keyword
MENU ▼
Read by QxMD icon Read
search

Oncometabolite

keyword
https://www.readbyqxmd.com/read/29409060/pheochromocytoma-paraganglioma-a-poster-child-for-cancer-metabolism
#1
Sergei G Tevosian, Hans K Ghayee
Context: Pheochromocytomas (PCCs) are tumors that are derived from the chromaffin cells of the adrenal medulla. Extra-adrenal PCCs called paragangliomas (PGLs) are derived from the sympathetic and parasympathetic chain ganglia. PCCs secrete catecholamines which cause hypertension and have adverse cardiovascular consequences as a result of catecholamine excess. PGLs may or may not produce catecholamines depending on their genetic type and anatomical location. The most worrisome aspect of these tumors is their ability to become aggressive and metastasize, for which there are no known cures...
February 1, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29382206/tof-sims-analysis-of-an-isocitrate-dehydrogenase-1-mutation-associated-oncometabolite-in-cancer-cells
#2
Jungdae Park, Hee-Kyung Na, Hyun Kyong Shon, Hye Young Son, Yong-Min Huh, Sang-Won Lee, Tae Geol Lee
The development of analytical tools for accurate and sensitive detection of intracellular metabolites associated with mutated metabolic enzymes is important in cancer diagnosis and staging. The gene encoding the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) is mutated in various cancers, and mutant IDH1 could represent a good biomarker and potent target for cancer therapy. Owing to a mutation in an important arginine residue in the catalytic pocket, mutant IDH1 catalyzes the production of 2-hydroxyglutarate (2-HG) instead of its wild type product α-ketoglutarate (α-KG), which is involved in multiple cellular pathways involving the hydroxylation of proteins, ribonucleic acid, and deoxyribose nucleic acid (DNA)...
January 30, 2018: Biointerphases
https://www.readbyqxmd.com/read/29367352/seeding-of-proteins-into-amyloid-structures-by-metabolite-assemblies-may-clarify-certain-unexplained-epidemiological-associations
#3
REVIEW
Dorin Sade, Shira Shaham-Niv, Zohar A Arnon, Omid Tavassoly, Ehud Gazit
The accumulation of various metabolites appears to be associated with diverse human diseases. However, the aetiological link between metabolic alteration and the observed diseases is still elusive. This includes the correlation between the abnormally high levels of homocysteine and quinolinic acid in Alzheimer's disease, as well as the accumulation of oncometabolites in malignant processes. Here, we suggest and discuss a possible mechanistic insight into metabolite accumulation in conditions such as neurodegenerative diseases and cancer...
January 2018: Open Biology
https://www.readbyqxmd.com/read/29358170/2-hydroxyglutarate-mediated-autophagy-of-the-endoplasmic-reticulum-leads-to-an-unusual-downregulation-of-phospholipid-biosynthesis-in-mutant-idh1-gliomas
#4
Pavithra Viswanath, Marina Radoul, Jose Luis Izquierdo-Garcia, Wei Qiang Ong, Hema Artee Luchman, John Gregory Cairncross, Bo Huang, Russell O Pieper, Joanna J Phillips, Sabrina M Ronen
Tumor metabolism is reprogrammed to meet the demands of proliferating cancer cells. In particular, cancer cells upregulate synthesis of the membrane phospholipids phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdE) in order to allow for rapid membrane turnover. Nonetheless, we show here that, in mutant isocitrate dehydrogenase 1 (IDHmut) gliomas, which produce the oncometabolite 2-hydroxyglutarate (2-HG), PtdCho and PtdE biosynthesis is downregulated and results in lower levels of both phospholipids when compared to wild-type IDH1 cells...
January 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29342092/metabolic-alterations-in-cancer-cells-and-the-emerging-role-of-oncometabolites-as-drivers-of-neoplastic-change
#5
REVIEW
Zhengqiu Zhou, Elochukwu Ibekwe, Yevgen Chornenkyy
The mitochondrion is an important organelle and provides energy for a plethora of intracellular reactions. Metabolic dysregulation has dire consequences for the cell, and alteration in metabolism has been identified in multiple disease states-cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic glycolysis". Alterations in metabolism enable cancer cells to gain a growth advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic acids and lipids...
January 17, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29339836/the-role-of-metabolic-enzymes-in-mesenchymal-tumors-and-tumor-syndromes-genetics-pathology-and-molecular-mechanisms
#6
REVIEW
Inga-Marie Schaefer, Jason L Hornick, Judith V M G Bovée
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate...
January 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29321378/glutamine-derived-2-hydroxyglutarate-is-associated-with-disease-progression-in-plasma-cell-malignancies
#7
Wilson I Gonsalves, Vijay Ramakrishnan, Taro Hitosugi, Toshi Ghosh, Dragan Jevremovic, Tumpa Dutta, Dhananjay Sakrikar, Xuan-Mai Petterson, Linda Wellik, Shaji K Kumar, K Sreekumaran Nair
The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism and drives progression of asymptomatic precursor plasma cell (PC) malignancies to symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical significance in PC malignancies is unknown. By performing 13C stable isotope resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is derived predominantly from glutamine anaplerosis into the TCA cycle...
January 11, 2018: JCI Insight
https://www.readbyqxmd.com/read/29315915/a-comparison-of-2-hydroxyglutarate-detection-at-3-and-7%C3%A2-t-with-long-te-semi-laser
#8
Adam Berrington, Natalie L Voets, Sarah J Larkin, Nick de Pennington, James Mccullagh, Richard Stacey, Christopher J Schofield, Peter Jezzard, Stuart Clare, Tom Cadoux-Hudson, Puneet Plaha, Olaf Ansorge, Uzay E Emir
Abnormally high levels of the 'oncometabolite' 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2-HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2-HG detection. To combat this, several groups have proposed MRS methods at ultra-high field (≥7 T) where theoretical increases in signal-to-noise ratio and spectral resolution could improve 2-HG detection...
January 5, 2018: NMR in Biomedicine
https://www.readbyqxmd.com/read/29274619/circulating-oncometabolite-d-2-hydroxyglutarate-enantiomer-is-a-surrogate-marker-of-isocitrate-dehydrogenase-mutated-intrahepatic-cholangiocarcinomas
#9
Julia Delahousse, Loic Verlingue, Sophie Broutin, Clémence Legoupil, Mehdi Touat, Ludovic Doucet, Samy Ammari, Ludovic Lacroix, Michel Ducreux, Jean-Yves Scoazec, David Malka, Angelo Paci, Antoine Hollebecque
Therapeutic resources are limited for advanced biliary tract cancers and prognosis remains poor. Somatic mutations in isocitrate dehydrogenase (IDH)1/2 gene are found in 5-36% of patients with intrahepatic cholangiocarcinoma (ICC). The mutant forms of IDH1/2 catalyse the non-reversible accumulation of 2-hydroxyglutarate (2HG). Increasing numbers of indirect or direct-targeted therapies are developed to IDH1/2 mutations and could be assisted by a routinely feasible, rapid and inexpensive serum 2HG measurement by liquid chromatography coupled to tandem mass spectrometry...
December 20, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29249359/r-2hg-exhibits-anti-tumor-activity-by-targeting-fto-m6a-myc-cebpa-signaling
#10
Rui Su, Lei Dong, Chenying Li, Sigrid Nachtergaele, Mark Wunderlich, Ying Qing, Xiaolan Deng, Yungui Wang, Xiaocheng Weng, Chao Hu, Mengxia Yu, Jennifer Skibbe, Qing Dai, Dongling Zou, Tong Wu, Kangkang Yu, Hengyou Weng, Huilin Huang, Kyle Ferchen, Xi Qin, Bin Zhang, Jun Qi, Atsuo T Sasaki, David R Plas, James E Bradner, Minjie Wei, Guido Marcucci, Xi Jiang, James C Mulloy, Jie Jin, Chuan He, Jianjun Chen
R-2-hydroxyglutarate (R-2HG), produced at high levels by mutant isocitrate dehydrogenase 1/2 (IDH1/2) enzymes, was reported as an oncometabolite. We show here that R-2HG also exerts a broad anti-leukemic activity in vitro and in vivo by inhibiting leukemia cell proliferation/viability and by promoting cell-cycle arrest and apoptosis. Mechanistically, R-2HG inhibits fat mass and obesity-associated protein (FTO) activity, thereby increasing global N6-methyladenosine (m6A) RNA modification in R-2HG-sensitive leukemia cells, which in turn decreases the stability of MYC/CEBPA transcripts, leading to the suppression of relevant pathways...
December 11, 2017: Cell
https://www.readbyqxmd.com/read/29243965/enasidenib-a-targeted-inhibitor-of-mutant-idh2-proteins-for-treatment-of-relapsed-or-refractory-acute-myeloid-leukemia
#11
Eytan M Stein
Mutations in IDH2 genes (mIDH2) occur in approximately 12% of patients with acute myeloid leukemia. Enasidenib is an oral, small-molecule inhibitor of mIDH2 proteins. Enasidenib is shown to suppress the oncometabolite, 2-hydroxyglutarate, and promote differentiation of leukemic bone marrow blasts. In a Phase I dose-escalation and expansion study, 40.3% of patients with relapsed/refractory acute myeloid leukemia responded to enasidenib monotherapy, including 19.3% who achieved complete remission and 11% who proceeded to transplant...
January 2018: Future Oncology
https://www.readbyqxmd.com/read/29202474/adhfe1-is-a-breast-cancer-oncogene-and-induces-metabolic-reprogramming
#12
Prachi Mishra, Wei Tang, Vasanta Putluri, Tiffany H Dorsey, Feng Jin, Fang Wang, Donewei Zhu, Lauren Amable, Tao Deng, Shaofei Zhang, J Keith Killian, Yonghong Wang, Tsion Z Minas, Harry G Yfantis, Dong H Lee, Arun Sreekumar, Michael Bustin, Wei Liu, Nagireddy Putluri, Stefan Ambs
Metabolic reprogramming in breast tumors is linked to increases in putative oncogenic metabolites that may contribute to malignant transformation. We previously showed that accumulation of the oncometabolite, 2-hydroxyglutarate (2HG), in breast tumors was associated with MYC signaling, but not with isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for increased 2HG in breast cancer. Here, we determined that D-2HG is the predominant enantiomer in human breast tumors and show that the D-2HG-producing mitochondrial enzyme, alcohol dehydrogenase, iron-containing protein 1 (ADHFE1), is a breast cancer oncogene that decreases patient survival...
November 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29183865/intraventricular-glioblastoma-multiforme-in-a-child-with-l2-hydroxyglutaric-aciduria
#13
Ai Peng Tan, Kshitij Mankad
L2-hydroxyglutaric aciduria (L2-HGA) is a rare neurometabolic disease characterised by accumulation of L2-hydroxyglutarate (L2-HG), a potential oncometabolite resulting in significant lifetime risk for cerebral tumors. Here in, we present a case of intraventricular glioblastoma multiforme (GBM) in a 16-year-old child with L2-HGA who presented with rapid functional decline and persistent vomiting. The tumour was completely resected and the patient remained well at 2-year follow up. Clinicians should be aware of the usual insidious nature of the disease...
November 25, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#14
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29126125/highly-specific-determination-of-idh-status-using-edited-in-vivo-magnetic-resonance-spectroscopy
#15
Francesca Branzoli, Anna Luisa Di Stefano, Laurent Capelle, Chris Ottolenghi, Romain Valabrègue, Dinesh K Deelchand, Franck Bielle, Chiara Villa, Bertrand Baussart, Stéphane Lehéricy, Marc Sanson, Malgorzata Marjanska
Background: Mutations in the isocitrate dehydrogenase (IDH) enzyme affects 40% of gliomas and represent a major diagnostic and prognostic marker. The goals of this study were to evaluate the performance of noninvasive magnetic resonance spectroscopy (MRS) methods to determine the IDH status of patients with brain gliomas through detection of the oncometabolite 2-hydroxyglutarate (2HG), and to compare performance of these methods with DNA sequencing and tissue 2HG analysis. Methods: Twenty-four subjects with suspected diagnosis of low grade glioma were included prospectively in the study...
November 6, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29105933/sarcosine-influences-apoptosis-and-growth-of-prostate-cells-via-cell-type-specific-regulation-of-distinct-sets-of-genes
#16
Miguel A Merlos Rodrigo, Vladislav Strmiska, Eva Horackova, Hana Buchtelova, Petr Michalek, Marie Stiborova, Tomas Eckschlager, Vojtech Adam, Zbynek Heger
BACKGROUND: Sarcosine is a widely discussed oncometabolite of prostate cells. Although several reports described connections between sarcosine and various phenotypic changes of prostate cancer (PCa) cells, there is still a lack of insights on the complex phenomena of its effects on gene expression patterns, particularly in non-malignant and non-metastatic cells. METHODS: To shed more light on this phenomenon, we performed parallel microarray profiling of RNA isolated from non-malignant (PNT1A), malignant (22Rv1), and metastatic (PC-3) prostate cell lines treated with sarcosine...
November 6, 2017: Prostate
https://www.readbyqxmd.com/read/29097607/adaptive-evolution-of-the-gdh2-allosteric-domain-promotes-gliomagenesis-by-resolving-idh1-r132h-induced-metabolic-liabilities
#17
Matthew S Waitkus, Christopher J Pirozzi, Casey J Moure, Bill H Diplas, Landon J Hansen, Austin B Carpenter, Rui Yang, Zhaohui Wang, Brian O Ingram, Edward D Karoly, Robert P Mohney, Ivan Spasojeic, Roger E McLendon, Henry S Friedman, Yiping He, Darell D Bigner, Hai Yan
Hot-spot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malignant gliomas, IDH1(R132H) expression induces widespread metabolic reprogramming, possibly requiring compensatory mechanisms to sustain the normal biosynthetic requirements of actively proliferating tumor cells. We used genetically engineered mouse models of glioma and quantitative metabolomics to investigate IDH1(R132H)-dependent metabolic reprogramming and its potential to induce biosynthetic liabilities that can be exploited for glioma therapy...
November 2, 2017: Cancer Research
https://www.readbyqxmd.com/read/29090344/the-role-of-mutant-idh1-and-idh2-inhibitors-in-the-treatment-of-acute-myeloid-leukemia
#18
REVIEW
Samah Nassereddine, Coen J Lap, Faysal Haroun, Imad Tabbara
For decades, researchers have looked into the pathophysiology of acute myeloid leukemia (AML). With the advances in molecular techniques, the two-hit hypothesis was replaced by a multi-hit model, which also emphasizes the importance of aberrant epigenetic regulation in the pathogenesis of AML. IDH1 and IDH2 are two isoforms of isocitrate dehydrogenase that perform crucial roles in cellular metabolism. Somatic mutations in either of these two genes impart a neomorphic enzymatic activity upon the encoded enzymes resulting in the ability to convert α-ketoglutarate (αKG) into the oncometabolite R2-hydroxyglutarate (R2-HG), which can competitively inhibit multiple αKG-dependent dioxygenases...
December 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29078321/identification-of-a-tumor-promoter-cholesterol-metabolite-in-human-breast-cancers-acting-through-the-glucocorticoid-receptor
#19
Maud Voisin, Philippe de Medina, Arnaud Mallinger, Florence Dalenc, Emilie Huc-Claustre, Julie Leignadier, Nizar Serhan, Régis Soules, Grégory Ségala, Aurélie Mougel, Emmanuel Noguer, Loubna Mhamdi, Elodie Bacquié, Luigi Iuliano, Chiara Zerbinati, Magali Lacroix-Triki, Léonor Chaltiel, Thomas Filleron, Vincent Cavaillès, Talal Al Saati, Philippe Rochaix, Raphaelle Duprez-Paumier, Camille Franchet, Laetitia Ligat, Fréderic Lopez, Michel Record, Marc Poirot, Sandrine Silvente-Poirot
Breast cancer (BC) remains the primary cause of death from cancer among women worldwide. Cholesterol-5,6-epoxide (5,6-EC) metabolism is deregulated in BC but the molecular origin of this is unknown. Here, we have identified an oncometabolism downstream of 5,6-EC that promotes BC progression independently of estrogen receptor α expression. We show that cholesterol epoxide hydrolase (ChEH) metabolizes 5,6-EC into cholestane-3β,5α,6β-triol, which is transformed into the oncometabolite 6-oxo-cholestan-3β,5α-diol (OCDO) by 11β-hydroxysteroid-dehydrogenase-type-2 (11βHSD2)...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29057925/induction-of-synthetic-lethality-in-idh1-mutated-gliomas-through-inhibition-of-bcl-xl
#20
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Yiru Zhang, Chang Shu, Takashi Tsujiuchi, Matei A Banu, Franklin Garcia, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Markus D Siegelin
Certain gliomas often harbor a mutation in the activity center of IDH1 (R132H), which leads to the production of the oncometabolite 2-R-2-hydroxyglutarate (2-HG). In six model systems, including patient-derived stem cell-like glioblastoma cultures, inhibition of Bcl-xL induces significantly more apoptosis in IDH1-mutated cells than in wild-type IDH1 cells. Anaplastic astrocytoma samples with mutated IDH1 display lower levels of Mcl-1 than IDH1 wild-type tumors and specific knockdown of Mcl-1 broadly sensitizes glioblastoma cells to Bcl-xL inhibition-mediated apoptosis...
October 20, 2017: Nature Communications
keyword
keyword
16874
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"