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New methods of classification and prognosis in paragangliomas and pheochromocytomas
Guha, Anasuya ; Chovanec, Martin (advisor) ; Stárek, Ivo (referee) ; Bouček, Jan (referee)
Pheochromocytomas and paragangliomas are rare, mostly benign neuroendocrine tumors. Head and neck paragangliomas (HNPGLs) are extra-adrenal counterparts of pheochromocytomas, representing 3% of all head and neck tumors. These can occur as sporadic tumors or as part of a hereditary syndromes. Studies reporting HNPGLs in Czech Republic have been limited. We conducted a systematic review to ascertain gene mutations that are directly linked to HNPGLs. We also studied the phenotypic-genotypic profiles as well as treatment outcomes of HNPGLs. Genetic analysis was performed in Czech Republic and in collaboration with Bethesda, USA. Our review showed that ten genes contribute to the development of HNPGLs when mutated. Familial forms of the disease are most commonly associated with the SDHD gene. SDHB mutations are predisposed to malignant tumors. We assessed 30 patients (11 males; 19 females) of 34-80 years of age at our clinic between 2016 and 2021. Amongst all patients, 24 had solitary tumors and 6 showed multiple tumors. Jugular paragangliomas were the most frequently diagnosed HNPGL. Only 11.5% of all examined patients were positive for SDHD germline mutation; 50% of our younger patients with bilateral carotid body tumors had the SDHD mutation. Four patients with negative family history were diagnosed...
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Immunological aspects of head and neck cancer in relation to etiology
Koucký, Vladimír ; Bouček, Jan (advisor) ; Říhová, Blanka (referee) ; Smilek, Pavel (referee)
Tumor immunology is a progressively developing, multidisciplinary branch of biology. Results of basic research have already been successfully translated to clinical practice. The immediate success of new immunotherapeutic drugs, especially immune checkpoint inhibitors, has further supported the expansion of basic and clinical research in this field. In the case of head and neck squamous cell carcinoma (HNSCC), some immune system elements, such as CD8+ T cells, were shown to play an important role in the progression of the disease. Importantly, HNSCC is a diverse group of diseases, and a significant number of the tumors are induced by high-risk strains of human papillomavirus (HPV). HPV-associated tumors (HPV+ ) respond better to standard therapy, and the immune system was shown to be one of the crucial factors in this phenomenon. We focused on the analysis of phenotype, function, and prognostic value in tumor-infiltrating immune cells in HNSCC patients regarding the HPV status of the tumor. We were able to detect CD8+ tumor-infiltrating T cells reacting to HPV16 antigens in the majority of HPV+ oropharyngeal cancers. Moreover, activity of these T cells was enhanced after blockade of both PD-1 and TIM-3 immune-checkpoint pathways, supporting a concept of combined immunotherapy. In our...
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Polymer probes for guided endoscopic surgery of solid tumors
Horák, Dominik ; Etrych, Tomáš (advisor) ; Bouček, Jan (referee)
1 Abstract: This work focuses on development of both low- and high-molecular substances usable in fluorescent navigated endoscopic surgery with an emphasis on the characteristics of both tumor tissue and the substance itself. The usage of low-molecular substances, such as indocyanine green, has been abandoned over the past years, mostly due to poor localization and short circulation time. New polymer probes such as those based on pHPMA, were introduced to resolve these flaws. They benefit from the enhanced permeability and retention effect of the tumor tissue which is specific for macromolecules. The attachment of fluorophores to polymer carriers induces quenching, therefore novel systems are being designed to be able to release the fluorophore for example due to acidic environment of a tumor tissue or the overexpression of some peptidases. The experimental part of this work is dedicated to such polymer system with a pH-sensitive spacer-bound fluorophore. Keywords: polymer probes, fluorescence, pH-sensitive, nanomaterials, controlled release, quenching, Cyanine7 [IN CZECH]
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Immuno-biological Aspects of Head and Neck Squamous Cell Carcinoma
Bouček, Jan ; Říhová, Blanka (advisor) ; Fučíková, Terezie (referee) ; Šlapák, Ivo (referee)
The process of tumorigenesis is conditioned by change or the series of changes at a gene level. The development of cancer is largely pre-ordained by this change, but very important role is played by other factors. In case of solid tumors it is mainly a tumor microenvironment, where the tumor cells are in contact with stromal cells, especially fibroblasts, and immune cells. Tumor microenvironment can also critically modify the nature and intensity of anti- tumor immune response. Squamous cell carcinomas of the head and neck are the sixth most common cancer, which affect each year more than half a million patients worldwide. Despite advances and improvements in all treatment modalities, achieved therapeutic results even in Western countries are not satisfactory and remain at approximately the same values for several decades. At prezent, the 5 years survival rate, regardless of the location and stage of disease, is approximately only 40%. In the prezented work the immunological and biological aspects of squamous cell carcinoma of the head and neck are discussed. It summarizes the recent findings on the molecular basis of the behavior of tumor cells and the influence and significance of regulation of the immune system for the clinical course of disease and the modern therapeutic approaches.
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Application of special methods in diagnostics of benign and malignant mucosal lesions of upper aerodigestive tract.
Zábrodský, Michal ; Bouček, Jan (advisor) ; Čelakovský, Petr (referee) ; Šlapák, Ivo (referee)
Optical imaging methods incorporating observation of the mucosal surface of organs with narrowband filtered light are diagnostic tools with a significant development in recent years and have become an integral and inseparable part of the diagnostic process of benign and malignant pathologies of the mucosal surface of various anatomical systems of the human body. Malignant and premalignant lesions of the upper aero-digestive tract (UADT) are no exception. The present work demonstrates the benefits of evaluation of changes in microvascular architecture by narrowband imaging. Its major advantage is a more accurate diagnosis of premalignant and malignant mucosal pathologies in the head and neck region based on the identification of significant changes in superficial vascularity. There is a very strong correlation of these vascular changes with the final histopathological analysis. The present data have shown that videoendoscopic examination with narrowband imaging significantly improves the distinction between benign and malignant mucosal lesions even in the UADT pathologies with a similar tendency to neoangiogenesis (squamous cell papilloma vs. squamous cell carcinoma). It also refines the determination of surface extension of tumoral changes and helps to localize and accurately diagnose tumors of...
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Study of anti-tumor immune response in patients with lung cancer.
Myšíková, Dagmar ; Lischke, Robert (advisor) ; Bouček, Jan (referee) ; Palich Fučíková, Jitka (referee)
Lung cancer is the leading cause of cancer mortality worldwide. Understanding biological processes of specific antitumor immune response remains of an eminent interest and represents necessity for designing successful antitumor immunotherapeutic strategies. The theoretical part of the thesis describes components of the immune system that are involved in antitumor response and discusses their role in the hitherto known and used lung cancer immunotherapy. In the practical part of the thesis, two studies studying different aspects of anticancer immune response are described. Both studies were conducted in cooperation with 3rd Surgical Department 1st Faculty of Medicine, Charles University and University Hospital Motol and with the biotechnology company Sotio a.s. The first study is focused on the humoral component of the specific antitumor response and prospectively analyses serum frequency of antitumor antibodies against NY-ESO-1, Her2/neu and MAGE-A4 antigens in 121 patients with NSCLC. Here it was shown for the first time that tobacco smoking significantly increases the frequency of NY- ESO-1 antibodies in sera of smokers in comparison to ex-smokers and non-smokers. The second study is focused on the cellular component of the specific antitumor response investigating the activity of the dendritic...
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Jiří František Pacák and his work in eastern Bohemia
Bouček, Jan ; Oulíková, Petra (advisor) ; Adamcová, Kateřina (referee)
The diploma thesis deals with life and work of a baroque sculptor Jiří František Pacák in East Bohemia. The thesis focuses on Pacák's artistic beginnings in pilgrimage church in Chlumek u Luže. It illustrates influence of sculptor Matyáš Bernard Braun on Pacák's sculpture production and describes his artistic development in town of Žireč, Žacléř, Polička and other places in the region. The thesis includes a catalogue of Pacák's work
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Pavel Michna of Vacínov
Bouček, Jan ; Čechura, Jaroslav (advisor) ; Zdichynec, Jan (referee)
There are only a few works available dealing with the Czech Early New Times and not mentioning the name of Pavel Michna z Vacínova. The man who succeeded in overcoming barriers of his middle class origin and making himself an indispensable advisor to top representatives of the Czech Kingdom and even Emperor Ferdinand II and to manage elevation to Imperial Earldom towards the end of his life. Michna, a butcher's son from Budyně nad Ohří, became thanks to patronage of the High Chancellor of the Czech Kingdom Zdeněk Vojtěch Popel z Lobkowicz in the early part of the 17th century the Czech Kingdom Court Office Secretary and reinforced a group of catholic militants who gradually started to exploit the Czech Kingdom Court Office for the benefit of their own influence at the expense of Protestant majority. Even though Michna had signed the Imperial Charter of Rudolf II that guaranteed all subjects in the Kingdom freedom of worship, he alone prosecuted Protestants during his office period in the Czech Kingdom Court Office and was aiming to restrict their rights. The hate of Protestants against Michna culminated on May 23, 1618, when he should have been one of the victims of the Defenestration of Prague. He had learned of plans of the plotters on time and rescued himself fleeing to Vienna to the Imperial...
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