ArticleBMC cancer2017
Linking hypoxia, DNA damage and proliferation in multicellular tumor spheroids.
Article in BMC cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 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
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Cellular senescence and chronological age in various human tissues: A systematic review and meta-analysis.Aging cell · 2020Pooled it
- Anoxia tolerant DNA replication is supported by ATR kinase in the annual killifish Austrofundulus limnaeus.Journal of cell science · 2026Article
- Using advanced cell models for targeted radionuclide therapy evaluation: increased efficacy in 3D versus 2D.EJNMMI research · 2026Article
- Metabolic starvation-induced cell swelling drives solid stress in tumors.bioRxiv : the preprint server for biology · 2026Article
- Short-term hypoxia and nutrient deprivation stress induced shifts in p53 isoform expression in HepG2 tumourspheres.Molecular biology reports · 2026Article
- Machine learning-supported identification of necrosis in colorectal and pancreatic cancer spheroids.PloS one · 2026Article
- A Combined SIRT5 Activation and SIRT3 Inhibition Prevents Breast Cancer Spheroids Growth by Reducing HIF-1α and Mitophagy.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Modeling immune responses of cattle tomSphere · 2025Article
- Goodbye flat lymphoma biology.FEBS letters · 2025Review
- TSG6 affects anti cancer drug resistance and angiogenesis in 3D spheroid model of canine mammary gland tumor cells.Scientific reports · 2025Article
- Modeling the effects of radiation on the bone tumor microenvironment: opportunities for exploring combination therapies in microphysiologic systems.Cellular & molecular biology letters · 2025Review
- Tumor hypoxia: Classification, detection, and its critical role in cancer progression.Biomolecules & biomedicine · 2025Review
- The 3D Language of Cancer: Communication via Extracellular Vesicles from Tumor Spheroids and Organoids.International journal of molecular sciences · 2025Review
- Biomimetic integration of functionally controlled modular tissue building blocks for engineering 3D vascularized adipose tissue.Bioactive materials · 2025Article
- Advancing Tissue Engineering Through a Portable Perfusion and Incubation System.Bioengineering (Basel, Switzerland) · 2025Article
- Review
- 3D Microtumors Representing Ovarian Cancer Minimal Residual Disease Respond to the Fatty Acid Oxidation Inhibitor Perhexiline.Advanced healthcare materials · 2025Article
- Modulating Cancer Stem Cell Characteristics in CD133+ Melanoma Cells through Hif1α, KLF4, and SHH Silencing.ACS omega · 2025Article
- Oxygen-Releasing Nanodroplets Relieve Intratumoral Hypoxia and Potentiate Photodynamic Therapy in 3D Head and Neck Cancer Spheroids.ACS biomaterials science & engineering · 2025Article
- Microenvironment matters: insights from the FOSTER consortium on microenvironment-driven approaches to osteosarcoma therapy.Cancer metastasis reviews · 2025Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMulticellular Tumor Spheroids are frequently used to mimic the regionalization of proliferation and the hypoxic environment within avascular tumors. Here we exploit these features to study the activation of DNA damage repair pathways and their correlation to developing hypoxia.
methodsActivation of DNA damage repair markers, proliferation, cell death, glycogen accumulation and developing hypoxia were investigated using immunofluorescence, immuno-histochemistry, EdU incorporation, Western blots, COMET assays, and pharmacological agents in A673 Ewing sarcoma spheroids and monolayer cultures.
resultsDNA damage marker γ-H2AX is observed in the hypoxic, peri-necrotic region of growing spheroids. While most proliferating cells are seen on the spheroid surface, there are also a few Ki-67 positive cells in the hypoxic zone. The hypoxia-induced phosphorylation of H2AX to form γ-H2AX in spheroids is attenuated by the ATM inhibitor KU55933, but not the ATR inhibitor VE-821.
conclusionTumor spheroids mimic tumor microenvironments such as the anoxic, hypoxic and oxic niches within solid tumors, as well as populations of cells that are viable, proliferating, and undergoing DNA damage repair processes under these different micro-environmental conditions. ATM, but not ATR, is the primary kinase responsible for γ-H2AX formation in the hypoxic core of A673 spheroids. Spheroids could offer unique advantages in testing therapeutics designed to target malignant cells that evade conventional treatment strategies by adapting to the hypoxic tumor microenvironment.
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.