Linked Life Data

20591650

Source:http://linkedlifedata.com/resource/pubmed/id/20591650

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2010-11-29
pubmed:abstractText
Insulin-like growth factor 1 receptor (IGF-1R) is overexpressed in many tumours and contributes to tumourigenicity, cell proliferation, metastasis and resistance, thus representing a promising therapeutic target. The human IGF-1R antagonistic monoclonal antibody EM164 (murine AVE1642) has shown activity in adult cancers and is being evaluated in patients with advanced malignancies. We investigated the EM164 for its therapeutic potential against childhood neuroblastoma. EM164 at 0.07, 0.7 and 7 ?g/mL exhibited anti-proliferative activity against all nine cell lines tested in (3)H-thymidine incorporation assay in vitro. Cell proliferation after EM164 exposure ranged between 24% and 80% compared to controls. Sensitivity was independent from culture serum conditions, intensity of IGF-1R expression and IGF-II secretion, although associated with inhibition of AKT activation. In vivo, EM164 administered intravenously at 40 mg/kg twice weekly for 4 weeks yielded significant tumour growth delays (TGD) of 13.4d in advanced stage IGR-N91 and 12.9 d in SK-N-AS tumours compared to controls (p = 0.02 and p = 0.0059, respectively). Simultaneous treatment of EM164 0.7 ?g/mL and temozolomide resulted in enhanced activity in vitro. In vivo, treatment with temozolomide at the maximum tolerated dose (100mg/kg/d for 5 consecutive days) and EM164 yielded a significantly greater TGD of 29.1d (p<0.01) and two complete tumour regressions (CR) compared to 18.1d (p = ns) and one CR for EM164 alone and 16.1d (p = ns) for temozolomide alone. Our results demonstrate the potential of the anti-IGF-1R antibody alone and in combination with alkylating agents and support the therapeutic development of the AVE1642 for aggressive neuroblastoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1879-0852
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3251-62
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20591650-Animals, pubmed-meshheading:20591650-Antibodies, Monoclonal, pubmed-meshheading:20591650-Antibodies, Monoclonal, Humanized, pubmed-meshheading:20591650-Antineoplastic Agents, Alkylating, pubmed-meshheading:20591650-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:20591650-Cell Line, Tumor, pubmed-meshheading:20591650-Cell Proliferation, pubmed-meshheading:20591650-Dacarbazine, pubmed-meshheading:20591650-Female, pubmed-meshheading:20591650-Humans, pubmed-meshheading:20591650-Mice, pubmed-meshheading:20591650-Mice, Nude, pubmed-meshheading:20591650-Mitogen-Activated Protein Kinases, pubmed-meshheading:20591650-Neuroblastoma, pubmed-meshheading:20591650-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20591650-Receptor, IGF Type 1, pubmed-meshheading:20591650-Xenograft Model Antitumor Assays
pubmed:year
2010
pubmed:articleTitle
Anti-insulin-like growth factor 1 receptor antibody EM164 (murine AVE1642) exhibits anti-tumour activity alone and in combination with temozolomide against neuroblastoma.
pubmed:affiliation
UPRES EA 3535, Pharmacology and New Treatments of Cancer, Université Paris-Sud XI, Institut Gustave Roussy, 94805 Villejuif, France. geoerger@igr.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't