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Mutual communication and relationship between tumor cells and the tumor microenvironment
Novák, Štěpán ; Szabo, Pavol (advisor) ; Krška, Zdeněk (referee) ; Grobárová, Valéria (referee)
The present dissertation addresses two main objectives. First, the interaction between four pancreatic ductal adenocarcinoma (PDAC) cell lines and conditioned media from normal/healthy fibroblasts was investigated, HF) and cancer- associated fibroblasts (CAFs) derived from PDAC (PDAC-derived CAFs, PANFs), cells derived from ascitic fluid of patients with end-stage PDAC and primary PDAC tumor. Subsequently, the genome-wide profile of PANFs was determined. The second aim was to differentiate squamous cell carcinoma (SCC) cells, surgical resection margin (MSR) cells and normal mucosa (NM) cells in patients operated for head and neck squamous cell carcinoma (HNSCC) by immunohistochemistry, using detection of tenascin (Ten), fibronectin (Fn) and galectin-1 (Gal-1), and to correlate these results with their clinical characteristics. Subsequently, whole-genome profiling of SCC, MSR and NM samples was performed based on Ten expression stratification. Results Cultivation of the four PDAC lines under the influence of conditioned media from HF and PANF was heterogeneous. After stimulation, the most aggressive behavior was obtained in the Panc-1 cell line while the PaTu-8902 line was rather inhibited by the media. The PANF transcriptome showed increased expression of some genes (e.g. IL-6, IL-8, MFGE8,...
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Phenotype of melanocytes under physiological and pathological conditions
Strnadová, Karolína ; Lacina, Lukáš (advisor) ; Mokrý, Jaroslav (referee) ; Balvan, Jan (referee)
In addition to the dominant keratinocytes and fibroblasts, melanocytes are also indispensable representatives of skin cell populations. Melanocytes are pigment cells whose primary function is to produce the pigment melanin, which is important for protecting keratinocytes from harmful ultraviolet radiation. Excessive exposure to this radiation is a risk factor for the development of skin tumours, including malignant melanoma of the skin, in which pathological transformation of melanocytes into melanoma cells occurs. The presented thesis focuses on 4 thematic areas associated mainly with malignant melanoma. In the first thematic area, the increasing incidence of malignant skin melanoma is associated with the ageing of the population. One of the reasons seems to be the more frequent occurrence of proinflammatory setting in the ageing organism. It prepares a suitable environment for tumour development. The second thematic area focuses on new approaches that could expand the range of diagnostic methods for the early detection of malignant melanoma. The first approach methodically uses the detection of proinflammatory molecules in the patient's serum. Higher serum levels of IL-6 and IL-8 correlate with an unfavourable patient prognosis. The second approach is based on the possibility of detecting a...
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