Single-step doxorubicin-selected cancer cells overexpress the ABCG2 drug transporter through epigenetic changes

Understanding the mechanisms of multidrug resistance (MDR) could improve clinical drug efficacy. Multidrug resistance is associated with ATP binding cassette (ABC) transporters, but the factors that regulate their expression at clinically relevant drug concentrations are poorly understood. We report that a single-step selection with low doses of anti-cancer agents, similar to concentrations reported in vivo, induces MDR that is mediated exclusively by ABCG2. We selected breast, ovarian and colon cancer cells (MCF-7, IGROV-1 and S-1) after exposure to 14 or 21 nM doxorubicin for only 10 days. We found that these cells overexpress ABCG2 at the mRNA and protein levels. RNA interference analysis confirmed that ABCG2 confers drug resistance. Furthermore, ABCG2 upregulation was facilitated by histone hyperacetylation due to weaker histone deacetylase 1-promoter association, indicating that these epigenetic changes elicit changes in ABCG2 gene expression. These studies indicate that the MDR phenotype arises following low-dose, single-step exposure to doxorubicin, and further suggest that ABCG2 may mediate early stages of MDR development. This is the first report to our knowledge of single-step, low-dose selection leading to overexpression of ABCG2 by epigenetic changes in multiple cancer cell lines

How do patients from eastern and western Germany compare with regard to their preferences for shared decision making?

Item does not contain fulltextBACKGROUND: Increasing emphasis is being placed on involving patients in decisions concerning their health. This shift towards more patient engagement by health professionals and towards more desire by patients for participation may be partly based on socio-political factors. METHODS: To compare the preferences for shared decision making of patients from eastern and western Germany we analysed five patient samples (n = 2318) (general practice patients and schizophrenia patients from eastern and western Germany). Patients' role preferences for shared decisions were measured using the decision-making subscale of the Autonomy Preference Index. RESULTS: Patients resident in eastern Germany expressed lower preferences for shared decision making than patients in western Germany. This was true after controlling for socio-demographic variables and for patient group. CONCLUSION: The cultural imprint (e.g. western vs. former communist society) seems to have a significant influence on patients' expectations and behaviour in the medical encounter. Health services providers need to be aware that health attitudes within the same health system might vary for historical and cultural reasons. The engagement of patients in medical decisions might not be susceptible to a 'one size fits all' approach; doctors should instead aim to accommodate the individual patient's desire for autonomy.1 augustus 201