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Selected Prognostic and Predictive Factors of Pituitary Tumours in Patients with Acromegaly
Soukup, Jiří ; Ryška, Aleš (advisor) ; Ehrmann, Jiří (referee) ; Fryšák, Zdeněk (referee)
Selected prognostic and predictive factors of pituitary tumours in patients with acromegaly (abstract) Pituitary tumours in patients with acromegaly (somatotroph adenomas, pituitary neuroendocrine tumours - PitNETs) are a rare disease with significant morbidity and high impact on economic resources of the health care system. The surgery is the first line of treatment, and while it cures a subset of the patients, another therapeutical approach combining radiotherapy and pharmacotherapy is needed in the rest. This usually includes treatment with costly somatostatin analogues (SSA). On the opposite, the therapeutic response to SSA is not a rule. This work aimed to perform precise clinicopathological characterisation of available tissue samples of PitNETs in acromegalic patients (n=110) from REgistr SEllárních Tumorů (RESET registry) and further explore potential factors related to clinically aggressive disease phenotype (tumour size, invasion, biochemical parameters) and factors that might predict therapeutic response to the first generation SSA. An extensive immunohistochemical evaluation was performed: tumours were histologically subclassified (expression of cytokeratins, prolactin, TSH) and proliferative activity was assessed (Ki67, p53, mitotic count) as well as expression of possible pharmacological...
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Serrated Lesions of Gastrointestinal Tract and Significance of Serrated Changes in Mucosa of Inflammatory Bowel Disease Patients
Kamarádová, Kateřina ; Laco, Jan (advisor) ; Hermanová, Markéta (referee) ; Ehrmann, Jiří (referee)
Patients with inflammatory bowel disease (IBD) have an elevated risk of developing colorectal carcinoma (CRC). IBD-dysplasia is regarded as a conventional precursor for IBD- associated carcinoma. (1-2) Other types of non-conventional mucosal changes with serrated and villous hypermucinous morphology have also been reported but their preneoplastic potential is still not well elucidated. (3-4) The aim of the study was to retrospectively review samples from IBD patients focusing on detection of mucosal lesions including non-conventional lesions and evaluate their relationship and immunohistochemical and molecular properties. Surgical specimens and/or endoscopical biopsy samples of IBD patients examined during a 10-year period were reviewed. Mucosal lesions were divided into three groups - group 1 of non-conventional lesions, group 2 of true serrated polyps, and group 3 of IBD-dysplasia and colorectal carcinoma. Detailed morphological evaluation, immunohistochemical analysis of mismatch repair proteins and/or MLH1, p53 and O6 -methylguanine DNA methyltransferase (MGMT) expression, and molecular analysis for KRAS, NRAS and BRAF gene mutation was performed in all lesions. Overall, samples from 309 IBD patients were reviewed. A total of 88 mucosal lesions were found in 51 patients. Most common were lesions...
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S100 Proteins in Inflammatory Bowel Disease and Colorectal Neoplasia
Morávková, Paula ; Kohoutová, Darina (advisor) ; Ehrmann, Jiří (referee) ; Zavoral, Miroslav (referee)
S100 proteins in inflammatory bowel disease and colorectal neoplasia Inflammatory bowel disease and colorectal cancer represent a serious medical and socio- economic problem worldwide. Despite the progress in diagnostic of both diseases, there is no specific serum maker, which would allow to detect risk group of patients. Our paper focused on importance of serum S100 proteins in inflammatory bowel disease and colorectal neoplasia: (1) association of serum S100A4 with inflammatory bowel disease, ulcerative colitis and Crohn's disease, (2) association of serum S100A6, S100A8, S100A9 and S100A11 with colorectal neoplasia and (3) association of serum S100P with colorectal cancer. A total of 253 subject were enrolled: 40 healthy controls, 16 patients with ulcerative colitis, 93 patients with Crohn's disease, 20 patients with non-advanced colorectal adenoma, 20 patients with advanced colorectal adenoma and 62 patients with colorectal cancer. We confirmed significantly higher serum concentrations of S100A4 protein in patients with ulcerative colitis and Crohn's disease. In Crohn's disease, serum S100A4 was significantly higher in patients with colonic and ileocolonic involvement. We did not confirm association of serum S100A4 with fibrostenosing phenotype of Crohn's diseases and with perianal involvement. We...
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Molecular mechanisms of iron transport across plasma membrane in mammalian cells
Balušíková, Kamila ; Kovář, Jan (advisor) ; Ehrmann, Jiří (referee) ; Krijt, Jan (referee)
Iron belongs among the trace elements and its role in humans is irreplaceable. Up to 5 g of iron can be found in adult body distributed among different compounds. Iron ions are therefore essential to all cells of our body and its homeostasis is thoroughly controlled. Iron uptake into the organism is mediated by enterocyte cells in the small intestine, where heme as well as non-heme forms of iron are absorbed. Non-heme iron is absorbed via Dcytb (duodenal cytochrome b), DMT1 (divalent metal transporter 1), ferroportin, hephaestin, and ceruloplasmin molecules. Although these molecules can also participate in non-transferrin- bound iron transport across plasma membranes within the whole organism, mechanisms of this transport are not yet fully elucidated. The aim of the present work was to contribute to our understanding of molecular mechanisms that are involved in non-transferrin-bound iron transport across the plasma membrane of mammalian cells. Our project was focused on the description of non-transferrin- bound iron transport in human cells in vitro and in vivo under conditions of iron deficiency or iron overload. Transformed cell lines, that represent the three main types of cells involved in iron homeostasis, and tissue samples of duodenal biopsies were used as experimental models. The expression...
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Effects of n-3 polyunsaturated fatty acids on development of non-alcoholic fatty liver disease in experiment, prevalence in patients with type 2 diabetes mellitus and metabolic syndrome, non-invasive diagnostics
Dvořák, Karel ; Brůha, Radan (advisor) ; Ehrmann, Jiří (referee) ; Lotková, Halka (referee)
This thesis focuses on the effects of n-3 polyunsaturated fatty acids (n-3 PUFA) on development of non-alcoholic fatty liver disease (NAFLD) in experiment, on prevalence of this condition in patients with type 2 diabetes mellitus and metabolic syndrome and also on non-invasive diagnostics. The aim was to study the effect of n-3 PUFA on NAFLD development in an experimental model and based on analysis of a group of patients with type 2 diabetes and metabolic syndrome to assess the prevalence of this condition. Lastly we aimed to evaluate non-invasive diagnostic methods of liver fibrosis and NASH. We demonstrated beneficial effects of n-3 PUFA administration on NAFLD development in a C57/Bl6 mice high fat methionin-cholin defficient dietary model of NAFLD. n-3 PUFA administration led to biochemical improvement, decrease of lipid accumulation in the liver as well as improvement of histology. These effects are determined by complex modulation of lipid metabolism, mainly due to decrease in availability of fatty acids for triglyceride synthesis in the liver, changes of adipokine levels and amelioration of proinflammatory status in the liver. In a group of type 2 diabetics we found NAFLD prevalence of almost 80%, 14% of these patients had also signs of liver fibrosis or cirrhosis. Non-invasive methods...
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The role of Nrf2 in selected models of liver injury
Mezera, Vojtěch ; Červinková, Zuzana (advisor) ; Brůha, Radan (referee) ; Ehrmann, Jiří (referee)
The role of Nrf2 in selected models of liver injury Oxidative stress accompanies various forms of liver injury, including liver resection and toxic liver injury. Two-thirds partial hepatectomy (PHx) is an established model for the study of liver regeneration after resection. We tested the effect of epigallocatechin gallate (EGCG), a green tea antioxidant, on the early phase of liver regeneration after PHx. Male Wistar rats received either water for injections or EGCG for 3 consecutive days and then were subjected either to laparotomy or hepatectomy. We observed a lower accumulation of bromodeoxyuridine pointing to lower DNA synthesis in hepatectomized rats receiving EGCG in a dose of 50 mg/kg than in hepatectomized rats treated with water. The activity of caspases 3/7, expression of p-p53 and tissue levels of IL-6 displayed a similar trend. EGCG in a dose of 20 mg/kg had no such effects. Next, male Wistar rats were subjected either to PHx or laparotomy. Twenty-four hours after the surgery, hepatocytes were isolated and treated with various concentrations of EGCG for 24 h. Morphological criteria, cell viability tests, and albumin synthesis revealed toxicity starting at 10 µmol/L. DNA synthesis was higher in hepatocytes isolated from rats after PHx and inhibited by EGCG. Furthermore, EGCG increased...
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Study of Epithelial Mesenchymal Interactions in Squamous Epithelium Derived Tumors
Kodet, Ondřej ; Lacina, Lukáš (advisor) ; Borovanský, Jan (referee) ; Ehrmann, Jiří (referee)
This thesis is focused on the epithelial mesenchymal interactions in tumors derived from squamous epithelium including tumors arising from minor cell population (melanocytes). This study is also reflecting aspects of epithelial glycobiology resp. the study of endogenous lectins, the galectins, in head and neck squamous carcinomas. Galectins represent, in the current concepts of cell and tumor biology molecules with a remarkable potential. Galectins participate, besides in regulation of pre- and postnatal homeostasis in normal tissues, also in many pathological processes such as autoimmune reactions or malignancies. In this thesis, we demonstrated the presence of galectin-1 and -2 and their glycoligands in interphasic and mitotic nuclei, which may contribute to regulation of the cell cycle. Furthermore, we demonstrated galectin-9 as a sensitive marker of transformation normal to the dysplastic squamous epithelium in head and neck. The epithelial mesenchymal interactions represent mechanisms, which are responsible for dynamic maintenance of the homeostasis of the organism during prenatal development, postnatal growth and during cyclic renewal of certain tissues. These interactions also participate in wound healing. On the other hand they play a crucial role in the process of tumor transformation,...
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Quantification of liver function using breath test with 13C labeled methacetin
Hendrichová, Miluše ; Horák, Jiří (advisor) ; Ehrmann, Jiří (referee) ; Martásek, Pavel (referee) ; Moťovská, Zuzana (referee)
Kvantifikace jaterních funkcí pomocí dechového testu s 13 C-methacetinem MUDr. Miluše HENDRICHOVÁ SUMMARY Efforts to evaluace and quantify liver functions has accompanied hepatology over the last 50 years at least. Quantification of liver function was hindered by multiple blood samploing, the low specificity of monitored parameters and the risk of allergic reactions when using conventional chromoexcretory tests. The introduction of breath tests using the non-radioactive isotope 13C allows non-invasive and highly accurate measurement of liver function. Especially 13C.methacetin is a very suitable substrate for evaluation demethylační and oxidative capacity of hepatocytes. Using the breath test with 13 C-methacetin is noninvasive, easy for patients and the results are reproducible. The aim of this thesis is to introduce the use of breath test with 13 C-methacetin into clinical practice as one of standard items in the care of patients with chronic liver diseases. In the first study we are evaluating liver function using breath test with 13 C-methacetin in patients with liver cirrhosis. The results show that the breath test reliably distinguishes patients with liver cirrhosis from patients without liver damage. Using ROC curves we demonstrate that the most advantageous time of the breath test that best predicts...
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