National Repository of Grey Literature 14 records found  1 - 10next  jump to record: Search took 0.00 seconds. 
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...
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%,...
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...
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...
Fanconi anemia and pancreatic cancer
Hucl, Tomáš ; Špičák, Julius (advisor) ; Nečas, Emanuel (referee) ; Vodička, Pavel (referee)
Inactivation of the Fanconi anemia (FA) pathway occurs in diverse human tumors including pancreatic cancer and renders those tumors hypersensitive to DNA interstrand-cross-linking agents (ICL). How to treat specificly pancreatic and other cancers harboring FA mutations has recently raised great interest, yet preclinical studies have been hampered by the lack of well-controlled human cancer models. We endogenously disrupted FANCC and FANCG in an adenokarcinoma cell line and observed a typical phenotype of FA pathway deficiency (abrogation of FANCD2 monoubiquitination; chromosomal instability, G2M arrest and decreased proliferation upon treatement with ICL, spontaneous chromosomal breakage). Homozygous deletion was achieved for FANCC and FANCG but not for FANCD2 and BRCA2/FANCD1 in RKO cells, suggesting a detrimental phenotype. It provided direct evidence for the paradoxical assumption that their inactivation could be predominantly selected against in cancer cells. Using high-throughput screening, we assessed the growth of our isogenic FANCC and FANCG cells upon treatment with 880 active drugs and 40 000 diverse compounds. The compound having the stronges effect, named 80136342, had a distinct mechanism of action from that of ICL agents. When applied in combination with ICL agents, 80136342 had at least...
Participation of some mechanisms of mucosal immunity in the pathogenesis of Crohn's disease and ulcerative colitis
Drastich, Pavel ; Špičák, Julius (advisor) ; Prokešová, Ludmila (referee) ; Nečas, Emanuel (referee)
In our study we contributed to clarifying the important role of mucosal immunity system in the pathogenesis of inflammatory bowel disease. We have shown that upregulated expression of TLR2, TLR4 and CD14 in patients with Crohn disease (CD) and ulcerative colitis (UC) reflects the consequences of the interaction of intestinal epithelial cells and macrophages in the lamina propria with intestinal microbiota. TLR2 expression in the terminal ileum is significantly increased regardless of whether assessed in active or remission stage of UC. Possible explanation of this unexpected finding could be that this upregulation reflects the activation of innate immunity cells by as yet unknown bacterial components also present in the proximal part of the gut of UC patients. Thus, it seems that the terminal ileum can sensitively react to "potentially pathogenic" but still undiscovered components of microbiota by immological mechanisms impairing the homeostasis in colonic tissue. Furthermore we showed that the mucosal interleukin- 6 (IL-6) could be expressed and produced in different parts of the intestine with different intensity. Unexpected high IL-6 mucosal level in the rectal mucosa without any signs of macroscopic inflammation could reflect the susceptibility of this area to perianal and perirectal disease and fistula...

National Repository of Grey Literature : 14 records found   1 - 10next  jump to record:
See also: similar author names
1 Špičák, Jakub
2 Špičák, Jan
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