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The expression of DNA damage checkpoint proteins and prognostic implication in metastatic brain tumors.
MedLine Citation:
PMID:  22329197     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The most important therapeutic tool in brain metastasis is radiation therapy. However, resistance to radiation is a possible cause of recurrence or treatment failure. Recently, DNA damage checkpoint signaling pathway activation after irradiation has received increasing attention. The association between the expression levels and survival outcome was evaluated to find possible therapeutic targets in brain metastasis. Radiosensitivity of human non-small cell lung cancer cell lines was determined by checking their viability after treatment with varying doses of ionizing radiation (IR). The expression of DNA checkpoint proteins was analyzed by Western blots and immunohistochemistry. On the basis of the clinical data for the patients, the association between the expression of the components and patients' survival was investigated. The expression levels of TopBP1 and phosphorylated Chk1 (P-Chk1) protein were higher in radioresistant lung cancer cell lines compared to radiosensitive cell lines. We previously assessed radiation survival of lung cancer cell lines after treating them with Chk1 inhibitor, AZD7762. AZD7762 significantly sensitized both radioresistant and radiosensitive cells to IR. We also observed a strong inverse relationship between progression-free survival (PFS) and expression level of P-Chk1 and TopBP1. This study, which is the first clinical report that connects DNA damage checkpoints and prognosis of brain metastasis, supports these two proteins to be promising targets for overcoming the radioresistance in brain metastasis.
Authors:
Ho Jun Seol; Hae Yong Yoo; Juyoun Jin; Kyeung Min Joo; Hyeong-Seok Kim; Su Jin Yoon; Seung Ho Choi; Yonghyun Kim; Hong Ryull Pyo; Do-Hoon Lim; Wook Kim; Hong-Duck Um; Jong Hyun Kim; Jung-Ii Lee; Do-Hyun Nam
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology research     Volume:  19     ISSN:  0965-0407     ISO Abbreviation:  Oncol. Res.     Publication Date:  2011  
Date Detail:
Created Date:  2012-02-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9208097     Medline TA:  Oncol Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  381-90     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
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