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Information × Registration Number 0216U000015, 0113U000283 , R & D reports Title Determine the molecular-genetic markers of different subtypes of neuroectodermal brain tumors for evaluation of invasiveness level, prediction of prolonged growth and optimization of treatment tactics popup.stage_title Head Zozulia Yuriy, Registration Date 14-01-2016 Organization State institution ''Institute of Neurosurgery n.acad. AP. Romodanov NAMS of Ukraine'' popup.description2 Object of study: neuroectodermal tumors (NETs) of different histogenesis and degree of malignancy. Research methods: general and neurological clinical methods used under existing standards in assessing the severity of the patients and the predominance of a particular symptom complex; instrumental methods, complex morphological (anatomical-topographic) methods to determine the structures involved in pathological process, histological (general overview and special) - to determine the neuronal damage and conduction paths changes; immunohistochemical (identification of intermediate filaments, rate of proliferation, apoptosis); electronic microscopic method - to determine ultrastructural changes in cells and blood vessels; molecular-genetic methods (analysis of gene expression); morphometric methods - for objectification and quantification of detected changes of the structure of certain cells and cellular elements; statistical methods - for assessing the informativeness of methods. Purpose: To identify molecular-genetic markers of brain tumors to assess the biological aggressiveness: invasive activity, forecasting of periods of extended growth for optimization and individualization of therapeutic tactics. Results: It was found significant heterogeneity of histological variants of neuroectodermal tumors and in their various areas. There were determined variants of invasive nature of the extension of primary brain tumors: 1) parenchymal, 2) parenchymal-mesenchymal, 3) mesenchymal, 4) mesenchymal / interstitial, 5) interstitial, that determines the directions of their preferred distribution. We assume that morphogenesis of invasion caused by molecular-genetic features. Fluctuations of proliferative and apoptotic activity, the distribution of markers of intermediate filaments were identified, that objectify tumor's degree of differentiation and phenotype. These indicators correlate with the age of patients: in the older age group (>65 years) proliferation rate of glioblastoma lower than in the comparison group (<65 years) ((18 ± 0,5) % and (26 ± 1,2) % correspondingly). In older patients indicators of apoptotic activity were higher than in the comparison group: (35.8 - 54.2) % and (61.3 - 37.9) % correspondingly (p <0.0001). Morphological signs of hypoxia were detected in 83% of cases, and the degree of their intensity were higher in malignant gliomas; and it was found correlations with the age of patients, due to the development of the metabolic syndrome. In older people glioblastomas were diagnosed more often (54.2%). Morphometry results show a statistically significant reduce in the number of mitochondria in the cytoplasm of tumor cells and qualitative changes (fluctuations of mitochondria size and/or changes in their fine ultrastructure), which correlates with the degree of anaplasia. The cells of differentiated tumors demonstrated immunophenotype: nestyn- / GFAP +, and the cells of low differentiated (malignant) tumors - nestyn + / GFAP-, which is similar to embryonic one. This suggests a role of pluripotential cells and cell of microenvironment in morphogenesis, activity of progression, ways and nature of invasion and spread of brain tumors. The clinical-morphological comparing of NETs of different histological structure showed that malignant forms of tumors tend to spread along the midline structures (median). It was found based on morphometric studies the presence of a statistically significant difference between the ultrastructure of cells and the nature of the damages of the structure of blood vessels of the polymorphocellular and isomorphocellular glioblastomas. That may indicate different ways of induction, progression and of individual metabolic characteristics that influence on the response of treatment factors. There is found the complex of structural and ultrastructural disturbances in blood-brain barrier system, reflecting the morphofunctional microcirculation dysfunction, which grows and increases with age, and probably exacerbates hypoxia, contributing to the progression and invasive spread of tumors and influences on its potential responce to chemotherapy and radiation exposure. The revealed structural-molecular, metabolic features detail morphogenetic characteristics of NETs cells, types of their invasive spread, which is important for surgical stage of treatment and theoretical foundation of molecular targets of therapy and development of statistically significant markers of prognosis. Integrated clinical-morphological-molecular criteria of invasiveness of tumor, predicting of their extended growth and optimization of the treatment strategy were developed. Comprehensive studies of patients' brain using clinical, morphological and molecular techniques will highlight important prognostic markers of invasiveness and variants of tumor for optimizing of treatment (timing and extent of removal), to predict the timing of their extended growth with providing a high quality of life in remission period. BRAIN TUMORS, DIAGNOSIS, TREATMENT, STRUCTURAL-MOLECULAR RECONSTRUCTION, HYPOXIA, FORECAST. Product Description popup.authors Іванова О.М. Булавка А.В. Васлович В.В. Вербова Л.М. Главацький О.Я. Зінькевич Я.П. Кваша М.С. Малишева Т.А. Розуменко В.Д. Сидоренко С.П. Слинько Є.І. Черненко О.Г. Яворський О.А. popup.nrat_date 2020-04-02 Close