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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1998-3-31
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pubmed:abstractText |
Buthionine sulphoximine (BSO) selectively inhibits glutathione (GSH) synthesis and may enhance the antineuroblastoma activity of melphalan (L-PAM). We determined the cytotoxicity of BSO (dose range 0-1000 microM) alone and in combination with L-PAM (dose range 0-0 microM) in a panel of 18 human neuroblastoma cell lines. BSO alone was highly cytotoxic with 16/18 neuroblastoma cell lines having IC90 values (range 2.1- > 1000 microM) below the clinically achievable steady-state plasma level of 500 microM BSO. Maximal cell killing correlated with GSH levels decreased to less than 10% baseline, and was partially reversed by the addition of exogenous anti-oxidants (GSH, vitamin E and ascorbate). Fluorocytometric analysis of DNA fragments by the Tunnel method detected 92% of a BSO sensitive cell line in apoptosis after a 48 h exposure to 500 microM BSO. The combination of L-PAM and BSO synergistically enhanced the cell killing of L-PAM alone by > 1-3 logs (combination index < 1). We conclude that BSO has significant single-agent cytotoxicity against neuroblastoma and enhances cell killing when combined with L-PAM.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Buthionine Sulfoximine,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Melphalan
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0959-8049
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2016-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9516845-Antineoplastic Agents,
pubmed-meshheading:9516845-Antioxidants,
pubmed-meshheading:9516845-Apoptosis,
pubmed-meshheading:9516845-Buthionine Sulfoximine,
pubmed-meshheading:9516845-Drug Screening Assays, Antitumor,
pubmed-meshheading:9516845-Drug Synergism,
pubmed-meshheading:9516845-Glutathione,
pubmed-meshheading:9516845-Humans,
pubmed-meshheading:9516845-Melphalan,
pubmed-meshheading:9516845-Neuroblastoma,
pubmed-meshheading:9516845-Tumor Cells, Cultured
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pubmed:year |
1997
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pubmed:articleTitle |
Buthionine sulphoximine alone and in combination with melphalan (L-PAM) is highly cytotoxic for human neuroblastoma cell lines.
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pubmed:affiliation |
Division of Hematology-Oncology, Childrens Hospital Los Angles, California 90027, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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