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Article: A mathematical model of the impact of infused targeted cytotoxic agents on brain tumours: Implications for detection, design and delivery

TitleA mathematical model of the impact of infused targeted cytotoxic agents on brain tumours: Implications for detection, design and delivery
Authors
Issue Date2002
PublisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CPR
Citation
Cell Proliferation, 2002, v. 35 n. 6, p. 343-361 How to Cite?
AbstractMotivated by the recent development of highly specific agents for brain tumours, we develop a mathematical model of the spatio-temporal dynamics of a brain tumour that receives an infusion of a highly specific cytotoxic agent (e.g. IL-4-PE, a cytotoxin comprised of IL-4 and a mutated form of Pseudomonas exotoxin). We derive an approximate but accurate mathematical formula for the tumour cure probability in terms of the tumour characteristics (size at time of detection, proliferation rate, diffusion coefficient), drug design (killing rate, loss rate and convection constants for tumour and tissue), and drug delivery (infusion rate, infusion duration). Our results suggest that high specificity is necessary but not sufficient to cure malignant gliomas; a nondispersed spatial profile of pretreatment tumour cells and/or good drug penetration are also required. The most important levers to improve tumour cure appear to be earlier detection, higher infusion rate, lower drug clearance rate and better convection into tumour, but not tissue. In contrast, the tumour cure probability is less sensitive to a longer infusion duration and enhancements in drug potency and drug specificity.
Persistent Identifierhttp://hdl.handle.net/10722/151566
ISSN
2015 Impact Factor: 3.084
2015 SCImago Journal Rankings: 1.176
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWein, LMen_US
dc.contributor.authorWu, JTen_US
dc.contributor.authorIanculescu, AGen_US
dc.contributor.authorPuri, RKen_US
dc.date.accessioned2012-06-26T06:24:46Z-
dc.date.available2012-06-26T06:24:46Z-
dc.date.issued2002en_US
dc.identifier.citationCell Proliferation, 2002, v. 35 n. 6, p. 343-361en_US
dc.identifier.issn0960-7722en_US
dc.identifier.urihttp://hdl.handle.net/10722/151566-
dc.description.abstractMotivated by the recent development of highly specific agents for brain tumours, we develop a mathematical model of the spatio-temporal dynamics of a brain tumour that receives an infusion of a highly specific cytotoxic agent (e.g. IL-4-PE, a cytotoxin comprised of IL-4 and a mutated form of Pseudomonas exotoxin). We derive an approximate but accurate mathematical formula for the tumour cure probability in terms of the tumour characteristics (size at time of detection, proliferation rate, diffusion coefficient), drug design (killing rate, loss rate and convection constants for tumour and tissue), and drug delivery (infusion rate, infusion duration). Our results suggest that high specificity is necessary but not sufficient to cure malignant gliomas; a nondispersed spatial profile of pretreatment tumour cells and/or good drug penetration are also required. The most important levers to improve tumour cure appear to be earlier detection, higher infusion rate, lower drug clearance rate and better convection into tumour, but not tissue. In contrast, the tumour cure probability is less sensitive to a longer infusion duration and enhancements in drug potency and drug specificity.en_US
dc.languageengen_US
dc.publisherBlackwell Publishing Ltd. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CPRen_US
dc.relation.ispartofCell Proliferationen_US
dc.subject.meshAntineoplastic Agents - Administration & Dosage - Toxicityen_US
dc.subject.meshBrain Neoplasms - Drug Therapy - Pathologyen_US
dc.subject.meshCell Division - Drug Effectsen_US
dc.subject.meshDrug Delivery Systems - Methodsen_US
dc.subject.meshDrug Designen_US
dc.subject.meshExotoxins - Administration & Dosage - Toxicityen_US
dc.subject.meshGlioma - Drug Therapy - Pathologyen_US
dc.subject.meshHumansen_US
dc.subject.meshInfusions, Intralesionalen_US
dc.subject.meshInterleukin-4 - Administration & Dosage - Toxicityen_US
dc.subject.meshModels, Theoreticalen_US
dc.subject.meshRecombinant Fusion Proteins - Administration & Dosage - Toxicityen_US
dc.titleA mathematical model of the impact of infused targeted cytotoxic agents on brain tumours: Implications for detection, design and deliveryen_US
dc.typeArticleen_US
dc.identifier.emailWu, JT:joewu@hkucc.hku.hken_US
dc.identifier.authorityWu, JT=rp00517en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1046/j.1365-2184.2002.00246.xen_US
dc.identifier.pmid12427253-
dc.identifier.scopuseid_2-s2.0-0036434384en_US
dc.identifier.volume35en_US
dc.identifier.issue6en_US
dc.identifier.spage343en_US
dc.identifier.epage361en_US
dc.identifier.isiWOS:000179574100003-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridWein, LM=35560766400en_US
dc.identifier.scopusauthoridWu, JT=7409256423en_US
dc.identifier.scopusauthoridIanculescu, AG=36830470100en_US
dc.identifier.scopusauthoridPuri, RK=7202045715en_US

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