Linked Life Data

10626354

Source:http://linkedlifedata.com/resource/pubmed/id/10626354

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2000-2-10
pubmed:abstractText
Study of the cellular pharmacology of the dinuclear platinum complexes, BBR3005 ([¿trans-PtCl(NH3)2¿2H2N(CH2)6NH2]2+), BBR3171 ([¿cis-PtCl(NH3)2¿2H2N(CH2)6NH2]2+) and the trinuclear platinum complex, BBR3464 ([¿trans-PtCl(NH3)2¿2 mu-¿trans-Pt(NH3)2(H2N(CH2)6NH2)2¿]4+) was undertaken in wild type and cisplatin-resistant L1210 murine leukemia cell lines. All complexes are potent cytotoxic agents against the wild type cell line. Only BBR3464 shows enhanced activity against the cisplatin-resistant cell line following a brief exposure. This enhanced activity is attributable, in part, to preserved accumulation, which contrasts with diminished accumulation of cisplatin and both dinuclear platinum complexes. The cisplatin-resistant cell line is relatively tolerant of DNA adducts induced by both cisplatin and BBR3464, but BBR3464 is much less affected. All complexes induce DNA interstrand cross-links. Di/trinuclear complex-induced interstrand cross-linking peaks early, suggesting rapid genomic access and interaction. Subsequent decay suggests susceptibility to DNA repair mechanisms. Peak and area-under-the-curve values for interstrand cross-linking among the complexes correlate poorly with cytotoxic effects, especially in the cisplatin-resistant cell line. This suggests that all interstrand cross-linking adducts are not equal in their cytotoxic effect, or other, non-interstrand cross-linking adducts are significant. BBR3464 has been selected for clinical development largely on the basis of results from in vivo activity and toxicity studies. These results show BBR3464 to have unique properties in the context of acquired cisplatin-resistance that enhance its candidacy as a potential anticancer agent.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0162-0134
pubmed:author
pubmed:issnType
Print
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Cellular pharmacology of polynuclear platinum anti-cancer agents.
pubmed:affiliation
Massey Cancer Center, Virginia Commonwealth University, Richmond 23284-2006, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't