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Study of the cytotoxicity of selected chemotherapeutics for the treatment of leukemia in human tumor cell lines.
Štorkánová, Jesika ; Novotná, Eva (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Jesika Štorkánová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Study of the cytotoxicity of selected chemotherapeutics for the treatment of leukemia in human tumor cell lines Leukemia represents a diverse group of malignant diseases with a hematopoietic disorder with different prognoses. As the incidence of patients with leukemia is increasing, is an effort to establish the treatment that will lead to successful therapy. One of the basic approaches to the treatment of leukemias is chemotherapy. Today it is known that the effectiveness of chemotherapy is influenced by a number of factors which can significantly affect the treatment strategy and thus decide on the outcome of the treatment itself. An important approach in chemotherapy is the selection of cytostatics with maximum efficacy for oncological disease and elimination cytostatics to which the cells are resistant based on the findings in in vitro conditions. The aim of this diploma thesis was to determine the inhibitory effects of in vitro selected chemotherapeutics in cell tumor lines. For determine the inhibitory effect, HCT116, HepG2 and HL-60 cell lines were selected using a colorimetric method based on the...
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Effect of selected cytostatics for the treatment of leukemia on the activity of human carbonyl reducing enzymes
Šmídlová, Monika ; Novotná, Eva (advisor) ; Wsól, Vladimír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical sciences Candidate: Bc. Monika Šmídlová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Effect of selected cytostatics for the treatment of leukemia on the activity of human carbonyl reducing enzymes Key words: reductases, leukemia, cytostatics, inhibition Anthracycline antibiotics, especially daunorubicin, are widely used for the treatment of acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Although the efficacy of these drugs is high, treatment is still limited due to cardiotoxicity and tumor cell resistance to anthracyclines. Mechanisms that contribute to the formation of anthracycline resistance include metabolic biotransformation (reduction) to less efficient secondary alcohols. The reduction is calatyzed by carbonyl reducing enzymes belonging to aldo-keto reductase (AKR) and short chain dehydrogenase/reductase (SDR) superfamilies. The discovery of AKR and SDR inhibitors could help to overcome anthracycline resistance and also reduce cardiotoxicity caused by these drugs. The aim of the diploma thesis was to find out whether all-trans-retinoic acid, cyclophosphamide, cytarabine, cladribine and prednisolone are able to inhibit anthracycline reductases AKR1A1, AKR1B10, AKR1C3, AKR7A2...
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Advances in chemotherapy and novel antitumor drugs
Kraus, Michal ; Kovář, Marek (advisor) ; Koudelková, Lenka (referee)
Cancer is among the leading causes of death worldwide. While some types of cancer became almost entirely curable, majority of malignant tumors are still potentially deadly diseases due to unsensitivity of tumors to conventional chemotherapy or diversity of cancer cells within the tumor and subsequent development of resistance. The underlying mechanism of action of conventional antitumor drugs is mostly related to cell division. DNA damage, inhibition of DNA synthesis and repair or disrupted formation of mitotic spindle are the most common mechanisms. However, it implies that most of the drugs are cytotoxic for rapidly dividing cells in general which results in variety of undesirable side effects for patients. Search for novel anticancer drugs targeting cancer cells more selectively has been point of interest of researchers for decades. Hundreds of new potential anticancer drugs are being described every year, some posessing so far unrecognized mechanisms of action. Process called drug repurposing examines drugs that have already been approved for clinical use in other than oncology field and results into discovering of interesting "novel" anticancer agents. Another general trend is represented by shift towards development of targeted therapy which is slowly replacing traditional cytotoxic...
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The role of biotransformation enzymes in the resistance of cancer cells against standard cytostatics
Giannitsi, Anna ; Hofman, Jakub (advisor) ; Čečková, Martina (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Giannitsi Supervisor: RNDr. Jakub Hofman, Ph.D Title of diploma thesis: The role of biotransformation enzymes in the resistance of cancer cells against standard cytostatics Drug resistance is currently one of the major problems of chemotherapy. Tumor cells are able to defend themselves against the effect of cytostatic drugs due to various mechanisms which leads to a failure of anticancer therapy. The effort to describe new mechanisms of resistance and to develop new therapeutic methods, which would limit this therapeutic obstacle, is logically the subject of many studies. The activity of drug metabolizing enzymes and the subsequent decrease of intercellular concentration of anticancer drugs belongs to one of the possible mechanisms of pharmacokinetic resistance. Enzymes of I. and II. phase of biotransformation participate in this phenomenon. Cytochromes P450, main enzymes of the I. phase, play a major role in the metabolism of many cytostatic agents producing either pharmacologically active or inactive metabolites. Increased expression in tumors and the involvement of individual isoforms into the overall metabolism of cytostatic, which is deactivated by their activity, seems to be one of the...
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Trends in Medicines Usage in ATC Group L01
Weber, Jakub ; Lešetický, Ondřej (advisor) ; Kostřiba, Jan (referee)
The work analyzes trends in medicines used in specialized medical centers from ATC (Anatomical-Therapeutic-Chemical Classification System) L01 in Czech Republic from perspective of the State Institute of Drug Control (SUKL) and of Czech Health Insurance Companies (Vseobecna zdravotni pojistovna Ceske republiky as the biggest one, and rest joined in Svaz zdravotnich pojišťoven Ceske republiky). SUKL perspective considers medicines delivered to healthcare facilities and the other side providing information regarding payments for L01 medicines between years 2012-2015. Conclusions presented show slightly decreasing trend in terms of number of packages delivered (935 ths. in 2012 and 931 ths. in 2015). On the other hand, value of medicines has increased from 5 067 mil. CZK in 2012 to 6 568 mil. CZK in 2015. The increase in value and decrease in volume in the same time (while prices remain stable or decreasing) indicates trend in increasing size of packaging or entry of new strength (with more active ingredient and therefore more expensive) e.g. entry of Herceptin 600 mg in 2014. This paper further identifies the most expensive medicines in ATC L01 group and starts a discussion about possible reasons of discrepancies between different sources of data which are for the most expensive medicines in hundreds of mil. CZK in value and ths. of packages in terms of volume (e.g. Avastin in 2014: difference 104 mil. CZK and 5 598 packages).
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Hydrophilic interaction liquid chromatography for separation of cytostatically active compounds
Voborná, Markéta ; Kalíková, Květa (advisor) ; Kozlík, Petr (referee)
This diploma thesis deals with optimization of separation conditions for the four groups of analytes related to 7-deazaadenosine (each group was composed of four derivatized nucleosides) using hydrophilic interaction liquid chromatography. All the sixteen analytes were synthesized as potentially cytostatically active compounds. The effect of the type of stationary phase in the chromatographic column, the ratio of organic and aqueous parts of the mobile phase, pH of the buffer used as the mobile phase component and the concentration of ammonium acetate in the buffer in the range of 5-50 mM were tested during the optimization process. Three stationary phases were tested - bare silica (Spherisorb® Silica column), silica- bonded amide (TSKgel Amide-80 column) and silica-bonded native cyclofructan 6 (Frulic-N column). The dimensions of all columns were 2504.6 mm i.d.; particle size 5 µm. During the optimization of separation the mechanism of HILIC was studied. It was found that the distribution of analytes between the aqueous layer partially coated on the surface of the stationary phase and the mobile phase and also the adsorption of analytes on the stationary phase participated in the retention and separation mechanism in all tested chromatographic systems. The three groups of analytes (SK1, SK3, SK4)...
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Depletion of Treg cells for potentiation of cancer treatment with HPMA copolymer-bound cytostatic drug conjugates"
Dvořáková, Barbora ; Kovář, Marek (advisor) ; Reiniš, Milan (referee)
Tumor diseases are severe problem worldwide with increasing number of patients suffering from various types of malignancies. Many of approved therapeutics cause serious side toxicities. Therefore, there are intensive efforts to improve cancer treatment protocols. The aim of this study was to deplete regulatory T (Treg) cells without affecting other immunocompetent cells playing a positive role in tumor eradication. Treg cells were reported to hamper anti-tumor immunity and promote tumor growth and survival. Thus, their selective elimination could lead to induction of anti-tumor responses and tumor rejection if combined with chemotherapy with selected N-(2- hydroxypropyl)methacrylamide (HPMA) copolymer-bound drug conjugates. Original approach was to deplete of Treg cells without the use of anti-CD25 mAb that has been widely exploited for Treg cell elimination; however, its long-term persistence in circulation together with inhibitory effect on activated effector cells (CD25+ ) are its main disadvantages. Thus, Treg cells were sensitized to cell cycle-specific cytostatic drugs via application of IL-2/anti-IL-2 JES6.1 mAb immunocomplexes that induce vigorous selective proliferation of this cell population. Subsequent application of cell cycle-specific cytostatics showed steep decrease of Treg cell...
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Nursing Childcare during Chemotherapeutic Treatment
CIMBÁLNÍKOVÁ, Eva
Current status: Children oncology is a field which has become an important part of medicine and thanks to its development it is possible to heal up to 80% of children oncological patients. In the children oncology, we can meet many kinds of cancer such as Hematopoietic Tissue tumors, Lymphomas and Central nervous system tumors. Children are usually cured using chemotherapy which has not only therapeutically effects, but also unwanted symptoms which decrease the quality of patient lives and can be even dangerous for children. Main aim of my bachelor thesis is to describe the core principles of the nursing childcare during chemotherapy and to set the basic rules concerning the right vein entry care as well as the principles of the right application of medicinal products through venous inlets. Another task is to describe the principles of manipulation with cytostatic and to demonstrate the key role of the nurse during the application of chemotherapy. Methodology: To process this bachelor thesis and to achieve the set aims a qualitative research examination was done while using the technique of secondary analysis of relevant resources. This research included looking for the information concerning the problem in the professional and scientific publications as well as gaining the experience during the internship in the Department of Pediatric Oncology in the Faculty Hospital Brno Results: This thesis describes key principles of the nursing childcare during chemotherapy focused mainly on the possible problems related side effects of cytostatic. The main task of the nurse is to watch a possible occurrence of these effects and to provide a careful nursing care. The nurse must always adapt the care to the current health condition and needs of the patient. Each child is individual and reacts differently to the cure. It is necessary during the chemotherapy to prevent from a possible infection by a very careful barrier nursing care. The task of the nurse is also to provide children and parents with a psychological support, to educate about the treatment regime in her competence, to ensure the safe cytostatic use while watching their effect and possible complications as well as to take a complex care of venous inlets. The thesis also finds out the right rules of the safe manipulations with cytostatic. The main rule during each manipulation is to protect your own health by using the protective equipment such as special Nitrile gloves, oral veils etc. and to work according to the rules of the safe manipulation with cytostatic which are available in each oncological department. Conclusions: This research work is treated as a theoretical overview work and its main benefit is presenting the theoretical knowledge about the oncology nursing childcare while describing a very important part of the nurse taking care of children oncological patients. The nurse must have a lot of both theoretical and practical knowledge which she uses during the nursing care. The results of this research should provide both professional and lay public enough information about the children oncology.
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The significance of platinum in the environment
Brestovská, Marta ; Holubová, Zuzana (referee) ; Sommer, Lumír (advisor)
This bachelor thesis deals with monitoring of individual platinum compounds in the environment (water, soil, air) and is also reviewing methods used for their analysis. The no less important determination of platinum in tissues and body fluids, when the platinum is used in form of a cisplatin as an anticancer drug, is also mentioned. Afterwards the anticancer drug itself or its derivatives and metabolites on the base of platinum complexes in clinical sample (urine, plasma) are determined. Mainly the ICP-AES, ICP-MS, ETA-AAS, HPLC methods are highlighted from the methods used for the determination of Pt. The on-line connection between some of these methods such as ICP-MS with HPLC or ICP-AES with HPLC seems to be useful. The spectrofotometric methods using organic and inorganic agents can also be used for the determination of platinum. These methods are mentioned here rather marginally, just for completeness. In terms of practical use they are difficultly reproducible and not very sensitive. The hydrolysis of platinum metals to form insoluble hydrated oxides makes also the determination difficult.
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