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Cancer metabolomics

Lihui Men, Zifeng Pi, Yuan Zhou, Mengying Wei, Yuanyuan Liu, Fengrui Song, Zhongying Liu
Obesity has become a global epidemic and public health challenge which associates with serious health issues including diabetes, cardiovascular disease, stroke, arthritis, and some types of cancer. To better understand obesity and obesity-related dysfunction, a high-fat diet (HFD) induced obese model was developed on Sprague-Dawley rats. Metabolomics based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was untilized to identify and analyze obesity related metabolites in rat urine samples...
October 14, 2016: Journal of Pharmaceutical and Biomedical Analysis
A Blomme, B Costanza, P de Tullio, M Thiry, G Van Simaeys, S Boutry, G Doumont, E Di Valentin, T Hirano, T Yokobori, S Gofflot, O Peulen, A Bellahcène, F Sherer, C Le Goff, E Cavalier, A Mouithys-Mickalad, F Jouret, P G Cusumano, E Lifrange, R N Muller, S Goldman, P Delvenne, E De Pauw, M Nishiyama, V Castronovo, A Turtoi
Myoferlin is a multiple C2-domain-containing protein that regulates membrane repair, tyrosine kinase receptor function and endocytosis in myoblasts and endothelial cells. Recently it has been reported as overexpressed in several cancers and shown to contribute to proliferation, migration and invasion of cancer cells. We have previously demonstrated that myoferlin regulates epidermal growth factor receptor activity in breast cancer. In the current study, we report a consistent overexpression of myoferlin in triple-negative breast cancer cells (TNBC) over cells originating from other breast cancer subtypes...
October 24, 2016: Oncogene
Raj Kumar Sharma, Kumudesh Mishra, Alvina Farooqui, Anu Behari, Vinay Kumar Kapoor, Neeraj Sinha
OBJECTIVE AND DESIGN: We present in this article (1)H nuclear magnetic resonance (NMR)-based metabolic approach to screen the serum metabolic alterations in human gallbladder inflammation with chronic cholecystitis (CC). MATERIAL/METHODS: Total of 71 human serum samples was divided into two groups, (n = 41, CC) and (n = 30 control). (1)H NMR metabolic profiling was carried out for investigation of metabolic alterations. Multivariate statistical analysis was applied for pattern recognition and identification of metabolites playing crucial role in gallbladder inflammation...
October 21, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Nina Holland
Environmental research and public health in the 21st century face serious challenges such as increased air pollution and global warming, widespread use of potentially harmful chemicals including pesticides, plasticizers, and other endocrine disruptors, and radical changes in nutrition and lifestyle typical of modern societies. In particular, exposure to environmental and occupational toxicants may contribute to the occurrence of adverse birth outcomes, neurodevelopmental deficits, and increased risk of cancer and other multifactorial diseases such as diabetes and asthma...
October 21, 2016: Reviews on Environmental Health
John J Guardiola, Juliane I Beier, K Cameron Falkner, Benjamin Wheeler, Craig James McClain, Matt Cave
BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS(2) analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed...
October 17, 2016: Toxicology and Applied Pharmacology
Marissa B Guzzo, Hoa T Nguyen, Thanh H Pham, Monika Wyszczelska-Rokiel, Hieronim Jakubowski, Kerstin A Wolff, Sam Ogwang, Joseph L Timpona, Soumya Gogula, Michael R Jacobs, Markus Ruetz, Bernhard Kräutler, Donald W Jacobsen, Guo-Fang Zhang, Liem Nguyen
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis...
October 2016: PLoS Pathogens
Theerawut Chanmee, Pawared Ontong, Tomomi Izumikawa, Miho Higashide, Nobutoshi Mochizuki, Chatchadawalai Chokchaitaweesuk, Manatsanan Khansai, Kazuki Nakajima, Ikuko Kakizaki, Prachya Kongtawelert, Naoyuki Taniguchi, Naoki Itano
Cancer stem cells (CSCs) represent a small subpopulation of self-renewing oncogenic cells. Like many other stem cells, metabolic reprogramming has been implicated to be a key characteristic of CSCs. However, little is known on how the metabolic features of cancer cells are controlled to orchestrate their CSC-like properties. We recently demonstrated that hyaluronan (HA) overproduction allowed plastic cancer cells to revert to stem-cell states. Here, we adopted stable isotope-assisted tracing and mass spectrometry profiling to elucidate the metabolic features of HA-overproducing breast cancer cells...
October 6, 2016: Journal of Biological Chemistry
Sanad Alonezi, Jonans Tusiimire, Jennifer Wallace, Mark J Dufton, John A Parkinson, Louise C Young, Carol J Clements, Jin Kyu Park, Jong Woon Jeon, Valerie A Ferro, David G Watson
In the present study, liquid chromatography-mass spectrometry (LC-MS) was employed to characterise the metabolic profiles of two human ovarian cancer cell lines A2780 (cisplatin-sensitive) and A2780CR (cisplatin-resistant) in response to their exposure to melittin, a cytotoxic peptide from bee venom. In addition, the metabolomics data were supported by application of Biolog microarray technology to examine the utilisation of carbon sources by the two cell lines. Data extraction with MZmine 2.14 and database searching were applied to provide metabolite lists...
October 13, 2016: Metabolites
Valentina Di Gialleonardo, Sui Seng Tee, Hannah N Aldeborgh, Vesselin Z Miloushev, Lidia S Cunha, George D Sukenick, Kayvan R Keshari
Nuclear magnetic resonance (NMR) spectroscopy is used in metabolomics to perform quantitative profiling of low-molecular weight compounds from biological specimens. The measurement of endogenous metabolites using NMR can identify new metabolic biomarkers in physiological and pathological conditions, and assess treatment response. In this study we present a rapid approach to indirectly quantify 13C enriched molecules using one-dimensional (1D) 1H NMR. We demonstrate this approach using isotopically labeled [1,6-13C]glucose and in 4 different cell lines...
October 17, 2016: Analytical Chemistry
Hailong Zhang, Liang Qiao, Xiaopeng Li, Yang Wan, Li Yang, Huijuan Wang
Lymph node metastasis is a decisive prognostic and therapeutic staging factor for colorectal cancer (CRC), which is one of the most prevalent types of cancer and a malignant tumor. The metabolic profiling of tissue samples from a large cohort of lymph node non‑metastatic CRC patients (n=73), lymph node metastatic CRC patients (n=52) and normal controls (n=41) was performed using 1H nuclear magnetic resonance (NMR) together with multivariate statistical analyses. Excellent separation was obtained between CRC patients and normal controls, and CRC patients were also perfectly classified according to lymph node metastasis...
October 14, 2016: Oncology Reports
Luisa Matos Do Canto, Catalin Marian, Rency S Varghese, Jaeil Ahn, Patricia A Da Cunha, Shawna Willey, Mary Sidawy, Janice D Rone, Amrita K Cheema, George Luta, Mohammad R Nezami Ranjbar, Habtom W Ressom, Bassem R Haddad
Identification of new biomarkers for breast cancer remains critical in order to enhance early detection of the disease and improve its prognosis. Towards this end, we performed an untargeted metabolomic analysis of breast ductal fluid using an ultra-performance liquid chromatography coupled with a quadrupole time-of-light (UPLC-QTOF) mass spectrometer. We investigated the metabolomic profiles of breast tumors using ductal fluid samples collected by ductal lavage (DL). We studied fluid from both the affected breasts and the unaffected contralateral breasts (as controls) from 43 women with confirmed unilateral breast cancer...
October 13, 2016: International Journal of Oncology
Jessica Brandi, Ilaria Dando, Elisa Dalla Pozza, Giulia Biondani, Rosalind Jenkins, Victoria Elliott, Kevin Park, Giuseppina Fanelli, Lello Zolla, Eithne Costello, Aldo Scarpa, Daniela Cecconi, Marta Palmieri
: Recently, we have shown that the secretome of pancreatic cancer stem cells (CSCs) is characterized by proteins that participate in cancer differentiation, invasion, and metastasis. However, the differentially expressed intracellular proteins that lead to the specific characteristics of pancreatic CSCs have not yet been identified, and as a consequence the deranged metabolic pathways are yet to be elucidated. To identify the modulated proteins of pancreatic CSCs, iTRAQ-based proteomic analysis was performed to compare the proteome of Panc1 CSCs and Panc1 parental cells, identifying 230 modulated proteins...
October 13, 2016: Journal of Proteomics
Xiaojing Liu, Iris L Romero, Lacey M Litchfield, Ernst Lengyel, Jason W Locasale
Repurposing metformin for cancer therapy is attractive due to its safety profile, epidemiological evidence, and encouraging data from human clinical trials. Although it is known to systemically affect glucose metabolism in liver, muscle, gut, and other tissues, the molecular determinants that predict a patient response in cancer remain unknown. Here, we carry out an integrative metabolomics analysis of metformin action in ovarian cancer. Metformin accumulated in patient biopsies, and pathways involving nucleotide metabolism, redox, and energy status, all related to mitochondrial metabolism, were affected in treated tumors...
October 12, 2016: Cell Metabolism
Ivana Jochmanova, Karel Pacak
Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics has allowed us to take a closer look at the metabolic changes present in pheochromocytomas (PHEO) and paragangliomas (PGL)...
October 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Travis C Salzillo, Jingzhe Hu, Linda Nguyen, Nicholas Whiting, Jaehyuk Lee, Joseph Weygand, Prasanta Dutta, Shivanand Pudakalakatti, Niki Zacharias Millward, Seth T Gammon, Frederick F Lang, Amy B Heimberger, Pratip K Bhattacharya
This article reviews existing and emerging techniques of interrogating metabolism in brain cancer from well-established proton magnetic resonance spectroscopy to the promising hyperpolarized metabolic imaging and chemical exchange saturation transfer and emerging techniques of imaging inflammation. Some of these techniques are at an early stage of development and clinical trials are in progress in patients to establish the clinical efficacy. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy; with the combined knowledge of genomics and proteomics a complete understanding of tumorigenesis in brain might be achieved...
November 2016: Magnetic Resonance Imaging Clinics of North America
Priyakshi Kalita-de Croft, Fares Al-Ejeh, Amy E McCart Reed, Jodi M Saunus, Sunil R Lakhani
Our understanding of the natural history of breast cancer has evolved alongside technologies to study its genomic, transcriptomic, proteomic, and metabolomics landscapes. These technologies have helped decipher multiple molecular pathways dysregulated in breast cancer. First-generation 'omics analyses considered each of these dimensions individually, but it is becoming increasingly clear that more holistic, integrative approaches are required to fully understand complex biological systems. The 'omics represent an exciting era of discovery in breast cancer research, although important issues need to be addressed to realize the clinical utility of these data through precision cancer care...
November 2016: Advances in Anatomic Pathology
Z Heger, T Eckschlager, M Stiborová, V Adam
BACKGROUND: Prostate cancer (PC) constitutes a heterogeneous group of diseases with high prevalence rates that are still increasing, particularly in western countries. Since 1980, prostate specific antigen (PSA) and other diagnostic approaches have been used for PC screening; however, some of these approaches are often deemed painful and cause invasive damage of tissue. Therefore, molecular approaches to PC diagnosis are attracting increasing attention, potentially providing patients with less stressful situations and providing better diagnoses and even prognostic information...
2016: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Eric L Allen, Danielle B Ulanet, David Pirman, Christopher E Mahoney, John Coco, Yaguang Si, Ying Chen, Lingling Huang, Jinmin Ren, Sung Choe, Michelle F Clasquin, Erin Artin, Zi Peng Fan, Giovanni Cianchetta, Joshua Murtie, Marion Dorsch, Shengfang Jin, Gromoslaw A Smolen
Although aberrant metabolism in tumors has been well described, the identification of cancer subsets with particular metabolic vulnerabilities has remained challenging. Here, we conducted an siRNA screen focusing on enzymes involved in the tricarboxylic acid (TCA) cycle and uncovered a striking range of cancer cell dependencies on OGDH, the E1 subunit of the alpha-ketoglutarate dehydrogenase complex. Using an integrative metabolomics approach, we identified differential aspartate utilization, via the malate-aspartate shuttle, as a predictor of whether OGDH is required for proliferation in 3D culture assays and for the growth of xenograft tumors...
October 11, 2016: Cell Reports
Zhe Wang
Biology research has entered into big data era. Systems biology approaches therefore become the powerful tools to obtain the whole landscape of how cell separate, grow, and resist the stresses. Fission yeast Schizosaccharomyces pombe is wonderful unicellular eukaryote model, especially studying its division and metabolism can facilitate to understanding the molecular mechanism of cancer and discovering anticancer agents. In this perspective, we discuss the recent advanced fission yeast systems biology tools, mainly focus on metabolomics profiling and metabolic modeling, protein-protein interactome and genetic interaction network, DNA sequencing and applications, and high-throughput phenotypic screening...
October 11, 2016: Current Genetics
Caroline H Johnson, Mary E Spilker, Laura Goetz, Scott N Peterson, Gary Siuzdak
The role of the host microbiome has come to the forefront as a potential modulator of cancer metabolism and could be a future target for precision medicine. A recent study revealed that in colon cancer, bacteria form polysaccharide matrices called biofilms at a high frequency in the proximal colon. Comprehensive untargeted and stable isotope-assisted metabolomic analysis revealed that the bacteria utilize polyamine metabolites produced from colon adenomas/carcinomas to build these protective biofilms and may contribute to inflammation and proliferation observed in colon cancer...
October 11, 2016: Cancer Research
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