keyword
MENU ▼
Read by QxMD icon Read
search

IDH2

keyword
https://www.readbyqxmd.com/read/29149454/melatonin-alleviates-adipose-inflammation-through-elevating-%C3%AE-ketoglutarate-and-diverting-adipose-derived-exosomes-to-macrophages-in-mice
#1
Zhenjiang Liu, Lu Gan, Tiantian Zhang, Qian Ren, Chao Sun
Obesity is associated with macrophage infiltration and metabolic inflammation, both of which promote metabolic disease progression. Melatonin is reported to possess anti-inflammatory properties by inhibiting inflammatory response of adipocytes and macrophages activation. However, the effects of melatonin on the communication between adipocytes and macrophages during adipose inflammation remain elusive. Here, we demonstrated melatonin alleviated inflammation and elevated α-ketoglutarate (αKG) level in adipose tissue of obese mice...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29120536/discovery-of-a-novel-class-of-pyridine-derivatives-that-selectively-inhibits-mutant-isocitrate-dehydrogenase-2
#2
Fangying Wang, Zhuolin Li, Tao Zhang, Guoyi Yan, Mingxing Hu, Lifeng Zhao, Yinglan Zhao, Yuanwei Chen
Current paper presents synthesis and Structure-Activity Relationship of pyridine derivatives as inhibitors of mutant isocitrate dehydrogenase 2 (IDH2). A series of 2,4,6-trisubsitituted pyridine derivatives have been prepared and evaluated in vitro. Among these compounds, 14n exhibited excellent inhibition activity with the IC50 of 54.6 nM, which is approximately 1-fold improvement compared to drug candidate AG-221 (Enasidenib) that is in Phase III trial. Exquisite selectivity of 14n for IDH2 R140Q mutant isoform was demonstrated by the poor activity against the wild-type IDH1 and IDH2...
November 9, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29090344/the-role-of-mutant-idh1-and-idh2-inhibitors-in-the-treatment-of-acute-myeloid-leukemia
#3
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...
October 31, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/29079473/discovery-and-structure-activity-relationship-study-of-novel-conformationally-restricted-indane-analogues-for-mutant-isocitric-dehydrogenase-1-idh1-inhibitors
#4
Qiangang Zheng, Shuai Tang, Xianlei Fu, Ziqi Chen, Yan Ye, Xiaojing Lan, Lei Jiang, Ying Huang, Jian Ding, Meiyu Geng, Min Huang, Huixin Wan
The discovery and optimization of various of indane amides as mutant IDH1 inhibitors via structure-based rational design were reported. The optimal compounds demonstrated both potent inhibition in IDH1(R132H) enzymatic activity and 2HG production in IDH1 mutant HT1080 cell line, favorable PK properties and great selectivity against IDH1(wt) and IDH2(R140Q).
October 16, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29064021/targeting-idh1-and-idh2-mutations-in-acute-myeloid-leukemia
#5
REVIEW
Brittany Knick Ragon, Courtney D DiNardo
PURPOSE OF REVIEW: Over the past decade, the pathogenic role of mutations in isocitrate dehydrogenases (IDH) 1 and 2, affecting approximately 20% of patients with AML, has been defined, allowing for the development of specific therapeutic strategies for IDH-mutant AML. In this review, the landscape and progress of targeted therapeutics aimed at IDH mutations in AML and related myeloid malignancies will be described. RECENT FINDINGS: Since 2013, several mutant IDH-targeted inhibitors have been developed, and nearly a dozen clinical trials have opened specifically for IDH-mutant hematologic malignancies...
October 24, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29058264/seom-clinical-guidelines-for-anaplastic-gliomas-2017
#6
C Balañá, M Alonso, A Hernandez, P Perez-Segura, E Pineda, A Ramos, A R Sanchez, P Teixidor, E Verger, M Benavides
The SEOM/GEINO clinical guidelines provide recommendations for radiological, and molecular diagnosis, treatment and follow-up of adult patients with anaplastic gliomas (AG). We followed the 2016 WHO classification which specifies the major diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and 1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first-line standard of care for AG with slight modifications according to molecular variables...
October 20, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29056515/in%C3%A2-vivo-imaging-of-glutamine-metabolism-to-the-oncometabolite-2-hydroxyglutarate-in-idh1-2-mutant-tumors
#7
Lucia Salamanca-Cardona, Hardik Shah, Alex J Poot, Fabian M Correa, Valentina Di Gialleonardo, Hui Lui, Vesselin Z Miloushev, Kristin L Granlund, Sui S Tee, Justin R Cross, Craig B Thompson, Kayvan R Keshari
The oncometabolite 2-hydroxyglutarate (2-HG) is a signature biomarker in various cancers, where it accumulates as a result of mutations in isocitrate dehydrogenase (IDH). The metabolic source of 2-HG, in a wide variety of cancers, dictates both its generation and also potential therapeutic strategies, but this remains difficult to access in vivo. Here, utilizing patient-derived chondrosarcoma cells harboring endogenous mutations in IDH1 and IDH2, we report that 2-HG can be rapidly generated from glutamine in vitro...
October 16, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29052597/syk-expression-in-monomorphic-epitheliotropic-intestinal-t-cell-lymphoma
#8
Grit Mutzbauer, Katja Maurus, Clara Buszello, Jordan Pischimarov, Sabine Roth, Andreas Rosenwald, Andreas Chott, Eva Geissinger
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as type II enteropathy associated T-cell lymphoma (type II EATL), is a rare, aggressive primary intestinal T-cell lymphoma with a poor prognosis and an incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases of EATL, formerly known as type I EATL, and comparatively investigated the T-cell receptor (TCR) itself and associated signaling molecules using immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing...
October 20, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29051180/midostaurin-enasidenib-cpx-351-gemtuzumab-ozogomycin-and-venetoclax-bring-new-hope-to-aml
#9
Andrew H Wei, Ing S Tiong
In 2017, four new drugs have so far received FDA marketing approval for the treatment of acute myeloid leukemia (AML), including targeted therapies for mutant FLT3 (midostaurin) and IDH2 (enasidenib), a novel liposomal cytarabine-daunorubicin formulation (CPX-351) for therapy-related AML and AML with myelodysplasia-related changes and finally, resurgence of an antibody-drug conjugate designed to target CD33 (gemtuzumab ozogomycin; GO). Promising results also emerged for the BCL-2 inhibitor venetoclax combined with low-intensity therapy in older patients with AML unfit for intensive chemotherapy...
October 19, 2017: Blood
https://www.readbyqxmd.com/read/29038504/the-contribution-of-saccharomyces-cerevisiae-replicative-age-to-the-variations-in-the-levels-of-trx2p-pdr5p-can1p-and-idh-isoforms
#10
Aglaia V Azbarova, Kseniia V Galkina, Maxim I Sorokin, Fedor F Severin, Dmitry A Knorre
Asymmetrical division can be a reason for microbial populations heterogeneity. In particular, budding yeast daughter cells are more vulnerable to stresses than the mothers. It was suggested that yeast mother cells could also differ from each other depending on their replicative age. To test this, we measured the levels of Idh1-GFP, Idh2-GFP, Trx2-GFP, Pdr5-GFP and Can1-GFP proteins in cells of the few first, most represented, age cohorts. Pdr5p and Can1p were selected because of the pronounced mother-bud asymmetry for these proteins distributions, Trx2p as indicator of oxidative stress...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29031038/isocitrate-dehydrogenase-mutations-are-better-prognostic-marker-than-o6-methylguanine-dna-methyltransferase-promoter-methylation-in-glioblastomas-a-retrospective-single-centre-molecular-genetics-study-of-gliomas
#11
M Houdova Megova, J Drábek, Z Dwight, R Trojanec, V Koudeláková, J Vrbková, O Kalita, S Mlcochova, M Rabcanova, M Hajdúch
BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are a promising prognostic biomarker of gliomas. The purpose of our study was to examine the clinical prognostic properties of IDH1/2 mutations in a glioma patient cohort from the Czech Republic using an improved platform for simple and reliable IDH genotyping. MATERIAL AND METHODS: We retrospectively analyzed a group of 145 glioma patients by testing for the three most frequent IDH mutations, IDH1 R132H, IDH1 R132C, and IDH2 R172K, through the competitive amplification of differentially melting amplicons (CADMA) polymerase chain reaction (PCR)...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28993730/molecular-guided-therapy-provides-sustained-clinical-response-in-refractory-choroid-plexus-carcinoma
#12
Albert Cornelius, Jessica Foley, Jeffrey Bond, Abhinav B Nagulapally, Julie Steinbrecher, William P D Hendricks, Maria Rich, Sangeeta Yendrembam, Genevieve Bergendahl, Jeffrey M Trent, Giselle S Sholler
Choroid plexus carcinomas (CPCs) are rare, aggressive pediatric brain tumors with no established curative therapy for relapsed disease, and poor survival rates. TP53 Mutation or dysfunction correlates with poor or no survival outcome in CPCs. Here, we report the case of a 4 month-old female who presented with disseminated CPC. After initial response to tumor resection and adjuvant-chemotherapy, the tumor recurred and metastasized with no response to aggressive relapse therapy suggesting genetic predisposition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28986582/assessing-inhibitors-of-mutant-isocitrate-dehydrogenase-using-a-suite-of-pre-clinical-discovery-assays
#13
Daniel J Urban, Natalia J Martinez, Mindy I Davis, Kyle R Brimacombe, Dorian M Cheff, Tobie D Lee, Mark J Henderson, Steven A Titus, Rajan Pragani, Jason M Rohde, Li Liu, Yuhong Fang, Surendra Karavadhi, Pranav Shah, Olivia W Lee, Amy Wang, Andrew McIver, Hongchao Zheng, Xiaodong Wang, Xin Xu, Ajit Jadhav, Anton Simeonov, Min Shen, Matthew B Boxer, Matthew D Hall
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that are mutated in a variety of cancers to confer a gain-of-function activity resulting in the accumulation of an oncometabolite, D-2-hydroxyglutarate (2-HG). Accumulation of 2-HG can result in epigenetic dysregulation and a block in cellular differentiation, suggesting these mutations play a role in neoplasia. Based on its potential as a cancer target, a number of small molecule inhibitors have been developed to specifically inhibit mutant forms of IDH (mIDH1 and mIDH2)...
October 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28986151/braf-v600e-mutation-is-a-significant-prognosticator-of-the-tumour-regrowth-rate-in-brainstem-gangliogliomas
#14
Xin Chen, Changcun Pan, Peng Zhang, Cheng Xu, Yu Sun, Hai Yu, Yuliang Wu, Yibo Geng, Pengcheng Zuo, Zhen Wu, Junting Zhang, Liwei Zhang
BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma's clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma's clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation...
December 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28980701/isocitrate-dehydrogenase-mutant-glioma-evolving-clinical-and-therapeutic-implications
#15
REVIEW
Julie J Miller, Helen A Shih, Ovidiu C Andronesi, Daniel P Cahill
The metabolic genes isocitrate dehydrogenase 1 (IDH1) and IDH2 are commonly mutated in low-grade glioma and in a subset of glioblastoma. These mutations co-occur with other recurrent molecular alterations, including 1p/19q codeletions and tumor suppressor protein 53 (TP53) and alpha thalassemia/mental retardation (ATRX) mutations, which together help to define a molecular signature that aids in the classification of gliomas and helps to better predict clinical behavior. A confluence of research suggests that glioma development in IDH-mutant and IDH wild-type tumors is driven by different oncogenic processes and responds differently to current treatment paradigms...
December 1, 2017: Cancer
https://www.readbyqxmd.com/read/28968976/the-distinct-clinical-features-of-giant-cell-tumor-of-bone-in-pagetic-and-non-pagetic-patients-are-associated-with-genetic-biochemical-and-histological-differences
#16
Giuseppina Divisato, Federica Scotto di Carlo, Laura Pazzaglia, Riccardo Rizzo, Domenico A Coviello, Maria Serena Benassi, Piero Picci, Teresa Esposito, Fernando Gianfrancesco
Giant Cell Tumor of Bone (GCT) is a tumor characterized by neoplastic mesenchymal stromal cells and a high number of osteoclast-like multinucleated giant cells. Rarely, GCT could arise in bones affected by Paget's disease of bone (GCT/PDB). Although it is already known that GCT/PDB and GCT show a different clinical profile regarding the age-onset and skeletal localization, our deep clinical comparison between the two GCT/PDB and GCT cohorts, permitted us to identify additional differences (e.g. focality, ALP serum levels, the 5-year survival rate and the familial recurrence), strongly suggesting a different molecular basis...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28948488/prognostication-in-philadelphia-chromosome-negative-myeloproliferative-neoplasms-a-review-of-the-recent-literature
#17
REVIEW
Amy Zhou, Amber Afzal, Stephen T Oh
PURPOSE OF REVIEW: The prognosis for patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is highly variable. All Ph-negative MPNs carry an increased risk for thrombotic complications, bleeding, and leukemic transformation. Several clinical, biological, and molecular prognostic factors have been identified in recent years, which provide important information in guiding management of patients with Ph-negative MPNs. In this review, we critically evaluate the recent published literature and discuss important new developments in clinical and molecular factors that impact survival, disease transformation, and thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis...
October 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28945625/expression-of-tfh-markers-and-detection-of-rhoa-p-g17v-and-idh2-p-r172k-s-mutations-in-cutaneous-localizations-of-angioimmunoblastic-t-cell-lymphomas
#18
Ariane Leclaire Alirkilicarslan, Aurélie Dupuy, Anaïs Pujals, Marie Parrens, Béatrice Vergier, Alistair Robson, Marie-Hélène Delfau-Larue, Saskia Ingen-Housz-Oro, Olivier Chosidow, Corinne Haioun, Marie Beylot-Barry, Jean-Philippe Merlio, Christiane Copie-Bergman, Philippe Gaulard, Nicolas Ortonne
Skin biopsies of 41 angioimmunoblastic T-cell lymphoma patients were retrospectively analyzed for the expression of follicular helper T-cell (TFH) markers, Epstein-Barr virus (EBV), and the presence of RHOA (p.G17V) and IDH2 (p.R172K/S) mutations using allele-specific polymerase chain reaction. We categorized cases into 4 distinctive patterns: (1) low-density lymphocytic perivascular infiltrates (n=11), (2) dense perivascular infiltrates with atypical cells and occasional inflammatory cells (n=13), (3) diffuse infiltrates reminiscent of angioimmunoblastic T-cell lymphoma (n=4), or (4) other aspects (n=13)...
December 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28938192/idh2-deficiency-increases-the-liver-susceptibility-to-ischemia-reperfusion-injury-via-increased-mitochondrial-oxidative-injury
#19
Sang Jun Han, Hong Seok Choi, Jee In Kim, Jeen-Woo Park, Kwon Moo Park
Mitochondrial NADP(+)-dependent isocitrate dehydrogenase 2 (IDH2) is a major producer of mitochondrial NADPH, required for glutathione (GSH)-associated mitochondrial antioxidant systems including glutathione peroxidase (GPx) and glutathione reductase (GR). Here, we investigated the role of IDH2 in hepatic ischemia-reperfusion (HIR)-associated mitochondrial injury using Idh2-knockout (Idh2(-/-)) mice and wild-type (Idh2(+/+)) littermates. Mice were subjected to either 60min of partial liver ischemia or sham-operation...
September 8, 2017: Redox Biology
https://www.readbyqxmd.com/read/28928092/idh2-deficiency-accelerates-renal-dysfunction-in-aged-mice
#20
Su Jeong Lee, Hanvit Cha, Seoyoon Lee, Hyunjin Kim, Hyeong Jun Ku, Sung Hwan Kim, Jung Hyun Park, Jin Hyup Lee, Kwon Moo Park, Jeen-Woo Park
The free radical or oxidative stress theory of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species (ROS) that are produced as by-products of normal metabolic processes in mitochondria. The oxidative stress may arise as a result of either increased ROS production or decreased ability to detoxify ROS. The availability of the mitochondrial NADPH pool is critical for the maintenance of the mitochondrial antioxidant system. The major enzyme responsible for generating mitochondrial NADPH is mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2)...
November 4, 2017: Biochemical and Biophysical Research Communications
keyword
keyword
29224
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"