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rdf:type |
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lifeskim:mentions |
umls-concept:C0001675,
umls-concept:C0017638,
umls-concept:C0030705,
umls-concept:C0038952,
umls-concept:C0044602,
umls-concept:C0285761,
umls-concept:C0681842,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1704259,
umls-concept:C1705325,
umls-concept:C1705987,
umls-concept:C1709305,
umls-concept:C1879547
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pubmed:issue |
1
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pubmed:dateCreated |
2010-2-1
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pubmed:abstractText |
Recent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway. Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 5'-promoter region of PTEN using methylation-specific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests. Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077). Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-11008486,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-11504908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-15010827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-15048678,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-15122205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-15455350,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-16969122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-17106834,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-17113461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-18215105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-18372248,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-19013721,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-19100904,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-19100913,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-7977648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19705067-8118823
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/PTEN protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfites,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/hydrogen sulfite
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1573-7373
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pubmed:author |
pubmed-author:BergerMitchel SMS,
pubmed-author:ChangSusan MSM,
pubmed-author:Haas-KoganDaphne ADA,
pubmed-author:LambornKathleen RKR,
pubmed-author:McBrideSean MSM,
pubmed-author:PerezDaniel ADA,
pubmed-author:PolleyMei-YinMY,
pubmed-author:PradosMichael DMD,
pubmed-author:SmithJustin SJS,
pubmed-author:StokoeDavidD,
pubmed-author:VandenbergScott RSR,
pubmed-author:WienckeJohn KJK,
pubmed-author:ZhengShichunS
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pubmed:issnType |
Electronic
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
33-40
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19705067-Adult,
pubmed-meshheading:19705067-Brain Neoplasms,
pubmed-meshheading:19705067-Female,
pubmed-meshheading:19705067-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19705067-Glioma,
pubmed-meshheading:19705067-Humans,
pubmed-meshheading:19705067-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:19705067-Kaplan-Meier Estimate,
pubmed-meshheading:19705067-Male,
pubmed-meshheading:19705067-Middle Aged,
pubmed-meshheading:19705067-PTEN Phosphohydrolase,
pubmed-meshheading:19705067-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19705067-Phosphorylation,
pubmed-meshheading:19705067-Predictive Value of Tests,
pubmed-meshheading:19705067-Protein-Serine-Threonine Kinases,
pubmed-meshheading:19705067-Retrospective Studies,
pubmed-meshheading:19705067-Serine,
pubmed-meshheading:19705067-Signal Transduction,
pubmed-meshheading:19705067-Statistics, Nonparametric,
pubmed-meshheading:19705067-Sulfites,
pubmed-meshheading:19705067-TOR Serine-Threonine Kinases,
pubmed-meshheading:19705067-Young Adult
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pubmed:year |
2010
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pubmed:articleTitle |
Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival.
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pubmed:affiliation |
Radiation Oncology Program, Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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