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The anti-inflammatory effects of natural and synthetic triterpenoid coumpounds.
Spáčilová, Pavla ; Hajdúch, Marián (advisor) ; Džubák, Petr (referee)
The thesis is focused on in vitro testing of biological activities related to inflammation, such as inhibition of nitric oxide production and inhibition of reactive oxygen species formation in activated cells. 65 triterpenoid derivatives were tested in experimental section of the thesis for nitric oxide sythesis inhibition in B10R cells stimulated with lipopolysaccharide. 15 compounds showed terapeutic index value higher than 4, including three compounds which showed IC50 value lower than 10 μmol/l. 115 triterpenoid compounds were tested for inhibition of reactive oxygen species formation in RAW 264.7 cells stimulated with opsonized zymosan. Two compounds showed IC50 value lower than 10 μmol/l. None of 115 tested compounds showed NO·-scavenging activity. Four compounds showed a moderate O2-·-scavenging activity. Powered by TCPDF (www.tcpdf.org)
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Expression and prognostic value of microRNAs in patients with early breast cancer.
Sochor, Marek ; Tesařová, Petra (advisor) ; Slabý, Ondřej (referee) ; Hajdúch, Marián (referee)
Breast cancer is the most frequent cancer in women and is prognostically very heterogeneous. Early breast cancer has an excellent overall prognosis with long-term survival above 90%. In this group we can also find patients with highly unfavourable progress with a risk of future disease relapse. Due to effective anticancer treatment is a main task of precise clinical decision to determine risk of an individual patient in the term of cancer relapse. We can use clinical (tumor diameter, lymph nodes) and pathological markers (grade, ER, PgR, HER2, and Ki-67), all of them have low individual sensitivity and specificity. Molecular tests based on multigene DNA or RNA assays have higher sensitivity and specificity but their interrelated concordance is low. One of the main scientific task is to find almost specific and sensitive prognostic biomarkers. microRNAs are small, highly stable, non-coding RNAs, which regulate tens of mRNAs and proteins inside cells. In cancerogenesis, they could act as oncogenes or tumor supressors as well and affect main steps of initiation and progression of cancer. One of the scientific directions is to determine their prognostic significance. Many experimental and clinical studies defining prognostic significance of miRs in early breast cancer was published but their data were...
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Study of genome and transcriptome variability employing data processing from massive parallel DNA sequencing.
Vojta, Petr ; Hajdúch, Marián (advisor) ; Budinská, Eva (referee) ; Mokrejš, Martin (referee)
Massive parallel sequencing (MPS) data analysis tasks are often computationally demanding and their execution time would take too long using standard computing machines. Thus there is a need for parallelization of this tasks and ability to execute them on a sufficiently powerful computing machines. In the first chapter we describe a newly created platform for resequencing analysis of MPS data - MOLDIMED and novel annotation tool, which is ready to deploy on HPC infrastructure. The second chapter describes MPS approaches in Diamond-Blackfan anaemia (DBA), which is predominantly underlined by mutations in genes encoding ribosomal proteins (RP); however, its etiology remains unexplained in approximately 25% of patients. We performed panel sequencing of all ribosomal genes in DBA patient without previously known molecular pathology. A novel heterozygous RPS7 mutation coding RPS7 p.V134F was found in one female patient and subsequently confirmed in two asymptomatic family members, in whom mild anemia were detected on further examination. Subsequently, we performed whole transcriptome analysis in all family members and patient with RPS7 mutation in comparison with healthy control group and with DBA patients with known mutation in RPS19. We observed dysregulation mainly in signal pathways of translation,...
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The anti-inflammatory effects of natural and synthetic triterpenoid coumpounds.
Spáčilová, Pavla ; Hajdúch, Marián (advisor) ; Džubák, Petr (referee)
The thesis is focused on in vitro testing of biological activities related to inflammation, such as inhibition of nitric oxide production and inhibition of reactive oxygen species formation in activated cells. 65 triterpenoid derivatives were tested in experimental section of the thesis for nitric oxide sythesis inhibition in B10R cells stimulated with lipopolysaccharide. 15 compounds showed terapeutic index value higher than 4, including three compounds which showed IC50 value lower than 10 μmol/l. 115 triterpenoid compounds were tested for inhibition of reactive oxygen species formation in RAW 264.7 cells stimulated with opsonized zymosan. Two compounds showed IC50 value lower than 10 μmol/l. None of 115 tested compounds showed NO·-scavenging activity. Four compounds showed a moderate O2-·-scavenging activity. Powered by TCPDF (www.tcpdf.org)
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