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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2009-9-18
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pubmed:abstractText |
Cisplatin is one of the most widely used anticancer agents for the treatment of solid tumors. The clinical use of cisplatin is associated with dose-limiting nephrotoxicity, which occurs in one-third of patients despite intensive prophylactic measures. Organic cation transporter 2 (OCT2) has been implicated in the cellular uptake of cisplatin, but its role in cisplatin-induced nephrotoxicity remains unknown. In mice, deletion of Oct1 and Oct2 resulted in significantly impaired urinary excretion of cisplatin without an apparent influence on plasma levels. Furthermore, the Oct1/Oct2-deficient mice were protected from severe cisplatin-induced renal tubular damage. Subsequently, we found that a nonsynonymous single-nucleotide polymorphism (SNP) in the OCT2 gene SLC22A2 (rs316019) was associated with reduced cisplatin-induced nephrotoxicity in patients. Collectively, these results indicate the critical importance of OCT2 in the renal handling and related renal toxicity of cisplatin and provide a rationale for the development of new targeted approaches to mitigate this debilitating side effect.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-10458260,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-11463829,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-11533095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-11561104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-12011098,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-13680535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-14560032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-15200426,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-16307453,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-16314463,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-16574999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-16951202,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-17473959,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-17686950,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-17700201,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-18272962,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-18401339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-18559608,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-19088030,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-19144690,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-3583421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-498147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-6685336,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-8398709,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-9000550,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19625999-9225947
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1532-6535
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
86
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
396-402
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pubmed:dateRevised |
2011-2-24
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pubmed:meshHeading |
pubmed-meshheading:19625999-Animals,
pubmed-meshheading:19625999-Antineoplastic Agents,
pubmed-meshheading:19625999-Cisplatin,
pubmed-meshheading:19625999-Humans,
pubmed-meshheading:19625999-Kidney Diseases,
pubmed-meshheading:19625999-Male,
pubmed-meshheading:19625999-Mice,
pubmed-meshheading:19625999-Mice, Knockout,
pubmed-meshheading:19625999-Organic Cation Transport Proteins,
pubmed-meshheading:19625999-Organic Cation Transporter 1,
pubmed-meshheading:19625999-Polymerase Chain Reaction,
pubmed-meshheading:19625999-Polymorphism, Single Nucleotide
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pubmed:year |
2009
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pubmed:articleTitle |
Contribution of organic cation transporter 2 (OCT2) to cisplatin-induced nephrotoxicity.
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pubmed:affiliation |
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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