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Cancer metabolomics

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https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#1
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213207/epimetabolites-discovering-metabolism-beyond-building-and-burning
#2
REVIEW
Megan R Showalter, Tomas Cajka, Oliver Fiehn
Enzymatic transformations of primary, canonical metabolites generate active biomolecules that regulate important cellular and physiological processes. Roles include regulation of histone demethylation in epigenetics, inflammation in tissue injury, insulin sensitivity, cancer cell invasion, stem cell pluripotency status, inhibition of nitric oxide signaling and others. Such modified compounds, defined as epimetabolites, have functions distinct from classic hormones as well as removed from generic anabolism and catabolism...
February 14, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28198377/nmr-metabolic-fingerprints-of-murine-melanocyte-and-melanoma-cell-lines-application-to-biomarker-discovery
#3
Arquimedes Paixão de Santana-Filho, Thiago Jacomasso, Daniel Suss Riter, Andersson Barison, Marcello Iacomini, Sheila Maria Brochado Winnischofer, Guilherme Lanzi Sassaki
Melanoma is the most aggressive type of skin cancer and efforts to improve the diagnosis of this neoplasia are largely based on the use of cell lines. Metabolomics is currently undergoing great advancements towards its use to screening for disease biomarkers. Although NMR metabolomics includes both 1D and 2D methodologies, there is a lack of data in the literature regarding heteronuclear 2D NMR assignments of the metabolome from eukaryotic cell lines. The present study applied NMR-based metabolomics strategies to characterize aqueous and lipid extracts from murine melanocytes and melanoma cell lines with distinct tumorigenic potential, successfully obtaining fingerprints of the metabolites from the extracts of the cell lines by means of 2D NMR HSQC correlation maps...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195169/untargeted-metabolomics-of-colonic-digests-reveals-kynurenine-pathway-metabolites-dityrosine-and-3-dehydroxycarnitine-as-red-versus-white-meat-discriminating-metabolites
#4
Caroline Rombouts, Lieselot Y Hemeryck, Thomas Van Hecke, Stefaan De Smet, Winnok H De Vos, Lynn Vanhaecke
Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194987/mass-defect-based-n-n-dimethyl-leucine-labels-for-quantitative-proteomics-and-amine-metabolomics-of-pancreatic-cancer-cells
#5
Ling Hao, Jillian Johnson, Christopher B Lietz, Amanda Buchberger, Dustin Frost, W John Kao, Lingjun Li
Mass spectrometry-based stable isotope labeling has become a key technology for protein and small-molecule analyses. We developed a multiplexed quantification method for simultaneous proteomics and amine metabolomics analyses via nano reversed-phase liquid chromatography-tandem mass spectrometry (nanoRPLC-MS/MS), called mass defect-based N,N-dimethyl leucine (mdDiLeu) labeling. The duplex mdDiLeu reagents were custom-synthesized with a mass difference of 20.5 mDa, arising from the subtle variation in nuclear binding energy between the two DiLeu isotopologues...
January 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28190989/candidate-serum-metabolite-biomarkers-for-differentiating-gastroesophageal-reflux-disease-barrett-s-esophagus-and-high-grade-dysplasia-esophageal-adenocarcinoma
#6
Matthew F Buas, Haiwei Gu, Danijel Djukovic, Jiangjiang Zhu, Lynn Onstad, Brian J Reid, Daniel Raftery, Thomas L Vaughan
INTRODUCTION/OBJECTIVES: Incidence of esophageal adenocarcinoma (EA), an often fatal cancer, has increased sharply over recent decades. Several important risk factors (reflux, obesity, smoking) have been identified for EA and its precursor, Barrett's esophagus (BE), but a key challenge remains identifying individuals at highest risk, since most with reflux do not develop BE, and most with BE do not progress to cancer. Metabolomics represents an emerging approach for identifying novel biomarkers associated with cancer development...
March 2017: Metabolomics: Official Journal of the Metabolomic Society
https://www.readbyqxmd.com/read/28185575/integration-of-metabolomics-lipidomics-and-clinical-data-using-a-machine-learning-method
#7
Animesh Acharjee, Zsuzsanna Ament, James A West, Elizabeth Stanley, Julian L Griffin
BACKGROUND: The recent pandemic of obesity and the metabolic syndrome (MetS) has led to the realisation that new drug targets are needed to either reduce obesity or the subsequent pathophysiological consequences associated with excess weight gain. Certain nuclear hormone receptors (NRs) play a pivotal role in lipid and carbohydrate metabolism and have been highlighted as potential treatments for obesity. This realisation started a search for NR agonists in order to understand and successfully treat MetS and associated conditions such as insulin resistance, dyslipidaemia, hypertension, hypertriglyceridemia, obesity and cardiovascular disease...
November 22, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28179577/investigations-in-the-possibility-of-early-detection-of-colorectal-cancer-by-gas-chromatography-triple-quadrupole-mass-spectrometry
#8
Shin Nishiumi, Takashi Kobayashi, Shuichi Kawana, Yumi Unno, Takero Sakai, Koji Okamoto, Yasuhide Yamada, Kazuki Sudo, Taiki Yamaji, Yutaka Saito, Yukihide Kanemitsu, Natsuko Tsuda Okita, Hiroshi Saito, Shoichiro Tsugane, Takeshi Azuma, Noriyuki Ojima, Masaru Yoshida
In developed countries, the number of patients with colorectal cancer has been increasing, and colorectal cancer is one of the most common causes of cancer death. To improve the quality of life of colorectal cancer patients, it is necessary to establish novel screening methods that would allow early detection of colorectal cancer. We performed metabolome analysis of a plasma sample set from 282 stage 0/I/II colorectal cancer patients and 291 healthy volunteers using gas chromatography/triple-quadrupole mass spectrometry in an attempt to identify metabolite biomarkers of stage 0/I/II colorectal cancer...
February 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28168355/study-of-early-stage-non-small-cell-lung-cancer-using-orbitrap-based-global-serum-metabolomics
#9
Agnieszka Klupczynska, Paweł Dereziński, Timothy J Garrett, Vanessa Y Rubio, Wojciech Dyszkiewicz, Mariusz Kasprzyk, Zenon J Kokot
PURPOSE: The aim of the project was to apply ultra-high-performance liquid chromatography-quadrupole-Orbitrap-high-resolution mass spectrometry for serum metabolite profiling of non-small-cell lung cancer (NSCLC). This Orbitrap-based methodology has been applied for a study of NSCLC potential markers for the first time. METHODS: After extraction using protein precipitation, sera were separated on the ACE Excel 2 C18-PFP (100 × 2.1 mm, 2.0 µm) column using gradient elution and analyzed within the range of 70-1000 m/z...
February 6, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28163917/mitochondrial-mutations-and-metabolic-adaptation-in-pancreatic-cancer
#10
Rae-Anne Hardie, Ellen van Dam, Mark Cowley, Ting-Li Han, Seher Balaban, Marina Pajic, Mark Pinese, Mary Iconomou, Robert F Shearer, Jessie McKenna, David Miller, Nicola Waddell, John V Pearson, Sean M Grimmond, Leonid Sazanov, Andrew V Biankin, Silas Villas-Boas, Andrew J Hoy, Nigel Turner, Darren N Saunders
BACKGROUND: Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28163219/probing-the-metabolic-phenotype-of-breast-cancer-cells-by-multiple-tracer-stable-isotope-resolved-metabolomics
#11
Andrew N Lane, Julie Tan, Yali Wang, Jun Yan, Richard M Higashi, Teresa W-M Fan
Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using (13)C6-glucose, (13)C-1+2-glucose, (13)C5,(15)N2-Gln, (13)C3-glycerol, and (13)C8-octanoate as tracers...
February 2, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28157703/discovery-and-validation-of-potential-urinary-biomarkers-for-bladder-cancer-diagnosis-using-a-pseudotargeted-gc-ms-metabolomics-method
#12
Yang Zhou, Ruixiang Song, Chong Ma, Lina Zhou, Xinyu Liu, Peiyuan Yin, Zhensheng Zhang, Yinghao Sun, Chuanliang Xu, Xin Lu, Guowang Xu
Bladder cancer (BC) is the second most prevalent malignancy in the urinary system and is associated with significant mortality; thus, there is an urgent need for novel noninvasive diagnostic biomarkers. A urinary pseudotargeted method based on gas chromatography-mass spectrometry was developed and validated for a BC metabolomics study. The method exhibited good repeatability, intraday and interday precision, linearity and metabolome coverage. A total of 76 differential metabolites were defined in the discovery sample set, 58 of which were verified using an independent validation urine set...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28152423/metabolomic-evidence-for-a-field-effect-in-histologically-normal-and-metaplastic-tissues-in-patients-with-esophageal-adenocarcinoma
#13
Michelle A C Reed, Rishi Singhal, Christian Ludwig, John B Carrigan, Douglas G Ward, Phillipe Taniere, Derek Alderson, Ulrich L Günther
Patients with Barrett's esophagus (BO) are at increased risk of developing esophageal adenocarcinoma (EAC). Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using (1)H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO...
January 30, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28149930/ten-years-of-proteomics-in-bladder-cancer-progress-and-future-directions
#14
REVIEW
Maria Frantzi, Antonia Vlahou
Research efforts targeting the identification of bladder cancer biomarkers have been extensive during the past decade. Investigations have been performed at the genome, transcriptome, proteome, and metabolome levels and outputs have started appearing including the sketching of disease molecular subtypes. Proteins are directly linked to cell phenotype hence they accumulate special interest as both biomarkers and therapeutic targets. Multiple technical challenges exist, of the main, being the protein concentration vast dynamic range and presence of proteins in modified forms...
January 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/28145887/organ-specific-isogenic-metastatic-breast-cancer-cell-lines-exhibit-distinct-raman-spectral-signatures-and-metabolomes
#15
Paul T Winnard, Chi Zhang, Farhad Vesuna, Jeon Woong Kang, Jonah Garry, Ramachandra Rao Dasari, Ishan Barman, Venu Raman
Molecular characterization of organ-specific metastatic lesions, which distinguish them from the primary tumor, will provide a better understanding of tissue specific adaptations that regulate metastatic progression. Using an orthotopic xenograft model, we have isolated isogenic metastatic human breast cancer cell lines directly from organ explants that are phenotypically distinct from the primary tumor cell line. Label-free Raman spectroscopy was used and informative spectral bands were ascertained as differentiators of organ-specific metastases as opposed to the presence of a single universal marker...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28138303/amino-acid-profiles-of-serum-and-urine-in-search-for-prostate-cancer-biomarkers-a-pilot-study
#16
Paweł Dereziński, Agnieszka Klupczynska, Wojciech Sawicki, Jerzy A Pałka, Zenon J Kokot
There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28132182/applications-of-metabolomics-in-cancer-studies
#17
Emily Grace Armitage, Michal Ciborowski
Since the start of metabolomics as a field of research, the number of studies related to cancer has grown to such an extent that cancer metabolomics now represents its own discipline. In this chapter, the applications of metabolomics in cancer studies are explored. Different approaches and analytical platforms can be employed for the analysis of samples depending on the goal of the study and the aspects of the cancer metabolome being investigated. Analyses have concerned a range of cancers including lung, colorectal, bladder, breast, gastric, oesophageal and thyroid, amongst others...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28125641/synergistic-action-of-genistein-and-calcitriol-in-immature-osteosarcoma-mg-63-cells-by-sgpl1-up-regulation
#18
Nadja Engel, Anna Adamus, Nicolas Schauer, Juliane Kühn, Barbara Nebe, Guido Seitz, Karin Kraft
BACKGROUND: Phytoestrogens such as genistein, the most prominent isoflavone from soy, show concentration-dependent anti-estrogenic or estrogenic effects. High genistein concentrations (>10 μM) also promote proliferation of bone cancer cells in vitro. On the other hand, the most active component of the vitamin D family, calcitriol, has been shown to be tumor protective in vitro and in vivo. The purpose of this study was to examine a putative synergism of genistein and calcitriol in two osteosarcoma cell lines MG-63 (early osteoblast), Saos-2 (mature osteoblast) and primary osteoblasts...
2017: PloS One
https://www.readbyqxmd.com/read/28122782/a-metabolomic-study-of-biomarkers-of-meat-and-fish-intake
#19
William Cheung, Pekka Keski-Rahkonen, Nada Assi, Pietro Ferrari, Heinz Freisling, Sabina Rinaldi, Nadia Slimani, Raul Zamora-Ros, Milena Rundle, Gary Frost, Helena Gibbons, Eibhlin Carr, Lorraine Brennan, Amanda J Cross, Valeria Pala, Salvatore Panico, Carlotta Sacerdote, Domenico Palli, Rosario Tumino, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Anna Floegel, Francesca Mancini, Marie-Christine Boutron-Ruault, Laura Baglietto, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Augustin Scalbert
BACKGROUND: Meat and fish intakes have been associated with various chronic diseases. The use of specific biomarkers may help to assess meat and fish intake and improve subject classification according to the amount and type of meat or fish consumed. OBJECTIVE: A metabolomic approach was applied to search for biomarkers of meat and fish intake in a dietary intervention study and in free-living subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) study...
January 25, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28121030/the-gut-microbiome-and-the-mechanism-of-surgical-infection
#20
REVIEW
J C Alverdy, S K Hyoju, M Weigerinck, J A Gilbert
BACKGROUND: Since the very early days of surgical practice, surgeons have recognized the importance of considering that intestinal microbes might have a profound influence on recovery from surgical diseases such as appendicitis and peritonitis. Although the pathogenesis of surgical diseases such as cholelithiasis, diverticulosis, peptic ulcer disease and cancer have been viewed as disorders of host biology, they are emerging as diseases highly influenced by their surrounding microbiota...
January 2017: British Journal of Surgery
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