Clayman G L, el-Naggar A K, Roth J A, Zhang W W, Goepfert H, Taylor D L, Liu T J
Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1995 Jan 1;55(1):1-6.
Developing gene therapy strategies may allow contemporary medicine to reassess its management of solid malignancies. We have demonstrated previously that the wild-type p53 adenovirus (Ad5CMV-p53) suppressed the growth of established tumors of the head and neck. In this paper we develop a microscopic residual model which mimics the postsurgical environment of head and neck cancer patients with advanced disease. Using this squamous cell carcinoma of the head and neck model, we prevented the establishment of tumors in nude mice in which tumor cells had been s.c. implanted by transiently introducing exogenous wild-type p53 via an adenoviral vector 2 days following tumor cell implantation. These effects were vector dose dependent but independent on the endogenous wild-type or mutated p53 status of the cells. Importantly, karyotypically normal and nontumorigenic fibroblast cell lines are inert to the p53 adenovirus treatment. These results pave the ground work for further development of molecular therapy for head and neck cancer and other solid malignancies.
开发基因治疗策略可能会使当代医学重新评估其对实体恶性肿瘤的治疗方法。我们之前已经证明，野生型p53腺病毒（Ad5CMV-p53）可抑制已形成的头颈肿瘤的生长。在本文中，我们建立了一个微观残留模型，该模型模拟了患有晚期疾病的头颈癌患者的术后环境。使用这种头颈鳞状细胞癌模型，我们通过在肿瘤细胞植入后2天经腺病毒载体短暂引入外源性野生型p53，防止了在已皮下植入肿瘤细胞的裸鼠中形成肿瘤。这些效应与载体剂量相关，但与细胞内源性野生型或突变型p53状态无关。重要的是，核型正常且无致瘤性的成纤维细胞系对p53腺病毒治疗无反应。这些结果为进一步开发头颈癌和其他实体恶性肿瘤的分子治疗奠定了基础。
