National Repository of Grey Literature 96 records found  previous11 - 20nextend  jump to record: Search took 0.01 seconds. 
Photochemical internalization of saporine by phthalocyanine photosensitisers
Vlková, Kateřina ; Macháček, Miloslav (advisor) ; Kozlíková, Magdaléna (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Student: Bc. Kateřina Vlková Supervisor: RNDr. Miloslav Macháček, Ph.D. Consultant: Mgr. Monika Rohlíčková Title of the diploma thesis: Photochemical internalization of saporine by phthalocyanine photosensitisers The application of therapeutic macromolecules is often affected by limited cellular uptake and lysosomal degradation, thus failing to reach their intracellular targets. Their cellular uptake can be increased through photochemical internalization. Photochemical internalization uses photosensitive agents that localize in the membranes of endosomes and induce drug release upon exposure to light. This diploma thesis is focused on the evaluation of the effect of saporin in the combination with non-symmetrical photosensitizers on HeLa cell line using photochemical internalization. Effect of various concentrations of these compounds on the viability of tumour cells was evaluated. Two approaches to deliver the energy from light were compared as well: before and after the administration of saporin (i.e., "light-before" and "light-after" approach). From obtained data, it is evident that saporin (administered alone) does not significantly reduce the viability of HeLa cells, even though it was applied in a...
Cell senescence in aging, cell stress and chemoresistance
Andrašková, Tereza ; Vokřál, Ivan (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Tereza Andrašková Supervisor: Prof. Dr. Alexandra K. Kiemer and PharmDr. Ivan Vokřál, PhD. Title of diploma thesis: Cell senescence in aging, cell stress, and chemoresistance The process of biological aging is connected with a loss of tissue function leading to the various pathologies, including cardiovascular diseases and cancer. Cellular senescence, the phenomenon characterized by permanent cell cycle arrest triggered by endogenous or exogenous stress plays a significant role in age-related metabolic diseases development. Senescent endothelial cells have been found in atherosclerotic plaque and due to the inflammation-inducing factors participate to its progression. Nevertheless, by triggering antiproliferative reaction, senescence may also have a potential as a cancer suppressor. The aim of this work was to establish assay determining senescence with different origins and subsequently, to analyse compounds with a potential to reduce H2O2-induced senescence as well as factors, which may be altered in the senescent phenotype. Senescence-associated β- galactosidase (SA-β-gal) assay in primary human endothelial cells revealed the senescence-inhibiting ability of statins and curcumin in contrast...
Characterization of different differentiation protocols of H9c2 cardiomyoblasts
Gardianová, Anna ; Jirkovský, Eduard (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Gardianová Supervisor: PharmDr. Eduard Jirkovský, Ph.D. Title of diploma thesis: Characterization of different differentiation protocols of H9c2 cardiomyoblasts Cell differentiation is a common process in the development of multicellular organisms leading to an alteration of cell's appearance and function. The process of differentiation plays a significant role in the reparation of damaged tissues too. Some chemicals may have negative effects on these processes and therefore affect human health. This thesis focuses on characterization of differentiation processes of H9c2 cell line using various published differentiation protocols, and to describe changes over time in the morphology (occurrence of multinucleated and elongated cells) and mRNA expression of selected markers typical for the cardiac (cTnT, Hand2, GATA4) or skeletal (myogenin) muscle phenotype. We monitored the process of the differentiation for 15 days and the individual protocols differed by the addition of fetal bovine serum (FBS, 1 % or 10 %) and all-trans- retinoic acid (ATRA, 10 nmol/L) to the growth medium Dulbecco's Modified Eagle's Medium. From what we have observed, the results show that all of the utilized protocols...
Monitoring the antioxidant activity of newly synthesized potential acetylcholinesterase modulators
Keratová, Žaneta ; Macháček, Miloslav (advisor) ; Kobrlová, Tereza (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Žaneta Keratová Supervisor: RNDr. Miloslav Macháček, Ph.D. Consultant: RNDr. Ľubica Múčková, Ph.D. Title of diploma thesis: Monitoring the antioxidant activity of newly synthesized potential acetylcholinesterase modulators. The theoretical part of the diploma thesis focuses on the characteristics of oxidative stress (OS) and antioxidant protection of the organism. In the next part, neurodegenerative diseases and the importance of OS in their development are discussed in detail. In the experimental part, the cytotoxicity of new potential acetylcholinesterase modulators was evaluated using the neuroblastoma cell line SH-SY5Y. The cytotoxicity of the compounds, expressed as IC50, was measured by a colorimetric method using the tetrazolium salt (MTT). This method was also used to determine the maximum tolerated concentration (MTC). These values were subsequently validated by measuring the apoptotic profile of cells in a physiological environment (without OS) and hydrogen peroxide (H2O2)-induced OS using microcapillary flow cytometry. The results showed that the compounds did not induce any statistically significant change in the distribution of cells in each population. Subsequently, the antioxidant...
Study of migration of cells affected by sulfur mustard
Mojská, Mária ; Macháček, Miloslav (advisor) ; Fikrová, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mária Mojská Supervisor: RNDr. Miloslav Macháček, PhD. Consultant: Mgr. Petr Jošt, PhD. Title of diploma thesis: Study of the migration of cells affected by sulfur mustard Sulfur mustard is a highly toxic chemical agent. From the point of view of toxicology, it is classified as a blistering agent, and its use is prohibited by the Chemical Weapons Convention. However, this substance has been used in several armed conflicts and terrorist attacks in the past. When it comes in contact with human skin, it produces typical blisters filled with a yellowish exudate. Sulfur mustard has cytotoxic and cytostatic effects on living tissue, and therefore the treatment of such lesions is extremely difficult. This thesis is focused on the in vitro evaluation of the possibility of employing growth factors IGF, KGF, and EGF in the wounding process of sulfur mustard-damaged tissue. The effect of these growth factors on collective migration of HaCaT keratinocytes and HDFa skin fibroblasts under in vitro conditions was evaluated using the "scratch wound healing assay" method. Our results show that the toxic effects of sulfur mustard inhibit cell migration to such an extent that the positive effect of the growth...
Isocitrate dehydrogenase 2 inhibitor enasidenib synergizes daunorubicin cytotoxicity by targeting aldo-keto reductase 1C3.
Haddad, Andro ; Wsól, Vladimír (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Andro Haddad Supervisor: prof. Ing. Vladimír Wsól, Ph.D. Consultant: Anselm Morell García, Ph.D. Title of diploma thesis: ISOCITRATE DEHYDROGENASE 2 INHIBITOR ENASIDENIB SYNERGIZES DAUNORUBICIN CYTOTOXICITY BY TARGETING ALDO-KETO REDUCTASE 1C3 Treatment with anthracyclines is crucial in treating several oncologic disorders. However, several molecular mechanisms hinder the effectivity of anthracyclines, which is a significant obstacle in cancer therapy. Carbonyl reducing enzymes (CREs), a type of NAD(P)H-dependent oxidoreductase, contribute to anthracycline resistance by reducing these drugs to fewer active alcohols. These enzymes also play a role in the proliferation and differentiation of cancer cells, leading to increased tumour aggressiveness. Therefore, targeting these enzymes is essential for effective anticancer therapy. This study aimed to uncover the potential off-targets of the isocitrate dehydrogenase (IDH) inhibitor enasidenib (ENA) that could counteract the resistance to anthracycline, specifically in relation to the detoxification role of CREs. For this, we screened the ability of ENA to inhibit different recombinant CREs that can reduce daunorubicin (Daun) to daunorubicinol...
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...
Peripherally substituted subphthalocyanines for photodynamic therapy with benzocrown or tyrosine methyl ester as axial ligands
Hlbočanová, Ingrid ; Macháček, Miloslav (advisor) ; Šimůnek, Tomáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Science Candidate: BSc. Ingrid Hlbočanová Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Peripherally substituted subphtalocyanines for photodynamic therapy with benzocrown or tyrosine methyl ester as axial ligands Tumor diseases are slowly but surely becoming the most widespread disease in the world. Malignant conditions affect a wide range of people who inherited a predisposition to the disease genetically, or were influenced by environmental factors. However, expensive therapy is a problem not only in developed countries, but especially in third world countries. Financial aspect and availability are only part of the problem. Early diagnosis, prevention before the onset of this type of disease and effective therapy are the key elements to succesfull treatment. Due to the high prevalence and mortality associated with malignant diseases, which are increasing every year, great efforts are devoted to the prevention of these diseases and the correct and timely diagnosis associated with a healthy lifestyle. Great attention is also paid to the research and development of new and effective anti-tumor drugs and therapeutic approaches. One such modern and promising method is photodynamic therapy (PDT)....
Study of the effectiveness of the original amphiphilic (aza)phthalocyanines bearing permanent positive charge
Rohlíčková, Monika ; Macháček, Miloslav (advisor) ; Pejchal, Jaroslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Monika Steklá Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Study of the effectiveness of the original amphiphilic (aza)phthalocyanines bearing permanent positive charge The neoplastic diseases are nowadays one of the most common reason of death in developed countries. That is the reason why is a great attention dedicated to the development of new methods for the treatment these diseases. One of such modern methods is the photodynamic therapy. This is a very selective, minimally invasive method with a minimum of side effects. The principle of this type of therapy is application of separately inactive compound, called photosensitizer, followed by exposure to light with suitable wavelength in the presence of molecular oxygen. Therefore, the photodynamic therapy needs three basic components: the photosensitizer, light and oxygen. Each of those components are non-toxic, when they occur separately. However, their combination lead to the inception of the photochemical reaction in which are generated reactive oxygen species, especially singlet oxygen. These very reactive molecules damage target cells, which subsequently die via apoptosis or necrosis. As has been said, the main...

National Repository of Grey Literature : 96 records found   previous11 - 20nextend  jump to record:
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