Figures Mindy R, Wobb Jessie, Araki Koji, Liu Tingyan, Xu Lei, Zhu Hanjing, O'Malley Bert W, Li Daqing
Department of Otorhinolaryngology-Head & Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Otolaryngol Head Neck Surg. 2009 Aug;141(2):177-83. doi: 10.1016/j.otohns.2009.04.024.
The current treatment for advanced head and neck squamous cell carcinoma continues to result in poor outcomes. The purpose of this study is to investigate the benefit of fibroblast growth factor 2-targeted adenovirus-mediated mutant-Rad50 (FGF2-Ad-Rad50) gene transfer in enhancing chemosensitization for head and neck squamous cell carcinoma and reducing chemotoxicity.
Randomized controlled laboratory study.
University of Pennsylvania, Philadelphia, PA.
Human head and neck squamous cell carcinoma tumor cells and a mouse model with human head and neck squamous cell carcinoma were used for this study. There were five mice in each study group. FGF2-fab' molecule was conjugated with an adenoviral mutant-Rad50 construct. FGF2-targeted transgene expression efficiency was evaluated in vitro. Tumor cytotoxicity and growth inhibition were examined after combined FGF2-Ad-Rad50 with cisplatin treatment in vitro and in vivo. Anti-tumor mechanisms were investigated.
FGF2-targeted gene transfer approach significantly improved transgene expression in head and neck squamous cell carcinoma tumor cells over a nontargeted approach (207.51+/-33.62 vs 51.44+/-8.28, respectively). FGF2-Ad-Rad50 with cisplatin demonstrated a superior tumor suppression effect (264.5+/-124.1 mm3 vs 567.1+/-267.6 mm3), increased DNA double-strand breaks (1349+/-51.67 vs 774+/-28.56), and anti-angiogenesis (%ROI: 0.76%+/-0.38% vs 2.10%+/-1.66%) in tumor cells over nontargeted adenovirus.
Combination of FGF2-Ad-Rad50 with cisplatin significantly improves anti-tumor effect by targeting DNA repair systems and tumor angiogenesis. The great benefit of this strategy supports clinical trial for novel treatment of head and neck squamous cell carcinoma.
晚期头颈部鳞状细胞癌的当前治疗效果仍然不佳。本研究的目的是探讨成纤维细胞生长因子2靶向腺病毒介导的突变型Rad50（FGF2-Ad-Rad50）基因转移在增强头颈部鳞状细胞癌化疗敏感性和降低化疗毒性方面的益处。
随机对照实验室研究。
宾夕法尼亚大学，费城，宾夕法尼亚州。
本研究使用人头颈部鳞状细胞癌肿瘤细胞和人源头颈部鳞状细胞癌小鼠模型。每个研究组有五只小鼠。FGF2-fab'分子与腺病毒突变型Rad50构建体偶联。在体外评估FGF2靶向转基因的表达效率。在体外和体内将FGF2-Ad-Rad50与顺铂联合治疗后，检测肿瘤细胞毒性和生长抑制情况。研究抗肿瘤机制。
与非靶向方法相比，FGF2靶向基因转移方法显著提高了头颈部鳞状细胞癌肿瘤细胞中的转基因表达（分别为207.51±33.62和51.44±8.28）。FGF2-Ad-Rad50与顺铂联合使用显示出更好的肿瘤抑制效果（264.5±124.1mm³对567.1±267.6mm³），增加了肿瘤细胞中的DNA双链断裂（1349±51.67对774±28.56），并具有抗血管生成作用（%ROI：0.76%±0.38%对2.10%±1.66%），优于非靶向腺病毒。
FGF2-Ad-Rad50与顺铂联合使用通过靶向DNA修复系统和肿瘤血管生成，显著提高了抗肿瘤效果。该策略的巨大益处支持对头颈部鳞状细胞癌进行新治疗方法的临床试验。
