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Immune cells infiltrating premalignant lesions and invasive carcinomas associated with HPV infection
Dalewská, Natálie ; Tachezy, Ruth (advisor) ; Španielová, Hana (referee)
The immune system participates in many defence mechanisms of the body which in- volve the action of different types of immune cells. Immune cells play an important role in tumour development and progression. They infiltrate tumours and contribute to the tumour microenvironment. They are also implicated in diseases associated with human papillomavi- rus infection. Human papillomaviruses are viruses with oncogenic potential which cause in- fection in a number of anatomical locations of the human body. Such infection can lead to benign lesions, pre-invasive lesions, and invasive tumours. Pre-invasive lesions often re- gress spontaneously, but at advanced stages of the disease, progression to malignancy can occur. The tendency to regress or progress varies depending on the HPV genotype involved in the lesion and the quantity, type, and location of infiltrating immune cells. The synergy of these factors influences the prognosis and treatment of the disease, and, therefore, deter- mining the immunological score as an important diagnostic parameter becomes of utmost relevance. The knowledge of the effect of immune cells on tumour cells is useful in immunotherapy, which is based on the activation of the patient's own anti-tumour immune mechanisms. Immunotherapy is used in combination with systemic therapy...
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Study of genetic factors modifying the risk of onset and progression of colorectal and pancreatic cancer
Mohelníková Duchoňová, Beatrice ; Souček, Pavel (advisor) ; Skálová, Lenka (referee) ; Macek, Milan (referee)
Introduction: The aim of this study was to evaluate the role of genetic and lifestyle factors in the risk of onset and progression of colorectal and pancreatic cancer. The first part deals with the etiological factors and the importance of polymorphisms in biotransformation enzymes and genetic alterations in the gene CHEK2 in the origin of these malignancies. In the second part, the ABC transporter genes were analyzed as potential prognostic and predictive markers of a treatment's outcome. Materials and methods: The polymorphisms and other genetic alterations were detected using real-time PCR, allelespecific PCR and PCR-RFLP methods in DNA which was extracted from the blood of patients. The frequency of polymorphisms was evaluated and their importance was assessed with regard to the available epidemiological data. Gene expressions were determined by qPCR in paired samples of tumor tissue and adjacent non-tumorous parenchyma. Results: A majority of the observed polymorphisms failed to show a relationship between their presence and the risk of any of these malignancies. CYP2A13 variant allele*7 coding inactive enzyme was found in 7 of 265 controls and in none of 235 pancreatic carcinoma patients. In contrast, GSTP1-codon 105 Val variant allele and GSTT1-null genotype were associated with an elevated...
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Immunoscore in 3D tissue
Novák, Jaromír ; Drbal, Karel (advisor) ; Procházka, Jan (referee)
Solid tumors are complex structures comprising besides the cancer cells vasculature, extracellular matrix (ECM), soluble molecules and a plethora of various other cell types. These components form a so-called tumour microenvironment. From the numerous cell types that are part of tumor microenvironment, tumor infiltrating lymphocytes (TILs) play a major role in patient prognosis. Their presence is also of major importance with regard to new biological therapies based on immune checkpoint inhibitors. Crucial role of TILs is also reflected by the new approaches in cancer diagnostics namely by Immunoscore method (currently used in clinical settings). Immunoscore is based on localization and quantification of CD3+ and CD8+ TILs in thin histological sections of tumor tissue. The question remains to which extent the information obtained from 2D slices reflects the situation in tumor microenvironment considering its spatial heterogeneity. The development of new methodological approaches allowing evaluation of histological information in 3D is the key to answer this question. The theoretical part of this work first describes the heterogeneity of the tumor microenvironment and the role of immune cells within it. Then, the role of spatial heterogeneity and its possible influence on the histopathological...
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Metabolismus sarkosinu a nádorová onemocnění prostaty =: Sarcosine metabolism and prostate cancer disease /
Strmiska, Vladislav
Prostate carcinoma is one of the most frequent cancer diseases of maturated men. Diagnose of this cancer disease is based on level of prostatic specific antigen and digital exam per rectum. However, presence of tumor, grade and stage must be examined by biopsy. This method may not to be accurate. This is the reason why are new diagnostic methods investigated, to increase the accuracy of diagnostic prostate cancer. Amino acid sarcosine is currently on of the most widely discussed biomarker, that can serve as a diagnostic biomarker for early stage detection in prostate cancer. The present work deals with the study of sarcosine metabolism in prostate cancer cell lines, mainly, but also by amino acid metabolism in cells in general. Understanding to importance of single amino acids in malignant and non-malignant cell pathways can significantly contribute to effective targeted therapy without side effect on healthy tissue. Prostate cancer cells in presence of sarcosine increase their migration potential, malignancy by increased doubling time, and concentration of sarcosine N-demethylation enzymes, sarcosine dehydrogenase and sarcosine oxidase. Through this biochemical pathway is increased synthesis of main methylation donor S-adenosilmethyonine (SAM) ad cellular methylation potential.
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Exprese CD47 a jeho topologie na povrchu primárních buněk karcinomu močového měchýře při interakci s makrofágy
Rajtmajerová, Marie ; Drbal, Karel (advisor) ; Brdička, Tomáš (referee)
CD47 is a so-called "don't eat me" signal, which protects cells from phagocytosis. Its high expresion on tumor cells brings new perspective to the tumor therapy. Monoclonal antibodies, which are these days undergoing clinical trials, prevent CD47 binding to the SIRPA inhibitory receptor on macrophages, and so they enhance their phagocytic functional capacity. In this way they enable phagocytic removal of tumor cells. Overall expression, structural conformation and stoichiometry of CD47 on a particular cell predestine whether it will be phagocytised. The aim of the thesis is to develop and test methods to characterise expression parameters of CD47 via flow cytometry (FCM), quantitative PCR (qPCR) and microscopy. To achieve this goal I performed competition tests of commercially available antibodies in order to characterise their binding epitopes on cell lines. After performing tSNE analysis of primary BCa patient samples I correlated CD47 expression with other cell surface markers. I focused on CD47 expression in various differentiation stages of the tumor. To better understand the relationship between CD47 expression and differentiation status of cells I performed qPCR analysis of particular transcription factors. Using cell lines I examined method for phagocytosis quantification, which will be...
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Radiotherapy of cervical cancer
KUBIŠOVÁ, Lucie
This bacherol thesis focuses on radiotherapy of cervical cancer. In the theorical part we describe the anatomy proportions of little pelvis, typology of the tumor, its occurance, risk factors that can cause this disease, symptoms and diagnostics. We put special attention on the questions related to the prevention of cervical carcinoma. In addition we are interested in the treatment for this malignant disease surgery solutions, teletherapy, brachytherapy and chemotherapy. The second part of the bacherol thesis is empirical and focuses the radiotherapeutical treatment of patients with cervical carcinoma, stressing the analysis of doses of irradiation for the critical organs with repercussion for posterior occurance of acute or late undesired effects. The major risk factor detected was the insufficient participation of the respondents on the preventive gynecology examinations. The collected data reflect that only one third of women are undergoing the regular screening by their doctors. When analyzing the facts, we wanted to focuse on the irradiation doses applied to the critical organs. The obtained results showed that neither doses nor fractions have demostrated even a little progress during seven years. At the same time the techniques of irradiation did not evolve very much during the same period. The only difference was the increase of application of the IMRT technique in 2017 in comparison to 2010. The original hypothesis of the thesis advocating that the improvement of verification systems, imaging machines and planning systems could have an impact on the reduction of undesired effects caused by irradiation of critical organs during radiotherapy of cervix, was rejected due to above mentioned results.
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Immune cells infiltrating premalignant lesions and invasive carcinomas associated with HPV infection
Dalewská, Natálie ; Tachezy, Ruth (advisor) ; Španielová, Hana (referee)
The immune system participates in many defence mechanisms of the body which in- volve the action of different types of immune cells. Immune cells play an important role in tumour development and progression. They infiltrate tumours and contribute to the tumour microenvironment. They are also implicated in diseases associated with human papillomavi- rus infection. Human papillomaviruses are viruses with oncogenic potential which cause in- fection in a number of anatomical locations of the human body. Such infection can lead to benign lesions, pre-invasive lesions, and invasive tumours. Pre-invasive lesions often re- gress spontaneously, but at advanced stages of the disease, progression to malignancy can occur. The tendency to regress or progress varies depending on the HPV genotype involved in the lesion and the quantity, type, and location of infiltrating immune cells. The synergy of these factors influences the prognosis and treatment of the disease, and, therefore, deter- mining the immunological score as an important diagnostic parameter becomes of utmost relevance. The knowledge of the effect of immune cells on tumour cells is useful in immunotherapy, which is based on the activation of the patient's own anti-tumour immune mechanisms. Immunotherapy is used in combination with systemic therapy...
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