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Cytokine expression in regressive melanoma on porcine MeLiM model
Miltrová, Veronika ; Skalníková, Helena (advisor) ; Krulová, Magdaléna (referee)
Cutaneous melanoma is a very aggressive cancer with increasing incidence. It originates from transformed pigmented skin cells (melanocytes). The main risk factor for melanoma development is exposure to UV light and repeated sunburns. In approximately 10 % of cases, melanoma occurs on hereditary basis. Patients with cutaneous melanoma diagnosed in early stages have very good prognosis, with surgical resection of the primary tumour being mostly sufficient for treatment. In contrast, the advanced melanoma stages with metastases are often progressive and refractory to conventional therapies. Cutaneous melanoma is referred to as an immunogenic tumour that is frequently infiltrated by cells of the immune system. Tumours with immune cell infiltration show better prognosis. Spontaneous regression may occur. Over the last few years, progress has been made in the treatment of melanoma using checkpoints molecules (anti-CTLA-4 and anti-PD-1) to activate patients own immune system to recognize tumour lesions. In the tumour microenvironment, cytokines play an important role, enabling communication between cells and regulation of cell proliferation and migration and thus the tumour development. Cytokines (IL-2, IFNα) can be used in adjuvant therapy of melanoma. This work analysed levels of expressed cytokines in...
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Function of adaptor protein NDFIP1 in T lymphocytes
Dvořáček, Tomáš ; Brdička, Tomáš (advisor) ; Macůrková, Marie (referee)
T lymphocytes specifically recognize and promote immune response against pathogenic agents, which endanger health of host organism. However, this ability must be tightly controlled to prevent response against innocuous or self-tissue antigens, which would unnecessarily damage an organism. For a maintenance of this tolerance, there is a number of molecular mechanisms regulating T lymphocytes. The protein NDFIP1 is important component of these mechanisms. This transmembrane adaptor protein binds to E3 ubiquitin ligases from the NEDD4 family, which are under normal circumstances in inactive state. Binding of NDFIP1 leads to their activation and facilitates regulation of T cell behaviour by these ligases. NDFIP1 deficiency in mice causes the development of inflammatory disease affecting the skin, lungs and gastrointestinal tract. It is characterized by increased numbers of activated CD4+ T lymphocytes and eosinophils, which infiltrate the affected tissues. The disease is ultimately fatal. The aim of this work is to describe the function of the NDFIP1 protein in T lymphocytes, which are essential for the development of this pathology. The absence of NDFIP1 in T cells disrupts several molecular mechanisms, including the degradation of the transcription factors JUNB and RORγT and the regulation of mTOR...
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Determination of inflammatory markers of the eye based on the analysis of tears - potential and limits
Mandíková, Šárka ; Daňková, Pavlína (advisor) ; Sičáková, Silvia (referee)
In this study, we aimed to determine the levels of cytokines IL-1β, IL-4, IL-10, IFN-γ, MIF and VEGF in tears derived from healthy subjects. We tested cytokines as potential markers of inflammation for their potential use in clinical practice. Having reliable method for measuring cytokine levels in tears would enable an early diagnosis of eye diseases. In two phases, cytokines in tears of healthy individuals were analyzed using Bio-Plex Cytokine Assay (Bio-Rad). We assessed the suitability of methods for diagnostic purposes as well as the suitability of our selected cytokines. Statistically significant positive correlations of cytokines were confirmed: IL-10 with IFN-γ (r = 0,81), MIF with VEGF (r = 0,42 / r = 0,49), IL-1β with IL-10 (r = 0,52), IL-1β with IFN-γ (r = 0,55), IL-1β with VEGF (r = 0,38), IFN-γ with VEGF (r = 0,45) and IL-4 with VEGF (r = 0,48) in healthy subjects in tears. IL-4 (r = -0,37) and IFN-γ (r = -0,42) correlate negatively with age. In healthy individuals, there seem to be no differences with regard to gender, BMI, body fat, time of meal consumption prior to tear collection, eye strain when using a computer, dry eyes. Thus, studied cytokines are suitable for diagnostic purposes. Significant differences in concentrations of four (IL-1β, IL-10, IFN-γ a VEGF) of the five...
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