PMID- 21367751
OWN - NLM
STAT- MEDLINE
DCOM- 20110915
LR  - 20211020
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 17
IP  - 9
DP  - 2011 May 1
TI  - Prevention of radiation-induced salivary hypofunction following hKGF gene 
      delivery to murine submandibular glands.
PG  - 2842-51
LID - 10.1158/1078-0432.CCR-10-2982 [doi]
AB  - PURPOSE: Salivary glands are significantly affected when head and neck cancer 
      patients are treated by radiation. We evaluated the effect of human keratinocyte 
      growth factor (hKGF) gene transfer to murine salivary glands on the prevention of 
      radiation-induced salivary hypofunction. EXPERIMENTAL DESIGN: A hybrid serotype 5 
      adenoviral vector encoding hKGF (AdLTR(2)EF1alpha-hKGF) was constructed. Female C3H 
      mice, 8 weeks old, were irradiated by single (15 Gy) or fractionated (6 Gy for 5 
      days) doses to induce salivary hypofunction. AdLTR(2)EF1alpha-hKGF or AdControl was 
      administered (10(8) - 10(10) particles per gland) to both submandibular glands 
      (SG) by retrograde ductal instillation before irradiation (IR). Salivary flow was 
      measured following pilocarpine stimulation. Human KGF levels were measured by 
      ELISA. SG cell proliferation was measured with bromodeoxyuridine labeling. 
      Endothelial and progenitor or stem cells in SGs were measured by flow cytometry. 
      The effect of SG hKGF production on squamous cell carcinoma (SCC VII) tumor 
      growth was assessed. RESULTS: In 3 separate single-dose IR experiments, salivary 
      flow rates of mice administered the AdLTR(2)EF1alpha-hKGF vector were not 
      significantly different from nonirradiated control mice (P > 0.05). Similarly, in 
      3 separate fractionated IR experiments, the hKGF-expressing vector prevented 
      salivary hypofunction dramatically. Transgenic hKGF protein was found at high 
      levels in serum and SG extracts. AdLTR(2)EF1alpha-hKGF-treated mice showed increased 
      cell proliferation and numbers of endothelial cells, compared with mice treated 
      with AdControl. hKGF gene transfer had no effect on SCC VII tumor growth +/- 
      radiation. CONCLUSIONS: hKGF gene transfer prevents salivary hypofunction caused 
      by either single or fractionated radiation dosing in mice. The findings suggest a 
      potential clinical application.
CI  - (c)2011 AACR.
FAU - Zheng, Changyu
AU  - Zheng C
AD  - Molecular Physiology and Therapeutics Branch, National Institute of Dental and 
      Craniofacial Research, Center for Cancer Research, National Cancer Institute, 
      Bethesda, Maryland 20892-1190, USA.
FAU - Cotrim, Ana P
AU  - Cotrim AP
FAU - Rowzee, Anne
AU  - Rowzee A
FAU - Swaim, William
AU  - Swaim W
FAU - Sowers, Anastasia
AU  - Sowers A
FAU - Mitchell, James B
AU  - Mitchell JB
FAU - Baum, Bruce J
AU  - Baum BJ
LA  - eng
GR  - Z99 DE999999/ImNIH/Intramural NIH HHS/United States
GR  - ZIA DE000336-30/ImNIH/Intramural NIH HHS/United States
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20110302
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 (FGF7 protein, human)
RN  - 0 (Recombinant Proteins)
RN  - 126469-10-1 (Fibroblast Growth Factor 7)
SB  - IM
MH  - Animals
MH  - Carcinoma/radiotherapy
MH  - Female
MH  - Fibroblast Growth Factor 7/administration & dosage/*genetics/physiology
MH  - Gene Transfer Techniques
MH  - Genetic Therapy
MH  - Head and Neck Neoplasms/radiotherapy
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Radiation Injuries, Experimental/complications/*prevention & control
MH  - Radiotherapy/adverse effects
MH  - Recombinant Proteins/administration & dosage/genetics
MH  - Salivary Gland Diseases/etiology/physiopathology/*prevention & control
MH  - Salivary Glands/metabolism/*physiopathology/radiation effects
MH  - Submandibular Gland/*metabolism/pathology/radiation effects
MH  - Tumor Cells, Cultured
PMC - PMC3651874
MID - NIHMS466979
COIS- Disclosure of Potential Conflicts of Interest No potential conflicts of interest 
      were disclosed.
EDAT- 2011/03/04 06:00
MHDA- 2011/09/16 06:00
PMCR- 2013/05/12
CRDT- 2011/03/04 06:00
PHST- 2011/03/04 06:00 [entrez]
PHST- 2011/03/04 06:00 [pubmed]
PHST- 2011/09/16 06:00 [medline]
PHST- 2013/05/12 00:00 [pmc-release]
AID - 1078-0432.CCR-10-2982 [pii]
AID - 10.1158/1078-0432.CCR-10-2982 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2011 May 1;17(9):2842-51. doi: 10.1158/1078-0432.CCR-10-2982. 
      Epub 2011 Mar 2.