Linked Life Data

12142057

Source:http://linkedlifedata.com/resource/pubmed/id/12142057

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2002-7-26
pubmed:abstractText
ZD0473 is a new generation hindered platinum agent currently undergoing worldwide Phase II clinical studies. The in vitro cytotoxicity of ZD0473 either alone or in combination with the anticancer drugs paclitaxel, gemcitabine, vinorelbine, topotecan and doxorubicin was determined using four human ovarian carcinoma cell lines and by the sulphorhodamine B assay (SRB). The lines included one model of acquired cisplatin resistance and one isogenic pair differing only in their p53 status. Notably, the simultaneous exposure to ZD0473 and paclitaxel for 96 h resulted in synergy (as defined by a median effect analysis) in all four cell lines (i.e. independent of cisplatin resistance and p53 status). In addition, synergy was observed in 3/4 lines and 2/4 lines following concomitant exposure to topotecan or gemcitabine, respectively. Sequencing studies with ZD0473 and paclitaxel revealed that, for three of the four cell lines, the combination of ZD0473 administered for 24 h prior to paclitaxel for 24 h conferred a greater growth inhibitory effect than the reverse sequential combination. This scheduling effect was particularly marked for the acquired cisplatin-resistant A2780CisR cell line; synergy being observed with ZD0473/paclitaxel, but antagonism with paclitaxel/ZD0473. This effect did not appear to be correlated with changes in drug-induced cell cycle checkpoints. These data suggest that ZD0473 may be usefully combined with various cytotoxics in the clinic, including paclitaxel, topotecan and gemcitabine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0959-8049
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1653-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Sequence-dependent synergism between the new generation platinum agent ZD0473 and paclitaxel in cisplatin-sensitive and -resistant human ovarian carcinoma cell lines.
pubmed:affiliation
CRC Centre for Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, Surrey SM2 5NG, Sutton, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't