Linked Life Data

15202007

Source:http://linkedlifedata.com/resource/pubmed/id/15202007

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-17
pubmed:abstractText
Pancreatic cancer is a devastating malignancy, characterized by low responsiveness to conventional chemotherapies. Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has shown clinical activity against EGFR-expressing tumors. Since pancreatic cancers frequently overexpress EGFR (ErbB-1) and its ligands, our aim was to investigate the potential role of gefitinib in this disease. The GI50 of gefitinib as well as the effects of gefitinib on growth factor actions in pancreatic cancer cell lines were analyzed using MTT assays. FACS analysis using Annexin and propidium iodide (PI) staining were performed to study cell cycle, apoptosis and cell death. Western blot analysis was carried out to investigate expression levels of the 4 members of the ErbB family of receptors in pancreatic cancer cell lines, as well as MAP kinase and EGFR phosphorylation. Soft agar assays were used to measure colony formations. Invasiveness of cancer cells was analyzed using Matrigel-coated filters. gefitinib inhibited cell proliferation of pancreatic cancer cell lines with GI50 concentrations ranging from 2.5 to over 10 micro M. Gefitinib completely inhibited EGF-induced cell proliferation, but did not significantly influence insulin-like growth factor (IGF)-induced mitogenesis. Gefitinib also completely abolished EGF-induced phosphorylation of EGFR and MAP kinase. Furthermore, gefitinib inhibited basal and EGF-induced anchorage-independent cell growth and invasion. Our data demonstrate that gefitinib inhibits pancreatic cancer cell growth through EGFR-dependent pathways. Gefitinib also inhibits anchorage-independent growth and invasiveness, suggesting that gefitinib may offer a new approach for the treatment of pancreatic cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1019-6439
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
203-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Gefitinib ('Iressa', ZD1839), a selective epidermal growth factor receptor tyrosine kinase inhibitor, inhibits pancreatic cancer cell growth, invasion, and colony formation.
pubmed:affiliation
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
pubmed:publicationType
Journal Article