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Changes in mitochondrial DNA in colorectal cancer patients
Danešová, Natálie ; Vodenková, Soňa (advisor) ; Büchler, Tomáš (referee)
Mitochondrial DNA (mtDNA) changes occur more frequently in the cell than alterations in nuclear DNA (nDNA) due to factors such as proximity to reactive oxygen species (ROS) or fewer DNA repair pathways. While nDNA damage is known to play a role in colorectal cancer (CRC), there is a lack of studies concerning mtDNA damage. Changes in mtDNA copy number, a possible indirect marker of mtDNA damage known as mtDNA content, have been reported in CRC with conflicting results. Various changes in mtDNA have been observed in multiple cancer types and proposed as potential biomarkers, including CRC; however, its exact role in disease progression, patients' prognosis, or prediction of treatment is yet to be determined. The primary hypothesis of this study was that mitochondrial dysfunctions resulting from mtDNA changes play a role in colorectal carcinogenesis and could serve as potential CRC biomarkers. To test this hypothesis, we measured mtDNA damage, mtDNA content, and the expression of selected DNA repair genes in both tumor and adjacent non-malignant mucosa. Initially, we conducted a Pilot study involving 7 patients, utilizing RNA sequencing and qPCR. Subsequently, a Validation study was performed on a larger cohort of 50 patients using qPCR. Our findings revealed that adjacent mucosa exhibited higher...
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A study of chemoresistance in patients with colorectal cancer treated with 5-fluorouracil
Dostál, Petr ; Vymetálková, Veronika (advisor) ; Šeborová, Karolína (referee)
The choice of treatment strategy in patients with malignant disease depends on various clinical and molecular biological factors. Although several molecular predictive biomarkers have already been proposed, only a few of them are used in clinical practice and the number is still not enough for reliable personalized medicine. Given the lack of treatment success results in many colorectal cancer (CRC) patients, there is an urgent need for personalized medicine to identify new predictive biomarkers. One of the main clinical challenges in the treatment of advanced CRC is the development of chemoresistance to systematic chemotherapy. Early detection of resistant cancer cells clones could lead to changes in treatment regimens but it requires a long-term follow up of patients and monitoring of specific markers of chemoresistance. The aim of this master's thesis has been to determine the biomarkers associated with chemoresistance to 5-FU drug, one of the most used chemotherapeutics in the treatment of CRC patients. In the first step, the whole transcriptome of maternal (sensitive) and resistant DLD-1 (line resistant to 40 µM 5-FU and line resistant to 160 µM 5-FU) cell lines using the next generation sequencing (NGS) has been analyzed. Through bioinformatic analyses, potential candidate genes (HIST1H2BE,...
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Mapping the influence of the Mediterranean (kosher diet) and traditional Czech diet on the incidence of colorectal cancer
Ben-Perets, Diana Ester ; Sládková, Petra (advisor) ; Svěcená, Kateřina (referee)
This diploma thesis deals with mapping the influence of the Mediterranean (kosher) diet and the traditional Czech diet on the occurrence of colorectal cancer. The aim of the study was to identify differences between the eating habits of Israelis and Czechs and to assess their potential impact on the development of this type of cancer. The methodology included an analysis of the eating habits of both groups, epidemiological data and a literature review of relevant studies. The results of the study indicate that there are differences between the eating habits of Israelis and Czechs, with the Israeli diet, although influenced by westernization, showing positive tendencies compared to the traditional Czech diet. This observed difference may play a key role in the prevention of colorectal cancer. Despite the fact that Israelis are not strictly limited to the Mediterranean diet, the study highlights its positive effect on reducing the risk of this disease. On the contrary, the negative contribution of the traditional Czech diet underlines the need to improve eating habits in the Czech population. This work contributes to the literature regarding the influence of diet on health and offers a comprehensive view of the differences between the Mediterranean and Czech diets in relation to colorectal cancer....
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Use of spectroscopic methods in colorectal cancer detection.
Miškovičová, Michaela ; Petruželka, Luboš (advisor) ; Soumarová, Renata (referee) ; Kiss, Igor (referee)
Colorectal cancer is one of the most common cancers and a global health problem. Approximately 8,000 new cases are diagnosed annually in the Czech Republic and about half of them die from this malignancy, with 20 % patients being under 60 years of age. It is still true that the greatest hope for successful treatment and management of the disease is given to patients by early diagnosis of cancer. There is still a remarkably high proportion of detection of colorectal cancer in the advanced stage, which is mainly due to the absence of reliable and sensitive clinical methods. The still unfavorable epidemiological situation is a clear challenge to further strengthen all activities aimed at active prevention and early diagnosis. Colorectal cancer is the best preventable disease of the gastrointestinal tract, it lasts for several years, when an invasive lesion gradually develops through a precursor lesion. This offers a sufficiently long diagnostic window, Therefore, attention is currently being focused to find affordable, sensitive and minimally invasive techniques that can provide early, simple, rapid, inexpensive and reliable diagnosis of this disease and could thus support or replace conventional diagnostic methods in the future. In our work, we focused on the use of completely new diagnostic...
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Sequence variants in metastatic colorectal cancer and their evolution during the disease course and treatment
Jandová, Eliška ; Boublíková, Ludmila (advisor) ; Vymetálková, Veronika (referee)
A deeper understanding of the molecular background of colorectal cancer (CRC) can help explain the development of the disease and its resistance to treatment, predict disease progression, and improve treatment prognosis. Some minimal molecular testing has been incorporated into standard clinical management to determine if a particular patient will benefit from a particular therapy, but more and more new genetic alterations are being discovered that appear to be associated with the development of resistance. Tissue biopsy of the tumor is the gold standard in terms of molecular testing, but there is an increasing demand for more non- invasive methods such as liquid biopsy. Using targeted next-generation sequencing, we analyzed sequence variants present in primary tumor, metastases, and cell-free tumor DNA - ctDNA of patients with metastatic CRC. The objectives were to analyze sequence variants of the primary tumor and identify possible pathogenic variants, to analyze differences between DNA of the primary tumor and metastases, to evaluate the use of ctDNA as a diagnostic tool, and to identify potential tumor-specific markers in ctDNA that can be used to monitor disease progression. Our results suggest the feasibility of using ctDNA for diagnostic purposes or even to monitor disease progression, but...
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Possibilities of primary prevention of colorectal cancer in terms of nutrition
Stárková, Klára ; Holcátová, Ivana (advisor) ; Kudlová, Eva (referee)
This diploma thesis is devoted to the possibilities of primary prevention of colorectal cancer from the point of view of nutrition. Although the incidence and mortality of colorectal cancer have been decreasing in the Czech Republic in recent years, it is still one of the most common cancers. It is a cancer, the occurrence of which can be influenced up to 50 % by a healthy lifestyle. The theoretical part is devoted to the latest findings in the field of influencing factors, although some have not yet been sufficiently explored. Processed meat, frequent modification of the diet by grilling, frying or baking (especially red meat and processed meat), overweight and obesity, regular alcohol consumption and smoking are identified as proven carcinogens. On the contrary, the protective factors are sufficient dietary fibre intake, sufficient physical activity and probably sufficient consumption of fish, milk and milk products, fruits and vegetables. In the practical part, two groups were examined - people aged 18-50 and patients diagnosed with colorectal cancer. Both groups were asked about eating habits, lifestyle factors and information about the possibilities of primary prevention of colorectal cancer. The assumption was that people aged 18-50 eat less risky and are better informed than patients...
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Circulating biomarkers in colorectal cancer and their application in diagnosis and prognosis
Červená, Klára ; Vymetálková, Veronika (advisor) ; Boublíková, Ludmila (referee) ; Václavíková, Radka (referee)
Despite all the advances in the field of clinical and molecular oncology, the numbers related to the incidence and mortality of colorectal cancer (CRC) remain at unacceptable levels. In recent years, liquid biopsy consisting of circulating biomarkers has come to the forefront of research, offering many advantages over conventional biopsy, such as providing timely information on tumor heterogeneity and the ease of repeated sampling. This dissertation thesis aimed to identify novel candidate circulating biomarkers from microRNAs, long non-coding RNAs, and cell-free DNA that could be used for earlier diagnosis, better prognosis, or prediction of therapy response of CRC patients and thus further advance personalized medicine. The main results of this work are: 1) Circulating microRNAs in plasma (miR-122-5p and miR- 142-5p) can distinguish patients with rectal cancer and cancer-free individuals and could predict therapy response in patients (both in primary and metastatic CRC patients). 2) Gene amplification of the long non-coding RNA MALAT1 can represent an important step in the transition of healthy mucosa to adenoma tissue. Plasma MALAT1 is overexpressed in patients with colorectal adenomas and CRC patients compared to cancer-free individuals and has the potential as a predictive biomarker for CRC...
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Circulating tumor DNA in urine and its use as a potential biomarker of colorectal cancer
Surkovová, Veronika ; Ptáčková, Renata (advisor) ; Dračínská, Helena (referee)
Colorectal cancer (CRC) is a serious disease whose incidence has been steadily increasing. There is a high chance of cure and a good quality of life, if the treatment is started in the early stages of this disease. The so-called liquid biopsy, in which biomarkers from various body fluids are obtained and analyzed, could help with early detection of the disease, monitoring of the patient's condition and appropriate determination of the diagnosis. The aim of this study is to isolate and analyse circulating tumor DNA (ctDNA) from the urine of patients with advanced CRC. In these patients the ctDNA was detected in plasma. The method used for analysis is based on the principle of PCR with the formation of heteroduplexes, followed by the separation of "wild type" and mutated DNA fragments by denaturing capillary electrophoresis. Unlike plasma samples, the presence of KRAS mutations was not confirmed in urine samples. Neither the established procedure for plasma analysis, the attempt to enrich ctDNA by so-called purification, nor other tested isolation kits using the selected detection method allowed detection of the KRAS mutation in urine via ctDNA. Although urine ctDNA testing in general appears to be a promising method for improving the treatment level of (colorectal) cancer, and although its use could...
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Development of diagnostic method in colorectal cancer
Pešková, Tereza ; Fikrová, Petra (advisor) ; Vašinová, Martina (referee)
The bachelor thesis is a review focused on colorectal cancer (CRC), its incidence, prevention, treatment, but especially on the methods of diagnosis that help to detect this disease. In the first part of the thesis, the colon is anatomically and histologically described. Next is presented the disease of the CRC, its origin, occurrence, symptoms, prevention, and finally treatment options. In the next part, the work focuses on specific methods of diagnosis. One of the most effective method for early detection of cancer is a screening program that uses the methods of examination of occult bleeding into the stool and colonoscopy. Colonoscopy itself is considered to be the gold standard for the diagnosis of CRC. Despite the development of new and more modern methods for diagnosis, colonoscopy is still one of the most widely used and most reliable methods. Furthermore, radiological methods, especially computed tomography (CT) or magnetic resonance imaging (MRI), are described. These methods have made a great move towards detecting lesions more accurately and earlier. These methods are also still often combined with colonoscopy to provide a more comprehensive and detailed picture for diagnosis. These new methods, such as virtual colonoscopy, positron emission tomography combined with CT (PET/CT), or...
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The role of circulating microRNAs in the therapy response prediction in colorectal cancer patients.
Landecká, Aneta ; Vymetálková, Veronika (advisor) ; Hlaváč, Viktor (referee)
Colorectal cancer (CRC) is one of the most common cancers both in the world and in the Czech Republic. Predispositions for the development of CRC include genetic and epigenetic changes, as well as environmental and microenvironmental factors. These tumours often respond very well to treatment, especially in the early stages, but some patients experience early recurrence of the disease. As the incidence of CRC has not declined in recent years, this is a current problem requiring a new approach aimed at improving diagnosis, survival and quality of life of patients with CRC. For this reason, liquid biopsy, which is a minimally invasive approach to the patient and allows real-time monitoring of changes in the body, is increasingly gaining prominence. One of the biomarkers that can be detected by liquid biopsy are small non-coding RNA molecules - microRNAs (miRNAs). In this thesis, the gene expression of two miRNAs, namely miR-122-5p and miR-142-5p, was analyzed in plasma and tissues of CRC patients and in plasma of a control group of healthy blood donors. In our study, we identified significant changes in the expression levels of both miRNAs in CRC patients compared to healthy cancer- free subjects. Specifically, higher expression levels of both miRNAs were observed in CRC patients compared to the...
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