Linked Life Data

9689134

Source:http://linkedlifedata.com/resource/pubmed/id/9689134

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1998-9-8
pubmed:abstractText
A new class of 16-membered macrolides, the epothilones (Epos), has been synthesized and evaluated for antitumor potential in vitro and in vivo. Recent studies in these and other laboratories showed that epothilones and paclitaxel (paclitaxel) share similar mechanisms of action in stabilizing microtubule arrays as indicated by binding-displacement studies, substitution for paclitaxel in paclitaxel-dependent cell growth, and electron microscopic examinations. The present study examined cell growth-inhibitory effects in two rodent and three human tumor cell lines and their drug-resistant sublines. Although paclitaxel showed as much as 1, 970-fold cross-resistance to the sublines resistant to paclitaxel, adriamycin, vinblastine, or actinomycin D, most epothilones exhibit little or no cross-resistance. In multidrug-resistant CCRF-CEM/VBL100 cells, IC50 values for EpoA (1), EpoB (2), desoxyEpoA (3) (dEpoA), desoxyEpoB (4) (dEpoB), and paclitaxel were 0.02, 0.002, 0.012, 0.017, and 4.14 microM, respectively. In vivo studies, using i.p. administration, indicated that the parent, EpoB, was highly toxic to mice and showed little therapeutic effect when compared with a lead compound, dEpoB. More significantly, dEpoB (25-40 mg/kg, Q2Dx5, i.p.) showed far superior therapeutic effects and lower toxicity than paclitaxel, doxorubicin, camptothecin, or vinblastine (at maximal tolerated doses) in parallel experiments. For mammary adenocarcinoma xenografts resistant to adriamycin, MCF-7/Adr, superior therapeutic effects were obtained with dEpoB compared with paclitaxel when i.p. regimens were used. For ovarian adenocarcinoma xenografts, SK-OV-3, dEpoB (i.p.), and paclitaxel (i. v.) gave similar therapeutic effects. In nude mice bearing a human mammary carcinoma xenograft (MX-1), marked tumor regression and cures were obtained with dEpoB.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-1358264, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-2359136, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-2790792, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-3409223, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-3469013, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-423966, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-6382953, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-7757983, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-8102012, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-8698639, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-8984658, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-9153390, http://linkedlifedata.com/resource/pubmed/commentcorrection/9689134-9269992
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9642-7
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Desoxyepothilone B: an efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone B.
pubmed:affiliation
Molecular Pharmacology and Therapeutics Program, 1275 York Avenue, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.