Core 3: Rexinoid Screening and Animal Core

Rexinoid筛选和动物核心（动物核心）是该计划项目拨款的关键组成部分。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有可能成为器官移植受者非黑色素瘤皮肤癌的化学预防剂。在正常小鼠和环孢菌素治疗小鼠中预防非黑色素瘤皮肤癌的有效剂量50 （ED50）将为每个候选雷辛类药物建立；我们目前的先导化合物UAB30的ED50将被用作比较物。新合成的rexinoids的药代动力学，耐受性，器官毒性和脂质异常也将被确定。Rexinoid Screening and Animal Core提供的另一项服务是维持Ptch+/-/SKH1小鼠菌落。在长期暴露于紫外线辐射后，这些小鼠会患上基底细胞癌、鳞状细胞癌和癌前光化性角化病。因此，他们仔细地复制了人类皮肤癌对紫外线的易感性。在项目2和项目3中提出的实验中，维持这些独特小鼠的繁殖群体将是特别重要的。这些小鼠的组织也将被储存起来，供项目调查人员分析。核心科学家还将协助制定实验方案，批准IACUC，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.