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Molecular genetic analysis of thyroid carcinomas in pediatric and adolescent patients
Bulanová, Barbora
Thyroid nodules are rare in pediatric and adolescent patients, but they are at greater risk of malignancy than adult patients. Thyroid carcinomas are the most common endocrine malignancy and their incidence is increasing. Although there are several types of thyroid carcinoma, 90% of cases in pediatric and adolescent patients are papillary thyroid carcinomas (PTCs). The aim of this study was to analyze a large cohort of PTCs from pediatric and adolescent patients, determine their genetic cause, and correlate the findings with clinical pathological data. Another aim was to characterize the most frequent findings and compare them with a cohort of adult patients with thyroid carcinoma positive for the same mutation. The final objective was to optimize a suitable methodology for detecting the most common findings in pediatric and adolescent patients for routine use. Thyroid tumor tissue samples were examined using molecular genetic methods, mostly using next-generation sequencing and real-time PCR analysis. We found that fusion genes were the most common cause of PTC in pediatric and adolescent patients, detected in 56% of patients. In total, 20 different types of fusion genes were identified, some of which have not been previously described in the literature. The fusion genes included the oncogenes...
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Microarray Data Interpretation
Ludwig, Petr ; Šilhavá, Jana (referee) ; Smrž, Pavel (advisor)
This Bachelor thesis explains the basics of biochip or microarray data interpretation, starting with short introduction to genetics, especially genetic information significance evaluating. The focus was set mainly on the set of scripts transforming and analyzing the sample data. The data used in this thesis are a result of biochip analysis of the Colon Tumor tissues. The secondary result represents disclosing the main marker for this particular type of cancer, the primary result is evaluation of marker significance in the context of signaling pathways. The resulting pathways are sorted by relevance.
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Molecular genetic analysis of thyroid carcinomas in pediatric and adolescent patients
Bulanová, Barbora ; Kuklíková, Vlasta (advisor) ; Ludvíková, Marie (referee) ; Vícha, Aleš (referee)
Thyroid nodules are rare in pediatric and adolescent patients, but they are at greater risk of malignancy than adult patients. Thyroid carcinomas are the most common endocrine malignancy and their incidence is increasing. Although there are several types of thyroid carcinoma, 90% of cases in pediatric and adolescent patients are papillary thyroid carcinomas (PTCs). The aim of this study was to analyze a large cohort of PTCs from pediatric and adolescent patients, determine their genetic cause, and correlate the findings with clinical pathological data. Another aim was to characterize the most frequent findings and compare them with a cohort of adult patients with thyroid carcinoma positive for the same mutation. The final objective was to optimize a suitable methodology for detecting the most common findings in pediatric and adolescent patients for routine use. Thyroid tumor tissue samples were examined using molecular genetic methods, mostly using next-generation sequencing and real-time PCR analysis. We found that fusion genes were the most common cause of PTC in pediatric and adolescent patients, detected in 56% of patients. In total, 20 different types of fusion genes were identified, some of which have not been previously described in the literature. The fusion genes included the oncogenes...
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Analysis of mutations in p53 gene by sequencing
BUŘIČOVÁ, Tereza
The task of this work is a detailed literature search to get acquainted with the methodology of the research part in the faculty laboratory of the University of South Bohemia at the Faculty of Health and Social Studies in České Budějovice. The tumor suppressor gene TP53 plays a key role in protection against tumor growth. This gene is mutated in more than 50 % of malignant tumors. In the first part, this bachelor thesis deals with cancer and tumor suppressor genes as a whole, and then in the next part it focuses on the above-mentioned tumor suppressor gene TP53 and mutations in it. The practical part of the work focuses on the analysis of mutations in exon 11. The analysis was performed on thirty samples, which were provided by anonymous probands. These were two groups of probands. Half of the samples, which are numbered 1-15, were provided by probands who had a family history of cancer. The other half consisted of samples, described by letters from A to O, from probands who were unaware that the cancer was in their family. These samples were isolated, amplified by PCR and sequenced by GenSeq s.r.o. in České Budějovice. In the "ocometric" evaluation, it was found that not a single heterozygous mutation was present in the samples. . After inserting the sequence into the NCBI Blast program, I thought that some samples might contain a homozygous mutation. However, after a proper examination, it was found that this was only an illegible part of the sequence. Thus, no mutation was present in any of the examined samples.
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Development of the number of the whole body skeletal scintigraphy in recent years (in the context of the number of PET and the numbers of patients with prostate, breast, and lung cancer)
KINSKÁ, Jana
This bachelor thesis deals with development of the number of the whole-body skeletal scintigraphy in recent years in the context of the numbers of PET and the number of patients with prostate, breast and lung cancer. The aim of this thesis is to give an overview of the development of the number of the whole-body skeletal scintigraphy in connection with the number of PET and the number of patients with prostate, breast and lung cancer from selected Departments of Nuclear Medicine since 2010. This thesis focuses on one particular question: "Has the number of the whole-body skeletal scintigraphy increase during the years?". The defined aim has been fulfilled and the question asked has been answered. The overview of the development of the number of the whole-body skeletal scintigraphy and of the numbers of PET, PET/CT scans was obtained by means of quantitative research in 13 Departments of Nuclear Medicine in the Czech Republic. The overview of the number of patients with prostate, breast and lung cancer is based on data available from the Institute of Health Information and Statistics of the Czech Republic. The results of the research show that the development of the number of the whole-body skeletal scintigraphy has a clear downward tendency during the evaluated years. An upward trend is observable in the course of the evaluated years in development of the number of PET, PET/CT scans compared to the skeletal scintigraphy. The upward development is also evident in the number of patients with prostate, breast and lung cancer in the evaluated years. For this reason, the PET, PET/CT scan is increasingly used as the number of patients with prostate, breast and lung cancer increase. This is a possible conclusion from the results generated. This examination is very suitable and very often used for their diagnosis, the measurement of the extent of cancer, but also for the evaluation of the therapy's efficiency and the possibility of relapse.
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Social determinants of knowledge of HPV infection and cancer risk
Stuchlíková, Tereza ; Kulhánová, Ivana (advisor) ; Hejtmánková, Alžběta (referee)
This diploma thesis deals with sexually transmitted human papillomavirus (HPV) infection and potential cancer risks that it causes. HPV is a factor of cervical cancer, one of the most common cancer cause of death in women, cervical cancer. Despite the fact that the majority of both female and male population become infected with HPV during their sexually active lives, especially before the age of 30, women are predominantly more susceptible to this infection. When young, the immune system can clear HPV within 2 years unnoticed but in the case of high-risk HPV, an innocent infection can be fatal. In recent years, the male population in particular has been increasingly affected by malignant neoplasms of the head and neck, such as oropharynx, which are caused by HPV. In recent years, HPV has ceased to be associated only with female genital cancer. However, this infection also causes penile and anal cancer in men so there is a need to better educate the population about the risks of HPV, especially the younger generation whose sexual behaviour is changing and therefore the virus in no longer only affecting genital tissue. The thesis deals with the description and epidemiology of these types of tumours and also with the social determinants that influence HPV infection. Knowledge of the risks of HPV is a...
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Surface phenotype of human carcinoma cancer stem cells (CSC)
Bočková, Marie ; Drbal, Karel (advisor) ; Čermák, Vladimír (referee)
Tumor is composed of a heterogenous mass of cells. Similar to normal healthy organs and tissues, these can be divided into individual cellular subpopulations according to morphology, function and expression patterns. A subpopulation of cells that are able to give rise to all of these cellular lineages is referred to as cancer stem cells (CSC). CSCs have the capabilities of normal stem cells such as the self-renewal and the ability to give rise to a heterogenous population of differentiated cells. Usually, this is the most resistant subpopulation within a tumor, highly non-responsive to therapy. Doing so, they are the cause of residual disease. Characterisation of CSC markers of individual tumor types is beneficial since it enables higher therapy efficacy via targeting this cell population. The -omics approaches to characterisation of the surface proteome bring a broader view into the field when searching for a unique gene signature of specific cancer stem cell types. It has been found that these cells can be identified based on the high expression levels of CD44, CD90 and CD49f. Among other markers, CD47 is an important marker for its immunosuppressive function.
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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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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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