Figure 6.
Elatol is well tolerated in mice up to 65 mg/kg and treatment slows tumor progression in vivo, but high doses show liver and cardiac toxicity. A) Complete blood counts for white blood cells, hemoglobin and platelets of SCID mice following treatment with 20 mg/kg elatol daily for 5 days. Mean ± SEM n=17 and 7 vehicle and elatol respectively. B) SCID mice were engrafted with 2×106 SU-DHL6 cells. Once tumors reached 60mm3 treatment began with 20 mg/kg i.p. daily for 5 days and tumor volume was measured twice per week. Mean ± SEM, n=8. C) Maximum tolerated dose study in normal CD1 mice. Cohorts of 5 mice were given a single indicated dose of elatol and observed daily for signs of morbidity. At time of death due to toxicity or at day 14 if no toxicities were observed mice were sacrificed for organ pathology. D) H&E staining of the heart and liver of mice treated with 50 or 100 mg/kg elatol. Representative images n=5. E) SCID mice were implanted with 1×106 serially transplanted OCI-Ly3 xenograft cells. When tumors reached at least 50 mm3 mice were pair matched and treatment began with either vehicle or 40 mg/kg of elatol i.p. twice weekly. Mean ± SEM, n=8. * = p< 0.05.