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Case study of physiotherapy treatment of a patient after hemicolectomy and middle pancreatectomy
Linhartová, Kamila ; Hassmannová, Kristina (advisor) ; Charvát, Robert (referee)
Author: Kamila Linhartová Title: Case study of physiotherapy treatment of a patient after hemicolectomy and middle pancreatectomy Aims: Aim of this bachelor thesis is to summarize theoretical information about hemicoletcomy and middle pancreatectomy and to demonstrate possible physiotherapy treatment on a case study of a patient after the surgical approaches mentioned above. Methods: Detailed research of theoretical background of oncological diseases of large intestine and pancreas, hemicolectomy, middle pancreatectomy and physiotherapy treatment after abdominal surgery was performed to process the general part of this bachelor thesis. The special part of this thesis consist of a case study of a patient after hemicolectomy and middle pancreatectomy, which originated from bachelor clinical practice at Institute of Clinical and Experimental Medicine in Prague, in the time period between 18. 1. 2021 and 12. 2. 2021. The case study includes anamnesis, entry kinesiological analysis, suggestion and goals of physiotherapy treatment, individual therapy sessions, output kinesiological analysis and an evaluation of effects of performed treatment. Results: During therapy interventions general condition and muscle strength in a patient increased, breathing stereotype adjusted, soft tissues in the abdominal...
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Mutations in MLH1 gene and MSI status as molecular characteristics of sporadic colorectal cancer
Čaja, Fabián
Colorectal carcinoma (CRC) is one of the most prevalent malignancies in the Czech Republic. In general, there are two molecular pathways leading to CRC: one is characterized by chromosomal instability, the other by the deficiency in DNA mismatch repair (MMR) genes. MutL homologue 1 (MLH1) gene, a member of the MMR gene-family, represents a key component of the MMR system, responsible for recognition of nucleotide mismatches occurring during DNA replication, and for the recruitment of repair proteins to correct the replication errors. According to literature, somatic mutations in MMR genes, and MLH1 in particular, hallmark sporadic, MMR deficient, CRC cases. We aimed at analyzing somatic events in MLH1 gene and the determination of microsatellite instability (MSI) status in 99 DNA samples from 96 patients with sporadic CRC. Mutations were screened by high resolution melting (HRM) curve analysis. Positive cases in each run were subsequently verified by automated sequencing. Mainly gene variants were found in MLH1 gene: We discovered two new variants, one in exon 2 at position c. 204 C>G, p. Ile68Met (98 C/C, 1C/G) and the other in exon 11 at position c. 973 C>T, p. Arg325Trp (98 C/C, 1 C/T). Only the latter variant c. 973 C>T was identified as somatic mutation. All other variants found in MLH1 gene...
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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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Colorectal cancer - from patogenesis to screening. Colorectal carcinogenesis in ulcerative colitis with primary sclerosing cholangitis and the issue of the screening of the colorectal cancer.
Wohl, Pavel ; Špičák, Julius (advisor) ; Škarda, Jozef (referee) ; Gregor, Martin (referee)
Colorectal carcinoma (CRC) ranks high in mortality and morbidity in most developed countries. Following theses focus on specific aspects of colorectal carcinoma pathogenesis including the issue of screening. The goal of the first study was assessment of expression of epithelial markers of colorectal carcinogenesis p53, COX-2, bcl-2. The study included patients with active ulcerative colitis (UCA), ulcerative colitis in remission (UCR), primary sclerosing cholangitis with ulcerative colitis (PSC-UC) (PSC), patients after liver transplantation for PSC (OLT) and a control group (N). We found significantly increased expression of tumour suppressor gene p53 in non-dysplastic mucosae in PSC-UC compared with UCA, UCR, OLT, and N, which may indicate higher neoplastic potential of PSC. Statistically significant correlation was found between PSC incidence and p53 expression. Surprisingly, OLT showed no p53 expression in non-dysplastic mucosa compared with PSC-UC. This indicates that PSC may contribute to increased expression of p53 and p53-induced colorectal carcinogenesis. Furthermore, a correlation between expression of p53 and COX-2 together with the increased expression of bcl-2 in UCA compared to N can support the role of inflammation in colorectal carcinogenesis. The goal of the second study was...
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Usage M. E. Levine model in clinical and community care in patients with colorectal cancer
DUŠIČKOVÁ, Tereza
The aim of the dissertation was to find out the specifics of nursing care in clinical and community practice with patients with colorectal cancer using the model of M. E. Levine. Furthermore, to find out which of these specifics are missing in the mentioned nursing model and to modify the nursing documentation according to the chosen conceptual model of M. E. Levine. In the empirical part we used a combination of qualitative and quantitative research which was carried out as part of the grant project GAJU 048/2015/S. The pre-research, conducted interviews with 8 informants was used to identify the key data for answering research questions and creating a custom-designed questionnaire. A non-standardized questionnaire was distributed across the Czech Republic to 300 patients with colorectal cancer. We also designed nursing documentation, which was verified by focus group with 35 nurses from clinical and community practice. The results show that patients are limited in areas of contact with friends, normal traffic, traveiling, and fear for themselves and their loved ones to maintain social integrity. In the principle of maintaining structural integrity, problems with diet, alcohol consumption, diarrhea, current treatment management, stoma and stoma type have been identified. In the field of energy conservation the influence of length of diagnosis and colonoscopy performed as part of preventive examination, pain sensation, and enough energy for normal daytime life have been confirmed. In the principle of conservation personality integrity, we have found that the length of time determines the fear of getting stoma, learning individuals with the same disease, experiencing negative feelings, and limiting private life. The work provides a comprehensive framework of the issue of patients with colorectal cancer. It provides evidence of the possibility of using M. E. Levine's conceptual model in colorectal cancer patients.
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Mutations in MLH1 gene and MSI status as molecular characteristics of sporadic colorectal cancer
Čaja, Fabián
Colorectal carcinoma (CRC) is one of the most prevalent malignancies in the Czech Republic. In general, there are two molecular pathways leading to CRC: one is characterized by chromosomal instability, the other by the deficiency in DNA mismatch repair (MMR) genes. MutL homologue 1 (MLH1) gene, a member of the MMR gene-family, represents a key component of the MMR system, responsible for recognition of nucleotide mismatches occurring during DNA replication, and for the recruitment of repair proteins to correct the replication errors. According to literature, somatic mutations in MMR genes, and MLH1 in particular, hallmark sporadic, MMR deficient, CRC cases. We aimed at analyzing somatic events in MLH1 gene and the determination of microsatellite instability (MSI) status in 99 DNA samples from 96 patients with sporadic CRC. Mutations were screened by high resolution melting (HRM) curve analysis. Positive cases in each run were subsequently verified by automated sequencing. Mainly gene variants were found in MLH1 gene: We discovered two new variants, one in exon 2 at position c. 204 C>G, p. Ile68Met (98 C/C, 1C/G) and the other in exon 11 at position c. 973 C>T, p. Arg325Trp (98 C/C, 1 C/T). Only the latter variant c. 973 C>T was identified as somatic mutation. All other variants found in MLH1 gene...
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Optimization of proces for detection of free tumor DNA in plasma and its clinical utility for colorectal cancer, lung cancer and pancreatic cancer patients
Belšánová, Barbora ; Benešová, Lucie (advisor) ; Tachezy, Ruth (referee)
In current days, examination of circulating tumor DNA (ctDNA) finds new use across different cancers. It is directed at tumor-derived short fragments of DNA present in peripheral blood of patiens (mainly in advanced stages). Due to its minimal invasivity, almost 100 % specificity and relatively high sensitivity in stage IV patients, this approch found its main potential clinical utility especially in early detection of disease relapse or progression after tumor resection (i.e. post-operative follow-up), prediction and monitoring of therapy response and estimation of prognosis. As a result of minute levels of ctDNA on a high background of other non-tumor DNA fragments present in plasma, a suitable method exhibiting highest sensitivity is the key for proper detection of this marker. The approach is predominantly based on initial identification of a mutation in tumor tissue and its subsequent detection in plasma. The present work is aimed at optimization of ctDNA isolation and method of its detection based on PCR amplification followed by heteroduplex analysis by denaturing capillary electrophoresis (DCE) to achieve highest sensitivity for detection of mutated fraction in plasma sample. I have applied the optimized protocol to examine ctDNA in three types of cancers, namely colorectal cancer (122...
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Utilisation of New Biomarkers for the Optimalization of Diagnostics and Therapy of Tumors of the Gastrointestinal Tract
Šafanda, Martin ; Kučera, Radek (advisor) ; Fínek, Jindřich (referee) ; Svobodová, Šárka (referee)
Utilisation of New Biomarkers for the Optimalization of Diagnostics and Therapy of Tumors of the Gastrointestinal Tract Introduction: Tumor markers are standard diagnostic tools. They are mainly used to monitor the course of the disease and to check the efficacy of the treatment. It is important to observe dynamics. Changing the level of the biomarker can prevent clinical manifestation and lead to early diagnosis of relapse, which in turn means improving the quality of life, including prolonging survival. Recently, we have encountered a number of diagnostic algorithms that suggest algorithms for estimating the risk of tumor presence or the risk of progression of cancer, using statistical methods. Objectives: The aim of this work is to verify new biomarkers for the diagnosis of gastric cancer and to develop an optimal algorithm for their use. Further, to evaluate the importance of cytokeratin markers - Tissue Polypeptide Antigen (TPA) and Tissue Polypeptide Specific Antigen (TPS) for the diagnosis of metastatic colorectal carcinoma in the liver. To carry out a pilot study of FGF23 levels in people with colorectal carcinoma and other gastrointestinal tumors. Methods and patients: Patient samples were analyzed using immunoradiometric, chemiluminescence and fluorescence assays. For each solved problem,...
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Characterization of tumor suppressor gene Hypermethylated in cancer 1 (Hic1) and its novel target genes in the intestinal epithelium and colorectal cancer
Baloghová, Nikol ; Janečková, Lucie (advisor) ; Doubravská, Lenka (referee)
Colorectal cancer is one of the most common cancer types worldwide. Both genetic and epigenetic alterations play a critical role in its initiation and progression. One of the genes frequently epigenetically silenced or lost in many types of human cancer is tumor suppressor gene Hypermethylated in Cancer 1 (HIC1). It encodes for transcriptional repressor regulating its target genes directly or indirectly. Twelve genes whose expression is repressed by HIC1 have been identified to date. These genes encode for transcription factors, cell cycle and apoptosis regulators or proteins involved in angiogenesis as well as cell migration and invasiveness. Employing mouse embryonic fibroblasts upon Hic1-conditional knockout we have revealed six novel genes potentially repressed by Hic1 including Toll-like receptor 2 (Tlr2). Here we show that Tlr2 is one of the Hic1 target genes and that Hic1 inactivation in the intestine leads to increased Tlr2 production. Moreover, enhanced inflammatory response upon chemical-induced colitis as well as increased tumor formation in ApcMin mice was observed in Hic1-deficient mice. Expression profiling in human fibroblast upon HIC1 knockdown revealed increased expression of another potential target gene, transcription factor E2F7. Our study describes a new relationship between HIC1 and...
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CIrcadian regulation of miRNA and clock-controlled genes in tumorigenesis
Balounová, Kateřina ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee)
The circadian clock generates circadian rhythms, which participate on regulation of a number of signalling pathways. Disruption of the circadian regulatory mechanism is linked to a development and a progression of certain types of cancer including colorectal tumorigenesis. Progression of tumorigenesis depends on the cell cycle machinery related to cell proliferation and apoptosis. MiRNAs play a role in initiation and progression of tumorigenesis because they interfere in regulatory pathways associated with tumorigenesis. The aim of the thesis was to determinate existence of circadian rhytms in clock controlled genes (Tef, Dbp), miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-155-5p, miR-192-3p) and genes of the cell cycle machinery (Ccnd1, Ccne1, Ccna1, Ccnb1) and apoptosis (Casp3, Bcl2, Bad). Further, to compare detected circadian rhythms during aging and neoplastic transformation of colon by quantitative RT-PCR. We have observed circadian expression of Tef, Dbp, Ccne1, Ccna1, Ccnb1, Casp3 and Bcl2 in young mice colon, Tef, Dbp, miR-1-3p, Ccne1, Ccna1 in old mice colon and Tef and Dbp in colorectal tumors. In summary, circadian expression of clock controlled genes varied but was maintained in mice colorectal tumors. In aging we demonstrated weakening of circadian rhythms of the genes of the cell...
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