{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:22:16Z","timestamp":1791490936434,"version":"4.3.4"},"reference-count":78,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018063","name":"Bowel Research UK","doi-asserted-by":"publisher","award":["SG\u201024003"],"award-info":[{"award-number":["SG\u201024003"]}],"id":[{"id":"10.13039\/100018063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In well\u2010perfused tissues, interstitial composition resembles capillary plasma. Solid tumors break this norm because cancer cell proliferation outpaces vascular expansion, leading to a diffusion\u2010limited tumor microenvironment (TME) that is notably depleted of oxygen and enriched in acids. The magnitude of tumor acidosis; its chemical composition in terms of [CO\n                    <jats:sub>2<\/jats:sub>\n                    ] and [HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    ] (components of the major extracellular buffer); and its relationship with hypoxia are not intuitive to predict but important to know for designing experiments and contextualising results. We address these timely questions using mathematical models of a monolayer, spheroid, and poorly\u2010perfused tissue. Our simulations suggest a physiologically realistic TME pH range of 6.7\u20137.4, reveal a prominence of hypercapnia, and indicate varying levels of HCO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    depletion or accumulation arising from fermentation and respiration, respectively. The trajectories of tumor hypoxia and acidosis depend on the balance between aerobic and anaerobic pathways, with important consequences on hypoxic signaling where many responses are pH\u2010sensitive.\n                  <\/jats:p>","DOI":"10.1002\/bies.70101","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T09:23:30Z","timestamp":1766395410000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Using Mathematical Modeling of Tumor Metabolism to Predict the Magnitude, Composition, and Hypoxic Interactions of Microenvironment Acidosis"],"prefix":"10.1002","volume":"48","author":[{"given":"Alzbeta","family":"Hulikova","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy &amp; Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Swietach","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy &amp; Genetics University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.016"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2015.00115"},{"key":"e_1_2_13_4_1","first-page":"6449","article-title":"Blood Flow, Oxygen and Nutrient Supply, and Metabolic Microenvironment of Human Tumors: A Review","volume":"49","author":"Vaupel P.","year":"1989","journal-title":"Cancer 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