Core 3: Rexinoid Screening and Animal Core

Rexinoid筛选和动物核心（动物核心）是计划项目赠款的重要组成部分。它通过提供由项目2设计的新型rexinoids的临床前疗效和安全性信息来支持该计划的目标和目的，这些rexinoids有可能用作器官移植受者非黑色素瘤皮肤癌的化学预防剂。对于每种候选rexinoid，将确定用于预防正常小鼠和环孢素治疗小鼠中非黑色素瘤皮肤癌的有效剂量50（ED 50）;我们目前的先导化合物UAB 30的ED 50将用作比较物。还将确定新合成的类rexinoids的药代动力学、耐受性、器官毒性和脂质异常。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。维持这些独特小鼠的繁殖群体对于项目2和项目3中提出的实验特别重要。这些小鼠的组织也将储存起来，供项目研究者分析。核心科学家还将在实验方案的制定、IACUC批准方面提供帮助，并帮助制定紫外线照射和免疫抑制方案。

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.