Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development.Delft Center for Systems and ControlMechanical, Maritime and Materials Engineerin

Searching for the "5H resonance for the t+n+n system

The unbound hydrogen isotopes "4","5H have been studied in the one-proton knockout channel of "6He (240 MeV/u) impinging on a carbon target. The triton fragments originating from this channel were detected in coincidence with neutrons. Relative energy spectra as well as energy and angular correlations have been studied for the t+n and t+n+n systems. The analysis of the energy and angular correlations by the method of hyperspherical harmonic expansion allows to determine the relative weights of the most relevant partial waves in the three-body t+n+n final state. It is shown that the neutrons to a large extent occupy the p-shell and that the I"#pi# = 1/2"+ state is strongly populated as expected for the "5H ground state. No evidence for a narrow resonance in the t+n+n system is obtained, instead a broad structure peaked at 3 MeV above the threshold with about 6 MeV as a full width at half maximum is observed. The two-body t+n system reveals a resonance compatible with earlier results for "4H. (orig.)SIGLEAvailable from TIB Hannover: RO 801(03-10) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Alcohol increases homocysteine and reduces B vitamin concentration in healthy male volunteers—a randomized, crossover intervention study

Background: Few studies have examined the effect of alcohol consumption on total homocysteine (tHcy) concentrations