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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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Tumor microenvironment of soft tissue sarcomas and it's predictive significance in modern oncological treatment
Ozaniak, Andrej ; Ozaniak Střížová, Zuzana (advisor) ; Büchler, Tomáš (referee) ; Posová, Helena (referee)
Soft tissue sarcomas (STSs) are malignant tumors of mesenchymal origin, characterized by an extreme heterogeneity in histological composition, biological behavior, and clinical manifestation. Most STSs are chemo- and radiotherapy resistant. A key prognostic factor predicting the risk of distant metastases and affecting the overall survival is the tumor grade. However, grade has not been associated with the risk of local recurrence. Radical surgical procedure is in many cases the only possible treatment modality or at least plays a main role in the multimodal treatment. For patients with distant metastases, the treatment options are very limited. The chemosensitivity of STSs is generally very low, with the exception of several less common subtypes, and accounts for only 5-10% of the cases. In many cases, radiotherapy is a standard part of the treatment protocol. It is usually given in either neoadjuvant or adjuvant settings. However, radiotherapy administration in generalized patients does not improve the prognosis. Cancer immunotherapy is a therapeutic modality that utilizes the physiological cytotoxic antitumoral abilities of the immune cells. Therefore, it does not target the rapidly proliferating tumor cells but rather stimulates the immune cells. A wide variety of different strategies have been...
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Possibilities of using advanced MR techniques in pelvic imaging
Ryznarová, Zuzana ; Malíková, Hana (advisor) ; Büchler, Tomáš (referee) ; Lisý, Jiří (referee)
(AJ) The three aims of the work were as follows: 1. Comparison of prostate magnetic resonance (MR) examination results from 1.5 T and 3 T scanners in patients with prostate carcinoma (PCa). MR findings of 103 patients (ages 44-72 years) were compared with histopathological results after radical prostatectomy. The work was focused on the accuracy of predicting local cancer staging and determining prostate tumour location. Patients were divided into three groups (A, B and C) based on the type of MR scanner and protocol used. Patient groups A and B were examined in 1.5T and 3T MR scanners equipped with surface coils in the identical multiparametric MR imaging protocol included dynamic contrast examination (DCE). Patient group C was examined in a 3T MR scanner without DCE. The highest accuracy of predicting the stage of PCa was seen in patients examined in 3 T MR scanner with DCE included in the protocol, however, no significant differences were seen between results from 1.5 T and 3.T MR scanners. No significant difference was also found in the accuracy of determining the location of prostate tumour between 1.5 T and 3T MR examinations, however, there were significant differences between sequences used, with the highest accuracy attained by using a combination of T2 weighted sequences and diffusion...
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Immunogenic cell death in tumor specimens in the clinics
Fejfarová, Adéla ; Drbal, Karel (advisor) ; Büchler, Tomáš (referee)
Tumor development and growth are under the control of the immune system in the human body. Danger-associated molecular pattern (DAMP) molecules trigger the anti-tumor response by binding to pattern recognition receptor (PRR) on myeloid cells which in turn activate an adaptive immune system. DAMP molecules are released from cancer cells during a process of immunogenic cell death (ICD) which is a form of regulated cell death (RCD). ICD is induced by a variety of treatments in experimental settings as well as by therapeutic modalities commonly used in medicine. A typical DAMP marker of ICD is calreticulin which is translocated from the endoplasmatic reticulum to the plasma membrane attached to the CD91 receptor. Another marker is the nuclear protein HMGB1 which is released into the tumor environment at the later stage of ICD. This bachelor thesis describes a variety of detection methods and the results of DAMP externalization after ICD induction in vitro in cancer cell lines and in tumor specimens from cancer patiens. Moreover, the link between DAMP molecules and cancer patient survival is discussed. Last, it also summarizes the current status of clinical trials concerning ICD. Keywords tumor, antitumor immunity, cell death, adjuvans, DAMP, chemotherapeutics, immunogenic cell death, clinical trials
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Risk factors for head and neck cancer
Licková, Kateřina ; Čoček, Aleš (advisor) ; Büchler, Tomáš (referee) ; Vaňásek, Jaroslav (referee)
Risk factors for head and neck cancer MUDr. Kateřina Licková, MBA We focused on the research of risk factors for head and neck cancer (HNC) and the aim of our study was to confirm the influence of known external risk factors (alcohol and smoking) and further correlate the overall clinical and socio-economic status of the patient with HNC. In contrast to previous studies, we confirmed the results of the study with a control group of patients with other heterogeneous oncological diagnoses (OOD). The research was carried out in the years 2015 to 2019 at the Radiotherapy and Oncology Clinic of the Royal Vinohrady University Hospital (FNKV) in Prague. The study included 200 patients with ZNHK and 200 patients with OOD. For the research of risk factors, we used a non-standardized questionnaire focused on socio-economic and behavioral risk factors. We used the Czech reading test (CRT) to measure premorbid intellect, the visual analog scale VAS (from 0 to 10 cm) to determine the quality of life, the GAD-7 questionnaire to detect anxiety, the BDI-II self-assessment questionnaire to detect depression and and clinical data were obtained retrospectively from medical records and from the UNIS database of the hospital system. The results of our work confirmed that cigarette smoking and alcohol consumption are the main...
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Diagnostic and prognostic markers in the era of targeted treatment of CRC.
Veškrňová, Veronika ; Büchler, Tomáš (advisor) ; Mohelníková Duchoňová, Beatrice (referee) ; Valík, Dalibor (referee)
Introduction: Colorectal cancer (CRC) is the most common malignant tumor in both sexes in the Czech Republic. Prognostic factors in CRC can be classified as clinical (stage at the time of diagnosis, histological type of tumor), genetic (RAS, BRAF), immunological (Immunoscore)and biochemical (CEA, CA 19-9, miRNA). MicroRNAs (miRNAs) regulate the expression of oncogenes and tumor suppressors. The regulatory function of miRNAs is influenced by single nucleotide polymorphisms (SNPs) of target miRNA binding sites (miRSNPs). Aims: To evaluate the currently available prognostic factors for CRC patients treated using targeted therapies and assess the role of novel ones, including miRNA. Methods: The thesis includes clinical works focused on targeted treatment of colorectal cancer, original work focused on the role of miRNA in colorectal cancer pathogenesis and especially as a prognostic and predictive marker, work focused on functional polymorphisms of DNA repair genes and a review article summarizing biochemical factors influencing the effect of fluoropyrimidine cytostatics in the treatment of colorectal cancer. Results: We have identified miR-17/92 as a non-invasive biomarker for predicting post-treatment prognosis in patients with a higher risk of relapse, as well as miRSNPs rs8679 polymorphisms as a...
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Possibilities of using advanced MR techniques in pelvic imaging
Ryznarová, Zuzana ; Malíková, Hana (advisor) ; Büchler, Tomáš (referee) ; Lisý, Jiří (referee)
(AJ) The three aims of the work were as follows: 1. Comparison of prostate magnetic resonance (MR) examination results from 1.5 T and 3 T scanners in patients with prostate carcinoma (PCa). MR findings of 103 patients (ages 44-72 years) were compared with histopathological results after radical prostatectomy. The work was focused on the accuracy of predicting local cancer staging and determining prostate tumour location. Patients were divided into three groups (A, B and C) based on the type of MR scanner and protocol used. Patient groups A and B were examined in 1.5T and 3T MR scanners equipped with surface coils in the identical multiparametric MR imaging protocol included dynamic contrast examination (DCE). Patient group C was examined in a 3T MR scanner without DCE. The highest accuracy of predicting the stage of PCa was seen in patients examined in 3 T MR scanner with DCE included in the protocol, however, no significant differences were seen between results from 1.5 T and 3.T MR scanners. No significant difference was also found in the accuracy of determining the location of prostate tumour between 1.5 T and 3T MR examinations, however, there were significant differences between sequences used, with the highest accuracy attained by using a combination of T2 weighted sequences and diffusion...
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Mechanisms of artralgia in targeted therapies for cancer
Mráčková, Monika ; Büchler, Tomáš (advisor) ; Šírová, Milada (referee)
Many targeted anti-tumor therapies result in arthralgia, the non-inflammatory joint pain. The mechanism of pain signaling in arthralgia is not entirely understood but many studies lead to a conclusion that inflammatory cytokines play an important role. Especially interleukin (IL)-6 has been detected in high levels in plasma of patients treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Although IL-6 seems to be the key factor causing arthralgia, other possible mechanisms have been described. This review focuses on the published data about the correlation between cytokines and cancer-related arthralgia. Possible treatments and future directions are also described.
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