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- W2053640003 abstract "The recombinant soluble human TRAIL mutant (DATR), derived from tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a promising agent for cancer therapy. The present study evaluated the toxicity of DATR in rats and monkeys. Based on the results, the safety and toxic doses of DATR intravenously injected to rats for 50 days were 60 and 180 mg/kg, respectively, and when delivered intravenously guttae to monkeys for 50 days, these levels were 10 and 30 mg/kg, respectively. The main toxic effects in rats were red blood cell count and haemoglobin decreases; blood urea nitrogen and creatinine increases. The main toxic effects in monkeys included red blood cell count and haemoglobin decreases; alanine aminotransferase and aspartate aminotransferase increases; high proliferation of karyocytes of the erythrocyte series; and regional hydropic degeneration of hepatic parenchymal cells. The TUNEL assay showed both 90 mg/kg DATR- and TRAIL-induced apoptosis of the liver in monkeys, which confirmed the hepatotoxicity of DATR. These findings indicated that the target toxic organs of DATR might be the haematological system. Furthermore, kidney in rats and liver in monkeys are also likely target toxic organs. The toxicity was reversible and did not differ from that associated with TRAIL administered at the same dosage." @default.
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- W2053640003 date "2011-11-01" @default.
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- W2053640003 title "Preclinical toxicity of DATR, a recombinant soluble human TRAIL mutant, in rats and cynomolgus monkeys" @default.
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- W2053640003 doi "https://doi.org/10.1016/j.yrtph.2011.08.002" @default.
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