Linked Life Data

17431120

Source:http://linkedlifedata.com/resource/pubmed/id/17431120

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-4-13
pubmed:abstractText
Head and neck squamous cell carcinoma (HNSCC) is characterized by epidermal growth factor receptor (EGFR) overexpression, where EGFR levels correlate with survival. To date, EGFR targeting has shown limited antitumor effects in head and neck cancer when administrated as monotherapy. We previously identified a gastrin-releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) aurocrine regulatory pathway in HNSCC, where GRP stimulates Src-dependent cleavage of EGFR proligands with subsequent EGFR phosphorylation and mitogen-activated protein kinase (MAPK) activation. To determine whether GRPR targeting can enhance the antitumor efficacy of EGFR inhibition, we investigated the effects of a GRPR antagonist (PD176252) in conjunction with an EGFR tyrosine kinase inhibitor (erlotinib). Combined blockade of GRPR and EGFR pathways significantly inhibited HNSCC, but not immortalized mucosal epithelial cell, proliferation, invasion, and colony formation. In addition, the percentage of apoptotic cells increased upon combined inhibition. The enhanced antitumor efficacy was accompanied by increased expression of cleaved poly(ADP-ribose) polymerase (PARP) and decreased phospho-EGFR, phospho-MAPK, and proliferating cell nuclear antigen (PCNA). Using reverse-phase protein microarray (RPPA), we further detected decreased expression of phospho-c-Jun, phospho-p70S6K, and phospho-p38 with combined targeting. Cumulatively, these results suggest that GRPR targeting can enhance the antitumor effects of EGFR inhibitors in head and neck cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1535-7163
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1414-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17431120-Antineoplastic Agents, pubmed-meshheading:17431120-Apoptosis, pubmed-meshheading:17431120-Cell Line, Tumor, pubmed-meshheading:17431120-Cell Proliferation, pubmed-meshheading:17431120-Dose-Response Relationship, Drug, pubmed-meshheading:17431120-Drug Screening Assays, Antitumor, pubmed-meshheading:17431120-Drug Synergism, pubmed-meshheading:17431120-G1 Phase, pubmed-meshheading:17431120-Head and Neck Neoplasms, pubmed-meshheading:17431120-Humans, pubmed-meshheading:17431120-Indoles, pubmed-meshheading:17431120-Neoplasm Invasiveness, pubmed-meshheading:17431120-Quinazolines, pubmed-meshheading:17431120-Receptor, Epidermal Growth Factor, pubmed-meshheading:17431120-Receptors, Bombesin, pubmed-meshheading:17431120-Signal Transduction, pubmed-meshheading:17431120-Tumor Markers, Biological, pubmed-meshheading:17431120-Tumor Stem Cell Assay
pubmed:year
2007
pubmed:articleTitle
Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal growth factor receptor targeting in head and neck cancer.
pubmed:affiliation
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural