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The impact of PET/CT scanning in the radioteraphy planning of non-small cell lung cancer
Vojtíšek, Radovan ; Petera, Jiří (advisor) ; Feltl, David (referee) ; Zemanová, Milada (referee)
The impact of PET/CT scanning in the radiotherapy planning of non-small cell lung cancer Background: In the current practice of radiotherapy planning and target volume determination in patients suffering from the non-small cell lung cancer (NSCLC), a contrast-enhanced CT is standard procedure. Contemporary studies have proven that PET/CT examination attains higher sensitivity and specificity in the diagnosis of lung cancer and also leads to higher accuracy in the process of target-volume delineation in NSCLC. Aim: To compare radiotherapy plans made according to CT and PET/CT examinations in the same patient and to investigate the impact of changes in target volume sizes on tumor control probability (TCP) and normal tissue complication probability (NTCP) and the impact of combined PET/CT examination on the staging of the disease and treatment strategy. Materials and Methods: Between October 2008 and November 2013, 42 patients suffering from pathologically proven inoperable locally advanced NSCLC that were referred to radical radiotherapy were involved in our study. They all underwent planning PET/CT examination. I carried out two separate delineations of target volumes and two radiotherapy plans, both with their own dose-volume histograms (DVH). I compared the following parameters of radiotherapy...
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Relationship of protein SIVA and signaling pathways Hedgehog/GLI and mTOR to the origin and progression of non-small cell lung cancer.
Vachtenheim, Jiří ; Lischke, Robert (advisor) ; Zemanová, Milada (referee) ; Vodička, Josef (referee)
Non-small cell lung cancer belongs to most frequent malignant tumours at all worldwide. Despite significant progress in knowledge about etiopathogenesis and targeted anticancer therapy, basic scientific research in this particular field and development of more effective treatment remains challenging. In case of its inadequate activation, the Hedgehog signaling pathway is involved in non-small cell cancer development. P53 is well known tumour suppressor gene, that serves as anticancer barrier. Its activity is mostly determined by the transcriptional activation of many pro-apoptotic genes, one of which is SIVA-1. Recently, it has been surprisingly shown, that SIVA-1 has also pro-oncogenic properties in a mouse model of non-small cell lung cancer. The aim of this study was to clarify the importance of Hedgehog signaling pathway and protein SIVA-1 and their potential relationship in development and progression of human non-small cell lung cancer. In selected cell lines of human non-small cell lung cancer, expression of each single component of Hedgehog signalign pathway was detected. In the tissue samples of tumour obtained from 39 patients that underwent surgery for non-small cell lung cancer and selected cell lines of the same tumour, expression of SIVA-1 protein was revealed. These findings indicate...
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Relationship of selected indicators of nutritional status and results of oesophageal cancer treatment with chemoradiotherapy and surgery
Zemanová, Milada ; Tvrzická, Eva (advisor) ; Vaňásek, Jaroslav (referee) ; Kazdová, Ludmila (referee)
The impact was assessed of clinical and nutritional factors on prognosis of 107 oesophageal cancer patients treated with neoadjuvant chemoradiotherapy (CHRT) and surgery. Individualised nutritional support, according to grade of dysphagia was carried out in all the patients. Serum leptin, soluble leptin receptors (SLR), TNF, IGF and fatty acid (FA) profiles in plasma phosphatidylcholine (PC) were studied as well. Addition of paclitaxel to carboplatin and continual fluorouracil significantly increased toxicity without influencing efficacy of the treatment. Post-operative node negativity, grade of dysphagia, weight loss and serum albumin were proved to be prognostic factors of survival and time to progression. CHRT led to decrease of SLR, palmitoleic and oleic acid and increase of n-3 polyunsaturated FA in PC. Lower concentrations of SLR were associated with improved survival of the patients. Key words: oesophageal cancer, neoadjuvant chemoradiotherapy, weight loss, paclitaxel, albumin, soluble leptin receptor, fatty acids
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Circulating tumor cells in breast cancer patients
Bielčiková, Zuzana ; Zemanová, Milada (advisor) ; Gürlich, Robert (referee) ; Fínek, Jindřich (referee)
Circulating tumor cells (CTCs) represent a systemic phase of the localised cancer disease. They can be distinguished and enriched from the peripheral blood and so from the surrounding leukocytes by either physical properties (e.g., density and size) or biological properties (e.g., expression of epithelial proteins such as EpCAM or cytokeratins) and are usually further characterized by immunostaining or RT-PCR assays. Selecting patients with the risk of disease relaps at the time of diagnosis is crucial for clinicians in deciding who should, and who should not, receive adjuvant chemotherapy. We know that CTCs are strong prognostic factor in patients with metastatic as well as localized breast cancer (BC). It is also known that the prognostic power of circulating tumor cells in women with BC is independent from the standard prognostic indicators. Testing of CTCs known recently as "liquid biopsy" could be informative not only as predictor of the disease relapse, but also as the predictor of therapy effectiveness. The clinical use of CTCs must be strictly encouraged by clinical trials results. Monitoring of CTCs in time could zoom in the mechanism of therapy resistance and/or may provide the identification of new druggable targets. The purpose of my work was therefore to assess the CTCs positivity rate...
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The anti-oxidative stress response in Drosophila malanogaster involvement of adipokinetic hormone and adenosine
Zemanová, Milada ; Kodrík, Dalibor
The anti-oxidative stress response was studied in Drosophila melanogaster larvae and adults with mutation in genes of adipokinetic hormone (Akh), and adenosine receptor (AdoR(1)), and both these genes together (Akh(1) AdoR1 double mutant). To elicit the oxidative stress we administered paraquat (PQ) in food. Mortality tests revealed the double mutant Akh(1) AdoR(1) was more sensitive to PQ toxicity than either of the single mutants. The PQ administration significantly increased the Drome-AKH hormone level in control w(1118) and AdoR(1) larvae. On the contrary, PQ significantly increased expression of glutathione S-transferase D1 (GstD1) gene. It seems that both functional adenosine receptor and AKH itself are important for the proper control of the GstD1 gene expression under oxidative stress. On the other hand, differences in glutathione S-transferase (GST) activity among the strains, and between untreated and PQ treated groups were minimal. Next, the glutathione (GSH) level was significantly lower in all untreated mutant groups as compared with untreated control w1118 flies and declined further when the flies were treated with PQ. Thus, we demonstrated the important role of AKH and adenosine in control of anti-stress response elicited by PQ in D. melanogaster model.
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The impact of PET/CT scanning in the radioteraphy planning of non-small cell lung cancer
Vojtíšek, Radovan ; Petera, Jiří (advisor) ; Feltl, David (referee) ; Zemanová, Milada (referee)
The impact of PET/CT scanning in the radiotherapy planning of non-small cell lung cancer Background: In the current practice of radiotherapy planning and target volume determination in patients suffering from the non-small cell lung cancer (NSCLC), a contrast-enhanced CT is standard procedure. Contemporary studies have proven that PET/CT examination attains higher sensitivity and specificity in the diagnosis of lung cancer and also leads to higher accuracy in the process of target-volume delineation in NSCLC. Aim: To compare radiotherapy plans made according to CT and PET/CT examinations in the same patient and to investigate the impact of changes in target volume sizes on tumor control probability (TCP) and normal tissue complication probability (NTCP) and the impact of combined PET/CT examination on the staging of the disease and treatment strategy. Materials and Methods: Between October 2008 and November 2013, 42 patients suffering from pathologically proven inoperable locally advanced NSCLC that were referred to radical radiotherapy were involved in our study. They all underwent planning PET/CT examination. I carried out two separate delineations of target volumes and two radiotherapy plans, both with their own dose-volume histograms (DVH). I compared the following parameters of radiotherapy...
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Relationship of selected indicators of nutritional status and results of oesophageal cancer treatment with chemoradiotherapy and surgery
Zemanová, Milada ; Tvrzická, Eva (advisor) ; Vaňásek, Jaroslav (referee) ; Kazdová, Ludmila (referee)
The impact was assessed of clinical and nutritional factors on prognosis of 107 oesophageal cancer patients treated with neoadjuvant chemoradiotherapy (CHRT) and surgery. Individualised nutritional support, according to grade of dysphagia was carried out in all the patients. Serum leptin, soluble leptin receptors (SLR), TNF, IGF and fatty acid (FA) profiles in plasma phosphatidylcholine (PC) were studied as well. Addition of paclitaxel to carboplatin and continual fluorouracil significantly increased toxicity without influencing efficacy of the treatment. Post-operative node negativity, grade of dysphagia, weight loss and serum albumin were proved to be prognostic factors of survival and time to progression. CHRT led to decrease of SLR, palmitoleic and oleic acid and increase of n-3 polyunsaturated FA in PC. Lower concentrations of SLR were associated with improved survival of the patients. Key words: oesophageal cancer, neoadjuvant chemoradiotherapy, weight loss, paclitaxel, albumin, soluble leptin receptor, fatty acids
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Anti-oxidative stress response in Drosophila melanogaster - The role of adipokinetic hormone and adenosine
ZEMANOVÁ, Milada
In this thesis, the phenomena of the oxidative stress (OS) and anti oxidative stress responses in insects are described in a comprehensive review, and the outcomes of the experimental work are presented. The focus of the work was on defence reactions and their putative control by the adipokinetic hormone (AKH) and adenosine in the Drosophila melanogaster model. For this purpose, we studied the effect of the paraquat (oxidative stressor) treatment on adult flies and larvae carrying mutations in Akh (Akh1) and adenosine receptor (AdoR1) genes, and in both these genes together (Akh1 AdoR1 double mutant). The initial mortality tests revealed the double mutant Akh1 AdoR1 was more sensitive to OS than either of the single mutants. The AKH synthesis under the OS condition seems to be out of the gene expression control, since the increase of an AKH amount in CNS was not linked with the stimulation of Akh gene expression after a paraquat treatment. Further, the gene expression of the antioxidant enzyme glutathione S transferase D1 (GstD1) increased rapidly with OS, though the enzyme activity increased negligibly regardless of both the OS and mutations. Interestingly, the relative expression of GstD1 gene was minimal in the double Akh1 AdoR1 mutant; thus, it was concluded that both AKH and adenosine are employed in the GstD1 gene expression control. Similarly, AKH and adenosine seem to act in tandem in glutathione (GSH) regeneration, since the GSH level was significantly lower in all untreated deficient flies with the maximal effect in the Akh1 AdoR1 double mutant; accordingly, the reduction in the GSH level was enhanced by paraquat treatment. Altogether, the important roles of both AKH and adenosine in the anti oxidative stress response in D. melanogaster were demonstrated.
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Poikilothermic traits in Mashona mole-rat (Fukomys darlingi). Reality or myth?
ZEMANOVÁ, Milada
The African mole-rats is a mammalian family well known for a variety of ecophysiological adaptations for strictly belowground life. The Mashona mole-rat (Fukomys darlingi) is supposed to have strong poikilothermic traits, because it is not able to maintain a stable body temperature at ambient temperatures below 20°C. In our study, we measured resting metabolic rate and body temperature of Mashona mole-rats across a gradient of ambient temperatures to test its poikilothermic traits. Tested mole-rats show typical mammalian pattern in resting metabolic rates. And their body temperature was stable at ambient temperatures from 10 to 25°C. We thus cannot confirm poikilothermic traits in this species.
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