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Information × Registration Number 0214U001425, 0110U006650 , R & D reports Title Study of genetic and epigenetic mechanisms of malignancy loss by tumor cells under interferon action popup.stage_title Head Koudriavets Iouri Iosifovich, Registration Date 13-02-2014 Organization R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology popup.description2 In the model of tumor cell lines from different genesis, the modified prolonged exposure to IFN, were found that a common characteristic of IFN-modified tumor cells are inhibition of their tumorigenecity signs in vitro. The highest efficiency of cytokine was shown on cells with the dominance of mesenchymal characteristics and less - on cells of epithelial characteristics. Thus, the most significant change of EMT profiles was detected in cell line COLO-205, and the lowest - in the cell line MCF-7. Inhibition of malignancy of tumor cells by IFN (T-47D, Hep-G2, COLO205, A- 549 , K -56 ) accompanied by a significant change in the expression of tumor suppressor genes (p14arf, p21Waf1/Cip1), the adapter protein Dab-2 and inhibition of EMT-associated transcription factors Twist and Slug: was found a significant reduction of Slug-positive cells (from 50 % to the total absence of expression in the nucleus of COLO 205 cells). In addition, under the influence of IFN was found significant inhibition (BCC) or complete disappearance (hepatoma cells) nuclear expression of another EMT marker - catenin. This IFN action also activates the IFN -regulatory factor IRF-3 in tumor cells. All these changes were accompanied with inhibition of cells malignancy by in vitro tests. Thus, we first found that a new important mechanism to reduce the malignancy of cancer cells under the action of IFN is the inhibition of EMT process. Using transduction of tumor cells (lung carcinoma and melanoma) with recombinant baculovirus gene with IFN-beta (RBV/IFN) was found that the effect of IFN is accompanied by significant inhibition of features of malignancy melanoma cells in vitro and in vivo, which is associated with inhibition of the expression of EMT associated transcription factors. For the first time was shown that intravenous injection into mice RBV/IFN with lung metastases of melanoma significantly inhibits their growth and leads to complete regression of metastases in some animals. In cytogenetic analysis was shown new mechanism of antitumor action of IFN: significant genotoxic effect on carcinoma cells with malignant mesenchymal characteristics and high selective activity of IFN, which limits the heterogeneity of the tumor population. The schemes of clinical application of alpha-interferon in the metronomic regimen treatment of inoperable colorectal cancer patients with liver metastases were developed, which extends the life of patients and improve quality of their life. We have developed a new method for detecting breast cancer patients with high risk of recurrence (for markers of disseminated tumor cells and high activity of TNF and M-CSF). This helps to conduct timely correction of further treatment, which significantly increases the duration of disease-free period. Product Description popup.authors Адаменко І.М. Бездєнєжних Н.О. Воронцова А.Л. Дошин І.Д. Завелевич М.П. Ковальова О.А. Кудрявець Ю.Й. Лихова О.О. Лупан В.Г. Марченко М.Л. Семесюк Н.І. Фільченков О.О. Цвір О.М. Шифрін К.Д. Ясинський Я.С. popup.nrat_date 2020-04-02 Close