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Design and Synthesis of Prodrugs of 6-Diazo-5-oxo-L-norleucine; Potential Treatment for Glioblastoma
Novotná, Kateřina ; Majer, Pavel (advisor) ; Rýček, Lukáš (referee)
6-Diazo-5-oxo-L-norleucine (DON, 1) is a non-standard amino acid with proven antitumor activity found in soil bacteria of the genus Streptomyces. However, due to the considerable systemic toxicity manifested mainly in the gastrointestinal tract, DON alone is not a suitable clinical candidate for the treatment of cancer. One of the ways to solve the problem of its toxicity is the reversible structural modification of this molecule by protecting both its amino group and carboxyl functional group, by preparing the so-called prodrug of DON. The prepared prodrug may suitably alter the distribution of DON in the body and at the same time increase its permeability to brain tissue. Due to this structural modification, its side effects can be eliminated and a substance for the treatment of brain tumors, such as glioblastoma multiforme (GBM), can potentially be formed. In my dissertation, five strategies for the specific delivery of DON to the brain using different types of its prodrugs are discussed. The new prodrugs are designed to be either capable of spontaneous penetration across the blood-brain barrier or of being a substrate for one of its influx transporters. At the same time, these prodrugs should be stable in other metabolically active organs and blood plasma in order to sufficiently reduce the...
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Analysis of brain tumors based on line of interest
Širůčková, K. ; Solár, P. ; Marcoň, P.
Due to the high resolution of soft tissue, magnetic resonance imaging plays a crucial role in the diagnosis and therapy planning in the neurosurgery field whereas it is necessary to determine which pathology in the brain tissue is involved. Glioblastoma multiforme, metastatic tumors and abscesses are examined in detail from magnetic resonance images. In clinical practice, all mentioned pathologies are diagnosed through invasive methods in the form of biopsy followed by histology of the affected tissue. This work is focused on an alternative non-invasive method of tumor diagnosis. The method is based on the data analysis from defined curves (drawn into the apparent diffusion images) that lead from the tumor area. The analysis of curves could lead to non-invasive diagnostics of the pathological tissue.
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Study of exosomes as drug delivery system in therapy of glioblastoma
Tomášková, Lucia ; Šimůnek, Tomáš (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucia Tomášková Supervisor: prof. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of exosomes as a drug delivery system in the treatment of glioblastoma Central nervous system disorders are among the most serious diseases affecting humans. They affect not only the patient's life, but also his/her surroundings. Therefore, their therapy, whether at the level of complete cure or alleviation of accompanying symptoms, is a challenge for scientific research. In our research, we focused on glioblastoma multiforme, a brain cancer not yet treatable. The main drawback in therapy is overcoming the blood-brain barrier. Exosomes, such as the body's natural nano-vesicles, have been shown to be a suitable system for delivering drugs to brain tissue. Our research has shown that by a suitable method we are able to obtain sufficient quality exosomes from macrophage and fill them very efficiently with antitumor agents paclitaxel, doxorubicin and temozolomide, while the delivered substances show higher efficacy and fewer side effects than the free form.
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Unconventional protocols in treatment of glioblastoma
Potomová, Petra ; Kubíková, Iva (advisor) ; Škvárová, Karolina (referee)
Glioblastoma multiforme is one of the tumours defying the treatment that is currently in use (radiotherapy and chemotherapy). Due to the failure in its complete repression, new methods were developed, methods that do not fulfil the traditional expectation about oncological treatment. But it's these methods that could lead to inhibition of further proliferation and growth of the tumour. Therapies, like anti-angiogenesis, ketogenic diet, photothermal therapy or ferroptosis, can be targeted against the tumour and significantly tip the oncological treatment in favour of patients and doctors. Despite the need to optimize them due to side effects, added toxicity or development of resistance, they play a vital role in the future of oncology. Keywords: glioblastoma multiforme, oncological treatment; anti-angiogenic therapy, ketogenic diet, photothermal therapy, ferroptosis
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Design and Synthesis of Prodrugs of 6-Diazo-5-oxo-L-norleucine; Potential Treatment for Glioblastoma
Novotná, Kateřina ; Majer, Pavel (advisor) ; Rýček, Lukáš (referee)
6-Diazo-5-oxo-L-norleucine (DON, 1) is a non-standard amino acid with proven antitumor activity found in soil bacteria of the genus Streptomyces. However, due to the considerable systemic toxicity manifested mainly in the gastrointestinal tract, DON alone is not a suitable clinical candidate for the treatment of cancer. One of the ways to solve the problem of its toxicity is the reversible structural modification of this molecule by protecting both its amino group and carboxyl functional group, by preparing the so-called prodrug of DON. The prepared prodrug may suitably alter the distribution of DON in the body and at the same time increase its permeability to brain tissue. Due to this structural modification, its side effects can be eliminated and a substance for the treatment of brain tumors, such as glioblastoma multiforme (GBM), can potentially be formed. In my dissertation, five strategies for the specific delivery of DON to the brain using different types of its prodrugs are discussed. The new prodrugs are designed to be either capable of spontaneous penetration across the blood-brain barrier or of being a substrate for one of its influx transporters. At the same time, these prodrugs should be stable in other metabolically active organs and blood plasma in order to sufficiently reduce the...
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Study of exosomes as drug delivery system in therapy of glioblastoma
Tomášková, Lucia ; Šimůnek, Tomáš (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucia Tomášková Supervisor: prof. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of exosomes as a drug delivery system in the treatment of glioblastoma Central nervous system disorders are among the most serious diseases affecting humans. They affect not only the patient's life, but also his/her surroundings. Therefore, their therapy, whether at the level of complete cure or alleviation of accompanying symptoms, is a challenge for scientific research. In our research, we focused on glioblastoma multiforme, a brain cancer not yet treatable. The main drawback in therapy is overcoming the blood-brain barrier. Exosomes, such as the body's natural nano-vesicles, have been shown to be a suitable system for delivering drugs to brain tissue. Our research has shown that by a suitable method we are able to obtain sufficient quality exosomes from macrophage and fill them very efficiently with antitumor agents paclitaxel, doxorubicin and temozolomide, while the delivered substances show higher efficacy and fewer side effects than the free form.
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The results of treatment of primary brain tumours
MRÁZKOVÁ, Tereza
The study is aimed to primary brain tumour patient's prognosis. The study is comprised of data processing, basic information summary of the issue, evaluation of overall survival of primary brain cancer patients and results comparison to the literature. The hypothesis says that the results gained at department of oncology are comparable with the literature. Patient's data were assembled from medical history of Oncology ward of České Budějovice hospital. Data collection was aimed of gender, age, tumour localization, histology, WHO staging, way of treatment, date of treatment initiation and current condition. Study included 116 patients with treatment initiation between 2011 - 2015 at the Oncology ward of České Budějovice hospital. Data were processed using Excel and survival rate was assessed by Kaplan - Meier analysis of the statistical program IBM SPSS Statistics. Overall survival was assessed in terms of the way of treatment (a combination of resection and radiation therapy, a combination of resection, radiation therapy and chemotherapy, palliative treatment), histology (astrocytoma, oligodendroglioma, glioblastoma multiforme), gender and age (younger than 50 years old, older than 50 years). Median overall survival of whole group under treatment was 12 months. In terms of overall survival analysis based on the histological results and treatment (combinations of resection, radiation therapy and chemotherapy) was at variance with literature. The acquired results should serve to further processing by students and as feedback for the oncology ward, because it assesses success of treatment on department.
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