Head and neck squamous cell carcinoma targeted chemosensitization.
Head and neck squamous cell carcinoma targeted chemosensitization.
复制标题
头颈鳞状细胞癌靶向化疗增敏。
DOI：
10.1016/j.otohns.2009.04.024
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Li,Daqing
中科院分区：
文献类型：
--
作者：
Figures,MindyR;Wobb,Jessie;Araki,Koji;Liu,Tingyan;Xu,Lei;Zhu,Hanjing;O'MalleyJr,BertW;Li,Daqing
目的：目前晚期头颈部鳞状细胞癌的治疗仍然导致不良结局。本研究的目的是研究成纤维细胞生长因子2靶向腺病毒介导的突变体Rad 50的益处。（FGF 2-Ad-Rad 50）基因转移增强头颈部鳞状细胞癌的化学增敏作用并降低化学毒性。研究设计：随机对照实验室研究。地点：宾夕法尼亚大学，费城，PA。对象和方法：本研究使用人头颈部鳞状细胞癌肿瘤细胞和患有人头颈部鳞状细胞癌的小鼠模型。每个研究组中有五只小鼠。将FGF 2-fab'分子与腺病毒突变体-Rad 50构建体缀合。在体外评估FGF 2靶向的转基因表达效率。体外和体内实验检测FGF 2-Ad-Rad 50联合顺铂对肿瘤细胞的杀伤作用和生长抑制作用。结果：与非靶向方法相比，FGF 2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的转基因表达（分别为207.51 ± 33.62和51.44 ± 8.28）。FGF 2-Ad-Rad 50联合顺铂具有上级抑瘤作用（264.5 ± 124.1 mm vs 567.1 ± 267.6 mm），DNA双链断裂增加（1349 ± 51.67 vs 774 ± 28.56），抗血管生成（%ROI：0.76% ± 0.38%vs 2.10% ± 1.66%）。FGF 2-Ad-Rad 50与顺铂的联合应用通过靶向DNA修复系统和肿瘤血管生成而显著提高抗肿瘤效果。该策略的巨大益处支持头颈部鳞状细胞癌新治疗的临床试验。
OBJECTIVE: 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.STUDY DESIGN: Randomized controlled laboratory study.SETTING: University of Pennsylvania, Philadelphia, PA.SUBJECTS AND METHODS: 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.RESULTS: 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 mm vs 567.1 ± 267.6 mm), 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.CONCLUSION: 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.