The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis.

Gliomas are highly aggressive primary brain tumors, with glioblastoma multiforme being the most severe and the most common one. Aberrations in sphingolipid metabolism are a hallmark of glioma cells. The sphingolipid rheostat represents the balance between the pro-apoptotic ceramide and pro-survival sphingosine-1-phosphate (S1P), and in gliomas it is shifted toward cell survival and proliferation, promoting gliomas' aggressiveness, cellular migration, metastasis, and invasiveness.

Comparative Targeted Metabolomics of Ischemic Stroke: Thrombi and Serum Profiling for the Identification of Stroke-Related Metabolites.

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Therefore, identifying reliable biomarkers for early detection, prognostics, and therapy can facilitate the early prediction and prevention of stroke.

Ion Mobility Mass Spectrometry Reveals Rare Sialylated Glycosphingolipid Structures in Human Cerebrospinal Fluid.

Gangliosides (GGs) represent an important class of biomolecules associated with the central nervous system (CNS). In view of their special role at a CNS level, GGs are valuable diagnostic markers and prospective therapeutic agents. By ion mobility separation mass spectrometry (IMS MS), recently implemented by us in the investigation of human CNS gangliosidome, we previously discovered a similarity between GG profiles in CSF and the brain.

Ganglioside Composition Distinguishes Anaplastic Ganglioglioma Tumor Tissue from Peritumoral Brain Tissue: Complementary Mass Spectrometry and Thin-Layer Chromatography Evidence.

Gangliosides serve as antitumor therapy targets and aberrations in their composition strongly correlate with tumor growth and invasiveness. Anaplastic ganglioglioma is a rare, poorly characterized, malignant neuronal-glial tumor type. We present the first comparative characterization of ganglioside composition in anaplastic ganglioglioma vs.

Cerebrospinal fluid: Profiling and fragmentation of gangliosides by ion mobility mass spectrometry.

The proximity of cerebrospinal fluid (CSF) with the brain, its permanent renewal and better availability for research than tissue biopsies, as well as ganglioside (GG) shedding from brain to CSF, impelled lately the development of protocols for the characterization of these glycoconjugates and discovery of central nervous system biomarkers expressed in CSF. Currently, the investigation of CSF gangliosides is focused on concentration measurements of the predominant classes and much less on their profiling and structural analysis. Since we have demonstrated recently the high performance of ion mobility separation mass spectrometry (IMS MS) for compositional and structural determination of human brain GGs, in the present study we have implemented for the first time IMS MS for the exploration of human CSF gangliosidome, in order to generate the first robust mass spectral database of CSF gangliosides.

Aberrant ganglioside composition in glioblastoma multiforme and peritumoral tissue: A mass spectrometry characterization.

Tumor cells are characterized by aberrant glycosylation of the cell surface glycoconjugates. Gangliosides are sialylated glycosphingolipids highly abundant in neural tissue and considered as tumor markers and therapeutic targets. In this study, a detailed characterization of native ganglioside mixtures from glioblastoma multiforme, corresponding peritumoral tissue and healthy human brain was performed using mass spectrometry and high performance thin layer chromatography in order to elucidate their roles as tumor-associated antigens.

Database and data analysis application for structural characterization of gangliosides and sulfated glycosphingolipids by negative ion mass spectrometry.

Gangliosides and sulfated glycosphingolipids, as building and functional components of animal cell membranes, participate in cell-to-cell interactions and signaling, but also in changes of cell architecture due to different pathophysiological events. In order to enable higher throughput and to facilitate structural characterization of gangliosides/sulfo-glycosphingolipids (GSL) and their neutral GSL counterparts by negative ion mass spectrometry (MS) and tandem MS techniques, a database and data analysis application have been developed. In silico developed glycosphingolipid database considers a high diversity of ceramide compositions, several sialic acid types (N-acetylneuraminic acid, N-glycolylneuraminic acid and 2-keto-3-deoxynononic acid) as well as possible additional substitutions/modifications of glycosphingolipids, such as O-acetylation, de-N-acetylation, fucosylation, glucuronosylation, sulfation, attachment of repeating terminal hexose-N-acetylhexosamine- (Hex-HexNAc-)1-6 extension, and possible lactone forms.

Structural analysis of brain ganglioside acetylation patterns in mice with altered ganglioside biosynthesis.

Gangliosides are sialylated membrane glycosphingolipids especially abundant in mammalian brain tissue. Sialic acid O-acetylation is one of the most common structural modifications of gangliosides which considerably influences their chemical properties. In this study, gangliosides extracted from brain tissue of mice with altered ganglioside biosynthesis (St8sia1 null and B4galnt1 null mice) were structurally characterized and their acetylation pattern was analyzed.

Profiling and sequence analysis of gangliosides in human astrocytoma by high-resolution mass spectrometry.

In this preliminary investigation, a low-grade astrocytoma (AcT) is investigated by high-resolution (HR) mass spectrometry (MS) aiming at characterization of gangliosides with potential biomarker value. The research was conducted towards a comparative mapping of ganglioside expression in AcT, its surrounding tissue (ST) and a normal control brain tissue (NT). HR MS was conducted in the negative ion mode nanoelectrospray ionization (nanoESI).

Assessment of the molecular expression and structure of gangliosides in brain metastasis of lung adenocarcinoma by an advanced approach based on fully automated chip-nanoelectrospray mass spectrometry.

Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor.