|
|
From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer?
Škrha, Pavel ; Anděl, Michal (advisor) ; Bendlová, Běla (referee) ; Krechler, Tomáš (referee)
From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer? Pavel Škrha Abstract Introduction: Pancreatic cancer ranks among the cancers with the worst prognosis. High lethality of the disease is caused by late diagnose and a lack of powerful and early markers. The goal of this study was to observe the presence of early unspecific signs of the disease (new-onset diabetes mellitus and weight loss) and to test selected miRNAs as markers of pancreatic cancer, with subanalysis according to specific criteria (diabetes mellitus/prediabetes, its type, weight loss, cancer stage and size of the primary tumor, presence of chronic pancreatitis in cancer patients). Patients and methods: We have included 77 patients with ductal pancreatic adenocarcinoma, 26 with chronic pancreatitis, 39 patients with type 2 diabetes mellitus without any tumor disease and 25 control subjects. In the cancer group, there were 60 patients who also had diabetes/prediabetes and 18 with chronic pancreatitis in their personal history. Significant weight loss (> 5 % of body weight in 3 months or > 10 % of body weight in 6 months) was observed in 52 patients with the cancer. Relative expressions of miRNAs (miR-21, miR-30, miR-192, miR-196, miR-200, miR-423) were measured in the serum by real-time PCR...
|
|
|
Adipose etrogenisation and other anthropological aspects of obesity
Novák, Jan ; Sedlak, Petr (advisor) ; Bezdíček, Ondřej (referee) ; Bendlová, Běla (referee)
This work presents an anthropological view of obesity. It introduces the concept of adipose estrogenization and describes its relationship to pelvic morphology. Further, secular changes in the prevalence of latent obesity, the consequences, and the etiology of this condition are described. The work also validates tools for assessing chronotype, subsequently associating these metrics with sociodemographic factors, including obesity. The key part of this project present study focused on changes in the morphology of the bony pelvis in the context of pubertal history of obesity. It is a longitudinal study (n = 238) with an anthropometric examination after 8 years and an estimation of sex hormones. The main observation was that adult men with a history of obesity had more gynoid (relatively wider) pelvic bone morphology and altered levels of sex hormones, i.e., reduced testosterone levels and an increased relative proportion of estradiol to testosterone, i.e., estrogenization. This was manifested with habitual pelvic feminization, which serves as a marker of estrogenization and a retrospective marker of obesity. In the context of this study, a Letter to the Editor is added as a correction to the publication, interpreting these findings as a possible explanation for the shorter second stage of labor in...
|
|
|
Variability of the MTNR1B Melatonin Receptor Gene in Relation to Type 2 Diabetes Mellitus
Chocholová, Denisa ; Vejražková, Daniela (advisor) ; Bendlová, Běla (referee)
The human MTNR1B gene has been identified as a candidate gene associated with the development of type 2 diabetes mellitus, a rapidly spreading disease characterised by hyperglycemia and insulin resistance. The strongest association with impaired glucose metabolism shows a single nucleotide polymorphism of this gene rs10830963. MTNR1B encodes the melatonin receptor 1B found in a variety of tissues, including human pancreatic beta cells. It is involved in the regulation of glucose homeostasis, especially affecting fasting glycemia and glucose-stimulated insulin secretion. Its ligand, the hormone melatonin, inhibits insulin production from the pancreatic beta cells, which contributes to hyperglycemia. Melatonin controls the regulation of circadian rhythm. In carriers of the minor G allele, the secretion of melatonin shifts towards a delayed rise in the evening and a slower decline in the morning. If these individuals are forced, for example by working hours, to have early breakfakt, late dinner or they have to eat at night due to night-time shifts, the concurrence of high melatonin levels and food intake significantly increases their risk of glucose tolerance disorders. This bachelor thesis presents the latest findings explaining disorders of glucose melabolism in connection with the variability of...
|
|
| |
|
|
An estimation of the development trends of the selected biomarkers for monitored population groups using data from the human biomonitoring in the Czech Republic
Grafnetterová, Anna ; Černá, Milena (advisor) ; Bendlová, Běla (referee)
The human biomonitoring is today an important tool for monitoring of people exposition to environmental pollutants. Mercury and cadmium are long-term monitored biomarkers in the Czech population. A developmental trend of mercury concentration level in urine and hair of children population as well as in urine and blood of adult population is investigated. These biomarkers were monitored in the years 1996 - 2011. Data originate from the NIPH (National Institute of Public Health) databases and from the international project COPHES/DEMOCOPHES. Adult blood donors at age of 18 to 64 were the first monitored group, the second one were children at age of 6 to 12, which were selected based on an agreement with elementary schools or with the paediatricians' cooperation. Available data were statistically processed; trends are presented in graphs as a dependence of geometric means on the time (the year of the biological samples collection). Results show an unstable development of biomarkers levels in different matrixes. A moderate decreasing trend of cadmium level in urine of adults was observed. GM values for adults decreased from 0.43 μg/g creatinine in 2009 to 0.24 μg/g creatinine in 2009. For year 2011, data are available only for women (GM = 0.21 μg/g creatinine). The downward trend was also found in the...
|
|
|
Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease
Václavíková, Eliška ; Bendlová, Běla (advisor) ; Dvořáková, Lenka (referee) ; Stárka, Luboslav (referee)
Genetic causes of medullary thyroid carcinoma and Hirschsprung's disease Abstract Medullary thyroid carcinoma (MTC) and Hirschsprung's disease (HSCR) are classified as simple neurocristopathies, i.e. diseases linked to neural crest-derived cells. MTC is derived from parafollicular cells of the thyroid and HSCR is characterized by absence of enteric ganglia in the gastrointestinal tract. The RET proto-oncogene is only expressed in neural crest-derived cells, including parafollicular cells and enteric neurons. The RET encodes a transmembrane tyrosinekinase receptor that plays an important role during proliferation, differentiation and cell survival, and activates many signaling pathways. If the strictly regulated activation fails, e.g. due to mutations in the specific gene locations, the RET becomes a highly effective oncogene. Activating germline mutations in the RET proto- oncogene lead to hereditary forms of MTC, whereas sporadic forms of MTC are caused by somatic mutations in the tumor tissue. On the contrary, inactivating mutations induce migration failure of ganglion cell precursors during the development of enteric nervous system and result in the development of HSCR. In rare cases, the coexistence of both diseases is caused by mutations with a dual gain-of-function and loss-of-function character....
|
|
|
Molecular aspects of genetic predisposition to type 2 diabetes mellitus and its monogenic forms
Pintérová, Daniela ; Černá, Marie (advisor) ; Bendlová, Běla (referee) ; Hubáček, Jaroslav (referee)
The aim of this work was to study some molecular aspects of genetic predisposition to T2DM and its monogenic forms. We searched for correlations of genotypes with many clinical and laboratory markers and tried to evaluate their significance. The consequences for possible changes in the treatment some particular patients were under discussion. Especially for those suffering from monogenic forms we were able to reach better compensation of DM, or at latest the same compensation for more acceptable therapy. We studied the associations of chosen candidate genes, PPAR, NF-B, its inhibitor IB, known polymorphisms and T2DM including diabetic complications. We used the association study approach to find out if there is any association between available genetic variants among our patients and T2DM with its phenotypic abnormalities (changed levels of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides, further the presence of diabetic complications).
|
|
| |
|
|
From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer?
Škrha, Pavel ; Anděl, Michal (advisor) ; Bendlová, Běla (referee) ; Krechler, Tomáš (referee)
From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer? Pavel Škrha Abstract Introduction: Pancreatic cancer ranks among the cancers with the worst prognosis. High lethality of the disease is caused by late diagnose and a lack of powerful and early markers. The goal of this study was to observe the presence of early unspecific signs of the disease (new-onset diabetes mellitus and weight loss) and to test selected miRNAs as markers of pancreatic cancer, with subanalysis according to specific criteria (diabetes mellitus/prediabetes, its type, weight loss, cancer stage and size of the primary tumor, presence of chronic pancreatitis in cancer patients). Patients and methods: We have included 77 patients with ductal pancreatic adenocarcinoma, 26 with chronic pancreatitis, 39 patients with type 2 diabetes mellitus without any tumor disease and 25 control subjects. In the cancer group, there were 60 patients who also had diabetes/prediabetes and 18 with chronic pancreatitis in their personal history. Significant weight loss (> 5 % of body weight in 3 months or > 10 % of body weight in 6 months) was observed in 52 patients with the cancer. Relative expressions of miRNAs (miR-21, miR-30, miR-192, miR-196, miR-200, miR-423) were measured in the serum by real-time PCR...
|
|
| |
guest ::
