Linked Life Data

10100715

Source:http://linkedlifedata.com/resource/pubmed/id/10100715

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-6-22
pubmed:abstractText
High-dose methotrexate is a major component of current protocols for the treatment of osteosarcoma, but some tumors seem to be resistant. Potential mechanisms of resistance include decreased transport through the reduced folate carrier (RFC) and increased expression of dihydrofolate reductase (DHFR). To investigate methotrexate resistance, tumors were obtained from 42 patients with high-grade osteosarcoma. RFC and DHFR mRNA expression were studied by semiquantitative reverse transcription-PCR. The RFC and DHFR genes were studied for deletions and amplification by Southern blot. Thirteen of 20 (65%) osteosarcoma samples were found to have decreased RFC expression at the time of initial biopsy. At definitive surgery and relapse, 10 of 22 (45%) were found to have decreased RFC expression. Seventeen of 26 (65%) samples with a poor response to chemotherapy had decreased RFC expression, whereas 5 of 14 (36%) samples with a good response had a decrease (P = 0.03). None of the samples had an RFC gene deletion. Two of 20 samples (10%) showed increased DHFR expression at initial biopsy. The frequency of increased DHFR expression was significantly higher in metastatic or recurrent tumors (62%, P = 0.014). None of the samples showed evidence of DHFR gene amplification. The high frequency of decreased RFC expression in the biopsy material suggests that impaired transport of methotrexate is a common mechanism of intrinsic resistance in osteosarcoma. Increased DHFR expression in the pulmonary metastases may be a mechanism of acquired methotrexate resistance or a difference between primary and metastatic lesions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
621-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10100715-Adolescent, pubmed-meshheading:10100715-Adult, pubmed-meshheading:10100715-Aged, pubmed-meshheading:10100715-Antimetabolites, Antineoplastic, pubmed-meshheading:10100715-Biological Transport, pubmed-meshheading:10100715-Blotting, Southern, pubmed-meshheading:10100715-Carrier Proteins, pubmed-meshheading:10100715-Child, pubmed-meshheading:10100715-Drug Resistance, Neoplasm, pubmed-meshheading:10100715-Female, pubmed-meshheading:10100715-Gene Amplification, pubmed-meshheading:10100715-Gene Deletion, pubmed-meshheading:10100715-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10100715-Humans, pubmed-meshheading:10100715-Male, pubmed-meshheading:10100715-Membrane Proteins, pubmed-meshheading:10100715-Membrane Transport Proteins, pubmed-meshheading:10100715-Methotrexate, pubmed-meshheading:10100715-Middle Aged, pubmed-meshheading:10100715-Osteosarcoma, pubmed-meshheading:10100715-RNA, Messenger, pubmed-meshheading:10100715-Reduced Folate Carrier Protein, pubmed-meshheading:10100715-Tetrahydrofolate Dehydrogenase
pubmed:year
1999
pubmed:articleTitle
Mechanisms of methotrexate resistance in osteosarcoma.
pubmed:affiliation
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't