Targeted Death of Prostatic Cancer Cells

前列腺癌细胞的靶向死亡

基本信息

批准号：
6574134
负责人：
JANET A SAWICKI
金额：
$ 33.38万
依托单位：
LANKENAU INSTITUTE FOR MEDICAL RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-01 至 2005-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6574134
关键词：
Adenoviridae androgen inhibitor biotechnology cell death cell growth regulation cell line combination cancer therapy diphtheria toxin gene delivery system gene targeting gene therapy green fluorescent proteins laboratory mouse metastasis neoplasm /cancer chemotherapy neoplasm /cancer relapse /recurrence neoplastic cell nonhuman therapy evaluation polymerase chain reaction prostate neoplasms terminal nick end labeling transfection /expression vector

Adenoviridae androgen inhibitor biotechnology cell death cell growth regulation cell line combination cancer therapy diphtheria toxin gene delivery system gene targeting gene therapy green fluorescent proteins laboratory mouse metastasis neoplasm /cancer chemotherapy neoplasm /cancer relapse /recurrence neoplastic cell nonhuman therapy evaluation polymerase chain reaction prostate neoplasms terminal nick end labeling transfection /expression vector

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项目摘要

DESCRIPTION (provided by applicant): The standard therapy for men with metastatic prostate cancer is to reduce tumor size by androgen ablation, either by bilateral orchiectomy or the use of luteinizing hormone-releasing hormone analogues. While many prostate cancer cells die in the absence of androgens, some cells are androgen-independent and do not require androgens for survival. With time, the surviving cells begin to grow aggressively. The result is that most men receiving this therapy develop recurrent tumors and die within two years. To improve the effectiveness of this therapy, we hypothesize that following androgen ablation therapy for the treatment of prostatic carcinoma, application of a regulated recombination system to target expression of diphtheria toxin (DT-A) to androgen independent cancer cells would be an effective way to arrest the development of recurrent tumors. We propose a strategy to use replicative-defective adenoviral vectors to deliver DT-A specifically to androgen-independent prostate cancer cells. The regulated expression of this highly toxic protein in cells will result in their death. We shall test the effectiveness of this approach in cultured human prostate cancer cells, in xenografts in mice developed from such cells, and in prostate tumors in a transgenic mouse model. We expect our investigations will lead to the development of a novel gene therapy for prostate cancer patients that will effectively arrest the development of recurrent tumors.

描述（由申请人提供）：针对前列腺癌男性的标准疗法是通过双侧果切除术或使用黄质激素释放激素类似物来减少雄激素消融的肿瘤大小。尽管许多前列腺癌细胞在没有雄激素的情况下死亡，但某些细胞是与雄激素无关的，不需要雄激素才能生存。随着时间的流逝，幸存的细胞开始积极生长。结果是大多数接受这种疗法的男性会在两年内发生复发性肿瘤并死亡。为了提高这种疗法的有效性，我们假设雄激素消融疗法用于治疗前列腺癌，应用调节的重组系统靶向靶向二骨毒素（DT-A）在雄激素独立癌细胞中的表达将是一种有效的方法来阻止复发性肿瘤的发育。我们提出了一种使用复制缺陷型腺病毒载体的策略，以将DT-A专门运送到雄激素独立的前列腺癌细胞中。这种剧毒蛋白在细胞中的调节表达将导致其死亡。我们应测试这种方法在从这种细胞中发育而成的小鼠的异种移植物以及转基因小鼠模型中前列腺肿瘤中的异种移植物中的有效性。我们预计我们的研究将导致为前列腺癌患者开发一种新型的基因疗法，该治疗将有效地阻止复发性肿瘤的发展。