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https://www.readbyqxmd.com/read/28079713/interrogating-idh-mutation-in-brain-tumor-magnetic-resonance-and-hyperpolarization
#1
Jingzhe Hu, Travis C Salzillo, Napapon Sailasuta, Frederick F Lang, Pratip Bhattacharya
Magnetic resonance spectroscopy (MRS) offers the possibility to noninvasively quantify 2HG concentration in the brain in the clinic, thereby serving as a valuable tool for patient-stratification as well as targeted treatment monitoring. Recently, hyperpolarized magnetic resonance techniques have opened up new opportunities for metabolic imaging not possible with conventional MRS in the brain. With over 10,000-fold increase in signal-to-noise ratio (SNR), dynamic metabolic processes can be interrogated in vivo with very high specificity by hyperpolarized MRI...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28053877/metabolomic-analysis-identifies-differentially-produced-oral-metabolites-including-the-oncometabolite-2-hydroxyglutarate-in-patients-with-head-and-neck-squamous-cell-carcinoma
#2
Pranab K Mukherjee, Pauline Funchain, Mauricio Retuerto, Richard J Jurevic, Nicole Fowler, Brian Burkey, Charis Eng, Mahmoud A Ghannoum
BACKGROUND: Metabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC. METHODS: Tumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS)...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28009351/s-2hg-is-an-immunometabolite-that-shapes-the-t-cell-response
#3
Rob A Cairns, Tak W Mak
No abstract text is available yet for this article.
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27982681/background-levels-of-neomorphic-2-hydroxyglutarate-facilitate-proliferation-of-primary-fibroblasts
#4
A Dvořák, J Zelenka, K Smolková, L Vítek, P JeŽek
Each cell types or tissues contain certain "physiological" levels of R-2-hydroxyglutarate (2HG), as well as enzymes for its synthesis and degradation. 2HG accumulates in certain tumors, possessing heterozygous point mutations of isocitrate dehydrogenases IDH1 (cytosolic) or IDH2 (mitochondrial) and contributes to strengthening their malignancy by inhibiting 2-oxoglutarate-dependent dioxygenases. By blocking histone de-methylation and 5-methyl-cytosine hydroxylation, 2HG maintains cancer cells de-differentiated and promotes their proliferation...
December 16, 2016: Physiological Research
https://www.readbyqxmd.com/read/27958198/pressure-dependence-of-the-metal-insulator-transition-in-%C3%AE%C2%BA-bedt-ttf-2hg-scn-2cl-optical-and-transport-studies
#5
A Löhle, E Rose, S Singh, R Beyer, E Tafra, T Ivek, E I Zhilyaeva, R N Lyubovskaya, M Dressel
The two-dimensional organic conductor κ-(BEDT-TTF)2-Hg(SCN)2Cl exhibits a pronounced metal-insulator transition at [Formula: see text] K. From the splitting of the molecular vibrations, the phase transition can be unambiguously assigned to charge-ordering with [Formula: see text]. We have investigated the pressure evolution of this behavior by temperature-dependent electrical transport measurements and optical investigations applying hydrostatic pressure up to 12 kbar. The data reveal a mean-field like down-shift of [Formula: see text] with a critical pressure of [Formula: see text] kbar and a metallic state above the suppression of the charge-ordered state; no traces of superconductivity could be identified down to T  =  1...
February 8, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/27956631/the-idh2-r172k-mutation-associated-with-angioimmunoblastic-t-cell-lymphoma-produces-2hg-in-t-cells-and-impacts-lymphoid-development
#6
François Lemonnier, Rob A Cairns, Satoshi Inoue, Wanda Y Li, Aurélie Dupuy, Sophie Broutin, Nadine Martin, Virginie Fataccioli, Romain Pelletier, Andrew Wakeham, Bryan E Snow, Laurence de Leval, Anais Pujals, Corinne Haioun, Angelo Paci, Erica R Tobin, Rohini Narayanaswamy, Katherine Yen, Shengfang Jin, Philippe Gaulard, Tak W Mak
Oncogenic isocitrate dehydrogenase (IDH)1 and IDH2 mutations at three hotspot arginine residues cause an enzymatic gain of function that leads to the production and accumulation of the metabolite 2-hydroxyglutarate (2HG), which contributes to the development of a number of malignancies. In the hematopoietic system, mutations in IDH1 at arginine (R) 132 and in IDH2 at R140 and R172 are commonly observed in acute myeloid leukemia, and elevated 2HG is observed in cells and serum. However, in angioimmunoblastic T-cell lymphoma (AITL), mutations are almost exclusively restricted to IDH2 R172, and levels of 2HG have not been comprehensively measured...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27889809/reversal-of-type-2-diabetes-in-youth-who-adhere-to-a-very-low-energy-diet-a-pilot-study
#7
Megan L Gow, Louise A Baur, Nathan A Johnson, Chris T Cowell, Sarah P Garnett
AIMS/HYPOTHESIS: The aim of the study was to investigate whether a very-low-energy diet (VLED) is a feasible and acceptable treatment option for type 2 diabetes in children and adolescents, and whether adherence can lead to rapid weight loss, reversal of type 2 diabetes and reduced liver fat as seen in adult studies. METHODS: Eight participants with type 2 diabetes and obesity, aged 7-16 years, non-medicated (n = 1) or treated with metformin (n = 7) and in some cases insulin (n = 3), followed a VLED (<3360 kJ/day) for 8 weeks, then transitioned to a hypocaloric diet (∼6300 kJ/day) that they followed to 34 weeks...
November 26, 2016: Diabetologia
https://www.readbyqxmd.com/read/27856334/quantitative-metabolic-flux-analysis-reveals-an-unconventional-pathway-of-fatty-acid-synthesis-in-cancer-cells-deficient-for-the-mitochondrial-citrate-transport-protein
#8
Lei Jiang, Adam Boufersaoui, Chendong Yang, Bookyung Ko, Dinesh Rakheja, Gerardo Guevara, Zeping Hu, Ralph J DeBerardinis
The mitochondrial citrate transport protein (CTP), encoded by SLC25A1, accommodates bidirectional trafficking of citrate between the mitochondria and cytosol, supporting lipid biosynthesis and redox homeostasis. Genetic CTP deficiency causes a fatal neurodevelopmental syndrome associated with the accumulation of L- and D-2-hydroxyglutaric acid, and elevated CTP expression is associated with poor prognosis in several types of cancer, emphasizing the importance of this transporter in multiple human pathologies...
November 14, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27836888/s-2-hydroxyglutarate-maintains-a-proliferative-cd8-t-cell-state
#9
(no author information available yet)
S-2HG acts as an immunometabolite to regulate CD8(+) T cell fate, promoting persistence and survival.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27824159/oncometabolite-d-2-hydroxyglurate-directly-induces-epithelial-mesenchymal-transition-and-is-associated-with-distant-metastasis-in-colorectal-cancer
#10
Hugh Colvin, Naohiro Nishida, Masamitsu Konno, Naotsugu Haraguchi, Hidekazu Takahashi, Junichi Nishimura, Taishi Hata, Koichi Kawamoto, Ayumu Asai, Kenta Tsunekuni, Jun Koseki, Tsunekazu Mizushima, Taroh Satoh, Yuichiro Doki, Masaki Mori, Hideshi Ishii
Deranged metabolism is a hallmark of cancer, playing a significant role in driving the disease process. One such example is the induction of carcinogenesis by the oncometabolite D-2 hydroxyglutarate (D-2HG), which is produced by the mutated enzyme isocitrate dehydrogenase (IDH) occurring in subsets of leukaemias and brain tumours. The oncogenic property of D-2HG appears to stem from its ability to interfere with the activities of α-ketoglutarate-dependent dioxygenases, including the Jumonji family histone demethylases...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27758882/mutant-idh1-expression-drives-tert-promoter-reactivation-as-part-of-the-cellular-transformation-process
#11
Shigeo Ohba, Joydeep Mukherjee, Tor-Christian Johannessen, Andrew Mancini, Tracy T Chow, Matthew Wood, Lindsey Jones, Tali Mazor, Roxanne E Marshall, Pavithra Viswanath, Kyle M Walsh, Arie Perry, Robert J A Bell, Joanna J Phillips, Joseph F Costello, Sabrina M Ronen, Russell O Pieper
Mutations in the isocitrate dehydrogenase gene IDH1 are common in low-grade glioma, where they result in the production of 2-hydroxyglutarate (2HG), disrupted patterns of histone methylation, and gliomagenesis. IDH1 mutations also cosegregate with mutations in the ATRX gene and the TERT promoter, suggesting that IDH mutation may drive the creation or selection of telomere-stabilizing events as part of immortalization/transformation process. To determine whether and how this may occur, we investigated the phenotype of pRb-/p53-deficient human astrocytes engineered with IDH1 wild-type (WT) or R132H-mutant (IDH1(mut)) genes as they progressed through their lifespan...
October 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27743650/meta-analysis-of-glucose-tolerance-insulin-and-insulin-resistance-in-antipsychotic-na%C3%A3-ve-patients-with-nonaffective-psychosis
#12
Anne Marie Greenhalgh, Leticia Gonzalez-Blanco, Clemente Garcia-Rizo, Emilio Fernandez-Egea, Brian Miller, Miguel Bernardo Arroyo, Brian Kirkpatrick
BACKGROUND: Some studies have suggested that antipsychotic-naïve patients with nonaffective psychosis (NAP) have glucose intolerance. AIMS: To conduct a systematic review and meta-analysis of fasting glucose (FG), two hour values in the oral glucose tolerance test (2HG), fasting insulin concentration (INS), and insulin resistance (IR). METHOD: We identified possibly relevant studies, then selected studies, following usual guidelines, with two authors reviewing the manuscripts...
January 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/27659543/non-invasive-detection-of-2-hydroxyglutarate-in-idh-mutated-gliomas-using-two-dimensional-localized-correlation-spectroscopy-2d-l-cosy-at-7-tesla
#13
Gaurav Verma, Suyash Mohan, MacLean P Nasrallah, Steven Brem, John Y K Lee, Sanjeev Chawla, Sumei Wang, Rajakumar Nagarajan, M Albert Thomas, Harish Poptani
BACKGROUND: Mutations in the isocitrate dehydrogenase enzyme are present in a majority of lower-grade gliomas and secondary glioblastomas. This mis-sense mutation results in the neomorphic reduction of isocitrate dehydrogenase resulting in an accumulation of the "oncometabolite" 2-hydroxyglutarate (2HG). Detection of 2HG can thus serve as a surrogate biomarker for these mutations, with significant translational implications including improved prognostication. Two dimensional localized correlated spectroscopy (2D L-COSY) at 7T is a highly-sensitive non-invasive technique for assessing brain metabolism...
September 22, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27624942/the-oncometabolite-2-hydroxyglutarate-activates-the-mtor-signalling-pathway
#14
Mélissa Carbonneau, Laurence M Gagné, Marie-Eve Lalonde, Marie-Anne Germain, Alena Motorina, Marie-Christine Guiot, Blandine Secco, Emma E Vincent, Anthony Tumber, Laura Hulea, Jonathan Bergeman, Udo Oppermann, Russell G Jones, Mathieu Laplante, Ivan Topisirovic, Kevin Petrecca, Marc-Étienne Huot, Frédérick A Mallette
The identification of cancer-associated mutations in the tricarboxylic acid (TCA) cycle enzymes isocitrate dehydrogenases 1 and 2 (IDH1/2) highlights the prevailing notion that aberrant metabolic function can contribute to carcinogenesis. IDH1/2 normally catalyse the oxidative decarboxylation of isocitrate into α-ketoglutarate (αKG). In gliomas and acute myeloid leukaemias, IDH1/2 mutations confer gain-of-function leading to production of the oncometabolite R-2-hydroxyglutarate (2HG) from αKG. Here we show that generation of 2HG by mutated IDH1/2 leads to the activation of mTOR by inhibiting KDM4A, an αKG-dependent enzyme of the Jumonji family of lysine demethylases...
September 14, 2016: Nature Communications
https://www.readbyqxmd.com/read/27621679/idh1-and-idh2-mutations-as-novel-therapeutic-targets-current-perspectives
#15
REVIEW
Johanna Mondesir, Christophe Willekens, Mehdi Touat, Stéphane de Botton
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to α-ketoglutarate. IDH1/2 mutations define distinct subsets of cancers, including low-grade gliomas and secondary glioblastomas, chondrosarcomas, intrahepatic cholangiocarcinomas, and hematologic malignancies. Somatic point mutations in IDH1/2 confer a gain-of-function in cancer cells, resulting in the accumulation and secretion in vast excess of an oncometabolite, the D-2-hydroxyglutarate (D-2HG). Overproduction of D-2HG interferes with cellular metabolism and epigenetic regulation, contributing to oncogenesis...
2016: Journal of Blood Medicine
https://www.readbyqxmd.com/read/27611701/serum-fibroblast-growth-factor-21-is-a-superior-biomarker-to-other-adipokines-in-predicting-incident-diabetes
#16
Yu Cho Woo, Chi Ho Lee, Carol H Y Fong, Aimin Xu, Annette W K Tso, Bernard M Y Cheung, Karen S L Lam
OBJECTIVE: Fibroblast growth factor 21 (FGF21) improves glucose and lipid metabolism, but high circulating levels are found in type 2 diabetes, suggesting FGF21 resistance. Serum FGF21 predicts incident diabetes, but its performance compared to established and emerging predictors is not known. We aimed to study the performance of FGF21 in diabetes prediction, relative to other adipokines and established risk factors including 2-h plasma glucose (2hG) during the oral glucose tolerance test (OGTT)...
January 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/27587950/in-vivo-proton-magnetic-resonance-spectroscopy-of-2-hydroxyglutarate-in-isocitrate-dehydrogenase-mutated-gliomas-a-technical-review-for-neuroradiologists
#17
REVIEW
Hyeonjin Kim, Sungjin Kim, Hyeong Hun Lee, Hwon Heo
The diagnostic and prognostic potential of an onco-metabolite, 2-hydroxyglutarate (2HG) as a proton magnetic resonance spectroscopy (1H-MRS) detectable biomarker of the isocitrate dehydrogenase (IDH)-mutated (IDH-MT) gliomas has drawn attention of neuroradiologists recently. However, due to severe spectral overlap with background signals, quantification of 2HG can be very challenging. In this technical review for neuroradiologists, first, the biochemistry of 2HG and its significance in the diagnosis of IDH-MT gliomas are summarized...
September 2016: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/27577048/the-oncometabolite-r-2-hydroxyglutarate-activates-nf-%C3%AE%C2%BAb-dependent-tumor-promoting-stromal-niche-for-acute-myeloid-leukemia-cells
#18
Jing-Yi Chen, You-Syuan Lai, Hui-Jen Tsai, Cheng-Chin Kuo, B Linju Yen, Su-Peng Yeh, H Sunny Sun, Wen-Chun Hung
Mutations of isocitrate dehydrogenase 1 (IDH1) and IDH2 in acute myeloid leukemia (AML) cells produce the oncometabolite R-2-hydroxyglutarate (R-2HG) to induce epigenetic alteration and block hematopoietic differentiation. However, the effect of R-2HG released by IDH-mutated AML cells on the bone marrow microenvironment is unclear. Here, we report that R-2HG induces IκB kinase-independent activation of NF-κB in bone marrow stromal cells. R-2HG acts via a reactive oxygen species/extracellular signal-regulated kinase (ERK)-dependent pathway to phosphorylate NF-κB on the Thr254 residue...
August 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27543339/in-vivo-brain-h1-mr-spectroscopy-identification-and-quantification-of-2-hydroxyglutarate-in-l-2-hydroxyglutaric-aciduria
#19
Elena Anghileri, Nicola Bertolino, Ettore Salsano, Luigi Antelmi, Patrizia Carpinelli, Barbara Castellotti, Ileana Zucca, Cinzia Gellera, Raffaele Bisogno, Claudio Caccia, Valeria Cuccarini
UNLABELLED: L-2-Hydroxyglutaric aciduria (L2HGA) is an extremely rare hereditary neurometabolic disease, characterized by increased L-2-hydroxyglutarate (L2HG) levels in the brain and biological fluids. 24-h urine 2HG level remains the biochemical hallmark for the diagnosis of L2HGA, whereas it is unknown the feasibility to measure in vivo the intracerebral levels of 2HG by using magnetic resonance spectroscopy (MRS). PATIENTS AND METHODS: We used at 3T H(1)-MRS Single-Voxel (SV) PRESS sequences tailored to detect 2HG, in three adult patients with the diagnosis of L2HGA and in healthy controls...
October 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27469509/a-small-molecule-inhibitor-of-mutant-idh2-rescues-cardiomyopathy-in-a-d-2-hydroxyglutaric-aciduria-type-ii-mouse-model
#20
Fang Wang, Jeremy Travins, Zhizhong Lin, Yaguang Si, Yue Chen, Josh Powe, Stuart Murray, Dongwei Zhu, Erin Artin, Stefan Gross, Stephanie Santiago, Mya Steadman, Andrew Kernytsky, Kimberly Straley, Chenming Lu, Ana Pop, Eduard A Struys, Erwin E W Jansen, Gajja S Salomons, Muriel D David, Cyril Quivoron, Virginie Penard-Lacronique, Karen S Regan, Wei Liu, Lenny Dang, Hua Yang, Lee Silverman, Samuel Agresta, Marion Dorsch, Scott Biller, Katharine Yen, Yong Cang, Shin-San Michael Su, Shengfang Jin
D-2-hydroxyglutaric aciduria (D2HGA) type II is a rare neurometabolic disorder caused by germline gain-of-function mutations in isocitrate dehydrogenase 2 (IDH2), resulting in accumulation of D-2-hydroxyglutarate (D2HG). Patients exhibit a wide spectrum of symptoms including cardiomyopathy, epilepsy, developmental delay and limited life span. Currently, there are no effective therapeutic interventions. We generated a D2HGA type II mouse model by introducing the Idh2R140Q mutation at the native chromosomal locus...
November 2016: Journal of Inherited Metabolic Disease
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