Linked Life Data

11550305

Source:http://linkedlifedata.com/resource/pubmed/id/11550305

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-9-11
pubmed:abstractText
Paclitaxel (Taxol), a cytotoxic natural product that disrupts microtubule integrity, is being clinically evaluated for use against gliomas. We examined paclitaxel-induced killing in seven cell lines derived from human malignant astrocytic gliomas and medulloblastomas with the goal of characterizing range of sensitivity, contribution of P-glycoprotein 170-mediated drug efflux to resistance, and cross-resistance with alkylating agents. Exposure to paclitaxel for 8 h or less produced biphasic survival curves for all lines, with 40-75% of cells comprising a subpopulation that was 9-26 times more resistant to paclitaxel than the more sensitive fraction. Increasing exposure to 24 h eliminated the resistant subpopulation, increasing sensitivity 50- to 400-fold. The dose producing one log of kill (LD10) after a 24-h exposure ranged from 4 to 18 nM, comparable to concentrations in the cerebrospinal fluid of brain tumor patients given a 3-h infusion of paclitaxel. Concurrent exposure to paclitaxel and either nimodipine or verapamil, inhibitors of P-glycoprotein activity, did not increase sensitivity, demonstrating that the fivefold range in sensitivity was not due to P-glycoprotein-mediated drug efflux. Importantly, there was no correlation between LD10 for paclitaxel and LD10 for 1,3-bis(2-chloroethyl)-1-nitrosourea, streptozotocin, and temozolomide, indicating no expression of cross-resistance to these different classes of tumoricidal agents. Our results suggest that greater clinical efficacy of paclitaxel against malignant brain tumors may be obtained by infusion for 24 h or longer and support the use of paclitaxel in combination with alkylating agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1522-8517
pubmed:author
pubmed:issnType
Print
pubmed:volume
1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
101-8
pubmed:dateRevised
2008-11-20
pubmed:meshHeading
pubmed-meshheading:11550305-Antineoplastic Agents, Alkylating, pubmed-meshheading:11550305-Antineoplastic Agents, Phytogenic, pubmed-meshheading:11550305-Astrocytoma, pubmed-meshheading:11550305-Brain Neoplasms, pubmed-meshheading:11550305-Calcium Channel Blockers, pubmed-meshheading:11550305-Cell Cycle, pubmed-meshheading:11550305-DNA, Neoplasm, pubmed-meshheading:11550305-Dose-Response Relationship, Drug, pubmed-meshheading:11550305-Drug Resistance, Multiple, pubmed-meshheading:11550305-Drug Resistance, Neoplasm, pubmed-meshheading:11550305-Humans, pubmed-meshheading:11550305-Medulloblastoma, pubmed-meshheading:11550305-Microtubules, pubmed-meshheading:11550305-Neoplasm Proteins, pubmed-meshheading:11550305-P-Glycoprotein, pubmed-meshheading:11550305-Paclitaxel, pubmed-meshheading:11550305-Tumor Cells, Cultured
pubmed:year
1999
pubmed:articleTitle
Characterization of paclitaxel (Taxol) sensitivity in human glioma- and medulloblastoma-derived cell lines.
pubmed:affiliation
Department of Neurological Surgery, University of Washington, Box 356470, 1959 N.E. Pacific St., Seattle, WA 98195-6470, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't