170 research outputs found
Subverting sterols: rerouting an oxysterol-signaling pathway to promote tumor growth.
Oxysterols are oxidized derivatives of cholesterol that are generated enzymatically or through autoxidation. Initially identified as important lipid signaling molecules in the context of atherosclerosis and inflammation, accumulated evidence indicates that these lipid-signaling molecules can have pleiotropic effects on the fate and function of the immune system. These effects range from the regulation of immune cell survival and proliferation to chemotaxis and antiviral immunity. New studies now indicate that tumor-derived oxysterols can serve to subvert the immune system by recruiting protumorigenic neutrophils into the tumor microenvironment. The consequence of this recruitment is the generation of proangiogenic factors and matrix metalloproteinase proteins that provide a tumor a significant growth and survival advantage. In combination with other recent studies, these data highlight the ongoing cross talk between sterol metabolism and the immune system, and they raise the intriguing possibility that targeting oxysterol pathways could serve as a novel therapeutic approach in the war on cancer
Doxycycline alters metabolism and proliferation of human cell lines.
The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells-including inhibition of the mitochondrial ribosome-there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism
Subverting sterols: rerouting an oxysterol-signaling pathway to promote tumor growth
Oxysterols are oxidized derivatives of cholesterol that are generated enzymatically or through autoxidation. Initially identified as important lipid signaling molecules in the context of atherosclerosis and inflammation, accumulated evidence indicates that these lipid-signaling molecules can have pleiotropic effects on the fate and function of the immune system. These effects range from the regulation of immune cell survival and proliferation to chemotaxis and antiviral immunity. New studies now indicate that tumor-derived oxysterols can serve to subvert the immune system by recruiting protumorigenic neutrophils into the tumor microenvironment. The consequence of this recruitment is the generation of proangiogenic factors and matrix metalloproteinase proteins that provide a tumor a significant growth and survival advantage. In combination with other recent studies, these data highlight the ongoing cross talk between sterol metabolism and the immune system, and they raise the intriguing possibility that targeting oxysterol pathways could serve as a novel therapeutic approach in the war on cancer
Dysregulation of mannose-6-phosphate–dependent cholesterol homeostasis in acinar cells mediates pancreatitis
Federal Reserve Bank of New York Meeting with AIG Notes
In this particular instance, AIG faced liquidity issues that threatened the company\u27s survival
Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies
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