Source:http://linkedlifedata.com/resource/pubmed/id/14508078
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4 Suppl 1
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| pubmed:dateCreated |
2003-9-25
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| pubmed:abstractText |
An obstacle to effective gene-based cancer therapies is the limited number of cancer-specific growth suppressing and apoptosis-inducing genes. Using a differentiation induction subtraction hybridization (DISH) approach with human melanoma cells, melanoma differentiation associated (mda) genes were isolated that display elevated expression as a function of irreversible growth arrest, cancer reversion and terminal differentiation. This screening paradigm resulted in the cloning of mda-7 in the context of terminal differentiation of human melanoma cells. Based on its structure, chromosomal location, sequence homology and cytokine-like properties, mda-7 has now been renamed IL-24 and classified as a member of the expanding IL-10 cytokine gene family. Expression of mda-7/IL-24 inversely correlates with melanoma progression and administration of mda-7/IL-24 by means of a replication incompetent adenovirus, Ad.mda-7, results in growth suppression and apoptosis in melanoma cells as well as in a broad-spectrum of additional cancer cell types. In contrast, Ad.mda-7 does not elicit deleterious effects in normal cells, including those of epithelial, fibroblast, astrocyte, melanocyte or endothelial origin. Based on these distinctive properties and anti-tumor and anti-angiogenic activities in human tumor xenograft animal models, mda-7/IL-24 has now entered the clinical arena. A Phase I/II clinical trial in patients with advanced carcinomas involving intratumoral administration of mda-7/IL-24 [using a replication incompetent adenovirus; ING241 (Ad.mda-7)] has documented that this gene is safe and well tolerated by patients and a single virus injection elicits apoptosis in a majority of the tumor. Current data suggests that mda-7/IL-24 may function as a dual-acting cytokine in which its normal physiological functions may be related to specific aspects of the immune system and over-expression culminates in cancer-specific apoptosis. This review will provide a prospectus of our current understanding of mda-7/IL-24.
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| pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/AG021875,
http://linkedlifedata.com/resource/pubmed/grant/CA090547,
http://linkedlifedata.com/resource/pubmed/grant/CA35675,
http://linkedlifedata.com/resource/pubmed/grant/CA72955,
http://linkedlifedata.com/resource/pubmed/grant/CA86587,
http://linkedlifedata.com/resource/pubmed/grant/CA86881,
http://linkedlifedata.com/resource/pubmed/grant/CA88906,
http://linkedlifedata.com/resource/pubmed/grant/CA89019,
http://linkedlifedata.com/resource/pubmed/grant/CA89778,
http://linkedlifedata.com/resource/pubmed/grant/CA90282,
http://linkedlifedata.com/resource/pubmed/grant/CA97318,
http://linkedlifedata.com/resource/pubmed/grant/CA97598,
http://linkedlifedata.com/resource/pubmed/grant/CA98712,
http://linkedlifedata.com/resource/pubmed/grant/DK52825,
http://linkedlifedata.com/resource/pubmed/grant/HL67962,
http://linkedlifedata.com/resource/pubmed/grant/P50-CA70907-5
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:issn |
1538-4047
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
2
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
S23-37
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:14508078-Adenoviridae,
pubmed-meshheading:14508078-Animals,
pubmed-meshheading:14508078-Apoptosis,
pubmed-meshheading:14508078-Cell Differentiation,
pubmed-meshheading:14508078-Cell Line, Tumor,
pubmed-meshheading:14508078-Clinical Trials as Topic,
pubmed-meshheading:14508078-Cytokines,
pubmed-meshheading:14508078-Disease Progression,
pubmed-meshheading:14508078-Gene Therapy,
pubmed-meshheading:14508078-Genes, Tumor Suppressor,
pubmed-meshheading:14508078-Humans,
pubmed-meshheading:14508078-Interleukins,
pubmed-meshheading:14508078-Melanoma,
pubmed-meshheading:14508078-Models, Biological,
pubmed-meshheading:14508078-Neoplasm Transplantation,
pubmed-meshheading:14508078-Neoplasms,
pubmed-meshheading:14508078-Neovascularization, Pathologic,
pubmed-meshheading:14508078-Nucleic Acid Hybridization
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| pubmed:articleTitle |
mda-7/IL-24, a novel cancer selective apoptosis inducing cytokine gene: from the laboratory into the clinic.
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| pubmed:affiliation |
Departments of Pathology, Neurosurgery and Urology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons; New York, New York 1032, USA. pbf1@columbia.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Review,
Research Support, Non-U.S. Gov't
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