P53 GENE THERAPY FOR LOCALLY ADVANCED BLADDER CANCER

描述：（申请人的摘要）用于肌肉的标准治疗- 浸润性膀胱癌是膀胱癌。虽然经常治愈，这是 一种毁损手术及其对生活质量的影响， 这是许多患者无法接受的。临床研究表明， 患有早期肌肉浸润性膀胱癌， p53、RB或两者的患者进展率较高， 单用环磷酰胺后的存活率。正在进行的临床研究的目的 研究是为了优化使用化疗，手术，和新的 肌肉浸润性肌内营养不良患者的治疗方式 改善p53或RB突变患者的预后 并在第一阶段的背景下开发膀胱癌的基因治疗 1项复制缺陷型腺病毒载体Ad-p53的临床试验， 局部膀胱灌注给药 晚期膀胱癌具体目标如下：1）行为 膀胱内给予Ad-p53的1期临床试验， 肌层浸润性膀胱癌患者; 2）显示感染 腺病毒介导p53基因的表达 膀胱内给药; 3）表征p53的体内作用 基因转移对膀胱癌细胞凋亡的影响; 4）研究基因转移对膀胱癌细胞凋亡的影响。 p53基因转染对膀胱癌血管生成的调控作用后 完成I期试验和相关实验室研究 如所述，申请人将开发一项II期研究， 早期肌层浸润性膀胱患者化疗及Ad-p53的临床研究 那些初次尝试器官保存失败的癌症患者。

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.