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Biodegradable high molecular weight polymeric conjugates for efficient delivery of cytostatic drugs into solid tumors.
Černý, Viktor ; Kovář, Marek (advisor) ; Palich Fučíková, Jitka (referee)
Cancer remains one of the most pressing issues of contemporary science and medicine. Incidence of malignant diseases is rising worldwide and they represent a major problem for the society due to both economic and ethical issues they cause. Although the progress in cancer biology, therapy and immunology has led to the introduction of many novel therapeutic protocols, approaches and drugs with specificity defined on a molecular level into clinical practice, many malignancies retain their poor prognosis. Therefore, intense research into new ways to increase our therapeutic options is warranted. Unfortunately, bringing a completely novel drug into clinical use takes extremely high amounts of time and money and entails a high risk of failure. Therefore, a promising approach has been recently adopted which lies in repurposing compounds already used in human medicine for cancer treatment. This form of research can advance through clinical trials for a new indication much easier, faster and cheaper than researching completely new drugs. The aim of this study was to examine the anticancer potential of one such drug, mebendazole. An anthelminthic from the family of benzimidazoles, mebendazole has been in common clinical use from the 1970s and is marked by its low toxicity as well as its very low solubility....
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Impact of stable ghrelin receptor agonists and antagonists on food intake regulation
Holubová, Martina
The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS- R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum...
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Impact of stable ghrelin receptor agonists and antagonists on food intake regulation
Holubová, Martina ; Maletínská, Lenka (advisor) ; Kopecký, Jan (referee) ; Sobotka, Luboš (referee)
The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS-R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum in...
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Animal models of obsessive-compulsive disorder
Radostová, Dominika ; Stuchlík, Aleš (advisor) ; Kopřivová, Jana (referee)
Obsessive compulsive disorder (OCD) is a widespread chronic psychiatric disorder, presenting itself with a wide range of symptoms. The heterogenity of OCD manifestations hinders the resarch and the interpretation of acquired results. Clinical studies are complemented by new insights collected from studies of animal models of OCD, which are nowdays integral to the resarch of OCD. During the course of the resarch many genetic, behavioral and pharmacologic animal models were developed. Number of works were not worked on further, however some models had been studied for a long time. Evaluation of individual models is dependant on many factors, and therefore the degree of validity and suitability for resarch differs between them. Powered by TCPDF (www.tcpdf.org)
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