Paradoxical regulation of Bcl-2 family proteins by 17β-oestradiol in human breast cancer cells MCF-7

Tumorigenesis is related to the dysregulation of cell growth or cell death pathways. Hence, elucidation of the mechanisms involved in the modulation of pro- or anti-apoptotic proteins is important in furthering understanding of breast cancer aetiology and may aid in designing prevention and treatment strategies. In the present study, we examined the role of 17β-oestradiol on the regulation of apoptosis in the breast cancer cell line MCF-7. Using multi-probe RNAase protection assays, we found changes in the mRNA levels of several Bcl-2 family proteins upon treatment of MCF-7 cells with 17β-oestradiol. Unexpectedly, we found a paradoxical effects of 17β-oestradiol on two anti-apoptotic proteins Bcl-2 and Bcl-x. Treatment with 17β-oestradiol resulted in up-regulation of Bcl-2 mRNA and protein, but down-regulated Bcl-x(L) mRNA and protein. The effect of 17β-oestradiol on Bcl-x(L) occurred at concentration-dependent fashion. The effect was specific to 17β-oestradiol since other steroid hormones exert no effect on Bcl-x(L). Tamoxifen, an anti-oestrogen, blocked the down-regulation of Bcl-x(L) by 17β-oestradiol demonstrating this effect is oestrogen receptor-dependent. We speculate that different members of the Bcl-2 family proteins may be regulated through different pathway and these pathways may be modulated by 17β-oestradiol. © 1999 Cancer Research Campaig

Rôle potentiel de la noradrénaline dans la dysfonction immune du sepsis [Potential role of norepinephrine in the immune dysfunction associated with sepsis]

Septic shock may be complicated by a state of immune suppression, with ominous prognosis significance. Although the underlying pathophysiological mechanisms are poorly understood, it is possible that norepinephrine, used to treat circulatory failure during septic shock, plays a significant contributing role. Indeed, besides its hemodynamic effects, norepinephrine exerts multiple immunosuppressive actions, which are primarily mediated by beta-2 adrenergic receptors expressed by immune cells. Furthermore, norepinephrine has the ability to promote the growth of numerous bacteria, and could thereby foster the development of nosocomial infections. Norepinephrine being one of the most prescribed drugs in intensive care medicine, knowledge of these particular immunological effects is essential for the intensive care physicians

Advanced vehicle dynamics through active aerodynamics and active body control

In this paper, the development procedure of an innovative control algorithm is shown, with the aim of improving handling performance of a high-end sport vehicle by actively controlling aerodynamic forces acting on the vehicle itself. The proposed control algorithm operates indirectly by modifying ride-heights of the vehicle through an active suspensions system. The vehicle dynamics analysis is conducted in parallel to the aerodynamics analysis performed in a concurrent engineering operation. The software used for control algorithms development is VICarRealTime, in co-simulation with Matlab-Simulink, with an extended use of the MaxPerformance package. Specific tracks have been implemented ad hoc to highlight the effects of the control systems operation in development phase. To better explore the potential of the technique, a fuzzy logic system was developed