LB-S&T-10 THREE INTRINSIC SUBTYPES OF PROSTATE CANCER WITH DISTINCT PATHWAY ACTIVATION PROFILES DIFFER IN PROGNOSIS AND TREATMENT RESPONSE

Abstract

receptors, competitively blocking muscarinic receptors and highly selective towards urinary bladder receptors. In anticipation of the clinical trial: “multicenter, open-label, randomized, comparative clinical study of efficiency and safety of medicinal product Imidafenacin, 0,2 mg per day and Tolterodinum, 4 mg per dayfor treatment of overactive bladder”, was conducted preclinical study. METHODS: The immunotoxic properties study included tests to evaluate humoral, cell-mediated, and non-specific immune responses conducted in mature male and female Balb/C mice. In all these tests, Imidafenacin was administered intragastrically at doses 0.083 mg/kg (TD) and 0.83 mg/kg (10TD) over a period of 28 days. The effects of the medicinal product on humoral immune response was evaluated by the antibody titre following an injection of sheep erythrocyte suspension. Study animals were administered the sheep erythrocyte suspension intraperitoneally to achieve immunization. In 7 days after immunization, the antibody titre in the serum was measured. Cell-mediated immune response was evaluated using the delayed-type hypersensitivity reaction to the hapten dinitrochlorobenzene (DNCB). Experimental animals were immunized by subcutaneous injection of 2 % DNCB solution in DMSO between the shoulder blades. Five days later, immunized mice were administered 0.1 % DNCB solution under the aponeurosis of a hind leg. In 24 hours after the challenging injection, the animals were euthanized and the DTH reaction index calculated by the difference between the weight of the experimental leg and that of the control leg. RESULTS: Statistical analyses of obtained data revealed no effect of multiple dose intragastric administration of imidafeniacin 0.083 mg/kg (TD) and 0.83 mg/kg (10TD) on the anti-sheep erythrocyte antibody titre in sexually mature male and female mice. The delayed-type hypersensitivity reaction test demonstrated that the investigational medicinal product administered over a 28-day period intragastrically at 0.083 mg/kg had no effect on the development of cell-mediated immune response in mice of either gender. Administration of Uritos at 0.83 mg/kg increased with statistical significance the cell-mediated immune response by 40 % in males and 45 % in female animals. The phagocytic activity test carried out on murine peritoneal macrophages demonstrated that the intragastric course of the TD and 10TD doses of Uritos increased, with statistical significance and in a dose-dependent manner, the non-specific immune response in male animals by 25 % and 43 %, respectively, and in female mice by 26 % and 40 %, respectively, as compared with animals given the vehicle. CONCLUSIONS: Imidafenacin administered at the 0.083 mg/kg (TD) or 0.83 mg/kg (10TD) dose demonstrated no immunotoxic properties