Application of gene therapy on squamous cell carcinoma of the head and neck (SCCHN)

根据最近的荟萃分析，化疗已被证明有利于提高头颈部鳞状细胞癌（SCCHN）患者的生存率。顺铂是治疗SCCHN患者的标准化疗药物。因此，顺铂耐药是提高生存率的主要障碍之一。首先，我们建立了顺铂耐药SCCHN细胞系。然后，我们建立了动物模型，皮下接种的SCCHN肿瘤即使每周腹腔注射顺铂也会进展。另一方面，我们也证明了以转化生长因子(TGF)-α为靶点的反义（AS）基因传递在体内可有效抑制SCCHN肿瘤的生长。这一次我们成功地证明了同时局部注射TGF-α AS质粒载体可增强体内顺铂对SCCHN的抗肿瘤作用。该动物设计为治疗顺铂耐药SCCHN提供了良好的临床前模型。

According to recent meta-analyses, chemotherapy has been proved to be beneficial in improving survival for the patients with squamous cell carcinoma of the head and neck (SCCHN). Cisplatin is the standard chemotherapeutic agent in treating SCCHN patients. Therefore cisplatin resistant is one of the major obstacles in improving survival. At first we established cisplatin-resistant SCCHN cell lines. Then we developed animal model where subcutaneously inoculated SCCHN tumor progresses even with cisplatin administration which were weekly injected intra-peritoneally (IP).On the other hand, we have also shown that antisense (AS) gene delivery targeting transforming growth factor (TGF)-α was effective in suppressing SCCHN tumor growth in vivo.This time we succeeded to show the results where simultaneous administration of TGF-α AS plasmid vector injected topically enhanced anti-tumor effects of cisplatin on SCCHN in vivo. This animal design provides a good preclinical model for the treatment of cisplatin-resistant SCCHN.