P53 Biomark er and Intervention in Occupational Cancer

P53 职业癌症生物标志物和干预

基本信息

批准号：
7657375
负责人：
Paul W Brandt-Rauf
金额：
$ 34.21万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7657375
关键词：
P53 Biomark er Intervention Occupational

项目摘要

DESCRIPTION (provided by applicant): Research Methods for Occupational Cancer are needed to develop early markers of adverse health effects from workplace exposures and to devise ways for interrupting the pathways between workplace exposures and resultant cancers. In this revision of a competing continuation application, we propose to expand on the success in the prior funding period which focused on p53 as a target for both of these approaches. For example, we have demonstrated that p53 autoantibody biomarkers have significant predictive value for the development of subsequent cancer in asbestosis cases but that the sensitivity is somewhat low. Therefore, in this renewal, we propose to utilize proteomic technology for additional biomarker discovery in the banked serum samples from this asbestosis cohort to improve the sensitivity for cancer detection; preliminary results on a small sub-set of these samples indicate the existence of a unique proteomic profile in these samples of high sensitivity and specificity. Therefore, analysis of all the samples and correlation of protein patterns with the subsequent development of cancer in the cohort members should ultimately yield a battery of protein biomarkers with high sensitivity and specificity as well as predictive value for the carcinogenic effects of asbestos exposure. Furthermore, we have also demonstrated that a unique protein sequence from p53 (C terminal amino acids 353-393 repeated as a palindromic tetramer) can cause apoptosis in mutant p53 lung cancer cells, similar to those that occur in the asbestosis cohort, in cell culture when delivered as the peptide with a leader sequence for cellular uptake or as a mini-gene in a plasmid via transfection or an adenovirus vector. Therefore, in this renewal, we propose to demonstrate the effectiveness of this therapy (delivered directly as the peptide or by adenovirus as the mini-gene) in vivo in animal models of nude mice xenografted with the same mutant p53 lung cancer cells. Such as peptide therapy would be useful for interrupting the p53-dependent carcinogenic pathway between asbestos exposure and resultant cancers.

描述（由申请人提供）：需要用于职业癌症的研究方法来发展工作场所暴露的不良健康影响的早期标记，并设计出中断工作场所暴露与导致癌症之间的途径的方法。在对竞争持续申请的这一修订中，我们建议扩大以前的资金期间的成功，该融资阶段的重点是P53作为这两种方法的目标。例如，我们已经证明p53自身抗体生物标志物在石棉病例中随后的癌症的发展具有显着的预测价值，但敏感性有些低。因此，在这种续签中，我们建议利用蛋白质组学技术在该石棉同类群中的银行血清样品中进行更多的生物标志物发现，以提高对癌症检测的敏感性；这些样品的一小部分子集的初步结果表明在这些高灵敏度和特异性样本中存在独特的蛋白质组学谱。因此，对所有样品的分析以及蛋白质模式与随后在队列成员中癌症发展的相关性最终应产生具有高灵敏度和特异性的蛋白质生物标志物，以及对石棉暴露的致癌作用的预测价值。此外，我们还证明，从p53（C末端氨基酸353-393）重复的独特蛋白质序列作为palindromic四聚体重复出现）会导致突变p53肺癌细胞中突变的肺癌细胞中的细胞凋亡，类似于在细胞中与细胞的细胞序列相似的细胞序列或在细胞中的细胞序列中的细胞序列，以替代细胞的细胞序列，以使其在细胞中脱落。转染或腺病毒载体。因此，在这种续约中，我们建议在体内在用相同的突变体p53肺癌细胞的裸鼠动物模型中证明这种疗法的有效性（直接作为肽或通过腺病毒为迷你基因）在体内中的有效性。例如肽疗法将有助于中断石棉暴露和导致癌症之间的p53依赖性致癌途径。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gene Therapy with p14/tBID Induces Selective and Synergistic Apoptosis in Mutant Ras and Mutant p53 Cancer Cells In Vitro and In Vivo.

DOI：
10.3390/biomedicines11020258
发表时间：
2023-01-18
期刊：
Biomedicines
影响因子：
4.7
作者：
通讯作者：

Serum growth factors in asbestosis patients.

石棉肺患者的血清生长因子。

DOI：
10.1080/13547500802676868
发表时间：
2009
期刊：
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals
影响因子：
0
作者：
Li,Yongliang;Karjalainen,Antti;Koskinen,Heikki;Vainio,Harri;Pukkala,Eero;Hemminki,Kari;Brandt-Rauf,PaulW
通讯作者：
Brandt-Rauf,PaulW