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Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine
Klusová, Natálie ; Beránek, Martin (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Natálie Klusová Supervisor: prof. PharmDr. Martin Beránek, Ph.D. Consultant: RNDr. Milada Šírová, Ph.D. Title of diploma thesis: Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine The diploma thesis is focused on the anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine (Gem). We investigated the effects of four polymer conjugates (P-Gem1-P-Gem4), which had similar molecular weight and carried approximately the same amount of the drug. The only difference were the used spacers for Gem linkage. We used the following spacers: β-Alanin (P-Gem1); glycyl-phenylalanyl- leucyl-glycyl (P-Gem2); aminocaproic acid (P-Gem3); valeric acid (P-Gem4). Based on the assessed IC50 values for tumor cell lines 4T1, LL2, Panc02, MiaPaca2 and Panc1 the samples were divided into two groups: a) samples with quick rate of Gem release (P- Gem1, P-Gem2); b) samples with slow rate of Gem release (P-Gem3, P-Gem4). The in vivo stability of the conjugate affects systemic toxicity and anti-tumor activity, which was proven by the experiment performed on BALB/c mice bearing murine mammary carcinoma cells (4T1). We enrolled significant...
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New fungal fucosidases and their synthetic potential
Glozlová, Michaela ; Beránek, Martin (advisor) ; Matoušková, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Michaela Glozlová Supervisor: prof. PharmDr. Martin Beránek, Ph.D. Consultants: doc. RNDr. Pavla Bojarová, Ph.D., Mgr. Pavlína Nekvasilová Title of diploma thesis: New fungal fucosidases and their synthetic potential The literary research focuses on α-L-fucosidases, their occurrence, functions, and use in the synthesis of fucosylated compounds, which were also a part of the research, particularly their presence in the human body and involvement in pathological conditions. Furthermore, it explores the oligosaccharides found in human milk, their impact on infant health, and their synthesis, which can be facilitated through the use of α-L-fucosidases. The experimental section involves the analysis of a library of filamentous fungi with the aim of identifying a representative strain with α-L-fucosidase activity towards pNP-α-L-fucoside. Recombinant α-L-fucosidases were selected based on searches in genetic databases and prepared. The feasibility of their production in Pichia pastoris and Escherichia coli was tested, and the produced enzymes were purified by ion exchange chromatography, characterized and their regioselectivity and synthetic potential for the synthesis of fucosylated...
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New fungal fucosidases and their synthetic potential
Glozlová, Michaela ; Beránek, Martin (advisor) ; Matoušková, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Michaela Glozlová Supervisor: prof. PharmDr. Martin Beránek, Ph.D. Consultants: doc. RNDr. Pavla Bojarová, Ph.D., Mgr. Pavlína Nekvasilová Title of diploma thesis: New fungal fucosidases and their synthetic potential The literary research focuses on α-L-fucosidases, their occurrence, functions, and use in the synthesis of fucosylated compounds, which were also a part of the research, particularly their presence in the human body and involvement in pathological conditions. Furthermore, it explores the oligosaccharides found in human milk, their impact on infant health, and their synthesis, which can be facilitated through the use of α-L-fucosidases. The experimental section involves the analysis of a library of filamentous fungi with the aim of identifying a representative strain with α-L-fucosidase activity towards pNP-α-L-fucoside. Recombinant α-L-fucosidases were selected based on searches in genetic databases and prepared. The feasibility of their production in Pichia pastoris and Escherichia coli was tested, and the produced enzymes were purified by ion exchange chromatography, characterized and their regioselectivity and synthetic potential for the synthesis of fucosylated...
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Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine
Klusová, Natálie ; Beránek, Martin (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Natálie Klusová Supervisor: prof. PharmDr. Martin Beránek, Ph.D. Consultant: RNDr. Milada Šírová, Ph.D. Title of diploma thesis: Anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine The diploma thesis is focused on the anti-tumor and immunomodulatory effect of polymer conjugates based on HPMA carrying gemcitabine (Gem). We investigated the effects of four polymer conjugates (P-Gem1-P-Gem4), which had similar molecular weight and carried approximately the same amount of the drug. The only difference were the used spacers for Gem linkage. We used the following spacers: β-Alanin (P-Gem1); glycyl-phenylalanyl- leucyl-glycyl (P-Gem2); aminocaproic acid (P-Gem3); valeric acid (P-Gem4). Based on the assessed IC50 values for tumor cell lines 4T1, LL2, Panc02, MiaPaca2 and Panc1 the samples were divided into two groups: a) samples with quick rate of Gem release (P- Gem1, P-Gem2); b) samples with slow rate of Gem release (P-Gem3, P-Gem4). The in vivo stability of the conjugate affects systemic toxicity and anti-tumor activity, which was proven by the experiment performed on BALB/c mice bearing murine mammary carcinoma cells (4T1). We enrolled significant...
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Single nucleotide polymorphisms in the pathogenesis of mature B-cell neoplasms
Wagnerová, Andrea ; Szotáková, Barbora (advisor) ; Beránek, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Andrea Wagnerová Supervisor: prof. Ing. Barbora Szotáková, Ph.D., Mgr. Kateřina Černá Pilátová, Ph.D. Title of diploma thesis: Single nucleotide polymorphism in the patogenesis of mature B-cell neoplasms Chronic lymphocytic leukemia (CLL) is a disease characterized by clonal proliferation of B-lymphocytes. CLL is a lymphoproliferative disorder with a number of defined risk factors, but its etiopathogenesis remains unresolved to some degree. Over the past 10-15 years, there have been several studies that primarily suggest a genetic predisposition to the disease. The influence of external factors on the etiology of CLL has not been demonstrated. There is also a defined asymptomatic condition associated with CLL called monoclonal B-lymphocytosis, which is often referred to as a precursor of CLL. Immunophenotyping of lymphocytes by flow cytometry was performed in subjects of the control group (100 subjects) and the CLL/MBL group (patients diagnosed with CLL or MBL, 50 subjects). All subjects in the control and CLL/MBL groups were screened for selected genetic polymorphisms (rs17483466, rs735665, rs7176508, rs872071, rs13397985) that have been associated with the occurrence of CLL and MBL in other...
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Single nucleotide polymorphisms in the pathogenesis of mature B-cell neoplasms
Wagnerová, Andrea ; Szotáková, Barbora (advisor) ; Beránek, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Andrea Wagnerová Supervisor: prof. Ing. Barbora Szotáková, Ph.D., Mgr. Kateřina Černá Pilátová, Ph.D. Title of diploma thesis: Single nucleotide polymorphism in the patogenesis of mature B-cell neoplasms Chronic lymphocytic leukemia (CLL) is a disease characterized by clonal proliferation of B-lymphocytes. CLL is a lymphoproliferative disorder with a number of defined risk factors, but its etiopathogenesis remains unresolved to some degree. Over the past 10-15 years, there have been several studies that primarily suggest a genetic predisposition to the disease. The influence of external factors on the etiology of CLL has not been demonstrated. There is also a defined asymptomatic condition associated with CLL called monoclonal B-lymphocytosis, which is often referred to as a precursor of CLL. Immunophenotyping of lymphocytes by flow cytometry was performed in subjects of the control group (100 subjects) and the CLL/MBL group (patients diagnosed with CLL or MBL, 50 subjects). All subjects in the control and CLL/MBL groups were screened for selected genetic polymorphisms (rs17483466, rs735665, rs7176508, rs872071, rs13397985) that have been associated with the occurrence of CLL and MBL in other...
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Hereditary hemochromatosis - Importance of molecular biology analysis of S65C mutation in HFE gene
Putzová, Daniela ; Beránek, Martin (advisor) ; Šimůnek, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Daniela Putzová Supervisor: Doc. PharmDr. Martin Beránek, Ph.D. Title of diploma thesis: Hereditary hemochromatosis - Importance of molecular biology analysis of S65C mutation in HFE gene Background: The aim of this work was to establish an investigative method PCR-RFLP for the detection of the mutation S65C in HFE gene which can be used for an analysis of real clinical samples and for determination of their S65C mutation occurrence. Methods: In this study, 140 samples from patients were analyzed (68 % (n = 95) of samples from men, 32 % (n = 45) from women, in the age from 20 to 83 years) for the presence of the mutation S65C in HFE gene using PCR-RFLP method. For amplification of required segments of HFE gene, primers (5'- ACA TGG TTA AGG CCT GTT GC - 3', 5'- GCC ACA TCT GGC TTG AAA TT - 3') were used. The enzyme HInfI was used for the restriction analysis. Results: S65C mutation allelic frequency was determined as 1.8 % in this cohort of patients. Five patients (3.6 %) were heterozygous for the mutation S65C; two of them (1.4 %) were identified as C282Y/S65C compound heterozygotes. Conclusions: PCR - RFLP procedure was successfully established for the determination of S65C mutation...
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