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https://www.readbyqxmd.com/read/29147863/prognostic-relevance-of-programmed-cell-death-ligand-1-expression-in-glioblastoma
#1
Kyu Sang Lee, Kyoungyul Lee, Sumi Yun, Seyoung Moon, Yujun Park, Jung Ho Han, Chae-Yong Kim, Hye Seung Lee, Gheeyoung Choe
The aim of this study was to determine the clinicopathological significance of programmed cell death ligand 1 (PD-L1) expression in glioblastoma (GBM). In a retrospective cohort of 115 consecutive patients with GBM, PD-L1 expression was determined using immunohistochemistry (IHC). Membranous and fibrillary PD-L1 staining of any intensity in > 5% neoplastic cells and tumour infiltrating immune cells (TIIs) was considered positive staining. In addition, isocitrate dehydrogenase-1 (IDH-1) (R132H) expression and cluster of differentiation 3 (CD3)-positive T-cell infiltration were investigated using IHC...
November 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#2
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29144447/bcat1-restricts-%C3%AE-kg-levels-in-aml-stem-cells-leading-to-idhmut-like-dna-hypermethylation
#3
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/29140606/mr-textural-analysis-on-t2-flair-images-for-the-prediction-of-true-oligodendroglioma-by-the-2016-who-genetic-classification
#4
Wenting Rui, Yan Ren, Yin Wang, Xinyi Gao, Xiao Xu, Zhenwei Yao
BACKGROUND: The genetic status of 1p/19q is important for differentiating oligodendroglioma, isocitrate-dehydrogenase (IDH)-mutant, and 1p/19q-codeleted from diffuse astrocytoma, IDH-mutant according to the 2016 World Health Organization (WHO) criteria. PURPOSE: To assess the value of magnetic resonance textural analysis (MRTA) on T2 fluid-attenuated inversion recovery (FLAIR) images for making a genetically integrated diagnosis of true oligodendroglioma by WHO guidelines...
November 15, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/29140514/idh-mutation-testing-in-gliomas-where-do-we-draw-the-line
#5
Farshad Nassiri, Gelareh Zadeh, Kenneth Aldape
No abstract text is available yet for this article.
November 11, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29133704/survival-trends-in-glioma-experience-at-a-tertiary-care-centre
#6
Ratnadip Bose, Karanjit S Narang, Deepak Bhangale, Rishabh Kedia, Vikas Sharma, Ajaya N Jha
BACKGROUND: Even after decades of research in the field of gliomas, the overall prognosis is still quite dismal. Several factors have been proposed that affect the outcome and survival length of patients with a glioma. Here, we present a series of 471 patients, who underwent surgical resection of their glioma at a tertiary level neurosurgical centre. MATERIALS AND METHODS: We noted retrospective data of patients' age, histological tumor grade, and whether or not intraoperative magnetic resonance imaging (MRI) was used, and assessed the survival length of these patients from the day of surgery...
November 2017: Neurology India
https://www.readbyqxmd.com/read/29130549/concomitant-idh-wildtype-glioblastoma-and-idh1-mutant-anaplastic-astrocytoma-in-a-patient-with-constitutional-mismatch-repair-deficiency-syndrome
#7
Francesca Galuppini, Enrico Opocher, Uri Tabori, Isabella Mammi, Melissa Edwards, Britany Campbell, Jacalyn Kelly, Alessandra Viel, Michele Quaia, Francesca Rivieri, Domenico D'Avella, Antonella Arcella, Felice Giangaspero, Matteo Fassan, Marina Paola Gardiman
Constitutional mismatch repair deficiency (CMMRD) is a rare and often under-recognized tumour predisposition syndrome, presenting with both extracranial and malignant brain tumours that occur in children and/or young adults [1]. The genetic defects underlying this disease are biallelic germline mutations in one of the DNA mismatch repair (MMR) genes leading to a constitutional DNA repair defect that causes a cancer predisposition syndrome with early onset [2]. This mechanism is different from Lynch syndrome (LS) where a heterozygous germline loss-of-function mutation is observed and the patients are more prone to develop colon and genitourinary cancers as adults [1]...
November 12, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29128551/transplant-decisions-in-patients-with-myelofibrosis-should-mutations-be-the-judge
#8
REVIEW
Rachel B Salit, H Joachim Deeg
The prognosis of myeloproliferative neoplasms (MPN), including primary myelofibrosis (PMF), polycythemia vera (PV; post-PV MF) and essential thrombocythemia (ET; post-EMF) varies considerably, between these disorders as well as within each diagnosis. Molecular studies have identified "driver mutations", in JAK2, MPL1 and CALR, and additional somatic DNA mutations, including ASXL1, EZH2, IDH1/2 and SRSF2, that affect prognosis differentially. Patients with mutations in CALR (type1) have a better outlook than patients with mutations in JAK2 or MPL, while patients without any of the driver mutations (triple negative) have the shortest life expectancy...
November 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29127555/continuous-monitoring-of-blood-pressure-by-analyzing-the-blood-flow-sound-of-arteriovenous-fistula-in-hemodialysis-patients
#9
Yuka Kamijo, Eiichiro Kanda, Hayato Horiuchi, Noriyuki Kounoue, Keisuke Ono, Keizo Maeda, Akane Yanai, Kazuya Honda, Ryuji Tsujimoto, Mai Yanagi, Yoshitaka Ishibashi, Masayuki Yoshida
BACKGROUND: Patients with end-stage renal disease undergoing hemodialysis (HD) have an elevated risk of cardiovascular disease-related morbidity and mortality. To prevent from such a life-threatening event, the continuous blood pressure (BP) monitoring system may contribute to detect BP decline in early stages and may help to do appropriate disposal. Our research team has introduced an electronic stethoscope (Asahi Kasei Co, Ltd., Tokyo, Japan), which translates sound intensity of Arteriovenous Fistula (AVF) to BP data using the technique of Fourier transformation that can predict continuous BP non-invasively...
November 10, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29126125/highly-specific-determination-of-idh-status-using-edited-in-vivo-magnetic-resonance-spectroscopy
#10
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/29124520/seom-clinical-guideline-of-diagnosis-and-management-of-low-grade-glioma-2017
#11
J M Sepúlveda-Sánchez, J Muñoz Langa, M Á Arráez, J Fuster, A Hernández Laín, G Reynés, V Rodríguez González, E Vicente, M Vidal Denis, Ó Gallego
Diffuse infiltrating low-grade gliomas include oligodendrogliomas and astrocytomas, and account for about 5% of all primary brain tumors. Treatment strategies for these low-grade gliomas in adults have recently changed. The 2016 World Health Organization (WHO) classification has updated the definition of these tumors to include their molecular characterization, including the presence of isocitrate dehydrogenase (IDH) mutation and 1p/19p codeletion. In this new classification, the histologic subtype of grade II-mixed oligoastrocytoma has also been eliminated...
November 9, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29122763/prediction-of-idh1-mutation-and-1p-19q-codeletion-status-using-preoperative-mr-imaging-phenotypes-in-lower-grade-gliomas
#12
Y W Park, K Han, S S Ahn, S Bae, Y S Choi, J H Chang, S H Kim, S-G Kang, S-K Lee
BACKGROUND AND PURPOSE: WHO grade II gliomas are divided into three classes: isocitrate dehydrogenase (IDH)-wildtype, IDH-mutant and no 1p/19q codeletion, and IDH-mutant and 1p/19q-codeleted. Different molecular subtypes have been reported to have prognostic differences and different chemosensitivity. Our aim was to evaluate the predictive value of imaging phenotypes assessed with the Visually AcceSAble Rembrandt Images lexicon for molecular classification of lower grade gliomas. MATERIALS AND METHODS: MR imaging scans of 175 patients with lower grade gliomas with known IDH1 mutation and 1p/19q-codeletion status were included (78 grade II and 97 grade III) in the discovery set...
November 9, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/29105198/braf-v600e-tert-promoter-mutations-and-cdkn2a-b-homozygous-deletions-are-frequent-in-epithelioid-glioblastomas-a-histological-and-molecular-analysis-focusing-on-intratumoral-heterogeneity
#13
Nozomi Nakajima, Sumihito Nobusawa, Satoshi Nakata, Mitsutoshi Nakada, Tatsuya Yamazaki, Nozomi Matsumura, Kenichi Harada, Hadzki Matsuda, Nobuaki Funata, Shoichi Nagai, Hideo Nakamura, Atsushi Sasaki, Jiro Akimoto, Junko Hirato, Hideaki Yokoo
Epithelioid glioblastoma (E-GBM) is a rare aggressive variant of IDH-wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E-GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E-GBM are recognized as primary/de novo lesions; however, several E-GBM with co- or pre-existing lower-grade lesions have been reported...
November 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/29104858/idh-mutational-status-and-the-immune-system-in-gliomas-a-tale-of-two-tumors
#14
Bryan D Choi, William T Curry
No abstract text is available yet for this article.
October 2017: Translational Cancer Research
https://www.readbyqxmd.com/read/29097607/adaptive-evolution-of-the-gdh2-allosteric-domain-promotes-gliomagenesis-by-resolving-idh1-r132h-induced-metabolic-liabilities
#15
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/29091765/low-grade-astrocytoma-mutations-in-idh1-p53-and-atrx-cooperate-to-block-differentiation-of-human-neural-stem-cells-via-repression-of-sox2
#16
Aram S Modrek, Danielle Golub, Themasap Khan, Devin Bready, Jod Prado, Christopher Bowman, Jingjing Deng, Guoan Zhang, Pedro P Rocha, Ramya Raviram, Charalampos Lazaris, James M Stafford, Gary LeRoy, Michael Kader, Joravar Dhaliwal, N Sumru Bayin, Joshua D Frenster, Jonathan Serrano, Luis Chiriboga, Rabaa Baitalmal, Gouri Nanjangud, Andrew S Chi, John G Golfinos, Jing Wang, Matthias A Karajannis, Richard A Bonneau, Danny Reinberg, Aristotelis Tsirigos, David Zagzag, Matija Snuderl, Jane A Skok, Thomas A Neubert, Dimitris G Placantonakis
Low-grade astrocytomas (LGAs) carry neomorphic mutations in isocitrate dehydrogenase (IDH) concurrently with P53 and ATRX loss. To model LGA formation, we introduced R132H IDH1, P53 shRNA, and ATRX shRNA into human neural stem cells (NSCs). These oncogenic hits blocked NSC differentiation, increased invasiveness in vivo, and led to a DNA methylation and transcriptional profile resembling IDH1 mutant human LGAs. The differentiation block was caused by transcriptional silencing of the transcription factor SOX2 secondary to disassociation of its promoter from a putative enhancer...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29090344/the-role-of-mutant-idh1-and-idh2-inhibitors-in-the-treatment-of-acute-myeloid-leukemia
#17
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/29089260/design-synthesis-and-biological-activity-of-3-pyrazine-2-yl-oxazolidin-2-ones-as-novel-potent-and-selective-inhibitors-of-mutant-isocitrate-dehydrogenase-1
#18
Tianfang Ma, Fangxia Zou, Stefan Pusch, Lijun Yang, Qihua Zhu, Yungen Xu, Yueqing Gu, Andreas von Deimling, Xiaoming Zha
Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (α-KG) generating carbon dioxide and NADPH/NADH. Evidence suggests that the specific mutations in IDH1 are critical to the growth and reproduction of some tumor cells such as gliomas and acute myeloid leukemia, emerging as an attractive antitumor target. In order to discovery potent new mutant IDH1 inhibitors, we designed, synthesized and evaluated a series of allosteric mIDH1 inhibitors harboring the scaffold of 3-pyrazine-2-yl-oxazolidin-2-ones...
October 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29081442/glioblastoma-treatment-in-the-elderly
#19
Masaki Okada, Keisuke Miyake, Takashi Tamiya
Although current treatment advances prolong patient survival, treatment for glioblastoma (GBM) in the elderly has become an emerging issue. The definition of "elderly" differs across articles; GBM predominantly occurs at an age ≥65 years, and the prognosis worsens with increasing age. Regarding molecular markers, isocitrate dehydrogenase (IDH) mutations are less common in the elderly with GBM. Meanwhile, O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation has been identified in approximately half of patients with GBM...
October 30, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/29071695/newer-strategies-for-the-management-of-low-grade-gliomas
#20
Karan Dixit, Jeffrey Raizer
Low-grade gliomas are infiltrative primary brain tumors that most commonly occur in young adults. They are relatively slow growing compared with high-grade gliomas. The World Health Organization classification system was updated in 2016 to define low-grade gliomas using molecular markers in addition to histology. IDH mutation is an independent marker associated with better outcomes. Management is individualized based on tumor histology, molecular characterization, and patient risk factors. Given the longer course and natural history of low-grade gliomas, the goals of treatment should be to prolong overall survival and minimize neurocognitive decline...
September 15, 2017: Oncology (Williston Park, NY)
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