Linked Life Data

19508175

Source:http://linkedlifedata.com/resource/pubmed/id/19508175

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-8-18
pubmed:abstractText
Interferon-a (IFN-a) is currently the most used cytokine in the treatment of cancer. However, the potential anti-tumour activity of IFN-a is limited by the activation of tumour resistance mechanisms. In this regard, we have shown that IFN-a, at growth inhibitory concentrations, enhances the EGF-dependent Ras-->Erk signalling and decreases the adenylate cyclase/cAMP pathway activity in cancer cells; both effects represent escape mechanisms to the growth inhibition and apoptosis induced by IFN-a. The selective targeting of these survival pathways might enhance the antitumor activity of IFN-ain cancer cells, as shown by: i) the combination of selective EGF receptor tyrosine kinase inhibitor (gefitinib) and IFN-a having cooperative anti-tumour effects; ii) the farnesyl-transferase inhibitor R115777 strongly potentiating the anti-tumour activity of IFN-a both in vitro and in vivo through the inhibition of different escape mechanisms that are dependent on isoprenylation of intracellular proteins such as ras; iii) the cAMP reconstituting agent (8-Br-cAMP) enhancing the pro-apoptotic activity of IFN-alpha. IFN-beta is a multifunctional cytokine binding the same receptor of IFN-alpha, but with higher affinity (10-fold) and differential structural interactions. We recently showed that IFN-beta is considerably more potent than IFN-alpha in its anti-tumour effect through the induction of apoptosis and/or cell cycle arrest in S-phase. The emergence of long-acting pegylated forms of IFN-beta makes this agent a promising anti-cancer drug. These observations open a new scenario of anticancer intervention able to strengthen the antitumor activity of IFN-alpha or to use more potent type I IFNs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1873-5576
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
690-704
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Emerging strategies to strengthen the anti-tumour activity of type I interferons: overcoming survival pathways.
pubmed:affiliation
Department of Biochemistry and Biophysics, II University of Naples, 80138, Naples, Italy. Michele.Caraglia@unina2.it
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't