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Information × Registration Number 0209U001251, 0105U005558 , R & D reports Title The elaboration of experimental test-systems and mathematical models of angiogenesis-dependent growth of malignant tumors to determine the markers of their sensitivity against antiangiogenic agents. popup.stage_title Head Solyanyk Galyna Ivanivna, Registration Date 26-01-2009 Organization R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology popup.description2 Experimental and mathematical models that form experimental test-system with possibility to screening in vitro and to performing preclinical trial of anticancer agents with antiangiogenic actions was elaborated. Metastatic variant LLC/R9 was developed and described. We have been shown that this variant, in difference from parental Lewis lung carcinoma (LLC), has significant angiogenesis dependent tumor growth and elevated sensibility to treatment by traditional anticancer antiangiogenic therapy (by anti-VEGF or by low doses of cyclophosphamide in metronomic routine). Two malignant tumor variants of the same origin, but with different sensibility to treatment by anticancer antiangiogenic therapy, gives us choice to perform experimental test-system for screening and performing preclinical trial of anticancer agents with antiangiogenic effects. As comparative analysis of LLC and LLC/R9 biological properties revealed, high cancer cell sensibility to treatment by anticancer antiangiogenic therapy correlatedwith low metastatic potential, high VEGF levels and high speed of tumor growth in vivo. Experimental test-system for study of antiangiogenic drugs influence on endothelial and cancer cell functional activity and their interaction was also elaborated. With use of this system was detected that high cancer sensibility to treatment by anticancer antiangiogenic therapy associated with low cancer cell surface charge and week adhesiveness to endothelium. Furthermore experimental test-system and mathematical model for study of nutritious deficit influence on functional cancer cell activity and survival was elaborated. Elaborated system (unfed culture) gives us possibility: а) to reveal cancer cell sensibility to nutritious deficit; б) to study mechanism of cancer cell survival under metabolic stress that appears in response to efficient cancer angiogenesis inhibition; г) to carry out screening and testing agents that increase cancer cell death throughout antiangiogenic therapy. Comparative analysis of functional LLCand LLC/R9 cell activity and survival in unfed culture revealed that high cancer sensibility to treatment by anticancer antiangiogenic therapy correlated with strong dependence of cancer cell switch to the resting state from glucose levels, fast speed of cell death, and increased capability to autophagy under nutritious deficit. Comparative analysis of functional mononuclear phagocyte activity in mice bearing LLC and LLC/R9 identified the tight correlation between the high cancer sensibility to anticancer antiangiogenic therapy and the increase of oxygen dependent metabolism, cytotoxic and phagocyte activities, and TNF? levels in macrophages. With the use of elaborated experimental test-system was demonstrated that aconitine containing plant drug "ВС1" with high anticancer and antimetastatic activities on LLC/R9 could perceive as promising anticancer antiangiogenic agent. Product Description popup.authors popup.nrat_date 2020-04-02 Close