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

Gene Therapy volume 21, pages 866–873 (2014)Cite this article

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Abstract

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 (AdLTR2EF1a-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.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant nos. 30430690, 81271164 and 81070843) and the National Special Foundation for Excellent PhD Paper No. 200778, and by the Division of Intramural Research of the National Institute of Dental and Craniofacial Research.

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Author notes

  1. L Guo and R Gao: These authors contributed equally to this work.

Authors and Affiliations

  1. Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, People’s Republic of China

    L Guo, R Gao, J Xu, L Jin, X Yan, Z Shan, B Hai, J Zhou, C Zhang & S Wang

  2. Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA

    A P Cotrim, C Zheng, C M Goldsmith & B J Baum

  3. Department of Biochemistry and Molecular Biology, School of Stomatology, Capital Medical University School of Basic Medical Sciences, Beijing, People’s Republic of China

    S Wang

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  1. L Guo
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Correspondence to S Wang.

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Guo, L., Gao, R., Xu, J. et al. AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine. Gene Ther 21, 866–873 (2014). https://doi.org/10.1038/gt.2014.63

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