Source:http://linkedlifedata.com/resource/pubmed/id/11146161
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2001-1-10
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| pubmed:abstractText |
In this study, the utility of DT388-granulocyte-macrophage colony-stimulating factor (GM-CSF) for the ex vivo purging and direct administration to patients with acute myeloid leukemia (AML) is tested using clonogenic assays, long-term cultures (LTC), and NOD/SCID mice as assays for leukemic progenitors. We compare the ability of 24-hour exposure to 0.3 microg/mL (4 nM) DT388-GM-CSF to kill AML colony forming cells (CFC) and the more primitive AML progenitors detected after 6 weeks in stromal cocultures (AML LTC-initiating cells or AML LTC-IC) and after 8 weeks in NOD/SCID mice.AML samples (n = 10), expressing a mean of 35 to 1466 GM-CSF receptors/blast, showed mean (range) percent kills of AML CFC and LTC-IC of 61 (17-98) and 46 (0-94) respectively with a direct correlation (r = 0.69) between the % kills detected in the in vitro assays. Among 5 evaluable samples the percent reduction in AML cell engraftment in NOD/SCID marrow following ex vivo DT388-GM-CSF treatment varied from 38% to 100%. 40% to 56% of normal bone marrow CFC and 31% to 48% of normal LTC-IC survived the same ex vivo treatment (n = 3). In subsequent experiments, NOD/SCID mice received AML blast cell injections intravenously followed in 24 hours by 1.5 microg DT388-GM-CSF daily intraperitoneally for 5 days. A reduction of marrow blast cells was seen with 7 of 9 samples tested 4 to 12 weeks post one course of toxin. Repeating the 5-day course of toxin 2 or 3 times at 4-week intervals did not improve the response, while delaying administration until 4 to 8 weeks post AML cell injection reduced the toxin's effectiveness (n = 5).This fusion toxin may prove useful for in vitro purging of stem cell harvests from selected AML patients and for direct administration to such patients.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Diphtheria Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0301-472X
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
28
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1390-400
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| pubmed:dateRevised |
2009-11-3
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| pubmed:meshHeading |
pubmed-meshheading:11146161-Animals,
pubmed-meshheading:11146161-Bone Marrow,
pubmed-meshheading:11146161-Bone Marrow Purging,
pubmed-meshheading:11146161-Cell Death,
pubmed-meshheading:11146161-Cytogenetic Analysis,
pubmed-meshheading:11146161-Diphtheria Toxin,
pubmed-meshheading:11146161-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:11146161-Hematopoietic Stem Cells,
pubmed-meshheading:11146161-Humans,
pubmed-meshheading:11146161-In Situ Hybridization, Fluorescence,
pubmed-meshheading:11146161-Leukemia, Myeloid, Acute,
pubmed-meshheading:11146161-Mice,
pubmed-meshheading:11146161-Mice, Inbred NOD,
pubmed-meshheading:11146161-Mice, SCID,
pubmed-meshheading:11146161-Neoplasm Transplantation,
pubmed-meshheading:11146161-Receptors, Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:11146161-Recombinant Fusion Proteins,
pubmed-meshheading:11146161-Spleen,
pubmed-meshheading:11146161-Tumor Cells, Cultured
|
| pubmed:year |
2000
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| pubmed:articleTitle |
Variable cytotoxicity of diphtheria toxin 388-granulocyte-macrophage colony-stimulating factor fusion protein for acute myelogenous leukemia stem cells.
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| pubmed:affiliation |
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|