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https://www.readbyqxmd.com/read/28629182/magnetic-resonance-spectroscopy-for-detection-of-2-hydroxyglutarate-as-a-biomarker-for-idh-mutation-in-gliomas
#1
REVIEW
Thomas Leather, Michael D Jenkinson, Kumar Das, Harish Poptani
Mutations in the isocitrate dehydrogenase (IDH)1/2 genes are highly prevalent in gliomas and have been suggested to play an important role in the development and progression of the disease. Tumours harbouring these mutations exhibit a significant alteration in their metabolism resulting in the aberrant accumulation of the oncometabolite 2-hydroxygluarate (2-HG). As well as being suggested to play an important role in tumour progression, 2-HG may serve as a surrogate indicator of IDH status through non-invasive detection using magnetic resonance spectroscopy (MRS)...
June 19, 2017: Metabolites
https://www.readbyqxmd.com/read/28534992/hif-1%C3%AE-inhibits-idh-1-expression-in-osteosarcoma
#2
Deng-Cheng Liu, Xun Zheng, Yong Zho, Wan-Rong Yi, Zong-Huan Li, Xiang Hu, Ai-Xi Yu
Recently, hypoxia inducible factor-1 (HIF-1) was reported to be correlated with isocitrate dehydrogenase 1 (IDH-1) in several types of tumors. However, the expression and significance of HIF-1 and IDH-1 in osteosarcoma is still unknown. In the present study, the expression levels of IDH-1 and HIF-1α in 35 formalin-fixed paraffin-embedded sections from osteosarcoma patients were investigated by immunohistochemistry. The expression levels of IDH-1 and HIF-1α in human osteosarcoma cell lines (MG-63 and 143B) were further detected by western blotting under normal and hypoxic conditions...
May 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28507382/prognostic-significance-of-idh-1-mutation-in-patients-with-glioblastoma-multiforme
#3
Inamullah Khan, Muhammad Waqas, Muhammad Shahzad Shamim
Focus of brain tumour research is shifting towards tumour genesis and genetics, and possible development of individualized treatment plans. Genetic analysis shows recurrent mutation in isocitrate dehydrogenase (IDH1) gene in most Glioblastoma multiforme (GBM) cells. In this review we evaluated the prognostic significance of IDH 1 mutation on the basis of published evidence. Multiple retrospective clinical analyses correlate the presence of IDH1 mutation in GBM with good prognostic outcomes compared to wild-type IDH1...
May 2017: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/28484589/idh1-or-2-mutations-do-not-predict-outcome-and-do-not-cause-loss-of-5-hydroxymethylcytosine-or-altered-histone-modifications-in-central-chondrosarcomas
#4
Arjen H G Cleven, Johnny Suijker, Georgios Agrogiannis, Inge H Briaire-de Bruijn, Norma Frizzell, Attje S Hoekstra, Pauline M Wijers-Koster, Anne-Marie Cleton-Jansen, Judith V M G Bovée
BACKGROUND: Mutations in isocitrate dehydrogenase (IDH)1 or -2 are found in ~50% of conventional central chondrosarcomas and in up to 87% of their assumed benign precursors enchondromas. The mutant enzyme acquires the activity to convert α-ketoglutarate into the oncometabolite d-2-hydroxyglutarate (d-2-HG), which competitively inhibits α-ketoglutarate dependent enzymes such as histone- and DNA demethylases. METHODS: We therefore evaluated the effect of IDH1 or -2 mutations on histone modifications (H3K4me3, H3K9me3 and H3K27me3), chromatin remodeler ATRX expression, DNA modifications (5-hmC and 5-mC), and TET1 subcellular localization in a genotyped cohort (IDH, succinate dehydrogenase (SDH) and fumarate hydratase (FH)) of enchondromas and central chondrosarcomas (n = 101) using immunohistochemistry...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28472509/multicenter-phase-ii-study-of-temozolomide-and-myeloablative-chemotherapy-with-autologous-stem-cell-transplant-for-newly-diagnosed-anaplastic-oligodendroglioma
#5
Alissa A Thomas, Lauren E Abrey, Robert Terziev, Jeffrey Raizer, Nina L Martinez, Peter Forsyth, Nina Paleologos, Matthew Matasar, Craig S Sauter, Craig Moskowitz, Stephen D Nimer, Lisa M DeAngelis, Thomas Kaley, Sean Grimm, David N Louis, J Gregory Cairncross, Katherine S Panageas, Samuel Briggs, Geraldine Faivre, Nimish A Mohile, Jayesh Mehta, Philip Jonsson, Debyani Chakravarty, Jianjiong Gao, Nikolaus Schultz, Cameron W Brennan, Jason T Huse, Antonio Omuro
Background: Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytomas (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT), as a potential strategy to defer radiotherapy. Methods: Patients with AO/AOA received 6 cycles of TMZ (200mg/m2 X5/28-day). Responding patients were eligible for HDC (thiotepa 250mg/m2/day X3 days then busulfan 3...
May 2, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28411277/long-term-survival-in-glioblastoma-with-cytomegalovirus-pp65-targeted-vaccination
#6
Kristen A Batich, Elizabeth A Reap, Gary E Archer, Luis Sanchez-Perez, Smita K Nair, Robert J Schmittling, Pam Norberg, Weihua Xie, James E Herndon, Patrick Healy, Roger E McLendon, Allan H Friedman, Henry S Friedman, Darell Bigner, Gordana Vlahovic, Duane A Mitchell, John H Sampson
Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival (PFS) and overall survival (OS)...
April 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28389139/emerging-molecular-therapeutic-targets-for-cholangiocarcinoma
#7
REVIEW
Sumera Rizvi, Gregory J Gores
Cholangiocarcinomas (CCAs) are diverse epithelial tumors arising from the liver or large bile ducts with features of cholangiocyte differentiation. CCAs are classified anatomically into intrahepatic (iCCA), perihilar (pCCA), and distal CCA (dCCA). Each subtype has distinct risk factors, molecular pathogenesis, therapeutic options, and prognosis. CCA is an aggressive malignancy with a poor overall prognosis and median survival of less than 2years in patients with advanced disease. Potentially curative surgical treatment options are limited to the subset of patients with early-stage disease...
April 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28324304/management-of-elderly-patients-with-glioblastoma
#8
REVIEW
Patrick Roth, Dorothee Gramatzki, Michael Weller
PURPOSE OF REVIEW: Glioblastoma represents one of the major challenges in neurooncology and approximately half of the patients are 60 years or older. We summarize the particular situation of elderly glioblastoma patients with a focus on therapeutic considerations. RECENT FINDINGS: Favorable molecular markers such as mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes are virtually absent in glioblastomas in elderly patients. Treatment options are similar to the situation in young patients and comprise surgical resection, radiation therapy, and alkylating chemotherapy...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28315400/multicolor-flow-cytometry-and-multigene-next-generation-sequencing-are-complementary-and-highly-predictive-for-relapse-in-acute-myeloid-leukemia-after-allogeneic-transplantation
#9
Bartlomiej M Getta, Sean M Devlin, Ross L Levine, Maria E Arcila, Abhinita S Mohanty, Ahmet Zehir, Martin S Tallman, Sergio A Giralt, Mikhail Roshal
Minimal residual disease (MRD) in acute myeloid leukemia (AML) is typically measured using multiparameter flow cytometry (MFC). Detection of leukemia mutations using multigene next-generation sequencing (NGS) can potentially be used to measure residual disease. We used a targeted 28-gene NGS panel to detect mutations and different-from-normal 10-color MFC to measure MRD in AML patients before allogeneic hematopoietic stem cell transplantation (HCT). Residual disease was defined when any abnormal blast population was detected using MFC and when any leukemia allele was detected with a variant allele frequency (VAF)  ≥ 5% using NGS...
March 15, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28193778/ag-221-a-first-in-class-therapy-targeting-acute-myeloid-leukemia-harboring-oncogenic-idh2-mutations
#10
Katharine Yen, Jeremy Travins, Fang Wang, Muriel D David, Erin Artin, Kimberly Straley, Anil Padyana, Stefan Gross, Byron DeLaBarre, Erica Tobin, Yue Chen, Raj Nagaraja, Sung Choe, Lei Jin, Zenon Konteatis, Giovanni Cianchetta, Jeffrey O Saunders, Francesco G Salituro, Cyril Quivoron, Paule Opolon, Olivia Bawa, Véronique Saada, Angelo Paci, Sophie Broutin, Olivier A Bernard, Stéphane de Botton, Benoît S Marteyn, Monika Pilichowska, YingXia Xu, Cheng Fang, Fan Jiang, Wentao Wei, Shengfang Jin, Lee Silverman, Wei Liu, Hua Yang, Lenny Dang, Marion Dorsch, Virginie Penard-Lacronique, Scott A Biller, Shin-San Michael Su
Somatic gain-of-function mutations in isocitrate dehydrogenases (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits α-ketoglutarate-dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the TET family, causing epigenetic dysregulation and a block in cellular differentiation. In vitro studies have provided proof of concept for mutant IDH inhibition as a therapeutic approach...
May 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28124097/pan-mutant-idh1-inhibitor-bay-1436032-for-effective-treatment-of-idh1-mutant-astrocytoma-in-vivo
#11
Stefan Pusch, Sonja Krausert, Viktoria Fischer, Jörg Balss, Martina Ott, Daniel Schrimpf, David Capper, Felix Sahm, Jessica Eisel, Ann-Christin Beck, Manfred Jugold, Viktoria Eichwald, Stefan Kaulfuss, Olaf Panknin, Hartmut Rehwinkel, Katja Zimmermann, Roman C Hillig, Judith Guenther, Luisella Toschi, Roland Neuhaus, Andrea Haegebart, Holger Hess-Stumpp, Markus Bauser, Wolfgang Wick, Andreas Unterberg, Christel Herold-Mende, Michael Platten, Andreas von Deimling
Mutations in codon 132 of isocitrate dehydrogenase (IDH) 1 are frequent in diffuse glioma, acute myeloid leukemia, chondrosarcoma and intrahepatic cholangiocarcinoma. These mutations result in a neomorphic enzyme specificity which leads to a dramatic increase of intracellular D-2-hydroxyglutarate (2-HG) in tumor cells. Therefore, mutant IDH1 protein is a highly attractive target for inhibitory drugs. Here, we describe the development and properties of BAY 1436032, a pan-inhibitor of IDH1 protein with different codon 132 mutations...
April 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28091987/expression-and-prognostic-value-of-micrornas-in-lower-grade-glioma-depends-on-idh1-2-status
#12
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/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
#13
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/27956631/the-idh2-r172k-mutation-associated-with-angioimmunoblastic-t-cell-lymphoma-produces-2hg-in-t-cells-and-impacts-lymphoid-development
#14
François Lemonnier, Rob A Cairns, Satoshi Inoue, Wanda Y Li, Aurélie Dupuy, Sophie Broutin, Nadine Martin, Virginie Fataccioli, Romain Pelletier, Andrew Wakeham, Bryan E Snow, Laurence de Leval, Anais Pujals, Corinne Haioun, Angelo Paci, Erica R Tobin, Rohini Narayanaswamy, Katherine Yen, Shengfang Jin, Philippe Gaulard, Tak W Mak
Oncogenic isocitrate dehydrogenase (IDH)1 and IDH2 mutations at three hotspot arginine residues cause an enzymatic gain of function that leads to the production and accumulation of the metabolite 2-hydroxyglutarate (2HG), which contributes to the development of a number of malignancies. In the hematopoietic system, mutations in IDH1 at arginine (R) 132 and in IDH2 at R140 and R172 are commonly observed in acute myeloid leukemia, and elevated 2HG is observed in cells and serum. However, in angioimmunoblastic T-cell lymphoma (AITL), mutations are almost exclusively restricted to IDH2 R172, and levels of 2HG have not been comprehensively measured...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27852048/igfbp2-expression-predicts-idh-mutant-glioma-patient-survival
#15
Lin Eric Huang, Adam L Cohen, Howard Colman, Randy L Jensen, Daniel W Fults, William T Couldwell
Mutations of the isocitrate dehydrogenase (IDH) 1 and 2 genes occur in ~80% of lower-grade (WHO grade II and grade III) gliomas. Mutant IDH produces (R)-2-hydroxyglutarate, which induces DNA hypermethylation and presumably drives tumorigenesis. Interestingly, IDH mutations are associated with improved survival in glioma patients, but the underlying mechanism for the difference in survival remains unclear. Through comparative analyses of 286 cases of IDH-wildtype and IDH-mutant lower-grade glioma from a TCGA data set, we report that IDH-mutant gliomas have increased expression of tumor-suppressor genes (NF1, PTEN, and PIK3R1) and decreased expression of oncogenes(AKT2, ARAF, ERBB2, FGFR3, and PDGFRB) and glioma progression genes (FOXM1, IGFBP2, and WWTR1) compared with IDH-wildtype gliomas...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/27849434/less-invasive-phenotype-found-in-isocitrate-dehydrogenase-mutated-glioblastomas-than-in-isocitrate-dehydrogenase-wild-type-glioblastomas-a-diffusion-tensor-imaging-study
#16
Stephen J Price, Kieren Allinson, Hongxiang Liu, Natalie R Boonzaier, Jiun-Lin Yan, Victoria C Lupson, Timothy J Larkin
Purpose To explore the diffusion-tensor (DT) imaging-defined invasive phenotypes of both isocitrate dehydrogenase (IDH-1)-mutated and IDH-1 wild-type glioblastomas. Materials and Methods Seventy patients with glioblastoma were prospectively recruited and imaged preoperatively. All patients provided signed consent, and the local research ethics committee approved the study. Patients underwent surgical resection, and tumor samples underwent immunohistochemistry for IDH-1 R132H mutations. DT imaging data were coregistered to the anatomic magnetic resonance study and reconstructed to provide the anisotropic and isotropic components of the DT...
April 2017: Radiology
https://www.readbyqxmd.com/read/27800031/long-term-survival-in-a-patient-with-glioblastoma-on-antipsychotic-therapy-for-schizophrenia-a-case-report-and-literature-review
#17
REVIEW
Shahdabul Faraz, Susan Pannullo, Marc Rosenblum, Andrew Smith, A Gabriella Wernicke
Glioblastoma is not only the most common primary brain tumor, but also the most aggressive. Currently, the most effective treatment of surgery, chemotherapy and radiation therapy allows for a modest median survival of 15 months. Here, we report a case of a 57-year-old male with histologically confirmed glioblastoma with unfavorable prognostic characteristics (poor performance status and persistent neurological symptoms after surgery), whose expected 5-year survival is 0%. Further genetic analysis offered a mixed prognostic picture with positive methylation of 0-6-methylguinine-DNA (deoxyribonucleic acid) methyltransferase (MGMT; favorable prognosis) and wild-type isocitrate dehydrogenase 1 (IDH-1; unfavorable prognosis)...
November 2016: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/27766560/dynamics-of-flair-volume-changes-in-glioblastoma-and-prediction-of-survival
#18
Rachel Grossman, Nir Shimony, Dror Shir, Tal Gonen, Razi Sitt, Tali Jonas Kimchi, Carmit Ben Harosh, Zvi Ram
BACKGROUND: The extent of tumor resection (EOTR) calculated by enhanced T1 changes in glioblastomas has been previously reported to predict survival. However, fluid-attenuated inversion recovery (FLAIR) volume may better represent tumor burden. In this study, we report the first assessment of the dynamics of FLAIR volume changes over time as a predictive variable for post-resection overall survival (OS). METHODS: Contemporary data from 103 consecutive patients with complete imaging and clinical data who underwent resection of newly diagnosed glioblastoma followed by the Stupp protocol between 2010 and 2013 were analyzed...
October 20, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27696222/gene-expression-profiling-stratifies-idh1-mutant-glioma-with-distinct-prognoses
#19
Wen Cheng, Xiufang Ren, Chuanbao Zhang, Jinquan Cai, Sheng Han, Anhua Wu
Isocitrate dehydrogenase (IDH)1 mutation is one of the most important genetic aberrations in glioma. Even several genetic events have refined its prognostic value, the genome-wide expression alteration has not been systematically profiled. In this work, RNA-seq expression data from 310 patients in the Chinese Glioma Genome Atlas database were included as training set, while another 297 patients with microarray data were used as internal validation set. An independent cohort of GSE16011 (n = 205) constituted an external validation set...
September 30, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27638721/concordance-analysis-and-diagnostic-test-accuracy-review-of-idh1-immunohistochemistry-in-glioblastoma
#20
Jung-Soo Pyo, Nae Yu Kim, Roy Hyun Jai Kim, Guhyun Kang
The study investigated isocitrate dehydrogenase (IDH) 1 immunohistochemistry (IHC) positive rate and concordance rate between IDH1 IHC and molecular test in glioblastoma. The current study included 1360 glioblastoma cases from sixteen eligible studies. Meta-analysis, including subgroup analysis by antibody clones and cut-off values, for IDH1 IHC positive rate was conducted. In addition, we performed a concordance analysis and diagnostic test accuracy review between IDH1 IHC and molecular tests. The estimated rates of IDH1 IHC were 0...
October 2016: Brain Tumor Pathology
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