| pubmed-article:2550374 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C0027651 | lld:lifeskim |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C1257890 | lld:lifeskim |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C0205208 | lld:lifeskim |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C0014939 | lld:lifeskim |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C1512505 | lld:lifeskim |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C0596402 | lld:lifeskim |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C0013203 | lld:lifeskim |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C1511636 | lld:lifeskim |
| pubmed-article:2550374 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:2550374 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:2550374 | pubmed:dateCreated | 1989-10-16 | lld:pubmed |
| pubmed-article:2550374 | pubmed:abstractText | Primary resistance to chemotherapeutic agents is a major problem in the management of advanced cancer. By using oestrogen to modulate the topoisomerase II content of T-47D human breast cancer cells, we show here that cell subpopulations resistant to the topoisomerase-II-interactive drug VPI6 (etoposide) can be identified and quantified using single-cell analytical techniques. Immunohistochemical studies reveal topoisomerase II to be present in approximately 10% of control cells compared with 30% of oestrogen-stimulated cells, and this difference is reflected in the proportions of cells exhibiting VPI6-induced cell-cycle delay. This moderate increase in overall cell sensitivity is accompanied by massive enhancement of clonogenic cell kill, suggesting that oestrogen enhances VPI6 cytotoxicity by recruiting a clonogenic cell subpopulation characterized by increased topoisomerase II content. Flow cytometry confirms that the increase in topoisomerase II is localized to an activated G1-phase cell subset. We conclude that (i) single-cell analysis of cellular topoisomerase II content is predictive of VPI6 chemosensitivity; (ii) the existence of resistant tumour-cell subpopulations does not necessarily indicate the presence of phenotypically divergent subclones; and (iii) rational strategies for eliminating tumour resistance may be based on biological manipulation of specific cytotoxic drug targets. | lld:pubmed |
| pubmed-article:2550374 | pubmed:language | eng | lld:pubmed |
| pubmed-article:2550374 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2550374 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:2550374 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2550374 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2550374 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:2550374 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:2550374 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:2550374 | pubmed:issn | 0020-7136 | lld:pubmed |
| pubmed-article:2550374 | pubmed:author | pubmed-author:BleehenN MNM | lld:pubmed |
| pubmed-article:2550374 | pubmed:author | pubmed-author:SmithP JPJ | lld:pubmed |
| pubmed-article:2550374 | pubmed:author | pubmed-author:WatsonJ VJV | lld:pubmed |
| pubmed-article:2550374 | pubmed:author | pubmed-author:WatersCC | lld:pubmed |
| pubmed-article:2550374 | pubmed:author | pubmed-author:EpsteinR JRJ | lld:pubmed |
| pubmed-article:2550374 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:2550374 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:2550374 | pubmed:volume | 44 | lld:pubmed |
| pubmed-article:2550374 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:2550374 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:2550374 | pubmed:pagination | 501-5 | lld:pubmed |
| pubmed-article:2550374 | pubmed:dateRevised | 2007-11-15 | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:meshHeading | pubmed-meshheading:2550374-... | lld:pubmed |
| pubmed-article:2550374 | pubmed:year | 1989 | lld:pubmed |
| pubmed-article:2550374 | pubmed:articleTitle | Oestrogen potentiates topoisomerase-II-mediated cytotoxicity in an activated subpopulation of human breast cancer cells: implications for cytotoxic drug resistance in solid tumours. | lld:pubmed |
| pubmed-article:2550374 | pubmed:affiliation | MRC Unit, Cambridge. | lld:pubmed |
| pubmed-article:2550374 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:2550374 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:2550374 | lld:pubmed |
