mda-7/IL-24: a unique member of the IL-10 gene family promoting cancer-targeted toxicity |
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Authors: | Dash Rupesh Bhutia Sujit K Azab Belal Su Zhao-zhong Quinn Bridget A Kegelmen Timothy P Das Swadesh K Kim Keetae Lee Seok-Geun Park Margaret A Yacoub Adly Rahmani Mohammed Emdad Luni Dmitriev Igor P Wang Xiang-Yang Sarkar Devanand Grant Steven Dent Paul Curiel David T Fisher Paul B |
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Institution: | Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States. |
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Abstract: | Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a unique member of the IL-10 gene family that displays nearly ubiquitous cancer-specific toxicity, with no harmful effects toward normal cells or tissues. mda-7/IL-24 was cloned from human melanoma cells by differentiation induction subtraction hybridization (DISH) and promotes endoplasmic reticulum (ER) stress culminating in apoptosis or toxic autophagy in a broad-spectrum of human cancers, when assayed in cell culture, in vivo in human tumor xenograft mouse models and in a Phase I clinical trial in patients with advanced cancers. This therapeutically active cytokine also induces indirect antitumor activity through inhibition of angiogenesis, stimulation of an antitumor immune response, and sensitization of cancer cells to radiation-, chemotherapy- and antibody-induced killing. |
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