P53 GENE THERAPY FOR LOCALLY ADVANCED BLADDER CANCER

P53 基因治疗局部晚期膀胱癌

• 批准号: 2752170
• 负责人: LANCE C PAGLIARO
• 金额: $ 14.59万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2752170
• 关键词: angiogenesis; antineoplastics; apoptosis; athymic mouse; biopsy; bladder neoplasm; carcinoma; clinical research; clinical trial phase I; combination cancer therapy; cystoscopy; cytotoxicity; disease /disorder model; gene expression; gene mutation; gene therapy; human subject; human therapy evaluation; neoplasm /cancer chemotherapy; neoplasm /cancer invasiveness; p53 gene /protein; prognosis; transfection /expression vector; tumor suppressor genes

DESCRIPTION: (Applicant's Abstract) The standard treatment for muscle- invasive bladder cancer is cystectomy. Though often curative, this is a mutilating procedure and its effects on quality of life are unacceptable to many patients. Clinical studies have shown that patients with early muscle-invasive bladder cancer whose tumors bear mutations of p53, RB, or both, have a higher rate of progression and decreased survival following cystectomy alone. An objective of ongoing clinical research is to optimize the use of chemotherapy, surgery, and novel therapeutic modalities in treatment of patients with muscle-invasive tumors to improve the prognosis of those that have p53 or RB mutations and to develop gene therapy for bladder cancer in the context of a Phase 1 clinical trial of the replication defective adenoviral vector Ad-p53, administered by intravesical instillation in patients with locally advanced bladder cancer. The specific aims are as follows: 1) conduct a Phase 1 clinical trial of intravesically administered Ad-p53 in patients with muscle-invasive bladder cancer; 2) demonstrate infection of tumor cells and expression of p53 gene by adenoviral vector through intravesical administration; 3) characterize the in vivo effect of p53 gene transfer on apoptosis in bladder cancer; 4) investigate effect of p53 gene transfer on regulation of angiogenesis in bladder cancer. Upon completion of the Phase 1 trial and correlative laboratory studies described, the applicant will develop a Phase II study of combined chemotherapy and Ad-p53 in patients with early muscle-invasive bladder cancer who have failed an initial attempt at organ preservation.

描述：（申请人摘要）肌-的标准治疗