The new platinum anticancer agent LA-12 induces Retinol Bionding Protein 4 in vivo
| Autoři | |
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| Rok publikování | 2011 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins which could potentially serve as markers of LA-12 treatment, response and therapy monitoring. Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) for 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis. We identified plasma retinol binding protein RBP4 as a protein correlating with LA-12 level in both rat plasma and plasma ultrafiltrate. Similar trend was observed for randomly selected patients involved in Phase I of clinical trials. RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs. |
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