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MDA-7/IL-24 as a cancer therapeutic: from bench to bedside Dent P; Yacoub A; Hamed HA; Park MA; Dash R; Bhutia SK; Sarkar D; Gupta P; Emdad L; Lebedeva IV; Sauane M; Su ZZ; Rahmani M; Broaddus WC; Young HF; Lesniak M; Grant S; Curiel DT; Fisher PBAnticancer Drugs 2010[Sep]; 21 (8): 725-31The novel cytokine melanoma differentiation associated gene-7 (mda-7) was identified by subtractive hybridization in the mid-1990s as a protein whose expression increased during the induction of terminal differentiation, and that was either not expressed or was present at low levels in tumor cells compared with non-transformed cells. On the basis of conserved structure, chromosomal location and cytokine-like properties, MDA-7, has now been classified as a member of the expanding interleukin (IL)-10 gene family and designated as MDA-7/IL-24. Multiple studies have shown that the expression of MDA-7/IL-24 in a wide variety of tumor cell types, but not in the corresponding equivalent non-transformed cells, causes their growth arrest and ultimately cell death. In addition, MDA-7/IL-24 has been noted to be a radiosensitizing cytokine, which is partly because of the generation of reactive oxygen species and ceramide that cause endoplasmic reticulum stress. Phase I clinical trial data has shown that a recombinant adenovirus expressing MDA-7/IL-24 [Ad.mda-7 (INGN-241)] was safe and had measurable tumoricidal effects in over 40% of patients, which strongly argues that MDA-7/IL-24 may have significant therapeutic value. This review describes what is known about the impact of MDA-7/IL-24 on tumor cell biology and its potential therapeutic applications.|*Apoptosis[MESH]|*Radiation Tolerance[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Cell Line, Tumor[MESH]|Cytokines/metabolism[MESH]|Female[MESH]|Genes, Tumor Suppressor[MESH]|Genetic Therapy[MESH]|Humans[MESH]|Interleukins/administration & dosage/genetics/metabolism/*therapeutic use[MESH]|Male[MESH]|Middle Aged[MESH]|Neoplasms/diagnostic imaging/*drug therapy/metabolism/pathology[MESH]|Radionuclide Imaging[MESH]|Signal Transduction[MESH] |
