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Morphology and Functional Characteristics of Human Gametes - the Potencial Clinical Application
Čedíková, Miroslava ; Králíčková, Milena (advisor) ; Ludvíková, Marie (referee) ; Hubičková Heringová, Lucie (referee)
Reduced fertility is a growing problem trough the population in fertile age. It currently affects 10-15% of couples; any method of assisted reproduction cannot help 10% of them. The effort to identify new prognostic markers that would help to improve the effectiveness of treatments of infertility assumes increasing significance. The first part of this publication is focused on the study of levels of selected hormones and markers of oxidative stress in follicular fluid of women with diagnosis of infertility compared to healthy and fertile donors of oocytes. Levels of prolactin, free T3 and T4 hormone, homocysteine, malonydiladehyd, glutathione peroxidase and total antioxidant capacity and were analyzed. Next part is devoted to the difference between these parameters in women with normal body mass index (BMI) compared to women suffering from overweight. The second half of this work is focused on the male factor of infertility. The aim of our study was to determine comprehensively mitochondrial respiratory activity of sperm with normal and reduced motility and to evaluate the impact of propolis on human sperm motility. Respiratory activity of sperm was measured using oxygraph Oroboros. The results showed significantly higher levels of prolactin and free T4 hormone in follicular fluid of infertile...
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Relation of tumor genotype and phenotype to diagnosis, prognosis and prediction of colorectal cancer
Pitule, Pavel ; Králíčková, Milena (advisor) ; Vožeh, František (referee) ; Slabý, Ondřej (referee)
Colorectal cancer is one of the most common type of malignity. Despite of the existence of numerous studies focused on this carcinoma, there are still many unknown features regarding its diagnosis, treatment or prognosis. In the thesis we focused on the identification of novel prognostics markers that could be useful for the stratification of patients based on the disease outcomes. In the first study we immunohistochemically assessed expression of two proteins associated with cancer stem cells in the samples of primary colorectal cancer and matched liver metastasis. Goal of the study was to evaluate relation among expression of CD44 and CD133 and overall survival and disease free interval in our set of patients. We observed that increased ratio of CD133 positive compared to CD133 negative tumor glands resulted in longer disease free interval, finding which is opposite to the general view on the CD133 role in the cancer development. Our hypothesis is that we analyzed confined group of patients and followed a bit different goal, where we measured ratio between positive and negative glands in the view-field and not the intensity of staining as the previous studies did. Our second study was focused on the transcriptional analysis of the selected set of twelve genes using frozen samples from colorectal...
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The influence of xenobiotic metabolizing enzymes and transporters on the incidence of colorectal cancer and chemotherapy outcome
Krus, Ivona ; Souček, Pavel (advisor) ; Králíčková, Milena (referee) ; Hodis, Jiří (referee)
Introduction: Colorectal cancer (CRC) is one of the most frequent malignancies and affects approximately 5% of worldwide population. More than 75% of CRC cases represent sporadic forms. Susceptibility to nonhereditary CRC is significantly influenced by polymorphisms and mutations in low-penetrance genes. Variations in biotransformation and DNA repair genes may result in acumulation of toxins and DNA damage in cells leading to the development of cancer. Furthermore, different gene expression profiles of membrane transporters affecting the accumulation of anticancer drugs in tumour cells, e.g. ABC drug transporters, may largely influence inter-individual variability in drug response and chemotherapy outcome. The aim of this study was to evaluate the role of genetic and lifestyle factors in the risk of onset and progression of colorectal cancer. This study followed selected genetic alterations in xenobiotic-metabolizing enzymes (CYP1B1, GSTM1, GSTT1, GSTP1, NQO1 and EPHX1) and genes involved in response to DNA damage (CHEK2 and NBN), as potential CRC susceptibility factors. Another aim of this study was to investigate expression profile of all human ABC transporter genes to follow their prognostic and predictive potential in colorectal carcinoma. Materials and methods: The polymorphisms and other...
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Morphology and Functional Characteristics of Human Gametes - the Potencial Clinical Application
Čedíková, Miroslava ; Králíčková, Milena (advisor) ; Ludvíková, Marie (referee) ; Hubičková Heringová, Lucie (referee)
Reduced fertility is a growing problem trough the population in fertile age. It currently affects 10-15% of couples; any method of assisted reproduction cannot help 10% of them. The effort to identify new prognostic markers that would help to improve the effectiveness of treatments of infertility assumes increasing significance. The first part of this publication is focused on the study of levels of selected hormones and markers of oxidative stress in follicular fluid of women with diagnosis of infertility compared to healthy and fertile donors of oocytes. Levels of prolactin, free T3 and T4 hormone, homocysteine, malonydiladehyd, glutathione peroxidase and total antioxidant capacity and were analyzed. Next part is devoted to the difference between these parameters in women with normal body mass index (BMI) compared to women suffering from overweight. The second half of this work is focused on the male factor of infertility. The aim of our study was to determine comprehensively mitochondrial respiratory activity of sperm with normal and reduced motility and to evaluate the impact of propolis on human sperm motility. Respiratory activity of sperm was measured using oxygraph Oroboros. The results showed significantly higher levels of prolactin and free T4 hormone in follicular fluid of infertile...
|
|
|
Relation of tumor genotype and phenotype to diagnosis, prognosis and prediction of colorectal cancer
Pitule, Pavel ; Králíčková, Milena (advisor) ; Vožeh, František (referee) ; Slabý, Ondřej (referee)
Colorectal cancer is one of the most common type of malignity. Despite of the existence of numerous studies focused on this carcinoma, there are still many unknown features regarding its diagnosis, treatment or prognosis. In the thesis we focused on the identification of novel prognostics markers that could be useful for the stratification of patients based on the disease outcomes. In the first study we immunohistochemically assessed expression of two proteins associated with cancer stem cells in the samples of primary colorectal cancer and matched liver metastasis. Goal of the study was to evaluate relation among expression of CD44 and CD133 and overall survival and disease free interval in our set of patients. We observed that increased ratio of CD133 positive compared to CD133 negative tumor glands resulted in longer disease free interval, finding which is opposite to the general view on the CD133 role in the cancer development. Our hypothesis is that we analyzed confined group of patients and followed a bit different goal, where we measured ratio between positive and negative glands in the view-field and not the intensity of staining as the previous studies did. Our second study was focused on the transcriptional analysis of the selected set of twelve genes using frozen samples from colorectal...
|
|
|
The influence of xenobiotic metabolizing enzymes and transporters on the incidence of colorectal cancer and chemotherapy outcome
Krus, Ivona ; Souček, Pavel (advisor) ; Králíčková, Milena (referee) ; Hodis, Jiří (referee)
Introduction: Colorectal cancer (CRC) is one of the most frequent malignancies and affects approximately 5% of worldwide population. More than 75% of CRC cases represent sporadic forms. Susceptibility to nonhereditary CRC is significantly influenced by polymorphisms and mutations in low-penetrance genes. Variations in biotransformation and DNA repair genes may result in acumulation of toxins and DNA damage in cells leading to the development of cancer. Furthermore, different gene expression profiles of membrane transporters affecting the accumulation of anticancer drugs in tumour cells, e.g. ABC drug transporters, may largely influence inter-individual variability in drug response and chemotherapy outcome. The aim of this study was to evaluate the role of genetic and lifestyle factors in the risk of onset and progression of colorectal cancer. This study followed selected genetic alterations in xenobiotic-metabolizing enzymes (CYP1B1, GSTM1, GSTT1, GSTP1, NQO1 and EPHX1) and genes involved in response to DNA damage (CHEK2 and NBN), as potential CRC susceptibility factors. Another aim of this study was to investigate expression profile of all human ABC transporter genes to follow their prognostic and predictive potential in colorectal carcinoma. Materials and methods: The polymorphisms and other...
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