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https://www.readbyqxmd.com/read/28091987/expression-and-prognostic-value-of-micrornas-in-lower-grade-glioma-depends-on-idh1-2-status
#1
Wen Cheng, Xiufang Ren, Chuanbao Zhang, Sheng Han, Anhua Wu
Histological and genomic characteristics are widely used in glioma management and research. This study investigated their relationship to the expression and prognostic value of microRNAs (miRNAs) in lower-grade glioma (LGG). A total of 447 LGG samples with available clinical and genomic information from The Cancer Genome Atlas database were reviewed. Samples with isocitrate dehydrogenase (IDH) 1/2 mutations (n = 366) were randomly divided into training and validation sets to establish and confirm a four-miRNA-based risk classifier...
January 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28089418/distant-spread-of-a-supratentorial-glioblastoma-to-the-spinal-cord
#2
Krishnan Ravindran, Frank Gaillard, Arian Lasocki
Extracranial spread from a glioblastoma is rare. We present a case of a 48year-old man with a previously radiologically-stable left temporal lobe glioblastoma presenting with symptoms referrable to the spinal cord. MRI revealed a spinal cord lesion, with the differential including transverse myelitis and tumour. Open surgical biopsy revealed high-grade astrocytoma. Genetic analysis of both the supratentorial and spinal tumours revealed R132H IDH1 mutations, providing evidence that the spinal cord lesion had spread from the supratentorial tumour...
January 12, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28076841/clonal-evolution-in-therapy-related-neoplasms
#3
Emiliano Fabiani, Giulia Falconi, Luana Fianchi, Marianna Criscuolo, Tiziana Ottone, Laura Cicconi, Stefan Hohaus, Simona Sica, Massimiliano Postorino, Antonino Neri, Marta Lionetti, Giuseppe Leone, Francesco Lo-Coco, Maria Teresa Voso
Therapy-related myeloid neoplasms (t-MN) may occur as a late effect of cytotoxic therapy for a primary malignancy or autoimmune diseases in susceptible individuals. We studied the development of somatic mutations in t-MN, using a collection of follow-up samples from 14 patients with a primary hematologic malignancy, who developed a secondary leukemia (13 t-MN and 1 t-acute lymphoblastic leukemia), at a median latency of 73 months (range 18-108) from primary cancer diagnosis.Using Sanger and next generation sequencing (NGS) approaches we identified 8 mutations (IDH1 R132H, ASXL1 Y591*, ASXL1 S689*, ASXL1 R693*, SRSF2 P95H, SF3B1 K700E, SETBP1 G870R and TP53 Y220C) in seven of thirteen t-MN patients (54%), whereas the t-ALL patient had a t(4,11) translocation, resulting in the KMT2A/AFF1 fusion gene...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075478/high-expression-of-rab43-predicts-poor-prognosis-and-is-associated-with-epithelial-mesenchymal-transition-in-gliomas
#4
Ming-Zhi Han, Bin Huang, An-Jing Chen, Xin Zhang, Ran Xu, Jian Wang, Xin-Gang Li
The Ras-related GTP-binding protein (RAB) family plays an important role in regulating signal transduction and cellular processes including vesicle transport, cytoskeleton formation and membrane trafficking. More recently, several RAB members have been reported to promote tumorigenesis in many types of cancers. However, the clinical significance and potential function of RAB43 in gliomas remain unclear. Herein, we found that RAB43 was upregulated and positively correlated with the grade of progression in glioma patients by in silico analysis and immunohistochemistry (IHC)...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074068/a-cpg-island-methylator-phenotype-in-acute-myeloid-leukemia-independent-of-idh-mutations-and-associated-with-a-favorable-outcome
#5
A D Kelly, H Kroeger, J Yamazaki, R Taby, F Neumann, S Yu, J T Lee, B Patel, Y Li, R He, S Liang, Y Lu, M Cesaroni, S A Pierce, S M Kornblau, C E Bueso-Ramos, F Ravandi, H M Kantarjian, J Jelinek, J-Pj Issa
Genetic changes are infrequent in acute myeloid leukemia (AML) compared to other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation (DREAM) data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CIMP (A-CIMP(+))...
January 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28073027/epileptic-features-and-survival-in-glioblastomas-presenting-with-seizures
#6
Manuel Toledo, Silvana Sarria-Estrada, Manuel Quintana, Xavier Maldonado, Francisco Martinez-Ricarte, Jordi Rodon, Cristina Auger, Miren Aizpurua, Javier Salas-Puig, Estevo Santamarina, Elena Martinez-Saez
INTRODUCTION: The prognostic value of seizures in patients with glioblastoma is currently under discussion. The objective of this research was to study the risk factors associated with seizures occurring at the diagnosis of glioblastoma and the role of seizures as a predictive factor for survival. MATERIAL AND METHODS: We prospectively analyzed the clinical data over the course of the disease, baseline MR imaging, and histological characteristics (p53 overexpression, the Ki67 proliferation index, and presence of the IDH1 R132H mutation), in glioblastomas treated in a single hospital from November 2012 to July 2014...
December 26, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/28059652/-pro-renin-receptor-is-crucial-for-glioma-development-via-the-wnt-%C3%AE-catenin-signaling-pathway
#7
Masaaki Kouchi, Yuki Shibayama, Daisuke Ogawa, Keisuke Miyake, Akira Nishiyama, Takashi Tamiya
OBJECTIVE The (pro)renin receptor (PRR) plays an essential role in the early development of the central nervous system by activating the Wnt/β-catenin signaling pathway. The authors investigated the potential role of the PRR in the pathogenesis of glioma. METHODS The authors performed immunohistochemical analysis to detect both the PRR and isocitrate dehydrogenase 1 with mutations involving arginine 132 (IDH1(R132H)) in paraffin sections of 31 gliomas. Expression of the PRR and Wnt pathway components in cultured human glioma cell lines (U251MG, U87MG, and T98G) was measured using Western blotting...
January 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28056258/-advance-of-molecular-subtyping-and-precise-treatment-for-gliomas
#8
W Hua, Y Mao
With the advance of genomics research, there have been a new breakthrough in the molecular classification of gliomas. Glioblastoma (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesochymal according to the mRNA expression. Lower grade gliomas (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p/19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and TERTp (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas...
January 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/28052098/idh1-r132h-mutation-enhances-cell-migration-by-activating-akt-mtor-signaling-pathway-but-sensitizes-cells-to-5-fu-treatment-as-nadph-and-gsh-are-reduced
#9
Huixia Zhu, Ye Zhang, Jianfeng Chen, Jiangdong Qiu, Keting Huang, Mindan Wu, Chunlin Xia
AIM OF STUDY: Mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) gene were recently discovered in vast majority of World Health Organization (WHO) grade II/III gliomas. This study is to understand the effects of IDH1 R132H mutation in gliomagenesis and to develop new strategies to treat glioma with IDH1 R132H mutation. MATERIALS AND METHODS: Over expression of IDH1 R132H in U87MG cells was done by transfecting cells with IDH1 R132H plasmid. MTT assay, scratch repair assay and western blot were performed to study effects of IDH1 R132H mutation on cell proliferation, migration, regulating AKT-mTOR signaling pathway and cell death respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28050146/personalized-oncogenomics-in-the-management-of-gastrointestinal-carcinomas-early-experiences-from-a-pilot-study
#10
B S Sheffield, B Tessier-Cloutier, H Li-Chang, Y Shen, E Pleasance, K Kasaian, Y Li, S J M Jones, H J Lim, D J Renouf, D G Huntsman, S Yip, J Laskin, M Marra, D F Schaeffer
BACKGROUND: Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. METHODS: We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma...
December 2016: Current Oncology
https://www.readbyqxmd.com/read/28042970/targeted-next-generation-sequencing-in-molecular-subtyping-of-lower-grade-diffuse-gliomas-application-of-the-world-health-organization-s-2016-revised-criteria-for-cns-tumors
#11
Jamal H Carter, Samantha N McNulty, Patrick J Cimino, Catherine E Cottrell, Jonathan W Heusel, Katinka A Vigh-Conrad, Eric J Duncavage
The 2007 World Health Organization Classification of Tumours of the Central Nervous System classifies lower-grade gliomas [LGGs (grades II to III diffuse gliomas)] morphologically as astrocytomas or oligodendrogliomas, and tumors with unclear ambiguous morphology as oligoastrocytomas. The World Health Organization's newly released (2016) classification incorporates molecular data. A single, targeted next-generation sequencing (NGS) panel was used for detecting single-nucleotide variation and copy number variation in 50 LGG cases originally classified using the 2007 criteria, including 36 oligoastrocytomas, 11 oligodendrogliomas, 2 astrocytomas, and 1 LGG not otherwise specified...
December 30, 2016: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28039446/5-hydroxymethylcytosine-correlates-with-epigenetic-regulatory-mutations-but-may-not-have-prognostic-value-in-predicting-survival-in-normal-karyotype-acute-myeloid-leukemia
#12
Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Seung Hyun Choi, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Szardenings Michael, Mark D Minden, Dennis Dong Hwan Kim
Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC). Both TET2 and IDH1/2 mutations can impair the production of 5hmC, thus decreasing 5hmC levels. TET2 or IDH1/2 mutations are commonly observed in acute myeloid leukemia (AML). However, the implications of 5hmC on survival in normal karyotype AML patients have not been fully evaluated. The 5hmC levels were analyzed in 375 patients using ELISA. The levels of 5hmC in DNA samples were converted to a log scale for the analysis and correlations with TET2 and/or IDH1/2 mutations were evaluated...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039367/efficacy-and-safety-results-of-abt-414-in-combination-with-radiation-and-temozolomide-in-newly-diagnosed-glioblastoma
#13
David A Reardon, Andrew B Lassman, Martin van den Bent, Priya Kumthekar, Ryan Merrell, Andrew M Scott, Lisa Fichtel, Erik P Sulman, Erica Gomez, JuDee Fischer, Ho-Jin Lee, Wijith Munasinghe, Hao Xiong, Helen Mandich, Lisa Roberts-Rapp, Peter Ansell, Kyle D Holen, Hui K Gan
BACKGROUND: The purpose of this study was to determine the maximum tolerated dose (MTD), recommended phase II dose (RPTD), safety, and pharmacokinetics of ABT-414 plus radiation and temozolomide in newly diagnosed glioblastoma. ABT-414 is a first-in-class, tumor-specific antibody-drug conjugate that preferentially targets tumors expressing overactive epidermal growth factor receptor (EGFR). METHODS: In this multicenter phase I study, patients received 0.5-3.2 mg/kg ABT-414 every 2 weeks by intravenous infusion...
December 29, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/28036297/c-jun-n-terminal-phosphorylation-regulates-dnmt1-expression-and-genome-wide-methylation-in-gliomas
#14
Dieter H Heiland, Roberto Ferrarese, Rainer Claus, Fangping Dai, Anie P Masilamani, Eva Kling, Astrid Weyerbrock, Teresia Kling, Sven Nelander, Maria S Carro
High-grade gliomas (HGG) are the most common brain tumors, with an average survival time of 14 months. A glioma-CpG island methylator phenotype (G-CIMP), associated with better clinical outcome, has been described in low and high-grade gliomas. Mutation of IDH1 is known to drive the G-CIMP status. In some cases, however, the hypermethylation phenotype is independent of IDH1 mutation, suggesting the involvement of other mechanisms. Here, we demonstrate that DNMT1 expression is higher in low-grade gliomas compared to glioblastomas and correlates with phosphorylated c-Jun...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032389/bithalamic-gliomas-may-be-molecularly-distinct-from-their-unilateral-high-grade-counterparts
#15
Alberto Broniscer, Scott N Hwang, Omar Chamdine, Tong Lin, Stanley Pounds, Arzu Onar-Thomas, Lei Chi, Sheila Shurtleff, Sariah Allen, Amar Gajjar, Paul Northcott, Brent A Orr
Bithalamic gliomas are rare cancers diagnosed based on poorly defined radiologic criteria. Infiltrative astrocytomas account for most cases. While some previous studies reported dismal outcomes for patients with bithalamic gliomas irrespective of therapy and histologic grade, others described better prognoses even without anticancer therapy. Little is known about their molecular characteristics. We reviewed clinical, radiologic, and histologic features of patients with bithalamic gliomas treated at our institution over 15 years...
December 28, 2016: Brain Pathology
https://www.readbyqxmd.com/read/28031426/molecular-profiling-to-determine-clonality-of-serial-magnetic-resonance-imaging-ultrasound-fusion-biopsies-from-men-on-active-surveillance-for-low-risk-prostate-cancer
#16
Ganesh S Palapattu, Simpa S Salami, Andi K Cani, Daniel H Hovelson, Lorena Lazo de la Vega, Kelly R Vandenberg, Jarred V Bratley, Chia-Jen Liu, Lakshmi P Kunju, Jeffery S Montgomery, Todd M Morgan, Shyam Natarajan, Jiaoti Huang, Scott A Tomlins, Leonard S Marks
PURPOSE: To determine whether MRI/ultrasound (MRI/US) fusion biopsy facilitates longitudinal resampling of the same clonal focus of prostate cancer and to determine whether high-grade cancers can evolve from low-grade clones. EXPERIMENTAL DESIGN: All men on active surveillance who underwent tracking MRI/US fusion biopsy of Gleason 6 prostate cancer, on at least two distinct occasions, between 2012 and 2014 were enrolled. MRI/US fusion was used to track and resample specific cancer foci...
October 7, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28030635/expression-and-prognostic-value-of-oct-4-in-astrocytic-brain-tumors
#17
Jeanette Krogh Petersen, Per Jensen, Mia Dahl Sørensen, Bjarne Winther Kristensen
BACKGROUND: Glioblastomas are the most frequent type of malignant primary brain tumor with a median overall survival less than 15 months. Therapy resistance of glioblastomas has been attributed to the presence of tumor initiating stem-like cells (TSCs). TSC-related markers have therefore been suggested to have promising potentials as prognostic markers in gliomas. METHODOLOGY/PRINCIPAL FINDINGS: The aim of the present study was to investigate the expression and prognostic impact of the TSC-related marker Oct-4 in astrocytic brain tumors of increasing grade...
2016: PloS One
https://www.readbyqxmd.com/read/28025701/flux-control-based-design-of-furfural-resistance-strains-of-saccharomyces-cerevisiae-for-lignocellulosic-biorefinery
#18
Pornkamol Unrean
We have previously developed a dynamic flux balance analysis of Saccharomyces cerevisiae for elucidation of genome-wide flux response to furfural perturbation (Unrean and Franzen, Biotechnol J 10(8):1248-1258, 2015). Herein, the dynamic flux distributions were analyzed by flux control analysis to identify target overexpressed genes for improved yeast robustness against furfural. The flux control coefficient (FCC) identified overexpressing isocitrate dehydrogenase (IDH1), a rate-controlling flux for ethanol fermentation, and dicarboxylate carrier (DIC1), a limiting flux for cell growth, as keys of furfural-resistance phenotype...
December 26, 2016: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28011762/idh1-deficiency-attenuates-gluconeogenesis-in-mouse-liver-by-impairing-amino-acid-utilization
#19
Jing Ye, Yu Gu, Feng Zhang, Yuanlin Zhao, Yuan Yuan, Zhenyue Hao, Yi Sheng, Wanda Y Li, Andrew Wakeham, Rob A Cairns, Tak W Mak
Although the enzymatic activity of isocitrate dehydrogenase 1 (IDH1) was defined decades ago, its functions in vivo are not yet fully understood. Cytosolic IDH1 converts isocitrate to α-ketoglutarate (α-KG), a key metabolite regulating nitrogen homeostasis in catabolic pathways. It was thought that IDH1 might enhance lipid biosynthesis in liver or adipose tissue by generating NADPH, but we show here that lipid contents are relatively unchanged in both IDH1-null mouse liver and IDH1-deficient HepG2 cells generated using the CRISPR-Cas9 system...
December 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28004160/noninvasive-idh1-mutation-estimation-based-on-a-quantitative-radiomics-approach-for-grade-ii-glioma
#20
Jinhua Yu, Zhifeng Shi, Yuxi Lian, Zeju Li, Tongtong Liu, Yuan Gao, Yuanyuan Wang, Liang Chen, Ying Mao
OBJECTIVE: The status of isocitrate dehydrogenase 1 (IDH1) is highly correlated with the development, treatment and prognosis of glioma. We explored a noninvasive method to reveal IDH1 status by using a quantitative radiomics approach for grade II glioma. METHODS: A primary cohort consisting of 110 patients pathologically diagnosed with grade II glioma was retrospectively studied. The radiomics method developed in this paper includes image segmentation, high-throughput feature extraction, radiomics sequencing, feature selection and classification...
December 21, 2016: European Radiology
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