The Rexinoid Screening and Animal Core (Animal Core) is a critical component of the Program Project Grant. It supports the goals and objectives of the Program by providing pre-clinical efficacy and safety information on novel rexinoids, designed by Project 2, that have the potential to be useful as chemopreventive agents for non-melanoma skin cancers in organ transplant recipients. Effective dose 50 (ED50) for prevention of non-melanoma skin cancer in normal and cyclosporine-treated mice will be established for each candidate rexinoid; the ED50 of our current lead compound, UAB30, which will be used as a comparator. Pharmacokinetics, tolerability, organ toxicity and lipid abnormalities of the newly synthesized rexinoids will also be determined. Another service provided by the Rexinoid Screening and Animal Core is to maintain a colony of Ptch+/-/SKH1 mice. Following chronic exposure to UV radiation, these mice develop basal cell carcinomas, squamous cell carcinomas and premalignant actinic keratoses. Thus, they carefully replicate human skin cancer susceptibility to UV. Maintaining a breeding colony of these unique mice will be particularly important for the experiments proposed in Projects 2 and Project 3. Tissues from these mice will also be banked and made available for analysis to Program investigators. Core scientists will also provide assistance in development of experimental protocols, IACUC approvals, and help with UV irradiation and immunosuppression protocols.
The Rexinoid Screening and Animal Core will provide in vivo efficacy and toxicity data for UAB30 and the novel rexinoids, designed and synthesized in Project 2 and Core 2, that show potential for clinical application for the prevention of non-melanoma skin cancer in organ transplant recipients. In addition to the needs of the Core, it will also supply Projects 2 and 3 with Ptch+/-/SKH1 mice and/or tissues from those mice for their studies.