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Comparing the effectiveness of selected methods of cancer treatment. Prostate cancer, breast cancer and lung cancer via survival analysis
Šimonková, Karolína ; Šimpach, Ondřej (advisor) ; Pechholdová, Markéta (referee)
This diploma thesis deals with various ways of treatment of selected oncological diseases and the effectiveness of treatment methods and evaluation of the influence of various factors influencing the survival of patients. The activity of individual healing processes is evaluated by survival analysis. The subjects of the study are patients with breast, lung and prostate cancer. The survival analysis considers the sex of the patient, the age and stage of his illness, and other factors to avoid distorted results. The aim of the work is to find out the effects of selected therapeutic procedures on patients' health and to identify factors that have a significant impact on the survival of patients. The data for the diploma thesis was provided by the Institute of Health Information and Statistics of the Czech Republic, the Statistical Office, the National Cancer Register (NOR), the US SEER database and the German Breast Cancer Study.
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Radiation-induced plasticity of prostate cancer cells
Kyjacová, Lenka ; Hodný, Zdeněk (advisor) ; Bouchal, Jan (referee) ; Vomastek, Tomáš (referee)
Resistance of various cancers to conventional therapies including radio- and chemo- therapy is one of the most investigated phenomena in the molecular and clinical oncology. Recurrent disease is characterized by the presence of metastases, which are responsible for 90% of cancer-related mortality. Fractionated ionizing radiation (fIR) combined with surgery or hormone therapy represent the first-choice treatment for medium to high risk localized prostate carcinoma (PCa). In PCa, the failure of radiotherapy (RT) is often caused by radioresistance and further dissemination of escaping (surviving) cells. To investigate the radioresistance-associated phenotype, we exposed four metastasis- derived human PCa cell lines (DU145, PC-3, LNCaP, and 22RV1) to clinically relevant daily fractions of ionizing radiation (fIR; 35 doses of 2 Gy) resulting in generation of two surviving populations: adherent senescent-like cells expressing common senescence-associated markers and non-adherent anoikis-resistant stem cell-like cells with active Notch signaling and expression of stem cell markers CD133, Oct-4, Sox2, and Nanog. While the radioresistant adherent cells were capable to resume proliferation shortly after the end of irradiation, the non- adherent cells started to proliferate only after their reattachment...
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Splice variants of the gene coding for GCPII and their role in cancer development
Jindrová, Helena ; Konvalinka, Jan (advisor) ; Liberda, Jiří (referee)
Alternative splicing is a mechanism of generating distinct proteins that are encoded by the same gene. These proteins differ in amino acid sequence, overall structure and function. Splicing dysregulations have been shown to be implicated in several pathologic processes including cancer. For example, non-physiological splicing of osteopontin was proved to play a key role in cell progression of breast cancer. Glutamate carboxypeptidase II (also called prostate specific membrane antigen, PSMA) is present in both normal prostate and prostate cancer. Several splice variants of PSMA have been described and it has been suggested that the overexpression of some of them could be involved in the progression of prostate cancer. Nevertheless, more detailed investigation of each of the PSMA splice variant in terms of their occurrence in prostate cancer cells remains to be performed. This thesis focuses on the exploration of the expression of PSMA splice variants with deleted exons 6 and 18 in samples of a cell line derived from human prostate cancer, benign prostate hyperplasia and prostate cancer. For this purpose, RT-PCR was utilized to determine the ratio of deletions of exons 6 and 18 in cDNA of the prostate specific membrane antigen. Furthermore, the ratio of deletions of exon 6 and 18 was determined in...
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Odpověď metastatických buněčných linií karcinomu prostaty na genotoxický stres
Imrichová, Terezie ; Hodný, Zdeněk (advisor) ; Rösel, Daniel (referee)
Prostate cancer is the fourth most frequent cause of cancer-related deaths in men worldwide. One of current successful approaches to treat prostate cancer is radical prostatectomy followed by radiotherapy. However, this treatment is not 100% successful, as 53% patients develop secondary tumors. Our hypothesis is, that ionizing radiation itself contributes to the development of metastases by inducing changes in cell phenotype, particularly in terms of epithelial-to-mesenchymal transition and stemness. To test this hypothesis, we irradiated the cells of metastatic prostate cancer cell line DU145 by fractionated radiation 2 x 10 Gy and we compared the expression of selected epithelial, mesenchymal and stem-cell markers prior to and after irradiation. Besides we focused on a subpopulation of so called floating cells which arise during irradiation. These cells can survive the radiation treatment and after some time they are able to reattach and give rise to readherent population. We wanted to asses what is the cell cycle profile of these cells and whether and how fast they proliferate. In this thesis we have shown that radiation causes only minor changes in epithelial/mesenchymal and stem-like character of adherent fraction of the DU145 cell line. However, we have also described that small population of...
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Preparation of affinity resin for the identification and preparation of glutamate carboxypeptidase II in biological material
Parolek, Jan ; Konvalinka, Jan (advisor) ; Bořek Dohalská, Lucie (referee)
For treatment of benign and malignant tumors it is desirable to find more specific and less burdening ways of therapy. The main objective of improving the treatment of inoperable tumors is as low as possible damage to healthy tissues during tumor tissue elimination. Using antibodies in research and therapy brought significant progress; antibodies are able not to only mark cells expressing certain molecules, but even to eliminate them. However, tumor cells are very similar to healthy cells and this similarity is one of the major problems in treatment of cancer; most of the substances toxic to tumor have also some adverse effect on the whole organism. For this reason, it is necessary to search new tumor-specific markers for treatment of tumor-based diseases. Monoclonal antibodies can be linked with a drug molecule (cytotoxic substance, radionuclide, etc.) and getting antibody- drug conjugate. These conjugates are very promising medicaments for carcinoma treatment because monoclonal antibody can find specific target and drug substance can be delivered locally with minimal harm to patient's organism. Glutamate carboxypeptidase II (GCPII) became one of the specific markers for the prostate cancer. GCPII is an integral membrane protein, which is highly expressed by epithelial cells of the prostate...
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Monitoring of immune parameters during anti-tumor immunotherapy
Bílková, Pavla ; Palich Fučíková, Jitka (advisor) ; Fialová, Anna (referee)
Dendritic cells are the most effective antigen presenting cells in humans, they stimulate naive T lymphocytes and thus initiate specific immune response. The discovery of dendritic cells and understanding of their functions contributed to the idea of usingdendritic cells for the treatment of cancer. Anti tumor immunotherapy is a therapeutic strategy that aims to induce and maintain immune responses against tumor cells. Currently, immunotherapy based on dendritic cells has strong position among other anti cancer therapies and seems to be a promising therapeutic option for patients with tumors. In this work, I evaluated the effectiveness of treatment in patients with prostate cancer treated with immunotherapy based on dendritic cells. I focused on the detection of antigen specific T lymphocytes in peripheral blood against tumor antigens, PSA, NY ESO 1, MAGE A1 and MAGE A3. Using a 3 day standard protocol for the detection of antigen specific T cells using intracellular cytokine staining we were able to detect only a small percentage of this minor population. Only after extension of the protocol, we increased the sensitivity setting and we detected a significantly increased frequency of antigen specific T lymphocytes in the peripheral blood after one year DC vaccines application.
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Characterisation of the cell line TRAMP-C2 side population, mouse model of prostate cancer
Žlabová, Anna ; Reiniš, Milan (advisor) ; Šmahel, Michal (referee)
Side population is a minor subpopulation (SP) of some cell lines, exporting staining dye Hoechst 33342 out of their cytoplasm. It is discussed as a possible source of "cancer stem cells", "tumour initiating cells" or "metastasis initiating cells". However, broad literature suggest, that stemness and other privileged properties of SP are very variable between different cell types, cell lines and stage of disease. Cell lines TRAMP are the only widely available murine models for testing of prostate cancer therapy. We noticed in literature a mention about existence of 1-2% of cells constituting side population, but detailed characteristic have not been described until now. In this diploma thesis, we worked on characterisation of SP of the TRAMP-C2 cell line in comparison to other cells (nonSP). In the first part, we compared stem properties of SP and nonSP. We started with checking the existence of SP by its verapamil sensitivity. Using mRNA analysis, we showed that neither SP nor nonSP have increased c-Kit expression and that there are no differences in Bmi-1 expression. We found that SP is heterogenic mixture of CD24-CD44-, CD24-CD44+ and CD24+CD44+ cells, while nonSP is almost solely CD24-CD44+. We documented that SP and nonSP returned back to original SP ratio during cultivation. Then we showed on...
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Comparison of doses in the target volume and critical organs for Intensity Modulated Radiation Therapy (IMRT) and proton therapy
STIEBLINGOVÁ, Tereza
The topic of this thesis is a view at the two selected modern irradiation techniques - IMRT (Intensity-Modulated Radiation Therapy) and proton therapy. I compared them at a general level in the theoretical part, and in the practical part I focused on the absorbed doses in selected critical organs in patients with prostate cancer. In the theoretical part I worked with specialized literature and articles from medical journals and also with a number of internet sources. For example I worked with a publication titled Radiační onkologie by Pavel Šlampa or Klinická onkológia a rádioterapia by Ľudovit Jurga. I made a concept based on the obtained information, which is composed of generally related topics, e.g. the position of radiotherapy in the treatment of oncological diseases, characteristics of ionizing radiation, the process of radiation treatment planning etc. After these introductory chapters I focused specifically on photon IMRT technique and proton therapy which are among the most modern methods of contemporary radiation oncology. In the theoretical part I set the description of these selected techniques as a goal, with an emphasis on their advantages and disadvantages. In the practical part I analyzed these two techniques in terms of received minimum, medium and maximum doses in selected critical organs rectum, bladder and both femoral heads using different fractionation schemes. The results were compared with information from the theoretical part. In the practical part, the testing of this hypothesis was set as my goal: During the treatment of prostate cancer with accelerated protons the healthy surrounding tissue and critical organs will receive smaller amount of radiation dose than IMRT technique. Proton Therapy Center (PTC) in Prague provided me with some irradiation plans including CT scans from 20 anonymous patients diagnosed with prostate cancer and treated with protons. Then I worked with these plans in planning program to create a photon IMRT plan for each proton plan and in order to be able compare these two techniques in each patient in different fractionation schemes. When I compared IMRT technique and proton therapy, both in norm-fractionated scheme, moderate doses were lower with protons in all 20 patients in all selected critical organs. The average difference in moderate doses of these techniques in all selected critical organs is 11,022 Gy. Specifically, from the results is further evident, that the bladder and the rectum absorb less minimal and medium dose if proton therapy has been used in any fractional mode (short, long, norm-fractionated scheme) than in the photon IMRT therapy. These results were obtained in all 20 patients. When I compared IMRT technique and proton therapy, both in short scheme or long scheme, in terms of the maximum doses in the bladder and rectum, the values were comparable in the both critical organs. In none of the literature used as a source is a mention of minimal and medium doses on heads of both femurs. But if I compare the median doses proton's therapy with doses IMRT's photon therapy, both in norm-fractionated scheme, the medium doses were lower if proton therapy had been used. The results of minimal doses are contradictory and conclusions are not so unequivocal. The values of the maximum doses of the right and left femoral head were lower in overwhelming majority of 20 patients in proton therapy (in the short and also in long scheme). The average difference in the left head of femur is 3,434 Gy (proton's short scheme vs. photon's short scheme), respectively 6,654 Gy (proton's long scheme vs. photon's long scheme). The average difference in the right head of femur is 5,422 Gy (proton's short scheme vs. photon's short scheme), respectively 9,273 Gy (proton's long scheme vs. photon's long scheme).
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On-chip and capillary electrophoresis for cancer research
Hájková, Tereza ; Babula, Petr (referee) ; Provazník, Ivo (advisor)
The thesis deals with cancer disease and its genesis. The prostate cancer is the second most dangerous disease in male population. It is very important to detect it in early stage. This thesis deals with the proteins which are or could be used as potential cancer markers. For example in current commonly used the prostate-specific antigen and newly the metallothionein. Metallothionein is a protein occuring in fauna and flora in four basic isoforms. There is a hypothesis that the isoform content or/and their ratio may have a diagnostic implication and could be used in clinical practise. For this reason they are studied and developed methods for specific and sensitive analysis of individual isoforms. In this work, capillary electrophoresis is used for the separation of the isoforms. The influence of the parameters such as type of background electrolyte, its pH and separation voltage etc. on the final separation are discussed.
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