{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:44:06Z","timestamp":1772171046578,"version":"3.50.1"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2009,5,29]],"date-time":"2009-05-29T00:00:00Z","timestamp":1243555200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000394","type":"journal-article","created":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T17:27:18Z","timestamp":1243531638000},"page":"e1000394","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":157,"title":["Structural Adaptation and Heterogeneity of Normal and Tumor Microvascular Networks"],"prefix":"10.1371","volume":"5","author":[{"given":"Axel R.","family":"Pries","sequence":"first","affiliation":[]},{"given":"Annemiek J. M.","family":"Cornelissen","sequence":"additional","affiliation":[]},{"given":"Anoek A.","family":"Sloot","sequence":"additional","affiliation":[]},{"given":"Marlene","family":"Hinkeldey","sequence":"additional","affiliation":[]},{"given":"Matthew R.","family":"Dreher","sequence":"additional","affiliation":[]},{"given":"Michael","family":"H\u00f6pfner","sequence":"additional","affiliation":[]},{"given":"Mark W.","family":"Dewhirst","sequence":"additional","affiliation":[]},{"given":"Timothy W.","family":"Secomb","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2009,5,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1056\/NEJM197111182852108","article-title":"Tumor angiogenesis: therapeutic implications.","volume":"285","author":"J Folkman","year":"1971","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/nm0901-987","article-title":"Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy.","volume":"7","author":"RK Jain","year":"2001","journal-title":"Nat Med"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1103\/PhysRevLett.75.2428","article-title":"Scale-invariant behavior and vascular network formation in normal and tumor tissue.","volume":"75","author":"Y Gazit","year":"1995","journal-title":"Phys Rev Lett"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1006\/mvre.1996.0031","article-title":"Role of tumor vascular architecture in nutrient and drug delivery: an invasion percolation-based network model.","volume":"51","author":"JW Baish","year":"1996","journal-title":"Microvasc Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1158\/1078-0432.CCR-06-2629","article-title":"Multiple etiologies of tumor hypoxia require multifaceted solutions.","volume":"13","author":"MW Dewhirst","year":"2007","journal-title":"Clin Cancer Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"44004","DOI":"10.1117\/1.2003369","article-title":"Hyperspectral imaging of hemoglobin saturation in tumor microvasculature and tumor hypoxia development.","volume":"10","author":"BS Sorg","year":"2005","journal-title":"J Biomed Opt"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1104819","article-title":"Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy.","volume":"307","author":"RK Jain","year":"2005","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/379088a0","article-title":"Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours.","volume":"379","author":"TG Graeber","year":"1996","journal-title":"Nature"},{"key":"ref9","first-page":"3387","article-title":"Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene.","volume":"62","author":"KM Comerford","year":"2002","journal-title":"Cancer Res"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/BF00437479","article-title":"A systems approach to cancer therapy. (Antioncogenics+standard cytotoxics\u2013&gt;mechanism(s) of interaction).","volume":"15","author":"BA Teicher","year":"1996","journal-title":"Cancer Metastasis Rev"},{"key":"ref11","first-page":"5491","article-title":"Pharmacodynamic-mediated reduction of temozolomide tumor concentrations by the angiogenesis inhibitor TNP-470.","volume":"61","author":"J Ma","year":"2001","journal-title":"Cancer Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"849","DOI":"10.2174\/092986706776361085","article-title":"Antiangiogenesis drug design: multiple pathways targeting tumor vasculature.","volume":"13","author":"H Zhong","year":"2006","journal-title":"Curr Med Chem"},{"key":"ref13","first-page":"1","article-title":"Angiogenesis and angiogenesis inhibition: an overview.","volume":"79","author":"J Folkman","year":"1997","journal-title":"EXS"},{"key":"ref14","first-page":"2199","article-title":"Prognostic value of angiogenesis in mammary tumors.","volume":"18","author":"V Goede","year":"1998","journal-title":"Anticancer Res"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nm0404-329a","article-title":"Recognition of tumor blood vessel normalization as a new antiangiogenic concept.","volume":"10","author":"K Hellmann","year":"2004","journal-title":"Nat Med"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1158\/0008-5472.CAN-06-4102","article-title":"Effect of vascular normalization by antiangiogenic therapy on interstitial hypertension, peritumor edema, and lymphatic metastasis: insights from a mathematical model.","volume":"67","author":"RK Jain","year":"2007","journal-title":"Cancer Res"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"3942","DOI":"10.1158\/1078-0432.CCR-07-0278","article-title":"Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy.","volume":"13","author":"PV Dickson","year":"2007","journal-title":"Clin Cancer Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3748\/wjg.14.1","article-title":"Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer.","volume":"14","author":"M Hopfner","year":"2008","journal-title":"World J Gastroenterol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"H1015","DOI":"10.1152\/ajpheart.2001.281.3.H1015","article-title":"Structural adaptation of microvascular networks: functional roles of adaptive responses.","volume":"281","author":"AR Pries","year":"2001","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-1-4419-8871-3_3","article-title":"Mathematical modelling of tumour-induced angiogenesis: network growth and structure.","volume":"117","author":"M Chaplain","year":"2004","journal-title":"Cancer Treat Res"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000090241","article-title":"A mathematical model for capillary formation and development in tumor angiogenesis: a review.","volume":"52","author":"S Pamuk","year":"2006","journal-title":"Chemotherapy"},{"key":"ref22","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":"IJ Stamper","year":"2007","journal-title":"Bull Math Biol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jtbi.2007.08.030","article-title":"A simple mechanistic model of sprout spacing in tumour-associated angiogenesis.","volume":"250","author":"B Addison-Smith","year":"2008","journal-title":"J Theor Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.jtbi.2005.12.022","article-title":"Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies.","volume":"241","author":"SR McDougall","year":"2006","journal-title":"J Theor Biol"},{"key":"ref25","first-page":"197","article-title":"Angioadaptation: keeping the vascular system in shape.","volume":"17","author":"A Zakrzewicz","year":"2002","journal-title":"News Physiol Sci"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1080\/10273660600968994","article-title":"Multiscale modelling of tumour growth and therapy: the influence of vessel normalisation on chemotherapy.","volume":"7","author":"T Alarcon","year":"2006","journal-title":"Computational and Mathematical Methods in Medicine"},{"key":"ref27","first-page":"165","article-title":"Structural Adaptation in Normal and Cancerous Vasculature.","author":"PK Maini","year":"2007"},{"key":"ref28","first-page":"H349","article-title":"Structural adaptation and stability of microvascular networks: theory and simulations.","volume":"275","author":"AR Pries","year":"1998","journal-title":"Am J Physiol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jtbi.2007.09.031","article-title":"Emergent vascular network inhomogeneities and resulting blood flow patterns in a growing tumor.","volume":"250","author":"M Welter","year":"2008","journal-title":"J Theor Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ijrobp.2006.10.002","article-title":"Effects of fluctuating oxygenation on tirapazamine efficacy: Theoretical predictions.","volume":"67","author":"LI Cardenas-Navia","year":"2007","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1002\/hep.510280610","article-title":"Enhanced expression of thrombospondin-1 and hypovascularity in human cholangiocarcinoma.","volume":"28","author":"N Kawahara","year":"1998","journal-title":"Hepatology"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1053\/sonc.2002.37263","article-title":"Role of angiogenesis in tumor growth and metastasis.","volume":"29","author":"J Folkman","year":"2002","journal-title":"Semin Oncol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1161\/01.HYP.0000184428.16429.be","article-title":"Remodeling of blood vessels: responses of diameter and wall thickness to hemodynamic and metabolic stimuli.","volume":"46","author":"AR Pries","year":"2005","journal-title":"Hypertension"},{"key":"ref34","first-page":"H545","article-title":"Relationship between structural and hemodynamic heterogeneity in microvascular networks.","volume":"270","author":"AR Pries","year":"1996","journal-title":"Am J Physiol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"H2224","DOI":"10.1152\/ajpheart.00491.2001","article-title":"Balance between myogenic, flow-dependent, and metabolic flow control in coronary arterial tree: a model study.","volume":"282","author":"AJ Cornelissen","year":"2002","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1161\/01.HYP.23.6.1113","article-title":"Cell-to-cell communication coordinates blood flow control.","volume":"23","author":"SS Segal","year":"1994","journal-title":"Hypertension"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1111\/j.1469-7793.2001.00937.x","article-title":"Role for endothelial cell conduction in ascending vasodilatation and exercise hyperaemia in hamster skeletal muscle.","volume":"536","author":"SS Segal","year":"2001","journal-title":"J Physiol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1152\/physiolgenomics.00169.2002","article-title":"Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion.","volume":"13","author":"C de Wit","year":"2003","journal-title":"Physiol Genomics"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/35025220","article-title":"Angiogenesis in cancer and other diseases.","volume":"407","author":"P Carmeliet","year":"2000","journal-title":"Nature"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1172\/JCI200320087","article-title":"What brings pericytes to tumor vessels?","volume":"112","author":"RK Jain","year":"2003","journal-title":"J Clin Invest"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"5740","DOI":"10.1158\/0008-5472.CAN-04-4552","article-title":"Mosaic tumor vessels: cellular basis and ultrastructure of focal regions lacking endothelial cell markers.","volume":"65","author":"E di Tomaso","year":"2005","journal-title":"Cancer Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1126\/science.3775368","article-title":"Flow control among microvessels coordinated by intercellular conduction.","volume":"234","author":"SS Segal","year":"1986","journal-title":"Science"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1159\/000092575","article-title":"Connexin-dependent communication within the vascular wall: contribution to the control of arteriolar diameter.","volume":"42","author":"C de Wit","year":"2006","journal-title":"Adv Cardiol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1152\/physiol.00008.2004","article-title":"Connexins: gaps in our knowledge of vascular function.","volume":"19","author":"XF Figueroa","year":"2004","journal-title":"Physiology (Bethesda)"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1152\/japplphysiol.00133.2004","article-title":"Connexin expression and conducted vasodilation along arteriolar endothelium in mouse skeletal muscle.","volume":"97","author":"RC Looft-Wilson","year":"2004","journal-title":"J Appl Physiol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1242\/jcs.114.6.1229","article-title":"VEGF transiently disrupts gap junctional communication in endothelial cells.","volume":"114","author":"S Suarez","year":"2001","journal-title":"J Cell Sci"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.neuroimage.2004.06.047","article-title":"New methods for the computer-assisted 3-D reconstruction of neurons from confocal image stacks.","volume":"23","author":"S Schmitt","year":"2004","journal-title":"Neuroimage"},{"key":"ref48","first-page":"H1324","article-title":"Generalization of the Fahraeus principle for microvessel networks.","volume":"251","author":"AR Pries","year":"1986","journal-title":"Am J Physiol"},{"key":"ref49","first-page":"327","article-title":"A versatile video image analysis system for microcirculatory research.","volume":"7","author":"AR Pries","year":"1988","journal-title":"Int J Microcirc Clin Exp"},{"key":"ref50","first-page":"H1713","article-title":"Structure and hemodynamics of microvascular networks: heterogeneity and correlations.","volume":"269","author":"AR Pries","year":"1995","journal-title":"Am J Physiol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1161\/01.RES.67.4.826","article-title":"Blood flow in microvascular networks. Experiments and simulation.","volume":"67","author":"AR Pries","year":"1990","journal-title":"Circ Res"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0026-2862(89)90018-6","article-title":"Red cell distribution at microvascular bifurcations.","volume":"38","author":"AR Pries","year":"1989","journal-title":"Microvasc Res"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1161\/01.RES.75.5.904","article-title":"Resistance to blood flow in microvessels in vivo.","volume":"75","author":"AR Pries","year":"1994","journal-title":"Circ Res"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1073\/pnas.12.3.207","article-title":"The physiological principle of minimum work. I.The vascular system and the cost of blood volume.","volume":"12","author":"CD Murray","year":"1926","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1161\/01.RES.77.5.1017","article-title":"Design principles of vascular beds.","volume":"77","author":"AR Pries","year":"1995","journal-title":"Circ Res"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"H2204","DOI":"10.1152\/ajpheart.00757.2002","article-title":"Structural response of microcirculatory networks to changes in demand: information transfer by shear stress.","volume":"284","author":"AR Pries","year":"2003","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/comjnl\/7.4.308","article-title":"A Simplex-Method for Function Minimization.","volume":"7","author":"JA Nelder","year":"1965","journal-title":"Computer Journal"},{"key":"ref58","first-page":"H2716","article-title":"Diameter variability and microvascular flow resistance.","volume":"272","author":"AR Pries","year":"1997","journal-title":"Am J Physiol"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000394","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T06:06:32Z","timestamp":1633500392000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000394"}},"subtitle":[],"editor":[{"given":"Jason A.","family":"Papin","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2009,5,29]]},"references-count":58,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2009,5,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000394","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1163658.625427","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,5,29]]}}}