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Histological examination of the colon
FEJKOVÁ, Karolína
This bachelor´s thesis deals with histological examination of the colon, namely the laboratory diagnosis of colorectal cancer. Colorectal cancer is a highly relevant issue today not only in the Czech Republic, not least because of its continually growing incidence worldwide. Laboratory analysis of this disease is not only important from the aspect of diagnosis per se. Determining the type and invasive stage of the disease is also crucial for the therapeutic strategy in a given patient. Immunohistochemistry testing of the colon also aids in the diagnosis of Lynch syndrome, a hereditary disease with a high risk of colorectal cancer. The first part of the thesis is theoretical and aims to introduce not only the subject of colorectal cancer but also the anatomical, histological and pathological features of the colon. This section also describes the methods used to obtain tissue samples from the colon and to process these in a histopathology laboratory. This information regarding the histopathological processing of colon tissue is then applied and described in detail in the methodology section of the thesis. This describes the process of routine staining methods such as haematoxylin-eosin and Alcian Blue. It also details the manually performed immunohistochemical methods and related reagents, including the use of antibodies. The next section presents a statistical analysis of a sample of patients with colorectal cancer treated at the Jihlava Hospital between 2018 and 2019. These data confirm the generally accepted fact that there is a higher incidence of colorectal cancer in men and that this cancer predominantly affects patients aged between 60 to 70 years. Furthermore, this work shows that defects in the MMR proteins associated with Lynch syndrome are not detected in even one half of the patients tested.
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Tracing intestinal tumorigenesis driven by BRAF V600E oncogene
Herrmannová, Terezie ; Hrčkulák, Dušan (advisor) ; Vomastek, Tomáš (referee)
Colorectal carcinoma is one of the most commonly diagnosed tumor diseases worldwide and is the cause of more than nine percent of deaths due to neoplasia. Colorectal cancer develops through different ways and one of them is the so-called serrated pathway, which is characterized by the presence of the BRAF V600E oncogenic mutation. Tumors arising through serrated pathway do not respond to classical therapy, and therefore are currently being studied at the molecular level. The oncogenic variant of the BRAF kinase activates MAPK signaling and is considered to be the main cause of serrated intestinal tumor formation. However, the mere presence of this oncogene is not sufficient for tumor development that requires further changes within the genome of the cell. In this thesis, we try to clarify what effect the BRAF V600E mutation has on the cells of the intestinal epithelium. In addition, we try to identify a possible cooperation between BRAF gene mutation and disruption of p53 and Wnt signaling, whose components are also frequently mutated in colorectal cancer. As a model for studying the processes associated with BRAF V600E activation, we use a mouse strain with conditional expression of a mutant variant of the Braf gene. We isolate intestinal organoids from these mice and subsequently perform in vitro...
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Influence of tumor microenvironment, cellular and humoral immunity on cancer pathogenesis.
Špaček, Jan ; Závadová, Eva (advisor) ; Petráková, Katarína (referee) ; Kopečková, Kateřina (referee)
Cancer is the second leading cause of death in the Czech Republic. Breast cancer and colorectal cancer have relatively high mortality rate. One of the areas of current clinical research in oncology is the study of prognostic biomarkers, which aims to optimize the decision-making process for a patient. Immune response and processes in the tumor microenvironment have been shown to influence to a large extent the biological nature of the tumor in terms of its aggressiveness and ability to metastasize in the host's body. There are certain tumors that could induce a strong immune response, while others do not. The ability to induce an anti-tumor cell response and to attract specific lymphocyte subpopulations directly into tumor tissue has been shown to be very closely related to the prognosis of cancer patients. There is evidence and correlation of the presence of so-called tumor infiltrating lymphocytes in tumor tissue and overall patient survival. Stratification of cancer patients based on immuno-predictors both in the plasma and directly in the tumor microenvironment makes it possible to identify suitable candidates for rediscovered modern anti-tumor immunotherapy, which can already be considered a standard therapeutic modality. In our projects, we focused on the identification of biomarkers that...
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Epidemiology of sporadic forms of colorectal cancer in terms of preventions and the possibility of early diagnostic.
Schneiderová, Michaela ; Bencko, Vladimír (advisor) ; Krška, Zdeněk (referee) ; Hudečková, Henrieta (referee)
Thanks to the latest achievements in diagnostics, surgery and oncology, the overall perspective of colorectal cancer has changed significantly. There are no doubts that we deal with a complex disease, requiring multidisciplinary approach and assessment. Only this approach can enable patients to survive longer and maintain acceptable quality of there lives. Taking a long view over several decades, the steep rise in incidence of this malignancy was strongly alarming. It is partly a penalty for a prolongation of life expectance, since one of the risk factors is age. Knowing the way of life and dietary customs of our ancestors, one cannot deny that the change of lifestyle including dietary habits, as well as decrease of physical activity, obesity, stress, unsuitable thermal processing of food produced in bulk, consumption of immoderate amount of red meat, limited intake of raw vegetable and fruits, excessive intake of xenobiotics, such as medication or cosmetic products, excessive alcohol consumption, particularly beer, nicotinism, environmental pollutants, etc. contribute to the increase of this cancer incidence. All the above mentioned factors have led over the time to a formation and development of numerous so called civilization diseases, among which rates the colorectal cancer (CRC). Despite the...
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Effect of colorectal cancer screening programs on lethality and incidence from this disease in the Czech Republic modeled by an APC approach
Čady, Ondřej ; Hulíková Tesárková, Klára (advisor) ; Kurtinová, Olga (referee)
This work will first introduce the problems related to the colorectal cancer - its epidemiology and screening possibilities. Next the main topic is addressed - i.e. to ascertain the influence of national screening programmes for colorectal cancer on really observed data of lethality and incidence of this disease. Group of so-called APC models was selected as a useful tool for this purpose. Applying these methods on data of The National Oncological Registry of the Czech Republic for the period between 1980 till 2009 this work aims to prove expected reducing effect of area-wide screening programme on incidence and lethality related to colorectal cancer. Using the AP model and data of previous period before the screening introduction (i.e. 1980-1999) the values of incidence and lethality were predicted for the period in question (i.e. 2000-2009). Mere comparison of this predicted values with really observed data showed that real lethality and incidence was significantly lower in both sexes as compared to the model without the screening intervention. Difference between predicted and real data corroborates positive influence of colorectal cancer screening.
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Diagnostic and prognostic impact of miR-122 and miR-142 in colorectal cancer
Kalkušová, Kateřina ; Červená, Klára (advisor) ; Král, Jan (referee)
Colorectal carcinoma is one of the most frequent cancers and it is also one of the most common causes of cancer related death. It is often diagnosed at a late stage which is associated with a worse prognosis. Therefore, there is an effort to identify new biomarkers that allow earlier diagnosis. These biomarkers could predict prognosis of disease and patient's response to treatment. Short noncoding RNAs - microRNA - appears to be promising candidates, these molecules are involved in many cellular processes through RNA interference. The aim of this thesis is to summarize knowledge about application of miR-122 and miR-142 as diagnostic and prognostic biomarkers for colorectal cancer. Keywords: microRNA, biomarkers, colorectal cancer, diagnostics, prognosis
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Histological methods used in the diagnosis of colorectal cancer.
Kowaliková, Šárka ; Hronek, Miloslav (advisor) ; Josková, Věra (referee)
This bachelor thesis is focused on tumor diseases of the colon, especially on the processing of biopsy material obtained by sampling during colonoscopy and colectomy. The theoretical part of this thesis describes general anatomy of the colon and assumptions of tumor formation in this location. It deals mainly with the risk factors which may be unaffectable, e.g. heredity and age, but also affectable, such as insufficient physical activity, excessive consumption of red meat, low fiber intake, smoking, alcohol consumption, overweight etc. The thesis also describes the possibility of prevention, which is closely related to the risk factors. Finally, some ways of taking biopsy samples and subsequent laboratory processing are listed. The practical part presents the methods used for tissue processing and staining histological slides with a focus on the advantages of faster tissue processing by continuous tissue processor. It also deals with immunohistochemical examination, which is an integral part of histopathological diagnostic procedure. The aim of the thesis was to describe how certain methods of histological processing can accelerate and especially clarify the diagnosis and the associated follow-up treatment. Keywords: colon , colorectal cancer, pathology , cancer , colonoscopy, colectomy,...
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Role of the FTO gene in the genetic determination of common multifactorial diseases
Dlouhá, Dana ; Hubáček, Jaroslav (advisor) ; Černá, Marie (referee) ; Rossmeislová, Lenka (referee)
Obesity is a risk factor for development of cardiovascular disease, diabetes type 2 and some cancers. Newly detected genetic risk factor for body weight is the FTO gene ("fat mass and obesity associated"). The aim of this thesis was determine 1) whether the presence of risk alleles correlate with BMI in Czech population and to determine 2) whether there is an association between variants in the FTO gene and risk of myocardial infarction/ acute coronary syndrome (MI/ ACS), 3) renal failure (ESRD), or 4) incidence of colorectal cancer (CRC). We analyzed polymorphisms rs17817449 (first intron) and rs17818902 (3rd intron) using by PCR-RFLP and then also RT PCR. We found an association of the first intron variant (but not the 3rd one) and BMI in Czech control population. We have detected an association of 1st intron SNP and BMI changes during the intervention study in obese children, but not in obese females. We found a correlation between the risk allele and increased risk of ACS (OR 1.49) in patients with MI. In patients with ESRD was detected association between the risk allele and the risk of disease (OR 1.37). We didn't confirmed the association between rs17817449 and the development of CRC. Representative selected groups of the Czech populations "MONICA" and "HAPPIE" were used as controls. One...
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Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee) ; Herichová, Iveta (referee)
AABBSSTTRRAACCTT The molecular circadian clock enables anticipation of environmental changes. In mammals, clocks are ubiquitously present in almost all tissues and they are comprised of transcriptional-translational feedback loops of the so-called clock genes. The central clock represents the intrinsic pacemaker which is located in suprachiasmatic nuclei (SCN) of hypothalamus and synchronizes peripheral clocks. Clockwork system in alimentary tract and its regulatory link to intestinal functions are poorly understood. Therefore the objective of the thesis was to characterize molecular clock in particular parts of the rat intestine and to elucidate its link to the intestinal transport, regulation of cell cycle and neoplastic transformation in colonic tissue. We used quantitative RT-PCR (qPCR) to determine circadian profiles of mRNA expression of clock genes in the epithelium of duodenum, jejunum, ileum, and colon of rat. Furthermore, we analysed the expression of genes coding sodium chloride transporters and channels as well as cell cycle regulators in colon. To focus more precisely on different structures of intestinal epithelia we used laser capture microdissection. In addition, we performed Ussing chamber measurements to determine the colonic electrogenic transport. To study the contribution of circadian...
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Inflammation and cancer in germ-free vs. conventionally reared animals
Čaja, Fabián ; Vannucci, Luca Ernesto (advisor) ; Tlaskalová - Hogenová, Helena (referee) ; Smrž, Daniel (referee)
Inflammation is considered as one of the main defence mechanisms of the immune system against threats that occur in the body. When present in its acute form, minimal or no detectable subsequent damage of original affected tissue exists. The more pathological form, chronic inflammation, is associated with permanent damage of the tissue and typically a hallmark of various diseases such as ulcerative colitis or colon carcinogenesis. These two pathologies are evolving in the unique colon microenvironment, where intensive interaction between the host cells and bacteria is present. The aim of our study was to investigate the immunological (ELISA, FACS, RT-PCR) and structural (histology, confocal microscopy) changes in the colon mucosa of Wistar-AVN rats induced by dextran sodium sulphate (DSS) to produce colon colitis and by azoxymethane (AOM) to produce colon carcinogenesis. Conventional (CV) and also germ-free (GF) reared animals were used to investigate the effects of the mucosal inflammation activated by the administered inducers as well as the role of colon microbiota - as promoters of a continuous immune activation - in the modulation of immunity and collagen scaffold remodelling. Our results showed that even in the early period after the induction, both inducers produced a smouldering...
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