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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/29776636/molecular-diagnostics-in-the-neoplasms-of-the-pancreas-liver-gallbladder-and-extrahepatic-biliary-tract-2018-update
#2
REVIEW
Lei Zhang, Martin H Bluth, Amarpreet Bhalla
Pancreatic neoplasms, including ductal adenocarcinoma, solid pseudopapillary neoplasm, pancreatic endocrine neoplasms, acinar cell carcinoma, and pancreatoblastoma, are associated with different genetic abnormalities. Hepatic adenomas with beta-catenin exon 3 mutation are associated with a high risk of malignancy. Hepatic adenoma with arginosuccinate synthetase 1 expression or sonic hedgehog mutations are associated with a risk of bleeding. Hepatocellular carcinoma and choangiocarcinoma display heterogeneity at both morphologic and molecular levels Cholangiocellular carcinoma is most commonly associated with IDH 1/2 mutations...
June 2018: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/29775073/diffuse-gliomas-for-nonneuropathologists-the-new-integrated-molecular-diagnostics
#3
Sunhee C Lee
Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified...
May 18, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29774877/-analysis-of-prognostic-factors-for-survival-in-elderly-patients-with-glioma
#4
Jinghui Liu, Miao Lou, Peigang Ji, Chen Li, Fuqiang Feng, Baofu Li, Meng Xu, Guodong Gao, Yan Qu, Liang Wang
To analyze the prognostic factors for survival in elderly patients with glioma.
 Methods: We performed a retrospective analysis of prognostic factors for elderly patients with glioma, who were treated by the same attending doctor during June 2014 and June 2016, to investigate the correlations of the age, dimension of pathology, histological grade, extent of resection, adjuvant therapy, preoperative Karnofsky Performance Scale (KPS) score, postoperative KPS score, molecular markers [isocitrate dehydrogenase-1 (IDH-1), O6-methylguanine DNA-transferase (MGMT), epidermal growth factor receptor (EGFR), Ki-67] with the prognosis...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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
#5
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
#6
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/29770897/machine-learning-a-useful-radiological-adjunct-in-determination-of-a-newly-diagnosed-glioma-s-grade-and-idh-status
#7
Céline De Looze, Alan Beausang, Jane Cryan, Teresa Loftus, Patrick G Buckley, Michael Farrell, Seamus Looby, Richard Reilly, Francesca Brett, Hugh Kearney
INTRODUCTION: Machine learning methods have been introduced as a computer aided diagnostic tool, with applications to glioma characterisation on MRI. Such an algorithmic approach may provide a useful adjunct for a rapid and accurate diagnosis of a glioma. The aim of this study is to devise a machine learning algorithm that may be used by radiologists in routine practice to aid diagnosis of both: WHO grade and IDH mutation status in de novo gliomas. METHODS: To evaluate the status quo, we interrogated the accuracy of neuroradiology reports in relation to WHO grade: grade II 96...
May 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29769206/targeting-the-idh2-pathway-in-acute-myeloid-leukemia
#8
Maria L Amaya, Daniel A Pollyea
Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis. A large percentage of patients succumb to this disease, in spite of aggressive treatments with chemotherapy. Recent advances with mutational analysis led to the discovery of isocitrate dehydrogenase (IDH) mutations in AML. IDH2 is an enzyme that catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate; its mutated version leads to the accumulation of the oncometabolite (R)-2 hydroxyglutarate, which disrupts several cell processes and leads to a blockage in differentiation...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29766299/molecularly-defined-diffuse-leptomeningeal-glioneuronal-tumor-dlgnt-comprises-two-subgroups-with-distinct-clinical-and-genetic-features
#9
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/29764444/molecular-and-clinical-characterization-of-ptpn2-expression-from-rna-seq-data-of-996-brain-gliomas
#10
Peng-Fei Wang, Hong-Qing Cai, Chuan-Bao Zhang, Yan-Michael Li, Xiang Liu, Jing-Hai Wan, Tao Jiang, Shou-Wei Li, Chang-Xiang Yan
BACKGROUND: Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling. METHODS: Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas...
May 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29761369/oligodendrogliomas-in-pediatric-and-teenage-patients-only-rarely-exhibit-molecular-markers-and-patients-have-excellent-survivals
#11
Yan-Xi Li, Abudumijiti Aibaidula, Zhifeng Shi, Hong Chen, Kay Ka-Wai Li, Nellie Yuk-Fei Chung, Ryan Rui Yang, Danny Tat-Ming Chan, Wai Sang Poon, Ka Lok Ryan Lee, Ying Mao, Jinsong Wu, Aden Ka-Yin Chan, Liangfu Zhou, Ho-Keung Ng
Although oligodendrogliomas appear histologically similar in adult and pediatric patients, the latter have only been rarely studied and most of those studies did not have long follow-up. We examined 55 oligodendroglial tumors from pediatric and teenage patients for their biomarkers with formalin-fixed paraffin-embedded tissues and studied their survival status. None of the tumors harbored 1p/19q codeletion or IDH mutation. Mutations in TERTp (4%), BRAF (11%), FGFR1 (3%) and H3F3A (5%), fusions of BRAF (8%) and FGFR1 (8%) were found sparingly and almost all in a mutually exclusive manner...
May 14, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29752851/idh-mutated-astrocytomas-with-19q-loss-constitute-a-subgroup-that-confers-better-prognosis
#12
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
#13
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
#14
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/29733378/assessing-the-predictability-of-idh-mutation-and-mgmt-methylation-status-in-glioma-patients-using-relaxation-compensated-multi-pool-cest-mri-at-7-0-tesla
#15
Daniel Paech, Johannes Windschuh, Johanna Oberhollenzer, Constantin Dreher, Felix Sahm, Jan-Eric Meissner, Steffen Goerke, Patrick Schuenke, Moritz Zaiss, Sebastian Regnery, Sebastian Bickelhaupt, Philipp Bäumer, Martin Bendszus, Wolfgang Wick, Andreas Unterberg, Peter Bachert, Mark Edward Ladd, Heinz-Peter Schlemmer, Alexander Radbruch
Background: Early identification of prognostic superior characteristics in glioma patients such as Isocitrate dehydrogenase(IDH)-mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promotor methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH-mutation status, MGMT promotor methylation, and differentiation of lower versus higher grade glioma (LGG vs. HGG) in newly-diagnosed patients employing relaxation-compensated multi-pool Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) at 7...
May 4, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29732524/integrated-analysis-of-dynamic-fet-pet-ct-parameters-histology-and-methylation-profiling-of-44-gliomas
#16
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
#17
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/29723602/non-small-cell-lung-cancers-with-isocitrate-dehydrogenase-1-or-2-idh1-2-mutations
#18
Laura N Toth, Francine B de Abreu, Laura J Tafe
Isocitrate dehydrogenase 1 and 2 (IDH1/2) are important metabolic enzymes that convert isocitrate to α-ketoglutarate. IDH1/2 mutations are associated with the development of multiple malignancies. In this study, we examine the prevalence and features of non-small cell lung cancers (NSCLC) with IDH1/2 mutations. From May 2013 - March 2017, 800 lung cancer samples were successfully sequenced for somatic mutations on the Ion Torrent PGM with the 50 gene AmpliSeq Cancer Hotspot Panel v2 on the Ion Torrent PGM (318 chip)...
April 30, 2018: Human Pathology
https://www.readbyqxmd.com/read/29721688/radiogenomics-correlation-between-mr-imaging-features-and-major-genetic-profiles-in-glioblastoma
#19
Eun Kyoung Hong, Seung Hong Choi, Dong Jae Shin, Sang Won Jo, Roh-Eul Yoo, Koung Mi Kang, Tae Jin Yun, Ji-Hoon Kim, Chul-Ho Sohn, Sung-Hye Park, Jae-Kyung Won, Tae Min Kim, Chul-Kee Park, Il Han Kim, Soon Tae Lee
OBJECTIVES: To assess the association between MR imaging features and major genomic profiles in glioblastoma. METHODS: Qualitative and quantitative imaging features such as volumetrics and histogram analysis from normalised CBV (nCBV) and ADC (nADC) were evaluated based on both T2WI and CET1WI. The imaging parameters of different genetic profile groups were compared and regression analyses were used for identifying imaging-molecular associations. Progression-free survival (PFS) was analysed by a Kaplan-Meier test and Cox proportional hazards model...
May 2, 2018: European Radiology
https://www.readbyqxmd.com/read/29721393/immune-heterogeneity-and-clinicopathologic-characterization-of-igfbp2-in-2447-glioma-samples
#20
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
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