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The importance of tumor markers and markers of angiogenesis for colorectal cancer prognosis
Levý, Miroslav ; Lipská, Ludmila (advisor) ; Třeška, Vladislav (referee) ; Šafarčík, Kristian (referee) ; Keil, Radan (referee)
Despite extensive progress in understanding of the molecular pattern of the tumor, growing possibilities of chemotherapy and surgical treatment, colorectal cancer remains the significant cause of death worldwide. Surgical treatment alone has already reached in oncologic radicality its limits, and therefore the surgeons turned to the molecular base of tumor growth in an effort to find markers that allow to operate patients at lower stages of the disease and thus improve the results and prognosis of the disease. And also to find markers, which, after currative operation will find a possible relapse in early stage to enable the surgeon to perform second curative intervention. Tumor markers are substances that often arise in connection with the changed metabolism transformed tumor cells, and therefore their levels increased in the presence of malignancy. Serum tumor markers are important parameters that may facilitate the prediction of the disease, its progression or regression (remission). Tumor markers are clinically used for screening, primary diagnosis, staging, prognosis, but particularly for predicting recurrence of disease, monitoring therapy. This work aims to summarize the current knowledge about the colorectal cancer markers, outline the possible development and present results of relationship...
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Incidence of multiple sclerosis in patiens with inflammatory bowel diseases (IBD)
Ročková, Petra ; Keil, Radan (advisor) ; Hep, Aleš (referee) ; Zádorová, Zdeňka (referee)
Ročková Summary Inflammatory bowel diseases (IBD) - Crohn's disease (CD) and ulcerative colitis (UC) are associated with various extraintestinal manifestations (EM). These manifestations may involve virtually any organ system. Neurological manifestations are not regarded as very common, but they are probably underdiagnosed. Patients with IBD have higher risk of developing multiple sclerosis (MS) regardless of therapy manner they use. There are quite a lot of publications describing relationship between developing multiple sclerosis and therapy with monoclonal antibody against tumor necrosis alpha (anti TNF-α). However, it remains to be shown whether anti-TNF-alpha itself causes MS or merely acts as a trigger, exacerbating preexisting subclinical CNS damage during chronic anti- TNF-α treatment. Majority of published cases support the second possibility. These results let us to define a hypothesis, that preselection of patients with IBD without any preclinical signs of demyelination before the initiation of anti TNF- a therapy may improve patient safety. The aim of our project was to develop neurological and magnetic resonance (MRI) screening of patients with IBD before anti TNF- α therapy initiation and subseqently exclusion of patients wth high risk of developing MS. The second aim was to follow up on the...
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Relationship between metabolism, autonomic neuropathy and vascular disease in patients with type 1 and 2 diabetes mellitus
Malá, Šárka ; Keil, Radan (advisor) ; Lhotská, Lenka (referee) ; Krčma, Michal (referee)
The study aims to evaluate the relationship between cardiac autonomic neuropathy (CAN) and intima-media thickness (IMT) of carotid arteries in patients with diabetes mellitus. Individuals with type 1 and type 2 diabetes mellitus were included, with non-diabetic controls. Medical history, anthropometric and biochemical data, IMT measurements and heart-rate- variability (HRV) analysis in all probands were evaluated. A model of semiparametric logistic regression from the class of generalized additive models was used for statistical analysis. CAN demonstrated significant increasing effects on IMT values in type 1 diabetes patients. The model showed greater IMT values in type 2 diabetes mellitus patients suffering from CAN, but the effect of CAN was not significant. The interaction of CAN and diabetes mellitus effects on IMT values was proven. The interactions of CAN and age, CAN and BMI were also demonstrated. In CAN positive groups, IMT values increased more quickly with greater age and BMI. The results suggest that CAN may play a role in the pathogenesis of atherosclerosis in patients with diabetes mellitus. The secondary objective was to evaluate the usage of the recurrence quantification analysis of HRV in CAN diagnostics. Between the group of healthy individuals and patients with vasovagal...
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Inflammatory bowel diseases in pregnancy
Koželuhová, Jana ; Matějovič, Martin (advisor) ; Keil, Radan (referee) ; Hep, Aleš (referee)
Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, can affect mainly young people in their reproductive years. IBD therefore has a major impact on patient's family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal disease control and drug safety. An unanswered question is the impact of the course of childbirth in women with preexisting IBD regarding anal sphincter function and development of anal or fecal incontinence. To this date there aren't any clinically relevant guidelines for managing childbirth in women with IBD. From gastroenterologist's point of view, a clear indication for Caesarean section (CS) is active perianal disease or active IBD with rectal involvement, a relative indication for CS is ileal-pouch-anal anastomosis (IPAA) or ileal-rectal anastomosis in women after colectomy for refractory UC. Studies have shown a lack of knowledge among both patients and physicians regarding reproductive issues in IBD. The main aim of this thesis was first to assess risk of vaginal delivery in development of anal incontince, second to evaluate the safety of biologic therapy during pregnancy in women with inflammatory bowel disease. We present a study researching the morbidity of children born to mothers treated with biological...
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New markers of colon cancer evolution in ulcerative colitis
Švec, Jiří ; Kment, Milan (advisor) ; Keil, Radan (referee) ; Hampl, Aleš (referee)
Background: Long-standing ulcerative colitis (UC) has an increased risk of evolving into colorectal cancer (CRC) and upregulated expression of cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK) and transcription factors c- MYB and TCF-4, has been implicated in the development and progression of sporadic colorectal cancer. Nevertheless much less is known about their role in the process of UC-associated colon carcinogenesis. Methods: We analyzed the gene expression of these markers during the transition of colonic mucosa from chronic inflammation to epithelial neoplasia in biopsies of UC patients using quantitative real-time polymerase chain reaction and immunohistochemistry, and compared the expression profiles of this gene panel in samples of patients with CRC and in human tumor xenografts of SW620 malignant colonic cells. Additionally, we determined the expression of these genes in mouse models of sporadic and colitis-associated CRC in A/J and ICR mouse strains using quantitative RT-PCR and laser microdissection. Results: The transcript levels of survivin, c-MYB, COX-2, iNOS, and TCF-4 showed statistically significant increase during neoplastic transformation of UC-patient colonic mucosa, whereas TERT and ILK...
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Diabetes mellitus and impairment of intestinal barier function
Hoffmanová, Iva ; Anděl, Michal (advisor) ; Haluzík, Martin (referee) ; Keil, Radan (referee)
Introduction: Impairment of intestinal barrier function is involved in pathogenesis of immune mediated diseases (such as type 1 diabetes mellitus or celiac disease) and metabolic diseases (such as type 2 diabetes mellitus). Aims of study: The first aim was to analyze impairment of mucosal part of intestinal barrier in both type of diabetes and to describe differences when compared to celiac disease, which is a typical condition associated with impairment of intestinal barrier function. The second aim was to find a correlation between duration or compensation of diabetes and intestinal barrier desintegration in patients with both type of diabetes, and to find a correlation between body mass index and intestinal barrier desintegration in patients with type 2 diabetes. The third aim was to assess influence of gluten-free diet on improvement of small intestinal mucosal integrity in patient with celiac disease. Methods: The study was performed on 166 individuals including healthy controls and five group of patients with: type 1 diabetes mellitus with fading insulitis (T1D), type 1 diabetes mellitus with ongoing insulitus (T1D/INS), type 2 diabetes mellitus (T2D), untreated celiac disease (CLD), and celiac disease on gluten-free diet (CLD-GFD). We tested the marker of epithelial apoptosis - cytokeratin 18...
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Clinical and genetic predictors of drug dependency in inflammatory bowel disease
Ďuricová, Dana ; Lukáš, Milan (advisor) ; Keil, Radan (referee) ; Špičák, Julius (referee)
IN ENGLISH Drug dependency in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), is a specific disease phenotype which determines disease prognosis and hence may be used as a prognostic marker for treatment management. Drug dependency in IBD has been well described in corticosteroid treatment and recently also in infliximab (IFX) therapy. The aims of this thesis were: 1) to assess the occurrence of IFX dependency in paediatric and adult patients with CD; further to search for clinical and genetic predictors of IFX outcome and to evaluate the impact of IFX dependency on surgical rate; 2) to assess in CD patients the outcome of the first course of 5-ASA monotherapy with emphasis on 5-ASA dependency and to define clinical predictors of 5-ASA treatment outcome. We found that 66% of children and 29% of adults with CD became IFX dependent. The high frequency in paediatrics is in agreement with previously published studies, while the finding in adult patients indicates a lower rate of IFX dependency in the only study to date. Perianal disease and no bowel surgery prior to IFX start were predicative of IFX dependency in paediatric patients. In adult cohort, 2 genetic variants LTA c.207 A>G and CASP9 c.93 C>T were associated with IFX outcome, whereas no relevant clinical...
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Pathophysiology of colorectal cancer. Colorectal cancer screening effect and the role of microRNA in pathophysiology of colorectal cancer.
Král, Jan ; Špičák, Julius (advisor) ; Keil, Radan (referee) ; Mohelníková Duchoňová, Beatrice (referee)
Colorectal cancer is a serious malignant disease with an incidence of over 1.8 million new cases per year worldwide. There are about 8 000 patients diagnosed with CRC in the Czech Republic each year, and about half of them present with an advanced disease. Screening program identifies patients in the early stages of CRC resulting in overall better prognosis and survival. There is also a lack of biomarkers of early CRC detection and of response to treatment. The first aim of our project was to conduct a national multicentre prospective observational study to evaluate the impact of CRC screening within the framework of a Czech population screening programme. Between March 2013 and September 2015, a total of 265 patients were enrolled in 12 centres across the Czech Republic. Patients were divided into screening and control groups and compared for pathology status and clinical characteristics. Screening was defined as a primary screening colonoscopy or a colonoscopy after a positive FOBT in an average-risk population. The distribution of CRC stages was significantly favourable in the screening group compared with the control group (stages 0, I and II, 63% versus 43.3%; p <0.001). The presence of distant (M1) and local metastases (N1 and N2) was significantly less prevalent in the screening group (0%,...
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Incidence of multiple sclerosis in patiens with inflammatory bowel diseases (IBD)
Ročková, Petra ; Keil, Radan (advisor) ; Hep, Aleš (referee) ; Zádorová, Zdeňka (referee)
Ročková Summary Inflammatory bowel diseases (IBD) - Crohn's disease (CD) and ulcerative colitis (UC) are associated with various extraintestinal manifestations (EM). These manifestations may involve virtually any organ system. Neurological manifestations are not regarded as very common, but they are probably underdiagnosed. Patients with IBD have higher risk of developing multiple sclerosis (MS) regardless of therapy manner they use. There are quite a lot of publications describing relationship between developing multiple sclerosis and therapy with monoclonal antibody against tumor necrosis alpha (anti TNF-α). However, it remains to be shown whether anti-TNF-alpha itself causes MS or merely acts as a trigger, exacerbating preexisting subclinical CNS damage during chronic anti- TNF-α treatment. Majority of published cases support the second possibility. These results let us to define a hypothesis, that preselection of patients with IBD without any preclinical signs of demyelination before the initiation of anti TNF- a therapy may improve patient safety. The aim of our project was to develop neurological and magnetic resonance (MRI) screening of patients with IBD before anti TNF- α therapy initiation and subseqently exclusion of patients wth high risk of developing MS. The second aim was to follow up on the...
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Inflammatory bowel diseases in pregnancy
Koželuhová, Jana ; Matějovič, Martin (advisor) ; Keil, Radan (referee) ; Hep, Aleš (referee)
Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, can affect mainly young people in their reproductive years. IBD therefore has a major impact on patient's family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal disease control and drug safety. An unanswered question is the impact of the course of childbirth in women with preexisting IBD regarding anal sphincter function and development of anal or fecal incontinence. To this date there aren't any clinically relevant guidelines for managing childbirth in women with IBD. From gastroenterologist's point of view, a clear indication for Caesarean section (CS) is active perianal disease or active IBD with rectal involvement, a relative indication for CS is ileal-pouch-anal anastomosis (IPAA) or ileal-rectal anastomosis in women after colectomy for refractory UC. Studies have shown a lack of knowledge among both patients and physicians regarding reproductive issues in IBD. The main aim of this thesis was first to assess risk of vaginal delivery in development of anal incontince, second to evaluate the safety of biologic therapy during pregnancy in women with inflammatory bowel disease. We present a study researching the morbidity of children born to mothers treated with biological...
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