Linked Life Data

1749020

Source:http://linkedlifedata.com/resource/pubmed/id/1749020

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1992-1-22
pubmed:abstractText
Dolastatins 10 and 15, isolated from the shell-less marine mollusk Dolabella auricularia, are potent antineoplastic agents with unknown myelotoxic effects in vivo. The goal of this study was to determine whether the dolastatins inhibit the proliferation of normal hematopoietic progenitor cells. Assays to test inhibition of colony formation and of cell proliferation were performed in vitro with bone marrow cell preparations enriched for progenitor cells and with progenitor cell lines, respectively, using varying drug concentrations and exposure times. Dolastatins 10 and 15 both inhibited human and murine bone marrow cell colony formation in a concentration-dependent manner, with the concentration required for half maximal inhibition ranging from 0.1 to 1 pg/mL for dolastatin 10 and from 10 to 100 pg/mL for dolastatin 15. These concentrations are 25-fold to 100-fold lower than the concentration required for antineoplastic activity. Complete inhibition of human bone marrow cell colony formation was observed at concentrations of 10-100 pg/mL for dolastatin 10 and 1000-10,000 pg/mL for dolastatin 15. Committed progenitor cells and multipotential progenitor cells were similarly inhibited. The magnitude of inhibition of human hematopoietic cell colony formation was dependent on pre-exposure time to dolastatins 10 and 15, with a reversible effect up to 8 hours and with a 24-hour preincubation resulting in maximal (100%) and irreversible inhibition. Dolastatin 10 at a concentration of 10-100 pg/mL limited the proliferation of six human and four murine hematopoietic progenitor cell lines, as measured by tritiated thymidine incorporation, to between 34% and 83% of that occurring in the absence of the drug. These results indicate that the dolastatins are potent inhibitors of normal hematopoietic progenitor cell proliferation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0027-8874
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1672-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Antineoplastic dolastatins: potent inhibitors of hematopoietic progenitor cells.
pubmed:affiliation
Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.