Core 3: Rexinoid Screening and Animal Core

核心 3：Rexinoid 筛选和动物核心

基本信息

批准号：
10007604
负责人：
Mohammad Athar
金额：
$ 29.8万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10007604
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

项目摘要

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.

Rexinoid 筛选和动物核心（Animal Core）是该计划的重要组成部分项目补助金。它通过提供临床前支持来支持该计划的目的和目标由项目 2 设计的新型 rexinoid 的功效和安全性信息，具有潜力可用作器官移植中非黑色素瘤皮肤癌的化学预防剂收件人。有效剂量 50 (ED50) 可预防正常人和非黑色素瘤皮肤癌将为每个候选rexinoid建立环孢菌素处理的小鼠；我们的 ED50 目前的先导化合物 UAB30，将用作比较剂。药代动力学，新合成的类固醇的耐受性、器官毒性和脂质异常也将受到影响决定。 Rexinoid 筛选和 Animal Core 提供的另一项服务是维持 Ptch+/-/SKH1 小鼠群体。长期暴露于紫外线辐射后，这些小鼠发展为基底细胞癌、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敏感性。维持繁殖这些独特小鼠的群体对于中提出的实验特别重要项目 2 和项目 3。这些小鼠的组织也将被储存并可供向计划调查员进行分析。核心科学家也将提供开发协助实验方案、IACUC 批准以及紫外线照射和帮助免疫抑制方案。