66 research outputs found

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

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    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)

    Compilation of basal metabolic and blood perfusion rates in various multi-compartment, whole-body thermoregulation models

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    The assignments of basal metabolic rates (BMR), basal cardiac outputs (BCO) and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5% relative to the lowest value, with a mean of 84.3±2 Watts, and in the BCO it was 8% with a mean of 4.70±0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax and abdomen: ±7.8% BMR and ±5.9% BBPR) and in the combined head (head, face, and neck: ±9.9% BMR and ±10.9% BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117%), followed by the BBPR in the arms (±61.3%). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen and legs. The brain, lung and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities.Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts, subject to appropriate adjustment of values to conform to most recently available and reliable data

    Colorimetric Determination of Primary Mononitroparaffins

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