| Cardiac glycosides exert anticancer effects by inducing immunogenic cell death. | |
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MedLine Citation:
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PMID: 22814852 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Some successful chemotherapeutics, notably anthracyclines and oxaliplatin, induce a type of cell stress and death that is immunogenic, hence converting the patient's dying cancer cells into a vaccine that stimulates antitumor immune responses. By means of a fluorescence microscopy platform that allows for the automated detection of the biochemical hallmarks of such a peculiar cell death modality, we identified cardiac glycosides (CGs) as exceptionally efficient inducers of immunogenic cell death, an effect that was associated with the inhibition of the plasma membrane Na(+)- and K(+)-dependent adenosine triphosphatase (Na(+)/K(+)-ATPase). CGs exacerbated the antineoplastic effects of DNA-damaging agents in immunocompetent but not immunodeficient mice. Moreover, cancer cells succumbing to a combination of chemotherapy plus CGs could vaccinate syngeneic mice against a subsequent challenge with living cells of the same type. Finally, retrospective clinical analyses revealed that the administration of the CG digoxin during chemotherapy had a positive impact on overall survival in cohorts of breast, colorectal, head and neck, and hepatocellular carcinoma patients, especially when they were treated with agents other than anthracyclines and oxaliplatin. |
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Authors:
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Laurie Menger; Erika Vacchelli; Sandy Adjemian; Isabelle Martins; Yuting Ma; Shensi Shen; Takahiro Yamazaki; Abdul Qader Sukkurwala; Mickaël Michaud; Grégoire Mignot; Frederic Schlemmer; Eric Sulpice; Clara Locher; Xavier Gidrol; François Ghiringhelli; Nazanine Modjtahedi; Lorenzo Galluzzi; Fabrice André; Laurence Zitvogel; Oliver Kepp; Guido Kroemer |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Science translational medicine Volume: 4 ISSN: 1946-6242 ISO Abbreviation: Sci Transl Med Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-07-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101505086 Medline TA: Sci Transl Med Country: United States |
Other Details:
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Languages: eng Pagination: 143ra99 Citation Subset: IM |
Affiliation:
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INSERM, U848, F-94805 Villejuif, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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