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In vitro saturation study of radiolabelled monoclonal antibody carotuximab
Sladká, Anežka ; Bárta, Pavel (advisor) ; Nový, Zbyněk (referee)
v anglickém jazyce Charles University Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Student: Anežka Sladká Supervisor: Mgr. Pavel Bárta, Ph.D. Thesis title: In vitro saturation study of radiolabeled monoclonal antibody carotuximab Angiogenesis, or the formation of new blood vessels from existing ones, is currently one of the processes targeted by cancer therapy, as the formation of new blood vessels is a prerequisite for successful tumor growth and eventual expansion in the body in the form of metastasis. One of the receptors involved in signalling leading to angiogenesis is endoglin (CD105). This receptor is also targeted by the chimeric monoclonal antibody carotuximab. The aim of this thesis was to perform indirect labelling of the monoclonal antibody carotuximab with the radionuclide gallium-67 using the bifunctional chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). During the labelling process, the NODAGA:carotuximab molar ratio was optimized (1:20, 1:50 and 1:100). The prepared radiopharmaceutical [67 Ga]Ga-NODAGA-carotuximab was subsequently determined for its radiochemical purity by HPLC with radiometric detection. This was followed by in vitro binding experiments on human renal tumor cell culture involving internalization,...
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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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Immunohistochemical analysis of TRC105 effects on the liver fibrosis
Hamerníková, Veronika ; Němečková, Ivana (advisor) ; Svobodová, Zuzana (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department: Department of Biological and Medicinal Sciences Studijní obor: Pharmacy Author: Veronika Hamerníková Supervisor: RNDr. Ivana Němečková, Ph.D. Title of master thesis: Immunohistochemical analysis of TRC105 effects on the liver fibrosis The subject of this diploma thesis was the analysis of the expression of liver fibrosis biomarkers in mice liver. The aim of our work was to test the effect of the drug TRC105 (carotuximab) on a fibrotic liver model after 4 weeks of DDC (3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-colidine) administration. Collagen deposition and expression of α-SMA, GFAP and endoglin were examined and compared. Animals were divided into 3 groups: control group (n=6), DDC group (n=6) and TRC105 group (n=6). The control group was fed a standard diet, while the DDC and the TRC105 groups were fed a diet with 0.1% DDC. Physiological solution was administered to the control and DDC groups while carotuximab was administered to the TRC105 group. The analysis of fibrosis biomarker expression was then performed on fixed liver sections. Collagen expression was evaluated by Picro-Sirius Red staining and α-SMA, GFAP and endoglin expression by immunohistochemistry with fluorescence imaging. Histological staining of collagen...
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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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