pancreatitis (CP) and 50 patients with pancreatic cancer (PC), compared to...
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Glutathione and glutathione-dependent enzymes in various pathophysiological states.
Kodydková, Jana
Backround: Oxidative stress (OS) has been implicated in pathogenesis of human disorders such as depressive disorder, sepsis, cardiovascular disease, acute and chronic pancreatitis, and cancer. Increased OS is result of imbalance between increased reactive oxygen and nitrogen species (RONS) production and / or insufficient activity of antioxidant defence system. Antioxidant system, which is composed of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidases (GPX), glutathione reductase (GR) and non- enzymatic antioxidant reduced glutathione (GSH) plays an important role in the protection of cells against enhanced OS. The aim of this study was to assess the OS markers and antioxidant enzymes in different pathophysiological states. Materials and methods: Activities of erythrocyte glutathione peroxidase (GPX1), GR and concentration of GSH as well as levels of OS markers were analysed in six different pathophysiologic states. These parameters were measured in 35 women with depressive disorder (DD), 40 patients with metabolic syndrome (MetS), 30 septic patients (S) followed up in the course of sepsis; 15 non-septic critically ill patients (NC), 13 patients with acute pancreatitis (AP), 50 with chronic pancreatitis (CP) and 50 patients with pancreatic cancer (PC), compared to...
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The importance of biosynthetic and catabolic pathway of cholesterol in inflammatory and tumor diseases
Leníček, Martin ; Vítek, Libor (advisor) ; Haluzík, Martin (referee) ; Mareček, Zdeněk (referee)
This thesis focuses on the importance of intermediate products of biosynthetic and catabolic pathway of cholesterol. The aim of the first part of the thesis is mainly to investigate, whether statins (HMG- CoA reductase inhibitors) possess antitumor properties and to compare the differences in antitumor potential of individual statins. The other part of the thesis aims at the utilization of 7α-hydroxycholest-4-en-3-one (C4), a promising marker of cholesterol 7α-monooxygenase (CYP7A1) activity and bile acid malabsorption. We demonstrated antitumor effect of statins on an experimental model of pancreatic cancer. Individual statins, however, differed significantly in their efficacy, depending on their physico-chemical properties. Our data suggests, that the most likely (but not the only) mechanism of antitumor effect of statins is decreased prenylation of signaling proteins, especially Ras protooncogene. We set up a reliable method for measurement of C4, which facilitated our research in CYP7A1 regulation. We demonstrated, that promoter polymorphism -203A>C might affect CYP7A1 activity, that diurnal variability of CYP7A1 activity might be triggered by insulin, and that insulin resistance in patients with non-alcoholic fatty liver disease impedes the feedback regulation of CYP7A1, which may lead to disease...
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