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https://www.readbyqxmd.com/read/29924369/precision-oncology-in-the-era-of-radiogenomics-the-case-of-d-2hg-as-an-imaging-biomarker-for-mutant-idh-gliomas
#1
Ovidiu C Andronesi
No abstract text is available yet for this article.
June 18, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29900057/d-2-hydroxyglutarate-interferes-with-hif-1%C3%AE-stability-skewing-t-cell-metabolism-towards-oxidative-phosphorylation-and-impairing-th17-polarization
#2
Martin Böttcher, Kathrin Renner, Raffaela Berger, Kristin Mentz, Simone Thomas, Zugey Elizabeth Cardenas-Conejo, Katja Dettmer, Peter J Oefner, Andreas Mackensen, Marina Kreutz, Dimitrios Mougiakakos
D-2-hydroxyglutarate (D-2HG) is released by various types of malignant cells including acute myeloid leukemia (AML) blasts carrying isocitrate dehydrogenase (IDH) gain-of-function mutations. D-2HG acting as an oncometabolite promotes proliferation, anoikis, and differentiation block of hematopoietic cells in an autocrine fashion. However, prognostic impact of IDH mutations and high D-2HG levels remains controversial and might depend on the overall mutational context. An increasing number of studies focus on the permissive environment created by AML blasts to promote immune evasion...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29879375/idh1-mutant-cancer-cells-are-sensitive-to-cisplatin-and-an-idh1-mutant-inhibitor-counteracts-this-sensitivity
#3
Mohammed Khurshed, Niels Aarnoudse, Renske Hulsbos, Vashendriya V V Hira, Hanneke W M van Laarhoven, Johanna W Wilmink, Remco J Molenaar, Cornelis J F van Noorden
Isocitrate dehydrogenase ( IDH1)-1 is mutated in various types of human cancer, and the presence of this mutation is associated with improved responses to irradiation and chemotherapy in solid tumor cells. Mutated IDH1 (IDH1MUT ) enzymes consume NADPH to produce d-2-hydroxyglutarate (d-2HG) resulting in the decreased reducing power needed for detoxification of reactive oxygen species (ROS), for example. The objective of the current study was to investigate the mechanism behind the chemosensitivity of the widely-used anticancer agent cisplatin in IDH1MUT cancer cells...
June 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29872866/the-lncrna-mir4435-2hg-promotes-lung-cancer-progression-by-activating-%C3%AE-catenin-signalling
#4
Haiyun Qian, Li Chen, Jiangping Huang, Xianghui Wang, Shengwei Ma, Fenghe Cui, Liyun Luo, Li Ling, Kai Luo, Guopei Zheng
Recently, emerging evidence has suggested that long noncoding RNAs (lncRNAs) have crucial roles in cancer progression. Here, we demonstrated that the lncRNA MIR4435-2HG was highly expressed in lung cancer tissues and correlated with histological grades and lymph node metastasis. Phenotypic analysis indicated that MIR4435-2HG knockdown inhibited lung cancer cell proliferation and invasion in vitro and in vivo. Notably, MIR4435-2HG knockdown suppressed the EMT (epithelial-mesenchymal transition) process and cancer stem cell traits of lung cancer cells...
June 5, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29773061/development-of-novel-therapeutics-targeting-isocitrate-dehydrogenase-mutations-in-cancer
#5
Horrick Sharma
Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH 1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumor types, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyze αKG conversion to (R)-2-hydroxyglutarate ((R)-2HG)...
May 17, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29738972/steroids-from-ganoderma-sinense-as-new-natural-inhibitors-of-cancer-associated-mutant-idh1
#6
Mengzhu Zheng, Ruotian Tang, Yue Deng, Kaiyin Yang, Lixia Chen, Hua Li
Isocitrate dehydrogenase (IDH) is one of the key enzymes in the tricarboxylic acid cycle, and IDH mutations have been associated with many cancers, including glioblastoma, sarcoma, acute myeloid leukemia, etc. Three natural steroids 1-3 from Ganoderma sinense, a unique and rare edible-medicinal fungi in China, were found as potential IDH1 inhibitors by virtual ligand screening method. Among the three compounds, 3 showed the highest binding affinity to IDH1 with significant calculated binding free energy. Enzymatic kinetics demonstrated that 3 inhibited mutant enzyme in a noncompetitive manner...
April 30, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29662077/pharmacodynamics-of-mutant-idh1-inhibitors-in-glioma-patients-probed-by-in-vivo-3d-mrs-imaging-of-2-hydroxyglutarate
#7
Ovidiu C Andronesi, Isabel C Arrillaga-Romany, K Ina Ly, Wolfgang Bogner, Eva M Ratai, Kara Reitz, A John Iafrate, Jorg Dietrich, Elizabeth R Gerstner, Andrew S Chi, Bruce R Rosen, Patrick Y Wen, Daniel P Cahill, Tracy T Batchelor
Inhibitors of the mutant isocitrate dehydrogenase 1 (IDH1) entered recently in clinical trials for glioma treatment. Mutant IDH1 produces high levels of 2-hydroxyglurate (2HG), thought to initiate oncogenesis through epigenetic modifications of gene expression. In this study, we show the initial evidence of the pharmacodynamics of a new mutant IDH1 inhibitor in glioma patients, using non-invasive 3D MR spectroscopic imaging of 2HG. Our results from a Phase 1 clinical trial indicate a rapid decrease of 2HG levels by 70% (CI 13%, P = 0...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29568832/neutral-and-cationic-cyclic-alkyl-amino-carbene-mercury-caac-hg-ii-complexes-scope-of-hydroamination-of-alkynes-with-organomercury-compounds
#8
Deependra Bawari, Bhupendra Goswami, Sabari V R, Sandeep Kumar Thakur, R V Varun Tej, Angshuman Roy Choudhury, Sanjay Singh
This study demonstrates the first synthesis of cyclic (alkyl)(amino)carbene (cAAC) adducts of Hg(ii), [cAACMe·HgBr(μ-Br)]2 (1a) and [cAACcy·HgBr(μ-Br)]2 (1b). Adduct 1b catalyzes intermolecular hydroamination of aromatic alkynes and amines under mild conditions to afford aromatic imines. The quest to prepare an electrophilic Hg(ii) complex resulted in the synthesis of cationic [(cAACcy)2Hg(H2O)]2+2[NO3]- (3) by reacting 1b with AgNO3.
May 8, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29528543/samarium-polystibides-derived-from-highly-activated-nanoscale-antimony
#9
Christoph Schoo, Sebastian Bestgen, Alexander Egeberg, Svetlana Klementyeva, Claus Feldmann, Sergey N Konchenko, Peter W Roesky
Zintl ions in molecular compounds are of fundamental interest for basic research and application. Two reactive antimony sources are presented that allow direct access to molecular polystibide compounds. These are Sb amalgam (Sb/Hg) and ultrasmall Sb0 nanoparticles (d=6.6±0.8 nm), which were used independently as precursors for the synthesis of the largest f-element polystibide, [(Cp*2 Sm)4 Sb8 ]. Whereas the reaction of the nanoparticles with [Cp*2 Sm] directly led to [(Cp*2 Sm)4 Sb8 ], Sm/Sb/Hg intermediates were isolated when using Sb/Hg as the precursor...
May 14, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29522955/validation-of-a-routine-gas-chromatography-mass-spectrometry-method-for-2-hydroxyglutarate-quantification-in-human-serum-as-a-screening-tool-for-detection-of-idh-mutations
#10
Esther Fernández-Galán, Núria Massana, Marina Parra-Robert, Susana Hidalgo, Gregori Casals, Jordi Esteve, Wladimiro Jiménez
High circulating levels of 2-hydroxyglutarate (2HG) have been reported in patients with determinate isocitrate dehydrogenase (IDH) mutated tumors. Recent studies indicate that in malignancies such as acute myeloid leukemia (AML), measurements of 2HG in serum provide useful diagnostic and prognostic information and improve patient selection and monitoring of IDH-targeted treatments. In the current study, we validated a sensitive and specific gas chromatography mass spectrometry (GC-MS) method specifically intended to quantify serum levels of 2HG in routine clinical laboratories...
April 15, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29499756/rapid-detection-of-2-hydroxyglutarate-in-frozen-sections-of-idh-mutant-tumors-by-maldi-tof-mass-spectrometry
#11
Rémi Longuespée, Annika K Wefers, Elena De Vita, Aubry K Miller, David E Reuss, Wolfgang Wick, Christel Herold-Mende, Mark Kriegsmann, Peter Schirmacher, Andreas von Deimling, Stefan Pusch
All isocitrate dehydrogenase (IDH) mutant solid neoplasms exhibit highly elevated levels of D-2-hydroxyglutarate (D-2HG). Detection of 2HG in tumor tissues currently is performed by gas or liquid chromatography-mass spectrometry (GC- or LC-MS) or biochemical detection. While these methods are highly accurate, a considerable amount of time for tissue preparation and a relatively high amount of tissue is required for testing. We here present a rapid approach to detect 2HG in brain tumor tissue based on matrix-assisted laser desorption ionization - time of flight mass spectrometry (MALDI-TOF)...
March 2, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29479068/mutational-profiling-of-isolated-myeloid-sarcomas-and-utility-of-serum-2hg-as-biomarker-of-idh1-2-mutations
#12
Christophe Willekens, Aline Renneville, Sophie Broutin, Véronique Saada, Jean-Baptiste Micol, Julia Delahousse, Vianney Poinsignon, Claire Bories, Céline Berthon, Raphael Itzykson, Nicolas Boissel, Cyril Quivoron, Marie Terroir-Cassou-Mounat, Jacques Bosq, Claude Preudhomme, Angelo Paci, Virginie Penard-Lacronique, Stéphane De Botton
No abstract text is available yet for this article.
February 26, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29459295/the-link-between-insulin-resistance-parameters-and-serum-uric-acid-is-mediated-by-adiposity
#13
Mohsen Mazidi, Niki Katsiki, Dimitri P Mikhailidis, Maciej Banach
BACKGROUND AND AIMS: Conflicting results suggest a link between serum uric acid (SUA), inflammation and glucose/insulin homeostasis; however, the role of adiposity in this relationship is not clear. Therefore, we evaluated the role of different adiposity factors, including central body mass index (BMI), peripheral waist circumference (WC), and visceral adiposity [visceral adipose tissue (apVAT)], on the association between SUA, inflammation and glucose/insulin homeostasis among US adults...
March 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29438510/diagnostic-accuracy-of-2-hydroxyglutarate-magnetic-resonance-spectroscopy-in-newly-diagnosed-brain-mass-and-suspected-recurrent-gliomas
#14
Min Zhou, Yue Zhou, Huijun Liao, Benjamin C Rowland, Xiangquan Kong, Nils D Arvold, David A Reardon, Patrick Y Wen, Alexander P Lin, Raymond Y Huang
Background: Isocitrate dehydrogenase (IDH) mutations result in abnormal accumulation of 2-hydroxyglutarate (2HG) in gliomas that can be detected by MRS. We examined the diagnostic accuracy of 2HG single-voxel spectroscopy (SVS) and chemical shift imaging (CSI) in both newly-diagnosed and post-treatment settings. Methods: Long-TE (97 ms) SVS and CSI were acquired in 85 subjects, including a discovery cohort of 39 patients who had postoperative residual or recurrent glioma with confirmed IDH-mutation status and 6 normal volunteers, a prospective preoperative validation cohort of 24 patients with newly-diagnosed brain mass, and a prospective recurrent-lesion validation cohort of 16 previously-treated IDH-mutant glioma patients with suspected tumor recurrence...
February 9, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29337019/prediabetes-is-associated-with-microalbuminuria-reduced-kidney-function-and-chronic-kidney-disease-in-the-general-population-the-kora-cooperative-health-research-in-the-augsburg-region-f4-study
#15
M R P Markus, T Ittermann, S E Baumeister, C Huth, B Thorand, C Herder, M Roden, U Siewert-Markus, W Rathmann, W Koenig, M Dörr, H Völzke, S Schipf, C Meisinger
BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study...
March 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29287025/2-hydroxyglutarate-detection-by-short-echo-time-magnetic-resonance-spectroscopy-in-routine-imaging-study-of-brain-glioma-at-3-0-t
#16
Girolamo Crisi, Silvano Filice, Maria Michiara, Pellegrino Crafa, Silvia Lana
OBJECTIVE: The objective of this study was to assess the effective performance of short echo time magnetic resonance spectroscopy (short TE MRS) for 2HG detection as biomarker of isocitrate dehydrogenase (IDH) status in all grade glioma (GL). METHODS: A total of 82 GL patients were prospectively investigated by short TEMRS at 3.0 T as part of a multimodal magnetic resonance imaging study protocol. Spectral analysis was performed using linear combination model. Tumor specimens were diagnosed as IDH mutant or wild type according to the 2016 World Health Organization (WHO) classification of brain tumors...
December 28, 2017: Journal of Computer Assisted Tomography
https://www.readbyqxmd.com/read/29274619/circulating-oncometabolite-d-2-hydroxyglutarate-enantiomer-is-a-surrogate-marker-of-isocitrate-dehydrogenase-mutated-intrahepatic-cholangiocarcinomas
#17
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...
February 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29249359/r-2hg-exhibits-anti-tumor-activity-by-targeting-fto-m-6-a-myc-cebpa-signaling
#18
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 (m6 A) 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...
January 11, 2018: Cell
https://www.readbyqxmd.com/read/29202474/adhfe1-is-a-breast-cancer-oncogene-and-induces-metabolic-reprogramming
#19
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...
January 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29167927/new-diagnostic-criteria-for-gestational-diabetes-mellitus-and-their-impact-on-the-number-of-diagnoses-and-pregnancy-outcomes
#20
Sarah H Koning, Jelmer J van Zanden, Klaas Hoogenberg, Helen L Lutgers, Alberdina W Klomp, Fleurisca J Korteweg, Aren J van Loon, Bruce H R Wolffenbuttel, Paul P van den Berg
AIMS/HYPOTHESIS: Detection and management of gestational diabetes mellitus (GDM) are crucial to reduce the risk of pregnancy-related complications for both mother and child. In 2013, the WHO adopted new diagnostic criteria for GDM to improve pregnancy outcomes. However, the evidence supporting these criteria is limited. Consequently, these new criteria have not yet been endorsed in the Netherlands. The aim of this study was to determine the impact of these criteria on the number of GDM diagnoses and pregnancy outcomes...
April 2018: Diabetologia
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