{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T21:58:47Z","timestamp":1761861527230,"version":"build-2065373602"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Mathematical Biosciences"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1016\/j.mbs.2022.108909","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T01:46:52Z","timestamp":1662947212000},"page":"108909","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["A simulation of parental and glycolytic tumor phenotype competition predicts observed responses to pH changes and increased glycolysis after anti-VEGF therapy"],"prefix":"10.1016","volume":"352","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9797-1134","authenticated-orcid":false,"given":"Frederika","family":"Rentzeperis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Miller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arig","family":"Ibrahim-Hashim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Gillies","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Gatenby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothy","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"29","key":"10.1016\/j.mbs.2022.108909_b1","doi-asserted-by":"crossref","first-page":"8177","DOI":"10.1073\/pnas.1608247113","article-title":"Probe for the measurement of cell surface pH in vivo and ex vivo","volume":"113","author":"Anderson","year":"2016","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"2","key":"10.1016\/j.mbs.2022.108909_b2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/PPO.0000000000000102","article-title":"Metabolism and its sequelae in cancer evolution and therapy","volume":"21","author":"Gillies","year":"2015","journal-title":"Cancer J."},{"issue":"1\u20132","key":"10.1016\/j.mbs.2022.108909_b3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10555-018-09777-y","article-title":"Tumor pH and metastasis: a malignant process beyond hypoxia","volume":"38","author":"Thews","year":"2019","journal-title":"Cancer Metastasis Rev."},{"issue":"19","key":"10.1016\/j.mbs.2022.108909_b4","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1080\/15384101.2016.1231284","article-title":"Phenotypic changes of acid-adapted cancer cells push them toward aggressiveness in their evolution in the tumor microenvironment","volume":"16","author":"Damaghi","year":"2016","journal-title":"Cell Cycle"},{"issue":"16","key":"10.1016\/j.mbs.2022.108909_b5","first-page":"6020","article-title":"Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo","volume":"61","author":"Fukumura","year":"2001","journal-title":"Cancer Res."},{"issue":"1","key":"10.1016\/j.mbs.2022.108909_b6","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1080\/14756366.2016.1252760","article-title":"Systemic alkalinisation delays prostate cancer cell progression in TRAMP mice","volume":"32","author":"Astigiano","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"issue":"2","key":"10.1016\/j.mbs.2022.108909_b7","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.juro.2012.03.113","article-title":"Systemic buffers inhibit carcinogenesis in TRAMP mice","volume":"188","author":"Ibrahim-Hashim","year":"2012","journal-title":"J. Urol."},{"issue":"11","key":"10.1016\/j.mbs.2022.108909_b8","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrc1478","article-title":"Why do cancers have high aerobic glycolysis?","volume":"4","author":"Gatenby","year":"2004","journal-title":"Nature Rev. Cancer"},{"issue":"3191","key":"10.1016\/j.mbs.2022.108909_b9","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of cancer cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"issue":"7","key":"10.1016\/j.mbs.2022.108909_b10","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1158\/0008-5472.CAN-19-2669","article-title":"Towards multidrug adaptive therapy","volume":"80","author":"West","year":"2020","journal-title":"Cancer Res."},{"issue":"0025\u20135564","key":"10.1016\/j.mbs.2022.108909_b11","article-title":"Predicting the results of competition between two breast cancer lines grown in 3-D spheroid culture","volume":"336","author":"Rodriguez\u00a0Messan","year":"2021","journal-title":"Math. Biosci."},{"issue":"4908","key":"10.1016\/j.mbs.2022.108909_b12","first-page":"1","article-title":"Frequency-dependent interactions determine outcome of competition between two breast cancer cell lines","volume":"11","author":"Freischel","year":"2021","journal-title":"Sci. Rep."},{"issue":"8","key":"10.1016\/j.mbs.2022.108909_b13","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1007\/s11538-018-0441-3","article-title":"Predictive modeling of neuroblastoma growth dynamics in xenograft model after bevacizumab anti-VEGF therapy","volume":"80","author":"He","year":"2018","journal-title":"Bull. Math. Biol."},{"issue":"5","key":"10.1016\/j.mbs.2022.108909_b14","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.semcancer.2008.03.011","article-title":"Adaptation to hypoxia and acidosis in carcinogenesis and tumor progression","volume":"18","author":"Fang","year":"2008","journal-title":"Semin. Cancer Biol."},{"key":"10.1016\/j.mbs.2022.108909_b15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/3628124","article-title":"A model for spheroid versus monolayer response of SK-N-SH neuroblastoma cells to treatment with 15-deoxy-PGJ2","volume":"2016","author":"Wallace","year":"2016","journal-title":"Comput. Math. Methods Med."},{"key":"10.1016\/j.mbs.2022.108909_b16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.apm.2022.05.006","article-title":"Local and global sensitivity analysis of spheroid and xenograft models of the acid-mediated development of tumor malignancy","volume":"109","author":"Rentzeperis","year":"2022","journal-title":"Appl. Math. Model."},{"issue":"3","key":"10.1016\/j.mbs.2022.108909_b17","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.gpb.2018.12.006","article-title":"Warburg effects in cancer and normal proliferating cells: two tales of the same name","volume":"17","author":"Sun","year":"2019","journal-title":"Genom. Proteomics Bioinform."},{"issue":"7","key":"10.1016\/j.mbs.2022.108909_b18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0159675","article-title":"Extracellular pH modulates neuroendocrine prostate cancer cell metabolism and susceptibility to the mitochondrial inhibitor niclosamide","volume":"11","author":"Ippolito","year":"2016","journal-title":"PLoS One"},{"issue":"52","key":"10.1016\/j.mbs.2022.108909_b19","doi-asserted-by":"crossref","first-page":"86026","DOI":"10.18632\/oncotarget.13323","article-title":"Acidic pH reduces VEGF-mediated endothelial cell responses by downregulation of VEGFR-2; relevance for anti-angiogenic therapies.","volume":"7","author":"Faes","year":"2016","journal-title":"Oncotarget"},{"issue":"28","key":"10.1016\/j.mbs.2022.108909_b20","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1038\/sj.onc.1202792","article-title":"Role of RhoA activation in the growth and morphology of a murine prostate tumor cell line","volume":"18","author":"Ghosh","year":"1999","journal-title":"Oncogene"},{"issue":"10","key":"10.1016\/j.mbs.2022.108909_b21","first-page":"3171s","article-title":"Growth and characterization of lncap prostate cancer cell spheroids","volume":"5","author":"Ballangrud","year":"1999","journal-title":"Clin. Cancer Res."},{"issue":"2","key":"10.1016\/j.mbs.2022.108909_b22","first-page":"451","article-title":"Genetic algorithm: Review and application","volume":"2","author":"Kumar","year":"2010","journal-title":"Int. J. Inf. Technol. Knowl. Manag."},{"issue":"6","key":"10.1016\/j.mbs.2022.108909_b23","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s10334-005-0013-z","article-title":"Microscopic images of intraspheroidal pH by 1 h magnetic resonance chemical shift imaging of pH sensitive indicators","volume":"18","author":"Alvarez-P\u00e9rez","year":"2005","journal-title":"Magn. Reson. Mater. Phys. Biol. Med."},{"issue":"9","key":"10.1016\/j.mbs.2022.108909_b24","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1158\/0008-5472.CAN-16-2844","article-title":"Defining cancer subpopulations by adaptive strategies rather than molecular properties provides novel insights into intratumoral evolution","volume":"77","author":"Ibrahim-Hashim","year":"2017","journal-title":"Cancer Res."},{"issue":"2","key":"10.1016\/j.mbs.2022.108909_b25","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1208\/s12248-012-9342-9","article-title":"Pharmacokinetics, lymph node uptake, and mechanistic PK model of near-infrared dye-labeled bevacizumab after IV and SC administration in mice","volume":"14","author":"Wu","year":"2012","journal-title":"AAPS J."},{"issue":"7","key":"10.1016\/j.mbs.2022.108909_b26","first-page":"485","article-title":"Tumor necrosis factor-alpha promotes tumor growth by inducing vascular endothelial growth factor","volume":"29","author":"Jing","year":"2011","journal-title":"Cancer Invest."},{"issue":"37","key":"10.1016\/j.mbs.2022.108909_b27","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.1038\/onc.2011.567","article-title":"Breaking the \u2018harmony\u2019 of TNF-\u03b1 signaling for cancer treatment","volume":"31","author":"Sasi","year":"2012","journal-title":"Oncogene"},{"issue":"28","key":"10.1016\/j.mbs.2022.108909_b28","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1038\/sj.onc.1204500","article-title":"Regulation of vascular endothelial growth factor expression by acidosis in human cancer cells","volume":"20","author":"Shi","year":"2001","journal-title":"Oncogene"},{"issue":"8","key":"10.1016\/j.mbs.2022.108909_b29","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1007\/s10585-013-9595-4","article-title":"Acidic pH via NF-\u03baB favours VEGF-C expression in human melanoma cells","volume":"30","author":"Peppicelli","year":"2013","journal-title":"Clin. Exp. Metastasis"},{"issue":"1","key":"10.1016\/j.mbs.2022.108909_b30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s12307-008-0013-4","article-title":"Microenvironment changes (in pH) affect VEGF alternative splicing","volume":"1","author":"Elias","year":"2008","journal-title":"Cancer Microenviron."},{"issue":"10","key":"10.1016\/j.mbs.2022.108909_b31","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jgg.2011.09.006","article-title":"Cell competition and its implications for development and cancer","volume":"38","author":"Tamori","year":"2011","journal-title":"J. Genet. Genom."},{"issue":"2","key":"10.1016\/j.mbs.2022.108909_b32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nrc2252","article-title":"Is cell competition relevant to cancer?","volume":"8","author":"Moreno","year":"2008","journal-title":"Nature Rev. Cancer"},{"issue":"4","key":"10.1016\/j.mbs.2022.108909_b33","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.bulm.2003.10.001","article-title":"Competition and natural selection in a mathematical model of cancer","volume":"66","author":"Nagy","year":"2004","journal-title":"Bull. Math. Biol."},{"key":"10.1016\/j.mbs.2022.108909_b34","article-title":"Predicting the results of competition between two breast cancer lines grown in 3-D spheroid culture","volume":"336","author":"Messan","year":"2021","journal-title":"Math. Biosci."},{"issue":"2","key":"10.1016\/j.mbs.2022.108909_b35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/jcp.22766","article-title":"Cellular modeling of cancer invasion: integration of in silico and in vitro approaches","volume":"227","author":"Kam","year":"2012","journal-title":"J. Cell. Physiol."},{"issue":"6","key":"10.1016\/j.mbs.2022.108909_b36","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1158\/0008-5472.CAN-08-2394","article-title":"The potential role of systemic buffers in reducing intratumoral extracellular pH and acid-mediated invasion","volume":"69","author":"Silva","year":"2009","journal-title":"Cancer Res."},{"issue":"7","key":"10.1016\/j.mbs.2022.108909_b37","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1002\/cam4.1032","article-title":"Tris\u2013base buffer: a promising new inhibitor for cancer progression and metastasis","volume":"6","author":"Ibrahim-Hashim","year":"2017","journal-title":"Cancer Med."},{"issue":"8","key":"10.1016\/j.mbs.2022.108909_b38","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s10585-011-9415-7","article-title":"Reduction of metastasis using a non-volatile buffer","volume":"28","author":"Ibrahim\u00a0Hashim","year":"2011","journal-title":"Clin. Exp. Metastasis"},{"issue":"1","key":"10.1016\/j.mbs.2022.108909_b39","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1373\/49.1.32","article-title":"Angiogenesis assays: a critical overview","volume":"49","author":"Auerbach","year":"2003","journal-title":"Clin. Chem."},{"key":"10.1016\/j.mbs.2022.108909_b40","doi-asserted-by":"crossref","DOI":"10.1155\/2020\/8857428","article-title":"An overview of in vitro, in vivo, and computational techniques for cancer-associated angiogenesis studies","volume":"2020","author":"Rahman","year":"2020","journal-title":"BioMed Res. Int."},{"issue":"8","key":"10.1016\/j.mbs.2022.108909_b41","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1007\/s11538-007-9253-6","article-title":"Modelling the role of angiogenesis and vasculogenesis in solid tumour growth","volume":"69","author":"Stamper","year":"2007","journal-title":"Bull. Math. Biol."},{"issue":"3","key":"10.1016\/j.mbs.2022.108909_b42","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.jtbi.2005.01.014","article-title":"On the role of endothelial progenitor cells in tumor neovascularization","volume":"235","author":"Komarova","year":"2005","journal-title":"J. Theoret. Biol."},{"issue":"1","key":"10.1016\/j.mbs.2022.108909_b43","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1004712","article-title":"Spatial metrics of tumour vascular organisation predict radiation efficacy in a computational model","volume":"12","author":"Scott","year":"2016","journal-title":"PLoS Comput. Biol."},{"issue":"2","key":"10.1016\/j.mbs.2022.108909_b44","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1137\/19M1293971","article-title":"Modeling the emergence of phenotypic heterogeneity in vascularized tumors","volume":"81","author":"Villa","year":"2021","journal-title":"SIAM J. Appl. Math."},{"issue":"4","key":"10.1016\/j.mbs.2022.108909_b45","article-title":"Using fractal geometry and universal growth curves as diagnostics for comparing tumor vasculature and metabolic rate with healthy tissue and for predicting responses to drug therapies","volume":"18","author":"Savage","year":"2013","journal-title":"Discrete Contin. Dyn. Syst. Ser. B"},{"issue":"584","key":"10.1016\/j.mbs.2022.108909_b46","first-page":"1","article-title":"Resistance to anti-angiogenic therapies: A mechanism depending on the time of exposure to the drugs","volume":"8","author":"Montemagno","year":"2020","journal-title":"Front. Cell Dev. Biol."}],"container-title":["Mathematical Biosciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0025556422000980?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0025556422000980?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T01:23:57Z","timestamp":1758417837000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0025556422000980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":46,"alternative-id":["S0025556422000980"],"URL":"https:\/\/doi.org\/10.1016\/j.mbs.2022.108909","relation":{},"ISSN":["0025-5564"],"issn-type":[{"type":"print","value":"0025-5564"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A simulation of parental and glycolytic tumor phenotype competition predicts observed responses to pH changes and increased glycolysis after anti-VEGF therapy","name":"articletitle","label":"Article Title"},{"value":"Mathematical Biosciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mbs.2022.108909","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108909"}}