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Oral microbiome and carcinogenesis
Šimáčková, Šárka ; Šmahelová, Jana (advisor) ; Horníková, Lenka (referee)
Microorganisms that colonize human body participate to well functioning of human organism and they are very important for human health. The composition of these communities (microbiomes) is specific for everyone and changes in the composition may participate to induce and progression of disease. These diseases also include carcinogenesis and tumors. Main goal of this work are specially tumors in head and neck area which risk factors are smoking, alcohol consumption and human papillomaviruses infection. Depending on these factors is influenced the composition of microbiome of oral cavity. Many studies show differences between oral microbiomes of patients with head and neck cancer and healthy people as controls. Keywords: microbiome, oral cavity, head and neck cancer, papillomavirus
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Virom of lower urinary tracts
Cirbusová, Adéla ; Saláková, Martina (advisor) ; Španielová, Hana (referee)
The human urinary tract was considered to be a sterile environment for many years. However, studies over the past decade have shown that urine harbours rich microbial community which includes also viruses. Nevertheless, there is only very little known about urinary virome so far. Optimised Next Generation Sequencing (NGS) protocol was used to describe the urinary virome of three individuals. However, characterization of the virome from urine samples using NGS proved to be quite challenging, mainly due to observed viral genomes fragmentation. Despite this problem, it was possible to identify human endogenous retroviruses in all individuals and also JC polyomavirus in two of them. Quantitative PCR was further used to characterize part of the urinary virome represented by human DNA viruses. Possible differences in prevalence and viral load of human DNA viruses were observed in individuals with and without bladder carcinoma (bc). Urine of these patients was obtained from different sites of the urinary tract to further establish, if there is a difference in these samples. Torque Teno virus and JC polyomavirus were found as the most common viruses. Torque Teno virus was detected in 75 % patients with and 60 % patients without bc, JC polyomavirus in 43,8 % patients with and 50 % patients without bc. BK...
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The role of APOBEC proteins in HPV-induced carcinogenesis
Frolíková, Daniela ; Šmahelová, Jana (advisor) ; Šroller, Vojtěch (referee)
Apolipoprotein B mRNA editing enzyme, catalytic polypeptide (APOBEC) are a family of evolutionarily conserved cytidine deaminases with the ability to bind and modify RNA and/or ssDNA. APOBEC1-4 have a number of functions in cells. Members of the APOBEC3 subfamily cause restriction of foreign nucleic acids, retrotransposons and viruses, including human papillomaviruses (HPV), and may contribute to the clearance of infection. Certain HPVs are referred to as oncogenic viruses because of their ability to induce immortalization and transformation of epithelial cells via E5, E6 and E7 oncoproteins. E6 and E7 can also induce transcription or inhibit degradation of some APOBEC3. This results in an increase in their levels in cells. APOBEC3 also act as cellular mutators, as they can catalyze deaminations on transiently produced ssDNA during replication or transcription. Deregulation of APOBEC3 caused by oncoproteins may contribute to mutagenesis. This bachelor thesis focuses on APOBEC proteins, their activation and function during HPV-induced carcinogenesis, and in particular the extent and consequences of APOBEC3 mutations. Keywords: APOBEC, mutagenesis, papillomavirus, oncoproteins, carcinogenesis
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The detection of hypoxic markers in head and neck tumours
Šťovíčková, Eliška ; Šmahelová, Jana (advisor) ; Rösel, Daniel (referee)
Head and neck cancers (HNSCC) are heterogeneous group of tumours. Risk factors are mainly smoking and alcohol consumption. Some of these tumours are associated with human papillomavirus (HPV) infection, which is a significant positive prognostic factor. These tumours differ from HPV-negative tumours in clinicopathological characteristics, tumour microenvironment and response to treatment. Hypoxia is commonly found in tumors including HNSCC and is a significant prognostic and predictive factor. Elucidating the degree of hypoxia in relation to HPV infection could partly explain the differences in prognosis of these patients and allow more appropriate choice of therapy. Aspartate-β-hydroxylase is also a significant negative prognostic factor in a number of tumours, but its role in HNSCC has not yet been investigated. I focused on the detection of hypoxic markers and aspartate-β-hydroxylase expression in samples from HNSCC patients at the mRNA level by quantitative PCR and at the protein level by multispectral immunohistochemistry. The expression levels of these markers were compared in tumors stratified according to viral etiology and other characteristics such as smoking, localization or tumor stage. HPV infection had the highest impact on the expression of these markers, but the results cannot point to a...
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Analysis of miRNAs in HPV-associated carcinomas
Pagáčová, Lucie ; Tachezy, Ruth (advisor) ; Vopálenský, Václav (referee)
Papillomaviruses are small DNA viruses that are associated with the induction of epithelial tumors. HPV is an important infectious agent causing almost 100 % of cervical tumors but it can also cause tumors in other anogenital and head and neck locations in both men and women. Active HPV infection induces changes in miRNA expression that contribute to the tumor formation and progression. It is already known that papillomaviruses do not encode their own viral miRNAs but they affect the expression of cellular miRNAs. In my thesis I have in selected epithelial tumors (vulva, cervix, anus and tonsils) determined their etiology and analyzed the presence of miRNAs in tissues by next generation sequencing. From these data I determined the expression profiles of deregulated miRNAs in tumors relation to healthy tissues of corresponding location. Even though, sufficient number of samples was analyzed, it was not possible to detect HPV-core miRNA common to all analyzed HPV-induced tumors due to the absence of statistically relevant differentially expressed miRNAs in HPV positive vulvar tumors. Among the tumors of the other sites I found an overlap in three miRNAs. One of these miRNAs (miR-139-5p) and another one (miR-9-5p) which I have selected based on the study of other published data, were used for...
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Analysis of miRNAs in HPV-associated carcinomas
Pagáčová, Lucie ; Tachezy, Ruth (advisor) ; Vopálenský, Václav (referee)
Papillomaviruses are small DNA viruses that are associated with the induction of epithelial tumors. HPV is an important infectious agent causing almost 100 % of cervical tumors but it can also cause tumors in other anogenital and head and neck locations in both men and women. Active HPV infection induces changes in miRNA expression that contribute to the tumor formation and progression. It is already known that papillomaviruses do not encode their own viral miRNAs but they affect the expression of cellular miRNAs. In my thesis I have in selected epithelial tumors (vulva, cervix, anus and tonsils) determined their etiology and analyzed the presence of miRNAs in tissues by next generation sequencing. From these data I determined the expression profiles of deregulated miRNAs in tumors relation to healthy tissues of corresponding location. Even though, sufficient number of samples was analyzed, it was not possible to detect HPV-core miRNA common to all analyzed HPV-induced tumors due to the absence of statistically relevant differentially expressed miRNAs in HPV positive vulvar tumors. Among the tumors of the other sites I found an overlap in three miRNAs. One of these miRNAs (miR-139-5p) and another one (miR-9-5p) which I have selected based on the study of other published data, were used for...
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