Linked Life Data

9563482

Source:http://linkedlifedata.com/resource/pubmed/id/9563482

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1998-5-21
pubmed:abstractText
Intratumoral injection of recombinant human tumor necrosis factor (TNF) for inoperable pancreatic cancer has shown some efficacy in suppressing tumor growth or decreasing tumor markers. However, complete regression has not yet been achieved, possibly due to a lack of TNF receptors on tumor cells or an abundance of intracellular resistance factors. Recently, two distinct types of TNF receptors, R55 and R75, were identified, which are responsible for signaling of cytotoxicity and of proinflammation, respectively. In this study, a novel type of suicide gene therapy is proposed that is based on transfection of the R55 gene into human pancreatic cancer cells (AsPC-1 and PANC-1) and subsequent administration of TNF. The transfectants from both cell lines showed higher TNF susceptibility than their parental cells. In vivo tumor formation of an AsPC-1 clone (clone 10) inoculated in nude mice was substantially suppressed by administration of TNF. For practical use of this strategy, however, the adverse effects of TNF may become an obstacle. We previously produced mutein TNF 471, which had a higher affinity for R55, superior antitumor activity, and fewer adverse effects. This mutein TNF 471 manifested greater antitumor activity against clone 10. Because the R55 receptor is known to be involved in augmentation of cellular immunity by TNF, mutein TNF 471 is also expected to be highly potent in this function. In fact, the mutein TNF 471 induced higher splenic natural killer cell activity in nude mice inoculated with clone 10 than did native TNF. This property of augumenting cellular responses may be advantageous in the eradication of viable tumor cells left untransfected in practical gene therapy regimens in which 100% transfection of the R55 gene into tumors is not feasible. Thus, gene therapy combining transfection of the TNF-R55 gene with administration of mutein TNF 471 may provide a new modality for the treatment of pancreatic cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1677-83
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
An apoptosis-inducing gene therapy for pancreatic cancer with a combination of 55-kDa tumor necrosis factor (TNF) receptor gene transfection and mutein TNF administration.
pubmed:affiliation
Fourth Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan.
pubmed:publicationType
Journal Article