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Role of Telomeres / DNA Repair in Solid Tumors
Tomášová, Kristýna ; Vodička, Pavel (advisor) ; Dušinská, Mária (referee) ; Campa, Daniele (referee)
Loss of telomere function and unrepaired DNA damage contribute to chromosome integrity disruption and genomic instability development, which can initiate malignant transformation of the cells. This dissertation focused on telomeres and their maintenance and regulation mechanisms in sporadic colorectal, breast, and ovarian tumors. In colorectal cancer (CRC), a place was also dedicated to research on base excision repair glycosylases. The findings of the Thesis are elaborated in detail in seven attached Manuscripts. The main results of each of the articles are as follows: I) Mitochondrial DNA copy number changes and telomere length (TL) shortening already occur in precancerous lesions of CRC, but in early carcinomas, the association between their mitochondrial DNA content and TL diminishes; II) TL of leukocytes in peripheral blood of patients with CRC can be affected by postoperative cytostatic treatment based on 5-fluorouracil; III) CRC liver metastases maintain the same TL as primary tumors. In addition, neoadjuvant treatment with (chemo)radiotherapy applied to patients with rectal cancer probably causes telomere shortening in the primary tumor and the surrounding rectal cells in addition to DNA damage; IV) TL of ovarian cancer cells can be influenced by epigenetic regulations and expressions of...
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Evalution of DNA Damage and Repair in patients with Non-small Cell Lung Cancer Due to Drug Therapy with Platinum Derivatives
Fikrová, Petra ; Hronek, Miloslav (advisor) ; Herink, Josef (referee) ; Dušinská, Mária (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Candidate: Mgr. Petra Fikrová Supervisor: Doc. PharmDr. Miloslav Hronek, Ph.D. Consultant: Prof. RNDr. Rudolf Štětina, CSc. Title of doctoral thesis: Evaluation of DNA damage and repair in patients with non-small cell lung cancer due to drug therapy with platinum derivatives Lung cancer is the most common worldwide cause of cancer-related death. This type of cancer is divided into two subtypes, the small cell and non-small cell lung cancer. Platinum- based chemotherapy is the mainstay of treatment of advanced stages non-small cell lung cancer, to that is this work focused on. The aim of this study was to investigate whether it is possible to use the comet assay method for monitoring the progress of treatment in these patients, and if it is possible to predict a patient's response to treatment or patient's survival. Standard version or modifications of comet assay were used for the measurement of DNA damage or oxidative DNA damage and we also validated a modification of comet assay for measuring DNA crosslinks. This evaluation was carried out either in vitro in HeLa cells and in peripheral blood lymphocytes from healthy donors from Transfusion department of University Hospital in Hradec...
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Evalution of DNA Damage and Repair in patients with Non-small Cell Lung Cancer Due to Drug Therapy with Platinum Derivatives
Fikrová, Petra ; Hronek, Miloslav (advisor) ; Herink, Josef (referee) ; Dušinská, Mária (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Biological and Medical Sciences Candidate: Mgr. Petra Fikrová Supervisor: Doc. PharmDr. Miloslav Hronek, Ph.D. Consultant: Prof. RNDr. Rudolf Štětina, CSc. Title of doctoral thesis: Evaluation of DNA damage and repair in patients with non-small cell lung cancer due to drug therapy with platinum derivatives Lung cancer is the most common worldwide cause of cancer-related death. This type of cancer is divided into two subtypes, the small cell and non-small cell lung cancer. Platinum- based chemotherapy is the mainstay of treatment of advanced stages non-small cell lung cancer, to that is this work focused on. The aim of this study was to investigate whether it is possible to use the comet assay method for monitoring the progress of treatment in these patients, and if it is possible to predict a patient's response to treatment or patient's survival. Standard version or modifications of comet assay were used for the measurement of DNA damage or oxidative DNA damage and we also validated a modification of comet assay for measuring DNA crosslinks. This evaluation was carried out either in vitro in HeLa cells and in peripheral blood lymphocytes from healthy donors from Transfusion department of University Hospital in Hradec...
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