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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1998-7-14
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pubmed:abstractText |
Topographical image measures have been used to characterize the subnuclear distribution of DNA topoisomerase I in human tumor cell lines. This topographical analysis allowed a mathematical description of staining patterns to be produced that did not depend on subjective grading. The redistribution of topoisomerase I in response to increasing concentrations of topotecan was then monitored by this method. The cell lines were stained for topoisomerase I by indirect immunofluorescence methods. Digital imaging microscopy and image analysis were used to extract the nucleus from each cell, and nine parameters describing the topography of the distribution of topoisomerase I within the nucleus were computed for each. Use of multivariate analysis of variance enabled this nine-parameter set to be reduced to a single canonical variable, representing 60-90% of the observed internuclear variance. Plotting the canonical variable vs drug concentration resulted in dose-response curves that could be fitted well by a simple Emax model. From these curve fits, EC50 and Emax values for drug-induced redistribution of topoisomerase I were determined. Our results indicate that neither the maximum extent of topoisomerase I redistribution (Emax) nor the EC50 for drug-induced redistribution correlated well with the growth inhibition produced by continuous exposure to topotecan in these cell lines. However, the EC50 determined for the 1-h high-concentration exposure did reflect the growth inhibition produced in cells exposed to the drug for 1 h. The methodology described may also be generally applied to any antigen of interest.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0014-4827
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1998 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
241
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
332-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9637775-Biological Transport,
pubmed-meshheading:9637775-Cell Nucleus,
pubmed-meshheading:9637775-DNA Topoisomerases, Type I,
pubmed-meshheading:9637775-Humans,
pubmed-meshheading:9637775-Image Processing, Computer-Assisted,
pubmed-meshheading:9637775-Models, Theoretical,
pubmed-meshheading:9637775-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
Characterization of topotecan-mediated redistribution of DNA topoisomerase I by digital imaging microscopy.
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pubmed:affiliation |
Cancer Therapy and Research Center, Institute for Drug Development, 8122 Datapoint, Suite 700, San Antonio, Texas, 78229-3264, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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