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The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats.

Publication ,  Journal Article
Chen, L; Brizel, DM; Rabbani, ZN; Samulski, TV; Farrell, CL; Larrier, N; Anscher, MS; Vujaskovic, Z
Published in: Int J Radiat Oncol Biol Phys
December 1, 2004

PURPOSE: Radiation-induced lung toxicity is a significant dose-limiting side effect of radiotherapy for thoracic tumors. Recombinant human keratinocyte growth factor (rHuKGF) has been shown to be a mitogen for type II pneumocytes. The purpose of this study was to determine whether rHuKGF prevents or ameliorates the severity of late lung damage from fractionated irradiation in a rat model. METHODS AND MATERIALS: Female Fisher 344 rats were irradiated to the right hemithorax with a dose of 40 Gy/5 fractions/5 days. rHuKGF at dose of 5 mg/kg or 15 mg/kg was given via a single intravenous injection 10 min after the last fraction of irradiation. Animals were followed for 6 months after irradiation. RESULTS: The breathing rate increased beginning at 6 weeks and reached a peak at 14 weeks after irradiation. The average breathing frequencies in the irradiated groups with rHuKGF (5 mg/kg and 15 mg/kg) treatment were significantly lower than that in the group receiving radiation without rHuKGF (116.5 +/- 1.0 and 115.2 +/- 0.8 vs 123.5 +/- 1.2 breaths/min, p < 0.01). The severity of lung fibrosis and the level of immunoreactivity of integrin alphavbeta6, TGFbeta1, type II TGFbeta receptor, Smad3, and phosphorylated Smad2/3 were significantly decreased only in the group receiving irradiation plus high-dose rHuKGF treatment compared with irradiation plus vehicle group, suggesting a dose response for the effect of rHuKGF. CONCLUSIONS: This study is the first to demonstrate that rHuKGF treatment immediately after irradiation protects against late radiation-induced pulmonary toxicity. These results suggest that restoration of the integrity of the pulmonary epithelium via rHuKGF stimulation may downregulate the TGF-beta-mediated fibrosis pathway. These data also support the use of rHuKGF in a clinical trial designed to prevent radiation-induced lung injury.

Duke Scholars

Published In

Int J Radiat Oncol Biol Phys

DOI

ISSN

0360-3016

Publication Date

December 1, 2004

Volume

60

Issue

5

Start / End Page

1520 / 1529

Location

United States

Related Subject Headings

  • Respiration
  • Recombinant Proteins
  • Rats, Inbred F344
  • Rats
  • Radiation-Protective Agents
  • Radiation Pneumonitis
  • Radiation Injuries, Experimental
  • Oncology & Carcinogenesis
  • Lung
  • Humans
 

Citation

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MLA
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Chen, L., Brizel, D. M., Rabbani, Z. N., Samulski, T. V., Farrell, C. L., Larrier, N., … Vujaskovic, Z. (2004). The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats. Int J Radiat Oncol Biol Phys, 60(5), 1520–1529. https://doi.org/10.1016/j.ijrobp.2004.07.729
Chen, Liguang, David M. Brizel, Zahid N. Rabbani, Thaddeus V. Samulski, Catherine L. Farrell, Nicole Larrier, Mitchell S. Anscher, and Zeljko Vujaskovic. “The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats.Int J Radiat Oncol Biol Phys 60, no. 5 (December 1, 2004): 1520–29. https://doi.org/10.1016/j.ijrobp.2004.07.729.
Chen L, Brizel DM, Rabbani ZN, Samulski TV, Farrell CL, Larrier N, et al. The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats. Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1520–9.
Chen, Liguang, et al. “The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats.Int J Radiat Oncol Biol Phys, vol. 60, no. 5, Dec. 2004, pp. 1520–29. Pubmed, doi:10.1016/j.ijrobp.2004.07.729.
Chen L, Brizel DM, Rabbani ZN, Samulski TV, Farrell CL, Larrier N, Anscher MS, Vujaskovic Z. The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats. Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1520–1529.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

ISSN

0360-3016

Publication Date

December 1, 2004

Volume

60

Issue

5

Start / End Page

1520 / 1529

Location

United States

Related Subject Headings

  • Respiration
  • Recombinant Proteins
  • Rats, Inbred F344
  • Rats
  • Radiation-Protective Agents
  • Radiation Pneumonitis
  • Radiation Injuries, Experimental
  • Oncology & Carcinogenesis
  • Lung
  • Humans