Comparative assessment of subsipopulations of tumor-associated macrophages in breast cancer depending on the response to chemotherapy

The key cells of the immune system that determine the relationship between tumor cells and the microenvironment, beginning with early stages of tumor growth, including regulation of neoangiogenesis and the terminal stage of malignant process, are tumor-associated macrophages (TAM). In the present study, identification of TAM markers in breast tumors in patients with neoadjuvant chemotherapy and a comparative assessment of the differences in the macrophages subpopulation in tumors with different response to chemotherapy were carried out. The data we obtained indicate the functional differences between TAM subpopulations that have various phenotypes, that are confirmed at the level of associative links with the effectiveness of chemotherapy

Анализ напряженно-деформированного состояния компенсаторов при проектировании нефтепроводов с использованием программного комплекса ANSYS

В работе рассмотрены характеристики исследуемого объекта – термокомпенсационные блоки на участке нефтепровода "Заполярье-Пурпе". Приведен расчет толщины стенки трубопровода, проверка его прочности и устойчивости, расчет компенсатора и его компенсирующей способности. Выполнено моделирование компенсаторов различного типа в программном комплексе Autodesk Inventor. Проведен анализ напряженно-деформированного состояния конструкций в программной среде ANSYS.The paper describes the characteristics of the studied object - thermal compensation blocks on the section of the Zapolyarye-Purpe oil pipeline. The calculation of the wall thickness of the pipeline, the verification of its strength and stability, the calculation of the compensator and its compensating ability. Compensators of various types have been simulated in the Autodesk Inventor software package. The analysis of the stress-strain state of structures in the ANSYS program is carried out

Region specific characterization of the cuprizone model for Multiple Sclerosis and impairment of remyelination by corticosteroids

Multiple sclerosis is a widespread demyelinating disease where primary oligodendrocyte dysfunction represents a possible underlying mechanism of myelin loss. Cuprizone intoxication which causes primary oligodendrocyte apoptosis, mimics some aspects of this disease. In the first part of my thesis, the extent and pattern of demyelination in this MS animal model was analyzed. Additionally, the innate immune responses to the cuprizone challenge were investigated. Our results regarding the cerebellum were included in this thesis, and the different pattern of demyelination in the basal ganglia, hippocampus, and cerebellum was highlighted. Striking differences were found in the magnitude of demyelination between different white and grey matter areas. Distinct cerebellar white matter regions, the cerebellar cortical grey matter, the medial basal ganglia, and the hippocampal fimbria were resistant to the cuprizone challenge. In contrast, other regions displayed severe myelin loss and activation of microglia and astroglia. We discuss the advantages and limitations of this model with regard to regional differences and “protection”. In the second part of this work, we used the cuprizone model to investigate the impact of corticosteroid (CS) treatment on spontaneously remyelinating lesions and addressed the underlying mechanisms by several in vitro and in vivo approaches. We are able to demonstrate that while CS-treatment accelerates the differentiation of oligodendrocyte progenitors in vitro, it impairs endogenous remyelination in vivo. We additionally identified CS-induced changes in the growth factor expression profile of cultured astrocytes that might explain the impairment of repair processes in the brain. The importance of astrocytes for early and late repair processes was further highlighted by our finding that astrocytosis but not microgliosis persists after an acute demyelinating event. Our data clearly show that promotion of the intrinsic oligodendroyte differentiation program might negatively affect myelin repair in vivo. We speculate that CS treatment induces a preterm oligodendrocytes differentiation and, thus, might impair endogenous remyelination cascades. Furthermore, beneficial steroidal effects during inflammation have to be balaced against possible remyelination-inhibiting effects. In the third part of the presented thesis, we focused on astrocyte’s response during an acute demyelinating event. The amyloid precursor protein (APP) which is well known to be expressed in activated astroglia, microglia and stressed neurons in several disease models, was in the focus of the study. We found that the expression of APP is strongly induced during acute cuprizone-induced demyelination. Exclusively astrocytes express APP during cuprizone-induced demyelination. Our in vitro experiments using primary astrocyte cultures indicate that this is a highly specific response to toxic demyelination. The cuprizone model, therefore, is a suitable tool to study the role of astrocyte derived APP in a MS animal model. The results of my thesis significantly broaden the knowledge regarding the potential of the cuprizone model as a tool for studying underlying mechanisms of de- and remyelination