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Cellular processing of platinum anticancer drugs.

Nature reviews. Drug discovery

Tumor Cells, Cultured, drug effects, Signal Transduction, pharmacology, chemistry, Organoplatinum Compounds, Molecular Structure, Humans, DNA Repair, DNA Damage, Cell Survival, Apoptosis, Antineoplastic Agents, Animals

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      Abstract

      Cisplatin, carboplatin and oxaliplatin are platinum-based drugs that are widely used in cancer chemotherapy. Platinum-DNA adducts, which are formed following uptake of the drug into the nucleus of cells, activate several cellular processes that mediate the cytotoxicity of these platinum drugs. This review focuses on recently discovered cellular pathways that are activated in response to cisplatin, including those involved in regulating drug uptake, the signalling of DNA damage, cell-cycle checkpoints and arrest, DNA repair and cell death. Such knowledge of the cellular processing of cisplatin adducts with DNA provides valuable clues for the rational design of more efficient platinum-based drugs as well as the development of new therapeutic strategies.

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      Most cited references 190

      • Record: found
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      Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis.

       J Folkman,  D Hanahan (1996)
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        • Record: found
        • Abstract: found
        • Article: not found

        Release of chromatin protein HMGB1 by necrotic cells triggers inflammation.

        High mobility group 1 (HMGB1) protein is both a nuclear factor and a secreted protein. In the cell nucleus it acts as an architectural chromatin-binding factor that bends DNA and promotes protein assembly on specific DNA targets. Outside the cell, it binds with high affinity to RAGE (the receptor for advanced glycation end products) and is a potent mediator of inflammation. HMGB1 is secreted by activated monocytes and macrophages, and is passively released by necrotic or damaged cells. Here we report that Hmgb1(-/-) necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours. Apoptotic cells do not release HMGB1 even after undergoing secondary necrosis and partial autolysis, and thus fail to promote inflammation even if not cleared promptly by phagocytic cells. In apoptotic cells, HMGB1 is bound firmly to chromatin because of generalized underacetylation of histone and is released in the extracellular medium (promoting inflammation) if chromatin deacetylation is prevented. Thus, cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.
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          Signal transduction by the JNK group of MAP kinases.

           Tessa Davis (2000)
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            Author and article information

            Journal
            10.1038/nrd1691
            15789122

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