Nuclear oxidative damage correlates with poor survival in colorectal cancer.

Hdl Handle:
http://hdl.handle.net/10147/207473
Title:
Nuclear oxidative damage correlates with poor survival in colorectal cancer.
Authors:
Sheridan, J; Wang, L-M; Tosetto, M; Sheahan, K; Hyland, J; Fennelly, D; O'Donoghue, D; Mulcahy, H; O'Sullivan, J
Affiliation:
Centre for Colorectal Disease, St Vincent's University Hospital, Elm Park Dublin , 4, Republic of Ireland.
Citation:
Br J Cancer. 2009 Jan 27;100(2):381-8. Epub 2008 Dec 9.
Journal:
British journal of cancer
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207473
DOI:
10.1038/sj.bjc.6604821
PubMed ID:
19066606
Abstract:
Oxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2'-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal cancer (CRC). We examined levels of 8-oxo-dG in sporadic CRC to determine its relationship with pathological stage and outcome. A total of 143 CRC patients and 105 non-cancer patients were studied. Nuclear and cytoplasmic 8-oxo-dG was assessed using immunohistochemistry. Double immunofluorescence using 8-oxo-dG and manganese superoxide dismutase (MnSOD) antibodies localised cytoplasmic 8-oxo-dG. Apoptosis was detected using TUNEL. Nuclear staining levels were similar in tumour tissue and matched normal mucosa in both epithelial (P=0.22) and stromal (P=0.85) cells. Epithelial cytoplasmic staining was greater in tumour tissue (P<0.001). Double immunofluorescence localised cytoplasmic 8-oxo-dG to mitochondria. Epithelial and stromal nuclear 8-oxo-dG decreased with local disease spread, but highest levels were found in distant disease (P<0.01). Survival was related to epithelial nuclear and stromal staining in normal mucosa (P<0.001) and tumour (P<0.01) but was unrelated to cytoplasmic staining. Normal control cells in tissue from cancer patients with high levels of 8-oxo-dG failed to undergo cell death. 8-oxo-dG may be an important biomarker of disease risk, progression and survival for CRC patients.
Language:
eng
MeSH:
Adolescent; Adult; Aged; Aged, 80 and over; Apoptosis/physiology; Case-Control Studies; Cell Nucleus/*metabolism; Colon/metabolism/pathology; Colorectal Neoplasms/*metabolism/*mortality/pathology; Cytoplasm/metabolism; Deoxyguanosine/*analogs & derivatives/metabolism; Disease Progression; Female; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; In Situ Nick-End Labeling; Male; Middle Aged; Rectum/metabolism/pathology; Superoxide Dismutase/metabolism; Survival Rate; Tissue Array Analysis; Tumor Markers, Biological/*metabolism; Young Adult
ISSN:
1532-1827 (Electronic); 0007-0920 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorSheridan, Jen_GB
dc.contributor.authorWang, L-Men_GB
dc.contributor.authorTosetto, Men_GB
dc.contributor.authorSheahan, Ken_GB
dc.contributor.authorHyland, Jen_GB
dc.contributor.authorFennelly, Den_GB
dc.contributor.authorO'Donoghue, Den_GB
dc.contributor.authorMulcahy, Hen_GB
dc.contributor.authorO'Sullivan, Jen_GB
dc.date.accessioned2012-02-01T10:28:49Z-
dc.date.available2012-02-01T10:28:49Z-
dc.date.issued2012-02-01T10:28:49Z-
dc.identifier.citationBr J Cancer. 2009 Jan 27;100(2):381-8. Epub 2008 Dec 9.en_GB
dc.identifier.issn1532-1827 (Electronic)en_GB
dc.identifier.issn0007-0920 (Linking)en_GB
dc.identifier.pmid19066606en_GB
dc.identifier.doi10.1038/sj.bjc.6604821en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207473-
dc.description.abstractOxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2'-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal cancer (CRC). We examined levels of 8-oxo-dG in sporadic CRC to determine its relationship with pathological stage and outcome. A total of 143 CRC patients and 105 non-cancer patients were studied. Nuclear and cytoplasmic 8-oxo-dG was assessed using immunohistochemistry. Double immunofluorescence using 8-oxo-dG and manganese superoxide dismutase (MnSOD) antibodies localised cytoplasmic 8-oxo-dG. Apoptosis was detected using TUNEL. Nuclear staining levels were similar in tumour tissue and matched normal mucosa in both epithelial (P=0.22) and stromal (P=0.85) cells. Epithelial cytoplasmic staining was greater in tumour tissue (P<0.001). Double immunofluorescence localised cytoplasmic 8-oxo-dG to mitochondria. Epithelial and stromal nuclear 8-oxo-dG decreased with local disease spread, but highest levels were found in distant disease (P<0.01). Survival was related to epithelial nuclear and stromal staining in normal mucosa (P<0.001) and tumour (P<0.01) but was unrelated to cytoplasmic staining. Normal control cells in tissue from cancer patients with high levels of 8-oxo-dG failed to undergo cell death. 8-oxo-dG may be an important biomarker of disease risk, progression and survival for CRC patients.en_GB
dc.language.isoengen_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshApoptosis/physiologyen_GB
dc.subject.meshCase-Control Studiesen_GB
dc.subject.meshCell Nucleus/*metabolismen_GB
dc.subject.meshColon/metabolism/pathologyen_GB
dc.subject.meshColorectal Neoplasms/*metabolism/*mortality/pathologyen_GB
dc.subject.meshCytoplasm/metabolismen_GB
dc.subject.meshDeoxyguanosine/*analogs & derivatives/metabolismen_GB
dc.subject.meshDisease Progressionen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFluorescent Antibody Techniqueen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunoenzyme Techniquesen_GB
dc.subject.meshIn Situ Nick-End Labelingen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshRectum/metabolism/pathologyen_GB
dc.subject.meshSuperoxide Dismutase/metabolismen_GB
dc.subject.meshSurvival Rateen_GB
dc.subject.meshTissue Array Analysisen_GB
dc.subject.meshTumor Markers, Biological/*metabolismen_GB
dc.subject.meshYoung Adulten_GB
dc.titleNuclear oxidative damage correlates with poor survival in colorectal cancer.en_GB
dc.contributor.departmentCentre for Colorectal Disease, St Vincent's University Hospital, Elm Park Dublin , 4, Republic of Ireland.en_GB
dc.identifier.journalBritish journal of canceren_GB
dc.description.provinceLeinster-

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