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Immunological features of esophageal carcinoma in prognosis and therapy
Šnajdauf, Martin ; Lischke, Robert (advisor) ; Vrba, Radek (referee) ; Stříž, Ilja (referee)
Esophageal cancer belongs to the gastrointestinal malignancies with the worst prognosis. Current treatment options, including surgical resection, chemotherapy, radiotherapy, or a combination of these methods, have low efficacy and the five-year survival rate for patients with esophageal cancer is approximately 10 to 15 %. In the last decade, immunotherapy has become the leading treatment modality for metastatic tumors. However, the success of immunotherapeutic approaches does not only depend on the infiltration of the tumor microenvironment with immune cells but also on the phenotype of these infiltrating cells. The aim of this project was to evaluatethe immunological features of tumor-infiltrating lymphocytes obtained from different tissue compartments (tumor, peritumoral tissue, adjacent healthy tissue, and lymph node) of patients during surgical resection and to compare them with clinical and histopathological data of patients. We observed that the distribution of NK (natural killer) cells, CD8 and CD4 positive T cells was different in each tissue compartment. While the lymph nodes had the highest percentage of T cells, the opposite was seen in NK cells. The proportion of NK cells was the lowest in the lymph nodes. The expression of death receptors FasR and DR3 (death receptor 3) was the lowest...
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Ischemia-reperfusion injury in lungs after transplantation and the role of radical oxygen species
Mrázková, Hana ; Lischke, Robert (advisor) ; Třeška, Vladislav (referee) ; Kittnar, Otomar (referee)
Keywords: Lung Tx, EVLP, NHBD, IR injury, ROS, hypercapnia, gender differences This dissertation thesis deals with a very topical issue of the lack of donor organs for lung transplants. As with other organs, the number of patients on waiting lists in terminal stages of their diseases is also constantly rising but there is not an adequate increase in donor organs. We focused our experimental work on the development of research concerning the solution which is most successful in a long-term perspective, i.e. organ transplants from non- heart-beating donors (NHBDs), in an ex vivo lung transplant protocol (EVLP) on an animal model (Wistar rats). This is a method which is clinically established worldwide (in the Czech Republic only experimentally) and is constantly subject to further research. Based on earlier studies, we focused the first experimental part of this work on the potential protective effect of hypercapnic ventilation on ischemia-reperfusion (IR) lung injury in EVLP. The study proved that the hypercapnic ventilation has a protective effect on the generation of reactive oxygen species (ROS) in IR lung injury, but only when used in the period of reperfusion. In the second experimental study, we followed up a very topical issue of the effect of gender on IR lung injury in EVLP in...
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Peritoneal lavage cytology and biochemistry in cases of upper GI tumours
Hoskovec, David ; Antoš, František (advisor) ; Lischke, Robert (referee) ; Aujeský, René (referee)
Introduction: Intraperitoneal tumor seeding is a common form of recurrence after surgery for GI tumours. Early diagnosis and treatment may influence the course of disease. Hypothesis and objectives of the work The finding of free tumor cells and / or elevation of tumor markers in peritoneal fluid predicts intraperitoneal tumor recurrence. The results of these tests can be used to indicate HIPEC. Aim of this work is to determine the sensitivity and specificity of cytology and tumor markers levels and importance of these tests for early diagnosis and prognosis of recurrence. Another objective was to confirm the applicability of RT PCR for identification of free tumor cells. Patients and methods . Materials are sourced both during initial surgery (220 patients) and by the dispensary controls (25 patients). The peritoneal fluid was examined cytologically and biochemically too. 50 samples was exemined by RT PCR. Results Elevation of tumor markers or finding of free intraperitoneal tumor cells predicts recurrence. The prognosis of these patients corresponds to stage IV TNM classification, regardless of other parameters TNM. Low sensitivity of these tests (34% for cytology, 53% for tumor markers) does not allow its use as an indicator of HIPEC. Due to degradation of RNA we did not confirm the value of RT...
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Contribution of New Immunosuppressants after Heart Transplantation
Skalická, Blanka ; Málek, Ivan (advisor) ; Horký, Karel (referee) ; Lischke, Robert (referee)
Background: Acute cellular rejection and graft vascular disease are major factors limiting the survival after orthotopic heart transplantation (OHTx). Tacrolimus could be more potent than cyclosporin A in therapy of recurrent acute rejection episodes in OHTx patients. Dyslipidemia is one of the risk factors involved in the development of graft vascular disease. Statins are common part of standard drug regimen after OHTx. On the other hand, they are potentially dangerous as they could interact with cyclosporin A. Study in healthy volunteers showed that tacrolimus should have no interactions with statins. Aim: In the first study we retrospectively assessed the effect of switching patients after OHTx with recurrent cellular rejection episodes from cyclosporin A to tacrolimus. In the second (prospective) study we evaluated the efficacy and safety of combined therapy with tacrolimus and atorvastatin in patients after OHTx with dyslipidemia. (...) Conclusions: Tacrolimus has a beneficial effect not only on recurrent acute rejection episodes in heart transplant recipients but it also decreases the incidence of future rejection episodes. In patients after OHTx with dyslipidemia switching to tacrolimus and atorvastatin could be a suitable therapeutic option, because this combination is safe and effective in...
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Experimental pulmonary embolism - pathophysiological aspects
Mizera, Roman ; Herget, Jan (advisor) ; Lischke, Robert (referee) ; Vízek, Martin (referee)
- Experimental pulmonary embolism, pathophysiological aspects MUDr. Roman Mizera Theoretical part of the thesis deals with mechanisms of pulmonary hypertension after pulmonary embolism (PE) and summarizes the knowledge of literary sources in this issue. Peripherally deals with the mechanical obstruction of pulmonary vessels, particularly discusses vasoconstriction after the PE. In the experimental part are described three separate experiments. The first experiment tested effect of reactive oxygen species (ROS) and preventive administration their scavenger - superoxide dismutase inhibitor tempol on basal perfusion pressure, vasoconstriction, NO synthase activity and the production of NOx after acute PE. Results show that after PE grows NO synthase activity and the production of NOx, the administration of tempol reduces basal perfusion pressure and vasoconstriction after PE. In the second experiment, we measured basal perfusion pressure and vasoconstriction after PE in lungs exposed to 5 day chronic hypoxia. We tested influence of PDE-5 inhibitor sildenafil on the pulmonary vessels tone. Sildenafil decreased basal pressure after PE in chronic hypoxia, its administration does not affect the pulmonary vasoconstriction of pulmonary vessels, but increases their compliance. The last project tested effect...
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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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Study of anti-tumor immune response in patients with lung cancer.
Myšíková, Dagmar ; Lischke, Robert (advisor) ; Bouček, Jan (referee) ; Palich Fučíková, Jitka (referee)
Lung cancer is the leading cause of cancer mortality worldwide. Understanding biological processes of specific antitumor immune response remains of an eminent interest and represents necessity for designing successful antitumor immunotherapeutic strategies. The theoretical part of the thesis describes components of the immune system that are involved in antitumor response and discusses their role in the hitherto known and used lung cancer immunotherapy. In the practical part of the thesis, two studies studying different aspects of anticancer immune response are described. Both studies were conducted in cooperation with 3rd Surgical Department 1st Faculty of Medicine, Charles University and University Hospital Motol and with the biotechnology company Sotio a.s. The first study is focused on the humoral component of the specific antitumor response and prospectively analyses serum frequency of antitumor antibodies against NY-ESO-1, Her2/neu and MAGE-A4 antigens in 121 patients with NSCLC. Here it was shown for the first time that tobacco smoking significantly increases the frequency of NY- ESO-1 antibodies in sera of smokers in comparison to ex-smokers and non-smokers. The second study is focused on the cellular component of the specific antitumor response investigating the activity of the dendritic...
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Experimental pulmonary embolism - pathophysiological aspects
Mizera, Roman ; Herget, Jan (advisor) ; Lischke, Robert (referee) ; Vízek, Martin (referee)
- Experimental pulmonary embolism, pathophysiological aspects MUDr. Roman Mizera Theoretical part of the thesis deals with mechanisms of pulmonary hypertension after pulmonary embolism (PE) and summarizes the knowledge of literary sources in this issue. Peripherally deals with the mechanical obstruction of pulmonary vessels, particularly discusses vasoconstriction after the PE. In the experimental part are described three separate experiments. The first experiment tested effect of reactive oxygen species (ROS) and preventive administration their scavenger - superoxide dismutase inhibitor tempol on basal perfusion pressure, vasoconstriction, NO synthase activity and the production of NOx after acute PE. Results show that after PE grows NO synthase activity and the production of NOx, the administration of tempol reduces basal perfusion pressure and vasoconstriction after PE. In the second experiment, we measured basal perfusion pressure and vasoconstriction after PE in lungs exposed to 5 day chronic hypoxia. We tested influence of PDE-5 inhibitor sildenafil on the pulmonary vessels tone. Sildenafil decreased basal pressure after PE in chronic hypoxia, its administration does not affect the pulmonary vasoconstriction of pulmonary vessels, but increases their compliance. The last project tested effect...
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Peritoneal lavage cytology and biochemistry in cases of upper GI tumours
Hoskovec, David ; Antoš, František (advisor) ; Lischke, Robert (referee) ; Aujeský, René (referee)
Introduction: Intraperitoneal tumor seeding is a common form of recurrence after surgery for GI tumours. Early diagnosis and treatment may influence the course of disease. Hypothesis and objectives of the work The finding of free tumor cells and / or elevation of tumor markers in peritoneal fluid predicts intraperitoneal tumor recurrence. The results of these tests can be used to indicate HIPEC. Aim of this work is to determine the sensitivity and specificity of cytology and tumor markers levels and importance of these tests for early diagnosis and prognosis of recurrence. Another objective was to confirm the applicability of RT PCR for identification of free tumor cells. Patients and methods . Materials are sourced both during initial surgery (220 patients) and by the dispensary controls (25 patients). The peritoneal fluid was examined cytologically and biochemically too. 50 samples was exemined by RT PCR. Results Elevation of tumor markers or finding of free intraperitoneal tumor cells predicts recurrence. The prognosis of these patients corresponds to stage IV TNM classification, regardless of other parameters TNM. Low sensitivity of these tests (34% for cytology, 53% for tumor markers) does not allow its use as an indicator of HIPEC. Due to degradation of RNA we did not confirm the value of RT...
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