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Comparison of novel amphiphilic anionic phthalocyanine photosensitizers with their hydrophilic analogues
Hasoňová, Kateřina ; Macháček, Miloslav (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kateřina Hasoňová Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Comparison of new amphiphilic anionic photosensitizers based on phthalocyanines with their hydrophilic analogues. Currently, one of the most common causes of death in our population is cancer. There are a number of treatment modalities how to treat tumours, but none of them is ideal, and a large number of people are still dying of cancer. For this reason, intensive research and studies are ongoing, focusing on cancer treatment options. In recent years, photodynamic therapy has been increasingly used to treat both cancerous and non-malignant diseases. It is a modern method that has minimal side effects, is highly selective and minimally invasive. Its principle is a photochemical reaction, which proceeds when a combination of three basic components occurs - light, oxygen and photosensitizer. Separately, these components are nontoxic, but when the photosensitizer is exposed to oxygen, toxic reactive oxygen species are produced, whose subsequently cause destruction of the tumour tissue. A photosensitizer is a compound that is able to absorb radiation of a certain wavelength and then convert it into energy, which...
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Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05
Douděrová, Aneta ; Macháček, Miloslav (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Aneta Douděrová Supervisor: RNDr. Miloslav Macháček, PhD. Consultants: pplk. doc. PharmDr. Aleš Tichý, PhD. Title of diploma thesis: Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05 Nowadays, tumor diseases belong to the world's main causes of death. Research in the area of tumor treatment deals with the development of new methods that improve the health of patients. The aim of my diploma thesis was to find out if the usage of autophagy inhibitors in combination with ionizing radiation (IR) contributed to radiosensitization of non-small cell lung cancer cells H1299. It was based on an assumption that autophagy was a cytoprotective mechanism leading to a cell survival during stress conditions such as IR. In order to examine qualitative changes of H1299 cells pre-treated by the new autophagy inhibitor Lys05 or well known autophagy inhibitor Bafilomycin A1 we used fluorescence microscopy in combination with green staining by LysoSensor green DND-189. The intensity of fluorescence was quantified by flow cytometry. The results have shown that pre-treatment by autophagy inhibitors in combination with IR led to morphological changes of cells and to...
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Study of the effectiveness of the original amphiphilic (aza)phthalocyanines bearing permanent positive charge
Steklá, 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...
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Evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of tumorous diseases.
Půlkrábková, Martina ; Macháček, Miloslav (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Martina Půlkrábková Supervisor: Mgr. Miloslav Macháček, Ph.D. Title of diploma thesis: Evaluation of photodynamic activity of tetrapyridoporphyrazine derivatives for treatment of tumorous diseases. Cancerous diseases are one of the most common causes of death, especially in industrialized countries. Their more effective treatment requires development of new potential anti-tumor agents and therapeutic methods. Photodynamic therapy (PDT) is a clinically approved method for the treatment of both tumorous and some other diseases. Its main advantages are non-invasiveness and potential for high selectivity to target cells, which distinguishes it from current conventional anticancer treatments (chemotherapy, radiotherapy). The effect of PDT is based on a combination of three effective components - molecular oxygen, light and photosensitiser (PS). These substances are inherently non-toxic, but they can form reactive oxygen species (ROS) if combined. Then, ROS significantly damages cellular structures in target cells, which can result in cell death. PS is a substance capable of absorbing light of suitable wavelength and transferring the received energy to surrounding molecules, to molecular oxygen in...
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Comparison of the effect of sphingoid bases on cell lines derived from fibroblasts and keratinocytes
Šulcová, Kristýna ; Macháček, Miloslav (advisor) ; Kuchařová, Monika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kristýna Šulcová Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Comparison of the effect of sphingoid bases on cell lines derived from fibroblasts and keratinocytes The skin is the largest organ of the human body which fulfills several tasks during the whole human lifespan. Apart from the esthetic function it creates a organism cover which functions as a barrier between the inner and outer environment. In this way it contributes to homeostasis and defense of the whole organism. The skin diseases are widespread and might occur in all ages. They can affect any part of the human body. The consequence of this is a great variety of those disorders. The seriousness can range from a rash to the life-threatening conditions. Atopic dermatitis, psoriasis, scabies and acne ranks among the most common and widespread illnesses of this kind. These are mostly non-infectious illnesses which can develop even into local inflammation as affected skin is often a place of the input of various pathogens. Affected people often suffer from dry skin lesions, itched rashes, cracking crusts, blisters and peeling skin. The skin of the patients is more sensitive to outer conditions which makes their...
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Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05
Douděrová, Aneta ; Macháček, Miloslav (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Aneta Douděrová Supervisor: RNDr. Miloslav Macháček, PhD. Consultants: pplk. doc. PharmDr. Aleš Tichý, PhD. Title of diploma thesis: Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05 Nowadays, tumor diseases belong to the world's main causes of death. Research in the area of tumor treatment deals with the development of new methods that improve the health of patients. The aim of my diploma thesis was to find out if the usage of autophagy inhibitors in combination with ionizing radiation (IR) contributed to radiosensitization of non-small cell lung cancer cells H1299. It was based on an assumption that autophagy was a cytoprotective mechanism leading to a cell survival during stress conditions such as IR. In order to examine qualitative changes of H1299 cells pre-treated by the new autophagy inhibitor Lys05 or well known autophagy inhibitor Bafilomycin A1 we used fluorescence microscopy in combination with green staining by LysoSensor green DND-189. The intensity of fluorescence was quantified by flow cytometry. The results have shown that pre-treatment by autophagy inhibitors in combination with IR led to morphological changes of cells and to...
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Biological evaluation of photodynamic activity of amphiphilic anionic photosensitizers
Halašková, Marie ; Macháček, Miloslav (advisor) ; Šimůnek, Tomáš (referee)
1 ABSTRACT Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Marie Halašková Supervisor: RNDr. Miloslav Macháček, Ph.D. Title of diploma thesis: Biological evaluation of photodynamic activity of amphiphilic anionic photosensitizers Tumor diseases are a global health problem and one of the most common causes of death in developed countries. Therefore, considerable effort is devoted to research and develop novel anticancer drugs. Common conventional therapies, such as chemotherapy, radiotherapy, surgery, or their combination, are often associated with severe side effects and high treatment costs. Photodynamic therapy (PDT) is therefore being increasingly recognized as an alternative treatment modality for the treatment of many malignant and non-malignant conditions. PDT is a clinically approved non-invasive treatment which consists of two relatively simple procedures: administration of a photosensitive drug and subsequent radiation of the tumor by light to activate the photosensitizer (PS). The activated photosensitizer reacts with molecular oxygen to form highly reactive oxygen species (ROS). This creates a state of oxidative stress in the tumor which leads to tumor cell death, tumor (micro)vasculature shutdown and induction of anti-tumor immune...
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In vitro assessment of cytotoxic action of novel potential nitro group-containing potential antitubercular agents
Turoňová, Dorota ; Macháček, Miloslav (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Depatrment of Biochemical Sciences Candidate: Bc. Dorota Turoňová Supervisor: RNDr. Miloslav Macháček, Ph.D. Consultant: doc. PharmDr. Jaroslav Roh, Ph.D. Title of diploma thesis: In vitro assessment of cytotoxic action of novel potencial nitro group-containing antitubercular agents More than 10 million new cases of tuberculosis occur every year. Lack of efficient antituberculotic drugs and their unavailability, poor diagnostic and especially inappropriate treatment are drawbacks complicating and even precluding eradication of tuberculosis. An already serious disorder has become even more serious in the last years, especially because of the occurrence of drug-resistant tuberculosis, especially MDR-TB and XDR-TB. Due to chromosomal mutations that make bacteria resistant to drugs it is still necessary to develop new effective drugs to replace those in current use, which are often toxic and associated with the occurrence of side effects. The research group at the Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, which has been researching new antitubercular agents for many years, has created new structures of aromatic nitrocompounds with very high antimycobacterial effect. The aim of this...
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