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Resumo:
In the lead-up to the creation of a Eurasian Economic Union in 2015, the Customs Union and the Common Economic Space between Russia, Belarus and Kazakhstan represent two elements of the most ambitious regional integration project launched in the post-Soviet era since 1991. This CEPS Special Report examines both the potential and the limits of Eurasian economic integration. For the purpose of assessing the Eurasian integration process, CEPS applied a modified version of a framework first developed by Ernest B. Haas and Philippe C. Schmitter in 1964 to project whether economic integration of a group of countries automatically engenders political unity. Taking the data available for the early stages of the European integration process as a benchmark, the results for the Customs Union and the Common Economic Space point to a rather unfavourable outlook for Eurasian economic integration.
Resumo:
Human breast cancer cells (MCF-7, T-47-D and ZR-75-1) can adapt to circumvent any reduced growth rate during long-term oestrogen deprivation, and this provides three model systems to investigate mechanisms of endocrine resistance in breast cancer. In this paper we report consistent differences in the effects of three growth inhibitors following long-term oestrogen deprivation in all three cell models. Long-term oestrogen deprivation of MCF-7, T-47-D and ZR-75-1 cells resulted in reduced growth inhibition by PD98059 (2–10 µg/ml), implying a loss of dependence on mitogen-activated protein kinase pathways for growth. The growth inhibitor LY294002 (2–10 µM) inhibited growth of both oestrogen-maintained and oestrogen-deprived cells with similar dose–responses, implying continued similar dependence on phosphoinositide 3-kinase (PI3K) pathways with no alteration after adaptation to oestrogen independent growth. However, by contrast, long-term oestrogen deprivation resulted in an increased sensitivity to growth inhibition by rapamycin, which was not reduced by readdition of oestradiol. The enhanced inhibition of long-term oestrogen-deprived MCF-7-ED, T-47-D-ED and ZR-75-1-ED cell growth by combining rapamycin with LY294002 at concentrations where each alone had little effect, offers preclinical support to the development of therapeutic combinations of rapamycin analogues with other PI3K inhibitors in endocrine-resistant breast cancer.