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Cancer metabolomics

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https://www.readbyqxmd.com/read/28323032/metabolic-re-wiring-of-isogenic-breast-epithelial-cell-lines-following-epithelial-to-mesenchymal-transition
#1
Skarphedinn Halldorsson, Neha Rohatgi, Manuela Magnusdottir, Kumari Sonal Choudhary, Thorarinn Guðjónsson, Erik Knutsen, Anna Barkovskaya, Bylgja Hilmarsdottir, Maria Perander, Gunhild M Mælandsmo, Steinn Gudmundsson, Óttar Rolfsson
Epithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype...
March 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28322027/rapid-differentiating-colorectal-cancer-and-colorectal-polyp-using-dried-blood-spot-mass-spectrometry-metabolomic-approach
#2
Yu Jing, Xue Wu, Peng Gao, Zhongze Fang, Jingjing Wu, Qingjun Wang, Chen Li, Zhitu Zhu, Yunfeng Cao
Colorectal cancer (CRC) is the third leading causes of cancer mortality, and the early-stage detection could significantly enhance survival rates. Cancer influences the important metabolic pathways and the changes in metabolite levels had been used in many studies as the potential biomarkers. This study is aimed at screening metabolite biomarkers with CRC diagnosis potentials. The direct infusion mass spectrometry (MS) metabolomic analysis based on dried blood spot was used to distinguish CRC from polyp. The target metabolites were composed of 23 amino acids and 26 acylcarnitines...
March 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28315235/identification-and-quantitation-of-malonic-acid-biomarkers-of-in-born-error-metabolism-by-targeted-metabolomics
#3
Chandra Shekar R Ambati, Furong Yuan, Lutfi A Abu-Elheiga, Yiqing Zhang, Vivekananda Shetty
Malonic acid (MA), methylmalonic acid (MMA), and ethylmalonic acid (EMA) metabolites are implicated in various non-cancer disorders that are associated with inborn-error metabolism. In this study, we have slightly modified the published 3-nitrophenylhydrazine (3NPH) derivatization method and applied it to derivatize MA, MMA, and EMA to their hydrazone derivatives, which were amenable for liquid chromatography- mass spectrometry (LC-MS) quantitation. 3NPH was used to derivatize MA, MMA, and EMA, and multiple reaction monitoring (MRM) transitions of the corresponding derivatives were determined by product-ion experiments...
March 17, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28303220/anemone-medicinal-plants-ethnopharmacology-phytochemistry-and-biology
#4
REVIEW
Da-Cheng Hao, Xiaojie Gu, Peigen Xiao
The Ranunculaceae genus Anemone (order Ranunculales), comprising more than 150 species, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine. Various medicinal compounds have been found in Anemone plants, especially triterpenoid saponins, some of which have shown anti-cancer activities. Some Anemone compounds and extracts display immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial activities. More than 50 species have ethnopharmacological uses, which provide clues for modern drug discovery...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28296891/englerin-a-induces-an-acute-inflammatory-response-and-reveals-lipid-metabolism-and-er-stress-as-targetable-vulnerabilities-in-renal-cell-carcinoma
#5
Ayse Batova, Diego Altomare, Kim E Creek, Robert K Naviaux, Lin Wang, Kefeng Li, Erica Green, Richard Williams, Jane C Naviaux, Mitchell Diccianni, Alice L Yu
Renal cell carcinoma (RCC) is among the top ten most common forms of cancer and is the most common malignancy of the kidney. Clear cell renal carcinoma (cc-RCC), the most common type of RCC, is one of the most refractory cancers with an incidence that is on the rise. Screening of plant extracts in search of new anti-cancer agents resulted in the discovery of englerin A, a guaiane sesquiterpene with potent cytotoxicity against renal cancer cells and a small subset of other cancer cells. Though a few cellular targets have been identified for englerin A, it is still not clear what mechanisms account for the cytotoxicity of englerin A in RCC, which occurs at concentrations well below those used to engage the targets previously identified...
2017: PloS One
https://www.readbyqxmd.com/read/28290700/metabolic-response-to-everolimus-in-patient-derived-triple-negative-breast-cancer-xenografts
#6
Leslie R Euceda, Deborah K Hill, Endre Stokke, Rana Hatem, Rania El Botty, Ivan Bièche, Elisabetta Marangoni, Tone F Bathen, Siver A Moestue
Patients with triple negative breast cancer (TNBC) are unresponsive to endocrine and anti-HER2 pharmacotherapy, limiting their therapeutic options to chemotherapy. TNBC is frequently associated with abnormalities in the PI3K/AKT/mTOR signaling pathway; drugs targeting this pathway are currently being evaluated in these patients. However, response is variable, partly due to heterogeneity within TNBC, conferring a need to identify biomarkers predicting response and resistance to targeted therapy. In this study, we used a metabolomics approach to assess response to the mTOR inhibitor everolimus in a panel of TNBC patient-derived xenografts (PDX) (n=103 animals)...
March 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28290443/inhibition-of-hepatic-lipogenesis-enhances-liver-tumorigenesis-by-increasing-antioxidant-defence-and-promoting-cell-survival
#7
Marin E Nelson, Sujoy Lahiri, Jenny D Y Chow, Frances L Byrne, Stefan R Hargett, David S Breen, Ellen M Olzomer, Lindsay E Wu, Gregory J Cooney, Nigel Turner, David E James, Jill K Slack-Davis, Carolin Lackner, Stephen H Caldwell, Kyle L Hoehn
The metabolic pathway of de novo lipogenesis is frequently upregulated in human liver tumours, and its upregulation is associated with poor prognosis. Blocking lipogenesis in cultured liver cancer cells is sufficient to decrease cell viability; however, it is not known whether blocking lipogenesis in vivo can prevent liver tumorigenesis. Herein, we inhibit hepatic lipogenesis in mice by liver-specific knockout of acetyl-CoA carboxylase (ACC) genes and treat the mice with the hepatocellular carcinogen diethylnitrosamine (DEN)...
March 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28288142/serine-hydroxymethyl-transferase-1-stimulates-pro-oncogenic-cytokine-expression-through-sialic-acid-to-promote-ovarian-cancer-tumor-growth-and-progression
#8
R Gupta, Q Yang, S K Dogra, N Wajapeyee
High-grade serous (HGS) ovarian cancer accounts for 90% of all ovarian cancer-related deaths. However, factors that drive HGS ovarian cancer tumor growth have not been fully elucidated. In particular, comprehensive analysis of the metabolic requirements of ovarian cancer tumor growth has not been performed. By analyzing The Cancer Genome Atlas mRNA expression data for HGS ovarian cancer patient samples, we observed that six enzymes of the folic acid metabolic pathway were overexpressed in HGS ovarian cancer samples compared with normal ovary samples...
March 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28287022/metabolic-map-of-osthole-and-its-effect-on-lipids
#9
Qi Zhao, Xin-Mei Li, Hong-Ning Liu, Frank J Gonzalez, Fei Li
1. Osthole, a coumarin compound from plants, is a promising agent for the treatment of metabolic diseases, including hyperglycemia, fatty liver, and cancers. Studies indicate that the peroxisome proliferator-activated receptors (PPAR) α and γ are involved in the pharmacological effects of osthole. The in vitro and in vivo metabolism of osthole, and its biological activity are not completely understood. 2. In this study, UPLC-ESI-QTOFMS-based metabolomics was used to determine the metabolic pathway of osthole and its influence on the levels of endogenous metabolites...
March 13, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28281355/systemic-effects-of-ionizing-radiation-at-the-proteome-and-metabolome-levels-in-the-blood-of-cancer-patients-treated-with-radiotherapy-the-influence-of-inflammation-and-radiation-toxicity
#10
Karol Jelonek, Monika Pietrowska, Piotr Widlak
Purpose Blood is the most common replacement tissue used to study systemic responses of organisms to different types of pathological conditions and environmental insults. Local irradiation during cancer radiotherapy induces whole body responses that can be observed at the blood proteome and metabolome levels. Hence, comparative blood proteomics and metabolomics are emerging approaches used in the discovery of radiation biomarkers. These techniques enable the simultaneous measurement of hundreds of molecules and the identification of sets of components that can discriminate different physiological states of the human body...
March 10, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28269041/multi-omic-approaches-for-characterization-of-hepatocellular-carcinoma
#11
Habtom W Ressom, Cristina Di Poto, Alessia Ferrarini, Yunli Hu, Mohammad R Nezami Ranjbar, Ehwang Song, Rency S Varghese, Minkun Wang, Shiyue Zhou, Rui Zhu, Yiming Zuo, Mahlet G Tadesse, Yehia Mechref
Multi-omic approaches offer the opportunity to characterize complex diseases such as cancer at various molecular levels. In this paper, we present transcriptomic, proteomic/glycoproteomic, glycomic, and metabolomic (TPGM) data we acquired by analysis of liver tissues from hepatocellular carcinoma (HCC) cases and patients with liver cirrhosis. We evaluated changes in the levels of transcripts, proteins, glycans, and metabolites between tumor and cirrhotic tissues by statistical methods. We demonstrated the potential of multi-omic approaches and network analysis to investigate the interactions among these biomolecules in the progression of liver cirrhosis to HCC...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28262773/metabolomics-for-clinical-use-and-research-in-chronic-kidney-disease
#12
REVIEW
Berthold Hocher, Jerzy Adamski
Chronic kidney disease (CKD) has a high prevalence in the general population and is associated with high mortality; a need therefore exists for better biomarkers for diagnosis, monitoring of disease progression and therapy stratification. Moreover, very sensitive biomarkers are needed in drug development and clinical research to increase understanding of the efficacy and safety of potential and existing therapies. Metabolomics analyses can identify and quantify all metabolites present in a given sample, covering hundreds to thousands of metabolites...
March 6, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28258651/nmr-metabolomics-highlights-sphingosine-kinase-1-as-a-new-molecular-switch-in-the-orchestration-of-aberrant-metabolic-phenotype-in-cancer-cells
#13
Caterina Bernacchioni, Veronica Ghini, Francesca Cencetti, Lukasz Japtok, Chiara Donati, Paola Bruni, Paola Turano
Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase (SK) 1 in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR-based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction of CO2 production...
March 4, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28256598/volatile-metabolomic-signature-of-human-breast-cancer-cell-lines
#14
Catarina L Silva, Rosa Perestrelo, Pedro Silva, Helena Tomás, José S Câmara
Breast cancer (BC) remains the most prevalent oncologic pathology in women, causing huge psychological, economic and social impacts on our society. Currently, the available diagnostic tools have limited sensitivity and specificity. Metabolome analysis has emerged as a powerful tool for obtaining information about the biological processes that occur in organisms, and is a useful platform for discovering new biomarkers or make disease diagnosis using different biofluids. Volatile organic compounds (VOCs) from the headspace of cultured BC cells and normal human mammary epithelial cells, were collected by headspace solid-phase microextraction (HS-SPME) and analyzed by gas chromatography combined with mass spectrometry (GC-MS), thus defining a volatile metabolomic signature...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28256041/metabolic-characterization-of-invaded-cells-of-the-pancreatic-cancer-cell-line-panc-1
#15
Mayumi Fujita, Kaori Imadome, Takashi Imai
We previously reported that about 0.4% of cells in the cultured human pancreatic cancer cell line, PANC-1, can invade matrigel during the transwell invasion assay, suggesting that these invaded PANC-1 cells may have specific characteristics to keep their invasive potential. To identify the metabolic characterization specific in the invaded PANC-1 cells, metabolome analysis of the invaded PANC-1 compared with the whole cultured PANC-1 was performed using CE-TOFMS, and concentrations of 110 metabolites were measured...
March 3, 2017: Cancer Science
https://www.readbyqxmd.com/read/28255294/multilevel-pharmacokinetics-driven-modeling-of-metabolomics-data
#16
Emilia Daghir-Wojtkowiak, Paweł Wiczling, Małgorzata Waszczuk-Jankowska, Roman Kaliszan, Michał Jan Markuszewski
INTRODUCTION: Multilevel modeling is a quantitative statistical method to investigate variability and relationships between variables of interest, taking into account population structure and dependencies. It can be used for prediction, data reduction and causal inference from experiments and observational studies allowing for more efficient elucidation of knowledge. OBJECTIVES: In this study we introduced the concept of multilevel pharmacokinetics (PK)-driven modelling for large-sample, unbalanced and unadjusted metabolomics data comprising nucleoside and creatinine concentration measurements in urine of healthy and cancer patients...
2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28251574/dapne-with-micro-capillary-separatory-chemistry-coupled-to-maldi-ms-for-the-analysis-of-polar-and-non-polar-lipid-metabolism-in-one-cell
#17
Jason S Hamilton, Roberto Aguilar, Robby A Petros, Guido F Verbeck
The cellular metabolome is considered to be a representation of cellular phenotype and cellular response to changes to internal or external events. Methods to expand the coverage of the expansive physiochemical properties that makeup the metabolome currently utilize multi-step extractions and chromatographic separations prior to chemical detection, leading to lengthy analysis times. In this study, a single-step procedure for the extraction and separation of a sample using a micro-capillary as a separatory funnel to achieve analyte partitioning within an organic/aqueous immiscible solvent system is described...
March 1, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28249239/simultaneous-quantification-of-estrogens-their-precursors-and-conjugated-metabolites-in-human-breast-cancer-cells-by-lc-hrms-without-derivatization
#18
Stefan Poschner, Martin Zehl, Alexandra Maier-Salamon, Walter Jäger
Liquid chromatography-mass spectrometry (LC-MS) is the state of the art technique for quantification of steroid hormones. Currently used methods are typically limited by the need of pre-column derivatization to increase ionization efficiency; however, this causes hydrolysis of conjugated metabolites. Our newly established LC-HRMS method is able to simultaneously quantify conjugated and unconjugated steroids without prior derivatization using deuterated internal standards and solid-phase extraction. This assay was validated according to ICH Q2(R1) guidelines for the analysis of the 10 main steroids of the estrogenic pathway, namely 4-androstene-3,17-dione, dehydroepiandrosterone (DHEA), DHEA-3-sulfate, estrone, 17β-estradiol, estriol (16α-OH-17β-estradiol), estrone-3-sulfate, 17β-estradiol-3-(β-d-glucuronide), 17β-estradiol-3-sulfate and testosterone...
February 22, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28248089/mapping-novel-metabolic-nodes-targeted-by-anti-cancer-drugs-that-impair-triple-negative-breast-cancer-pathogenicity
#19
Lindsay S Roberts, Peter Yan, Leslie A Bateman, Daniel K Nomura
Triple-negative breast cancers (TNBCs) are estrogen receptor, progesterone receptor, and HER2 receptor-negative subtypes of breast cancers that show the worst prognoses and lack targeted therapies. Here, we have coupled the screening of ~400 anti-cancer agents that are under development or in the clinic with chemoproteomic and metabolomic profiling to identify novel metabolic mechanisms for agents that impair TNBC pathogenicity. We identify 20 anti-cancer compounds that significantly impaired cell survival across multiple types of TNBC cells...
March 1, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28244322/impact-of-the-pd2spermine-chelate-on-osteosarcoma-metabolism-an-nmr-metabolomics-study
#20
Inês Lamego, M Paula M Marques, Iola F Duarte, Ana S Martins, Helena Oliveira, Ana M Gil
A metabolomics study of Pd2Spermine(Spm) on osteosarcoma MG-63 and osteoblastic HOb cells is presented to assess the impact of the potential palladium drug on cell metabolism compared with cisplatin (cDDP). Despite its higher cytotoxicity, Pd2Spm induced lower (and reversible) metabolic impact on MG-63 cells and the absence of apoptosis; conversely, it induced significant deviations in osteoblastic amino acid metabolism. However, when in combination with doxorubicin and methotrexate, Pd2Spm induced strong metabolic deviations on lipids, choline compounds, amino acids, nucleotides, and compounds related to antioxidative mechanisms (e...
March 14, 2017: Journal of Proteome Research
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