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Regulation of histone post-translational modifications and its use in the diagnosis and treatment of lung cancer
Marada, Kryštof ; Janoštiak, Radoslav (advisor) ; Červená, Klára (referee)
The aim of this bachelor's thesis is to summarize the epigenetic mechanisms, namely DNA methylation, non-coding RNA and post-translational modification of histones, within the scope of which the five currently most researched types are described, i.e. acetylation, methylation, phosphorylation, ubiquitinylation and sumoylation. Furthermore, a summary of the modifying enzymes whose function is to add and remove these epigenetic components. And also the description of the proteins that recognize these components. The following is a description of how epigenetic processes are involved in the course of cancer. The remaining part of the work is devoted to lung cancer, its most common causes, what methods are currently used to treat it, and how post-translational modifications of histones could be used in its treatment. Most of this chapter is devoted to histone deacetylase inhibitors, as these inhibitors represent potential as a new component of lung cancer treatment, which also makes them the target of much research.
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Circulating biomarkers in colorectal cancer and their application in diagnosis and prognosis
Červená, Klára ; Vymetálková, Veronika (advisor) ; Boublíková, Ludmila (referee) ; Václavíková, Radka (referee)
Despite all the advances in the field of clinical and molecular oncology, the numbers related to the incidence and mortality of colorectal cancer (CRC) remain at unacceptable levels. In recent years, liquid biopsy consisting of circulating biomarkers has come to the forefront of research, offering many advantages over conventional biopsy, such as providing timely information on tumor heterogeneity and the ease of repeated sampling. This dissertation thesis aimed to identify novel candidate circulating biomarkers from microRNAs, long non-coding RNAs, and cell-free DNA that could be used for earlier diagnosis, better prognosis, or prediction of therapy response of CRC patients and thus further advance personalized medicine. The main results of this work are: 1) Circulating microRNAs in plasma (miR-122-5p and miR- 142-5p) can distinguish patients with rectal cancer and cancer-free individuals and could predict therapy response in patients (both in primary and metastatic CRC patients). 2) Gene amplification of the long non-coding RNA MALAT1 can represent an important step in the transition of healthy mucosa to adenoma tissue. Plasma MALAT1 is overexpressed in patients with colorectal adenomas and CRC patients compared to cancer-free individuals and has the potential as a predictive biomarker for CRC...
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Diagnostic and prognostic impact of miR-122 and miR-142 in colorectal cancer
Kalkušová, Kateřina ; Červená, Klára (advisor) ; Král, Jan (referee)
Colorectal carcinoma is one of the most frequent cancers and it is also one of the most common causes of cancer related death. It is often diagnosed at a late stage which is associated with a worse prognosis. Therefore, there is an effort to identify new biomarkers that allow earlier diagnosis. These biomarkers could predict prognosis of disease and patient's response to treatment. Short noncoding RNAs - microRNA - appears to be promising candidates, these molecules are involved in many cellular processes through RNA interference. The aim of this thesis is to summarize knowledge about application of miR-122 and miR-142 as diagnostic and prognostic biomarkers for colorectal cancer. Keywords: microRNA, biomarkers, colorectal cancer, diagnostics, prognosis
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Cell Surface Markers in Colorectal Cancer
Červená, Klára ; Španielová, Hana (advisor) ; Plocek, Vítězslav (referee)
Colorectal cancer is the most frequent cancer in the Czech Republic. Retrospective analysis of patients with colorectal cancer have led and still lead to the discovery of new biomarkers that may be important in treatment, prediction or prognosis of cancer. The main aim of this thesis was to desribe discovered cell surface proteins (biomarkers) of colorectal cancer, that correlate with colorectal cancer progression, metastasis and patient outcome, and discusses the possibilities of their utilization as cancer cell targets for theranostic purposes. Keywords: colorectal cancer, biomarkers, targeting, theranostics, prediction, prognosis
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Dysregulation of E3 ubiquitin ligases in inflammatory bowel diseases
Armerová, Eliška ; Petrezsélyová, Silvia (advisor) ; Červená, Klára (referee)
E3 ubiquitin ligases are a large family of enzymes involved in many cellular processes such as DNA damage repair, transport of membrane proteins, chromatin modification, cell cycle and apoptosis. E3 ubiquitin ligases have been shown to play a significant role in the maintenance of intestinal homeostasis, and their abnormal function associated with their deregulation contributes to inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In recent years, GWAS has identified approximately 200 risk loci that are susceptible to these diseases. Including those encoding E3 ubiquitin ligases.The aim of this work is to compare the already identified E3 ubiquitin ligases associated with these diseases and to give an overview of them with a focus on the regulation of intestinal homeostasis. Key words: E3, ubiquitination, inflammatory bowel diseases, intestinal homeostasis, CD, UC
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Dysregulation of E3 ubiquitin ligases in inflammatory bowel diseases
Armerová, Eliška ; Petrezsélyová, Silvia (advisor) ; Červená, Klára (referee)
E3 ubiquitin ligases are a large family of enzymes involved in many cellular processes such as repair of damaged DNA, transport of membrane proteins, chromatin modification, cell cycle and apoptosis. E3 ubiquitin ligase has been shown to play a significant role in the maintenance of intestinal homeostasis, and their abnormal function associated with their deregulation contributes to inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In recent years, approximately 200 risk loci have been identified that are susceptible to these diseases, including those encoding E3 ubiquitin ligase. 10 of them have been identified. The aim of this work is to compare the already identified E3 ubiquitin ligases associated with these diseases and to give an overview of them with a focus on the regulation of intestinal homeostasis. Key words: E3, ubiquitination, inflammatory bowel diseases, intestinal homeostasis, CD, UC
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Diagnostic and prognostic impact of miR-122 and miR-142 in colorectal cancer
Kalkušová, Kateřina ; Červená, Klára (advisor) ; Král, Jan (referee)
Colorectal carcinoma is one of the most frequent cancers and it is also one of the most common causes of cancer related death. It is often diagnosed at a late stage which is associated with a worse prognosis. Therefore, there is an effort to identify new biomarkers that allow earlier diagnosis. These biomarkers could predict prognosis of disease and patient's response to treatment. Short noncoding RNAs - microRNA - appears to be promising candidates, these molecules are involved in many cellular processes through RNA interference. The aim of this thesis is to summarize knowledge about application of miR-122 and miR-142 as diagnostic and prognostic biomarkers for colorectal cancer. Keywords: microRNA, biomarkers, colorectal cancer, diagnostics, prognosis
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Circulating microRNAs in rectal cancer
Červená, Klára ; Vodička, Pavel (advisor) ; Pitule, Pavel (referee)
Colorectal cancer (CRC) is the third most common cancer and one of the most common cause of cancer-related death worldwide. Early detection of colorectal cancer or precancerous lesion is a precondition for decreasing incidence and mortality CRC. Therefore, the search for new biomarkers to enable facilitate early diagnosis, prognosis and individualized treatment is particularly warranted. MicroRNA (miRNAs) are small non-coding RNA molecules involved in the post- transcriptional and translational regulation of gene expression. The discovery that miRNAs may act either as oncogenes or tumor suppressors has initiated extensive research. MiRNAs pose several advantages such as high stability, easy detection or presence in almost all body fluids. Due to these and other characteristics, circulating miRNAs aspirate to diagnostic, prognostic and predictive biomarkers of colorectal cancer. In our study, we analysed gene expression of fifteen selected miRNAs (miR-17, miR- 18a, miR-18b, miR-19a, miR-19b, miR-20a, miR-20b, miR-21, miR-103, miR-106a, miR- 133a, miR-143, miR-497, miR-564 and miR-6752) in the plasma of patients with rectal cancer and in the plasma of control group, which comprised by healthy donors of blood. In order to diminish tumour heterogeneity, we focused on rectal cancer. We discovered that...
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Cell Surface Markers in Colorectal Cancer
Červená, Klára ; Španielová, Hana (advisor) ; Plocek, Vítězslav (referee)
Colorectal cancer is the most frequent cancer in the Czech Republic. Retrospective analysis of patients with colorectal cancer have led and still lead to the discovery of new biomarkers that may be important in treatment, prediction or prognosis of cancer. The main aim of this thesis was to desribe discovered cell surface proteins (biomarkers) of colorectal cancer, that correlate with colorectal cancer progression, metastasis and patient outcome, and discusses the possibilities of their utilization as cancer cell targets for theranostic purposes. Keywords: colorectal cancer, biomarkers, targeting, theranostics, prediction, prognosis
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