Core 3: Rexinoid Screening and Animal Core

Rexinoid筛选和动物核心（动物核心）是该计划的关键组成部分 格兰特计划它支持该计划的目标和目的，提供临床前 由项目2设计的新型rexinoids的疗效和安全性信息， 在器官移植中用作非黑素瘤皮肤癌的化学预防剂 受惠人士预防正常和非黑色素瘤皮肤癌的有效剂量50（ED 50） 将针对每种候选rexinoid建立环孢霉素处理的小鼠;我们的实验的ED 50将是100。 目前的铅化合物，UAB 30，将被用作比较。药代动力学， 新合成的类Rexinoids的耐受性、器官毒性和脂质异常也将被 测定Rexinoid筛选和动物中心提供的另一项服务是 维持Ptch+/-/SKH 1小鼠的群体。在长期暴露于紫外线辐射后，这些小鼠 发生基底细胞癌、鳞状细胞癌和癌前光化性角化病。 因此，他们仔细复制了人类皮肤癌对紫外线的敏感性。保持一种繁殖 这些独特的小鼠群体将是特别重要的实验中提出的 项目2和项目3。来自这些小鼠的组织也将被储存并可用于 对项目调查人员进行分析。核心科学家还将在开发方面提供帮助 实验协议，IACUC批准，并帮助紫外线照射， 免疫抑制方案。

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.