Document Details

Document Type : Article In Journal 
Document Title :
Radiation-enhanced lung cancer progression in a transgenic mouse model of lung cancer is predictive of outcomes in human lung and breast cancer
Radiation-enhanced lung cancer progression in a transgenic mouse model of lung cancer is predictive of outcomes in human lung and breast cancer
 
Document Language : English 
Abstract : Carcinogenesis is an adaptive process between nascent tumor cells and their microenvironment, including the modification of inflammatory responses from antitumorigenic to protumorigenic. Radiation exposure can stimulate inflammatory responses that inhibit or promote carcinogenesis. The purpose of this study is to determine the impact of radiation exposure on lung cancer progression in vivo and assess the relevance of this knowledge to human carcinogenesis. EXPERIMENTAL DESIGN: K-ras(LA1) mice were irradiated with various doses and dose regimens and then monitored until death. Microarray analyses were performed using Illumina BeadChips on whole lung tissue 70 days after irradiation with a fractionated or acute dose of radiation and compared with age-matched unirradiated controls. Unique group classifiers were derived by comparative genomic analysis of three experimental cohorts. Survival analyses were performed using principal component analysis and k-means clustering on three lung adenocarcinoma, three breast adenocarcinoma, and two lung squamous carcinoma annotated microarray datasets. RESULTS: Radiation exposure accelerates lung cancer progression in the K-ras(LA1) lung cancer mouse model with dose fractionation being more permissive for cancer progression. A nonrandom inflammatory signature associated with this progression was elicited from whole lung tissue containing only benign lesions and predicts human lung and breast cancer patient survival across multiple datasets. Immunohistochemical analyses suggest that tumor cells drive predictive signature. CONCLUSIONS: These results demonstrate that radiation exposure can cooperate with benign lesions in a transgenic model of cancer by affecting inflammatory pathways, and that clinically relevant similarities exist between human lung and breast carcinogenesis. 
ISSN : 1078-0432 
Journal Name : Clinical Cancer Research 
Volume : 20 
Issue Number : 6 
Publishing Year : 1435 AH
2014 AD 
Article Type : Article 
Added Date : Wednesday, March 9, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Oliver DelgadoDelgado, Oliver Investigator  
Kimberly G BattenBatten, Kimberly G Researcher  
James A RichardsonRichardson, James A Researcher  
Xian-Jin XieXie, Xian-Jin Researcher  
Adi F GazdarGazdar, Adi F Researcher  
Aadil A KaisaniKaisani, Aadil A Researcher  
Luc GirardGirard, Luc Researcher  
Carmen BehrensBehrens, Carmen Researcher  
Milind SuraokarSuraokar, Milind Researcher  
Gail FascianiFasciani, Gail Researcher  
Jerry W ShayShay, Jerry W Researcher  

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