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Information × Registration Number 0223U000037, (0118U003471) , R & D reports Title Phenotype and genotype of cells under the influence of tumor-associated genes and potential therapeutic cytotoxic agents popup.stage_title Фенотип і генотип клітин за дії пухлино-асоційованих генів та потенційних терапевтичних цитотоксичних агентів Head Areshkov Pavlo O., Кандидат біологічних наукSkrypkina Inessa Ya., Кандидат біологічних наук Registration Date 01-01-2023 Organization Institute of Molecular Biology and Genetics of NAS of Ukraine popup.description1 popup.description2  Object of the study: glioma-associated genes CHI3L1 and CHI3L2 and clinical cytotoxic first-line glioma therapy temozolomide as effectors of chromosomal instability and acquisition of drug resistance in tumor cells. The aim of the project is to establish the consequences of overexpression of CHI3L1 and CHI3L2 genes associated with tumor development and long-term treatment with temozolomide systemic cytotoxic agent on the karyotype and phenotype of cells of tumor and non-tumor origin as predictive factors in the development of new therapeutic strategies for cancer. Methods used: reverse transcription-polymerase chain reaction, mammalian cell culture, transfection and lentiviral transduction, molecular cloning, Western blot analysis, cell colony formation assay in semi-liquid medium, cell viability and karyotyping assay, whole transcriptome NGS analysis. In this work, we found that the progression of random karyotypes and the acquisition of malignant transformation features by cells of glial tumor (U251) and non-tumor (NEK293) origin is due to the action of tumor-associated CHI3L1 and CHI3L2, rather than the transfer of foreign DNA as a factor of genome stochasticity. Also, it was confirmed that the evolution of spontaneous karyotypes of transgenic tumor cells U251 under the action of long-term treatment with clinical cytotoxic first-line therapy of glioblastoma temozolomide (TMZ) leads to inhibition of cell growth. However, it has been clearly demonstrated that among other transgenes, ectopic expression of CHI3L1 enhances the proliferative TMZ-resistant potential of cells with an increased random generation of spontaneous genetic abnormalities. By conducting a deep analysis of transcriptomes (mRNA-sequencing) of parental U251 cells and transgenic derivatives and TMZ-resistant derivatives, a list of transgene and TMZ-specific genes was identified - promising molecular genetic targets for the development of new therapeutic strategies for the treatment of gliomas. Product Description popup.authors Hanna M. Svitina Shablii Volodymyr A. Anopriienko Olha V. Shablii Yulia M Romantsova Olena S. popup.nrat_date 2023-01-01 Close