De novo production of phosphatidic acid (PA) in tumor cells is required for phospholipid biosynthesis and growth of tumor cells. In addition, PA production by phospholipase D has been cited among the effects of certain oncogenes and growth factors. In this report, it has been demonstrated that enhanced phospholipid metabolism through PA in tumor cells can be exploited pharmacologically for development of anticancer agents, such as CT-2584, a cancer chemotherapeutic drug candidate currently in Phase II clinical trials.
View Article and Find Full Text PDFAnimal communication theory holds that many signals have evolved from nonsignal precursors. This field and laboratory study of California ground squirrels (Spermophilus beecheyi) provides evidence for the coexistence of such a precursor with its derived display. The precursor is an ancient, endogenously sequenced (syntactic) pattern of cephalocaudal grooming movements (CCGs) shared by all rodent suborders.
View Article and Find Full Text PDFLisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] decreases lipid peroxidation in vitro and in vivo suppresses proinflammatory cytokine expression in models of lung injury due to sepsis, blood loss, and oxidative damage. In the present experiments, we used a murine hyperoxia model to examine the effects of lisofylline on the activation of nuclear transcriptional regulatory factors [nuclear factor-kappaB and cAMP response element binding protein (CREB)], the expression of proinflammatory cytokines in the lungs, and the circulating levels of oxidized free fatty acids as well as on hyperoxia-induced lung injury and mortality. Treatment with lisofylline inhibited hyperoxia-associated increases in tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in the lungs as well as decreased the levels of hyperoxia-induced serum-oxidized free fatty acids.
View Article and Find Full Text PDF1. Lipid A and LPS stimulate LPAAT activity (and hence unsaturated PA formation) in RMC membranes and whole cells. 2.
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