Human Gene Set: MITSIADES_RESPONSE_TO_APLIDIN_DN


Standard name MITSIADES_RESPONSE_TO_APLIDIN_DN
Systematic name M11318
Brief description Genes down-regulated in the MM1S cells (multiple myeloma) after treatment with aplidin [PubChem=44152164], a marine-derived compound with potential anti-cancer properties.
Full description or abstract Despite recent progress in its treatment, multiple myeloma (MM) remains incurable, thus necessitating identification of novel anti-MM agents. We report that the marine-derived cyclodepsipeptide Aplidin exhibits, at clinically achievable concentrations, potent in vitro activity against primary MM tumor cells and a broad spectrum of human MM cell lines, including cells resistant to conventional (e.g., dexamethasone, alkylating agents, and anthracyclines) or novel (e.g., thalidomide and bortezomib) anti-MM agents. Aplidin is active against MM cells in the presence of proliferative/antiapoptotic cytokines or bone marrow stromal cells and has additive or synergistic effects with some of the established anti-MM agents. Mechanistically, a short in vitro exposure to Aplidin induces MM cell death, which involves activation of p38 and c-jun NH(2)-terminal kinase signaling, Fas/CD95 translocation to lipid rafts, and caspase activation. The anti-MM effect of Aplidin is associated with suppression of a constellation of proliferative/antiapoptotic genes (e.g., MYC, MYBL2, BUB1, MCM2, MCM4, MCM5, and survivin) and up-regulation of several potential regulators of apoptosis (including c-JUN, TRAIL, CASP9, and Smac). Aplidin exhibited in vivo anti-MM activity in a mouse xenograft model. The profile of the anti-MM activity of Aplidin in our preclinical models provided the framework for its clinical testing in MM, which has already provided favorable preliminary results.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18593922   Authors: Mitsiades CS,Ocio EM,Pandiella A,Maiso P,Gajate C,Garayoa M,Vilanova D,Montero JC,Mitsiades N,McMullan CJ,Munshi NC,Hideshima T,Chauhan D,Aviles P,Otero G,Faircloth G,Mateos MV,Richardson PG,Mollinedo F,San-Miguel JF,Anderson KC
Exact source Table 3S
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced


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