| pubmed-article:16988940 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16988940 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:16988940 | lifeskim:mentions | umls-concept:C0815000 | lld:lifeskim |
| pubmed-article:16988940 | lifeskim:mentions | umls-concept:C0140079 | lld:lifeskim |
| pubmed-article:16988940 | lifeskim:mentions | umls-concept:C0164786 | lld:lifeskim |
| pubmed-article:16988940 | lifeskim:mentions | umls-concept:C0312418 | lld:lifeskim |
| pubmed-article:16988940 | lifeskim:mentions | umls-concept:C1514761 | lld:lifeskim |
| pubmed-article:16988940 | lifeskim:mentions | umls-concept:C0036667 | lld:lifeskim |
| pubmed-article:16988940 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:16988940 | pubmed:dateCreated | 2006-10-26 | lld:pubmed |
| pubmed-article:16988940 | pubmed:abstractText | The potential of the novel insulin-like growth factor receptor (IGF-IR) inhibitor NVP-AEW541 as an antiproliferative agent in human neuroblastoma was investigated. Proliferation of a panel of neuroblastoma cell lines was inhibited by NVP-AEW541 with IC(50) values ranging from 0.15 to 5 microM. Experiments using an IGF-IR neutralizing antibody confirmed that the IGF-IR was essential to support growth of neuroblastoma cell lines. The expression levels of the IGF-IR in individual neuroblastoma cell lines did not correlate with the sensitivities to NVP-AEW541, while coexpression of the IGF-IR and the insulin receptor (IR) correlated with lower sensitivity to the inhibitor in some cell lines. Intriguingly, high levels of activation of Akt/protein kinase B (PKB) and phosphorylation of the ribosomal S6 protein were observed in neuroblastoma cell lines with decreased sensitivities to NVP-AEW541. Inhibition of Akt/PKB activity restored the sensitivity of neuroblastoma cells to the IGF-IR inhibitor. Transfection of neuroblastoma cells with activated Akt or ribosomal protein S6 kinase (S6K) decreased the sensitivity of the cells to NVP-AEW541. IGF-I-stimulated proliferation of neuroblastoma cell lines was completely blocked by NVP-AEW541, or by a combination of an inhibitor of phosphoinositide 3-kinase and rapamycin. In addition to its antiproliferative effects, NVP-AEW541 sensitized neuroblastoma cells to cisplatin-induced apoptosis. Together, our data demonstrate that NVP-AEW541 in combination with Akt/PKB inhibitors or chemotherapeutic agents may represent a novel approach to target human neuroblastoma cell proliferation. | lld:pubmed |
| pubmed-article:16988940 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16988940 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16988940 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16988940 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16988940 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16988940 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16988940 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16988940 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16988940 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:16988940 | pubmed:issn | 0020-7136 | lld:pubmed |
| pubmed-article:16988940 | pubmed:author | pubmed-author:ArcaroAlexand... | lld:pubmed |
| pubmed-article:16988940 | pubmed:author | pubmed-author:GrotzerMichae... | lld:pubmed |
| pubmed-article:16988940 | pubmed:author | pubmed-author:ShalabyTarekT | lld:pubmed |
| pubmed-article:16988940 | pubmed:author | pubmed-author:BollerDaniell... | lld:pubmed |
| pubmed-article:16988940 | pubmed:author | pubmed-author:GuerreiroAna... | lld:pubmed |
| pubmed-article:16988940 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16988940 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:16988940 | pubmed:volume | 119 | lld:pubmed |
| pubmed-article:16988940 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16988940 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16988940 | pubmed:pagination | 2527-38 | lld:pubmed |
| pubmed-article:16988940 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
| pubmed-article:16988940 | pubmed:meshHeading | pubmed-meshheading:16988940... | lld:pubmed |
| pubmed-article:16988940 | pubmed:meshHeading | pubmed-meshheading:16988940... | lld:pubmed |
| pubmed-article:16988940 | pubmed:meshHeading | pubmed-meshheading:16988940... | lld:pubmed |
| pubmed-article:16988940 | pubmed:meshHeading | pubmed-meshheading:16988940... | lld:pubmed |
| pubmed-article:16988940 | pubmed:meshHeading | pubmed-meshheading:16988940... | lld:pubmed |
| pubmed-article:16988940 | pubmed:meshHeading | pubmed-meshheading:16988940... | lld:pubmed |
| pubmed-article:16988940 | pubmed:meshHeading | pubmed-meshheading:16988940... | lld:pubmed |
| pubmed-article:16988940 | pubmed:meshHeading | pubmed-meshheading:16988940... | lld:pubmed |
| pubmed-article:16988940 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16988940 | pubmed:articleTitle | Protein kinase B modulates the sensitivity of human neuroblastoma cells to insulin-like growth factor receptor inhibition. | lld:pubmed |
| pubmed-article:16988940 | pubmed:affiliation | Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, CH-8032 Zurich, Switzerland. | lld:pubmed |
| pubmed-article:16988940 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16988940 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16988940 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:16988940 | lld:pubmed |
