Optimizing a Pre-Clinical Mouse Model for Cancer Chemotherapy: Thirty-two Fold Increase in Maximum Tolerated Dose for a Novel Amidoxime with Anti-Cancer Properties
Chemotherapy treatment often follows tumor removal, with goals of preventing regrowth or metastasis from remaining cancerous cells. Our laboratory uses a mouse model for breast cancer chemotherapy, treating with novel compounds developed by Drs. Johnson and Bergel. We have demonstrated that the recently patented amidoxime JJMB9 affected mouse mammary tumor volume and metastasis. These results used a maximum tolerated dose (MTD) of JJMB9 established with a sesame oil-DMSO vehicle. Several mice receiving vehicle only died during those experiments, while an oil-free vehicle used in the last experiment resulted in no deaths. Accordingly, we have performed experiments to re-establish a maximum tolerated dose (90% survival) by progressively doubling the original 0.78 mg/kg dose. Each concentration increase resulted in zero deaths, establishing MTD of 25 mg/kg, thirty-two times the previous MTD. A further increase to 50 mg/kg compromised the mice’s health. These results allow more effective chemotherapy in our mouse model system.
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