ArticleFrontiers in oncology2014
Increased Tumor Ascorbate is Associated with Extended Disease-Free Survival and Decreased Hypoxia-Inducible Factor-1 Activation in Human Colorectal Cancer.
Article in Frontiers in oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
- High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.Genes & diseases · 2026Review
- Review
- Two-color spheroid model for determining the OJournal of biological engineering · 2026Article
- Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.Journal of medicinal chemistry · 2025Review
- Effective oxygen metabolism-based prognostic signature for colorectal cancer.Frontiers in oncology · 2023Article
- Ascorbate content of clinical glioma tissues is related to tumour grade and to global levels of 5-hydroxymethyl cytosine.Scientific reports · 2022Article
- High-Dose Vitamin C for Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Diverse antitumor effects of ascorbic acid on cancer cells and the tumor microenvironment.Frontiers in oncology · 2022Review
- Increased Ascorbate Content of Glioblastoma Is Associated With a Suppressed Hypoxic Response and Improved Patient Survival.Frontiers in oncology · 2022Article
- High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Review
- Gene and Protein Expression Is Altered by Ascorbate Availability in Murine Macrophages Cultured under Tumour-Like Conditions.Antioxidants (Basel, Switzerland) · 2021Article
- The Role of 2-Oxoglutarate Dependent Dioxygenases in Gliomas and Glioblastomas: A Review of Epigenetic Reprogramming and Hypoxic Response.Frontiers in oncology · 2021Review
- Low Vitamin C Status in Patients with Cancer Is Associated with Patient and Tumor Characteristics.Nutrients · 2020Article
- Vitamin C Administration by Intravenous Infusion Increases Tumor Ascorbate Content in Patients With Colon Cancer: A Clinical Intervention Study.Frontiers in oncology · 2020Article
- Causes and Consequences of A Glutamine Induced Normoxic HIF1 Activity for the Tumor Metabolism.International journal of molecular sciences · 2019Article
- Mitophagy in Cancer: A Tale of Adaptation.Cells · 2019Review
- Vitamin C increases DNA breaks and suppresses DNA damage-independent activation of ATM by bleomycin.Free radical biology & medicine · 2019Article
- Targeting cancer vulnerabilities with high-dose vitamin C.Nature reviews. Cancer · 2019Review
- Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.BMC cancer · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 (p < 0.001) but overall levels varied considerably. HIF-1α, VEGF, and BNIP3 were elevated in tumor samples (p < 0.01). There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation (p = 0.002) and tumor size (p = 0.018). Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p = 0.006), with 141-1,094 additional disease-free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated with decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.
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