Core 3: Rexinoid Screening and Animal Core

核心 3：Rexinoid 筛选和动物核心

• 批准号: 10263928
• 负责人: Mohammad Athar
• 金额: $ 18.62万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10263928
• 关键词: Animals; Applications Grants; Basal cell carcinoma; Binding; Biological Availability; Breeding; Chemoprevention; Chemopreventive Agent; Chronic; Clinical Trials; Cyclosporine; Data; Development; Dose; Drug Kinetics; Evaluation; Exposure to; Genotype; Goals; Histologic; Human; IACUC; Immunocompetent; Immunosuppression; In Vitro; Inbred HRS Mice; Lead; Lipids; Malignant Epithelial Cell; Morbidity - disease rate; Mus; Oral; Organ; Organ Transplantation; Play; Predisposition; Prevention; Program Research Project Grants; Protocols documentation; RXR; Research Personnel; Role; Safety; Scientist; Serum; Services; Skin; Skin Cancer; Skin Carcinoma; Skin Neoplasms; Squamous cell carcinoma; Stains; Testing; Tissues; Toxic effect; Toxicology; Transplant Recipients; Triglycerides; UVB induced; Ultraviolet Rays; animal breeding; animal data; animal tissue; base; cancer chemoprevention; clinical application; design; experimental study; immunosuppressed; in vivo; mortality; mouse model; novel; pre-clinical; preclinical efficacy; premalignant; programs; receptor; response; screening; skin cancer prevention; skin lesion; tool; tumorigenesis; ultraviolet irradiation

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.

Rexinid筛选和动物核心(Animal Core)是该计划的关键组成部分 格兰特项目。它通过提供临床前服务来支持计划的目标和目的 由项目2设计的新型Rexinoid的有效性和安全性信息，这些信息具有潜在的 可作为器官移植中非黑色素瘤皮肤癌的化学预防药物 收件人。预防非黑色素瘤皮肤癌的有效剂量50(ED50) 将为每个候选rexinid建立环孢素A治疗的小鼠；我们的 目前的铅化合物，UAB30，将用作比较器。药代动力学， 新合成的类维A酸类药物的耐受性、器官毒性和血脂异常也将 下定决心。Rexinid筛选和动物核心提供的另一项服务是 维持一群pTch+/-/SKH1小鼠。在长期暴露于紫外线辐射之后，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，他们小心翼翼地复制了人类皮肤癌对紫外线的敏感性。维持一种繁殖 这些独特的小鼠的群体将对在 项目2和项目3。这些小鼠的组织也将被储存并提供给 向项目调查人员提供分析。核心科学家还将在发展方面提供援助 实验方案，IACUC批准，并帮助紫外线照射和 免疫抑制方案。