Linked Life Data

7528598

Source:http://linkedlifedata.com/resource/pubmed/id/7528598

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-2-2
pubmed:abstractText
Targeting with toxic EGF-based conjugates against tumour cells with amplified EGF-receptors might be a possible approach towards improved therapy of certain malignancies such as gliomas and squamous carcinomas. In this study, the penetration and binding of 125I delivered by EGF-dextran conjugates were analysed in cultured spheroids applied as a tumour nodule model. The spheroids consisted of human glioma cells, U-343MGaCl2:6, with large amounts of EGF-receptors. The penetration and binding patterns of 125I delivered by 125I-EGF and 125I-dextran were analysed for comparison. The EGF-dextran associated 125I-activity showed a rather slow penetration but after some hours significant amounts of radioactivity had reached the deeper regions and good penetration was obtained within 5 hours. The penetration seemed somewhat faster when the 125I-activity was delivered with EGF possibly dependent on the lower molecular weight allowing for faster diffusion. Furthermore, EGF-dextran associated 125I seemed to penetrate somewhat faster after the EGF-receptors were blocked with non-radioactive EGF, probably due to the lack of binding preventing free diffusion. After administration of 125I-EGF-dextran or 125I-EGF, the binding patterns were superimposed on the penetration patterns. In the penetration studies, the superimposed accumulations due to binding were removed by presaturation of the receptors with non-radioactive EGF. After a 1 hour incubation, binding of EGF-dextran associated 125I-activity could be seen only in an outer region, with an approximative thickness of 50 microns, of the viable cell layer. Extensive receptor specific binding in the deeper regions, at a depth of 100-200 microns, was seen after several hours incubation. In addition, low levels of non-specific binding in the central regions were seen when the 125I-activity was delivered with dextran without EGF. A similar low background binding was seen also in the centre of spheroids incubated with 125I-EGF-dextran or 125I-EGF after saturation of the receptors with non-radioactive EGF. However, the major amount of radioactivity delivered as 125I-EGF-dextran or 125I-EGF had a receptor specific binding and, also in inner regions, it could be displaced by non-radioactive EGF. Thus, EGF-dextran, which is a candidate compound for targeted therapy, allowed penetration of the applied radioactivity and binding could be observed, after some hours, also in the inner regions of the spheroids.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1062-8401
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
145-58
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Penetration and binding of epidermal growth factor-dextran conjugates in spheroids of human glioma origin.
pubmed:affiliation
Department of Radiation Sciences, Uppsala University, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't