title: AdLTR2EF1α-FGF2-mediated prevention of fractionated irradiation-induced salivary hypofunction in swine.
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.
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: R
authors.initials: R
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Jin
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Cotrim
authors.affiliation: 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.
authors.forename: X
authors.initials: X
authors.lastname: Yan
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Goldsmith
authors.affiliation: 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.
authors.forename: Z
authors.initials: Z
authors.lastname: Shan
authors.affiliation: 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.
authors.forename: B
authors.initials: B
authors.lastname: Hai
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Baum
authors.affiliation: 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 [2] Department of Biochemistry and Molecular Biology, School of Stomatology, Capital Medical University School of Basic Medical Sciences, Beijing, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000528:radiation effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D010306:Parotid Gland / Q000166:cytology / Q000503:physiopathology* / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control*; D012463:Saliva / Q000166:cytology / Q000528:radiation effects; D013552:Swine; D013556:Swine, Miniature
chemical_list: D016222:Fibroblast Growth Factor 2