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Patient-derived xenograft models of human lymphomas for experimental immunotherapy
Jakša, Radek ; Klener, Pavel (advisor) ; Škarda, Jozef (referee) ; Kalinová, Markéta (referee)
Non-Hodgkin lymphomas (NHL) represent the most common hematologic malignancies. Patient-derived xenografts (PDX) are used for various aspects of translational research including preclinical in vivo validation of experimental treatment approaches. While it was repeatedly demonstrated that PDX keep majority of somatic mutations with the primary lymphoma samples, from which they were derived, the composition of PDX tumor microenvironment (TME) has not been extensively studied. We derived 15 PDX models from patients with various subtypes of aggressive lymphomas. We implemented complex genetic and immunohistochemical analysis of the established PDX models head-to-head with the patient's primary lymphoma cells, from which the PDXs were derived. We clearly confirmed that the established PDX cells shared majority of somatic mutations with the patient's primary cells, from which they were derived. Thus, from the genetic perspective the PDX models represent relevant tools for the study of lymphoma biology. Immunohistochemistry analysis of selected antigens revealed some differences between the PDXs and patients' primary cells. Importantly, the analysis demonstrated complete loss of non-malignant cellular components of the tumor microenvironment frequently observed in lymphoma infiltrated lymph nodes,...
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The role of microRNAs in lymphomas with a focus on miR-155
Hušková, Hana ; Stopka, Tomáš (advisor) ; Svoboda, Petr (referee)
MicroRNAs (miRNAs) are 19-25 nucleotide noncoding RNAs which regulate the expression of target mRNAs at both posttranscriptional and translational level. The physiological functions of miRNAs include development, differentiation, cell cycle regulation and apoptosis. miRNA deregulation has been found in various human diseases, including lymphoproliferative disorders. This Bachelor thesis provides introduction to delineate roles of miRNAs in normal hematopoiesis and cites recent publications on miRNAs in lymphomas with a focus on the role of miR-155. Key words microRNA, hematopoiesis, lymphoma, miR-155
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Magnetic resonance imaging of central nervous system lymphoma.
Koubská, Eva ; Malíková, Hana (advisor) ; Kalvach, Pavel (referee) ; Druga, Rastislav (referee)
Background: The aim of this study was to describe the morphological signs of the central nervous system lymphoma (CNSL) in magnetic resonance imaging (MRI). We compared morphological characteristics of primary CNSL (PCNSL) and secondary CNSL (SCNSL) and also of PCNSL and glioblastoma (GBM). Methods: We included 64 patients with PCNSL (ten of them were immunocompromised), 21 patients with SCNSL and 54 patients with GBM. The diagnosis was confirmed histologically in all patients. We evaluated morphological signs on the first MRI examination. Additionally, in patients with PCNSL, we evaluated the development of the disease on follow-up examination before histological confirmation of the diagnosis, if available. Results: In most patients with PCNSL (62.5%) the tumor was localized supratentorially and presented as multiple lesions (53.1%) or as a diffuse infiltrative lesion (23.4%). In 87.5% of the patients the lesions reached the brain surface. Infiltration of ependyma was seen in 56.3%, infiltration of meninges in 39.1% and infiltration of cranial nerves in 48.5% of patients. Restriction of diffusion in some part of the tumor was apparent in nearly all patients (97.6%) with PCNSL. After administration of contrast media, marked enhancement was usually seen. In immunocompetent patients, homogenous...
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Resenzitalizace leukemických a lymfomavých buněk k trailerem indukované apoptóze
Molinský, Jan ; Klener, Pavel (advisor) ; Hyršlová Vaculová, Alena (referee) ; Vyoral, Daniel (referee)
Apoptosis serves as a natural barrier to cancer development, and the resistance to apoptosis represents one of the key capabilities acquired during tumor development or progression. Impairment of the intrinsic apoptotic pathway exemplifies one of the established mechanisms of constitutive or acquired drug resistance. As most of the currently used cytotoxic drugs initiate tumor cell death by direct or indirect triggering of the intrinsic apoptotic pathway, impairment of the intrinsic pathway is associated with therapy failure. Targeting of the death receptors, however, enables induction of apoptosis even in the chemotherapy resistant cancer cells. TRAIL is a death ligand belonging to the TNFα superfamily that specifically kills tumor cells while sparing healthy tissues. Much enthusiasm has been generated for TRAIL as a highly promising targeted anti-cancer agent. However, many primary tumors have been shown to be TRAIL resistant. In attempt to overcome such an intrinsic TRAIL resistance a wide array of agents have been shown to sensitize tumor cells to TRAIL. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. In this study we analyzed the sensitivity of diverse hematologic malignancies to TRAIL-induced apoptosis and measured the...
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Complex Preoperative Brain Tumor Imaging
Tupý, Radek ; Ferda, Jiří (advisor) ; Vymazal, Josef (referee) ; Tüdös, Zbyněk (referee)
Title Complex preoperative brain tumor imaging Abstract The differentiation of glioblastoma, metastases and brain lymphoma using modern diagnostic imaging methods has a major impact on the strategy of further diagnostic examinations and treatment. In a group of 67 patients with glioblastoma and 31 with cerebral metastasis, the ability to differentiate them according to the evaluation of perfusion parameters changes in peritumoral white matter by T1 dynamic post-contrast magnetic resonance imaging was verified, with the positive predictive value in glioblastoma detection up to 91%. In a group of 36 brain lymphoma patients the importance of imaging submodalities and contribution of a complex magnetic resonance imaging protocol to detect lymphoma up to 80% were evaluated. Key words brain, glioblastoma, lymphoma, magnetic resonance imaging, neoplasm metastasis
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Magnetic resonance imaging of central nervous system lymphoma.
Koubská, Eva ; Malíková, Hana (advisor) ; Kalvach, Pavel (referee) ; Druga, Rastislav (referee)
Background: The aim of this study was to describe the morphological signs of the central nervous system lymphoma (CNSL) in magnetic resonance imaging (MRI). We compared morphological characteristics of primary CNSL (PCNSL) and secondary CNSL (SCNSL) and also of PCNSL and glioblastoma (GBM). Methods: We included 64 patients with PCNSL (ten of them were immunocompromised), 21 patients with SCNSL and 54 patients with GBM. The diagnosis was confirmed histologically in all patients. We evaluated morphological signs on the first MRI examination. Additionally, in patients with PCNSL, we evaluated the development of the disease on follow-up examination before histological confirmation of the diagnosis, if available. Results: In most patients with PCNSL (62.5%) the tumor was localized supratentorially and presented as multiple lesions (53.1%) or as a diffuse infiltrative lesion (23.4%). In 87.5% of the patients the lesions reached the brain surface. Infiltration of ependyma was seen in 56.3%, infiltration of meninges in 39.1% and infiltration of cranial nerves in 48.5% of patients. Restriction of diffusion in some part of the tumor was apparent in nearly all patients (97.6%) with PCNSL. After administration of contrast media, marked enhancement was usually seen. In immunocompetent patients, homogenous...
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Education of patients with lymphoma
Marková, Naďa ; Kordulová, Pavla (advisor) ; Jankovcová, Kateřina (referee)
(v AJ) I chose the education of a patient with lymphoma as the topic for my bachelor thesis. I consider this topic very actual because the occurence of lymphoma is increasing (In: Linkos,2019). Lymphomas are referred as lymphocyte-derived tumors. I deal with the problem of lymphomas in the theoretical part. I mainly focus at diagnostic and treatment. I had started to prepare this bachelor thesis after the background research in the National Medical Library. I also drew the information from databases: BMČ, PubMed, EBSCOhost a Medline. I also used treatment recommendations - Cooperative Lymphoma Groups. Methology: I chose a case study of a patient with B-cell lymphoma from large cells, diffuse. I used the model of Marjora Gordon's - functional health model. A specific case is used for defining the treatment procedures, nursing standards, potentional risks and the prevention, education is also included. Objective: Focus on a nursing care - pacient with B-cell lymphoma diagnose, large cells, diffuse, who undergone chemotherapy. Results: Keeping nursing procedures and creation of educational material for patients. Conclusion: There are new methods of chemotherapy and new studies. A current study in Lymphoma: CITADEL 203, CITADEL 205, PCYC 1143 - SYMPATICO, ACELY - 308, PCYC 1141, BGB3311 - 212, IELSG37...
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Complex Preoperative Brain Tumor Imaging
Tupý, Radek ; Ferda, Jiří (advisor) ; Vymazal, Josef (referee) ; Tüdös, Zbyněk (referee)
Title Complex preoperative brain tumor imaging Abstract The differentiation of glioblastoma, metastases and brain lymphoma using modern diagnostic imaging methods has a major impact on the strategy of further diagnostic examinations and treatment. In a group of 67 patients with glioblastoma and 31 with cerebral metastasis, the ability to differentiate them according to the evaluation of perfusion parameters changes in peritumoral white matter by T1 dynamic post-contrast magnetic resonance imaging was verified, with the positive predictive value in glioblastoma detection up to 91%. In a group of 36 brain lymphoma patients the importance of imaging submodalities and contribution of a complex magnetic resonance imaging protocol to detect lymphoma up to 80% were evaluated. Key words brain, glioblastoma, lymphoma, magnetic resonance imaging, neoplasm metastasis
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Nursing care for patient suffering from lymphoma.
MURÁŇOVÁ, Kateřina
The main goal of the thesis was to map the specific needs of the patient with lymphoma and to determine the requirements for nursing care. In connection with these goals, four research questions have been identified. "What are the specific physical needs of a patient with lymphoma?"; "What are the specific psycho-social needs of a patient with lymphoma?"; "What nursing problems are there in a patient with lymphoma?"; "What is considered by patient with lymphoma in the context of nursing care a priority?". The empirical part of the bachelor´s thesis was processed through a qualitative research analysis, which was carried out by a depth interview. The depth interview was divided into four sections, which were further divided into different sections referring informants to specific questions. The first round focused on basic indentification data of informants. The second round focused on the specific physical and psychosocial needs of the patient with lymphoma. In the third round, the nursing problems of the patient with lymphoma were mentioned. The last fourth part dealt with the patient's priorities for nursing care. The obtained results were processed in the form of an open coding method "pencil-paper". The research group was consisted of five patients suffering from lymphoma. Based on the research, four categories were identified: the course of illness, the influence of physical needs of illnesses, the influence of psycho-social needs of illnesses and priorities in nursing care. The thesis provides an overview of the issue of lymphoma from the patient's perspective. The thesis takes into account the specific needs of patients with lymphoma and their requirements for nursing care. The results of the thesis can be used as a teaching material for students of health care disciplines or can be used by nurses in connection with take care of patients suffering from lymphoma.
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Resenzitalizace leukemických a lymfomavých buněk k trailerem indukované apoptóze
Molinský, Jan ; Klener, Pavel (advisor) ; Hyršlová Vaculová, Alena (referee) ; Vyoral, Daniel (referee)
Apoptosis serves as a natural barrier to cancer development, and the resistance to apoptosis represents one of the key capabilities acquired during tumor development or progression. Impairment of the intrinsic apoptotic pathway exemplifies one of the established mechanisms of constitutive or acquired drug resistance. As most of the currently used cytotoxic drugs initiate tumor cell death by direct or indirect triggering of the intrinsic apoptotic pathway, impairment of the intrinsic pathway is associated with therapy failure. Targeting of the death receptors, however, enables induction of apoptosis even in the chemotherapy resistant cancer cells. TRAIL is a death ligand belonging to the TNFα superfamily that specifically kills tumor cells while sparing healthy tissues. Much enthusiasm has been generated for TRAIL as a highly promising targeted anti-cancer agent. However, many primary tumors have been shown to be TRAIL resistant. In attempt to overcome such an intrinsic TRAIL resistance a wide array of agents have been shown to sensitize tumor cells to TRAIL. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL. In this study we analyzed the sensitivity of diverse hematologic malignancies to TRAIL-induced apoptosis and measured the...
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