Multifunctional Role of Bcl-2 in Malignant Transformation and Tumorigenesis of Cr(VI)-Transformed Lung Cells

B-cell lymphoma-2 (Bcl-2) is an antiapoptotic protein known to be important in the regulation of apoptosis in various cell types. However, its role in malignant transformation and tumorigenesis of human lung cells is not well understood. We previously reported that chronic exposure of human lung epithelial cells to the carcinogenic hexavalent chromium Cr(VI) caused malignant transformation and Bcl-2 upregulation; however, the role of Bcl-2 in the transformation is unclear. Using a gene silencing approach, we showed that Bcl-2 plays an important role in the malignant properties of Cr(VI)-transformed cells. Downregulation of Bcl-2 inhibited the invasive and proliferative properties of the cells as well as their colony forming and angiogenic activities, which are upregulated in the transformed cells as compared to control cells. Furthermore, animal studies showed the inhibitory effect of Bcl-2 knockdown on the tumorigenesis of Cr(VI)-transformed cells. The role of Bcl-2 in malignant transformation and tumorigenesis was confirmed by gene silencing experiments using human lung carcinoma NCI-H460 cells. These cells exhibited aggressive malignant phenotypes similar to those of Cr(VI)-transformed cells. Knockdown of Bcl-2 in the H460 cells inhibited malignant and tumorigenic properties of the cells, indicating the general role of Bcl-2 in human lung tumorigenesis. Ingenuity Pathways Analysis (IPA) revealed potential effectors of Bcl-2 in tumorigenesis regulation. Additionally, using IPA together with ectopic expression of p53, we show p53 as an upstream regulator of Bcl-2 in Cr(VI)-transformed cells. Together, our results indicate the novel and multifunctional role of Bcl-2 in malignant transformation and tumorigenesis of human lung epithelial cells chronically exposed to Cr(VI)

Simulation of Load Cycles in Pressurized SOFC Systems and Economic Evaluation

As known from literature [1], the pressurization of SOFC systems may lead to increased efficiencies and higher power output. These benefits will have to be utilized in future power generation in order to meet the requirements of higher electrical power demand as well as the goals of lower emissions. Operating a hybrid power plant at full load only is not always an option. Small power plants have to be able to run in load-following mode in order to keep the load of the grid low. By alternating the power of the gas turbine, a hybrid power plant would only be capable of following load in a band of 100 to 80%. Therefore, load alternation of the SOFC system is crucial for the operation of a hybrid power plant. The model of an SOFC system in a hybrid power plant has been presented before [2]. In this presentation we focus on the load-following capability of the modelled SOFC system. A series of step responses in load demand was applied to the system model, giving a close insight into the systems dynamic capabilities. These step responses will be discussed in detail and rules for dynamic system operation will be developed from these simulations. These rules have to be applied in order to keep the system within safe operation boundaries. Further complete load cycle simulations will be presented based on typical household load demands showing the dynamic capability of the pressurized fuel cell system. The prospects of pressurized SOFC systems in stationary power generation will be discussed on the basis of economical considerations. The operation of the SOFC at full load operation as well as at dynamic load conditions will be considered. 1. Virkar, The effect of pressure on solid oxide fuel cell performance. 1997, Westinghouse Electric Corporation, University of Utah, Department of Material's Science and Engineering. 2. F. Leucht and K. A. Friedrich, "SOFC System Modelling in the Hybrid Power Plant Project," in Proceedings of the 6th Symposium on Fuel Cell Modelling and Experimental Validation, Bad Herrenalb (Germany) (2009)