Cited by 1,050Cancer, Hypoxia, and MetabolismMathematical Biology Tumor GrowthAngiogenesis and VEGF in Cancer

The DOI matches its Crossref record; 126 of the 126 references it cites were found in a registry or an index.

Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response

Open access

McKeown, S R·2014·The British Journal of Radiology

DOI 10.1259/bjr.20130676PMC PMC4064601

Open this paper in CoChat — free account

Abstract

Tumour hypoxia is increasingly recognized as a major deleterious factor in cancer therapies, as it compromises treatment and drives malignant progression. This review seeks to clarify the oxygen levels that are pertinent to this issue. It is argued that normoxia (20% oxygen) is an extremely poor comparator for "physoxia", i.e. the much lower levels of oxygen universally found in normal tissues, which averages about 5% oxygen, and ranges from about 3% to 7.4%. Importantly, it should be recognized that the median oxygenation in untreated tumours is significantly much lower, falling between approximately 0.3% and 4.2% oxygen, with most tumours exhibiting median oxygen levels <2%. This is partially dependent on the tissue of origin, and it is notable that many prostate and pancreatic tumours are profoundly hypoxic. In addition, therapy can induce even further, often unrecognized, changes in tumour oxygenation that may vary longitudinally, increasing or decreasing during treatment in ways that are not always predictable. Studies that fail to take cognizance of the actual physiological levels of oxygen in tissues (approximately 5%) and tumours (approximately 1%) may fail to identify the real circumstances driving tumour response to treatment and/or malignant progression. This can be of particular importance in genetic studies in vitro when comparison to human tumours is required.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1259/bjr.20130676

Cites

126 of 126 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

1 retracted

Lysyl oxidase is essential for hypoxia-induced metastasis
Erler, J. T., Bennewith, K. L., Nicolau, M., Dornhöfer, N., Kong, C., Le, Q.-T., Chi, J.-T. A., Jeffrey, S. S., & Giaccia, A. J. (2006) · Nature · doi:10.1038/nature04695 · Cited by 1,309
Retracted
On the origin of cancer cells
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Molecular mechanisms and clinical applications of angiogenesis
Carmeliet, P., & Jain, R. K. (2011) · Nature · doi:10.1038/nature10144 · Cited by 5,467
Hypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177
Radiobiology for the Radiologist.
(1974) · Annals of Internal Medicine · doi:10.7326/0003-4819-80-3-438_1 · Cited by 3,498
Targeting hypoxia in cancer therapy
Wilson, W. R., & Hay, M. P. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3064 · Cited by 3,172
Modes of resistance to anti-angiogenic therapy
Bergers, G., & Hanahan, D. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2442 · Cited by 2,953
Exploiting tumour hypoxia in cancer treatment
Brown, J. M., & Wilson, W. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1367 · Cited by 2,828
Tumor Hypoxia: Definitions and Current Clinical, Biologic, and Molecular Aspects
Hockel, M., & Vaupel, P. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.4.266 · Cited by 2,662
Antiangiogenic Therapy Elicits Malignant Progression of Tumors to Increased Local Invasion and Distant Metastasis
Pàez‐Ribes, M., Allen, E., Hudock, J., Takeda, T., Okuyama, H., Viñals, F., Inoue, M., Bergers, G., Hanahan, D., & Casanovas, O. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.027 · Cited by 2,373

Show all 126 references

Research works printed but not linked: 8

Vaupel P, 2010, Exp Oncol, 32, 125
Vaupel P, 2003, Cancer Res, 63, 7634
Höckel M, 1991, Cancer Res, 51, 6098
Kallinowski F, 1995, Tumor oxygenation, 291
Kallinowski F, 1995, Tumor oxygenation, 205
Vaupel P, 2006, Eur J Gynaecol Oncol, 27, 142
Stone JE, 2005, Eur J Gynaecol Oncol, 26, 31
Cairns RA, 2001, Cancer Res, 61, 8903

Sorted by citations

Items 101–200 of 1,000

Non-coding RNAs shuttled via exosomes reshape the hypoxic tumor microenvironment
Wang, W., Han, Y., Jo, H. A., Lee, J., & Song, Y. S. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00893-3 · Cited by 84
Targeting tumor vascularization: promising strategies for vascular normalization
Zheng, R., Li, F., Li, F., & Gong, A. (2021) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-021-03701-8 · Cited by 84
The Synergistic Cooperation between TGF-β and Hypoxia in Cancer and Fibrosis
Mallikarjuna, P., Zhou, Y., & Landström, M. (2022) · Biomolecules · doi:10.3390/biom12050635 · Cited by 84
Activatable Nanocomposite Probe for Preoperative Location and Intraoperative Navigation for Orthotopic Hepatic Tumor Resection via MSOT and Aggregation-Induced Near-IR-I/II Fluorescence Imaging
Zeng, Z., Ouyang, J., Sun, L., Zeng, C., Zeng, F., & Wu, S. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c01596 · Cited by 80
Role of Short- and Long-Lived Reactive Species on the Selectivity and Anti-Cancer Action of Plasma Treatment In Vitro
Sklias, K., Sousa, J. S., & Girard, P.-M. (2021) · Cancers · doi:10.3390/cancers13040615 · Cited by 80
FLASH Dose Rate Helium Ion Beams: First In Vitro Investigations
Tessonnier, T., Mein, S., Walsh, D. W. M., Schuhmacher, N., Liew, H., Cee, R., Galonska, M., Scheloske, S., Schömers, C., Weber, U. A., et al. (2021) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2021.07.1703 · Cited by 78
Hypoxic exosomes orchestrate tumorigenesis: molecular mechanisms and therapeutic implications
Jafari, R., Rahbarghazi‬, R., Ahmadi, M., Hassanpour, M., & Rezaie, J. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02662-9 · Cited by 80
Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions
Day, R. A., Estabrook, D. A., Logan, J. K., & Sletten, E. M. (2017) · Chemical Communications · doi:10.1039/c7cc07038a · Cited by 76
Two-dimensional nanomaterials for tumor microenvironment modulation and anticancer therapy
Wu, M., Niu, X., Zhang, R., & Xu, Z. P. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114360 · Cited by 76
Metastasis in Pancreatic Ductal Adenocarcinoma: Current Standing and Methodologies
Pereira, M. A., & Chio, I. I. C. (2019) · Genes · doi:10.3390/genes11010006 · Cited by 75
Development and Verification of the Hypoxia- and Immune-Associated Prognostic Signature for Pancreatic Ductal Adenocarcinoma
Chen, D., Huang, H., Zang, L., Gao, W., Zhu, H., & Yu, X. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.728062 · Cited by 75
Investigation of PPIX-Lipo-MnO2 to enhance photodynamic therapy by improving tumor hypoxia
Chudal, L., Pandey, N. K., Phan, J., Johnson, O., Li, X., & Chen, W. (2019) · Materials Science and Engineering: C · doi:10.1016/j.msec.2019.109979 · Cited by 73
Emerging Nano-Based Strategies Against Drug Resistance in Tumor Chemotherapy
Cao, L., Zhu, Y., Wang, W., Wang, G., Zhang, S., & Cheng, H. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.798882 · Cited by 75
VDAC Modulation of Cancer Metabolism: Advances and Therapeutic Challenges
Heslop, K. A., Milesi, V., & Maldonado, E. N. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.742839 · Cited by 77
Modeling the effect of oxygen on the chemical stage of water radiolysis using GPU-based microscopic Monte Carlo simulations, with an application in FLASH radiotherapy
Lai, Y., Jia, X., & Chi, Y. (2020) · Physics in Medicine and Biology · doi:10.1088/1361-6560/abc93b · Cited by 71
Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment
Mimoto, F., Tatsumi, K., Shimizu, S., Kadono, S., Haraya, K., Nagayasu, M., Suzuki, Y., Fujii, E., Kamimura, M., Hayasaka, A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108542 · Cited by 71
Modified Bovine Milk Exosomes for Doxorubicin Delivery to Triple-Negative Breast Cancer Cells
Pullan, J. E., Dailey, K. M., Bhallamudi, S., Li, F., Alhalhooly, L., Froberg, J., Osborn, J., Sarkar, K., Molden, T., Sathish, V., et al. (2022) · ACS Applied Bio Materials · doi:10.1021/acsabm.2c00015 · Cited by 72
TGF-β in the microenvironment induces a physiologically occurring immune-suppressive senescent state
Matsuda, S., Revandkar, A., Dubash, T. D., Ravi, A., Wittner, B. S., Lin, M., Morris, R. T., Burr, R., Guo, H., Seeger, K., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112129 · Cited by 76
Hypoxia-induced therapy resistance: Available hypoxia-targeting strategies and current advances in head and neck cancer
López-Codony, V., & Tavassoli, M. (2021) · Translational Oncology · doi:10.1016/j.tranon.2021.101017 · Cited by 73
The role of metabolic reprogramming of tumor-associated macrophages in shaping the immunosuppressive tumor microenvironment
Li, L., & Tian, Y. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114504 · Cited by 75
Photoacoustic imaging for investigating tumor hypoxia: a strategic assessment
Nasri, D., Manwar, R., Kaushik, A. K., Er, E. E., & Avanaki, K. (2023) · Theranostics · doi:10.7150/thno.84253 · Cited by 70
Glutamine Synthetase: Localization Dictates Outcome
Castegna, A., & Menga, A. (2018) · Genes · doi:10.3390/genes9020108 · Cited by 75
The Role of Tumor Microenvironment in Genomic Instability of Malignant Tumors
Sonugür, F. G., & Akbulut, H. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.01063 · Cited by 68
Why Great Mitotic Inhibitors Make Poor Cancer Drugs
Yan, V. C., Butterfield, H. E., Poral, A. H., Yan, M. J., Yang, K. L., Pham, C.-D., & Müller, F. L. (2020) · Trends in cancer · doi:10.1016/j.trecan.2020.05.010 · Cited by 71
How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia
Mirchandani, A. S., Sánchez-García, M. A., & Walmsley, S. R. (2024) · Nature reviews. Immunology · doi:10.1038/s41577-024-01087-5 · Cited by 77
Human interpretable grammar encodes multicellular systems biology models to democratize virtual cell laboratories
Johnson, J., Bergman, D. R., da Rocha, H. L., Zhou, D. L., Cramer, E. M., McLean, I. C., Dance, Y. W., Booth, M. I., Nicholas, Z., Lopez-Vidal, T. Y., et al. (2025) · Cell · doi:10.1016/j.cell.2025.06.048 · Cited by 82
The cellular stress proteins CHCHD10 and MNRR1 (CHCHD2): Partners in mitochondrial and nuclear function and dysfunction
Purandare, N., Somayajulu, M., Hüttemann, M., Grossman, L. I., & Aras, S. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.001073 · Cited by 68
Targeting the tumour microenvironment in platinum-resistant ovarian cancer
Cummings, M., Freer, C., & Orsi, N. M. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.02.007 · Cited by 65
Enamine N -Oxides: Synthesis and Application to Hypoxia-Responsive Prodrugs and Imaging Agents
Kang, D., Cheung, S. T., Wong-Rolle, A., & Kim, J. (2021) · ACS Central Science · doi:10.1021/acscentsci.0c01586 · Cited by 66
The Photosensitizer Temoporfin ( m THPC ) – Chemical, Pre‐clinical and Clinical Developments in the Last Decade † ‡
Wiehe, A., & Senge, M. O. (2022) · Photochemistry and Photobiology · doi:10.1111/php.13730 · Cited by 70
Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis
Mitrakas, A. G., Tsolou, A., Didaskalou, S., Karkaletsou, L., Efstathiou, C., Eftalitsidis, E., Marmanis, K., & Koffa, M. D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086949 · Cited by 65
HIF-1 and HIF-2 in cancer: structure, regulation, and therapeutic prospects
Shi, Y., & Gilkes, D. M. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05537-0 · Cited by 81
Oxygen regulation of TET enzymes
Matulevičiūtė, R., Cunha, P. P., Johnson, R. S., & Foskolou, I. P. (2021) · FEBS Journal · doi:10.1111/febs.15695 · Cited by 69
Towards Physiologic Culture Approaches to Improve Standard Cultivation of Mesenchymal Stem Cells
Nikolits, I., Nebel, S., Egger, D., Kreß, S., & Kasper, C. (2021) · Cells · doi:10.3390/cells10040886 · Cited by 71
Regulation of the phosphoprotein phosphatase 2A system and its modulation during oxidative stress: A potential therapeutic target?
Elgenaidi, I. S., & Spiers, P. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.011 · Cited by 67
Hypoxia, a key factor in the immune microenvironment
Hu, J., Li, X., Yang, L., & Li, H. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113068 · Cited by 67
The Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics in Oral Cancer Management
Fuad, A. S. M., Amran, N. A., Nasruddin, N. S., Burhanudin, N. A., Dashper, S. G., & Arzmi, M. H. (2022) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-022-09985-7 · Cited by 69
Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours
Fu, Q., Zhang, S., Shen, S., Gu, Z., Chen, J., Song, D., Sun, P., Wang, C., Guo, Z., Gao, Y. Q., et al. (2024) · Nature Biomedical Engineering · doi:10.1038/s41551-024-01239-x · Cited by 63
High-throughput cancer hypothesis testing with an integrated PhysiCell-EMEWS workflow
Ozik, J., Collier, N. T., Wozniak, J. M., Macal, C. M., Cockrell, C., Friedman, S. H., Ghaffarizadeh, A., Heiland, R. W., An, G. C., & Macklin, P. (2018) · BMC Bioinformatics · doi:10.1186/s12859-018-2510-x · Cited by 68
Hypoxic non-small-cell lung cancer cell-derived exosomal miR-21 promotes resistance of normoxic cell to cisplatin
Dong, C., Liu, X., Wang, H., Li, J., Dai, L., Li, J., & Xu, Z. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s186922 · Cited by 62
HILPDA promotes NASH-driven HCC development by restraining intracellular fatty acid flux in hypoxia
Povero, D., Chen, Y., Johnson, S. M., McMahon, C. E., Pan, M., Bao, H., Petterson, X.-M. T., Blake, E., Lauer, K. P., O’Brien, D. R., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.03.041 · Cited by 63
How hypoxia regulate exosomes in ischemic diseases and cancer microenvironment?
Yaghoubi, S., Najminejad, H., Dabaghian, M., Karimi, M. H., Abdollahpour‐Alitappeh, M., Rad, F., Mahi‐Birjand, M., Mohammadi, S., Mohseni, F., Lari, M. S., et al. (2020) · IUBMB Life · doi:10.1002/iub.2275 · Cited by 63
Positronium as a biomarker of hypoxia
Moskal, P., & Stępień, E. Ł. (2021) · Bio-Algorithms and Med-Systems · doi:10.1515/bams-2021-0189 · Cited by 61
The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance
Jovanović, M., Podolski-Renić, A., Krasavin, M., & Pešić, M. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.883297 · Cited by 69
Extracellular Vesicles Are Key Regulators of Tumor Neovasculature
Kuriyama, N., Yoshioka, Y., Kikuchi, S., Azuma, N., & Ochiya, T. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.611039 · Cited by 58
Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models
Ziółkowska‐Suchanek, I. (2021) · Cells · doi:10.3390/cells10010141 · Cited by 61
Recent advances in ZnO-based photosensitizers: Synthesis, modification, and applications in photodynamic cancer therapy
Fatima, H., Jin, Z. Y., Shao, Z., & Chen, X. J. (2022) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2022.04.087 · Cited by 60
Bridging the gap between tumor-on-chip and clinics: a systematic review of 15 years of studies
Bouquerel, C., Dubrova, A., Hofer, I., Phan, D. T. T., Bernheim, M., Ladaigue, S., Cavaniol, C., Maddalo, D., Cabel, L., Mechta-Grigoriou, F., et al. (2023) · Lab on a Chip · doi:10.1039/d3lc00531c · Cited by 58
USP14 maintains HIF1-α stabilization via its deubiquitination activity in hepatocellular carcinoma
Lv, C., Wang, S., Lin, L., Wang, C., Zeng, K., Meng, Y., Sun, G., Wei, S., Liu, Y., & Zhao, Y. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04089-6 · Cited by 57
Calpain-2 regulates hypoxia/HIF-induced plasticity toward amoeboid cancer cell migration and metastasis
Boekhorst, V. T., Jiang, L., Mählen, M., Meerlo, M., Dunkel, G., Durst, F. C., Yang, Y., Levine, H., Burgering, B. M. T., & Friedl, P. (2021) · Current Biology · doi:10.1016/j.cub.2021.11.040 · Cited by 69
An Intelligent Nanoplatform for Orthotopic Glioblastoma Therapy by Nonferrous Ferroptosis
Cao, Y., Zhang, S., Lv, Z., Yin, N., Zhang, H., Song, P., Zhang, T., Chen, Y., Xu, H., Wang, Y., et al. (2022) · Advanced Functional Materials · doi:10.1002/adfm.202209227 · Cited by 58
Carbon Ions for Hypoxic Tumors: Are We Making the Most of Them?
Sokol, O., & Durante, M. (2023) · Cancers · doi:10.3390/cancers15184494 · Cited by 58
Crosstalk between CAFs and tumour cells in head and neck cancer
Li, X., González-Maroto, C., & Tavassoli, M. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02053-9 · Cited by 61
Colorectal cancer invasiveness in vitro: Predominant contribution of neonatal Nav1.5 under normoxia and hypoxia
Guzel, R. M., Ogmen, K., Ilieva, K. M., Fraser, S. P., & Djamgoz, M. B. A. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27399 · Cited by 59
Essential roles of mitochondrial and heme function in lung cancer bioenergetics and tumorigenesis
Kalainayakan, S. P., FitzGerald, K. E., Konduri, P. C., Vidal, C., & Li, Z. (2018) · Cell & Bioscience · doi:10.1186/s13578-018-0257-8 · Cited by 59
Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis
Sarem, M., Otto, O., Tanaka, S., & Shastri, V. P. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-018-1103-y · Cited by 58
Small Two-Photon Organic Fluorogenic Probes: Sensing and Bioimaging of Cancer Relevant Biomarkers
Singh, A. K., Nair, A. V., & Singh, N. D. P. (2021) · Analytical Chemistry · doi:10.1021/acs.analchem.1c04306 · Cited by 57
Engineering next generation vascularized organoids
Werschler, N., Quintard, C., Nguyen, S., & Penninger, J. M. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.118529 · Cited by 63
S100A7: from mechanism to cancer therapy
Padilla, L., Plaza, S. D., Adán, J., Masa, M., Martinez, J. M., Roque, L., Coll, T., Hervás, R., Calvis, C., Llinàs, L., et al. (2017) · Oncogene · doi:10.1038/onc.2017.283 · Cited by 57
The Role of Sumoylation in the Response to Hypoxia: An Overview
Filippopoulou, C., Simos, G., & Chachami, G. (2020) · Cells · doi:10.3390/cells9112359 · Cited by 56
Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence
Alharbi, M. G., Lai, A., Sharma, S., Croft, P. K., Godbole, N., Campos, A. V., Guanzon, D., Salas-Burgos, A., Carrión, F., Zuñiga, F. A., et al. (2021) · Cancers · doi:10.3390/cancers13143388 · Cited by 57
Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner
Udayasuryan, B., Zhou, Z., Ahmad, R. N., Sobol, P., Deng, C., Nguyen, T. T. D., Kodikalla, S., Morrison, R. G., Goswami, I., Slade, D. J., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-06201-w · Cited by 59
Homology-directed repair protects the replicating genome from metabolic assaults
Somyajit, K., Spies, J., Coscia, F., Kirik, U., Rask, M., Lee, J., Neelsen, K. J., Mund, A., Jensen, L. J., Paull, T. T., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.01.011 · Cited by 58
Obstructive Sleep Apnea Activates HIF-1 in a Hypoxia Dose-Dependent Manner in HCT116 Colorectal Carcinoma Cells
Martinez, C.-A., Kerr, B., Jin, C., Cistulli, P. A., & Cook, K. M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020445 · Cited by 55
Metabolic regulation of T cells in the tumor microenvironment by nutrient availability and diet
Zhao, S., Peralta, R. M., Avina-Ochoa, N., Delgoffe, G. M., & Kaech, S. M. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101485 · Cited by 58
Hypoxia induced cancer stem cell enrichment promotes resistance to androgen deprivation therapy in prostate cancer
O’Reilly, D., JOHNSON, P. A., & Buchanan, P. (2019) · Steroids · doi:10.1016/j.steroids.2019.108497 · Cited by 57
Progressive hypoxia‐on‐a‐chip: An in vitro oxygen gradient model for capturing the effects of hypoxia on primary hepatocytes in health and disease
Kang, Y. B., Eo, J., Bulutoglu, B., Yarmush, M. L., & Usta, O. B. (2019) · Biotechnology and Bioengineering · doi:10.1002/bit.27225 · Cited by 55
Tumor stressors induce two mechanisms of intracellular P-glycoprotein–mediated resistance that are overcome by lysosomal-targeted thiosemicarbazones
Al-Akra, L., Bae, D.-H., Sahni, S., Huang, M., Park, K. C., Lane, D. J. R., Jansson, P. J., & Richardson, D. R. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.772699 · Cited by 54
Clinical imaging of hypoxia: Current status and future directions
Bonnitcha, P., Grieve, S. M., & Figtree, G. A. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.08.019 · Cited by 64
Targeting autophagy in chemotherapy-resistant of hepatocellular carcinoma.
Sheng, J., Qin, H., Zhang, K., Li, B., & Zhang, X. (2018) · PubMed Central · Cited by 54
Inhibiting autophagy targets human leukemic stem cells and hypoxic AML blasts by disrupting mitochondrial homeostasis
Dykstra, K. M., Fay, H., Massey, A. C., Yang, N., Johnson, M., Portwood, S. M., Guzmán, M. L., & Wang, E. S. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020002666 · Cited by 55
Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer
Pratt, H. G., Steinberger, K. J., Mihalik, N. E., Ott, S., Whalley, T., Szomolay, B., Boone, B. A., & Eubank, T. D. (2021) · Cancers · doi:10.3390/cancers14010194 · Cited by 58
Supraphysiological Oxygen Levels in Mammalian Cell Culture: Current State and Future Perspectives
Alva, R., Gardner, G. L., Liang, P., & Stuart, J. A. (2022) · Cells · doi:10.3390/cells11193123 · Cited by 62
Efficacy and safety of the hypoxia-activated prodrug TH-302 in combination with gemcitabine and nab-paclitaxel in human tumor xenograft models of pancreatic cancer
Sun, J. D., Liu, Q., Ahluwalia, D., Li, W., Meng, F., Wang, Y., Bhupathi, D., Ruprell, A. S., & Hart, C. P. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2014.1003005 · Cited by 54
In vitro Models of Breast Cancer Metastatic Dormancy
Montagner, M., & Sahai, E. A. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00037 · Cited by 50
Electron dose rate and oxygen depletion protect zebrafish embryos from radiation damage
Pawelke, J., Brand, M., Hans, S., Hidéghety, K., Karsch, L., Leßmann, E., Löck, S., Schürer, M., Szabó, E. R., & Beyreuther, E. (2021) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2021.02.003 · Cited by 52
Quantifying the DNA-damaging Effects of FLASH Irradiation With Plasmid DNA
Perstin, A., Poirier, Y. P., Sawant, A. R., & Tambasco, M. (2022) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2022.01.049 · Cited by 51
Hypoxia as a potential inducer of immune tolerance, tumor plasticity and a driver of tumor mutational burden: Impact on cancer immunotherapy
Khouzam, R. A., Janji, B., Thiery, J., Zaarour, R. F., Chamseddine, A. N., Mayr, H., Savagner, P., Kiéda, C., Gad, S., Buart, S., et al. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.11.008 · Cited by 54
Determining the parameter space for effective oxygen depletion for FLASH radiation therapy
Rothwell, B., Kirkby, N. F., Merchant, M. J., Chadwick, A. L., Lowe, M., Mackay, R. I., Hendry, J. H., & Kirkby, K. J. (2021) · Physics in Medicine and Biology · doi:10.1088/1361-6560/abe2ea · Cited by 51
Exosomes Derived From Hypoxia-Conditioned Stem Cells of Human Deciduous Exfoliated Teeth Enhance Angiogenesis via the Transfer of let-7f-5p and miR-210-3p
Liu, P., Qin, L., Liu, C., Mi, J., Zhang, Q., Wang, S., Zhuang, D., Xu, Q., Chen, W., Guo, J., et al. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.879877 · Cited by 52
NF-κB mediated regulation of tumor cell proliferation in hypoxic microenvironment
Rastogi, S., Aldosary, S., Saeedan, A. S., Ansari, M. N., Singh, M., & Kaithwas, G. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1108915 · Cited by 50
The photodynamic and direct actions of methylene blue on mitochondrial energy metabolism: A balance of the useful and harmful effects of this photosensitizer
Klosowski, E. M., de Souza, B. T. L., Mito, M. S., Constantin, R. P., Mantovanelli, G. C., Mewes, J. M., Bizerra, P. F. V., Menezes, P. V. M. D. C., Gilglioni, E. H., Utsunomiya, K. S., et al. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.04.015 · Cited by 52
Microvascular Tissue Engineering—A Review
Vajda, J., Milojević, M., Maver, U., & Vihar, B. (2021) · Biomedicines · doi:10.3390/biomedicines9060589 · Cited by 52
Metabolism as a New Avenue for Hepatocellular Carcinoma Therapy
Gnocchi, D., Sabbà, C., Massimi, M., & Mazzocca, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043710 · Cited by 50
Androgen deprivation in LNCaP prostate tumour xenografts induces vascular changes and hypoxic stress, resulting in promotion of epithelial-to-mesenchymal transition
Byrne, N. M., Nesbitt, H., Ming, L., McKeown, S. R., Worthington, J., & McKenna, D. J. (2016) · British Journal of Cancer · doi:10.1038/bjc.2016.29 · Cited by 48
Self-citation
Photobiomodulation combined with photodynamic therapy using ruthenium phthalocyanine complexes in A375 melanoma cells: Effects of nitric oxide generation and ATP production
Negri, L. B., Martins, T. J., da Silva, R. S., & Hamblin, M. R. (2019) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2019.111564 · Cited by 47
Spatiotemporal Oxygen Sensing Using Dual Emissive Boron Dye–Polylactide Nanofibers
Bowers, D. T., Tanes, M. L., Das, A., Lin, Y., Keane, N. A., Neal, R. A., Ogle, M. E., Brayman, K. L., Fraser, C. L., & Botchwey, E. A. (2014) · ACS Nano · doi:10.1021/nn504332j · Cited by 48
Identification of a selective inhibitor of human monocarboxylate transporter 4
Futagi, Y., Kobayashi, M., Narumi, K., Furugen, A., & Iseki, K. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.10.025 · Cited by 47
A Microdevice Platform Recapitulating Hypoxic Tumor Microenvironments
Ando, Y., Ta, H. P., Yen, D. P., Lee, S., Raola, S., & Shen, K. (2017) · Scientific Reports · doi:10.1038/s41598-017-15583-3 · Cited by 49
Refined control of cell stemness allowed animal evolution in the oxic realm
Hammarlund, E. U., von Stedingk, K., & Påhlman, S. (2018) · Nature Ecology & Evolution · doi:10.1038/s41559-017-0410-5 · Cited by 46
PKM2 and HIF-1α regulation in prostate cancer cell lines
Hasan, D., Gamen, E., Tarboush, N. A., Ismail, Y. H. M., Pak, O., & Azab, B. (2018) · PLoS ONE · doi:10.1371/journal.pone.0203745 · Cited by 47
Hypoxia and its therapeutic possibilities in paediatric cancers
Bernauer, C., Man, Y. K. S., Chisholm, J., Lepicard, E. Y., Robinson, S. P., & SHIPLEY, J. M. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-01107-w · Cited by 50
High throughput microfluidic system with multiple oxygen levels for the study of hypoxia in tumor spheroids
Berger Fridman, I., Ugolini, G. S., VanDelinder, V., Cohen, S., & Konry, T. (2021) · Biofabrication · doi:10.1088/1758-5090/abdb88 · Cited by 46
Two Color Imaging of Different Hypoxia Levels in Cancer Cells
Wallabrègue, A., Bolland, H. R., Faulkner, S., Hammond, E. M., & Conway, S. J. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.2c12493 · Cited by 46
Searching for molecular hypoxia sensors among oxygen-dependent enzymes
Li, L., Shen, S. Q., Bickler, P. E., Jacobson, M. P., Wu, L. F., & Altschuler, S. J. (2023) · eLife · doi:10.7554/elife.87705 · Cited by 43
Integrated phosphorescence-based photonic biosensor (iPOB) for monitoring oxygen levels in 3D cell culture systems
Rivera, K. R., Pozdin, V. A., Young, A. T., Erb, P. D., Wisniewski, N. A., Magness, S. T., & Daniele, M. A.-A. (2018) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2018.07.035 · Cited by 44
A HMCuS@MnO 2 nanocomplex responsive to multiple tumor environmental clues for photoacoustic/fluorescence/magnetic resonance trimodal imaging-guided and enhanced photothermal/photodynamic therapy
Li, Q., Ren, J., Chen, Q., Liu, W., Xu, Z., Cao, Y., Kang, Y., & Xue, P. (2020) · Nanoscale · doi:10.1039/d0nr01547d · Cited by 45
Cultivation of Cells in a Physiological Plasmax Medium Increases Mitochondrial Respiratory Capacity and Reduces Replication Levels of RNA Viruses
Golikov, M. V., Karpenko, I. L., Lipatova, A. V., Ivanova, O. N., Тимофеевна, Ф. И., Филиппович, Л. В., Zakirova, N. F., Leonova, O. G., Попенко, В. И., Bartosch, B., et al. (2021) · Antioxidants · doi:10.3390/antiox11010097 · Cited by 45
Fluorescence microscopy imaging of mitochondrial metabolism in cancer cells
Gooz, M. B., & Maldonado, E. N. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1152553 · Cited by 44
Current views on mechanisms of the FLASH effect in cancer radiotherapy
Ma, Y., Zhang, W., Zhao, Z.-M., Lv, J., Chen, J., Yan, X., Lin, X., Zhang, J., Wang, B., Gao, S., et al. (2024) · National Science Review · doi:10.1093/nsr/nwae350 · Cited by 46

Authors: McKeown, S. R.
Affiliations: University of Ulster (GB)
Corresponding author: McKeown, S R
Venue: The British Journal of Radiology
Publisher: Oxford University Press (OUP)
Published: 2014-03
Volume: 87
Issue: 1035
Pages: 20130676
ISSN: 0007-1285 (ISSN-L)
1748-880X
DOI: 10.1259/bjr.20130676
PMC: PMC4064601
OpenAlex: W2018722597
Cited by: 1,050
References: 126
Citations by year: 2026: 84 · 2025: 122 · 2024: 129 · 2023: 139 · 2022: 137 · 2021: 152 · 2020: 107 · 2019: 68 · 2018: 56 · 2017: 33 · 2016: 13 · 2015: 5 · 2014: 4
FWCI: 1.82
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: British Journal of Radiology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords: tumor hypoxia, tumor oxygenation, normoxia, treatment response, prostate cancer, pancreatic cancer, malignant progression
MeSH terms: Animals, Hypoxia, Humans, Male, Neoplasms, Oxygen, Cell Hypoxia, Disease Progression

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks