Linked Life Data

8380727

Source:http://linkedlifedata.com/resource/pubmed/id/8380727

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1993-2-23
pubmed:abstractText
One of the differences between acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) is their sensitivity to vincristine. Although vincristine plays an important role in chemotherapeutic regimens for ALL, it does not possess clinically significant activity in AML. Horseradish peroxidase, a heme-centered peroxidase, oxidatively degrades Vinca derivatives and thereby abrogates their cytotoxic activity. This finding suggested that myeloperoxidase (MPO), a heme-centered peroxidase characteristically found in AML and not in ALL, might also degrade vincristine. We first examined the effects of MPO on vincristine in a cell-free system and demonstrated that this enzyme is capable of catalyzing vincristine's oxidative breakdown. We also observed that vincristine is more rapidly degraded in tissue culture by MPO-positive HL-60 cells than by a MPO-negative HL-60 subclone. The degree of MPO activity in these cell lines correlated in a positive manner with their degree of resistance to vincristine's cytotoxic activity. Moreover, the differential resistance to vincristine observed between these cell lines could be increased by increasing the concentration of H2O2 available to the enzyme. These data support the hypothesis that MPO-mediated oxidation of vincristine accounts in part for this drug's lack of activity in AML.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
482-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Myeloperoxidase: an enzyme involved in intrinsic vincristine resistance in human myeloblastic leukemia.
pubmed:affiliation
Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't