AUTHOR=Kuiper Caroline , Dachs Gabi , Munn Delwyn , Currie Margaret , Robinson Bridget , Pearson John F., Vissers Margreet C. TITLE=Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreased Hypoxia-Inducible Factor-1 Activation in Human Colorectal Cancer JOURNAL=Frontiers in Oncology VOLUME=4 YEAR=2014 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2014.00010 DOI=10.3389/fonc.2014.00010 ISSN=2234-943X ABSTRACT=
Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF)-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study, we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3, and vascular endothelial cell growth factor (VEGF). Patient survival was monitored for the first 6 years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (