Linked Life Data

1917158

Source:http://linkedlifedata.com/resource/pubmed/id/1917158

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1991-11-21
pubmed:abstractText
Free methotrexate (MTX) and 2 monoclonal antibody (MAb)-MTX conjugates were tested against mixed human tumour-cell cultures, in which 2 cell lines of differing antigenicity or drug sensitivity, pre-labelled with fluorescent dyes, were added together in microtitre wells. Conjugates were selectively cytotoxic for cells bearing high concentrations of the relevant antigen, and MTX was preferentially cytotoxic for wild-type cells rather than MTX-resistant variants when tested on separate cultures. In mixed cultures these selectivities were substantially retained, although there was a varying tendency towards intermediate cytotoxicity for each cell line of the pair. MTX was cytotoxic for cell line 79 IT grown as multicellular spheroids, but a MAb-MTX conjugate and a MAb-RTA immunotoxin showed little cytotoxicity against spheroids at the highest concentrations tested, although they were highly effective against monolayer cells. Mixed spheroids could be formed efficiently from most cell lines, although in some cases cell distribution was non-random. In mixed spheroids prepared between wild-type and MTX-resistant 79 IT variants, relative MTX sensitivities conformed broadly to those seen in separate monolayer cultures. Fluorescence-labelling was a reliable method for determining cell behaviour under the above conditions. We conclude that (a) selectivity of therapeutic agents in mixed cultures was partially, but not completely, impaired compared to that observed in separate cultures, and (b) that low Mr drugs are effective against 3-dimensional tumour-cell structures but antibody-targeted conjugates are not.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
566-72
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Efficacy and selectivity of monoclonal-antibody-targeted drugs and free methotrexate in fluorescence-labelled mixed tumour-cell monolayer cultures and multicellular spheroids.
pubmed:affiliation
Cancer Research Campaign Laboratory, University of Nottingham, University Park, UK.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't