Measurement of macromolecular diffusion coefficients in human tumors

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dc.contributor.author Nasser, Selim
dc.contributor.author Brown, Edward B.
dc.contributor.author Boucher, Yves
dc.contributor.author Jain, Rakesh K.
dc.date.accessioned 2017-02-02T10:12:54Z
dc.date.available 2017-02-02T10:12:54Z
dc.date.copyright 2004 en_US
dc.date.issued 2017-02-02
dc.identifier.issn 0026-2862 en_US
dc.identifier.uri http://hdl.handle.net/10725/5157
dc.description.abstract The diffusive transport of macromolecules in tumors is an important determinant of the delivery of many anticancer therapeutics. However, measurements of diffusive transport to date have only been performed in animal models. In this work, diffusion coefficients of BSA and IgM were measured in human tumor biopsies (cooled to 4–7°C to prevent degradation) using fluorescence recovery after photobleaching. To quantify the effects of excision and cooling, the diffusion coefficient of BSA and IgM was measured in human tumor xenografts in situ and after cooling and excision. The change in diffusion coefficients before and after excision of xenografts was used to calculate in vivo diffusion coefficients in human tumors from ex vivo measurements. Using this approach, we obtained the first quantitative determinations of macromolecular diffusion coefficients in human tumors and find that the diffusion coefficients of BSA and IgM in human colon were adenocarcinomas higher than those in xenografts. This difference is consistent with lower collagen content in the accessible regions of these human tumors. These measurements allow the quantitative prediction of the diffusive transport of like-sized macromolecular therapeutics in human tumors. These measurements should help in modeling the transport of novel large MW therapeutics, and hence in estimating their distribution and efficacy in tumors. en_US
dc.language.iso en en_US
dc.title Measurement of macromolecular diffusion coefficients in human tumors en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOM en_US
dc.author.idnumber 200804624 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Microvascular Research en_US
dc.journal.volume 67 en_US
dc.journal.issue 3 en_US
dc.article.pages 231-236 en_US
dc.keywords Extracellular matrix en_US
dc.keywords FRAP en_US
dc.keywords Drug transport en_US
dc.keywords Photobleaching en_US
dc.identifier.doi http://dx.doi.org/10.1016/j.mvr.2004.02.001 en_US
dc.identifier.ctation Brown, E. B., Boucher, Y., Nasser, S., & Jain, R. K. (2004). Measurement of macromolecular diffusion coefficients in human tumors. Microvascular research, 67(3), 231-236. en_US
dc.author.email selim.nasser@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://www.sciencedirect.com/science/article/pii/S0026286204000238 en_US
dc.author.affiliation Lebanese American University en_US

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