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The role of new pro-inflammatory and/or pro-fibrotic molecules in the pathogenesis of systemic sclerosis.
Tomčík, Michal ; Bečvář, Radim (advisor) ; Hrnčíř, Zbyněk (referee) ; Horák, Pavel (referee)
Introduction: Systemic sclerosis (SSc) is a generalized connective tissue disease affecting the skin and internal organs. The pathogenesis of SSc is characterized by inflammation, vasculopathy and fibrosis. To date, none of the tested drugs have demonstrated convincing efficacy in the treatment of SSc. S100A4 is involved in the regulation of cell motility, proliferation, apoptosis, angiogenesis and remodeling of the extracellular matrix. It was originally described as a promoter of metastasis in tumors, however, its pro-inflammatory properties have recently been demonstrated in inflammatory rheumatic diseases. The aim of this study was to assess the role of S100A4 in pathological activation of fibroblasts in SSc and in experimental models of dermal fibrosis. Results: The expression of S100A4 was increased in the skin of SSc patients, in SSc fibroblasts and in experimental fibrosis in a TGF-β / Smad dependent manner. Overexpression of S100A4 or stimulation with recombinant S100A4 induced an activated phenotype in resting normal fibroblasts. In contrast, inhibition of S100A4 or its complete deficit abrogated the pro-fibrotic effects of TGF-β and decreased the release of collagen. S100A4 knock-out mice (S100A4-/- ) were protected from bleomycin-induced skin fibrosis with reduced dermal thickening,...
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Revitalization program Cellulite - dermopanniculosis deformans and its verification in practice.
ŠPINDLEROVÁ, Martina
Diploma thesis deals with developing and testing of revitalization program which has positive effect on Cellulite-dermopanniculosis deformans. The research presents and evaluates results of revitalization program which took 6 months. Analysis of technical terms, that are closely related to cellulite, is presented in the theoretical part. There are presented views of Czech and foreign experts who deal with issues of cellulit. At the end of theoretical part we focused on available revitalizing methods that are aiming to elliminate cellulit. Experimental investigation was carried out on 60 women who were divided into experimental and control groups. Results are statisticaly processed in the form of graphs and tables and acompanied with discussion.
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The risk of chronic lesions after radiation therapy in patients with breast cancer
KŘÍŽOVÁ, Jana
Breast carcinoma is the most common cancer in women. In 2009, 5,975 new cases were diagnosed in the Czech Republic. One of the main treatment modalities is radiotherapy, which, besides bringing treatment effects, may also cause post-radiation changes that significantly influence patients? quality of life. The work focuses on monitoring the occurrence of post-radiation changes following radiotherapy as part of breast carcinoma treatment ? chronic radiodermatitis, hypodermic fibrosis and lymphedema, all at Masaryk Memorial Cancer Institute Brno. After the end of radiotherapeutic treatment these changes are monitored by the physicians during regular checks and classified on the RTOG/EORTC scale. I used a set of 98 patients (97 women and 1 man) treated at the Masaryk Memorial Cancer Institute Brno between 1998 and 2009 who suffered from the mentioned post-radiation changes. The data was assessed upon the purpose, radiation equipment used for the radiotherapy, and the degree of the studied conditions. Occurrence of lymphedema prior to radiotherapy was statistically analysed as well. All the patients received the same dose of 50 Gy with a standard fractionation scheme of 25 fractions by 2 Gy, and therefore no evaluation of coincidence of the applied dose with the risk of chronic changes occurrence was possible. Consequent changes occurred in 74 % of the studied patients. Statistics shows that patients who received radiation treatment of mamma or chest and regional lymph nodes were at higher risk of suffering chronic changes to the skin and higher risk of lymphedema, but at lower risk of hypodermic fibrosis.
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