Linked Life Data

10341880

Source:http://linkedlifedata.com/resource/pubmed/id/10341880

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-6-10
pubmed:abstractText
Cancer cachexia, characterized by anorexia, weight loss and progressive tissue wasting, has been postulated to be mediated by various cytokines. However, the precise mechanism of cachexia induction is not fully explained. We have developed synthetic double-stranded oligodeoxynucleotides (ODN) as 'decoy' cis-elements that block the binding of nuclear factors to promoter regions of targeted genes, resulting in the inhibition of gene transactivation in vivo as well as in vitro. This novel molecular strategy could be useful for treating a broad range of human diseases including cancer. In this study, we injected decoy ODN targeting the transcriptional factor, NF-kappa B (NF kappa B) binding cis-elements, which are essential for transactivation of gene expression of cytokines, directly into tumors of adenocarcinoma colon26 in mice, in order to examine whether or not cachexia is alleviated by inhibiting the action of cytokines. Tumor growth was not affected by transfection of NF kappa B decoy ODN as compared with scrambled decoy ODN. Nevertheless, transfection of NF kappa B decoy, but not scrambled decoy, ODN resulted in attenuation of the reductions in body weight, epididymal fat, gastrocnemius muscle mass and food intake, which were induced by the tumor presence. Interleukin 6 mRNA in the tumor was also markedly decreased by the transfection of NF kappa B decoy ODN. It is known that the transcriptional factor E2F plays a pivotal role in the coordinated transactivation of cell cycle regulatory genes. Therefore, we hypothesized that the introduction of synthetic double-stranded DNA with high affinity for E2F in vivo as 'decoy' cis-elements might inhibit the tumor growth of colon26, resulting in turn in inhibition of cachexia induction. However, injection of E2F decoy ODN failed to inhibit tumor growth and cachexia induction, as compared with mismatched decoy ODN. Overall, the present study demonstrated that cachexia induced by adenocarcinoma colon26 was inhibited by blocking of NF kappa B, using a novel molecular decoy strategy, without an effect on tumor growth, and also that tumor growth and cachexia induction in the colon26 model were not affected by E2F decoy ODN. These results suggest that cytokines regulated by NF kappa B may play a pivotal role in the induction of cachexia by colon26, providing a new therapeutic strategy for cancer cachexia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10341880-Adenocarcinoma, pubmed-meshheading:10341880-Animals, pubmed-meshheading:10341880-Binding Sites, pubmed-meshheading:10341880-Cachexia, pubmed-meshheading:10341880-Cell Cycle Proteins, pubmed-meshheading:10341880-Colonic Neoplasms, pubmed-meshheading:10341880-Cytokines, pubmed-meshheading:10341880-Gene Expression, pubmed-meshheading:10341880-Gene Therapy, pubmed-meshheading:10341880-Genetic Vectors, pubmed-meshheading:10341880-Injections, Intralesional, pubmed-meshheading:10341880-Interleukin-6, pubmed-meshheading:10341880-Liposomes, pubmed-meshheading:10341880-Male, pubmed-meshheading:10341880-Mice, pubmed-meshheading:10341880-Mice, Inbred BALB C, pubmed-meshheading:10341880-NF-kappa B, pubmed-meshheading:10341880-Oligonucleotides, pubmed-meshheading:10341880-RNA, Messenger, pubmed-meshheading:10341880-Respirovirus
pubmed:year
1999
pubmed:articleTitle
Intratumoral injection of oligonucleotides to the NF kappa B binding site inhibits cachexia in a mouse tumor model.
pubmed:affiliation
Pharmacological Research Laboratories, Fujisawa Pharmaceutical Company, Yodogawaku, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't