TOPS-Ester Modulation of UVB-Induced Immune Suppression

UVB 诱导的免疫抑制的 TOPS 酯调节

• 批准号: 6550150
• 负责人: Carleton Hsia
• 金额: $ 9.87万
• 依托单位: SYNZYME TECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6550150
• 关键词: antioxidants; cancer prevention; drug metabolism; drug screening /evaluation; free radical oxygen; hairless mouse; immunoregulation; nitrobenzene; radiation immunosuppression; skin hypersensitivity; skin neoplasms; topical drug application; ultraviolet radiation

DESCRIPTION (provided by applicant): A TOPS-ester, diethyl 2,2,6,6-tetramethyl-1-oxyl-4-piperidene succinate (DETOPS), is a topical drug selected for development for its unique ability to compartmentalize within skin cells and express antioxidant activity that limits oxidant mediated pathologies including psoriasis, sunburn, skin aging and skin cancer. The objective of this project is to reduce skin cancer by preventing UV radiation-induced immune suppression. The specific aim of this study is to test the capability of DETOPS to interfere with the suppression of the immune system in mice that normally follows biologically-relevant doses of UV radiation. The immune status of SKH-1 hairless mice will be assessed by measuring whether topical application of DETOPS alters UV radiation induced changes in contact hypersensitivity. UV exposed control and DETOPS treated animals will be sensitized by topical application of dinitrofluorobenzene (DNFB) to their unirradiated abdomens. The animals will be challenged six days after sensitization by topical application of DNFB to ears. The magnitude of the ear-swelling response will be measured 15-21 hours later. A reduction in ear-swelling normally results from UV radiation-induced immunosuppression. The capacity of DETOPS to prevent skin cancer will be assessed in SKH-1 hairless mice chronically exposed to a biologically-relevant dose of UV radiation. Groups of mice with and without DETOPS treatment will be exposed to UV radiation five days per week for 11 weeks and then monitored for an additional 13 weeks for the appearance of skin tumors. The endpoints of interest for this study are whether DETOPS retards the time to appearance of skin cancer and reduces the yield of tumors. The immune status and skin cancer experiments will be supported by following DETOPS metabolism via pharmacokinetic and pharmacodynamic studies.

描述（由申请人提供）：tops酯，二乙基2,2,6,6-四甲基-1-氧-4-胡椒丁琥珀酸二乙酯（DETOPS），是一种外用药物，因其在皮肤细胞内分区和表达抗氧化活性的独特能力而被选择用于开发，该能力限制氧化介导的病理，包括牛皮癣，晒伤，皮肤老化和皮肤癌。该项目的目的是通过防止紫外线辐射引起的免疫抑制来减少皮肤癌。本研究的具体目的是测试DETOPS干扰小鼠免疫系统抑制的能力，通常遵循生物相关剂量的紫外线辐射。