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Cancer Res ; 63(8): 1776-9, 2003 Apr 15.
Article in English | MEDLINE | ID: mdl-12702562

ABSTRACT

Uptake of platinum-based anticancer compounds into individual human ovarian andenocarcinoma cells was measured using an X-ray microprobe. The uptake of cisplatin, a platinum-based compound, in drug-resistant cells is decreased by approximately 50% after 24 h, compared with the uptake of the drug in nonresistant cells over the same time period. The Pt103 derivative of the drug, in contrast, showed an increased uptake by an order of magnitude in resistant cells over the same time period. Increased uptake appears to allow Pt103 to overcome the resistance mechanism developed by the cell. This work additionally shows that the X-ray microprobe is able to directly quantify Pt drug uptake on a subcellular level and can measure the mass of Pt down to a detectable limit of 20 attograms of Pt (2 x 10(-17) grams or 6 x 10(4) Pt atoms) in 1 s. Such exquisite elemental sensitivity combined with high spatial resolution paves the way for quantitative submicron three-dimensional mapping of elemental distributions within individual cells.


Subject(s)
Adenocarcinoma/metabolism , Antineoplastic Agents/pharmacokinetics , Cisplatin/pharmacokinetics , Electron Probe Microanalysis/methods , Ovarian Neoplasms/metabolism , Adenocarcinoma/drug therapy , Antineoplastic Agents/analysis , Antineoplastic Agents/pharmacology , Cisplatin/analysis , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Female , Humans , Ovarian Neoplasms/chemistry , Ovarian Neoplasms/drug therapy , Tumor Cells, Cultured
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