AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine

作者：Guo, L.; Gao, R.; Xu, J.; Jin, L.; Cotrim, A. P.; Yan, X.; Zheng, C.; Goldsmith, C. M.; Shan, Z.; Hai, B.; Zhou, J.; Zhang, C.; Baum, B. J.; Wang, S.^*

来源：Gene Therapy, 2014, 21(10): 866-873.

DOI：10.1038/gt.2014.63

• ADENOVIRAL-MEDIATED TRANSFER
• RADIATION-INDUCED APOPTOSIS
• INCREASED FLUID SECRETION
• HUMAN AQUAPORIN-1 CDNA
• QUALITY-OF-LIFE
• GASTROINTESTINAL SYNDROME
• IONIZING-RADIATION
• HEAD
• GLAND
• CERAMIDE

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.

• 出版日期2014-10
• 单位首都医科大学