Linked Life Data

15185340

Source:http://linkedlifedata.com/resource/pubmed/id/15185340

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-6-8
pubmed:abstractText
In addition to antiviral effects, Type I interferons (IFN) have potent antiproliferative and immunomodulatory activities. Because of these properties IFNs have been evaluated as therapeutics for the treatment of a number of human diseases, including cancer. Currently, IFNs have been shown to be efficacious for the treatment of only a select number of cancers. The reason for this is unclear. Recent evidence has demonstrated that some cancer cell types seem to be defective in their ability to respond to IFN. It has been suggested that defects in IFN signaling is one mechanism by which cancer cells escape responsiveness to Type I IFNs and growth control in general. We report that transfection and enhanced expression of the Type I IFN receptor chain (IFNAR2c) in 3 different human cancer cell lines markedly increases the sensitivity of these cells to the antiproliferative effects of IFNs. In cancer cells transfected with IFNAR2c, dose response curves demonstrate a significant decrease in the concentrations of IFN required to achieve maximum cell death. Furthermore, in these transfected cells, we observe a significant increase in the number of cells undergoing apoptosis, as measured by DNA fragmentation and Caspase 3 activation. In addition, using an in vivo xenograft tumor model we show an increase in the effectiveness of systemically delivered Betaseron in decreasing tumor burden in animals in which solid tumors were generated from IFNAR2c transfected cells. These data show that specific regulation of IFN receptor expression can play a major role in determining the clinical outcome of IFN-based cancer therapeutics by regulating the relative sensitivity of cancer cells to IFN-dependent growth control.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
111
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
32-42
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed-meshheading:15185340-Animals, pubmed-meshheading:15185340-Antineoplastic Agents, pubmed-meshheading:15185340-Apoptosis, pubmed-meshheading:15185340-Caspase 3, pubmed-meshheading:15185340-Caspases, pubmed-meshheading:15185340-Cell Line, Tumor, pubmed-meshheading:15185340-DNA Damage, pubmed-meshheading:15185340-Female, pubmed-meshheading:15185340-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15185340-Gene Therapy, pubmed-meshheading:15185340-Humans, pubmed-meshheading:15185340-Interferons, pubmed-meshheading:15185340-Mice, pubmed-meshheading:15185340-Mice, Nude, pubmed-meshheading:15185340-Receptor, Interferon alpha-beta, pubmed-meshheading:15185340-Receptors, Interferon, pubmed-meshheading:15185340-Signal Transduction, pubmed-meshheading:15185340-Transfection, pubmed-meshheading:15185340-Transplantation, Heterologous
pubmed:year
2004
pubmed:articleTitle
Interferon receptor expression regulates the antiproliferative effects of interferons on cancer cells and solid tumors.
pubmed:affiliation
Department of Immunology, Berlex Bioscience Inc., Richmond, CA 94804, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't