Linked Life Data

20104520

Source:http://linkedlifedata.com/resource/pubmed/id/20104520

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-8-30
pubmed:abstractText
Insulin-like growth factor-1 receptor (IGF-1R) and human epidermal growth factor receptor-2 (HER2) receptor expression has been found to be a key regulator of tumorigenesis. The purpose of our study was to establish the prognostic significance of IGF-1R in esophageal cancer and to determine the effect of IGF-1R and HER2 targeting with alpha-IR3 and Herceptin antibodies on the proliferation of esophageal cancer cells in vitro. IGF-1R expression and clinicopathological correlations were analyzed with a tissue microarray containing 234 esophageal cancer specimens (133 adenocarcinomas and 101 squamous cell carcinomas). Proliferation changes associated with Herceptin and alpha-IR3 blockage were evaluated with the unique human esophageal cancer cell lines Pt1590 and LN1590. IGF-1R and HER2 expression levels, activation and phosphorylation status of downstream signaling proteins involved in the activation pathways were analyzed by Western blotting. IGF-1R overexpression was detected in 121 (52%) of the 234 esophageal tumors examined. In the subgroup of 87 HER2-positive tumors, 93.1% showed concordant overexpression for IGF-1R. IGF-1R was identified as a variable associated with reduced overall survival for adenocarcinoma (p = 0.05), but not for squamous cell carcinoma. The combination of Herceptin and alpha-IR3 was more effective in inhibiting in vitro proliferation than treatment with either agent alone (p < 0.01). This was associated with a decrease in HER2 and IGF-1R protein levels and suppression of Akt- and MAP kinase phosphorylation. IGF-1R expression can be used as a novel prognostic marker for adenocarcinomas of the esophagus. Cotreatment with IGF-1R and HER2 antibodies might become a valuable and effective treatment option in esophageal adenocarcinoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1097-0215
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
127
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1931-40
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:20104520-Adenocarcinoma, pubmed-meshheading:20104520-Antibodies, Monoclonal, pubmed-meshheading:20104520-Antibodies, Monoclonal, Humanized, pubmed-meshheading:20104520-Blotting, Western, pubmed-meshheading:20104520-Carcinoma, Squamous Cell, pubmed-meshheading:20104520-Cell Proliferation, pubmed-meshheading:20104520-Esophageal Neoplasms, pubmed-meshheading:20104520-Esophagus, pubmed-meshheading:20104520-Humans, pubmed-meshheading:20104520-Immunoenzyme Techniques, pubmed-meshheading:20104520-Neoplasm Proteins, pubmed-meshheading:20104520-Phosphorylation, pubmed-meshheading:20104520-Prognosis, pubmed-meshheading:20104520-RNA, Messenger, pubmed-meshheading:20104520-Receptor, IGF Type 1, pubmed-meshheading:20104520-Receptor, erbB-2, pubmed-meshheading:20104520-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20104520-Tissue Array Analysis, pubmed-meshheading:20104520-Tumor Cells, Cultured, pubmed-meshheading:20104520-Tumor Markers, Biological
pubmed:year
2010
pubmed:articleTitle
Insulin-like growth factor-1 receptor as a novel prognostic marker and its implication as a cotarget in the treatment of human adenocarcinoma of the esophagus.
pubmed:affiliation
Department of General, Visceral- and Thoracic Surgery, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't