Show simple item record

dc.contributor.authorMok, W.en
dc.contributor.authorStylianopoulos, T.en
dc.contributor.authorBoucher, Y.en
dc.contributor.authorJain, R. K.en
dc.creatorMok, W.en
dc.creatorStylianopoulos, T.en
dc.creatorBoucher, Y.en
dc.creatorJain, R. K.en
dc.date.accessioned2019-05-06T12:24:10Z
dc.date.available2019-05-06T12:24:10Z
dc.date.issued2009
dc.identifier.urihttp://gnosis.library.ucy.ac.cy/handle/7/48635
dc.description.abstractPurpose: Although oncolytic viral vectors show promise for the treatment of various cancers, ineffective initial distribution and propagation throughout the tumor mass often limit the therapeutic response. A mathematical model is developed to describe the spread of herpes simplex virus from the initial injection site. Experimental Design: The tumor is modeled as a sphere of radius R. The model incorporates reversible binding, interstitial diffusion, viral degradation, and internalization and physiologic parameters. Three species are considered as follows: free interstitial virus, virus bound to cell surfaces, and internalized virus. Results: This analysis reveals that both rapid binding and internalization as well as hindered diffusion contain the virus to the initial injection volume, with negligible spread to the surrounding tissue. Unfortunately, increasing the dose to saturate receptors and promote diffusion throughout the tumor is not a viable option: the concentration necessary would likely compromise safety. However, targeted modifications to the virus that decrease the binding affinity have the potential to increase the number of infected cells by 1.5-fold or more. An increase in the effective diffusion coefficientcan result in similargains. Conclusions: This analysis suggests criteria by which the potential response of a tumor to oncolytic herpes simplex virus therapy can be assessed. Furthermore, it reveals the potential of modifications to the vector delivery method, physicochemical properties of the virus, and tumor extracellular matrix composition to enhance efficacy. © 2009 American Association for Cancer Research.en
dc.language.isoengen
dc.sourceClinical Cancer Researchen
dc.subjectModelsen
dc.subjectarticleen
dc.subjectmathematical modelen
dc.subjectNeoplasmsen
dc.subjectpriority journalen
dc.subjectsolid tumoren
dc.subjectsensitivity analysisen
dc.subjectnonhumanen
dc.subjectBiologicalen
dc.subjectAnimalsen
dc.subjectbinding affinityen
dc.subjectinternalizationen
dc.subjectKineticsen
dc.subjectdrug distributionen
dc.subjectDiffusionen
dc.subjectdegradationen
dc.subjectdiffusion coefficienten
dc.subjectGene Therapyen
dc.subjectGenetic Vectorsen
dc.subjectHerpes simplex virusen
dc.subjectoncolytic herpes virusen
dc.subjectoncolytic virotherapyen
dc.subjectOncolytic Virusesen
dc.subjectSimplexvirusen
dc.subjectviral gene delivery systemen
dc.subjectvirus attachmenten
dc.subjectVirus Internalizationen
dc.subjectvirus vectoren
dc.titleMathematical modeling of herpes simplex virus distribution in solid tumors: Implications for cancer gene therapyen
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1158/1078-0432.CCR-08-2082
dc.description.volume15
dc.description.startingpage2352
dc.description.endingpage2360
dc.author.facultyΠολυτεχνική Σχολή / Faculty of Engineering
dc.author.departmentΤμήμα Μηχανικών Μηχανολογίας και Κατασκευαστικής / Department of Mechanical and Manufacturing Engineering
dc.type.uhtypeArticleen
dc.contributor.orcidStylianopoulos, T. [0000-0002-3093-1696]
dc.description.totalnumpages2352-2360


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record