Linked Life Data

9988115

Source:http://linkedlifedata.com/resource/pubmed/id/9988115

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1999-4-29
pubmed:abstractText
Gemcitabine is a novel antimetabolite drug that acts by multiple mechanisms, including inhibition of ribonucleoside diphosphate reductase, of dCMP deaminase and of dCTP incorporation into DNA and RNA. Here, we report that gemcitabine induces cytotoxic and clonogenic death of 12 human malignant glioma cell lines at clinically relevant concentrations around 1 microM. Gemcitabine is thus approximately 100-fold more active than the congener drug, cytarabine. Gemcitabine cytotoxicity of glioma cells does not require wild-type p53 activity: (i) there was no difference in the susceptibility to gemcitabine between cell lines with wild-type p53 and cell lines with mutant or deleted p53; (ii) ectopic expression of a temperature-sensitive p53 protein either at wild-type (32.5 degrees C) or at mutant (38.5 degrees C) conformation had no significant influence on gemcitabine-induced cell death. Gemcitabine cytotoxicity was unaffected by the antioxidants, N-acetylcysteine and phenyl-N-tert-butyl-alpha-phenylnitrone. There was no correlation between the susceptibility to gemcitabine and the endogenous expression of the B cell lymphoma-2 (BCL-2)-family proteins BCL-2, BCL-XL, myeloid cell leukemia-1 (MCL-1), BCL-2-associated X protein (BAX), BCL-2 homologous antagonist/killer (BAK) and BCL-XS. Ectopic expression of BCL-2 moderately attenuated gemcitabine-induced cell death. Similarly, preexposure to the synthetic steroid, dexamethasone, which is commonly used to control cerebral edema in brain tumor patients, reduced gemcitabine cytotoxicity. We conclude that the clinical evaluation of gemcitabine for the adjuvant chemotherapy of malignant glioma is warranted.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
365
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
301-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Gemcitabine cytotoxicity of human malignant glioma cells: modulation by antioxidants, BCL-2 and dexamethasone.
pubmed:affiliation
Department of Neurology, University of Tübingen, School of Medicine, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't