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dc.date.accessioned2019-01-31T13:36:10Z
dc.date.available2019-01-31T13:36:10Z
dc.date.created2019-01-02T12:52:15Z
dc.date.issued2019
dc.identifier.citationBousquet, Paula Meltzer, Sebastian Sønstevold, Linda Esbensen, Qin Ying Dueland, Svein Flatmark, Kjersti Sitter, Beathe Bathen, Tone Frost Seierstad, Therese Redalen, Kathrine Eide, Lars Ree, Anne Hansen . Markers of mitochondrial metabolism in tumor hypoxia, systemic inflammation, and adverse outcome of rectal cancer. Translational Oncology. 2019, 12(1), 76-83
dc.identifier.urihttp://hdl.handle.net/10852/66370
dc.description.abstractTumor 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.en_US
dc.languageEN
dc.publisherTranslational Oncology, University of Michigan Medical Center, Ann Arbor, MI
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleMarkers of mitochondrial metabolism in tumor hypoxia, systemic inflammation, and adverse outcome of rectal canceren_US
dc.typeJournal articleen_US
dc.creator.authorBousquet, Paula
dc.creator.authorMeltzer, Sebastian
dc.creator.authorSønstevold, Linda
dc.creator.authorEsbensen, Qin Ying
dc.creator.authorDueland, Svein
dc.creator.authorFlatmark, Kjersti
dc.creator.authorSitter, Beathe
dc.creator.authorBathen, Tone Frost
dc.creator.authorSeierstad, Therese
dc.creator.authorRedalen, Kathrine
dc.creator.authorEide, Lars
dc.creator.authorRee, Anne Hansen
cristin.unitcode185,53,48,10
cristin.unitnameAvdeling for gastro- og barnekirurgi
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.cristin1648545
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Translational Oncology&rft.volume=12&rft.spage=76&rft.date=2019
dc.identifier.jtitleTranslational Oncology
dc.identifier.volume12
dc.identifier.issue1
dc.identifier.startpage76
dc.identifier.endpage83
dc.identifier.doi10.1016/j.tranon.2018.09.010
dc.identifier.urnURN:NBN:no-69567
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn1936-5233
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/66370/2/Bousquet%2BTranslOncol2018.pdf
dc.type.versionPublishedVersion


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Attribution-NonCommercial-NoDerivatives 4.0 International
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