|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0018270,
umls-concept:C0035412,
umls-concept:C0037083,
umls-concept:C0078058,
umls-concept:C0208973,
umls-concept:C0441712,
umls-concept:C0522537,
umls-concept:C0596087,
umls-concept:C0599894,
umls-concept:C0796512,
umls-concept:C0965644,
umls-concept:C1256770,
umls-concept:C1333897,
umls-concept:C1517892,
umls-concept:C1704666,
umls-concept:C1704838,
umls-concept:C1710082
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2006-6-22
|
|
pubmed:abstractText |
Angiogenesis is one of the critical steps in tumor growth and metastasis. The goal of this study was to evaluate whether the antitumor activity of CCI-779 is related to antiangiogenic effects in vivo in tumors of mice bearing human rhabdomyosarcoma (RMS) xenografts. We now demonstrate that CCI-779 rapidly inhibits mTOR activity, as indicated by S6 reduction and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation in two xenograft models of RMS within 24 hours of treatment. Treatment with a single 20-mg/kg dose of CCI-779 suppressed S6 phosphorylation for more than 72 hours and 4E-BP1 phosphorylation for more than 96 hours. Based on these data, an intermittent treatment schedule (every 3 days for 30 days) was chosen and displayed a significant suppression of both tumor growth and mTOR signaling. Western blot analysis and immunohistochemical studies demonstrated that the antitumor activity of CCI-779 was associated with antiangiogenesis, as indicated by impaired levels of hypoxia-inducible factor-1alpha (Hif-1alpha) and vascular endothelial growth factor (VEGF) protein expression and by decreased microvessel density in Rh30 and RD xenografts. Together, these data suggest that CCI-779 inhibits human RMS xenograft growth by an antiangiogenic mechanism associated with the targeting of mTOR/Hif-1alpha/VEGF signaling.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-10337369,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-10582706,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-10688871,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-10888419,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-10914727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11245461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11348591,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11410517,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11426655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11479208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11504907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11504908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11821896,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-11981271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12039858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12142733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12172553,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12192598,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12360276,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12516034,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12766775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12766776,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-12878853,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-13130303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-1377606,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-14526383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-14603261,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-14607085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-14729330,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-14990647,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-15122205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-15136596,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-15501979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-15781656,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-7525076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-7566123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-7794794,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-7884423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-7987636,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-8309312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-8752206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-8756616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-8869806,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-9223322,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-9544222,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16790088-9816116
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiogenesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/temsirolimus
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1476-5586
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
8
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
394-401
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
|
