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Morphological and Genomic Profiling of Circulating Tumor Cells in Metastatic Colorectal Cancer
Thiele, Jana-Aletta ; Pitule, Pavel (advisor) ; Mohelníková Duchoňová, Beatrice (referee) ; Kasimir-Bauer, Sabine (referee)
Colorectal cancer (CRC) is the third most common cancer worldwide; it is responsible for nearly 10% of all newly diagnosed cancers and is the second most cause of cancer related death in Europe. Biomarkers for therapy guidance, targeted therapy and survival prognosis are still limited. As CRC is a heterogeneous disease, different parts of the tumor might have varying molecular characteristics which may change during therapy or disease progression. Through solid biopsies and screenings, these local or temporal differences are impossible to monitor. To facilitate detection of these possible temporal changes, a regularly and non-invasively accessible biomarker is required for disease monitoring. Circulating tumor cells (CTCs) might represent such a biomarker as they have been shown to be fluid surrogates of the solid tumor. EpCAM positive CTCs have shown to be prognostic in CRC for survival, but their full potential has not yet been evaluated further. By using the High Definition Single Cell Analysis (HD-SCA) workflow, we were able to analyze the entire spectrum of CTCs and categorize them as the regular CTCs (HD-CTC), CTCs with a smaller nuclear area (CTC-Small), CTCs with low expression of epithelial marker cytokeratin (CTC-LowCK) and CTCs undergoing apoptosis and therefore releasing cell free DNA...
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Morphological and Genomic Profiling of Circulating Tumor Cells in Metastatic Colorectal Cancer
Thiele, Jana-Aletta ; Pitule, Pavel (advisor) ; Mohelníková Duchoňová, Beatrice (referee) ; Kasimir-Bauer, Sabine (referee)
Colorectal cancer (CRC) is the third most common cancer worldwide; it is responsible for nearly 10% of all newly diagnosed cancers and is the second most cause of cancer related death in Europe. Biomarkers for therapy guidance, targeted therapy and survival prognosis are still limited. As CRC is a heterogeneous disease, different parts of the tumor might have varying molecular characteristics which may change during therapy or disease progression. Through solid biopsies and screenings, these local or temporal differences are impossible to monitor. To facilitate detection of these possible temporal changes, a regularly and non-invasively accessible biomarker is required for disease monitoring. Circulating tumor cells (CTCs) might represent such a biomarker as they have been shown to be fluid surrogates of the solid tumor. EpCAM positive CTCs have shown to be prognostic in CRC for survival, but their full potential has not yet been evaluated further. By using the High Definition Single Cell Analysis (HD-SCA) workflow, we were able to analyze the entire spectrum of CTCs and categorize them as the regular CTCs (HD-CTC), CTCs with a smaller nuclear area (CTC-Small), CTCs with low expression of epithelial marker cytokeratin (CTC-LowCK) and CTCs undergoing apoptosis and therefore releasing cell free DNA...
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Circulating tumor cells in breast cancer patients
Bielčiková, Zuzana ; Zemanová, Milada (advisor) ; Gürlich, Robert (referee) ; Fínek, Jindřich (referee)
Circulating tumor cells (CTCs) represent a systemic phase of the localised cancer disease. They can be distinguished and enriched from the peripheral blood and so from the surrounding leukocytes by either physical properties (e.g., density and size) or biological properties (e.g., expression of epithelial proteins such as EpCAM or cytokeratins) and are usually further characterized by immunostaining or RT-PCR assays. Selecting patients with the risk of disease relaps at the time of diagnosis is crucial for clinicians in deciding who should, and who should not, receive adjuvant chemotherapy. We know that CTCs are strong prognostic factor in patients with metastatic as well as localized breast cancer (BC). It is also known that the prognostic power of circulating tumor cells in women with BC is independent from the standard prognostic indicators. Testing of CTCs known recently as "liquid biopsy" could be informative not only as predictor of the disease relapse, but also as the predictor of therapy effectiveness. The clinical use of CTCs must be strictly encouraged by clinical trials results. Monitoring of CTCs in time could zoom in the mechanism of therapy resistance and/or may provide the identification of new druggable targets. The purpose of my work was therefore to assess the CTCs positivity rate...
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Circulating cell-free DNA and its potential in oncology
Karasová, Dominika ; Žižková, Hana (advisor) ; Novák, Josef (referee)
The circulating free DNA ("Cell-free DNA",cfDNA) is a type of extracellular DNA present in blood, with clinical use in prenatal diagnosis. The cfDNA is given great emphasis in connection with tumor diseases, where there is a great potential for its use in oncology, where free circulating tumor DNA is the most commonly used type. A suitable alternative to classical biopsy, which is safer and less painful for the patient and reflects the heterogeneity of the tumor is called Liquid biopsy, which can be used to obtain free circulating DNA from the blood. Most studies show that cfDNA provides the same information as tissue DNA, regarding both genetic and epigenetic changes detected in tumor cells and in some cases it enabled more sensitive or earlier detection of relapse in comparison with routinely used examinations. The high specificity and sensitivity of this non-invasive approach can be a great benefit to patients. However, to confirm its diagnostic and prognostic significance, it is necessary to expand the group of patients with individual diagnoses and, not only for the purpose of data comparison, standardize methods for the isolation and detection of cfDNA, The aim of this thesis is to gain a general overview of free circulating DNA and its potential use in oncology. Keywords: circulating free...
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