Publications by authors named "Anthony S Fischl"

Inhibition of VEGFR signaling is an effective treatment for renal cell carcinoma, but resistance continues to be a major problem. Recently, the sphingosine phosphate (S1P) signaling pathway has been implicated in tumor growth, angiogenesis, and resistance to antiangiogenic therapy. S1P is a bioactive lipid that serves an essential role in developmental and pathologic angiogenesis via activation of the S1P receptor 1 (S1P1).

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Phosphatidylinositol (3,4,5) trisphosphate (PIP) is a biologically active membrane phospholipid that is essential for the growth and survival of all eukaryotic cells. We describe a new method that directly measures PIP and describe the HPLC separation and measurement of the positional isomers of phosphatidylinositol bisphosphate, PI(3,5)P, PI(3,4)P and PI(4,5)P. Mass spectrometric analyses were performed online using ultra-high performance liquid chromatography (UHPLC)-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in the negative multiple-reaction monitoring (MRM) modes.

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Purpose: To evaluate the reproducibility of the measurement of the total choline-to-water ratio, and the effect of repositioning the subject between scans, using (1) H-magnetic resonance spectroscopy in a mouse U87MG xenograft model.

Materials And Methods: In vivo single-voxel MR spectra at 7T from xenograft tumors were obtained using both a water-suppressed and a nonwater-suppressed point-resolved spectroscopy (PRESS) sequence. Reproducibility of the total choline/water ratio was evaluated under the conditions of immediate rescan with no change in position of the animal or voxel, immediate reposition, and reposition after 1 or 7 days.

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Phospholipid molecules such as ceramide and phosphoinositides play crucial roles in signal transduction pathways. Lipid-modifying enzymes including sphingomyelinase and phosphoinositide kinases regulate the generation and degradation of these lipid-signaling molecules and are important therapeutic targets in drug discovery. We now report a sensitive and convenient method to separate these lipids using microfluidic chip-based technology.

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Sphingolipid metabolism is implicated to play an important role in apoptosis. Here we show that dihydrosphingosine (DHS) and phytosphingosine (PHS), two major sphingoid bases of fungi, have potent fungicidal activity with remarkably high structural and stereochemical specificity against Aspergillus nidulans. In fact, only naturally occurring DHS and PHS are active.

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