PMID- 19584147
OWN - NLM
STAT- MEDLINE
DCOM- 20090928
LR  - 20211020
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 15
IP  - 14
DP  - 2009 Jul 15
TI  - Prevention of radiation-induced oral mucositis after adenoviral vector-mediated 
      transfer of the keratinocyte growth factor cDNA to mouse submandibular glands.
PG  - 4641-8
LID - 10.1158/1078-0432.CCR-09-0819 [doi]
AB  - PURPOSE: The study aims to evaluate if human keratinocyte growth factor (hKGF), 
      secreted after transduction of murine salivary glands with adenoviral vectors, 
      can prevent oral mucositis resulting from radiation. EXPERIMENTAL DESIGN: Two 
      serotype 5 adenoviral vectors encoding hKGF were constructed: AdEF1alpha-hKGF and 
      AdLTR(2)EF1alpha-hKGF. Female C3H mice, 8 weeks old, were irradiated by single 
      (22.5 Gy) or fractionated (5 x 8 Gy for 5 days) doses to induce oral mucositis 
      (ulcers on tongue). One day before irradiation, the above viral vectors or an 
      empty vector, Adcontrol, was given (10(10) particles per gland) to both 
      submandibular glands by retrograde ductal instillation. Each experiment included 
      five groups: no irradiation and irradiation (+/-Adcontrol, AdEF1alpha-hKGF, or 
      AdLTR(2)EF1alpha-hKGF). Blood, saliva, submandibular glands, and tongue were 
      collected on day 7 for single-dose studies or day 10 for fractionated dosing. 
      hKGF levels were measured by ELISA. RESULTS: In three separate single-dose 
      irradiation experiments, lingual ulcers were dramatically reduced after either 
      KGF-expressing vector. Similarly, in two separate fractionated irradiation 
      experiments, the hKGF-expressing vectors completely prevented ulcer formation. 
      QPCR data indicated that approximately 10(7) to 10(8) particles of each vector 
      remained in the targeted submandibular glands at the terminal time. Transgenic 
      hKGF protein was found at high levels in saliva, serum, and submandibular gland 
      extracts. CONCLUSIONS: hKGF gene transfer to salivary glands prevented 
      radiation-induced oral mucositis in mice. This proof of concept study suggests 
      that transgenic hKGF secreted from transduced salivary glands may be useful 
      clinically to prevent oral mucositis caused by radiation.
FAU - Zheng, Changyu
AU  - Zheng C
AD  - Molecular Physiology and Therapeutics Branch, National Institute of Dental and 
      Craniofacial Research, National Cancer Institute, Bethesda, Maryland, USA.
FAU - Cotrim, Ana P
AU  - Cotrim AP
FAU - Sunshine, Abraham N
AU  - Sunshine AN
FAU - Sugito, Takayuki
AU  - Sugito T
FAU - Liu, Lina
AU  - Liu L
FAU - Sowers, Anastasia
AU  - Sowers A
FAU - Mitchell, James B
AU  - Mitchell JB
FAU - Baum, Bruce J
AU  - Baum BJ
LA  - eng
GR  - Z01 DE000336-26/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20090707
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (DNA, Complementary)
RN  - 0 (FGF7 protein, human)
RN  - 126469-10-1 (Fibroblast Growth Factor 7)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Analysis of Variance
MH  - Animals
MH  - Cell Line
MH  - DNA, Complementary/genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Fibroblast Growth Factor 7/blood/genetics/*metabolism
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Radiation Injuries, Experimental/complications/*prevention & control
MH  - Saliva/chemistry
MH  - Stomatitis/etiology/pathology/*prevention & control
MH  - Submandibular Gland/metabolism/pathology/*radiation effects
MH  - Transduction, Genetic
PMC - PMC2769927
MID - NIHMS149125
COIS- Disclosure of Potential Conflicts of Interest No potential conflicts of interest 
      were disclosed.
EDAT- 2009/07/09 09:00
MHDA- 2009/09/29 06:00
PMCR- 2010/07/15
CRDT- 2009/07/09 09:00
PHST- 2009/07/09 09:00 [entrez]
PHST- 2009/07/09 09:00 [pubmed]
PHST- 2009/09/29 06:00 [medline]
PHST- 2010/07/15 00:00 [pmc-release]
AID - 1078-0432.CCR-09-0819 [pii]
AID - 10.1158/1078-0432.CCR-09-0819 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2009 Jul 15;15(14):4641-8. doi: 10.1158/1078-0432.CCR-09-0819. 
      Epub 2009 Jul 7.