MD Hana Faltová, Ph.D.
Supervisor: Prof. MD Lischke Robert, Ph.D.
Topic: The role of free oxygen radicals in ischemia-reperfusion lung damage and the possibility of preventing radical damage
Defense of the dissertation 20.02.2017/XNUMX/XNUMX
Dissertation abstract:
The main factor preventing a significant increase in the number of lung transplants is the critical lack of suitable donors, this leads to attempts to use for transplantation purposes, for example, lungs obtained from donors who died of cardiac arrest outside the hospital (non-heart-beating donors) or to use organs from marginal donors after prior stabilization of ventilation parameters during extracorporeal lung oxygenation (ex-vivo reconditioning). In terms of functional lung damage, the warm ischemia and reperfusion period is crucial, when ischemia-reperfusion (IR) injury often develops. The aim of the research was the interaction of free oxygen radicals (ROS) and the increase in NO production during IR damage, the possibility of protecting IR damage and investigating the influence of gender on radical lung damage.
MD Martina Fialová
Supervisor: MD Kubinyi Jozef, Ph.D., FEBNM
Trainer consultant: Doc. MD Petr Libánský, Ph.D.
Topic: Analysis of circulating epithelial cells in malignant and benign thyroid diseases
Annotation:
The aim of the dissertation is to detect the presence of circulating epithelial cells
(CEC-circulating epithelial cells) in patients with a nodule, focus on the group classified as Bethesda III and compare the findings with benign and malignant diseases of the pancreas. Part of the CEC detection process is also a molecular analysis of CTC (circulating tumor cells) focused on genes associated with the tumor, with the aim of improving the prognosis of the disease. The molecular character of CEC will be further correlated with clinical and histological findings.
In the case of detection of CECs with a cancerous character, i.e. CTCs, their use as a predictive biomarker in the indication of chemotherapy and radioisotope treatment is assumed.
Doc. MD Tomáš Haruštiak, Ph.D.
Supervisor: Doc. MD Alan Stolz, Ph.D.
Topic: Early evaluation of the effectiveness of neoadjuvant chemotherapy in esophageal and esophagogastric junction cancer using FDG-PET/CT examination
Grant: Grant IGA MZČR NT 12331-5 EudraCT number: 2011-001856-12, resolved in cooperation with the VFN Oncology Clinic and the Homolce Hospital PET Center
Defense of the dissertation: 18 September 09
"Optimization of preoperative and operative treatment of esophageal and esophagogastric junction cancer:
the use of PET/CT in the diagnosis and evaluation of the effectiveness of preoperative chemotherapy and the anastomosis construction technique as a factor of postoperative complications after esophagectomy"
Dissertation abstract:
Using a repeated FDG-PET/CT examination, performed before, 14 days after the start and 4 weeks after the end of neoadjuvant chemotherapy for adenocarcinoma of the esophagus or EGJ, we investigated the correlation of the decrease in the metabolic activity of the tumor expressed by the decrease in the consumption of 18 FDG in the tumor tissue (assessed according to PERCIST 1.0 criteria) timely (14 days) after the start of neoadjuvant treatment with the degree of histopathological regression of the tumor in the definitive histological resection specimen after surgery, which will follow after the end of neoadjuvant
treatment.
MD Pavel Hladík
Supervisor: Prof. MD Vladimír Bobek, Ph.D.
Topic: Biological heterogeneity of primary and disseminated tumor cells
Annotation:
The primary goal of the project is the molecular characterization of disseminated (DTC) as well as circulating tumor cells (CTC) in patients with solid tumors. Tumor cells will be isolated from blood (CTC) and from
of solid metastases (visceral and lymphatic). Depending on the obtained properties of the cells examined in this way (gene expression of tumor-associated genes, chemoresistance genes, mutational analysis), the biological heterogeneity between primary tumor cells and metastatic foci and also between metastatic foci will be evaluated. The goal is to divide patients into prognostic and treatment groups using the identification of cellular heterogeneity.
MD Silvia Jarosciakova
Supervisor: Doc. MD Tomáš Haruštiak, Ph.D.
Consultant: Prof. MD Robert Lischke, Ph.D., Prof. RNDr. Ondřej Slabý, Ph.D.
Topic: Significance of microRNAs in esophageal cancer
Annotation:
The doctoral study is focused on a group of patients with locally advanced adenocarcinoma of the distal esophagus and gastroesophageal junction who have undergone neoadjuvant chemotherapy. The aim of this work is to evaluate the importance of miRNA as a predictive biomarker in response to neoadjuvant treatment by analyzing miRNA profiles in so-called responders, patients with good histopathological response, who benefit from neoadjuvant treatment. With early identification of nonresponders, patients could be spared ineffective neoadjuvant treatment or, based on prediction of response, their treatment could be individualized, for example, by premature termination of therapy or change of treatment regimen. Another goal is to identify miRNA profiles that can be used in esophageal cancer as diagnostic and prognostic biomarkers.
MD Barbora Jíšová
Supervisor: MD Barbara East, Ph.D.
Topic: Biological nature of direct abdominal muscle diastasis and its clinical consequences
Annotation:
The rectus abdominis muscles are normally no more than 1-2 cm apart. Diastasis is defined as a condition in which their medial edges spread over 20 mm during life. It is a common pathology in middle-aged men with abdominal obesity and in young women after childbirth. Diastasis as such is not a true hernia and is not a life-threatening disease, but it is a significant risk factor for the development of primary ventral hernia and hernia in the scar even after minimally invasive procedures and the main risk factor for recurrence after plastic surgery of other ventral hernias. According to EBM, it should be treated together with other defects of the anterior abdominal wall.
While in patients with a hernia, in patients with diastasis of the rectus abdominis muscles, it is not clear whether it is only a simple mechanical overload of the otherwise high-quality connective tissue or whether a reduced ratio of collagen I leads to the formation of the diastasis
and III and, if so, whether this disparity is localized only on the fascia or is genetically determined by the phenotype of a specific patient and we will thus be able to detect it in other connective tissues as well (e.g. dermis).
If diastasis of the rectus muscles proved to be a genetic connective tissue disorder, we would explain the high number of recurrences after simple suturing of primary ventral hernias in the field of diastasis and we could also recommend prophylactic use of the net at abdominal closure and after minimally invasive procedures. . The correlation between the finding in the connective tissue of the fascia and the dermis would then help us determine the etiology of these biological changes.
In practice, demonstration of the biological nature of direct abdominal muscle diastasis would involve sampling from the linea alba tissue and skin sample around the wound for histological examination, in particular to determine the architecture of the collagen binder and the collagen I and III ratio. In the experiment, we would like to examine 25 patients of men with direct muscle diastasis, 25 men without diastasis, 25 women with diastasis and 25 women without it. In the form of multiregression analysis, we would like to reveal other factors associated with the presence of diastasis (age, smoking, obesity, number of pregnancies, diabetes).
MUDr. Jan Kolarik
Supervisor: Prof. MD Robert Lischke, Ph.D.
Topic: Lung transplantation, Ex vivo normothermic pulmonary perfusion, prediction of risk factors for primary graft dysfunction and possibilities of graft therapy ex vivo
Annotation:
A fundamental limit to a greater number of transplants, not only of lungs, is the lack of suitable donor organs and the associated high mortality on the waiting list. Therefore, in recent years, a method of normothermic ex vivo lung perfusion EVLP has been developed, enabling a longer and more detailed evaluation of lung functions. Ex vivo perfusion is just before being introduced into clinical practice in the Czech Republic. During the postgraduate studies, we focus on detailed research of lung graft metabolism and immunological effects in an effort to predict lung function after transplantation, reveal risk factors of primary lung dysfunction and the possibility of therapy for damaged lungs, e.g. by aspiration, both in clinical practice and in an animal portion model.
MD Dagmar Krbcová, Ph.D.
Supervisor: Prof. MD Robert Lischke, Ph.D.
Consultant: Prof. MUDr. Radek Spisek, Ph.D.
Topic: Study of antitumor immune response in patients with lung cancer
Defense of the dissertation 24.9. 2018
Dissertation abstract:
Lung cancer is the leading cause of death from malignant diseases worldwide. Understanding the biological processes of the specific antitumor immune response remains a priority interest and a necessity for designing successful immunotherapeutic strategies. In the theoretical part of this work, we deal with the components of the immune system that participate in the antitumor response, and their role in immunotherapy known and used so far. In the practical part, we describe two studies studying different aspects of the antitumor immune response, both realized in collaboration with III. surgical clinics of the 1st Faculty of Medicine of the UK and FNM with the company Sotio a.s. The first of the two studies is focused on the humoral component of the specific antitumor response and prospectively analyzes the serum frequencies of the antitumor antibodies NY-ESO-1, Her2/neu and MAGE-A4 in 121 patients with NSCLC. In this study, we demonstrate for the first time that tobacco smoking significantly affects the specific humoral immune response, the frequency of NY-ESO-1 antibodies being significantly higher in the sera of smokers and ex-smokers. The second of the two studies is more focused on the T cell component of the specific antitumor response and tests a vaccine prepared from dendritic cells presenting antigens of lung cancer cells killed by high hydrostatic pressure (DC-HHP vaccine). The DC-HHP vaccine exhibits a mature dendritic cell phenotype, produces pro-inflammatory cytokines, enhances chemotactic migration, and induces tumor-specific CD8+ and CD4+ T lymphocytes.
High hydrostatic pressure (HHP) induces immunogenic death in tumor cells, which is crucial for the induction of an effective antitumor immune response.
MD Vendula Martínková, Ph.D.
Supervisor: Prof. MD Martin Matějovič, Ph.D.
Study program: Internal Medicine, Charles University, Faculty of Medicine in Pilsen
Topic: Replacement and support of the function of vital organs in sepsis Pathophysiology and new treatment aspects
Dissertation defense 05.10.2020/XNUMX/XNUMX
Dissertation abstract:
Infectious diseases are a major cause of morbidity and mortality worldwide. Sepsis is the leading cause of death from infectious diseases. It is one of the most serious and at the same time one of the most difficult to treat conditions in contemporary medicine. Sepsis is the most common cause of death in intensive care units. There is no causal treatment yet. Thanks to a significant deepening of the knowledge of the patho/physiological mechanisms of sepsis, it is possible to model new preclinical experiments to verify the efficacy and safety of new therapeutic procedures. Large animal experiments of progressive sepsis using domestic pigs play an irreplaceable role. Long-term experience with this model and its similarity to humans enable the implementation of complex experiments with the potential of relevant translation of results into subsequent human clinical studies. The aim of this dissertation was to evaluate on a clinically relevant model 1) the effectiveness and safety of extracorporeal membrane oxygenation in the case of refractory vasoplegic septic shock; 2) the benefit of two innovative treatment approaches in the treatment of sepsis: a) intravenous application of mesenchymal cells and b) activation of the neuroinflammatory reflex.
MD René Novysedlák
Consultant: MUDr. Zuzana Strizova, Ph.D.
Topic: Early prediction and therapy of rejection after lung transplantation
Annotation:
Lung transplantation is one of the most demanding organ transplants. Despite rapid progress, the immunopathological mechanisms that lead to organ rejection are far from being understood. Both innate and adaptive immune responses are involved in the complex cellular interactions leading to rejection of a transplanted organ. For this reason, specific immunosuppressive therapy is used with the aim of achieving immune tolerance and long-term survival of the transplanted organ. However, a robust screening algorithm for the early detection of rejection in lung transplant patients is still lacking. Such an algorithm would allow early therapeutic intervention with possible modifications of immunosuppressive therapy.
In our project, we analyze clinical, pathological and immunological parameters in patients undergoing lung transplantation. Part of the project takes place in cooperation with the Institute of Pathology
and molecular medicine of the 2nd Faculty of Medicine of Charles University and Motol University of Applied Sciences. Immunological data are generated in cooperation with the Institute of Immunology of the 2nd Faculty of Medicine, Charles University
and FN Motol. As part of this collaboration, we collect samples from patients who have undergone a lung transplant.
These samples are then analyzed. Using flow cytometry
and Luminex, we focus on markers that could serve as potential therapeutic targets. Luminex enables functional analyzes of cells under various conditions and therapeutic regimens. All data will be correlated with each other
and statistically evaluated. The results will provide a basis for understanding the events that precede graft rejection.
MD Andrej Ozaniak, Ph.D.
Supervisor: MUDr. Zuzana Strizova, Ph.D.
Consultant: Prof. MD Robert Lischke, Ph.D.
Topic: Tumor microenvironment of soft tissue sarcomas and its predictive significance in modern oncological treatment
Defense of the dissertation: 25 September 05
Annotation:
Sarcomas, tumors of mesenchymal origin, are a heterogeneous group of diseases characterized in most cases by chemoresistance and radioresistance. Tumor grading is a key prognostic factor. Radical surgery is often the only possible treatment modality or at least plays a major role in therapy.
In a generalized disease, treatment options are very limited. The chemosensitivity of STSs is generally very low, with the exception of rhabdomyosarcoma and Ewing's sarcoma, and is only 5-10%. Radiotherapy is in many cases a standard part of the treatment protocol, especially in adjuvant administration, but its use in generalized patients is marginal and does not improve the prognosis. Antitumor immunotherapy is a therapeutic modality that uses the physiological abilities of immune system cells to fight cancer. It is therefore not based on the targeted elimination of rapidly proliferating tumor cells, but rather on the stimulation of immune cells in order to destroy tumor antigens. Countless different strategies have been tested in the field of immunotherapy of soft tissue sarcomas, but unlike other solid tumors, such as malignant melanoma or kidney cancer, these approaches did not lead to significant regression of the tumor mass in sarcomas. One of the main reasons is the huge histological heterogeneity of these tumors and the diverse infiltration of sarcomas by immune cells. The topic of the proposed project will be a detailed analysis of immune cells infiltrating the tumor microenvironment of soft tissue sarcomas. As part of the project, we will collect native tissues from patients who are operated on at the III surgical clinic for the diagnosis of STSs and, in cooperation with the Institute of Immunology and the Institute of Pathology and Molecular Medicine of the 2nd Faculty of Medicine, UK, we will evaluate selected cell populations in relation to clinicopathological data, such as tumor grade, stage, time without progression and recurrence of the disease.
MD Jan Pastor
Supervisor: Doc. PhDr. Ludmila Hlaváčková, CSc., Department of History of Medicine and Foreign Languages 1. LF UK
Topic: History of Jedlička School of Surgery
Annotation:
Mapping the development of Prague surgical clinics and schools with a focus on the personality, pupils and successors of prof. Rudolf Jedlička (axis Jedlička – Diviš – Pafko) as an addition to the already well-developed history of the Jiráskova school. In the first half of the 20th century, the question of relations between the Czech and German parts of the university. Special focus on the development of thoracic surgery in the given period, operative techniques, the importance of Czech schools for the development of world thoracic surgery.
MD Jiří Pozniak
Supervisor: Prof. MD Robert Lischke, Ph.D.
Topic: A surgical approach to monitoring lymphatic drug absorption in the rat
Annotation:
Cannulation of the mesenteric duct in the rat is the gold standard for determining the absorption of lipophilic substances into the lymphatic system. A model can be used in which the animal is kept under general anesthesia throughout the experiment. However, anesthesia can have an effect on slowed gastric emptying, fat absorption in the intestine and the own flow of lymph in the lymphatic vessels. Also, the administration of oil, which is administered before the start of surgery to better visualize the lymphatic ducts, can affect the absorption of strongly lipophilic substances into the lymph. The subject of my work is the development of a surgical technique that will allow the collection of lymph and the measurement of lymph concentrations of administered substances in rats, as well as the comparison of results in anesthetized and non-anesthetized animals.
MD Martin Šnajdauf, Ph.D.
Supervisor: Prof. MD Robert Lischke, Ph.D.
Consultant: MUDr. Zuzana Strizova, Ph.D.
Topic: Immunological features of esophageal carcinoma and their influence on prognosis and therapy
Dissertation defense on 19/10/2023
Annotation:
Esophageal cancer is among the malignancies of the gastrointestinal tract with the worst prognosis. Current treatment options, including surgical resection, chemotherapy, radiotherapy or a combination of these approaches, have low efficacy and the five-year survival rate for patients with esophageal cancer is only around 10 to 15%. Immunotherapy as an independent therapeutic modality has come to the fore in the treatment of a number of solid tumors in the last decade. However, the success of immunotherapeutic approaches depends not only on the infiltration of the tumor microenvironment by immune cells, but also on the phenotype of these infiltrating cells. Multiple studies have shown that the presence of tumor-infiltrating lymphocytes (TILs) in the tumor environment has a significant impact on the clinical course of the disease and is also related to risk factors for the development of the disease. Thus, tumor infiltrating lymphocytes have not only become an important prognostic marker, but have also found application in therapy, primarily as a source of cells for adoptive cell immunotherapy (ACI, adoptive cell transfer - ACT). Selective expansion of cells with high migratory and cytotoxic capacity may bring new insight into adoptive cell immunotherapy of esophageal cancer. Tumor infiltrating lymphocytes in esophageal cancer and their role in treatment and prognosis are far from clear. It is essential to identify and correctly define the most suitable TIL population for ACI. The aim of this project is to evaluate the immunological features of tumor-infiltrating lymphocytes obtained from tumor tissue of patients during surgical resection. The results of the proposed project may contribute to the understanding of the essential role of immune cells infiltrating esophageal cancer and also help to define the optimal source of cells for adoptive cell immunotherapy of carcinoma j.
MD Monika Švorcová
Supervisor: Prof. MD Robert Lischke, Ph.D., MD Jan Havlín, Ph.D.
Topic: Monitoring of Torque Teno Viru plasma levels and its relation to immunosuppression in lung transplant patients
Annotation:
The aim of the doctoral study is to prospectively measure the level of TTV in peripheral blood in patients after lung transplantation at the Motol Hospital and the subsequent evaluation of its dynamics in relation to rejection and infectious complications and their prediction during the first year after transplantation. A total of 60 newly transplanted patients will be included in the study, which can be achieved within two years given the current transplant activity. TTV viremia will be measured by a quantitative real-time PCR reaction once before transplantation and subsequently at regular intervals after transplantation. During the first year, approx. 20 measurements can be expected for one patient. At the same time as the TTV load, doses and levels of maintenance immunosuppression were monitored as standard, and basic lymphocyte subpopulations were determined at regular intervals. If we confirmed the predictive potential of TTV viremia for the development of rejection or infectious complications, it would be possible to individualize immunosuppressive treatment based on its dynamics and implement it as a new biomarker into routine clinical practice.
MD Markéta Vaculová
Supervisor: Doc. MD Petr Libánský, Ph.D.
Topic: Surgical solutions of various clinical forms of primary hyperparathyroidism
Annotation:
Primary hyperparathyroidism is a disorder of phosphocalcium metabolism in which there is an increase in calcium levels due to parathyroid hormone produced by the parathyroid glands. The only definitive effective and safe treatment is surgical removal of overproducing parathyroid tissue. It is the 3rd most common endocrine disease, affecting mostly women aged 60 years. The clinical picture is very varied, however, due to better laboratory diagnosis, asymptomatic, normocalcemic and normohormonal forms are increasing.
Normocalcemic primary hyperparathyroidism is characterized by repeated elevated parathyroid hormone levels without identifying the cause of these values. It can be the first stage of primary hyperparathyroidism, which later turns into a hypercalcemic form. It seems that these forms are accompanied by a lower level of parathyroid hormone, which
may be related to the size of the pathological parathyroid gland. If this were to be confirmed, it would mean that they are harder to show on preoperative localization examinations and also harder to find during surgery. Conversely, the surgeon in these asymptomatic, normohormonal and normocalcemic forms does not need to be as radical as in the symptomatic form. In practice, the level of intact parathyroid hormone would be determined preoperatively by a standardized method at one workplace in selected patients who have the above-mentioned form. Furthermore, the level of total and ionized calcium would be determined, which would be compared with the size of the removed pathological parathyroid gland.
MD Jiří Vachtenheim
Supervisor: Prof. MD Robert Lischke, Ph.D.
Field: Experimental surgery
Topic: Relationship of SIVA protein and Hedgehog/GLI and mTOR signaling pathways to tumorigenesis, progression and frequency of metastasis in non-small cell lung cancer.
Defense of the dissertation 20.10.2021/XNUMX/XNUMX
Dissertation abstract:
Non-small cell lung cancer is one of the most common malignant diseases worldwide. Despite all the progress in the knowledge of its etiopathogenesis or the development of targeted antitumor therapy, basic research in the field of this disease and its more effective treatment continue to be a challenge. In the case of its inappropriate activation, the Hedgehog signaling pathway contributes to the development of non-small cell lung cancer through an oncogenic effect. P53 is a well-known tumor suppressor gene acting as a barrier against the formation of tumors. This effect is primarily due to transcriptional activation
of various proapoptotic genes, one of which is the gene encoding the protein SIVA-1. Recently, however, it was surprisingly found that SIVA-1 has a pro-oncogenic function in non-small cell lung cancer in a mouse tumor model.
The aim of this work was to further clarify the significance of the Hedghog signaling pathway and the SIVA-1 protein in human non-small cell lung cancer and possibly clarify their possible interrelationship in the development and progression of human non-small cell lung cancer. The expression of individual components of the Hedgehog signaling pathway was verified on selected tumor cell lines of human non-small cell lung cancer. Protein expression was confirmed in samples obtained from 39 patients operated on for non-small cell lung cancer and in selected cell lines of this tumor
GRAY-1. These findings confirm the importance of both the Hedgehog pathway and the SIVA-1 protein in the development of non-small cell lung cancer.
The completely new and original finding that the SIVA-1 protein activates the Hedgehog pro-oncogenic signaling pathway can be considered a fundamental finding of this work. This finding is consistent with previous evidence that SIVA-1 protein has an oncogenic role specifically in non-small cell lung cancer.
MD Jakub Woleský
Supervisor: MD Barbara East, Ph.D.
Topic: Liquid nanofiber carriers in the prevention of hernia in the scar
Annotation:
Hernia in the scar is the most common reason for reoperation after a laparotomy. Prophylactic use of the net is recommended in some cases according to valid guidelines. However, the presence of permanent foreign material carries with it a lifelong risk. Biodegradable mesh seems to be the solution. However, effectiveness has not yet been proven.
Polycaprolactone is an FDA-approved nanomaterial for human use that has already been tested with promising results in animal models in the treatment of scar hernia prevention. The pitfalls of its use are its fragility and the difficulty of handling in the form of nanofibers.
The aim of the work is to test the hypothesis, whether nanofibers in liquid form improve the quality of the scar after laparotomy closure and thus lead to a reduction in the risk of a hernia in the scar. That is develop and test Polycaprolactone nanofibers in the form of a liquid hernia mesh that could be easily applied in the operating room. The hypothesis is still the same. The huge surface area of nanofibers is independent of their length, so even short fibers mixed with a gel medium in liquid form should not lose their ability to support the migration and proliferation of fibroblasts into the newly formed tissue.
An animal experiment on a small animal (rabbit) has taken place and we are now in the phase of collecting results, which according to the already available histological examinations and biomechanical testing seem promising.
The research part of the project is supported by a grant from the AZV CR.