PubMed

Related Articles Sialic Acid Derivatization for the Rapid Subclass- and Sialic Acid Linkage-Specific MALDI-TOF-MS Analysis of IgG Fc-Glycopeptides. Methods Mol Biol. 2017;1503:49-62 Authors: de Haan N, Reiding KR, Wuhrer M Abstract Matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)-mass spectrometry (MS) is a highly suitable method for the rapid analysis of IgG glycopeptides, providing a wealth of structural information. A limitation of this approach is that it generates a bias when analyzing sialylated species due to the labile nature of sialic acid glycosidic linkages. One way to overcome this problem is by chemical derivatization of the sialic acids. The method presented here results in both the stabilization of the sialic acids, as well as the differentiation of α2,3- and α2,6-linked sialic acids by mass. Described in this chapter are the isolation of IgG from plasma or serum, tryptic digestion of the samples, derivatization, and finally MALDI-TOF-MS measurement and data analysis. PMID: 27743358 [PubMed - in process]

Related Articles High-Throughput Analysis of IgG Fc Glycopeptides by LC-MS. Methods Mol Biol. 2017;1503:31-47 Authors: Falck D, Jansen BC, de Haan N, Wuhrer M Abstract This chapter contains a nanoscale liquid chromatography-mass spectrometry method for the glycoform profiling of the conserved Fc N-glycosylation site of monoclonal and polyclonal immunoglobulin G (IgG). It describes in detail LaCyTools, a program for automated data (pre-)processing of the obtained LC-MS data. The minimal sample preparation necessary is explained as well as an optional method for affinity purification of (polyclonal) antibodies from serum or plasma.After (optional) affinity purification, the pure IgG is cleaved with trypsin. The tryptic glycopeptides are separated almost exclusively on their peptide backbone. This ensures similar response factors for all glycoforms in the MS detection and allows the collection of separate glycoform profiles for different IgG isoforms or allotypes. LaCyTools automatically performs label-free (relative) quantitation of the obtained data after minimal manual input and additionally calculates several quality criteria which can be used for data curation at the level of both individual analytes and entire LC-MS runs. PMID: 27743357 [PubMed - in process]

Related Articles Development and application of a comprehensive lipidomic analysis to investigate Tripterygium wilfordii-induced liver injury. Anal Bioanal Chem. 2016 Jun;408(16):4341-55 Authors: Xie T, Zhou X, Wang S, Lu Y, Zhu H, Kang A, Deng H, Xu J, Shen C, Di L, Shan J Abstract Lipid metabolic pathways play pivotal roles in liver function, and disturbances of these pathways are associated with various diseases. Thus, comprehensive characterization and measurement of lipid metabolites are essential to deciphering the contributions of lipid network metabolism to diseases or its responses to drug intervention. Here, we report an integrated lipidomic analysis for the comprehensive detection of lipid metabolites. To facilitate the characterization of untargeted lipids through fragmentation analysis, nine formulas were proposed to identify the fatty acid composition of lipids from complex MS (n) spectrum information. By these formulas, the co-eluted isomeric compounds could be distinguished. In total, 250 lipids were detected and characterized, including diacylglycerols, triacylglycerols, glycerophosphoethanolamines, glycerophosphocholines, glycerophosphoserines, glycerophosphoglycerols, glycerophosphoinositols, cardiolipins, ceramides, and sphingomyelins. Integrated with the targeted lipidomics, a total of 27 inflammatory oxylipins were also measured. To evaluate the aberrant lipid metabolism involved in liver injury induced by Tripterygium wilfordii, lipid network metabolism was further investigated. Results indicated that energy lipid modification, membrane remodeling, potential signaling lipid alterations, and abnormal inflammation response were associated with injury. Because of the important roles of lipids in liver metabolism, this new method is expected to be useful in analyzing other lipid metabolism diseases. PMID: 27086014 [PubMed - in process]

Related Articles Editorial: Managing Strategies for Diverse Diseases: Challenges from Bench to Bedside Translation in Successful Drug Discovery and Development (Part B). Curr Pharm Des. 2016;22(20):2923-5 Authors: Kamal MA, Greig NH PMID: 27063488 [PubMed - in process]

Capillary electrophoresis-mass spectrometry for targeted and untargeted analysis of the sub-5 kDa urine metabolome of patients with prostate or bladder cancer: A feasibility study. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 07;1074-1075:79-85 Authors: MacLennan MS, Kok MGM, Soliman L, So A, Hurtado-Coll A, Chen DDY Abstract Targeted and untargeted analyses of the sub-5 kDa urine metabolome of genitourinary cancer patients (prostate and/or bladder) were performed without chemical derivatization using capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS). For targeted analysis, endogenous levels of sarcosine and 5 other amino acid metabolites implicated in the progression of prostate cancer were quantified in four patients and in a pooled urine sample from healthy volunteers. An untargeted analysis (m/z 50 to 850) of patient urine was performed using the same CE-ESI-MS system identifying over 400 distinct molecular features per patient. All patient urine samples were collected at prostatectomy/cystectomy via catheter. Patient urine samples were filtered by centrifugation, with endogenous sarcosine enriched by solid-phase extraction, and the processed samples loaded onto CE-ESI-MS for analysis. Diagnostic information, digital pathological slides, and tissue samples were collected and stored in a comprehensive biobanking database. The introduction of urine sample collection into the surgery workflow was facile and is a promising strategy for addressing the translational research challenge of moving smoothly from "chromatogram to nomogram". PMID: 29334632 [PubMed - as supplied by publisher]

Comparative performance of different scale-down simulators of substrate gradients in Penicillium chrysogenum cultures: the need of a biological systems response analysis. Microb Biotechnol. 2018 Jan 15;: Authors: Wang G, Zhao J, Haringa C, Tang W, Xia J, Chu J, Zhuang Y, Zhang S, Deshmukh AT, van Gulik W, Heijnen JJ, Noorman HJ Abstract In a 54 m3 large-scale penicillin fermentor, the cells experience substrate gradient cycles at the timescales of global mixing time about 20-40 s. Here, we used an intermittent feeding regime (IFR) and a two-compartment reactor (TCR) to mimic these substrate gradients at laboratory-scale continuous cultures. The IFR was applied to simulate substrate dynamics experienced by the cells at full scale at timescales of tens of seconds to minutes (30 s, 3 min and 6 min), while the TCR was designed to simulate substrate gradients at an applied mean residence time (τc) of 6 min. A biological systems analysis of the response of an industrial high-yielding P. chrysogenum strain has been performed in these continuous cultures. Compared to an undisturbed continuous feeding regime in a single reactor, the penicillin productivity (qPenG ) was reduced in all scale-down simulators. The dynamic metabolomics data indicated that in the IFRs, the cells accumulated high levels of the central metabolites during the feast phase to actively cope with external substrate deprivation during the famine phase. In contrast, in the TCR system, the storage pool (e.g. mannitol and arabitol) constituted a large contribution of carbon supply in the non-feed compartment. Further, transcript analysis revealed that all scale-down simulators gave different expression levels of the glucose/hexose transporter genes and the penicillin gene clusters. The results showed that qPenG did not correlate well with exposure to the substrate regimes (excess, limitation and starvation), but there was a clear inverse relation between qPenG and the intracellular glucose level. PMID: 29333753 [PubMed - as supplied by publisher]

Report of an Italian family carrying a typical Indian variant of the Nilgiris tribal groups resulting from a de novo occurrence. Hum Genome Var. 2018;5:17057 Authors: Canu G, Mazzuccato G, Urbani A, Minucci A Abstract G6PD deficiency is quite common in Italy where it is characterized by extreme molecular and biochemical heterogeneity. We report a 15-year-old Italian boy with G6PD Nilgiri (c.593G>A, p.Arg198His), a typical Indian variant of the Nilgiris tribal groups. Further, this variant was biochemically characterized, and the molecular screening of the family highlighted a de novo mutational event. To date, this family is the first Caucasian family carrying the G6PD Nilgiri variant. PMID: 29333274 [PubMed]

Novel Filtration Markers for GFR Estimation. EJIFCC. 2017 Dec;28(4):277-288 Authors: Karger AB, Inker LA, Coresh J, Levey AS, Eckfeldt JH Abstract Creatinine-based glomerular filtration rate estimation (eGFRcr) has been improved and refined since the 1970s through both the Modification of Diet in Renal Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD-EPI) equation in 2009, with current clinical practice dependent primarily on eGFR for accurate assessment of GFR. However, researchers and clinicians have recognized limitations of relying on creatinine as the only filtration marker, which can lead to inaccurate GFR estimates in certain populations due to the influence of non-GFR determinants of serum or plasma creatinine. Therefore, recent literature has proposed incorporation of multiple serum or plasma filtration markers into GFR estimation to improve precision and accuracy and decrease the impact of non-GFR determinants for any individual biomarker. To this end, the CKD-EPI combined creatinine-cystatin C equation (eGFRcr-cys) was developed in 2012 and demonstrated superior accuracy to equations relying on creatinine or cystatin C alone (eGFRcr or eGFRcys). Now, the focus has broadened to include additional novel filtration markers to further refine and improve GFR estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two filtration markers with established assays that have been proposed as candidates for improving both GFR estimation and risk prediction. GFR estimating equations based on B2M and BTP have been developed and validated, with the CKD-EPI combined BTP-B2M equation (eGFRBTP-B2M) demonstrating similar performance to eGFR and eGFR. Additionally, several studies have demonstrated that both B2M and BTP are associated with outcomes in CKD patients, including cardiovascular events, ESRD and mortality. This review will primarily focus on these two biomarkers, and will highlight efforts to identify additional candidate biomarkers through metabolomics-based approaches. PMID: 29333147 [PubMed]

Highlight report: Metabolomics in hepatotoxicity testing. EXCLI J. 2017;16:1323-1325 Authors: Ghallab A PMID: 29333135 [PubMed]

A robust and extendable sheath flow interface with minimal dead volume for coupling CE with ESI-MS. Talanta. 2018 Apr 01;180:376-382 Authors: Fang P, Pan JZ, Fang Q Abstract In this paper, we describe a robust sheath flow-based CE-MS interface with minimal interface dead volume based on an extended pattern. A 20µm i.d. × 90µm o.d. fused-silica capillary with a chemically-etched thin-wall tip (30µm o.d.) was used as the separation capillary as well as electrospray emitter, and a 200µm i.d. × 375µm o.d. capillary with a tapered tip (40µm o.d.) was used as the sheath flow capillary. An extendable sheath-flow interface mode was adopted by decreasing the thickness of separation capillary tip and extending the separation capillary tip out from the sheath flow capillary tip, and allowing the sheath flow to be transferred to the separation capillary tip along its outer surface, forming a surface sheath flow to mix with sample flow at the separation capillary tip. Such a strategy could significantly reduce the interface dead volume and thus improve the CE separation efficiency and detection sensitivity, as well as evidently enhance the working reliability of the CE-MS interface. We investigated various factors affecting the interface performance, including capillary extending distance, emitter diameters, sheath flow capillary shape, and sheath flow rate. Under the optimized conditions, a minimal interface dead volume of ca. 4pL was obtained which is the smallest one compared with previously-reported sheath flow-based CE-MS interfaces. The feasibility and applicability of the present CE-MS interface were demonstrated in the separation of a peptide mixture with high separation efficiency of 2.07-3.38µm plate heights and good repeatabilities (< 6.1% RSD, n = 5). We except such a simple and robust interface could provide a possible solution for the development of commercial CE-MS interfaces differing from the currently-used ones, and has the potentials to be applied in routine analytical laboratories for various studies such as proteomics, metabolomics, or single cell analysis. PMID: 29332826 [PubMed - in process]

Salivary metabolomics profile of patients with recurrent aphthous ulcer as revealed by liquid chromatography-tandem mass spectrometry. J Int Med Res. 2018 Jan 01;:300060517745388 Authors: Li Y, Wang D, Zeng C, Liu Y, Huang G, Mei Z Abstract Objective We compared the salivary nontargeted metabolite profiles between patients with recurrent aphthous ulcer (RAU) and healthy individuals to investigate the metabolic alterations associated with RAU. Methods Saliva samples were collected from 45 patients with RAU and 49 healthy individuals, and the salivary metabolites were quantified using liquid chromatography-tandem mass spectrometry. The metabolomic profiles were then analyzed using multivariate and univariate statistical methods, and enrichment of the metabolites in various biological pathways was assessed. Results In total, 206 significant differentiating metabolites (Wilcoxon test, false discovery rate [FDR] of <0.05) were identified between patients with RAU and healthy individuals. These metabolites were implicated in tryptophan metabolism, steroid hormone biosynthesis, and other metabolic pathways. Two commonly circulating steroids, estrone sulfate and dehydroepiandrosterone sulfate, were significantly lower in the saliva of patients with RAU (Wilcoxon test, FDR < 0.05, power > 0.9). Principal component analysis and partial least-squares discriminant analysis revealed metabolic perturbations involving RAU, and receiver operating characteristic curve analysis with several metabolites showed good diagnostic ability for RAU. Conclusions The results of this study indicate that patients with RAU are characterized by metabolic imbalances. Psychogenic factors, endocrinopathies, and immunosuppression may contribute to the onset of RAU. PMID: 29332424 [PubMed - as supplied by publisher]

Related Articles Highly Time-Resolved Metabolic Reprogramming toward Differential Levels of Phosphate in Chlamydomonas reinhardtii. J Microbiol Biotechnol. 2017 Jun 28;27(6):1150-1156 Authors: Jang CH, Lee G, Park YC, Kim KH, Lee DY Abstract Understanding phosphorus metabolism in photosynthetic organisms is important as it is closely associated with enhanced crop productivity and pollution management for natural ecosystems (e.g., algal blooming). Accordingly, we exploited highly time-resolved metabolic responses to different levels of phosphate deprivation in Chlamydomonas reinhardtii, a photosynthetic model organism. We conducted non-targeted primary metabolite profiling using gas-chromatography time-of-flight mass spectrometric analysis. Primarily, we systematically identified main contributors to degree-wise responses corresponding to the levels of phosphate deprivation. Additionally, we systematically characterized the metabolite sets specific to different phosphate conditions and their interactions with culture time. Among them were various types of fatty acids that were most dynamically modulated by the phosphate availability and culture time in addition to phosphorylated compounds. PMID: 28372038 [PubMed - indexed for MEDLINE]

Related Articles Molecular Identification, Enzyme Assay, and Metabolic Profiling of Trichoderma spp. J Microbiol Biotechnol. 2017 Jun 28;27(6):1157-1162 Authors: Bae SJ, Park YH, Bae HJ, Jeon J, Bae H Abstract The goal of this study was to identify and characterize selected Trichoderma isolates by metabolic profiling and enzyme assay for evaluation of their potential as biocontrol agents against plant pathogens. Trichoderma isolates were obtained from the Rural Development Administration Genebank Information Center (Wanju, Republic of Korea). Eleven Trichoderma isolates were re-identified using ribosomal DNA internal transcribed spacer (ITS) regions. ITS sequence results showed new identification of Trichoderma isolates. In addition, metabolic profiling of the ethyl acetate extracts of the liquid cultures of five Trichoderma isolates that showed the best anti-Phytophthora activities was conducted using gas chromatography-mass spectrometry. Metabolic profiling revealed that Trichoderma isolates shared common metabolites with well-known antifungal activities. Enzyme assays indicated strong cell walldegrading enzyme activities of Trichoderma isolates. Overall, our results indicated that the selected Trichoderma isolates have great potential for use as biocontrol agents against plant pathogens. PMID: 28372034 [PubMed - indexed for MEDLINE]

Related Articles Transcriptomic and metabolic analyses provide new insights into chilling injury in peach fruit. Plant Cell Environ. 2017 Aug;40(8):1531-1551 Authors: Wang K, Yin XR, Zhang B, Grierson D, Xu CJ, Chen KS Abstract Low temperature conditioning (LTC) alleviates peach fruit chilling injury but the underlying molecular basis is poorly understood. Here, changes in transcriptome, ethylene production, flesh softening, internal browning and membrane lipids were compared in fruit maintained in constant 0 °C and LTC (pre-storage at 8 °C for 5 d before storage at 0 °C). Low temperature conditioning resulted in a higher rate of ethylene production and a more rapid flesh softening as a result of higher expression of ethylene biosynthetic genes and a series of cell wall hydrolases. Reduced internal browning of fruit was observed in LTC, with lower transcript levels of polyphenol oxidase and peroxidase, but higher lipoxygenase. Low temperature conditioning fruit also showed enhanced fatty acid content, increased desaturation, higher levels of phospholipids and a preferential biosynthesis of glucosylceramide. Genes encoding cell wall hydrolases and lipid metabolism enzymes were coexpressed with differentially expressed ethylene response factors (ERFs) and contained ERF binding elements in their promoters. In conclusion, LTC is a special case of cold acclimation which increases ethylene production and, operating through ERFs, promotes both softening and changes in lipid composition and desaturation, which may modulate membrane stability, reducing browning and contributing to alleviation of peach fruit chilling injury. PMID: 28337785 [PubMed - indexed for MEDLINE]

Related Articles Global Functional Analysis of Butanol-Sensitive Escherichia coli and Its Evolved Butanol-Tolerant Strain. J Microbiol Biotechnol. 2017 Jun 28;27(6):1171-1179 Authors: Jeong H, Lee SW, Kim SH, Kim EY, Kim S, Yoon SH Abstract Butanol is a promising alternative to ethanol and is desirable for use in transportation fuels and additives to gasoline and diesel fuels. Microbial production of butanol is challenging primarily because of its toxicity and low titer of production. Herein, we compared the transcriptome and phenome of wild-type Escherichia coli and its butanol-tolerant evolved strain to understand the global cellular physiology and metabolism responsible for butanol tolerance. When the ancestral butanol-sensitive E. coli was exposed to butanol, gene activities involved in respiratory mechanisms and oxidative stress were highly perturbed. Intriguingly, the evolved butanol-tolerant strain behaved similarly in both the absence and presence of butanol. Among the mutations occurring in the evolved strain, cis-regulatory mutations may be the cause of butanol tolerance. This study provides a foundation for the rational design of the metabolic and regulatory pathways for enhanced biofuel production. PMID: 28335589 [PubMed - indexed for MEDLINE]

Related Articles Unravelling early events in the Taphrina deformans-Prunus persica interaction: an insight into the differential responses in resistant and susceptible genotypes. Plant Cell Environ. 2017 Aug;40(8):1456-1473 Authors: Svetaz LA, Bustamante CA, Goldy C, Rivero N, Müller GL, Valentini GH, Fernie AR, Drincovich MF, Lara MV Abstract Leaf peach curl is a devastating disease affecting leaves, flowers and fruits, caused by the dimorphic fungus Taphrina deformans. To gain insight into the mechanisms of fungus pathogenesis and plant responses, leaves of a resistant and two susceptible Prunus persica genotypes were inoculated with blastospores (yeast), and the infection was monitored during 120 h post inoculation (h.p.i.). Fungal dimorphism to the filamentous form and induction of reactive oxygen species (ROS), callose synthesis, cell death and defence compound production were observed independently of the genotype. Fungal load significantly decreased after 120 h.p.i. in the resistant genotype, while the pathogen tended to grow in the susceptible genotypes. Metabolic profiling revealed a biphasic re-programming of plant tissue in susceptible genotypes, with an initial stage co-incident with the yeast form of the fungus and a second when the hypha is developed. Transcriptional analysis of PRs and plant hormone-related genes indicated that pathogenesis-related (PR) proteins are involved in P. persica defence responses against T. deformans and that salicylic acid is induced in the resistant genotype. Conducted experiments allowed the elucidation of common and differential responses in susceptible versus resistant genotypes and thus allow us to construct a picture of early events during T. deformans infection. PMID: 28244594 [PubMed - indexed for MEDLINE]

Reprogramming the metabolome rescues retinal degeneration. Cell Mol Life Sci. 2018 Jan 13;: Authors: Park KS, Xu CL, Cui X, Tsang SH Abstract Metabolomics studies in the context of ophthalmology have largely focused on identifying metabolite concentrations that characterize specific retinal diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy have shown that individuals suffering from retinal diseases exhibit metabolic profiles that markedly differ from those of control individuals, supporting the notion that metabolites may serve as easily identifiable biomarkers for specific conditions. An emerging branch of metabolomics resulting from biomarker studies, however, involves the study of retinal metabolic dysfunction as causes of degeneration. Recent publications have identified a number of metabolic processes-including but not limited to glucose and oxygen metabolism-that, when perturbed, play a role in the degeneration of photoreceptor cells. As a result, such studies have led to further research elucidating methods for prolonging photoreceptor survival in an effort to halt degeneration in its early stages. This review will explore the ways in which metabolomics has deepened our understanding of the causes of retinal degeneration and discuss how metabolomics can be used to prevent retinal degeneration from progressing to its later disease stages. PMID: 29332245 [PubMed - as supplied by publisher]

Urinary metabolomics study the mechanism of Taohong Siwu Decoction intervention in acute blood stasis model rats based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 02;1074-1075:51-60 Authors: Zhang X, Li P, Hua Y, Ji P, Yao W, Ma Q, Yuan Z, Wen Y, Yang C, Wei Y Abstract Taohong Siwu Decoction (TSD) is a classic prescription in traditional Chinese medicine and is widely used to promote blood circulation to remove blood stasis. However, the effect mechanisms are not yet well understood. Here, a urinary metabolomic approach based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC/Q-TOF-MS) was conducted to explore the changes in the endogenous metabolites and to assess the integral efficacy of TSD on acute blood stasis model rats. Then, parameters for hemorheology and coagulation functions were detected. Principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) was used to investigate the global metabolite alterations and to evaluate the preventive effects of TSD in rats. Potential metabolite markers were found using OPLS-DA and t-test. Furthermore, metabolic pathway analysis was performed to construct metabolic networks. The results showed that TSD could significantly decrease whole blood viscosity and plasma viscosity. It also significantly prolonged partial thromboplastin time (APPT) and prothrombin time (PT), increased thrombin time (TT) and lowered fibrinogen content (FIB). Moreover, 24 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees after TSD administration. In metabolic networks, amino acid metabolism (arginine and proline metabolism; histidine metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; phenylalanine metabolism) and lipid metabolism (glycerophospholipid metabolism; linoleic acid metabolism; alpha-linolenic acid metabolism) were closely related with the intervention mechanism of TSD on acute blood stasis. The urinary metabolomic approach can be applied to clarify the mechanism of TSD in promoting blood circulation to remove acute blood stasis and to provide the theoretical basis for further research on the therapeutic mechanism of TSD in clinical practice. PMID: 29331744 [PubMed - as supplied by publisher]

Related Articles Hypoxia-Induced Metabolomic Alterations in Pancreatic Cancer Cells. Methods Mol Biol. 2018;1742:95-105 Authors: Gunda V, Kumar S, Dasgupta A, Singh PK Abstract Hypoxic conditions in the pancreatic tumor microenvironment lead to the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which acts as the master regulator of cancer cell metabolism. HIF-1α-mediated metabolic reprogramming results in large-scale metabolite perturbations. Characterization of the metabolic intermediates and the corresponding metabolic pathways altered by HIF-1α would facilitate the identification of therapeutic targets for hypoxic microenvironments prevalent in pancreatic ductal adenocarcinoma and other solid tumors. Targeted metabolomic approaches are versatile in quantifying multiple metabolite levels in a single platform and, thus, enable the characterization of multiple metabolite alterations regulated by HIF-1α. In this chapter, we describe a detailed metabolomic approach for characterizing the hypoxia-induced metabolomic alterations using pancreatic cancer cell lines cultured in normoxic and hypoxic conditions. We elaborate the methodology of cell culture, hypoxic exposure, metabolite extraction, and relative quantification of polar metabolites from normoxia- and hypoxia-exposed cell extracts, using a liquid chromatography-coupled tandem mass spectrometry approach. Herein, using our metabolomic data, we also present the methods for metabolomic data representation. PMID: 29330793 [PubMed - in process]

Related Articles A Metabolomics Pilot Study on Desmoid Tumors and Novel Drug Candidates. Sci Rep. 2018 Jan 12;8(1):584 Authors: Mercier KA, Al-Jazrawe M, Poon R, Acuff Z, Alman B Abstract Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors that lack the ability to metastasize. There are no directed therapies or standard treatment plan, and chemotherapeutics, radiation, and surgery often have temporary effects. The majority of desmoid tumors are related to T41A and S45F mutations of the beta-catenin encoding gene (CTNNB1). Using broad spectrum metabolomics, differences were investigated between paired normal fibroblast and desmoid tumor cells from affected patients. There were differences identified, also, in the metabolomics profiles associated with the two beta-catenin mutations, T41A and S45F. Ongoing drug screening has identified currently available compounds which inhibited desmoid tumor cellular growth by more than 50% but did not affect normal fibroblast proliferation. Two drugs were investigated in this study, and Dasatinib and FAK Inhibitor 14 treatments resulted in unique metabolomics profiles for the normal fibroblast and desmoid tumor cells, in addition to the T41A and S45F. The biochemical pathways that differentiated the cell lines were aminoacyl-tRNA biosynthesis in mitochondria and cytoplasm and signal transduction amino acid-dependent mTORC1 activation. This study provides preliminary understanding of the metabolic differences of paired normal and desmoid tumors cells, their response to desmoid tumor therapeutics, and new pathways to target for therapy. PMID: 29330550 [PubMed - in process]