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Biophysical interpretation of quantitative phase imaging of live cells generated by coherence-controlled holographic microscopy
Šuráňová, Markéta ; Rösel,, Daniel (referee) ; Vomastek, Tomáš (referee) ; Veselý, Pavel (advisor)
The dissertation thesis deals with the biophysical interpretation of quantitative phase imaging (QPI – Quantitative Phase Imaging) obtained using coherence-controlled holographic microscopy (CCHM – Coherence-Controlled Holographic Microscopy) in the Q-PHASE microscope, Telight, Brno). The theoretical part of this thesis deals with the characteristics of quantitative phase imaging, which provides non-invasive information on the activity of living cells in vitro. The main part of the work consists in elaborating a concept and verifying it of a new methodology (PAMP – Primary Assessment of Migrastatic Potential) for the first critical evaluation of drugs for expected anti-migratory/metastatic potential. The result of this method is considered the first sorting evaluation when considering specific migrastatic agents for future complex oncological treatment. PAMP evaluates the speed of cell migration, the growth of tumor cells and controls the risk of appearance of invasive phenotypes. Furthermore, the correlation microscopy method between the Q-PHASE microscope and the laser scanning confocal microscope (LSCM) is proposed to evaluate cell behavior and the occurrence of focal adhesions after drug application. The quantitative phase image obtained using the Q-PHASE microscope is compared with the quantitative phase image from the HoloMonitor (PHI AB, Sweden), on which the PAMP method has been positively verified.
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Resistance mechanisms in therapy of acute myeloid leukemia
Suchá, Simona ; Čečková, Martina (advisor) ; Žák, Pavel (referee) ; Matoušková, Petra (referee)
IN ENGLISH LANGUAGE Candidate: Mgr. Simona Suchá Supervisor: Assoc. Prof. PharmDr. Martina Čečková, PhD. Title of the doctoral thesis: Resistance mechanisms in therapy of acute myeloid leukemia Acute myeloid leukemia (AML) is a hematologic cancer known for its extensive heterogeneity, poor treatment outcomes and high relapse rate. Therapy outcome is often compromised by highly resistant leukemic clones present at diagnosis, which evade chemotherapy and continue to spread the disease. Identification of their cellular features is, therefore, a key in successful targeting and eliminating of these resistant leukemic cells. AML cells can, however, develop drug resistance even overtime due to prolonged drug exposure. Extremely high adaptability of leukemic cells enables them to survive whenever therapeutic stress stimuli occur. Uncovering molecular mechanisms that cells utilize to activate their survival mode is crucial in selection of treatment leading to maximal efficacy. Based on these grounds, two main aims of this thesis were set. First, to determine clinical relevance of ABC efflux transporters in AML and to evaluate the effect of targeted agents on chemotherapy. The focus was put on agents belonging to either FLT3 inhibitors (midostaurin) or CDK4/6 inhibitors (abemaciclib, palbociclib,...
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Resistance mechanisms in therapy of acute myeloid leukemia
Suchá, Simona ; Čečková, Martina (advisor) ; Žák, Pavel (referee) ; Matoušková, Petra (referee)
IN ENGLISH LANGUAGE Candidate: Mgr. Simona Suchá Supervisor: Assoc. Prof. PharmDr. Martina Čečková, PhD. Title of the doctoral thesis: Resistance mechanisms in therapy of acute myeloid leukemia Acute myeloid leukemia (AML) is a hematologic cancer known for its extensive heterogeneity, poor treatment outcomes and high relapse rate. Therapy outcome is often compromised by highly resistant leukemic clones present at diagnosis, which evade chemotherapy and continue to spread the disease. Identification of their cellular features is, therefore, a key in successful targeting and eliminating of these resistant leukemic cells. AML cells can, however, develop drug resistance even overtime due to prolonged drug exposure. Extremely high adaptability of leukemic cells enables them to survive whenever therapeutic stress stimuli occur. Uncovering molecular mechanisms that cells utilize to activate their survival mode is crucial in selection of treatment leading to maximal efficacy. Based on these grounds, two main aims of this thesis were set. First, to determine clinical relevance of ABC efflux transporters in AML and to evaluate the effect of targeted agents on chemotherapy. The focus was put on agents belonging to either FLT3 inhibitors (midostaurin) or CDK4/6 inhibitors (abemaciclib, palbociclib,...
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Acquired chromosomal aberrationns in peripheral blood lymphocytes of patients with newly diagnosed cancer and healthy control individuals.
Vodenková, Soňa ; Polívková, Zdeňka (advisor) ; Langová, Martina (referee)
The majority of human cancers arise due to cells inabitily to maintain genomic stability. Cytogenetic changes (especially chromosomal aberrations) in peripheral blood lymphocytes which reflect not only the individual exposure to genotoxic factors, but also individual sensitivity to genotoxic effect and the tumor is late consequence to genotoxic effect. Summary epidemiological prospective studies over the last ten years have shown that increased level of chromosomal aberrations in peripheral blood lymphocytes is predictive of cancer risk. This thesis is focused on the detection of particular types of chromosomal damage in patients with choosed types of newly diagnosed cancers compared to healthy control persons. We cytogenetically analyzed 100 patients with colorectal cancer and 298 controls and 123 patients with breast cancer and 123 controls - healthy women. We compared the percentage of aberrant cells, the percentage of total aberrations, the percentages of chromatid and chromosome aberrations found in patients with both types of tumors and in controls and we verified the predictive value of chromosomal aberrations as a biomarker of cancer risk. In patients with colorectal cancer was statistically significantly increased only the level of chromatid aberrations (CHTA) (1,45±1,28) compared to...
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Acquired chromosomal aberrationns in peripheral blood lymphocytes of patients with newly diagnosed cancer and healthy control individuals.
Vodenková, Soňa ; Polívková, Zdeňka (advisor) ; Langová, Martina (referee)
The majority of human cancers arise due to cells inabitily to maintain genomic stability. Cytogenetic changes (especially chromosomal aberrations) in peripheral blood lymphocytes which reflect not only the individual exposure to genotoxic factors, but also individual sensitivity to genotoxic effect and the tumor is late consequence to genotoxic effect. Summary epidemiological prospective studies over the last ten years have shown that increased level of chromosomal aberrations in peripheral blood lymphocytes is predictive of cancer risk. This thesis is focused on the detection of particular types of chromosomal damage in patients with choosed types of newly diagnosed cancers compared to healthy control persons. We cytogenetically analyzed 100 patients with colorectal cancer and 298 controls and 123 patients with breast cancer and 123 controls - healthy women. We compared the percentage of aberrant cells, the percentage of total aberrations, the percentages of chromatid and chromosome aberrations found in patients with both types of tumors and in controls and we verified the predictive value of chromosomal aberrations as a biomarker of cancer risk. In patients with colorectal cancer was statistically significantly increased only the level of chromatid aberrations (CHTA) (1,45±1,28) compared to...
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