ArticleCells2021
Resistance of Hypoxic Cells to Ionizing Radiation Is Mediated in Part via Hypoxia-Induced Quiescence.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Magnetic-Based Human Tissue 3D Cell Culture: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Basis and prospects of radiotherapy combined with high-intensity focused ultrasound ablation (Review).Oncology letters · 2026Review
- Comparison of In Vitro and Clinical Alpha/Beta Estimates With Potential Impact of Tumor Heterogeneity.Advances in radiation oncology · 2026Article
- Ubiquitination of DDX21 by HERC2 induces a dormancy-like phenotype via the NUCKS1-p21/p27 axis to promote radio-resistance in colorectal cancer cells.Cell death & disease · 2026Article
- Promising Targets and Drugs for Improving Head and Neck Cancer Response to Radiotherapy.Current pharmaceutical design · 2026Review
- The Aptamer bi-(AID-1-T) Synergizes with Radiation to Inhibit Proliferation of Human Glioma Cells.Pharmaceutics · 2025Article
- Effect of Reoxygenation on Radioresistance of Chronically Hypoxic A549 Non-Small Cell Lung Cancer (NSCLC) Cells Following X-Ray and Carbon Ion Exposure.International journal of molecular sciences · 2025Article
- Hypoxia-augmented chemotherapy potentiates imaging-guided combinatorial radionuclide-sonodynamic therapy for pancreatic cancer.Journal of nanobiotechnology · 2025Article
- HIF-1α-Mediated Disruption of Cellular Junctions: The Impact of Hypoxia on the Tumor Microenvironment and Invasion.International journal of molecular sciences · 2025Review
- From conventional to cutting edge: an exploration of osteosarcoma treatments.Medical oncology (Northwood, London, England) · 2025Review
- Key Structural Features of Microvascular Networks Leading to the Formation of Multiple Equilibria.Bulletin of mathematical biology · 2025Article
- A novel lineage-tracing tool reveals that hypoxic tumor cells drive tumor relapse after radiotherapy.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2025Article
- DNA Damage and Inflammatory Response of p53 Null H358 Non-Small Cell Lung Cancer Cells to X-Ray Exposure Under Chronic Hypoxia.International journal of molecular sciences · 2024Article
- Mechanisms of HIF1A-mediated immune evasion in gastric cancer and the impact on therapy resistance.Cell biology and toxicology · 2024Article
- Gd-GQDs as nanotheranostic platform for the treatment of HPV-positive oropharyngeal cancer.Medical oncology (Northwood, London, England) · 2024Article
- Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours.Frontiers in oncology · 2024Review
- A simplified protocol to induce hypoxia in a standard incubator: A focus on retinal cells.Experimental eye research · 2023Article
- Article
- Functional Imaging of Hypoxia: PET and MRI.Cancers · 2023Review
- Quiescent Cancer Cells-A Potential Therapeutic Target to Overcome Tumor Resistance and Relapse.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Double strand breaks (DSBs) are highly toxic to a cell, a property that is exploited in radiation therapy. A critical component for the damage induction is cellular oxygen, making hypoxic tumor areas refractory to the efficacy of radiation treatment. During a fractionated radiation regimen, these hypoxic areas can be re-oxygenated. Nonetheless, hypoxia still constitutes a negative prognostic factor for the patient's outcome. We hypothesized that this might be attributed to specific hypoxia-induced cellular traits that are maintained upon reoxygenation. Here, we show that reoxygenation of hypoxic non-transformed RPE-1 cells fully restored induction of DSBs but the cells remain radioresistant as a consequence of hypoxia-induced quiescence. With the use of the cell cycle indicators (FUCCI), cell cycle-specific radiation sensitivity, the cell cycle phase duration with live cell imaging, and single cell tracing were assessed. We observed that RPE-1 cells experience a longer G1 phase under hypoxia and retain a large fraction of cells that are non-cycling. Expression of HPV oncoprotein E7 prevents hypoxia-induced quiescence and abolishes the radioprotective effect. In line with this, HPV-negative cancer cell lines retain radioresistance, while HPV-positive cancer cell lines are radiosensitized upon reoxygenation. Quiescence induction in hypoxia and its HPV-driven prevention was observed in 3D multicellular spheroids. Collectively, we identify a new hypoxia-dependent radioprotective phenotype due to hypoxia-induced quiescence that accounts for a global decrease in radiosensitivity that can be retained upon reoxygenation and is absent in cells expressing oncoprotein E7.
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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 Socratic graph.