{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:01:04Z","timestamp":1787313664624,"version":"build-2736575974"},"reference-count":170,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Endeavor Health","award":["GRT03672"],"award-info":[{"award-number":["GRT03672"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Tumor oxygenation is a key determinant of cancer biology and treatment response, correlating with angiogenesis, recurrence, and malignant progression. Hypoxia is a defining feature of glioblastoma (GBM) and adult diffuse gliomas, generating low-oxygen niches that promote invasion, stem-like states, immune suppression, and resistance to radiotherapy and temozolomide, contributing to poor outcomes. Measuring tissue partial pressure of oxygen (pO2) and mapping its spatial heterogeneity can, therefore, inform mechanistic understanding and therapeutic development, including hypoxia-activated prodrugs, hypoxia-responsive gene therapy, and optimized radiotherapy planning. Although direct pO2 assessment is challenging, invasive probes and multimodal imaging can characterize regional hypoxia pre-operatively, support patient stratification, monitor treatment effects, and improve outcome prediction. This review summarizes oxygen dynamics in GBM; analyzes causes of hypoxia (rapid growth outpacing supply, diffusion-limited hypoxia, and abnormal\/chaotic vasculature); compares methods to quantify oxygenation from direct measurements to noninvasive imaging surrogates; and evaluates preclinical and clinical strategies that target hypoxia to enhance standard therapy, including barriers to translation. We further integrate oxygenation with cell signaling and redox biology: oxygen gradients are transduced via hypoxia-inducible factor programs and redox-sensitive pathways (NRF2\/KEAP1, NOX-derived ROS, nitric oxide\/S-nitrosylation, and sulfur metabolic routes), shaping mesenchymal-like transitions and cell-death programs such as ferroptosis. Framing oxygenation as both a microenvironmental and redox-signaling variable positions oxygen imaging as an entry point to biomarker-guided therapies that exploit oxidative vulnerabilities.<\/jats:p>","DOI":"10.3390\/antiox15040505","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:37:42Z","timestamp":1776677862000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Heterogeneity, Measurement, and Clinical Implications of Oxygenation, Cell Signaling, and Redox Biology in Glioblastoma and Adult Diffuse Gliomas, with Context from Other Brain Tumors"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0086-4760","authenticated-orcid":false,"given":"Arabinda","family":"Das","sequence":"first","affiliation":[{"name":"Endeavor Health Research Institute, Evanston, IL 60201, USA"},{"name":"Pritzker School of Medicine,  Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian E.","family":"Bailes","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Endeavor Health, Evanston, IL 60201, USA"},{"name":"Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Barlow","sequence":"additional","affiliation":[{"name":"Pritzker School of Medicine,  Chicago, IL 60637, USA"},{"name":"Department of Neurosurgery, Endeavor Health, Evanston, IL 60201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4599-0290","authenticated-orcid":false,"given":"Daniil P.","family":"Aksenov","sequence":"additional","affiliation":[{"name":"Department of Radiology, Endeavor Health, Evanston, IL 60201, USA"},{"name":"Department of Anesthesiology, Endeavor Health, Evanston, IL 60201, USA"},{"name":"Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA"},{"name":"Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A Summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.12786\/bn.2022.15.e23","article-title":"Classification and Diagnosis of Adult Glioma: A Scoping Review","volume":"15","author":"Byun","year":"2022","journal-title":"Brain Neurorehabilit."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1007\/s11060-025-05356-8","article-title":"Staging Prognostic Discussions about Glioblastoma","volume":"176","author":"Fortunato","year":"2026","journal-title":"J. Neurooncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Angom, R.S., Nakka, N.M.R., and Bhattacharya, S. (2023). Advances in Glioblastoma Therapy: An Update on Current Approaches. Brain Sci., 13.","DOI":"10.3390\/brainsci13111536"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e70516","DOI":"10.1111\/cns.70516","article-title":"Roles and Impacts of Integrative Medical Interventions in Central Nervous System Tumor Treatment: Multi-Technology Convergence and the Paradigm Shift Toward Functional Reconstruction","volume":"31","author":"Lai","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e14541","DOI":"10.14814\/phy2.14541","article-title":"How Best to Interpret Measures of Levels of Oxygen in Tissues to Make Them Effective Clinical Tools for Care of Patients with Cancer and Other Oxygen-dependent Pathologies","volume":"8","author":"Swartz","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Feldman, L. (2024). Hypoxia within the glioblastoma tumor microenvironment: A master saboteur of novel treatments. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1384249"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/neuonc\/now258","article-title":"Hypoxia in the Glioblastoma Microenvironment: Shaping the Phenotype of Cancer Stem-like Cells","volume":"19","author":"Colwell","year":"2017","journal-title":"Neuro Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41598-017-18310-0","article-title":"Radiogenomic Analysis of Hypoxia Pathway Is Predictive of Overall Survival in Glioblastoma","volume":"8","author":"Beig","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3892\/mco.2015.494","article-title":"Extracranial Metastasis of Gliobastoma: Three Illustrative Cases and Current Review of the Molecular Pathology and Management Strategies","volume":"3","author":"Ray","year":"2015","journal-title":"Mol. Clin. Oncol."},{"key":"ref_11","first-page":"878","article-title":"Tissue pO2 of Orthotopic 9L and C6 Gliomas and Tumor-Specific Response to Radiotherapy and Hyperoxygenation","volume":"73","author":"Khan","year":"2009","journal-title":"Int. J. Radiat."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cruickshank, G.S., Rampling, R.P., and Cowans, W. (1994). Direct Measurement of the PO2 Distribution in Human Malignant Brain Tumours. Oxygen Transport to Tissue XV. Advances in Experimental Medicine and Biology, Springer.","DOI":"10.1007\/978-1-4615-2468-7_62"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106992","DOI":"10.1016\/j.jmr.2021.106992","article-title":"Estimation of pO2 Distribution in EPR Oximetry","volume":"328","author":"Demidenko","year":"2021","journal-title":"J. Magn. Reson."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/978-1-4939-3023-4_39","article-title":"Spontaneous Fluctuations of PO2 in the Rabbit Somatosensory Cortex","volume":"876","author":"Linsenmeier","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_15","first-page":"427","article-title":"Direct Measurement of pO2 Distribution and Bioreductive Enzymes in Human Malignant Brain Tumors","volume":"29","author":"Rampling","year":"1994","journal-title":"Int. J. Radiat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1089\/ars.2007.1628","article-title":"Detection and Characterization of Tumor Hypoxia Using pO2 Histography","volume":"9","author":"Vaupel","year":"2007","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1080\/10715762.2017.1388506","article-title":"Quantitative Imaging of pO2 in Orthotopic Murine Gliomas: Hypoxia Correlates with Resistance to Radiation","volume":"51","author":"Yasui","year":"2017","journal-title":"Free Radic. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/bs.mcb.2024.10.016","article-title":"Quantitative Pre-Clinical Imaging of Hypoxia and Vascularity Using MRI and PET","volume":"191","author":"Kanli","year":"2025","journal-title":"Methods Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jneumeth.2011.10.026","article-title":"Repeated Assessment of Orthotopic Glioma pO2 by Multi-Site EPR Oximetry: A Technique with the Potential to Guide Therapeutic Optimization by Repeated Measurements of Oxygen","volume":"204","author":"Khan","year":"2012","journal-title":"J. Neurosci. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1667\/RR1207.1","article-title":"Imaging and Analytical Methods as Applied to the Evaluation of Vasculature and Hypoxia in Human Brain Tumors","volume":"170","author":"Evans","year":"2008","journal-title":"Radiat. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0167-8140(99)00121-8","article-title":"Polarographic Measurements of Oxygen Tension in Human Glioma and Surrounding Peritumoural Brain Tissue","volume":"53","author":"Collingridge","year":"1999","journal-title":"Radiother. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1158\/1078-0432.CCR-07-4995","article-title":"Regional Hypoxia in Glioblastoma Multiforme Quantified with [18F]Fluoromisonidazole Positron Emission Tomography before Radiotherapy: Correlation with Time to Progression and Survival","volume":"14","author":"Spence","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_23","first-page":"100940","article-title":"Magnetic Resonance Imaging to Detect Tumor Hypoxia in Brain Malignant Disease: A Systematic Review of Validation Studies","volume":"52","author":"Bai","year":"2025","journal-title":"Clin. Transl. Radiat. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gascoigne, D.A., Minhaj, M.M., and Aksenov, D.P. (2022). Neonatal Anesthesia and Oxidative Stress. Antioxidants, 11.","DOI":"10.3390\/antiox11040787"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jamali, F., Lan, K., Sabri, S., Abdulkarim, B., Daniel, P., and Petrecca, K. (2024). Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of P53 in Glioblastoma Stem Cells. Antioxidants, 13.","DOI":"10.20944\/preprints202409.0790.v1"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Guequ\u00e9n, A., Zamorano, P., C\u00f3rdova, F., Koning, T., Torres, A., Ehrenfeld, P., Boric, M.P., Salazar-Onfray, F., Gavard, J., and Dur\u00e1n, W.N. (2019). Interleukin-8 Secreted by Glioblastoma Cells Induces Microvascular Hyperpermeability Through NO Signaling Involving S-Nitrosylation of VE-Cadherin and p120 in Endothelial Cells. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00988"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Esteban-Roman, N.F., Taddei, E., Castro-Velazquez, E., Villafuentes-Vidal, L., Velez-Herrera, A., Rubio-Osornio, M., and Rubio, C. (2025). Redox-Regulated Pathways in Glioblastoma Stem-like Cells: Mechanistic Insights and Therapeutic Implications. Brain Sci., 15.","DOI":"10.3390\/brainsci15080884"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"vdad160","DOI":"10.1093\/noajnl\/vdad160","article-title":"Exploring the Multifaceted Role of NRF2 in Brain Physiology and Cancer: A Comprehensive Review","volume":"6","author":"Moubarak","year":"2023","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S145","DOI":"10.1259\/bjr\/82292521","article-title":"Imaging Hypoxia in Gliomas","volume":"84","author":"Mendichovszky","year":"2011","journal-title":"Br. J. Radiol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Corroyer-Dulmont, A., Chakhoyan, A., Collet, S., Durand, L., MacKenzie, E.T., Petit, E., Bernaudin, M., Touzani, O., and Valable, S. (2015). Imaging Modalities to Assess Oxygen Status in Glioblastoma. Front. Med., 2.","DOI":"10.3389\/fmed.2015.00057"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hirata, K., Yamaguchi, S., Shiga, T., Kuge, Y., and Tamaki, N. (2019). The Roles of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography in Glioma Treatment. J. Clin. Med., 8.","DOI":"10.3390\/jcm8081088"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"G\u00e9rard, M., Corroyer-Dulmont, A., Lesueur, P., Collet, S., Ch\u00e9rel, M., Bourgeois, M., Stefan, D., Limkin, E.J., Perrio, C., and Guillamo, J.-S. (2019). Hypoxia Imaging and Adaptive Radiotherapy: A State-of-the-Art Approach in the Management of Glioma. Front. Med., 6.","DOI":"10.3389\/fmed.2019.00117"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1016\/j.yexcr.2012.07.017","article-title":"Hypoxia and Hypoxia-Inducible Factors in Glioblastoma Multiforme Progression and Therapeutic Implications","volume":"318","author":"Yang","year":"2012","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E8","DOI":"10.3171\/2014.9.FOCUS14496","article-title":"Hypoxia-Inducible Factor-1 and Associated Upstream and Downstream Proteins in the Pathophysiology and Management of Glioblastoma","volume":"37","author":"Womeldorff","year":"2014","journal-title":"Neurosurg. Focus"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Monteiro, A., Hill, R., Pilkington, G., and Madureira, P.A. (2017). The Role of Hypoxia in Glioblastoma Invasion. Cells, 6.","DOI":"10.3390\/cells6040045"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Dom\u00e8nech, M., Hern\u00e1ndez, A., Plaja, A., Mart\u00ednez-Balibrea, E., and Bala\u00f1\u00e0, C. (2021). Hypoxia: The Cornerstone of Glioblastoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212608"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Park, J.H., and Lee, H.K. (2022). Current Understanding of Hypoxia in Glioblastoma Multiforme and Its Response to Immunotherapy. Cancers, 14.","DOI":"10.3390\/cancers14051176"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Begagi\u0107, E., Be\u010duli\u0107, H., D\u017eidi\u0107-Krivi\u0107, A., Kadi\u0107 Vukas, S., Had\u017ei\u0107, S., Meki\u0107-Abazovi\u0107, A., \u0160egalo, S., Papi\u0107, E., Muchai Echengi, E., and Pugonja, R. (2024). Understanding the Significance of Hypoxia-Inducible Factors (HIFs) in Glioblastoma: A Systematic Review. Cancers, 16.","DOI":"10.3390\/cancers16112089"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41419-024-06904-2","article-title":"Preclinical and Clinical Advances to Overcome Hypoxia in Glioblastoma Multiforme","volume":"15","author":"Burckel","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_40","first-page":"156","article-title":"Role of Redox Status in Development of Glioblastoma","volume":"7","author":"Sotelo","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Rinaldi, M., Caffo, M., Minutoli, L., Marini, H., Abbritti, R.V., Squadrito, F., Trichilo, V., Valenti, A., Barresi, V., and Altavilla, D. (2016). ROS and Brain Gliomas: An Overview of Potential and Innovative Therapeutic Strategies. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17060984"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"342","DOI":"10.2174\/1570159X16666180302120925","article-title":"The Delicate Equilibrium between Oxidants and Antioxidants in Brain Glioma","volume":"17","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Olivier, C., Oliver, L., and Lalier, L. (2021). Vallette Drug Resistance in Glioblastoma: The Two Faces of Oxidative Stress. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.620677"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, S., Dong, L., Shi, W., Zheng, Z., Liu, Z., Meng, L., and Xin, Y. (2022). Jiang Potential targets and treatments affect oxidative stress in gliomas: An overview of molecular mechanisms. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.921070"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12672-022-00556-4","article-title":"Exploring the Role of Nrf2 Signaling in Glioblastoma Multiforme","volume":"13","author":"Awuah","year":"2022","journal-title":"Discov. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yang, Y.-C., Zhu, Y., Sun, S.-J., Zhao, C.-J., Bai, Y., Wang, J., and Ma, L.-T. (2023). ROS regulation in gliomas: Implications for treatment strategies. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1259797"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Nowacka, A., Sniegocki, M., and Ziolkowska, E. (2025). Oxidative Stress and Antioxidants in Glioblastoma: Mechanisms of Action, Therapeutic Effects and Future Directions. Antioxidants, 14.","DOI":"10.3390\/antiox14091121"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e224","DOI":"10.1016\/j.acra.2018.09.011","article-title":"Evaluation of Tumor Hypoxia in C6 Glioma Rat Model with Dynamic Contrast-Enhanced Magnetic Resonance Imaging","volume":"26","author":"Hou","year":"2019","journal-title":"Acad. Radiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"20130676","DOI":"10.1259\/bjr.20130676","article-title":"Defining Normoxia, Physoxia and Hypoxia in Tumours-Implications for Treatment Response","volume":"87","author":"McKeown","year":"2014","journal-title":"Br. J. Radiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1007\/s00723-021-01383-6","article-title":"Oxygenation Status of Malignant Tumors vs. Normal Tissues: Critical Evaluation and Updated Data Source Based on Direct Measurements with pO2 Microsensors","volume":"52","author":"Vaupel","year":"2021","journal-title":"Appl. Magn. Reson."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.semcancer.2023.11.001","article-title":"Hypoxia Signaling and Metastatic Progression","volume":"97","author":"Schito","year":"2023","journal-title":"Semin. Cancer Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Jordan, B.F., and Sonveaux, P. (2012). Targeting Tumor Perfusion and Oxygenation to Improve the Outcome of Anticancer Therapy. Front. Pharmacol., 3.","DOI":"10.3389\/fphar.2012.00094"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/mrm.1118","article-title":"In Vivo BOLD Contrast MRI Mapping of Subcutaneous Vascular Function and Maturation: Validation by Intravital Microscopy","volume":"45","author":"Neeman","year":"2001","journal-title":"Magn. Reson. Med."},{"key":"ref_54","first-page":"CD011551","article-title":"Magnetic Resonance Perfusion for Differentiating Low-Grade from High-Grade Gliomas at First Presentation","volume":"2018","author":"Abrigo","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1177\/0271678X20947546","article-title":"Association between Tissue Hypoxia, Perfusion Restrictions, and Microvascular Architecture Alterations with Lesion-Induced Impairment of Neurovascular Coupling","volume":"42","author":"Stadlbauer","year":"2020","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/sj.neo.7900037","article-title":"Causes and Effects of Heterogeneous Perfusion in Tumors","volume":"1","author":"Gillies","year":"1999","journal-title":"Neoplasia"},{"key":"ref_57","first-page":"761","article-title":"Histogram Analysis versus Region of Interest Analysis of Dynamic Susceptibility Contrast Perfusion MR Imaging Data in the Grading of Cerebral Gliomas","volume":"28","author":"Law","year":"2007","journal-title":"Am. J. Neuroradiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5223","DOI":"10.7150\/thno.84947","article-title":"Visualizing Vasculature and Its Response to Therapy in the Tumor Microenvironment","volume":"13","author":"Lin","year":"2023","journal-title":"Theranostics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.pharmthera.2015.06.006","article-title":"Modulation of the Tumor Vasculature and Oxygenation to Improve Therapy","volume":"153","author":"Siemann","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.trecan.2015.10.009","article-title":"Glioblastoma: Defining Tumor Niches","volume":"1","author":"Hambardzumyan","year":"2015","journal-title":"Trends Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1093\/neuonc\/nou035","article-title":"GBM\u2019s Multifaceted Landscape: Highlighting Regional and Microenvironmental Heterogeneity","volume":"16","author":"Vartanian","year":"2014","journal-title":"Neuro Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Ohmura, K., Tomita, H., and Hara, A. (2023). Peritumoral Edema in Gliomas: A Review of Mechanisms and Management. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102731"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e31","DOI":"10.1097\/WNO.0000000000000950","article-title":"Neuro-Ophthalmic Manifestations of Intracranial Malignancies","volume":"40","author":"Dermarkarian","year":"2020","journal-title":"J. Neuroophthalmol."},{"key":"ref_64","unstructured":"Anwar, A., Gudlavalleti, A., and Ramadas, P. (2026, March 01). Carcinomatous Meningitis, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK560816\/."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zhong, J., Sakaki, M., Okada, H., and Ahrens, E.T. (2013). In Vivo Intracellular Oxygen Dynamics in Murine Brain Glioma and Immunotherapeutic Response of Cytotoxic T Cells Observed by Fluorine-19 Magnetic Resonance Imaging. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059479"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Hsieh, C.-H., Shyu, W.-C., Chiang, C.-Y., Kuo, J.-W., Shen, W.-C., and Liu, R.-S. (2011). NADPH Oxidase Subunit 4-Mediated Reactive Oxygen Species Contribute to Cycling Hypoxia-Promoted Tumor Progression in Glioblastoma Multiforme. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023945"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.freeradbiomed.2012.06.009","article-title":"NADPH Oxidase Subunit 4 Mediates Cycling Hypoxia-Promoted Radiation Resistance in Glioblastoma Multiforme","volume":"53","author":"Hsieh","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1631\/jzus.B2200269","article-title":"Hypoxia-Induced ROS Aggravate Tumor Progression through HIF-1\u03b1-SERPINE1 Signaling in Glioblastoma","volume":"24","author":"Zhang","year":"2023","journal-title":"J. Zhejiang Univ."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4196","DOI":"10.1038\/ncomms5196","article-title":"Disruption of Astrocyte\u2013Vascular Coupling and the Blood\u2013Brain Barrier by Invading Glioma Cells","volume":"5","author":"Watkins","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Guyon, J., Chapouly, C., Andrique, L., Bikfalvi, A., and Daubon, T. (2021). The Normal and Brain Tumor Vasculature: Morphological and Functional Characteristics and Therapeutic Targeting. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.622615"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Ballato, M., Germana, E., Ricciardi, G., Giordano, W.G., Tralongo, P., Buccarelli, M., Castellani, G., Ricci-Vitiani, L., D\u2019Alessandris, Q.G., and Giuffre, G. (2025). Understanding Neovascularization in Glioblastoma: Insights from the Current Literature. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062763"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1177\/1971400915576641","article-title":"Cerebral Blood Flow Changes in Glioblastoma Patients Undergoing Bevacizumab Treatment Are Seen in Both Tumor and Normal Brain","volume":"28","author":"Andre","year":"2015","journal-title":"Neuroradiol. J."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Agarwal, S., Welker, K.M., Black, D.F., Little, J.T., DeLone, D.R., Messina, S.A., Passe, T.J., Bettegowda, C., and Pillai, J.J. (2023). Detection and Mitigation of Neurovascular Uncoupling in Brain Gliomas. Cancers, 15.","DOI":"10.3390\/cancers15184473"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Liu, X., Czosnyka, M., Robba, C., and Ming, D. (2022). Editorial: Cerebral autoregulation and neurovascular coupling in brain disorders. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.1001342"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11060-016-2350-3","article-title":"Assessment of Vascularity in Glioblastoma and Its Implications on Patient Outcomes","volume":"132","author":"McGahan","year":"2017","journal-title":"J. Neurooncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.neuropharm.2018.03.030","article-title":"Brain Tissue Oxygen Regulation in Awake and Anesthetized Neonates","volume":"135","author":"Aksenov","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Aksenov, D.P., Gascoigne, D.A., Duan, J., and Drobyshevsky, A. (2022). Function and development of interneurons involved in brain tissue oxygen regulation. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.1069496"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.neulet.2012.07.019","article-title":"Effect of Isoflurane on Brain Tissue Oxygen Tension and Cerebral Autoregulation in Rabbits","volume":"524","author":"Aksenov","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"116034","DOI":"10.1016\/j.neuroimage.2019.116034","article-title":"Role of the Inhibitory System in Shaping the BOLD fMRI Response","volume":"201","author":"Aksenov","year":"2019","journal-title":"NeuroImage"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"110364","DOI":"10.1016\/j.mri.2025.110364","article-title":"Blood-oxygenation-Level-Dependent (BOLD) MRI Responses to CO2 and O2 Inhalation in Brain Gliomas","volume":"119","author":"Akinwale","year":"2025","journal-title":"Magn. Reson. Imaging"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.crad.2016.04.012","article-title":"Evaluation of Tumour Vascular Distribution and Function Using Immunohistochemistry and BOLD fMRI with Carbogen Inhalation","volume":"71","author":"Xu","year":"2016","journal-title":"Clin. Radiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1002\/mrm.24873","article-title":"Dynamic Contrast Enhanced MRI Parameters and Tumor Cellularity in a Rat Model of Cerebral Glioma at 7 T","volume":"71","author":"Aryal","year":"2013","journal-title":"Magn. Reson. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Sharma, V., Fernando, V., Letson, J., Walia, Y., Zheng, X., Fackelman, D., and Furuta, S. (2021). S-Nitrosylation in Tumor Microenvironment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094600"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"14","DOI":"10.18383\/j.tom.2019.00023","article-title":"Assessment of the Prognostic Value of Radiomic Features in 18F-FMISO PET Imaging of Hypoxia in Postsurgery Brain Cancer Patients: Secondary Analysis of Imaging Data from a Single-Center Study and the Multicenter ACRIN 6684 Trial","volume":"6","author":"Muzi","year":"2020","journal-title":"Tomography"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"10210","DOI":"10.1038\/s41598-017-08646-y","article-title":"FMISO-PET-Derived Brain Oxygen Tension Maps: Application to Glioblastoma and Less Aggressive Gliomas","volume":"7","author":"Chakhoyan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s11060-012-0918-0","article-title":"Molecular Imaging of Pediatric Brain Tumors: Comparison of Tumor Metabolism Using 18F-FDG-PET and MRSI","volume":"109","author":"Hipp","year":"2012","journal-title":"J. Neurooncol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Gouel, P., Decazes, P., Vera, P., Gardin, I., Thureau, S., and Bohn, P. (2023). Advances in PET and MRI imaging of tumor hypoxia. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1055062"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"121334","DOI":"10.1016\/j.neuroimage.2025.121334","article-title":"The Diagnostic Potential of Resting State Functional MRI: Statistical Concerns","volume":"317","author":"Doubovikov","year":"2025","journal-title":"NeuroImage"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1002\/mrm.10318","article-title":"How Does Blood Oxygen Level-Dependent (BOLD) Contrast Correlate with Oxygen Partial Pressure (pO2) inside Tumors?","volume":"48","author":"Baudelet","year":"2002","journal-title":"Magn. Reson. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1053\/j.semnuclmed.2014.10.006","article-title":"F-18 Fluoromisonidazole for Imaging Tumor Hypoxia: Imaging the Microenvironment for Personalized Cancer Therapy","volume":"45","author":"Rajendran","year":"2015","journal-title":"Semin. Nucl. Med."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Yang, Y., More, S., De Smet, F., De Vleeschouwer, S., and Agostinis, P. (2024). Antioxidant network-based signatures cluster glioblastoma into distinct redox-resistant phenotypes. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1342977"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1002\/mrm.27185","article-title":"Wireless Implantable Coil with Parametric Amplification for in Vivo Electron Paramagnetic Resonance Oximetric Applications","volume":"80","author":"Enomoto","year":"2018","journal-title":"Magn. Reson. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1002\/mrm.21212","article-title":"In Vivo Imaging of Changes in Tumor Oxygenation during Growth and after Treatment","volume":"57","author":"Bratasz","year":"2007","journal-title":"Magn. Reson. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1449242024","DOI":"10.1523\/JNEUROSCI.1449-24.2024","article-title":"Abnormal Local Cortical Functional Connectivity Due to Interneuron Dysmaturation after Neonatal Intermittent Hypoxia","volume":"45","author":"Goussakov","year":"2025","journal-title":"J. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1111\/ejn.13384","article-title":"Blood Oxygenation Level Dependent Signal and Neuronal Adaptation to Optogenetic and Sensory Stimulation in Somatosensory Cortex in Awake Animals","volume":"44","author":"Aksenov","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1002\/mrm.30559","article-title":"Improving Quantitative BOLD\u2013Based Measures of Oxygen Extraction Fraction Using Hyperoxia BOLD\u2013Derived Measures of Blood Volume","volume":"94","author":"Stone","year":"2025","journal-title":"Magn. Reson. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"118952","DOI":"10.1016\/j.neuroimage.2022.118952","article-title":"Whole-Brain 3D Mapping of Oxygen Metabolism Using Constrained Quantitative BOLD","volume":"250","author":"Lee","year":"2022","journal-title":"NeuroImage"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"e70120","DOI":"10.1002\/nbm.70120","article-title":"Comparison of Brain Oxygen Metabolic Parameters Between Constrained qBOLD and Whole-Brain Oximetric Methods at Baseline and in Response to a Physiologic Stimulus","volume":"38","author":"Jaroszynski","year":"2025","journal-title":"NMR Biomed."},{"key":"ref_99","first-page":"100563","article-title":"Oxygen-Enhanced MRI and Radiotherapy in Patients with Oropharyngeal Squamous Cell Carcinoma","volume":"39","author":"Bluemke","year":"2023","journal-title":"Clin. Transl. Radiat. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1158\/0008-5472.CAN-15-2062","article-title":"Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models","volume":"76","author":"Boult","year":"2016","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1158\/1078-0432.CCR-14-0990","article-title":"Imaging Intratumor Heterogeneity: Role in Therapy Response, Resistance, and Clinical Outcome","volume":"21","author":"Rose","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.mric.2017.01.002","article-title":"Principles of Simultaneous PET\/MR Imaging","volume":"25","author":"Catana","year":"2017","journal-title":"Magn. Reson. Imaging Clin. N. Am."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1053\/j.semnuclmed.2008.02.001","article-title":"Positron Emission Tomography\/Magnetic Resonance Imaging: The Next Generation of Multimodality Imaging?","volume":"38","author":"Pichler","year":"2008","journal-title":"Semin. Nucl. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1002\/jmri.25711","article-title":"PET\/MRI: Where Might It Replace PET\/CT?","volume":"46","author":"Ehman","year":"2017","journal-title":"J. Magn. Reson. Imaging JMRI"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s40580-023-00377-3","article-title":"Functional Photoacoustic Imaging: From Nano- and Micro- to Macro-Scale","volume":"10","author":"Park","year":"2023","journal-title":"Nano Converg."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6096","DOI":"10.1118\/1.3497677","article-title":"Photoacoustic Angiography of the Breast","volume":"37","author":"Kruger","year":"2010","journal-title":"Med. Phys."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"76007","DOI":"10.1117\/1.JBO.18.7.076007","article-title":"Assessing the Effects of Norepinephrine on Single Cerebral Microvessels Using Optical-Resolution Photoacoustic Microscope","volume":"18","author":"Liu","year":"2013","journal-title":"J. Biomed. Opt."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.radonc.2011.06.036","article-title":"Assessment of Tumor Hypoxia and Interstitial Fluid Pressure by Gadomelitol-Based Dynamic Contrast-Enhanced Magnetic Resonance Imaging","volume":"101","author":"Gulliksrud","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.radonc.2010.12.016","article-title":"Differentiation between Hypoxic and Non-Hypoxic Experimental Tumors by Dynamic Contrast-Enhanced Magnetic Resonance Imaging","volume":"98","author":"Gulliksrud","year":"2011","journal-title":"Radiother. Oncol."},{"key":"ref_110","first-page":"138","article-title":"Tumour Oxygenation Measurements Using Computed Tomography and Magnetic Resonance Imaging","volume":"2","author":"Hermans","year":"2015","journal-title":"Cancer Imaging"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"145029","DOI":"10.1088\/1361-6560\/adece1","article-title":"Mapping Cell Density and Hypoxia in Glioblastoma Using Time-Dependent Diffusion MRI: Improved Cell Density Assessment Compared to Conventional Diffusion Metrics","volume":"70","author":"Jokivuolle","year":"2025","journal-title":"Phys. Med. Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"31864","DOI":"10.18632\/oncotarget.16256","article-title":"Investigation of Hypoxia Conditions Using Oxygen-Enhanced Magnetic Resonance Imaging Measurements in Glioma Models","volume":"8","author":"Fan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0969-8051(01)00298-0","article-title":"Imaging and Quantitation of the Hypoxic Cell Fraction of Viable Tumor in an Animal Model of Intracerebral High Grade Glioma Using [18F]Fluoromisonidazole (FMISO)","volume":"29","author":"Sachinidis","year":"2002","journal-title":"Nucl. Med. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1002\/jmri.20800","article-title":"Quantitative Analysis of Whole-tumor Gd Enhancement Histograms Predicts Malignant Transformation in Low-grade Gliomas","volume":"25","author":"Tofts","year":"2006","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/mrm.21931","article-title":"High-resolution Longitudinal Assessment of Flow and Permeability in Mouse Glioma Vasculature: Sequential Small Molecule and SPIO Dynamic Contrast Agent MRI","volume":"61","author":"Pike","year":"2009","journal-title":"Magn. Reson. Med."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Huang, M., Law, H.K.W., and Tam, S.Y. (2025). Use of Radiomics in Characterizing Tumor Hypoxia. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26146679"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"eadj3301","DOI":"10.1126\/sciadv.adj3301","article-title":"Hypoxia Coordinates the Spatial Landscape of Myeloid Cells within Glioblastoma to Affect Survival","volume":"10","author":"Haley","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/neuonc\/noab269","article-title":"Cancer Cell Heterogeneity and Plasticity: A Paradigm Shift in Glioblastoma","volume":"24","author":"Yabo","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1038\/s41467-022-31340-1","article-title":"Spatiotemporal Analysis of Glioma Heterogeneity Reveals COL1A1 as an Actionable Target to Disrupt Tumor Progression","volume":"13","author":"Comba","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_120","first-page":"189383","article-title":"Spatial Heterogeneity in Glioblastoma: Decoding the Role of Perfusion","volume":"1880","author":"Saha","year":"2025","journal-title":"BBA\u2014Rev. Cancer"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e170397","DOI":"10.1172\/JCI170397","article-title":"Multiomic Screening of Invasive GBM Cells Reveals Targetable Transsulfuration Pathway Alterations","volume":"134","author":"Garcia","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"e176879","DOI":"10.1172\/JCI176879","article-title":"Should I Stay or Should I Go? Transsulfuration Influences Invasion and Growth in Glioblastoma","volume":"134","author":"Ponti","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yao, Y., Xu, Y., Liu, S., Xue, F., Wang, B., Qin, S., Sun, X., and He, J. (2022). Predicting the grade of meningiomas by clinical\u2013radiological features: A comparison of precontrast and postcontrast MRI. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1053089"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1052-5149(02)00029-1","article-title":"Hypoxia Imaging in Brain Tumors","volume":"12","author":"Yetkin","year":"2002","journal-title":"Neuroimaging Clin. N. Am."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Zhang, H.-W., Liu, X.-L., Zhang, H.-B., Li, Y.-Q., Wang, Y., Feng, Y.-N., Deng, K., Huang, Y., Huang, B., and Lin, F. (2022). Differentiation of Meningiomas and Gliomas by Amide Proton Transfer Imaging: A Preliminary Study of Brain Tumour Infiltration. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.886968"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1148\/radiol.2015142156","article-title":"Differentiation of Low- and High-Grade Pediatric Brain Tumors with Highb-Value Diffusion-Weighted MR Imaging and a Fractional Order Calculus Model","volume":"277","author":"Sui","year":"2015","journal-title":"Radiology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e251","DOI":"10.5001\/omj.2021.59","article-title":"Differentiating between Low- and High-Grade Glioma Tumors Measuring Apparent Diffusion Coefficient Values in Various Regions of the Brain","volume":"36","author":"Momeni","year":"2021","journal-title":"Oman Med. J."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Csutak, C., \u0218tefan, P.-A., Lenghel, L.M., Mihu, C.M., Lebovici, A., Moro\u0219anu, C.O., Lupean, R.-A., and \u0218imonca, L. (2020). Differentiating High-Grade Gliomas from Brain Metastases at Magnetic Resonance: The Role of Texture Analysis of the Peritumoral Zone. Brain Sci., 10.","DOI":"10.3390\/brainsci10090638"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.32604\/or.2025.066308","article-title":"Identification of a Novel Oxidative Stress-Based Molecular Classification and Treatment Vulnerabilities in WHO Grade 2\/3 Meningiomas","volume":"33","author":"Luo","year":"2025","journal-title":"Oncol. Res."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Pinker, B., and Barciszewska, A.-M. (2022). mTOR Signaling and Potential Therapeutic Targeting in Meningioma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23041978"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1093\/neuonc\/noab114","article-title":"MEF2C Silencing Downregulates NF2 and E-Cadherin and Enhances Erastin-Induced Ferroptosis in Meningioma","volume":"23","author":"Bao","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s11060-025-05208-5","article-title":"NOTCH3 Drives Fatty Acid Oxidation and Ferroptosis Resistance in Aggressive Meningiomas","volume":"175","author":"Sadagopan","year":"2025","journal-title":"J. Neurooncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/jjco\/hyr181","article-title":"Reoxygenation of Glioblastoma Multiforme Treated with Fractionated Radiotherapy Concomitant with Temozolomide: Changes Defined by 18F-Fluoromisonidazole Positron Emission Tomography: Two Case Reports","volume":"42","author":"Narita","year":"2011","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"11882","DOI":"10.18632\/oncotarget.3592","article-title":"Activation of Hypoxia Signaling Induces Phenotypic Transformation of Glioma Cells: Implications for Bevacizumab Antiangiogenic Therapy","volume":"6","author":"Xu","year":"2015","journal-title":"Oncotarget"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"26","DOI":"10.4143\/crt.2025.200","article-title":"Understanding Immune Cell Adaptation to Tumor Hypoxia for Maximized Therapeutic Efficacy of Immunotherapy: Biology and Non-Invasive Imaging Application","volume":"58","author":"Oh","year":"2026","journal-title":"Cancer Res. Treat."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Chen, Z., and Hambardzumyan, D. (2018). Immune Microenvironment in Glioblastoma Subtypes. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01004"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Meleiro, M., and Henrique, R. (2025). Epigenetic Alterations in Glioblastoma Multiforme as Novel Therapeutic Targets: A Scoping Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125634"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1016\/j.cell.2024.03.029","article-title":"Integrative Spatial Analysis Reveals a Multi-Layered Organization of Glioblastoma","volume":"187","author":"Greenwald","year":"2024","journal-title":"Cell"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"103866","DOI":"10.1016\/j.redox.2025.103866","article-title":"Hydrogen Sulfide Inhibits Recruitment of Monocyte-Derived Tumor Associated Macrophages in Glioblastoma by Downregulating CXCL12","volume":"86","author":"Camarano","year":"2025","journal-title":"Redox Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10409238.2013.838205","article-title":"Transcriptional Regulation by Hypoxia Inducible Factors","volume":"49","author":"Dengler","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e11306","DOI":"10.7717\/peerj.11306","article-title":"The Regulation of Immune Checkpoints by the Hypoxic Tumor Microenvironment","volume":"9","author":"Hu","year":"2021","journal-title":"PeerJ"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 Is a Novel Direct Target of HIF-1\u03b1, and Its Blockade under Hypoxia Enhanced MDSC-Mediated T Cell Activation","volume":"211","author":"Noman","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s11060-015-1889-8","article-title":"Reactive Oxygen Species Production Has a Critical Role in Hypoxia-Induced Stat3 Activation and Angiogenesis in Human Glioblastoma","volume":"125","author":"Yu","year":"2015","journal-title":"J. Neurooncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/s41419-022-05044-9","article-title":"High Levels of NRF2 Sensitize Temozolomide-Resistant Glioblastoma Cells to Ferroptosis via ABCC1\/MRP1 Upregulation","volume":"13","author":"Monteiro","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1089\/ars.2023.0262","article-title":"Redox Homeostasis and Beyond: The Role of Wild-Type Isocitrate Dehydrogenases for the Pathogenesis of Glioblastoma","volume":"39","author":"Murnan","year":"2023","journal-title":"Antioxid. Redox Signal."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1089\/ars.2013.5378","article-title":"The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities","volume":"21","author":"Walsh","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Morello, G., La Cognata, V., Guarnaccia, M., Gentile, G., and Cavallaro, S. (2025). Artificial Intelligence-Driven Multi-Omics Approaches in Glioblastoma. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199362"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Vijayanathan, Y., and Ho, I.A.W. (2025). The Impact of Metabolic Rewiring in Glioblastoma: The Immune Landscape and Therapeutic Strategies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020669"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/s41416-020-0794-x","article-title":"Serine-Dependent Redox Homeostasis Regulates Glioblastoma Cell Survival","volume":"122","author":"Engel","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"74630","DOI":"10.18632\/oncotarget.11858","article-title":"Temozolomide Toxicity Operates in a xCT\/SLC7a11 Dependent Manner and Is Fostered by Ferroptosis","volume":"7","author":"Sehm","year":"2016","journal-title":"Oncotarget"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/s41420-025-02744-x","article-title":"Harnessing Ferroptosis to Transform Glioblastoma Therapy and Surmount Treatment Resistance","volume":"11","author":"Singh","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s11060-024-04918-6","article-title":"Mifepristone Achieves Tumor Suppression and Ferroptosis through PR\/P53\/HO1\/GPX4 Axis in Meningioma Cells","volume":"172","author":"Dai","year":"2025","journal-title":"J. Neurooncol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"e179854","DOI":"10.1172\/jci.insight.179854","article-title":"Hypoxia-Induced Complement Component 3 Promotes Aggressive Tumor Growth in the Glioblastoma Microenvironment","volume":"9","author":"Rosberg","year":"2024","journal-title":"JCI Insight"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Chmelyuk, N., Kordyukova, M., Sorokina, M., Sinyavskiy, S., Meshcheryakova, V., Belousov, V., and Abakumova, T. (2025). Inhibition of Thioredoxin-Reductase by Auranofin as a Pro-Oxidant Anticancer Strategy for Glioblastoma: In Vitro and In Vivo Studies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052084"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1179\/1743132814Y.0000000401","article-title":"Physiological Oxygen Concentration Alters Glioma Cell Malignancy and Responsiveness to Photodynamic Therapy in Vitro","volume":"36","author":"Albert","year":"2014","journal-title":"Neurol. Res."},{"key":"ref_156","first-page":"e67129","article-title":"Tumor Hypoxia Assessment: In Vivo 3D Oxygen Imaging Through Electron Paramagnetic Resonance","volume":"216","author":"Dziurman","year":"2025","journal-title":"J. Vis. Exp."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Godet, I., Doctorman, S., Wu, F., and Gilkes, D.M. (2022). Detection of Hypoxia in Cancer Models: Significance, Challenges, and Advances. Cells, 11.","DOI":"10.3390\/cells11040686"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Alpuim Costa, D., Sampaio-Alves, M., Netto, E., Fernandez, G., Oliveira, E., Teixeira, A., Daniel, P.M., Bernardo, G.S., and Amaro, C. (2022). Hyperbaric Oxygen Therapy as a Complementary Treatment in Glioblastoma\u2014A Scoping Review. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.886603"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"420","DOI":"10.4103\/mgr.MEDGASRES-D-24-00096","article-title":"Hyperbaric Oxygen Therapy as an Adjunt Treatment for Glioma and Brain Metastasis: A Literature Review","volume":"15","author":"Cai","year":"2025","journal-title":"Med. Gas Res."},{"key":"ref_160","first-page":"220","article-title":"The role of hyperbaric oxygenation in glioma therapy\u2014A review of experimental studies","volume":"71","author":"Iwan","year":"2025","journal-title":"Postepy Biochem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s12032-016-0814-0","article-title":"Hyperbaric Oxygen as an Adjunctive Therapy in Treatment of Malignancies, Including Brain Tumours","volume":"33","author":"Ostrowski","year":"2016","journal-title":"Med. Oncol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"807","DOI":"10.3109\/02841869409083952","article-title":"Carbogen Breathing in Patients with Glioblastoma Multiforme Submitted to Radiotherapy Assessment of Gas Exchange Parameters","volume":"33","author":"Fatigante","year":"1994","journal-title":"Acta Oncol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.ajpath.2017.01.010","article-title":"Hypoxia-Mediated Mechanisms Associated with Antiangiogenic Treatment Resistance in Glioblastomas","volume":"187","author":"Mahase","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1308573","article-title":"A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma","volume":"370","author":"Gilbert","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJMoa1308345","article-title":"Bevacizumab plus Radiotherapy-Temozolomide for Newly Diagnosed Glioblastoma","volume":"370","author":"Chinot","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1158\/1078-0432.CCR-16-0895","article-title":"Molecular Pathways: Hypoxia-Activated Prodrugs in Cancer Therapy","volume":"23","author":"Baran","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Varalli, L., Berlet, R., Abenojar, E., McDaid, J., Gascoigne, D.A., Bailes, J., and Aksenov, D.P. (2025). Applications and Efficacy of Iron Oxide Nanoparticles in the Treatment of Brain Tumors. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17040499"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s11060-025-05217-4","article-title":"Photodynamic Therapy for Glioblastoma: A Narrative Review","volume":"175","author":"Price","year":"2025","journal-title":"J. Neurooncol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"E7","DOI":"10.3171\/2024.6.FOCUS24338","article-title":"A Review of Sonodynamic Therapy for Brain Tumors","volume":"57","author":"Hutton","year":"2024","journal-title":"Neurosurg. Focus"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"vdaf162","DOI":"10.1093\/noajnl\/vdaf162","article-title":"Assessment of the Emerging Role of AI in Diagnosing Gliomas Using MRI: Systematic Review and Meta-Analysis","volume":"7","author":"Alsaedi","year":"2025","journal-title":"Neuro-Oncol. Adv."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/505\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:48:25Z","timestamp":1776934105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/505"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,19]]},"references-count":170,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["antiox15040505"],"URL":"https:\/\/doi.org\/10.3390\/antiox15040505","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,19]]}}}