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Information × Registration Number 0216U005338, 0115U005604 , R & D reports Title Investigation of the mechanisms of glioma chemoresistance and development of the approaches to glioma complex therapy popup.stage_title Head Dmitrenko Vladimir Vladimirovich, Registration Date 22-01-2016 Organization Institute of Molecular Biology and Genetics of NASU popup.description2 The aim of the project was to develop the new approaches to the complex therapy directed to multiple tragets in malignant tumors of the human brain, particularly, the potential oncoproteins - chitinase 3-like protein 1 (CHI3L1) and minichromosomes supported protein 7 (MCM7), as well as the elucidation of the changes in karyotype and phenotype of glioblastoma cell line during the resistance development to the clinical drug temozolomide. It was planned in the course of the project to create a combination of new anticancer compounds and commonly used anticancer clinical chemotherapy drugs, promoting the development of high efficiency therapeutic regimens with low toxicity for the treatment of gliomas. Furthermore, we studied the consequences of temozolomide resistance development in glioblastoma cell culture at the level of genotype and phenotype. The investigation of the cytotoxic activity of a number of peptide and non-peptide antagonists of bradykinin of new generation was performed using different types of malignant cells. The most active compounds were identified. The effect of the combination of temozolomide with bradykinin antagonists on the viability of human glioma cells was analized. It was achieved a significant increase of the temozolomide efficiency in concentrations much lower than that used in the clinic when combined with bradykinin antagonists. This should reduce at several times temozolomide dose for the patient treatment, thereby reducing its toxic effects and the cost of therapy as it is. To analyze the effect of inhibition of glioma-associated oncoprotein CHI3L1 production via short antisense oligonucleotides on the HeLa cells malignant phenotype, the HeLa_CHI3L cells were established, that stably produce CHI3L1 protein. Two variants of U251 human glioblastoma cell lines resistant to temozolomide were obtained. It has been shown that long-term treatment of tumor cells with this drug leads to the significant changes in karyotype, genetic heterogeneity and phenotype. Therapy-mediated stress can contribute to the evolution of the tumor by the selection of genetic variations, as well as by creating new variations through increasing the level of chromosomal instability. Product Description popup.authors Авдєєв Станіслав Сергійович Дмитренко Володимио Володимирович Степаненко Олексій Анатолійович Чаусоський Тімур Йосипович popup.nrat_date 2020-04-02 Close