ArticleBMC cancer2019
Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Clinicopathological and prognostic value of hypoxia-inducible factor-1α in breast cancer: a meta-analysis including 5177 patients.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Pooled it
- High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.Genes & diseases · 2026Review
- Limitation-circumventing and strength-capitalizing hydrogel potentiates durable antitumor immunity and robust abscopal effect in radiotherapy.Theranostics · 2026Article
- Article
- Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.Journal of medicinal chemistry · 2025Review
- Integrative bioinformatics and experimental validation unveil CRISP3 as a hypoxia-, epithelial mesenchymal transition-, and immune-related prognostic biomarker and therapeutic target in breast cancer.Frontiers in immunology · 2025Article
- OFrontiers in cellular and infection microbiology · 2025Article
- Analysis of High-Dose Ascorbate-Induced Cytotoxicity in Human Glioblastoma Cells and the Role of Dehydroascorbic Acid and Iron.Antioxidants (Basel, Switzerland) · 2024Article
- Joint multi-omics discriminant analysis with consistent representation learning using PANDA.Research square · 2024Article
- Drug repurposing for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Proton pump inhibitors display anti-tumour potential in glioma.Cell proliferation · 2023Review
- Loss of exosomal miR-200b-3p from hypoxia cancer-associated fibroblasts promotes tumorigenesis and reduces sensitivity to 5-Flourouracil in colorectal cancer via upregulation of ZEB1 and E2F3.Cancer gene therapy · 2023Article
- Expression profile of interleukin-6, 4-hydroxy-2-nonenal, and hypoxia-inducible factor 1-α in women with breast cancer and their association with clinicopathological parameters.Contemporary oncology (Poznan, Poland) · 2023Article
- Article
- Exploring Amodiaquine's Repurposing Potential in Breast Cancer Treatment-Assessment of In-Vitro Efficacy & Mechanism of Action.International journal of molecular sciences · 2022Article
- Bioinformatics analysis reveals the potential target of rosiglitazone as an antiangiogenic agent for breast cancer therapy.BMC genomic data · 2022Article
- Ascorbate content of clinical glioma tissues is related to tumour grade and to global levels of 5-hydroxymethyl cytosine.Scientific reports · 2022Article
- Metabolomics and EMT Markers of Breast Cancer: A Crosstalk and Future Perspective.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022Review
- Repurposing Vitamin C for Cancer Treatment: Focus on Targeting the Tumor Microenvironment.Cancers · 2022Review
- Hypoxia-induced circWSB1 promotes breast cancer progression through destabilizing p53 by interacting with USP10.Molecular cancer · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer.
methodsIn a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1α, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters.
resultsHIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival.
conclusionsOur findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.