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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1997-12-9
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pubmed:abstractText |
The potential to selectively eliminate acute myeloid leukaemia (AML) cells with the GM-CSF-diphtheria toxin fusion protein (DT-GM-CSF) was studied under conditions of autonomous proliferation in vitro with no growth factors (GFs) added and after growth stimulation with a mixture of human (hu)G-CSF, huIL-3 and huSCF. DNA synthesis was maximally inhibited after 48 h exposure to DT-GM-CSF. Cell viability and AML colony forming ability in vitro were reduced. 18/22 samples were found to be sensitive to DT-GM-CSF, with 50% inhibition of DNA synthesis (ID50) at concentrations ranging from 0.1 to 16 ng/ml, and four samples were minimally or not sensitive to DT-GM-CSF (ID50 > or = 99 ng/ml). From the 15 samples which showed autonomous proliferation, 13 were sensitive to inhibition of proliferation by DT-GM-CSF. The level of GM-CSF receptor (GM-CSFR) expression was determined by flow cytometry after labelling with specific antibodies for the alpha and beta subunits. Although the toxicity to DT-GM-CSF was specifically mediated by the GM-CSFR, no correlation was found between the level of expression of the GM-CSFR alpha or beta subunit and the sensitivity for DT-GM-CSF. These in vitro studies show that the DT-GM-CSF fusion protein can be used for specifically targeting and eliminating leukaemic cells in the majority of AML cases.
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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 |
Sep
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pubmed:issn |
0007-1048
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:volume |
98
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
952-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9326195-Acute Disease,
pubmed-meshheading:9326195-Cell Division,
pubmed-meshheading:9326195-Diphtheria Toxin,
pubmed-meshheading:9326195-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:9326195-Humans,
pubmed-meshheading:9326195-Leukemia, Myeloid,
pubmed-meshheading:9326195-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Sensitivity of human acute myeloid leukaemia to diphtheria toxin-GM-CSF fusion protein.
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pubmed:affiliation |
Institute of Haematology, Erasmus University, Rotterdam, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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