Abstract:
:Tumor hypoxia contributes to therapy resistance and metastatic progression of locally advanced rectal cancer (LARC). We postulated that the tumor mitochondrial metabolism, manifested by reactive oxygen species (ROS) and mitochondrial DNA (mtDNA) damage, reflects how hypoxic conditions connect to cancer-induced systemic inflammation and poor outcome. Levels of ROS and mtDNA damage were analyzed in three colorectal cancer (CRC) cell lines cultured for 24 hours under normoxia (21% O2) or hypoxia (0.2% O2) and serum sampled at the time of diagnosis from 35 LARC patients participating in a prospective therapy study. Compared with normoxia, ROS were significantly repressed and mtDNA damage was significantly enhanced in the hypoxic CRC cell lines; hence, a low ratio of ROS to mtDNA damage was an indicator of hypoxic conditions. In the LARC patients, low serum ROS were associated with elevated levels of circulating carcinoembryonic antigen and tumor choline concentration, both indicative of unfavorable biology, as well as adverse progression-free and overall survival. A low ratio of ROS to mtDNA damage in serum was associated with poor local tumor response to the neoadjuvant treatment and, of note, elevated systemic inflammation factors (C-reactive protein, the interleukin-1 receptor antagonist, and factors involved in tumor necrosis factor signaling), indicating that deficient treatment response locally and detrimental inflammation systemically link to a hypoxic mitochondrial metabolism. In conclusion, serum ROS and damaged mtDNA may be markers of the mitochondrial metabolism driven by the state of oxygenation of the primary tumor and possibly implicated in systemic inflammation and adverse outcome of LARC.
journal_name
Transl Oncoljournal_title
Translational oncologyauthors
Bousquet PA,Meltzer S,Sønstevold L,Esbensen Y,Dueland S,Flatmark K,Sitter B,Bathen TF,Seierstad T,Redalen KR,Eide L,Ree AHdoi
10.1016/j.tranon.2018.09.010subject
Has Abstractpub_date
2019-01-01 00:00:00pages
76-83issue
1issn
1936-5233pii
S1936-5233(18)30257-2journal_volume
12pub_type
杂志文章abstract::Esophageal squamous cell carcinoma (ESCC) is a frequent and lethal neoplasia. As recent advances in targeted therapy have not improved ESCC prognosis, characterization of molecular alterations associated to this tumor is of foremost relevance. In this study, we analyze, for the first time, the complete genomic profile...
journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.08.002
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.12.008
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.05.006
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.03.008
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.09.003
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.05.001
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.12.003
更新日期:2020-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1593/tlo.13844
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journal_title:Translational oncology
pub_type: 杂志文章,评审
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更新日期:2020-10-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2017.12.012
更新日期:2018-04-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.02.004
更新日期:2018-04-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.100791
更新日期:2020-09-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.11.005
更新日期:2020-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
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journal_title:Translational oncology
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journal_title:Translational oncology
pub_type: 杂志文章,评审
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2014.04.014
更新日期:2014-05-12 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2015.06.006
更新日期:2015-08-01 00:00:00
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journal_title:Translational oncology
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doi:10.1016/j.tranon.2020.100747
更新日期:2020-04-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2019.10.015
更新日期:2020-02-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2020.101007
更新日期:2021-01-06 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2009-08-18 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
doi:10.1016/j.tranon.2018.01.015
更新日期:2018-04-01 00:00:00
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journal_title:Translational oncology
pub_type: 杂志文章
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