An NF-kB inhibitor as a post-carcinogen lung cancer chemopreventive agent

NF-kB 抑制剂作为致癌后肺癌化学预防剂

基本信息

批准号：
8045025
负责人：
CHENGGUO XING
金额：
$ 7.32万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-07 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8045025
关键词：
A/J Mouse Apoptosis Benzo(a)pyrene Biological Markers Butanones Carcinogens Chalcone Chalcones Chemoprevention Chemopreventive Agent Clinical Trials Consumption Data Development Evaluation Future Goals Grant Interdisciplinary Study Investigation Lead Literature Lung Adenoma Lung Neoplasms Malignant Neoplasms Malignant neoplasm of lung Modification NF-kappa B Oral Outcomes Research Pathway interactions Pharmaceutical Chemistry Premalignant Prevention Prevention Research Quality of life Relative (related person)Reporting Research Smoker Structure of parenchyma of lung Testing Tissues Treatment Protocols Work Xenograft procedure anticancer activity base cancer chemoprevention cancer prevention cellular targeting design experience improved in vivo inhibitor/antagonist innovation insight lung tumorigenesis p65 prevent programs response tumor growth tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Chalcone-based NF-?B inhibition for post-carcinogen lung cancer chemoprevention Chalcone-based compounds have demonstrated chemopreventive activities against various types of malignancies, including post-carcinogen lung tumorigenesis, potentially via inhibiting the activation of NF-?B pathway. Their chemopreventive efficacy, however, has never been optimized, which may potentially delay the translational development and reduce their potential impact to cancer prevention. We have recently optimized chalcone-based compounds to improve their NF-?B inhibitory activities, leading to a set of lead candidates with distinct NF-?B inhibitory profiles and one lead compound demonstrating potent anticancer activity in vivo against lung cancer xenograft, which is hypothesized to have significantly more potent chemopreventive activity against post-carcinogen lung tumorigenesis. The goal of this research is to identify a safe and more efficacious chalcone-based chemopreventive agent against post-carcinogen lung cancer development, which may eventually help former smoker to prevent lung cancer development, and to establish the importance of NF-?B inhibition in chemoprevention. Experimentally, we will synthesize six chalcone lead compounds, including the one that has demonstrated post-carcinogen lung cancer chemopreventive activity. These chalcones will be evaluated in A/J mice for their post-carcinogen chemopreventive efficacy. The chemopreventive efficacies among these candidates in combination with their pre-determined NF-?B inhibitory activities will establish the relationship between chemoprevention and NF-?B inhibition, which will indirectly determine the relative importance of NF-?B inhibition in chalcone-induced chemoprevention. The relevance of NF-?B inhibition to chemoprevention will be further explored by analyzing NF-?B biomarkers, such as I?Ba and p-P65, in the lung adenoma tissues.

描述（由申请人提供）：基于Chalcone基于Chalcone的NF-？B抑制了在白菜后肺癌化学预防化合物基于Chalcone的化合物已经证明了针对各种恶性肿瘤的化学预防活性，包括癌后肺肿瘤发生，潜在地通过抑制NF- b途径的激活来抑制。然而，他们的化学预防功效从未得到优化，这可能会延迟翻译发展并减少对预防癌症的潜在影响。 We have recently optimized chalcone-based compounds to improve their NF-?B inhibitory activities, leading to a set of lead candidates with distinct NF-?B inhibitory profiles and one lead compound demonstrating potent anticancer activity in vivo against lung cancer xenograft, which is hypothesized to have significantly more potent chemopreventive activity against post-carcinogen lung tumorigenesis. 这项研究的目的是确定针对卡霉素后肺癌开发的安全性，更有效的基于Chalcone的化学预防剂，该剂最终可能有助于前吸烟者预防肺癌的发展，并确定NF-b-抑制作用在化学预防中的重要性。在实验上，我们将合成六种Chalcone铅化合物，其中包括表现出癌后肺癌化学预防活性的铅化合物。这些chalcones将在A/J小鼠中评估其毒性后化学预防功效。这些候选者之间的化学预防效力以及其预先确定的NF-？B抑制活性将确定化学预防与NF-？B抑制作用之间的关系，哪些将间接确定NF-？B抑制在CHALCONE诱导的化学上的相对重要性。通过在肺腺瘤组织中分析NF-？B生物标志物（例如I？ba和P-P65），将进一步探索NF-？B抑制与化学预防的相关性。