HHSN261201200020I/HHSN26100007Preclinical In Vitro and In Vivo Development Assays for Cancer Preventative Reagent. Project Title: Chemoprevention by Aerosolized Bexarotene in Mouse Models of All T

HHSN261201200020I/HHSN26100007癌症预防试剂的临床前体外和体内开发测定。

• 批准号: 8945362
• 负责人: CHINTHALAPALLY RAO
• 金额: $ 60.71万
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-12 至 2016-09-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8945362
• 关键词: Adenocarcinoma; Adverse effects; Aerosols; Apoptosis; Bexarotene; Biological Markers; Blood; Cell Proliferation; Cells; Characteristics; Chemoprevention; Chemopreventive Agent; Cholesterol; Clinical Trials; Contractor; Contracts; Data; Development; Drug Formulations; Drug Kinetics; Ensure; Goals; Guidelines; Histopathology; Human; Immunologic Markers; In Vitro; Incidence; Infiltration; Inflammation; Lung; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Mus; Oral; Oral Administration; Particle Size; Patients; Pharmacodynamics; Phase; Plasma; Preparation; Property; RNA; Reagent; Reverse Transcription; Signal Pathway; Signal Transduction; Slide; Small Cell Carcinoma; Source; Squamous cell carcinoma; Structure of parenchyma of lung; Tissue Sample; Tissues; Triglycerides; Work; aerosolized; assay development; drug efficacy; in vivo; mouse model; particle; pre-clinical; research study

This contract is to develop an aerosolized formulation of bexarotene; determine the chemopreventive efficacy of the aerosolized bexarotene formulation in three mouse models representative of the three major histological subtypes of lung cancer; and perform preliminary proof-of-principle pharmacokinetic/pharmacodynamic studies to assess the plasma and lung tissue levels of bexarotene, the effects of bexarotene on triglyceride and cholesterol levels in the blood plasma, and the effects of bexarotene on biomarkers of drug efficacy. The goal of the Statement of Work is to develop an aerosol formulation of bexarotene that is effective against all 3 major subtypes of lung cancer while eliminating the toxic side effects of oral bexarotene administration that would provide the necessary preclinical data to support further development to phase I/II clinical trials.

该合同的目的是开发一种贝沙罗汀雾化制剂;确定雾化贝沙罗汀制剂在代表肺癌三种主要组织学亚型的三种小鼠模型中的化学预防功效;并进行初步的原理验证药代动力学/药效学研究以评估贝沙罗汀的血浆和肺组织水平，贝沙罗汀对血浆中甘油三酯和胆固醇水平的影响，以及贝沙罗汀对药效生物标志物的影响。本工作说明书的目标是开发一种贝沙罗汀气雾剂制剂，该制剂对所有3种主要肺癌亚型有效，同时消除口服贝沙罗汀给药的毒副作用，从而提供必要的临床前数据，以支持进一步开展I/II期临床试验。