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Information × Registration Number 0221U106908, 0117U004387 , R & D reports Title Development of methods for combined enzyme therapy and chemotherapy of malignantly transformed human cells using arginine-degrading enzymes popup.stage_title Head Stasyk Oleh V., Кандидат біологічних наук Registration Date 22-12-2021 Organization Institute of Cell Biology popup.description2 The Department of Cell Signaling of the Institute of Cell Biology of the National Academy of Sciences of Ukraine conducted the studies to improve the effectiveness of metabolic therapy based on arginine starvation for malignant cells of different types. In particular, to investigate the molecular mechanisms of acquired resistance, through repeated rounds of cell incubation in culture medium with added recombinant arginase for the first time were selected sublines of head and neck cancer cells with different sensitivity to arginine starvation. A comparative analysis of conditionally resistant to arginine starvation subline SAS-R9 and the original "parent" line of head and neck cancer SAS cells on several functional parameters we performed. The fasting-adapted subline SAS-R9 was found to show an increased clonogenic potential and invasive properties, as well as an increased expression of markers of epithelial-mesenchymal transition. The effects of combinational metabolic therapy using structural analogues of arginine (canavanine or indospicin) on the model of B16F10 mouse melanoma cells in vitro were also studied. B16F10 cells were generally more resistant to such kind of therapy than human melanoma cells. The combination regimen based on pegylated arginase and canavanine was tested in vivo experiments and analysed whether these factors could cause signs of acute toxicity in experimental animals. Our studies on C57/Bl6 laboratory mice with implanted B16F10 mouse melanoma have shown that combination therapy based on arginase and low doses of canavanine is non-toxic to animals and significantly inhibits melanoma growth. The obtained results will be used in the further development and testing of combination antitumor therapy based on amino acid starvation.   Product Description popup.authors Bobak Yaroslav P Vovk Olena Ivanivna Hruba Olena Ivanivna Danyleichenko Valerii Vasyl'ovych Polishchuk Nikita Valentynovych Stasyk Olena Н. Chen Oleg I Chernyshuk Svitlana V Shuvayeva Galina Yuriivna popup.nrat_date 2021-12-22 Close