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The effect of aspartate β-hydroxylase inhibition on immune reactions
Krausová, Kateřina ; Šmahel, Michal (advisor) ; Filipp, Dominik (referee)
Aspartate β-hydroxylase (ASPH) is an enzyme that contributes to tumor progression by enhancing the proliferation, migration and invasiveness of cancer cells. Its expression is mostly negligible in normal cells, whereas it is often overexpressed in cancer cells. An inhibitory effect of ASPH on immune cells, specifically on natural killer cells, has also been demonstrated. Thus, the ASPH enzyme could be a new target for cancer immunotherapy. The aim of this thesis was to show the effect of ASPH inhibition on the immune response. Firstly, it was found that ASPH inhibition contributes to the anti-tumor effect of DNA vaccination. The reduction of tumors induced by ASPH inhibition in combination with DNA vaccination was shown to be mainly caused by CD8+ T lymphocytes. Subsequently, the specific activation of T lymphocytes was confirmed by the ELISPOT assay. In case of non-specific activation of T lymphocytes, ASPH inhibition had no effect on the direct activation of CD8+ T lymphocytes. Finally, it was found that plasmacytoid dendritic cells did not contribute to CD8+ T lymphocyte activation after ASPH inhibition. Thus, the results demonstrate that inhibition of ASPH contributes to the activation of adaptive immunity induced by DNA vaccination, but the mechanism of this activation remains unknown.
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Role of Zinc-α2-glycoprotein in tumors
Kotvalová, Hanka ; Šmahel, Michal (advisor) ; Kubů, Martin (referee)
The Zinc-α2-glycoprotein (ZAG) encoded by the AZGP1 gene particularly contributes to the regulation of lipid and glucose metabolism. In different types of tumors, its altered production was found and the association of the ZAG level with the patient's prognosis was suggested. However, the role of ZAG in tumor progression can differ in individual malignancy types and mechanisms of ZAG function are not sufficiently identified. The objectives of the bachelor's thesis are a description of the structure of the ZAG protein and the regulation of AZGP1 expression, a summary of the identified ZAG functions in nonmalignant diseases, and a focus on the role of ZAG in tumors, particularly on the mechanisms of its action and its potential use as a biomarker.
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Options of treatment for childhood cancer
GREGOROVÁ, Tereza
This bachelor thesis focuses on oncological diseases in children and adolescents. It deals with differences between pediatric patients and adults, what are the causes of their malignant diseases, prevention, symptoms and treatment. In the practical part I focused on radiation therapy in children, using photon beam and proton beam, their advantages and disadvantages. I dealt with the incidence of the most common malignancies in children aged 0-19 years in the period 1996-2016. I analyzed the data from the National Cancer Registry and processed it into graphs and tables. I also looked at the data on the long-term survival of cured patients. The collected data show rather a decreasing tendency in the incidence of childhood malignancies in the monitored period 1996-2016. Tumor mortality in children has been decreasing in the period under review, after an initial sharp decline in recent years rather slightly. The higher incidence of malignancies in children aged 0-19 is in boys. I also graphically processed the age distribution of patients, where the first wave of increased incidence is recorded in the youngest patients under 4 years and the second wave in adolescents aged 15-19 years, which is different from the distribution of tumor incidence in the adult population where the risk of cancer increases with age. The relative percentage of five-year survival in pediatric cancer patients over time has increased with the development of cancer treatment and supportive care and dispenzarzation. The content of this work can serve as a basic overview of cancer of children and adolescents for health professionals and the general public.
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Insulin like and other growth factors and tumors
Kučera, Radek ; Topolčan, Ondřej (advisor) ; Klimeš, Jiří (referee) ; Šafarčík, Kristian (referee)
Inzulinu podobné a jiné růstové faktory a nádory Insulin like and other growth factors and tumors Disertační práce Plzeň 2011 Mgr. Radek Kučera Summary The interaction between growth factors and cancer incidence and development has been discussed recently. First works suggesting possible connection between increased production of insulin like growth factors with an increased incidence of tumors came already from early 80s of the last century. The aim of my work was focused on evaluation of possible relation between insulin like growth factors or their binding proteins and tumors from different perspectives, to assess their significance and try to determine what role the IGFs and IGFBPs may play in the current tumor diagnostics. The work itself is divided into two parts, the theoretical and practical ones. In the theoretical part, I summarized the action of IGF in human body and also focused on previous findings on the role of IGF system in cancer diagnoses. In the practical part, divided into three subsections, I focused on investigation of relations in a large set of patients with different cancer diagnoses, in a group of women with breast cancer and, finally, I focused on changes of IGF1 levels during follow-up. Theoretical part Insulin-like growth factors (IGF) are peptides, that participate on growth...
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Correlation of Immunohistochemistry and Molecular Biologic Methods in The Diagnosis of Tumors
Michal, Michael ; Skálová, Alena (advisor) ; Rychlý, Boris (referee) ; Zambo, Iva (referee)
This thesis is a collection of commentaries on altogether 13 first-authored and 20 co- authored publications where morphology, immunohistochemistry (IHC) and molecular genetic methods were used to provide novel clues for arriving at an accurate diagnosis of tumors, as well as to propose novel approaches and refinement of classification of certain tumors. The presented manuscripts are the result of the postgraduate studies of MUDr. Michael Michal at the Charles University in Prague, Faculty of Medicine in Pilsen in the period between 2015-2018. The author focused the main part of his research, particularly his first-authored manuscripts, on soft tissue tumors but also largely participated in research activities focusing on other body systems. Over the course of his studies, four main areas of interests within the topic of soft tissue pathology emerged. The first is oriented on soft tissue tumors of presumed (but unconfirmed) fibroblastic lineage. First two publications regard two related low-grade sarcomas called Myxoinflammatory fibroblastic sarcoma (MIFS) and Pleomorphic hyalinizing angiectatic tumor (PHAT). In the first manuscript, a high-grade variant of the former is described. The latter publication is focused on the morphological and IHC similarities between both MIFS and PHAT. The third and...
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Insulin like and other growth factors and tumors
Kučera, Radek ; Topolčan, Ondřej (advisor) ; Klimeš, Jiří (referee) ; Šafarčík, Kristián (referee)
Inzulinu podobné a jiné růstové faktory a nádory Insulin like and other growth factors and tumors Disertační práce Plzeň 2011 Mgr. Radek Kučera Summary The interaction between growth factors and cancer incidence and development has been discussed recently. First works suggesting possible connection between increased production of insulin like growth factors with an increased incidence of tumors came already from early 80s of the last century. The aim of my work was focused on evaluation of possible relation between insulin like growth factors or their binding proteins and tumors from different perspectives, to assess their significance and try to determine what role the IGFs and IGFBPs may play in the current tumor diagnostics. The work itself is divided into two parts, the theoretical and practical ones. In the theoretical part, I summarized the action of IGF in human body and also focused on previous findings on the role of IGF system in cancer diagnoses. In the practical part, divided into three subsections, I focused on investigation of relations in a large set of patients with different cancer diagnoses, in a group of women with breast cancer and, finally, I focused on changes of IGF1 levels during follow-up. Theoretical part Insulin-like growth factors (IGF) are peptides, that participate on growth...
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Modification of murine tumor cell lines with CRISPR/Cas9 system and their characterization
Lhotáková, Karolína ; Poláková, Ingrid (advisor) ; Brábek, Jan (referee)
MHCI molecules are constitutively expressed in all nucleated cells and play a key role in antigen presentation to CD8+ T lymphocytes. One of the tumor immune evasion strategies is MHCI expression downregulation. This leads to an impaired recognition of tumor antigens by CD8+ T lymphocytes that are unable to start the immune response. Since the MHCI expression downregulation occurs in up to 90 % of some tumors it is neccesary to have a clinical relevant tumor model without a MHCI surface expression that would be used for testing of immunotherapeutic approaches. This thesis describes a production of new model cell lines of TC-1 tumor cells with irreversibly downregulated MHCI. That was achieved by an inactivation of B2m, which is a part of MHCI, by gene editing using CRISR/Cas9. The B2m inactivation was confirmed by flow cytometry, western blot and sanger sequencing of single alleles. The inactivation slowed down the cell growth for both in vitro and in vivo. The cell metastatic activity was not affected. The tumors established by cells without the B2m expression are not sensitive to DNA vaccine against HPV16 E7 oncoprotein by a pBSC/PADRE.E7GGG vaccine. The main effector function against these tumors possess the NK1.1+ cells. In a therapeutic vaccination experiment it was repeatedly achieved of...
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Correlation of Immunohistochemistry and Molecular Biologic Methods in The Diagnosis of Tumors
Michal, Michael ; Skálová, Alena (advisor) ; Rychlý, Boris (referee) ; Zambo, Iva (referee)
This thesis is a collection of commentaries on altogether 13 first-authored and 20 co- authored publications where morphology, immunohistochemistry (IHC) and molecular genetic methods were used to provide novel clues for arriving at an accurate diagnosis of tumors, as well as to propose novel approaches and refinement of classification of certain tumors. The presented manuscripts are the result of the postgraduate studies of MUDr. Michael Michal at the Charles University in Prague, Faculty of Medicine in Pilsen in the period between 2015-2018. The author focused the main part of his research, particularly his first-authored manuscripts, on soft tissue tumors but also largely participated in research activities focusing on other body systems. Over the course of his studies, four main areas of interests within the topic of soft tissue pathology emerged. The first is oriented on soft tissue tumors of presumed (but unconfirmed) fibroblastic lineage. First two publications regard two related low-grade sarcomas called Myxoinflammatory fibroblastic sarcoma (MIFS) and Pleomorphic hyalinizing angiectatic tumor (PHAT). In the first manuscript, a high-grade variant of the former is described. The latter publication is focused on the morphological and IHC similarities between both MIFS and PHAT. The third and...
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The specifics of children´s radiotherapy
KŘIŠTOVÁ, Pavla
This bachelor thesis focuses on a medical treatment of small children who are cured of cancer and how to cure by the radiotherapy. It also deals with differences between small kids and adults how to cure them properly and what are the causes of their illnesses. I wanted to show the differences among children's tumors and their treatments by radiotherapy. I have been to the radiotherapy center at Motol Hospital and I described some concrete cases of small children and I wanted to emphasize how important is to be individually as much as possible in every piece of this job. There are also graphical projections of the illness according to child's age and child's diagnosis. And there are also researching questions: Are there more children who are ill and need radiotherapy in the Czech Republic? The answer is done by graphical projection and it deals in period of 18 years since 1993 to 2013. . In the final part of my bachelor thesis you can find the results of the children medical treatment and also information from the written sources. It is interesting that the diagnosis of a concrete small child is different from a diagnosis from his or her adulthood. It is clear that a small child´s tumor is more often caused by a genetically bottom not by a bad lifestyle which is typical of an adult´s tumors. My bachelor thesis contains a basic overview of child´s tumors and it is meant especially for students of some medical branches.
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