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https://www.readbyqxmd.com/read/28315235/identification-and-quantitation-of-malonic-acid-biomarkers-of-in-born-error-metabolism-by-targeted-metabolomics
#1
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/28302921/deciphering-the-acute-cellular-phosphoproteome-response-to-irradiation-with-x-rays-protons-and-carbon-ions
#2
Martin Winter, Ivana Dokic, Julian Schlegel, Uwe Warnken, Jürgen Debus, Amir Abdollahi, Martina Schnölzer
Radiotherapy is a cornerstone of cancer therapy. The recently established particle therapy with raster-scanning protons and carbon ions landmarks a new era in the field of high-precision cancer medicine. However, molecular mechanisms governing radiation induced intracellular signaling remain elusive. Here, we present the first comprehensive proteomic and phosphoproteomic study applying stable isotope labeling by amino acids in cell culture (SILAC) in combination with high-resolution mass spectrometry to decipher cellular response to irradiation with X-rays, protons and carbon ions...
March 16, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28300784/the-molecular-basis-of-toxins-interactions-with-intracellular-signaling-via-discrete-portals
#3
REVIEW
Adi Lahiani, Ephraim Yavin, Philip Lazarovici
An understanding of the molecular mechanisms by which microbial, plant or animal-secreted toxins exert their action provides the most important element for assessment of human health risks and opens new insights into therapies addressing a plethora of pathologies, ranging from neurological disorders to cancer, using toxinomimetic agents. Recently, molecular and cellular biology dissecting tools have provided a wealth of information on the action of these diverse toxins, yet, an integrated framework to explain their selective toxicity is still lacking...
March 16, 2017: Toxins
https://www.readbyqxmd.com/read/28292895/diagnosis-of-prostate-cancer-by-desorption-electrospray-ionization-mass-spectrometric-imaging-of-small-metabolites-and-lipids
#4
Shibdas Banerjee, Richard N Zare, Robert J Tibshirani, Christian A Kunder, Rosalie Nolley, Richard Fan, James D Brooks, Geoffrey A Sonn
Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28283400/vdac-in-cancer
#5
REVIEW
N M Mazure
The voltage-dependent anion channel (VDAC) is a pore located at the outer membrane of the mitochondrion. It allows the entry and exit of numerous ions and metabolites between the cytosol and the mitochondrion. Flux through the pore occurs in an active way: first, it depends on the open or closed state and second, on the negative or positive charges of the different ion species passing through the pore. The flux of essential metabolites, such as ATP, determines the functioning of the mitochondria to a noxious stimulus...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28252952/new-iminodiacetate-thiosemicarbazone-hybrids-and-their-copper-ii-complexes-are-potential-ribonucleotide-reductase-r2-inhibitors-with-high-antiproliferative-activity
#6
Mirela F Zaltariov, Marta Hammerstad, Homayon J Arabshahi, Katarina Jovanović, Klaus W Richter, Maria Cazacu, Sergiu Shova, Mihaela Balan, Niels H Andersen, Siniša Radulović, Jóhannes Reynisson, K Kristoffer Andersson, Vladimir B Arion
As ribonucleotide reductase (RNR) plays a crucial role in nucleic acid metabolism, it is an important target for anticancer therapy. The thiosemicarbazone Triapine is an efficient R2 inhibitor, which has entered ∼20 clinical trials. Thiosemicarbazones are supposed to exert their biological effects through effectively binding transition-metal ions. In this study, six iminodiacetate-thiosemicarbazones able to form transition-metal complexes, as well as six dicopper(II) complexes, were synthesized and fully characterized by analytical, spectroscopic techniques (IR, UV-vis; (1)H and (13)C NMR), electrospray ionization mass spectrometry, and X-ray diffraction...
March 2, 2017: Inorganic Chemistry
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
#7
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/28247296/detection-of-metastatic-breast-and-thyroid-cancer-in-lymph-nodes-by-desorption-electrospray-ionization-mass-spectrometry-imaging
#8
Jialing Zhang, Clara L Feider, Chandandeep Nagi, Wendong Yu, Stacey A Carter, James Suliburk, Hop S Tran Cao, Livia S Eberlin
Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues...
February 28, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28246447/transcriptomic-comparison-of-primary-bovine-horn-core-carcinoma-culture-and-parental-tissue-at-early-stage
#9
Sharadindu Shil, R S Joshi, C G Joshi, A K Patel, Ravi K Shah, Namrata Patel, Subhash J Jakhesara, Sumana Kundu, Bhaskar Reddy, P G Koringa, D N Rank
AIM: Squamous cell carcinoma or SCC of horn in bovines (bovine horn core carcinoma) frequently observed in Bos indicus affecting almost 1% of cattle population. Freshly isolated primary epithelial cells may be closely related to the malignant epithelial cells of the tumor. Comparison of gene expression in between horn's SCC tissue and its early passage primary culture using next generation sequencing was the aim of this study. MATERIALS AND METHODS: Whole transcriptome sequencing of horn's SCC tissue and its early passage cells using Ion Torrent PGM were done...
January 2017: Veterinary World
https://www.readbyqxmd.com/read/28207290/fatty-acid-and-mineral-receptors-as-drug-targets-for-gastrointestinal-disorders
#10
Pawin Pongkorpsakol, Aekkacha Moonwiriyakit, Chatchai Muanprasat
Nutrient-sensing receptors, including fatty acid receptors (FFA1-FFA4), Ca(2+)-sensing receptors and Zn(2+)-sensing receptors, are involved in several biological processes. These receptors are abundantly expressed in the GI tract, where they have been shown to play crucial roles in regulating GI function. This review provides an overview of the GI functions of fatty acid and mineral receptors, including the regulation of gastric and enteroendocrine functions, GI motility, ion transport and cell growth. Recently, several lines of evidence have implicated these receptors as promising therapeutic targets for the treatment of GI disorders, for example, inflammatory bowel disease, colorectal cancer, metabolic syndrome and diarrheal diseases...
February 16, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28202602/cancer-cell-behaviors-mediated-by-dysregulated-ph-dynamics-at-a-glance
#11
REVIEW
Katharine A White, Bree K Grillo-Hill, Diane L Barber
Dysregulated pH is a common characteristic of cancer cells, as they have an increased intracellular pH (pHi) and a decreased extracellular pH (pHe) compared with normal cells. Recent work has expanded our knowledge of how dysregulated pH dynamics influences cancer cell behaviors, including proliferation, metastasis, metabolic adaptation and tumorigenesis. Emerging data suggest that the dysregulated pH of cancers enables these specific cell behaviors by altering the structure and function of selective pH-sensitive proteins, termed pH sensors...
February 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28198817/dynamic-properties-of-calcium-activated-chloride-currents-in-xenopus-laevis-oocytes
#12
Ildefonso M De la Fuente, Iker Malaina, Alberto Pérez-Samartín, María Dolores Boyano, Gorka Pérez-Yarza, Carlos Bringas, Álvaro Villarroel, María Fedetz, Rogelio Arellano, Jesus M Cortes, Luis Martínez
Chloride is the most abundant permeable anion in the cell, and numerous studies in the last two decades highlight the great importance and broad physiological role of chloride currents mediated anion transport. They participate in a multiplicity of key processes, as for instance, the regulation of electrical excitability, apoptosis, cell cycle, epithelial secretion and neuronal excitability. In addition, dysfunction of Cl(-) channels is involved in a variety of human diseases such as epilepsy, osteoporosis and different cancer types...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193528/cellular-acidification-as-a-new-approach-to-cancer-treatment-and-to-the-understanding-and-therapeutics-of-neurodegenerative-diseases
#13
REVIEW
Salvador Harguindey, Daniel Stanciu, Jesús Devesa, Khalid Alfarouk, Rosa Angela Cardone, Julian David Polo Orozco, Pablo Devesa, Cyril Rauch, Gorka Orive, Eduardo Anitua, Sébastien Roger, Stephan J Reshkin
During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversed proton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, a translational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intracellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cells have never been described in any other disease and now appear to be a specific hallmark of malignancy...
February 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28167419/comparative-pharmacokinetic-profiles-of-selected-irreversible-tyrosine-kinase-inhibitors-neratinib-and-pelitinib-with-apigenin-in-rat-plasma-by-uplc-ms-ms
#14
Hadir M Maher, Nourah Z Alzoman, Shereen M Shehata, Ashwag O Abahussain
Neratinib (NER) and pelitinib (PEL) are irreversible tyrosine kinase inhibitors (TKIs) that have been recently employed in cancer treatment. Apigenin (API), among other flavonoids, is known to have antioxidant, anti-proliferative, and carcinogenic effect. API can potentiate the antitumor effect of chemotherapeutic agents and/or alleviate the side effects of many anticancer agents. Since TKIs are mostly metabolized by CYP3A4 enzymes and that API could alter the enzymatic activity, potential drug interactions could be expected following their co-aministration...
January 31, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28111813/chemometric-based-identification-and-validation-of-specific-chemical-markers-for-geographical-seasonal-and-gender-variations-in-tinospora-cordifolia-stem-using-hplc-esi-qtof-ms-analysis
#15
Vikas Bajpai, Sunil Kumar, Awantika Singh, Jyotsana Singh, M P S Negi, Sumit Kumar Bag, Nikhil Kumar, Rituraj Konwar, Brijesh Kumar
INTRODUCTION: Tinospora cordifolia is a widely distributed medicinal plant used in various traditional and commercial Ayurvedic formulations. Due to the wide use of this plant it is important to know the extent of variability in the metabolite profile resulting from geographical location, season and gender. OBJECTIVE: To develop a statistical approach based on phytochemical markers for confident prediction of variations in metabolic profile and cytotoxicity due to geographical, seasonal and gender difference in T...
January 23, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28104391/na-h-exchanger-mediated-hydrogen-ion-extrusion-as-a-carcinogenic-signal-in-triple-negative-breast-cancer-etiopathogenesis-and-prospects-for-its-inhibition-in-therapeutics
#16
REVIEW
Schammim Ray Amith, Larry Fliegel
Breast cancer is the leading cause of cancer-related death in women in Europe and North America, and metastasis is the primary cause of fatality in patients with breast cancer. While some breast cancers are quite treatable, the triple-negative breast cancers are more metastatic and resistant to chemotherapy. There is clearly an urgent need for better treatments for this form of the disease. Breast cancer is characterized by genetically complex intra-tumour heterogeneity, particularly within the triple-negative clinical subtype...
January 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28101932/amino-acid-profiling-of-zinc-resistant-prostate-cancer-cell-lines-associations-with-cancer-progression
#17
Monika Kratochvilova, Martina Raudenska, Zbynek Heger, Lukas Richtera, Natalia Cernei, Vojtech Adam, Petr Babula, Marie Novakova, Michal Masarik, Jaromir Gumulec
BACKGROUND: Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed...
January 19, 2017: Prostate
https://www.readbyqxmd.com/read/28088622/reactive-oxygen-species-and-cancer-paradox-to-promote-or-to-suppress
#18
REVIEW
Sehamuddin Galadari, Anees Rahman, Siraj Pallichankandy, Faisal Thayyullathil
Reactive oxygen species (ROS), a group of highly reactive ions and molecules, are increasingly being appreciated as powerful signaling molecules involved in the regulation of a variety of biological processes. Indeed, their role is continuously being delineated in a variety of pathophysiological conditions. For instance, cancer cells are shown to have increased ROS levels in comparison to their normal counterparts. This is partly due to an enhanced metabolism and mitochondrial dysfunction in cancer cells. The escalated ROS generation in cancer cells contributes to the biochemical and molecular changes necessary for the tumor initiation, promotion and progression, as well as, tumor resistance to chemotherapy...
March 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28039486/cd147-a-small-molecule-transporter-ancillary-protein-at-the-crossroad-of-multiple-hallmarks-of-cancer-and-metabolic-reprogramming
#19
Agnieszka A Kendrick, Johnathon Schafer, Monika Dzieciatkowska, Travis Nemkov, Angelo D'Alessandro, Deepika Neelakantan, Heide L Ford, Chad G Pearson, Colin D Weekes, Kirk C Hansen, Elan Z Eisenmesser
Increased expression of CD147 in pancreatic cancer has been proposed to play a critical role in cancer progression via CD147 chaperone function for lactate monocarboxylate transporters (MCTs). Here, we show for the first time that CD147 interacts with membrane transporters beyond MCTs and exhibits a protective role for several of its interacting partners. CD147 prevents its interacting partner's proteasome-dependent degradation and incorrect plasma membrane localization through the CD147 transmembrane (TM) region...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28038952/metabotypes-of-breast-cancer-cell-lines-revealed-by-non-targeted-metabolomics
#20
Sébastien Dubuis, Franziska Baenke, Nina Scherbichler, Leila T Alexander, Almut Schulze, Nicola Zamboni
We present an analysis of intracellular metabolism by non-targeted, high-throughput metabolomics profiling of 18 breast cell lines. We profiled >900 putatively annotated metabolite ions for >100 samples collected under both normoxic and hypoxic conditions and revealed extensive heterogeneity across all metabolic pathways and cell lines. Cell line-specific metabolome profiles dominated over patterns associated with malignancy or with the clinical nomenclature of breast cancer cells. Such characteristic metabolome profiles were reproducible across different laboratories and experiments and exhibited mild to robust changes with change in experimental conditions...
December 27, 2016: Metabolic Engineering
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