Linked Life Data

16467200

Source:http://linkedlifedata.com/resource/pubmed/id/16467200

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-5-4
pubmed:abstractText
The association of fibroblast growth factor receptor 3 (FGFR3) expression with t(4;14) multiple myeloma (MM) and the demonstration of the transforming potential of this receptor tyrosine kinase (RTK) make it a particularly attractive target for drug development. We report here a novel and highly specific anti-FGFR3-neutralizing antibody (PRO-001). PRO-001 binds to FGFR3 expressed on transformed cells and inhibits FGFR3 autophosphorylation and downstream signaling. The antibody inhibited the growth of FGFR3-expressing FDCP cells (IC(50) of 0.5 microg/mL) but not that of cells expressing FGFR1 or FGFR2, and potently inhibited FGFR3-dependent solid tumor growth in a mouse xenograft model. Furthermore, PRO-001 inhibited the growth of the FGFR3-expressing, human myeloma cell line, UTMC2. Inhibition of viability was still observed when cells were cocultured with stroma or in the presence of IL-6 or IGF-1. PRO-001 did not inhibit constitutive activation of K650E, G384D, and Y373C FGFR3 in myeloma cell lines and failed to inhibit the growth of these cells. Most importantly, however, PRO-001 induced cytotoxic responses in primary t(4;14)(+) MM samples with an increase in apoptotic index of 20% to 80% as determined by annexin V staining. The data demonstrate that PRO-001 is a potent and specific inhibitor of FGFR3 and deserves further study for the treatment of FGFR3-expressing myeloma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4039-46
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells.
pubmed:affiliation
University Health Network, Princess Margaret Hospital, McLaughlin Centre of Molecular Medicine, 620 University Avenue, Rm 8204, Toronto, Ontario, Canada M5G 2C1. strudel@uhnres.utoronto.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't