scholarly journals Mass Spectrometry-Based Metabolomics Analysis of Obese Patients’ Blood Plasma

2020 ◽  
Vol 21 (2) ◽  
pp. 568 ◽  
Author(s):  
Petr G. Lokhov ◽  
Elena E. Balashova ◽  
Oxana P. Trifonova ◽  
Dmitry L. Maslov ◽  
Elena A. Ponomarenko ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Metabolic Diseases ◽  
Enrichment Analysis ◽  
Blood Analysis ◽  
Response To Treatment ◽  
Estrogen Metabolism ◽  
Obese Patients ◽  
Complex Samples ◽  
Additional Information ◽  
Metabolite Set Enrichment Analysis

Scientists currently use only a small portion of the information contained in the blood metabolome. The identification of metabolites is a huge challenge because only highly abundant and well-separated compounds can be easily identified in complex samples. However, new approaches that enhance the identification of compounds have emerged; among them, the identification of compounds based on their involvement in a particular biological context is a recent development. In this work, this approach was first applied to identify metabolites in complex samples and, together with metabolite set enrichment analysis, was used for the evaluation of blood plasma from obese patients. The proposed approach was found to provide a statistically sound overview of the biochemical pathways, thus presenting additional information on obesity. Obesity progression was demonstrated to be accompanied by marked alterations in steroidogenesis, androstenedione metabolism, and androgen and estrogen metabolism. The findings of this study suggest that the workflow used for blood analysis is sufficient to demonstrate obesity at the biochemical pathway level as well as to monitor the response to treatment. This workflow is also expected to be suitable for studying other metabolic diseases.

scholarly journals The use of hyperpolarised 13C-MRI in clinical body imaging to probe cancer metabolism

2021 ◽  
Author(s):  
Ramona Woitek ◽  
Ferdia A. Gallagher
Keyword(s):  
Cancer Metabolism ◽  
Signal To Noise Ratio ◽  
Response Assessment ◽  
Early Response ◽  
Multiparametric Mri ◽  
Metabolic Reprogramming ◽  
Response To Treatment ◽  
Additional Information ◽  
Positron Emission ◽  
Breast And Prostate Cancer

AbstractMetabolic reprogramming is one of the hallmarks of cancer and includes the Warburg effect, which is exhibited by many tumours. This can be exploited by positron emission tomography (PET) as part of routine clinical cancer imaging. However, an emerging and alternative method to detect altered metabolism is carbon-13 magnetic resonance imaging (MRI) following injection of hyperpolarised [1-13C]pyruvate. The technique increases the signal-to-noise ratio for the detection of hyperpolarised 13C-labelled metabolites by several orders of magnitude and facilitates the dynamic, noninvasive imaging of the exchange of 13C-pyruvate to 13C-lactate over time. The method has produced promising preclinical results in the area of oncology and is currently being explored in human imaging studies. The first translational studies have demonstrated the safety and feasibility of the technique in patients with prostate, renal, breast and pancreatic cancer, as well as revealing a successful response to treatment in breast and prostate cancer patients at an earlier stage than multiparametric MRI. This review will focus on the strengths of the technique and its applications in the area of oncological body MRI including noninvasive characterisation of disease aggressiveness, mapping of tumour heterogeneity, and early response assessment. A comparison of hyperpolarised 13C-MRI with state-of-the-art multiparametric MRI is likely to reveal the unique additional information and applications offered by the technique.

scholarly journals Identifying Personalized Metabolic Signatures in Breast Cancer

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 20
Author(s):  
Priyanka Baloni ◽  
Wikum Dinalankara ◽  
John C. Earls ◽  
Theo A. Knijnenburg ◽  
Donald Geman ◽  
...  
Keyword(s):  
Drug Targets ◽  
Metabolic Networks ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas ◽  
Estrogen Metabolism ◽  
Acid Oxidation ◽  
A Genome ◽  
Context Specific

Cancer cells are adept at reprogramming energy metabolism, and the precise manifestation of this metabolic reprogramming exhibits heterogeneity across individuals (and from cell to cell). In this study, we analyzed the metabolic differences between interpersonal heterogeneous cancer phenotypes. We used divergence analysis on gene expression data of 1156 breast normal and tumor samples from The Cancer Genome Atlas (TCGA) and integrated this information with a genome-scale reconstruction of human metabolism to generate personalized, context-specific metabolic networks. Using this approach, we classified the samples into four distinct groups based on their metabolic profiles. Enrichment analysis of the subsystems indicated that amino acid metabolism, fatty acid oxidation, citric acid cycle, androgen and estrogen metabolism, and reactive oxygen species (ROS) detoxification distinguished these four groups. Additionally, we developed a workflow to identify potential drugs that can selectively target genes associated with the reactions of interest. MG-132 (a proteasome inhibitor) and OSU-03012 (a celecoxib derivative) were the top-ranking drugs identified from our analysis and known to have anti-tumor activity. Our approach has the potential to provide mechanistic insights into cancer-specific metabolic dependencies, ultimately enabling the identification of potential drug targets for each patient independently, contributing to a rational personalized medicine approach.

scholarly journals Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in Postmenopausal Women

2017 ◽  
Vol 102 (12) ◽  
pp. 4588-4595 ◽  
Author(s):  
Natalia Hetemäki ◽  
Hanna Savolainen-Peltonen ◽  
Matti J Tikkanen ◽  
Feng Wang ◽  
Hanna Paatela ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Postmenopausal Women ◽  
Messenger Rna ◽  
Metabolic Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Subcutaneous Fat ◽  
Estrogen Metabolism ◽  
Serum Samples ◽  
Estrogen Exposure

Abstract Context In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. Objective We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. Design, Setting, Patients, and Interventions AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. Results Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). Conclusions Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.

scholarly journals Metabolomic Profiling Reveals a Role for Caspase-2 in Lipoapoptosis

2013 ◽  
Vol 288 (20) ◽  
pp. 14463-14475 ◽  
Author(s):  
Erika Segear Johnson ◽  
Kelly R. Lindblom ◽  
Alexander Robeson ◽  
Robert D. Stevens ◽  
Olga R. Ilkayeva ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Metabolic Diseases ◽  
Response To Treatment ◽  
Alcoholic Fatty Liver ◽  
Metabolomic Profiling ◽  
Egg Extracts ◽  
Attractive Therapeutic Target ◽  
Caspase 2 ◽  
Induced Apoptosis ◽  
Alcoholic Fatty Liver Disease

The accumulation of long-chain fatty acids (LCFAs) in non-adipose tissues results in lipid-induced cytotoxicity (or lipoapoptosis). Lipoapoptosis has been proposed to play an important role in the pathogenesis of several metabolic diseases, including non-alcoholic fatty liver disease, diabetes mellitus, and cardiovascular disease. In this report, we demonstrate a novel role for caspase-2 as an initiator of lipoapoptosis. Using a metabolomics approach, we discovered that the activation of caspase-2, the initiator of apoptosis in Xenopus egg extracts, is associated with an accumulation of LCFA metabolites. Metabolic treatments that blocked the buildup of LCFAs potently inhibited caspase-2 activation, whereas adding back an LCFA in this scenario restored caspase activation. Extending these findings to mammalian cells, we show that caspase-2 was engaged and activated in response to treatment with the saturated LCFA palmitate. Down-regulation of caspase-2 significantly impaired cell death induced by saturated LCFAs, suggesting that caspase-2 plays a pivotal role in lipid-induced cytotoxicity. Together, these findings reveal a previously unknown role for caspase-2 as an initiator caspase in lipoapoptosis and suggest that caspase-2 may be an attractive therapeutic target for inhibiting pathological lipid-induced apoptosis.

scholarly journals Establishment of a Pretreatment Nomogram to Predict the 6-Month Mortality Rate of Patients with Advanced Biliary Tract Cancers Undergoing Gemcitabine-Based Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3139
Author(s):  
Chiao-En Wu ◽  
Wen-Kuan Huang ◽  
Wen-Chi Chou ◽  
Chia-Hsun Hsieh ◽  
John Wen-Cheng Chang ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Mortality Rate ◽  
Biliary Tract ◽  
Mortality Risk ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Cytotoxic Agents ◽  
Response To Treatment ◽  
Tract Cancer ◽  
Additional Information

Background: The estimation of mortality risk among patients diagnosed with advanced cancer provides important information for clinicians and patients in clinical practice. Currently, gemcitabine-based chemotherapy regimens are the standard treatment for patients with advanced biliary tract cancer (BTC). We aimed to develop a nomogram to predict the 6-month mortality rate among patients with advanced BTC to help physicians evaluate treatment options and outcomes. Patients: We conducted a retrospective analysis to evaluate the 6-month mortality rate among patients with advanced BTC who underwent gemcitabine-based chemotherapy from 2012 to 2018. Data regarding pretreatment factors and the clinical response to treatment were collected. Univariate and multivariate analyses were performed to identify independent factors for nomogram creation. Results: A total of 202 advanced BTC patients who were treated with gemcitabine-based chemotherapy were included in this analysis. No difference in survival was identified between patients undergoing gemcitabine monotherapy and those treated with gemcitabine combined with other cytotoxic agents. The univariate analysis revealed 10 significant factors, while the multivariate analysis identified four independent factors, including gender, monocyte to lymphocyte ratio (MLR), alkaline phosphatase (ALP), and liver metastasis, which were used to establish the nomogram. The performance of this nomogram for the prediction of 6-month mortality risk was found to be promising and feasible based on logistic regression. Conclusion: A nomogram based on four independent pretreatment factors, including gender, MLR, ALP, and liver metastasis, was established to predict the 6-month mortality risk in patients with advanced BTC; it can provide clinicians and patients with additional information when evaluating treatment outcomes.

Aortomesenteric Fat Thickness With Ultrasound Predicts Metabolic Diseases in Obese Patients

2014 ◽  
Vol 347 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Luigi Monaco ◽  
Laura Castaldo ◽  
Giuseppe Castaldo ◽  
Mario Monaco ◽  
Luigi Di Tommaso ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Obese Patients ◽  
Fat Thickness

scholarly journals Preliminary results using PET/MR in glioblastoma patients treated with regorafenib: an 18F-FET and DWI-ADC comparison

2021 ◽  
Author(s):  
Alessandro Spimpolo ◽  
Giuseppe Lombardi ◽  
Sara Berti ◽  
Cristina Campi ◽  
Maria Giulia Anglani ◽  
...  
Keyword(s):  
Early Response ◽  
Recurrent Glioblastoma ◽  
Response To Treatment ◽  
Fet Pet ◽  
Additional Information ◽  
Rano Criteria ◽  
Percentage Difference ◽  
Before And After ◽  
The Difference ◽  
Cancer Network

Abstract Introduction: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. DWI and 18F–FET PET are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in DWI/ADC- and 18F-FET PET-derived parameters in patients who underwent PET/MR at both baseline and soon after starting regorafenib. Method: We retrospectively selected 16 consecutive GBM patients who underwent 18F–FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze 4 SD patients who underwent a third PET/MR after another 4 cycles of regorafenib. 18F–FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and soon after treatment. A number of metrics were then derived and compared. Result: The average increases in FET and ADC pathological volumes were higher in PD than in SD patients, although in neither case did the difference reach significance. However, when the percentage difference in FET volumes was plotted against the corresponding percentage difference in ADC, a correlation was observed (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Conclusion: In recurrent glioblastoma patients treated with regorafenib, 18F-FET and ADC metrics, being obtained from completely different measures, could serve as semi-quantitative independent biomarkers of response to treatment. These promising parameters should be tested in a larger cohort of glioblastoma patients treated with regorafenib.

MODELS AND METHODS OF INFORMATION TECHNOLOGY OF ADVANCED NEONOTAL SCREENING

2021 ◽  
Vol 6 ◽  
pp. 129-147
Author(s):  
Yekaterina Kovalоva ◽  
◽  
Vladimir Lyfar ◽  
◽  
Keyword(s):  
Information Technology ◽  
Neonatal Screening ◽  
Metabolic Diseases ◽  
Block Diagram ◽  
Information Model ◽  
Blood Analysis ◽  
Hereditary Diseases ◽  
Information Support ◽  
Information Flows ◽  
Hereditary Metabolic Diseases

The paper considers the problems of informational implementation of neonatal screening of newborns in order to improve the overall picture of the nation's health and prevent the development of hereditary diseases. The methodology for solving the problems of complete neonatal screening is based on the methods and mathematical apparatus of discrete mathematics, web technologies, data warehouses, and data mining methods. An information model of the dynamic processes of neonatal screening is proposed, based on the specific processing of data presented by a tuple, which contains coherent sequential processes for obtaining the results of tests for blood analysis of newborns, conducting genetic studies and determining pathologies and deviations from an expanded list (currently up to 44 indicators for the purpose of exiting for more than 60). The block diagram of information support of information technology in the decision support system for carrying out neonatal screening of hereditary metabolic diseases is presented. On the basis of LLC «CDC «PHARMBIOTEST», the research of the algorithm for performing sequential procedures of neonatal screening was carried out. The described algorithm of actions has been tested and fully tested for the continuity of information flows, the stability of the information model graph. As a result of the research, the sufficiency and completeness of the chronological indicators of the processing of information flows have been proved. The criteria for confirming the authenticity of methods for obtaining a diagnosis have been developed.

Identification and Analysis of lncRNAs by Whole-Transcriptome Sequencing in Porcine Preadipocytes Induced by BMP2

2019 ◽  
Vol 158 (3) ◽  
pp. 133-144
Author(s):  
Sheng Li ◽  
Chengzhen Chen ◽  
Menglong Chai ◽  
Jiawei Wang ◽  
Bao Yuan ◽  
...  
Keyword(s):  
Target Genes ◽  
Metabolic Diseases ◽  
Enrichment Analysis ◽  
Fat Deposition ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Whole Transcriptome Sequencing ◽  
Mirna Sponges ◽  
Whole Transcriptome ◽  
First Time

Bone morphogenetic protein 2 (BMP2) can mediate the signaling of R-Smads and regulate different biological functions, including adipocyte differentiation. Long noncoding RNAs (lncRNAs) can be involved in many important biological processes, including fat metabolism, as miRNA sponges. This study aimed to investigate the molecular mechanism of fat deposition and to provide useful information for the prevention and treatment of lipid-related diseases. lncRNA sequencing was performed to compare and analyze, for the first time, the expression of lncRNAs in BMP2-induced and non-BMP2-induced preadipocytes from Junmu1 pigs. In addition, functional annotation and enrichment analysis of differentially expressed lncRNA target genes were carried out. lncRNAs and mRNAs were compared and analyzed. lncRNAs were identified that may regulate adipogenesis and lipid metabolism. The results give a theoretical basis for further studies on fat deposition mechanisms and provide potential therapeutic targets for metabolic diseases.

Peripheral immunological response to treatment with checkpoint inhibitor in recurrent/metastatic nasopharyngeal carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18519-e18519
Author(s):  
Dora Lai Wan Kwong ◽  
Ngar-Woon Kam ◽  
Ho-Yin Luk ◽  
Tae Yang Desmond Hung ◽  
Man Kim Yim ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Checkpoint Inhibitors ◽  
Immunological Response ◽  
Blood Analysis ◽  
Response To Treatment ◽  
Chemotherapy Response ◽  
Group 2 ◽  
Drug Responsiveness ◽  
Cellular Phenotypes

e18519 Background: A better understanding of peripheral cellular phenotypes in association with checkpoint inhibitors (CPI) responsiveness in recurrent/metastatic NPC could profoundly impact our knowledge of NPC immunopathology. Methods: Blood were collected from 11 patients with recurrent/metastatic NPC who received CPI (pembrolizumab) after failing second-line chemotherapy. Response to pembrolizumab was assessed by imaging and EBV DNA. Patients who achieved CR/PR were considered responsive and those with SD/PD were considered non-responsive. Four patients in the responsive group also had baseline blood before pembrolizumab. PBMC were freshly isolated and stored until analysis. For surface staining, cells were rested overnight at 37°C before resuspended in BD Brilliant stain with 2.5ng/µl Fc block for 15mins. Cells were then co-stained: 7-AAD, CD19-BV510, CD3-Alexa Fluo 700, CD4-BV510, CD279(PD-1)-BB515, CD197(CCR7)-BV421, CD45RO-APC, CD45RA-Pe-Cy5, CD8-APC-H7, CD27-PE, CD95-PE-Cy7, incubated on ice for 30mins. Samples were washed and acquired on NovoCyte Quanteon. Immune phenotypes were correlated with clinical response. Results: We found that: 1) %CD3 was upregulated in responsive group; 2) CD4/CD8 ratio did not directly stratify drug responsiveness; 3) frequency of PD1-expressing CD8+ T cells was significantly reduced in responsive group; 4) lower frequency of CCR7+PD1+CD8+ T cells in responsive group, suggesting that these may be highly differentiated and have the ability to move into peripheral sites in response to inflammatory chemokines; 5) frequency of naïve and TEMRA CD8+ T cells, but not Tscm was upregulated in responsive group; 6) finally, an interesting finding of sustained CD19+ subsets was observed in non-responsive group. Conclusions: Our results suggest that peripheral blood analysis may provide valuable insights into NPC patients’ responses to PD-1-targeted therapies. [Table: see text]

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