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Carotuximab effects on inflammation during liver fibrosis development
Sharif, Navid ; Rathouská, Jana (advisor) ; Němečková, Ivana (referee)
Chronic liver inflammation is a process that results in the distortion of the liver parenchyma. Constant damage caused by inflammation would lead to formation of fibrotic tissue which can impair the normal liver physiology. Liver fibrosis is one of the common causes of morbidity and mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) is a pathological state that is characterised by excessive accumulation of lipid in the hepatocytes (hepatic steatosis) which can trigger the inflammatory response in the liver. Carotuximab (TRC 105) is a monoclonal antibody that has been used for the treatment of a number of cancers, including hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of carotuximab in liver inflammation in a mouse model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis. Eighteen 3-month-old C57BL/6 male mice were recruited in this study. They were divided into three groups: control group (n=6) - fed chow diet for the period of 4 weeks, DDC group (n=6) - fed DDC diet for the period of 4 weeks, DDC group treated with carotuximab (DDC+TRC, n=6) - fed DDC diet for the period of 4 weeks and to that TRC 105 (15mg/kg) was administered. The impact of the diet and TRC 105 on mouse weight, as well as the effect on liver damage (levels...
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Carotuximab effects on inflammation during liver fibrosis development
Sharif, Navid ; Rathouská, Jana (advisor) ; Němečková, Ivana (referee)
Chronic liver inflammation is a process that results in the distortion of the liver parenchyma. Constant damage caused by inflammation would lead to formation of fibrotic tissue which can impair the normal liver physiology. Liver fibrosis is one of the common causes of morbidity and mortality worldwide. Non-alcoholic fatty liver disease (NAFLD) is a pathological state that is characterised by excessive accumulation of lipid in the hepatocytes (hepatic steatosis) which can trigger the inflammatory response in the liver. Carotuximab (TRC 105) is a monoclonal antibody that has been used for the treatment of a number of cancers, including hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of carotuximab in liver inflammation in a mouse model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis. Eighteen 3-month-old C57BL/6 male mice were recruited in this study. They were divided into three groups: control group (n=6) - fed chow diet for the period of 4 weeks, DDC group (n=6) - fed DDC diet for the period of 4 weeks, DDC group treated with carotuximab (DDC+TRC, n=6) - fed DDC diet for the period of 4 weeks and to that TRC 105 (15mg/kg) was administered. The impact of the diet and TRC 105 on mouse weight, as well as the effect on liver damage (levels...
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The role of ADAM17 and other metalloproteases in liver pathological processes
Žbodáková, Oľga ; Sedláček, Radislav (advisor) ; Muchová, Lucie (referee) ; Stříšovský, Kvido (referee)
1 Abstract Liver fibrosis is a condition described by extensive accumulation of scar tissue in the liver. With further progression, it leads to cirrhosis or even to hepatocellular carcinoma. Liver fibrosis accompanies every chronic liver disease and its prevalence in adult European population is estimated to be around 4%. During my dissertation work, I studied the function of three members of Metzincin family of metalloproteinases - ADAM17, ADAM10 and MMP-19, in liver fibrosis and liver regeneration using mouse genetic models. ADAM17 and ADAM10 are important regulators of signalling pathways which are involved in immune response as well as differentiation. Both proteases are able to cleave ectodomains of their substrates from cell membrane, affecting bioavailability of ligands and functionality of receptors. Several of their substrates are involved in liver pathologies. MMP-19 on the other hand, is a metalloprotease mainly involved in extracellular matrix cleavage, important process in fibrosis development, as well as resolution of fibrosis. Our results demonstrate that ablation of ADAM10 results in increased susceptibility to liver fibrosis in mice, both spontaneous and toxin induced. ADAM10 deficiency affected biliary epithelium, as we detected higher markers of biliary damage in serum of ADAM10 deficient...
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New markers of liver fibrosis
Skřebská, Lenka ; Čepová, Jana (advisor) ; Průša, Richard (referee)
This material is talking about problems of liver fibrosis. It Is a very fundamental liver's disease which is bringing about a chronic harm of the liver's tissue. An effect of it is a process defect of fibrogenesis and fibrolysis which has to be balanced. A diagnosis of liver fibrosis on time is important for start an efficient therapy. At this time we are getting diagnosis of the liver fibrosis by liver's biopsy which is bringing many risks for patients and it is disadvantageus for them. This situation is running us to search for a new non-invasive methods. It is a lot of calculations they are using a specific and unspecific markers to determine fundamental measures of specific fibrotisation and nonspecific too. A goal of this work it is to get a contrast between a new automatic imunochemicle ELF test which is using specific markers for the liver fibrosis and using calculations APRI and the Hepascore until now. Powered by TCPDF (www.tcpdf.org)
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