Document Detail


Effects of radiation on the epidermal growth factor receptor pathway in the heart.
MedLine Citation:
PMID:  23488537     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Radiation-induced heart disease (RIHD) is a serious side-effect of thoracic radiotherapy. The epidermal growth factor receptor (EGFR) pathway is essential for the function and survival of cardiomyocytes. Hence, agents that target the EGFR pathway are cardiotoxic. Tocotrienols protect from radiation injury, but may also enhance the therapeutic effects of EGFR pathway inhibitors in cancer treatment. This study investigated the effects of local irradiation on the EGFR pathway in the heart and tests whether tocotrienols may modify radiation-induced changes in this pathway.
METHODS: Male Sprague-Dawley rats received image-guided localized heart irradiation with 21 Gy. Twenty four hours before irradiation, rats received a single dose of tocotrienol-enriched formulation or vehicle by oral gavage. At time points from 2 h to 9 months after irradiation, left ventricular expression of EGFR pathway mediators was studied.
RESULTS: Irradiation caused a decrease in the expression of epidermal growth factor (EGF) and neuregulin-1 (Nrg-1) mRNA from 6 h up to 10 weeks, followed by an upregulation of these ligands and the receptor erythroblastic leukemia viral oncogene homolog (ErbB)4 at 6 months. In addition, the upregulation of Nrg-1 was statistically significant up to 9 months after irradiation. A long-term upregulation of ErbB2 protein did not coincide with changes in transcription or post-translational interaction with the chaperone heat shock protein 90 (HSP90). Pretreatment with tocotrienols prevented radiation-induced changes at 2 weeks.
CONCLUSIONS: Local heart irradiation causes long-term changes in the EGFR pathway. Studies have to address how radiation may interact with cardiotoxic effects of EGFR inhibitors.
Authors:
Vijayalakshmi Sridharan; Sunil K Sharma; Eduardo G Moros; Peter M Corry; Preeti Tripathi; Benjamin J Lieblong; Chandan Guha; Martin Hauer-Jensen; Marjan Boerma
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-04-16
Journal Detail:
Title:  International journal of radiation biology     Volume:  89     ISSN:  1362-3095     ISO Abbreviation:  Int. J. Radiat. Biol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-01     Completed Date:  2013-09-05     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  8809243     Medline TA:  Int J Radiat Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  539-47     Citation Subset:  IM; S    
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MeSH Terms
Descriptor/Qualifier:
Animals
Heart / drug effects*,  radiation effects*
Male
Myocardium / metabolism*
Radiation Tolerance / drug effects,  physiology*
Radiation-Protective Agents / pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Epidermal Growth Factor / metabolism*
Signal Transduction / physiology*,  radiation effects
Tocotrienols / pharmacology*
Grant Support
ID/Acronym/Agency:
CA148679/CA/NCI NIH HHS; CA71382/CA/NCI NIH HHS; R01 CA071382/CA/NCI NIH HHS; R01 CA148679/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Radiation-Protective Agents; 0/Tocotrienols; EC 2.7.10.1/Receptor, Epidermal Growth Factor
Comments/Corrections
Comment In:
Int J Radiat Biol. 2014 Apr;90(4):334-5   [PMID:  24456545 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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