Linked Life Data

10423407

Source:http://linkedlifedata.com/resource/pubmed/id/10423407

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-9-7
pubmed:abstractText
Current paradigms in cancer therapy suggest that activation of nuclear factor-kappaB (NF-kappaB) by a variety of stimuli, including some cytoreductive agents, may inhibit apoptosis. Thus, inhibiting NF-kappaB activation may sensitize cells to anticancer therapy, thereby providing a more effective treatment for certain cancers. E-1-deleted adenoviral (Ad) vectors encoding a "superrepressor" form of the NF-kappaB inhibitor IkappaBalpha (AdIkappaBalphaSR) or beta-galactosidase (AdLacZ) were tested alone and in combination with tumor necrosis factor-alpha (TNF-alpha) in lung cancer cells for sensitization of the cells to death. Following transduction with AdIkappaBalphaSR, lung cancer cells expressed IkappaBalphaSR in a dose-dependent manner. Probing nuclear extracts of lung cancer cells with NF-kappaB-sequence-specific oligonucleotides indicated that there was a minimal amount of NF-kappaB in the nucleus at baseline and an expected and dramatic increase in nuclear NF-kappaB following exposure of cells to TNF-alpha. Control E-1-deleted AdLacZ did not promote NF-kappaB activation. Importantly, AdIkappaBalphaSR-mediated gene transfer resulted in the complete block of nuclear translocation of NF-kappaB by specific binding of its p65/relA component with transgenic IkappaBalphaSR. At the cellular level, transduction with AdIkappaBalphaSR resulted in increased cytotoxicity in lung cancer cells as opposed to transduction with equivalent doses of AdLacZ. In addition, whereas the parental cells were resistant to TNF-alpha-mediated cytotoxicity, IkappaBalphaSR-transduced cells could be sensitized to TNF-alpha. Consequently, AdIkappaBalphaSR transduction followed by exposure to TNF-alpha uniformly resulted in the death of non-small-cell lung cancer cells. These data suggest that novel approaches incorporating IkappaBalpha gene therapy may have a role in the treatment of lung cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
238-45
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
IkappaBalpha gene transfer is cytotoxic to squamous-cell lung cancer cells and sensitizes them to tumor necrosis factor-alpha-mediated cell death.
pubmed:affiliation
Department of Medicine, The Wadsworth Pulmonary Immunology Laboratory, Los Angeles, California, USA. Batra.Raj_K@west-la.va.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't