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https://www.readbyqxmd.com/read/29777252/noninvasively-evaluating-the-grading-and-idh1-mutation-status-of-diffuse-gliomas-by-three-dimensional-pseudo-continuous-arterial-spin-labeling-and-diffusion-weighted-imaging
#1
Tingting Liu, Guang Cheng, Xiaowei Kang, Yibin Xi, Yuanqiang Zhu, Kai Wang, Chao Sun, Jing Ye, Ping Li, Hong Yin
PURPOSE: To noninvasively evaluate the value of three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) and diffusion-weighted imaging (DWI) in diffuse gliomas grading as well as isocitrate dehydrogenase (IDH) 1 mutation status. METHODS: Fifty-six patients with pathologically confirmed diffuse gliomas with preoperative 3D pCASL and DWI were enrolled in this study. The Student's t test and Mann-Whitney U test were used to evaluate differences in parameters of DWI and 3D pCASL between low and high grade as well as between mutant and wild-type IDH1 diffuse gliomas; receiver operator characteristic (ROC) analysis was used to assess the diagnostic performance...
May 18, 2018: Neuroradiology
https://www.readbyqxmd.com/read/29773892/metabolite-cycled-density-weighted-concentric-rings-k-space-trajectory-dw-crt-enables-high-resolution-1-h-magnetic-resonance-spectroscopic-imaging-at-3-tesla
#2
Adam Steel, Mark Chiew, Peter Jezzard, Natalie L Voets, Puneet Plaha, Michael Albert Thomas, Charlotte J Stagg, Uzay E Emir
Magnetic resonance spectroscopic imaging (MRSI) is a promising technique in both experimental and clinical settings. However, to date, MRSI has been hampered by prohibitively long acquisition times and artifacts caused by subject motion and hardware-related frequency drift. In the present study, we demonstrate that density weighted concentric ring trajectory (DW-CRT) k-space sampling in combination with semi-LASER excitation and metabolite-cycling enables high-resolution MRSI data to be rapidly acquired at 3 Tesla...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773061/development-of-novel-therapeutics-targeting-isocitrate-dehydrogenase-mutations-in-cancer
#3
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/29766299/molecularly-defined-diffuse-leptomeningeal-glioneuronal-tumor-dlgnt-comprises-two-subgroups-with-distinct-clinical-and-genetic-features
#4
Maximilian Y Deng, Martin Sill, Jason Chiang, Jens Schittenhelm, Martin Ebinger, Martin U Schuhmann, Camelia-Maria Monoranu, Till Milde, Andrea Wittmann, Christian Hartmann, Clemens Sommer, Werner Paulus, Jutta Gärtner, Wolfgang Brück, Thomas Rüdiger, Alfred Leipold, Zane Jaunmuktane, Sebastian Brandner, Felice Giangaspero, Paolo Nozza, Jaume Mora, Andres Morales la Madrid, Ofelia Cruz Martinez, Jordan R Hansford, Torsten Pietsch, Anna Tietze, Pablo Hernáiz-Driever, Iris Stoler, David Capper, Andrey Korshunov, David W Ellison, Andreas von Deimling, Stefan M Pfister, Felix Sahm, David T W Jones
Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs...
May 15, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29752851/idh-mutated-astrocytomas-with-19q-loss-constitute-a-subgroup-that-confers-better-prognosis
#5
Ryohei Otani, Takeo Uzuka, Fumi Higuchi, Hadzki Matsuda, Masashi Nomura, Shota Tanaka, Akitake Mukasa, Koichi Ichimura, Phyo Kim, Keisuke Ueki
IDH-mutant gliomas are classified into astrocytic or oligodendroglial tumors by 1p/19q status in WHO 2016 classification, with the latter presenting with characteristic morphology and better prognosis in general. However, the morphological and genetic features within each category are varied, and there may be distinguishable subtypes. We analyzed 170 WHO grade II to IV gliomas resected in our institution. 1p/19q status was analyzed by microsatellite analysis, and genetic mutations were analyzed by next-generation sequencing and Sanger sequencing...
May 12, 2018: Cancer Science
https://www.readbyqxmd.com/read/29741737/genetic-and-epigenetic-features-of-rapidly-progressing-idh-mutant-astrocytomas
#6
Timothy E Richardson, Adwait Amod Sathe, Mohammed Kanchwala, Gaoxiang Jia, Amyn A Habib, Guanghua Xiao, Matija Snuderl, Chao Xing, Kimmo J Hatanpaa
IDH-mutant astrocytomas are significantly less aggressive than their IDH-wildtype counterparts. We analyzed The Cancer Genome Atlas dataset (TCGA) and identified a small group of IDH-mutant, WHO grade II-III astrocytomas (n = 14) with an unexpectedly poor prognosis characterized by a rapid progression to glioblastoma and death within 3 years of the initial diagnosis. Compared with IDH-mutant tumors with the typical, extended progression-free survival in a control group of age-similar patients, the tumors in the rapidly progressing group were characterized by a markedly increased level of overall copy number alterations ([CNA]; p = 0...
May 7, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29738972/steroids-from-ganoderma-sinense-as-new-natural-inhibitors-of-cancer-associated-mutant-idh1
#7
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/29732524/integrated-analysis-of-dynamic-fet-pet-ct-parameters-histology-and-methylation-profiling-of-44-gliomas
#8
Manuel Röhrich, Kristin Huang, Daniel Schrimpf, Nathalie L Albert, Thomas Hielscher, Andreas von Deimling, Ulrich Schüller, Antonia Dimitrakopoulou-Strauss, Uwe Haberkorn
PURPOSE: Dynamic 18 F-FET PET/CT is a powerful tool for the diagnosis of gliomas.18 F-FET PET time-activity curves (TAC) allow differentiation between histological low-grade gliomas (LGG) and high-grade gliomas (HGG). Molecular methods such as epigenetic profiling are of rising importance for glioma grading and subclassification. Here, we analysed dynamic 18 F-FET PET data, and the histological and epigenetic features of 44 gliomas. METHODS: Dynamic 18 F-FET PET was performed in 44 patients with newly diagnosed, untreated glioma: 10 WHO grade II glioma, 13 WHO grade III glioma and 21 glioblastoma (GBM)...
May 7, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29727696/h3-k27-m-mutant-diffuse-midline-gliomas-in-different-anatomical-locations
#9
Leiming Wang, Zhuo Li, Ming Zhang, Yueshan Piao, Li Chen, Huiying Liang, Yukui Wei, Zeliang Hu, Lihong Zhao, Lianghong Teng, Dehong Lu
The histone H3 K27 M mutation has been frequently reported in the majority of diffuse midline gliomas. However, the relationship between the H3 K27 M mutation and clinical outcomes of gliomas from different anatomical locations is still not fully understood. A total of 120 patients with diffuse midline gliomas were selected for this retrospective observational study. The status of H3 K27 M, ATRX, TP53 and IDH was evaluated using immunohistochemistry and Sanger sequencing. Of the 120 cases aged from 4 to 76years (median=27years), 61 (50...
May 1, 2018: Human Pathology
https://www.readbyqxmd.com/read/29721393/immune-heterogeneity-and-clinicopathologic-characterization-of-igfbp2-in-2447-glioma-samples
#10
Jinquan Cai, Qun Chen, Yuqiong Cui, Jiawei Dong, Meng Chen, Pengfei Wu, Chuanlu Jiang
Glioblastoma is an immunosuppressive, deadly brain tumor. IGFBP2, a circulating biomarker for cancer diagnosis and a potential immunotherapeutic target, is attracting more and more attention from oncologists and clinicians. Thus, it is urgent to thoroughly investigate the immune biological process of IGFBP2 to understand tumor immune complexity and provide potential evidence for anti-IGFBP2 therapy. Through authoritative public databases, we enrolled a total of 2447 glioma samples with gene expression profiles...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29720725/inhibition-of-gpr158-by-microrna-449a-suppresses-neural-lineage-of-glioma-stem-progenitor-cells-and-correlates-with-higher-glioma-grades
#11
Ningning Li, Ying Zhang, Kastytis Sidlauskas, Matthew Ellis, Ian Evans, Paul Frankel, Joanne Lau, Tedani El-Hassan, Loredana Guglielmi, Jessica Broni, Angela Richard-Loendt, Sebastian Brandner
To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In a microRNA screen we first identified microRNA-449a as most significantly differentially expressed between these two tumour types. miR-449a has a target dependent effect, inhibiting cell growth and migration by downregulation of CCND1 and suppressing neural phenotypes by inhibition of G protein coupled-receptor (GPR) 158...
May 3, 2018: Oncogene
https://www.readbyqxmd.com/read/29718398/targetable-gene-fusions-associate-with-the-idh-wild-type-astrocytic-lineage-in-adult-gliomas
#12
Sherise D Ferguson, Shouhao Zhou, Jason T Huse, John F de Groot, Joanne Xiu, Deepa S Subramaniam, Shwetal Mehta, Zoran Gatalica, Jeffrey Swensen, Nader Sanai, David Spetzler, Amy B Heimberger
Gene fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. Using RNA-sequencing, we interrogated a large cohort of gliomas to assess for the incidence of targetable genetic fusions. Gliomas (n = 390) were profiled using the ArcherDx FusionPlex Assay. Fifty-two gene targets were analyzed and fusions with preserved kinase domains were investigated. Overall, 36 gliomas (9%) harbored a total of 37 potentially targetable fusions, the majority of which were found in astrocytomas (n = 34)...
April 27, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29692895/metabolic-characterization-of-isocitrate-dehydrogenase-idh-mutant-and-idh-wildtype-gliomaspheres-uncovers-cell-type-specific-vulnerabilities
#13
Matthew Garrett, Jantzen Sperry, Daniel Braas, Weihong Yan, Thuc M Le, Jack Mottahedeh, Kirsten Ludwig, Ascia Eskin, Yue Qin, Rachelle Levy, Joshua J Breunig, Frank Pajonk, Thomas G Graeber, Caius G Radu, Heather Christofk, Robert M Prins, Albert Lai, Linda M Liau, Giovanni Coppola, Harley I Kornblum
Background: There is considerable interest in defining the metabolic abnormalities of IDH mutant tumors to exploit for therapy. While most studies have attempted to discern function by using cell lines transduced with exogenous IDH mutant enzyme, in this study, we perform unbiased metabolomics to discover metabolic differences between a cohort of patient-derived IDH1 mutant and IDH wildtype gliomaspheres. Methods: Using both our own microarray and the TCGA datasets, we performed KEGG analysis to define pathways differentially enriched in IDH1 mutant and IDH wildtype cells and tumors...
2018: Cancer & Metabolism
https://www.readbyqxmd.com/read/29687258/novel-improved-grading-system-s-for-idh-mutant-astrocytic-gliomas
#14
Mitsuaki Shirahata, Takahiro Ono, Damian Stichel, Daniel Schrimpf, David E Reuss, Felix Sahm, Christian Koelsche, Annika Wefers, Annekathrin Reinhardt, Kristin Huang, Philipp Sievers, Hiroaki Shimizu, Hiroshi Nanjo, Yusuke Kobayashi, Yohei Miyake, Tomonari Suzuki, Jun-Ichi Adachi, Kazuhiko Mishima, Atsushi Sasaki, Ryo Nishikawa, Melanie Bewerunge-Hudler, Marina Ryzhova, Oksana Absalyamova, Andrey Golanov, Peter Sinn, Michael Platten, Christine Jungk, Frank Winkler, Antje Wick, Daniel Hänggi, Andreas Unterberg, Stefan M Pfister, David T W Jones, Martin van den Bent, Monika Hegi, Pim French, Brigitta G Baumert, Roger Stupp, Thierry Gorlia, Michael Weller, David Capper, Andrey Korshunov, Christel Herold-Mende, Wolfgang Wick, David N Louis, Andreas von Deimling
According to the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO), IDH-mutant astrocytic gliomas comprised WHO grade II diffuse astrocytoma, IDH-mutant (AIIIDHmut ), WHO grade III anaplastic astrocytoma, IDH-mutant (AAIIIIDHmut ), and WHO grade IV glioblastoma, IDH-mutant (GBMIDHmut ). Notably, IDH gene status has been made the major criterion for classification while the manner of grading has remained unchanged: it is based on histological criteria that arose from studies which antedated knowledge of the importance of IDH status in diffuse astrocytic tumor prognostic assessment...
April 23, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29683816/immunohistochemical-detection-and-molecular-characterization-of-idh-mutant-sinonasal-undifferentiated-carcinomas
#15
Jeffrey K Mito, Justin A Bishop, Peter M Sadow, Edward B Stelow, William C Faquin, Stacey E Mills, Jeffrey F Krane, Christopher A French, Christopher D M Fletcher, Jason L Hornick, Lynette M Sholl, Vickie Y Jo
Recent studies have identified recurrent isocitrate dehydrogenase 2 (IDH2) mutations in a subset of sinonasal undifferentiated carcinomas (SNUCs); however, the true frequency of IDH mutations in SNUC is unknown. We evaluated the utility of mutation-specific IDH1/2 immunohistochemistry (IHC) in a large multi-institutional cohort of SNUC and morphologic mimics. IHC using a multispecific antibody for IDH1/2 (R132/R172) mutant protein was performed on 193 sinonasal tumors including: 53 SNUCs, 8 poorly differentiated carcinomas (PDCARs) and 132 histologic mimics...
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29676695/huge-heterogeneity-in-survival-in-a-subset-of-adult-patients-with-resected-wild-type-isocitrate-dehydrogenase-status-who-grade-ii-astrocytomas
#16
Gaëtan Poulen, Catherine Gozé, Valérie Rigau, Hugues Duffau
OBJECTIVE World Health Organization grade II gliomas are infiltrating tumors that inexorably progress to a higher grade of malignancy. However, the time to malignant transformation is quite unpredictable at the individual patient level. A wild-type isocitrate dehydrogenase (IDH-wt) molecular profile has been reported as a poor prognostic factor, with more rapid progression and a shorter survival compared with IDH-mutant tumors. Here, the oncological outcomes of a series of adult patients with IDH-wt, diffuse, WHO grade II astrocytomas (AII) who underwent resection without early adjuvant therapy were investigated...
April 20, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29675936/pediatric-ganglioglioma-with-an-h3-k27m-mutation-arising-from-the-cervical-spinal-cord
#17
Tomohiro Okuda, Nobuhiro Hata, Satoshi O Suzuki, Koji Yoshimoto, Koichi Arimura, Takeo Amemiya, Yojiro Akagi, Daisuke Kuga, Utako Oba, Yuhki Koga, Shouichi Ohga, Toru Iwaki, Koji Iihara
The 2016 edition of the World Health Organization Classification of Tumors of the Central Nervous System introduced "diffuse midline glioma H3 K27M mutant" as a new diagnostic entity. These tumors predominately affect pediatric patients and arise from midline structures such as the brainstem, thalamus and spinal cord. Here, we report a rare patient with spinal ganglioglioma carrying an H3 K27M mutation. A 10-year-old boy presented with an intramedullary tumor in the cervical spinal cord. The lesion was partially removed and histologically diagnosed as ganglioglioma...
April 19, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29666413/texture-analysis-and-support-vector-machine-assisted-diffusional-kurtosis-imaging-may-allow-in-vivo-gliomas-grading-and-idh-mutation-status-prediction-a-preliminary-study
#18
Sotirios Bisdas, Haocheng Shen, Steffi Thust, Vasileios Katsaros, George Stranjalis, Christos Boskos, Sebastian Brandner, Jianguo Zhang
We sought to investigate, whether texture analysis of diffusional kurtosis imaging (DKI) enhanced by support vector machine (SVM) analysis may provide biomarkers for gliomas staging and detection of the IDH mutation. First-order statistics and texture feature extraction were performed in 37 patients on both conventional (FLAIR) and mean diffusional kurtosis (MDK) images and recursive feature elimination (RFE) methodology based on SVM was employed to select the most discriminative diagnostic biomarkers. The first-order statistics demonstrated significantly lower MDK values in the IDH-mutant tumors...
April 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29663171/prognostic-relevance-of-mutations-and-copy-number-alterations-assessed-with-targeted-next-generation-sequencing-in-idh-mutant-grade-ii-glioma
#19
Maarten M J Wijnenga, Pim J French, Hendrikus J Dubbink, Winand N M Dinjens, Peggy N Atmodimedjo, Johan M Kros, Ruth Fleischeuer, Clemens M F Dirven, Arnaud J P E Vincent, Martin J van den Bent
BACKGROUND: At current prognostication of low grade glioma remains suboptimal and might be improved with additional markers. These may guide treatment decisions, in particular on early adjuvant therapy versus wait and see after surgery. METHODS: We used a targeted Next-Generation Sequencing panel to assess mutational and copy number status of selected genes and chromosomes in a consecutive series of adult grade II supratentorial glioma, and assessed the impact of molecular markers of interest on overall survival...
April 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29642588/crystal-structure-of-the-isocitrate-dehydrogenase-2-from-acinetobacter-baumannii-abidh2-reveals-a-novel-dimeric-structure-with-two-monomeric-idh-like-subunits
#20
Peng Wang, Yatao Wu, Jie Liu, Ping Song, Shan Li, Xinxin Zhou, Guoping Zhu
Monomeric isocitrate dehydrogenases (IDHs) have a single polypeptide sizing around 85 kDa. The IDH2 from the opportunistic bacterium Acinetobacter baumannii (AbIDH2) with a mass of 83 kDa was formerly recognized as a typical monomeric IDH. However, both size exclusion chromatography and analytical ultracentrifugation analysis indicated that AbIDH2 exists as a homodimer in solution. The crystallographic study of the substrate/coenzyme-free AbIDH2 gave a dimeric structure and each subunit contained a domain I and a domain II...
April 10, 2018: International Journal of Molecular Sciences
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