Document Detail

Prevention of radiation-induced pneumonitis by recombinant adenovirus-mediated transferring of soluble TGF-beta type II receptor gene.
MedLine Citation:
PMID:  16710346     Owner:  NLM     Status:  MEDLINE    
To investigate whether radiation-induced pneumonitis in the mouse-irradiated lung could be prevented by recombinant adenovirus-mediated soluble transforming growth factor-beta (TGF-beta) type II receptor gene therapy. Radiation fibrosis-prone mice (C57BL/6J) were randomly divided into four groups consisting of a (1) control group (sham-irradiated); (2) radiation (RT)-alone group; (3) RT+AdCMVsTbetaR group and (4) RT+AdCMVluc group. The RT-alone and sham-irradiated mice were killed at several time points after thoracic irradiation with a single dose of 9 Gy, and then the TGF-beta1 concentrations in serum and broncho-alveolar lavage fluid (BALF) were quantified by enzyme-linked immunosorbent assay (ELISA). We used an adenoviral vector expressing a soluble TGF-beta type II receptor (AdCMVsTbetaR), which can bind to TGF-beta and then block the TGF-beta receptor-mediated signal transduction. The C57BL/6J mice were intraperitoneally (i.p.) injected with either 5 x 10(8) plaque-forming units of AdCMVsTbetaR or AdCMVluc, a control adenovirus-expressing luciferase, a week preceding and a week following the X-ray thoracic irradiation. Four weeks after irradiation, the mice were killed and the concentration of TGF-beta1 in the serum and BALF were then measured using ELISA and the lung tissue specimens were examined histopathologically. Following thoracic irradiation with a single dose of 9 Gy, radiation-induced TGF-beta1 release in the serum reached the first peak concentration at 12 h and then declined. It reached a maximal value at 2 weeks after irradiation. In the BALF, the TGF-beta1 concentration was appreciable within the first hour and thereafter declined. It reached a maximal value at 3 days after irradiation. A one-time i.p. injection of AdCMVsTbetaR 1 week before irradiation could not completely suppress the two peaks of the radiation-induced TGF-beta1 increase, whereas an injection a week preceding and a week following thoracic irradiation was able to suppress those two peaks thoroughly. The TGF-beta1 was completely suppressed in the AdCMVsTbetaR-treated mouse serum and BALF; however, no statistical difference was observed in the serum and BALF between the AdCMVluc-infected mice and the control mice at 4 weeks after irradiation (P < 0.05). A histopathological examination showed only mild radiation pneumonitis in the irradiated lungs of AdCMVsTbetaR-treated mice in comparison to the AdCMVluc-infected and RT-alone mice. Our results demonstrated that TGF-beta1 plays an important role in radiation pneumonitis, thus suggesting that the adenovirus-mediated overexpression in soluble TGF-beta type II receptor gene therapy may be a potentially feasible and effective strategy for the prevention of radiation pneumonitis.
Z Haiping; K Takayama; J Uchino; A Harada; Y Adachi; S Kura; Z Caicun; T Tsuzuki; Y Nakanishi
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2006-05-19
Journal Detail:
Title:  Cancer gene therapy     Volume:  13     ISSN:  0929-1903     ISO Abbreviation:  Cancer Gene Ther.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-16     Completed Date:  2006-10-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9432230     Medline TA:  Cancer Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  864-72     Citation Subset:  IM    
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Adenoviridae / genetics*
Bronchoalveolar Lavage Fluid / chemistry
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Fibronectins / metabolism
Gene Therapy / methods*
Genetic Vectors / genetics*
Mice, Inbred C57BL
Protein-Serine-Threonine Kinases
Radiation Pneumonitis / genetics,  pathology,  prevention & control*
Receptors, Transforming Growth Factor beta / blood,  genetics*,  metabolism
Reg. No./Substance:
0/Fibronectins; 0/Receptors, Transforming Growth Factor beta; EC 1.13.12.-/Luciferases; EC Kinases; EC growth factor-beta type II receptor

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