Linked Life Data

12110502

Source:http://linkedlifedata.com/resource/pubmed/id/12110502

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2002-7-11
pubmed:abstractText
Cellular determinants of sensitivity to the bifunctional alkylating agent 4-[N,N-bis(2-iodoethyl)amino]phenol (ZD2767D), the active drug produced by ZD2767 antibody-directed enzyme prodrug therapy (ADEPT), were studied. The prodrug 4-[N,N-bis(2-iodoethyl)amino]phenoxycarbonyl L-glutamic acid (ZD2767P)+activating enzyme carboxypeptidase G2 (CPG2) displayed growth inhibitory activity (IC(50) 0.04-2.2 microM) in colorectal tumour and non-small cell lung cancer (NSCLC) cell lines, and was more potent than a monofunctional ZD2767D analogue (colorectal cell lines-IC(50) 18-38 microM), synthesized for the first time. ZD2767P + CPG2 rapidly formed DNA-DNA interstrand cross-links (maximal at 10 min), and semi-quantitative analyses indicate that levels were similar in 3 of 4 cell lines studied (25-75 rad equivalents) at equitoxic (10 x IC(50)/LC(50)) concentrations. In matched HCT116 TP53 functional/non-functional cell lines, there was no significant difference in the sensitivity to ZD2767P+CPG2. Together, these results suggest that cellular sensitivity to ZD2767P+CPG2 is, in part, related to the levels of interstrand crosslinks, but that TP53 status does not markedly effect chemosensitivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0959-8049
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1543-52
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
DNA interstrand cross-linking and TP53 status as determinants of tumour cell sensitivity in vitro to the antibody-directed enzyme prodrug therapy ZD2767.
pubmed:affiliation
Cancer Research Unit, University of Newcastle, Framlington Place, NE2 4HH, Newcastle upon Tyne, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't