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Spontaneous Regression of Melanoma in Pigs of the MeLiM Strain
Plánská, Daniela ; Horák, Vratislav (advisor) ; Smetana, Karel (referee) ; Bartůňková, Jiřina (referee)
Melanoma is a skin tumour arising from melanocytes - skin cells bearing pigment melanin. Melanoma belongs among immunogenic tumours, which is probably associated with a relatively high incidence of partial spontaneous regression (SR). Melanoma-bearing Libechov Minipigs (MeLiM) represent a specially bred animal model that is mostly affected by nodular melanomas, which fully regressed in about 2/3 of the affected animals. Our interest was to examine immune response (associated with melanoma cell destruction) and the role of proteins related to the extracellular matrix (reflecting tissue remodeling) during SR of MeLiM melanoma. We performed an extensive time-lapse study of skin melanomas taken from individuals of the MeLiM strain at 3, 4, 6, 8, 10, 12, 20 and 32 weeks (5-10 samples in each age category) in which we immunohistochemically detected the expression of collagen IV, laminin, fibronectin, tenascin C, as well as MMP-2 and we monitored the proportion of basic immune subpopulations in blood and tumour by flow cytometry. The higher expression of collagen IV, laminin and MMP-2 positively correlated with the appearance of melanoma cells. The expression of collagen IV and laminin indicates a possible survival of tumour cells due to the interaction with these proteins, the presence of MMP-2 in these...
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The role of dendritic cells in various pathological states
Sochorová, Klára ; Bartůňková, Jiřina (advisor) ; Tučková, Ludmila (referee) ; Stříž, Ilja (referee)
Dendritic cells (DCs) represent one of the most important components of the immune system. DCs are the most effective antigen presenting cells with a unique ability to stimulate naive T cells. They ensure the crosstalk between innate and adaptive immunity. They participate in anti-infectious and anti-tumor immune reaction as well as in the induction of tolerance. It is clear, that the defect in DC can be fatal for the organism. In our work we studied the biology of DCs and the disturbances of DCs function in pathological states. We analyzed DCs in patients with Bruton's tyrosin kinase deficiency, we compared the effect of vitamin D analogs, calcitriol and paricalcitol, on DCs and we set up the protocol of DC generation for the immunotherapy of ovarian cancer. In the study concerning btk deficiency and dendritic cell function we found profound impairment of IL-6 and TNF production in response to the stimulation by Toll-like receptor ligand 8. In the second part of our work we compared the effect of calcitriol and paricalcitol on DCs. Both drugs inhibited DCs maturation and decreased their ability to induce proliferation of antigen specific T cells. In the third part of our work we set up the protocol for the DCs, which are able to induce tumor specific immune responses. We optimized the form of tumor antigen...
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Dendritic cells and their importance in immune response
Vávrová, Jitka ; Rožková, Daniela (advisor) ; Bartůňková, Jiřina (referee)
Dendritic cell (DC) is the most effective antigen presenting cell in human organism. Dendritic cells plays important role in immunity response because they stimulate naive T-lymfocytes. This propeliy is very useful in immunotherapy of tumor diseases. The general aim of this work was to optimalize operating protocol for preparation vaccine containing dendritic cell s for patients with ovarian carcinoma. We examined single parts of process of preparation and their impact on result of whole process. We were interested in used plastic, from which are culture bottle made, and its impact to maturation of dendritic cells. Next thing that we examined was if we use the same kind of maturation reagent, type poly I:C, from different producers, will be dendritic cells maturated in the same way. After made vaccines are freezed to -80DC to keep their immunosupresive properties. We examined if DCs after defrosting have the same properties like before. We also examined diferent types of medium used for freezing and their impact to fenotype and service life ofDCs. Powered by TCPDF (www.tcpdf.org)
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Immunocompetent cells and their importance in immunopathological conditions
Podrazil, Michal ; Bartůňková, Jiřina (advisor) ; Reiniš, Milan (referee) ; Smetana, Karel (referee)
Pokroky v současné imunologii vedou k lepšímu porozumění interakcí mezi imunitním systémem a nádory, což vzbuzuje zájem o využití imunitního systému v léčbě nádorových onemocnění. V úvodní části práce jsou shrnuty teoretické poznatky o mechanismech protinádorové imunitní odpovědi a jednotlivých složkách imunitního systému podílejících se na tomto procesu. Ústřední úlohu v této interakci reprezentují dendritické buňky. Právě jejich využitím v klinické medicíně se dlouhodobě zabývá naše pracoviště. V této práci se věnuji několika dílčím cílům. První z nich je analýza zastoupení jednotlivých subpopulací imunokompetentních buněk v imunoterapeutickém léčivém přípravku na bázi dendritických buněk proti karcinomu prostaty- DCVAC/PCa vyvinutého na Ústavu imunologie, dále praktickým aspektům přípravy této formy aktivní buněčné imunoterapie a její optimalizaci za podmínek správné výrobní praxe. Výsledky této části byly součástí farmaceutické dokumentace, která vedla ke schválení výrobního postupu i zahájení klinických studií u pacientů s karcinomem prostaty regulačními autoritami. Dalším krokem bylo následné praktické testování imunoterapie DCVAC/PCa nejprve v pilotní "first-in-men" aplikaci u pacienta s pokročilým metastatickým karcinomem prostaty a následně klinické hodnocení tohoto preparátu v rámci 2...
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Mechanisms of muscle inflammation and clinical manifestations in patients polymyositis and dermatomyositis
Studýnková-Tomasová, Jana ; Vencovský, Jiří (advisor) ; Bartůňková, Jiřina (referee) ; Hrnčíř, Zbyněk (referee)
Idiopathic inflammatory myopathies (IIM) is a heterogeneous group of acquired diseases with varying course and prognosis nehnisavým caused by inflammation of striated muscle. Clinically they are characterized primarily by proximal muscular weakness. On the basis of specific clinical, histopathological, immunological and demographic features of the breakers can be divided into three subgroups dermatomyositis (DM), polymyositis (PM) and inclusion bodies with myositis (IBM). The aetiology of these diseases is unknown and there is also rooted difficulties with their treatment. The common objective of the project was to try to map out the mechanisms leading to inflammatory infiltration of muscles, muscle tissue edema and tissue damage, and subsequently to clinical manifestations of disease in patients with PM and DM.
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Adoptive transfer of tumor-specific lymphocytes for cancer immunotherapy
Vávrová, Kateřina ; Bartůňková, Jiřina (advisor) ; Němečková, Šárka (referee) ; Reiniš, Milan (referee)
Prostate cancer is the second leading cause of cancer death in men in Europe and the US. In the context of previous preclinical experiments and clinical studies there are certain assumptions predicating successful application of immunotherapy in the treatment of patients with prostate cancer. Promising results have been achieved by a combination of different treatment modalities which provide a synergistic antitumor effect. One of these combinatorial options is the use of antitumor vaccines and adoptive T cell transfer. The topic of this thesis is to provide a fresh insight into the past and current trends following the long-term candidate's department program in the field of anti-tumor immunotherapy. The experimental part of this thesis revolves around our own results published in this field. The introductory chapter delivers a basic overview of cellular mechanisms of anti-tumor immunity and the role of individual immune components in these processes. Following chapters are dedicated to current immunotherapeutic approaches with emphasis on the adoptive T cell transfer and implication of this technology in the treatment of prostate cancer. The results section describes the establishment of our protocol for adoptive T cell transfer as well as the protocol for ex vivo enrichment of human T cell...
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Oncolytic viruses in cancer immunotherapy
Zupko, Jakub ; Bartůňková, Jiřina (advisor) ; Janovec, Václav (referee)
Oncolytic virotherapy is a field dedicated to exploiting viruses in the battle against cancer, where their specific cytolytic effects are sorely needed. This work focuses on the mechanisms and limitations of oncolytic virotherapy, on the recent advances in the field and on the potential oncolytic viruses hold for the future.
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