RESUMEN
Recently it has been shown that phosphorylation of the Ser8 residue in amyloid-beta (pS8-Abeta) is tightly involved in the pathogenesis ofAlzheimer's disease. Since this modification occurs in the key metal-binding domain of amyloid-beta, and thus should seriously affect the interaction of pS8-Abeta with zinc ions, this isoform might be a potential precursor of pathogenic oligomeric forms of amyloid beta. Hence the level of pS8-Abeta in human biological fluids (such as blood, urine, cerebral spinal fluid) might resemble the different stages of the pathogenesis of Alzhe- imer's disease. The aim of this workwas to develop a prototype of an analytical method for quantitative determination of the level of pS8-Abeta isoform in binary mixtures with native amyloid-beta in order to further use it to determine the levels of phosphorylated amyloid-beta in blood plasma samples of patients with Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/sangre , Péptidos beta-Amiloides/sangre , Péptidos beta-Amiloides/metabolismo , Espectrometría de Masas/métodos , Secuencia de Aminoácidos , Calibración , Humanos , Datos de Secuencia Molecular , Fosforilación , Serina/metabolismoRESUMEN
Significant metabolism alteration is accompanying the cell malignization process. Energy metabolism disturbance leads to the activation of de novo synthesis and beta-oxidation processes of lipids and fatty acids in a cancer cell, which becomes an indicator of pathological processes inside the cell. The majority of studies dealing with lipid metabolism alterations in glial tumors are performed using the cell lines in vitro or animal models. However, such conditions do not entirely represent the physiological conditions of cell growth or possible cells natural variability. This work presents the results of the data obtained by applying ambient mass spectrometry to human glioblastoma multiform tissues. By analyzing a relatively large cohort of primary and secondary glioblastoma samples, we identify the alterations in cells lipid composition, which accompanied the development of grade IV brain tumors. We demonstrate that primary glioblastomas, as well as ones developed from astrocytomas, are enriched with mono- and diunsaturated phosphatidylcholines (PC 26:1, 30:2, 32:1, 32:2, 34:1, 34:2). Simultaneously, the saturated and polyunsaturated phosphatidylcholines and phosphatidylethanolamines decrease. These alterations are obviously linked to the availability of the polyunsaturated fatty acids and activation of the de novo lipid synthesis and beta-oxidation pathways under the anaerobic conditions in the tumor core.
Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioblastoma , Animales , Humanos , Metabolismo de los Lípidos , FosfatidilcolinasRESUMEN
Express MS identification of biological tissues has become a much more accessible research method due to the application of direct specimen ionization at atmospheric pressure. In contrast to traditional methods of analysis employing GC-MS methods for determining the molecular composition of the analyzed objects it eliminates the influence of mutual ion suppression. Despite significant progress in the field of direct MS of biological tissues, the question of mass spectrometric profile attribution to a certain type of tissue still remains open. The use of modern machine learning methods and protocols (e.g., "random forests") enables us to trace possible relationships between the components of the sample MS profile and the result of brain tumor tissue classification (astrocytoma or glioblastoma). It has been shown that the most pronounced differences in the mass spectrometric profiles of these tumors are due to their lipid composition. Detection of statistically significant differences in lipid profiles of astrocytoma and glioblastoma may be used to perform an express test during surgery and inform the neurosurgeon what type of malignant tissue he is working with. The ability to accurately determine the boundaries of the neoplastic growth significantly improves the quality of both surgical intervention and postoperative rehabilitation, as well as the duration and quality of life of patients.
Asunto(s)
Astrocitoma , Biomarcadores de Tumor , Neoplasias Encefálicas , Glioblastoma , Lípidos , Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Humanos , Lípidos/análisis , Masculino , Calidad de VidaRESUMEN
In this work, we demonstrate a new approach for assessing the stability and reproducibility of mass spectra obtained via ambient ionization methods. This method is suitable for both comparing experiments during which only one mass spectrum is measured and for evaluating the internal homogeneity of mass spectra collected over a period of time. The approach uses Pearson's r coefficient and the cosine measure to compare the spectra. It is based on the visualization of dissimilarities between measurements, thus leading to the analysis of dissimilarity patterns. The cosine measure and correlations are compared to obtain better metrics for spectra homogeneity. The method filters out unreliable scans to prevent the analyzed sample from being wrongly characterized. The applicability of the method is demonstrated on a set of brain tumor samples. The developed method could be employed in neurosurgical applications, where mass spectrometry is used to monitor the intraoperative tumor border.
RESUMEN
The majority of research in the biomedical sciences is carried out with the highest resolution accessible to the scientist, but, in the clinic, cost constraints necessitate the use of low-resolution devices. Here, we compare high- and low-resolution direct mass spectrometry profiling data and propose a simple pre-processing technique that makes high-resolution data suitable for the development of classification and regression techniques applicable to low-resolution data, while retaining high accuracy of analysis. This work demonstrates an approach to de-noising spectra to make the same representation for both high- and low-resolution spectra. This approach uses noise threshold detection based on the Tversky index, which compares spectra with different resolutions, and minimizes the percentage of resolution-specific peaks. The presented method provides an avenue for the development of analytical algorithms using high-resolution mass spectrometry data, while applying these algorithms in the clinic using low-resolution mass spectrometers.