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    Nuclear oxidative damage correlates with poor survival in colorectal cancer.

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    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.
    Issue Date
    2012-02-01T10:28:49Z
    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
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    Citation
    Br J Cancer. 2009 Jan 27;100(2):381-8. Epub 2008 Dec 9.
    Journal
    British journal of cancer
    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
    ISSN
    1532-1827 (Electronic)
    0007-0920 (Linking)
    ae974a485f413a2113503eed53cd6c53
    10.1038/sj.bjc.6604821
    Scopus Count
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    St. Vincent's University Hospital

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