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Significance of mitochondrial DNA in colorectal cancer
Danešová, Natálie ; Vodenková, Soňa (advisor) ; Polívková, Zdeňka (referee)
Colorectal cancer is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer death. It is a heterogeneous and multifactorial disease, the development of which takes up to 15 years. In addition to genetic risk factors, external, influenceable factors also contribute to the development of the disease. Patients are often diagnosed in the late stages of the disease, which significantly reduces the chances of their successful treatment. It is therefore necessary to identify appropriate screening, diagnostic, prognostic and predictive biomarkers of the disease. Mitochondria are organelles found in almost all eukaryotic cells and their dysfunction is often involved in the development of cancer. Because mitochondria have their own DNA its changes could serve as a potential biomarker for a closer understanding of the pathogenesis and progression of colorectal cancer. The main goal of this bachelor thesis was to summarize previous studies focused on mitochondrial DNA changes in patients with colorectal cancer and their possible use in clinical practise. Keywords: Colorectal cancer; biomarkers; mitochondria; mtDNA
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Acquired chromosomal aberrationns in peripheral blood lymphocytes of patients with newly diagnosed cancer and healthy control individuals.
Vodenková, Soňa ; Polívková, Zdeňka (advisor) ; Langová, Martina (referee)
The majority of human cancers arise due to cells inabitily to maintain genomic stability. Cytogenetic changes (especially chromosomal aberrations) in peripheral blood lymphocytes which reflect not only the individual exposure to genotoxic factors, but also individual sensitivity to genotoxic effect and the tumor is late consequence to genotoxic effect. Summary epidemiological prospective studies over the last ten years have shown that increased level of chromosomal aberrations in peripheral blood lymphocytes is predictive of cancer risk. This thesis is focused on the detection of particular types of chromosomal damage in patients with choosed types of newly diagnosed cancers compared to healthy control persons. We cytogenetically analyzed 100 patients with colorectal cancer and 298 controls and 123 patients with breast cancer and 123 controls - healthy women. We compared the percentage of aberrant cells, the percentage of total aberrations, the percentages of chromatid and chromosome aberrations found in patients with both types of tumors and in controls and we verified the predictive value of chromosomal aberrations as a biomarker of cancer risk. In patients with colorectal cancer was statistically significantly increased only the level of chromatid aberrations (CHTA) (1,45±1,28) compared to...
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Molecular biomarkers related to DNA damage and repair: their role in carcinogenesis, patients' treatment and monitoring
Vodenková, Soňa
Genome instability represents one of the leading forces driving the onset and development of cancer. It arises as a consequence of the combined effect of DNA damage and errors made by the DNA repair system. In many cancers, DNA damage tolerance and DNA repair pathways are disrupted or deregulated, thereby promoting cancer progression. DNA repair also appears to play a substantial role in cancer therapy response. This Dissertation Thesis was performed in response to several unclear and unresolved issues of the role of DNA damage and DNA repair in cancer pathogenesis. The aim of the Thesis was to search for potential novel biomarkers and confirmation of the validity of already existing biomarkers related to DNA damage and DNA repair, which may be associated with cancer susceptibility and patient's clinical outcome. We also explored the biological basis of different biomarkers and their associations. The major outcomes of this Thesis are: 1) The elevated chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) may serve as a biomarker of cancer susceptibility and partially affects patients' clinical outcome. While telomere shortening contributes to the formation of CAs in PBLs only in healthy individuals, less efficient DNA double- strand break repair in PBLs is associated with telomere...
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Molecular biomarkers related to DNA damage and repair: their role in carcinogenesis, patients' treatment and monitoring
Vodenková, Soňa ; Vodička, Pavel (advisor) ; Anděra, Ladislav (referee) ; Černá, Marie (referee)
Genome instability represents one of the leading forces driving the onset and development of cancer. It arises as a consequence of the combined effect of DNA damage and errors made by the DNA repair system. In many cancers, DNA damage tolerance and DNA repair pathways are disrupted or deregulated, thereby promoting cancer progression. DNA repair also appears to play a substantial role in cancer therapy response. This Dissertation Thesis was performed in response to several unclear and unresolved issues of the role of DNA damage and DNA repair in cancer pathogenesis. The aim of the Thesis was to search for potential novel biomarkers and confirmation of the validity of already existing biomarkers related to DNA damage and DNA repair, which may be associated with cancer susceptibility and patient's clinical outcome. We also explored the biological basis of different biomarkers and their associations. The major outcomes of this Thesis are: 1) The elevated chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) may serve as a biomarker of cancer susceptibility and partially affects patients' clinical outcome. While telomere shortening contributes to the formation of CAs in PBLs only in healthy individuals, less efficient DNA double- strand break repair in PBLs is associated with telomere...
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Effects of natural substances on DNA damage and repair capacity in colorectal cell lines
Vodenková, Soňa ; Opattová, Alena ; Čumová, Andrea ; Slíva, D. ; Vodička, Pavel
Colorectal carcinoma)CRC) represents serious ilness with high incidence and mortality worldwide. Generaly, there is a lack of reliable predictive and prognostic biomarkers, implicated late diagnosis. The effectivity of treatment is rather low - about 50%. Main agent used in CRC treatment is 5 fluorouracil (5-FU), alone or in combination with other cytostatics. 5-FU is halogenated pyrimidine, which is or directly incorporated into DNA or disrupts thymidine synthesis in tumour cells. This damage is repaired by base excision repair (BBR) or mismatch repair. The aim of this study is to investigate the effect of 5FU together with extracts of Ganoderma lucidum (GL) and the role of BER in various lines of colorectal cancer cell lines. Results show increased oxidative damage after GL and 5FU+GL treatment and in the same time decrease of DNA repair in colorectal cell lines. This fact could contribute to improve of 5FU efficacy.
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Natural compounds and their effect on 5-fluorouracil in colorectal cancer cell lines
Čumová, Andrea ; Opattová, Alena ; Vodenková, Soňa ; Horák, Josef ; Slíva, D. ; Vodička, Pavel
Colorectal cancer (CRC) is the second most common type of cancer and the second most common cause of cancer related deaths in Europe. 5-Fluorouracil (5-FU) is widely used in treatment of various cancers including CRC, but apart from the cytotoxic effect on cancer cells may also cause adverse toxic side effects. 5-FU is an anti-metabolite with chemical structure similar to that of the pyrimidine molecules of DNA and RNA. However, response to chemotherapy is often limited by drug resistance. The p53 protein is one of the most widely studied tumour suppressors and mutations in TP53 gene are frequently detected in different types of tumours. \nGanoderma Lucidum (GLC) is a mushroom used in Traditional Eastern Medicine which exhibits anti-cancer and anti-proliferative effects in vitro\nThe aim of our study is to define the role of p53 in the interaction between 5-FU and GLC extract and their simultaneous effect on survival in CRC cell lines.\nOur results suggest that GLC extract significantly increases cytotoxicity and genotoxicity of 5-FU in CRC lines with different p53 status and may potentially modulate the response of p53 knock-out cells which are less sensitive to 5-FU treatment. Interaction of conventional chemotherapeutics with natural compounds introduces a novel aspect in cancer research and therapy.\n\n
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Acquired chromosomal aberrationns in peripheral blood lymphocytes of patients with newly diagnosed cancer and healthy control individuals.
Vodenková, Soňa ; Polívková, Zdeňka (advisor) ; Langová, Martina (referee)
The majority of human cancers arise due to cells inabitily to maintain genomic stability. Cytogenetic changes (especially chromosomal aberrations) in peripheral blood lymphocytes which reflect not only the individual exposure to genotoxic factors, but also individual sensitivity to genotoxic effect and the tumor is late consequence to genotoxic effect. Summary epidemiological prospective studies over the last ten years have shown that increased level of chromosomal aberrations in peripheral blood lymphocytes is predictive of cancer risk. This thesis is focused on the detection of particular types of chromosomal damage in patients with choosed types of newly diagnosed cancers compared to healthy control persons. We cytogenetically analyzed 100 patients with colorectal cancer and 298 controls and 123 patients with breast cancer and 123 controls - healthy women. We compared the percentage of aberrant cells, the percentage of total aberrations, the percentages of chromatid and chromosome aberrations found in patients with both types of tumors and in controls and we verified the predictive value of chromosomal aberrations as a biomarker of cancer risk. In patients with colorectal cancer was statistically significantly increased only the level of chromatid aberrations (CHTA) (1,45±1,28) compared to...
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