Linked Life Data

11912147

Source:http://linkedlifedata.com/resource/pubmed/id/11912147

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-3-25
pubmed:abstractText
The relative cytotoxicity of a diphtheria toxin (DT) human interleukin 3(IL3) fusion protein (DT(388)IL3) was tested against primitive normal (n = 3)and acute myeloid leukemia (AML) progenitors (n = 7). After 24-h culture with 50 ng/ml DT(388)IL3, the mean percentages of kill of AML colony-forming cells (CFCs), long-term culture-initiating cells (LTC-ICs), and suspension culture-ICs (SC-ICs) were 82% (range, 47-100), 56% (range, 28-91), and 74% (range, 43-87), respectively, with most surviving progenitors being cytogenetically normal. Engraftment of DT(388)IL-3-treated AML cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice followed for 16 weeks was eradicated for two of these samples. In contrast, with normal bone marrow, mean percentages of CFC kill of 49 and 64% were seen with 50 or 250 ng/ml DT(388)IL3, respectively, whereas no significant kills were observed in the LTC-IC and SC-IC assays. The NOD/SCID mouse repopulating cell (RC) frequency in normal BM cells was also not reduced by DT(388)IL3 treatment. In subsequent experiments, NOD/SCID mice that received AML blasts i.v. followed in 24 h by 0.045 microg/g DT(388)IL3 daily i.p. x 5 showed mean percentages of reduction in AML engraftment of 83% (range, 14-100) and 57% (range, 0-98) after 4 and 12 weeks, respectively (n = 6). No evidence of leukemia was detected with two of six AML samples 12 weeks after one 5-day course of DT(388)IL3. Repeating the DT(388)IL3 treatment every 4 weeks enhanced its effectiveness against two additional samples. Thus, DT(388)IL3 kills primitive leukemic progenitors from a proportion of AML patients but shows no significant toxicity against equivalent normal cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1730-6
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11912147-Acute Disease, pubmed-meshheading:11912147-Adult, pubmed-meshheading:11912147-Aged, pubmed-meshheading:11912147-Animals, pubmed-meshheading:11912147-Antineoplastic Agents, pubmed-meshheading:11912147-Diphtheria Toxin, pubmed-meshheading:11912147-Female, pubmed-meshheading:11912147-Humans, pubmed-meshheading:11912147-In Situ Hybridization, Fluorescence, pubmed-meshheading:11912147-Interleukin-3, pubmed-meshheading:11912147-Leukemia, Monocytic, Acute, pubmed-meshheading:11912147-Leukemia, Myeloid, pubmed-meshheading:11912147-Leukemia, Myeloid, Acute, pubmed-meshheading:11912147-Leukemia, Myelomonocytic, Acute, pubmed-meshheading:11912147-Male, pubmed-meshheading:11912147-Mice, pubmed-meshheading:11912147-Mice, Inbred NOD, pubmed-meshheading:11912147-Mice, SCID, pubmed-meshheading:11912147-Middle Aged, pubmed-meshheading:11912147-Myeloid Progenitor Cells, pubmed-meshheading:11912147-Neoplastic Stem Cells, pubmed-meshheading:11912147-Recombinant Fusion Proteins, pubmed-meshheading:11912147-Xenograft Model Antitumor Assays
pubmed:year
2002
pubmed:articleTitle
A diphtheria toxin-interleukin 3 fusion protein is cytotoxic to primitive acute myeloid leukemia progenitors but spares normal progenitors.
pubmed:affiliation
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, V5Z 1L3 Canada.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't