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lüll mda-7/IL-24, a novel cancer selective apoptosis inducing cytokine gene: from the laboratory into the clinic Fisher PB; Gopalkrishnan RV; Chada S; Ramesh R; Grimm EA; Rosenfeld MR; Curiel DT; Dent PCancer Biol Ther 2003[Jul]; 2 (4 Suppl 1): S23-37An 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.|*Apoptosis[MESH]|Adenoviridae/genetics[MESH]|Animals[MESH]|Cell Differentiation[MESH]|Cell Line, Tumor[MESH]|Clinical Trials as Topic[MESH]|Cytokines/metabolism[MESH]|Disease Progression[MESH]|Genes, Tumor Suppressor[MESH]|Genetic Therapy[MESH]|Humans[MESH]|Interleukins/*physiology[MESH]|Melanoma/metabolism/pathology[MESH]|Models, Biological[MESH]|Neoplasm Transplantation[MESH]|Neoplasms/*drug therapy/*pathology[MESH]|Neovascularization, Pathologic[MESH]|Nucleic Acid Hybridization[MESH] |