title: The new platinum-based anticancer agent LA-12 induces retinol binding protein 4 in vivo.
abstract: BACKGROUND
  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 that serve as markers of LA-12 treatment, response and therapy monitoring.
  
  
  METHODS
  Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) in 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.
  
  
  RESULTS
  We identified Retinol-binding protein 4 (RBP4) whose level correlated with LA-12 level in treated rats. Similar results were observed in randomly selected patients involved in Phase I clinical trials.
  
  
  CONCLUSIONS
  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.
authors: Masaryk Memorial Cancer Institute, Regional Centre for Applied Molecular Oncology, Zluty kopec 7, 656 53 Brno, Czech Republic. vojtesek@mou.cz.
authors: Pavel
authors: P
authors: Bouchal
authors: Jiri
authors: J
authors: Jarkovsky
authors: Kristyna
authors: K
authors: Hrazdilova
authors: Monika
authors: M
authors: Dvorakova
authors: Iva
authors: I
authors: Struharova
authors: Lenka
authors: L
authors: Hernychova
authors: Jiri
authors: J
authors: Damborsky
authors: Petr
authors: P
authors: Sova
authors: Borivoj
authors: B
authors: Vojtesek