AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine
AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine
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DOI：
10.1038/gt.2014.63
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发表时间：
2014-10-01
期刊：
影响因子：
5.1
通讯作者：
Wang, S.
中科院分区：
文献类型：
--
作者：
Guo, L.;Gao, R.;Wang, S.
口腔和口咽癌患者在接受放射治疗(IR)后，经常会出现唾液功能丧失。在本实验中，我们测试了转移成纤维细胞生长因子-2(FGF2)基因是否可以限制小型猪(小型猪)分割IR(7.5或9Gy5天连续5天)后的唾液功能障碍。腮腺唾液流量在IR后16周内稳定下降，而靶向腮腺的血流量在IR开始后3天开始下降。到了2周，IR后唾液血流量减少了50%，在这一点上，它在研究的其余部分保持稳定。单次预先注射编码FGF2的5型腺病毒载体(AdLTR(2)EF1a-FGF2)可保护腮腺微血管内皮细胞免受IR损伤，并显著抑制腮腺唾液流量的下降。我们的结果表明，针对涎腺内皮细胞的局部治疗可能对口腔和口咽癌接受IR的患者有利。
Patients frequently experience a loss of salivary function following irradiation (IR) for the treatment of an oral cavity and oropharyngeal cancer. Herein, we tested if transfer of fibroblast growth factor-2 (FGF2) cDNA could limit salivary dysfunction after fractionated IR (7.5 or 9 Gy for 5 consecutive days to one parotid gland) in the miniature pig (minipig). Parotid salivary flow rates steadily decreased by 16 weeks post-IR, whereas blood flow in the targeted parotid gland began to decrease 3 days after beginning IR. By 2 weeks, post-IR salivary blood flow was reduced by 50%, at which point it remained stable for the remainder of the study. The single preadministration of a hybrid serotype 5 adenoviral vector encoding FGF2 (AdLTR(2)EF1a-FGF2) resulted in the protection of parotid microvascular endothelial cells from IR damage and significantly limited the decline of parotid salivary flow. Our results suggest that a local treatment directed at protecting salivary gland endothelial cells may be beneficial for patients undergoing IR for oral cavity and oropharyngeal cancer.