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https://www.readbyqxmd.com/read/28531337/correlation-of-immune-phenotype-with-idh-mutation-in-diffuse-glioma
#1
Anna Sophie Berghoff, Barbara Kiesel, Georg Widhalm, Dorothee Wilhelm, Orsolya Rajky, Sebastian Kurscheid, Philip Kresl, Adelheid Wöhrer, Christine Marosi, Monika E Hegi, Matthias Preusser
Background: Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Methods: Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database...
May 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28513762/water-fluoridation-in-brazilian-cities-at-the-first-decade-of-the-21st-century
#2
Paulo Frazão, Paulo Capel Narvai
OBJECTIVE: To assess the coverage of the fluoridation of the public water supply in Brazilian municipalities at the first decade of the 21st century, according to population size and municipal human development index (MHDI). METHODS: We have used data produced by national information agencies and the United Nations Development Programme. Population size was separated into < 10,000, 10,000-50,000, and > 50,000 inhabitants. The MHDI was classified into < 0...
May 15, 2017: Revista de Saúde Pública
https://www.readbyqxmd.com/read/28508328/mir-424-functions-as-a-tumor-suppressor-in-glioma-cells-and-is-down-regulated-by-dna-methylation
#3
Chen Jin, Minhong Li, Yian Ouyang, Zhigang Tan, Yugang Jiang
Glioma is one of the most lethal malignancies, and increasing reports revealed that microRNAs (miRNAs), a class of small non-coding RNAs, play a critical role in the development and pathology of human gliomas. MiR-424 has been found to be dysregulated in many different types of human cancers. However, the clinical significance and function of miR-424 in glioma remains unclear. Here, based on RTq-PCR analysis in 148 clinical specimens, we found miR-424 expression was significantly decreased in glioma tumor tissues than in adjacent non-neoplastic brain tissues, and decreased miR-424 expression was associated with glioma KPS (P = 0...
May 15, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28507382/prognostic-significance-of-idh-1-mutation-in-patients-with-glioblastoma-multiforme
#4
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/28498812/structure-based-discovery-of-clomifene-as-a-potent-inhibitor-of-cancer-associated-mutant-idh1
#5
Mengzhu Zheng, Weiguang Sun, Suyu Gao, Shanshan Luan, Dan Li, Renqi Chen, Qian Zhang, Lixia Chen, Jiangeng Huang, Hua Li
Isocitrate dehydrogenase (IDH) plays an indispensable role in the tricarboxylic acid cycle, and IDH mutations are present in nearly 75% of glioma and 20% of acute myeloid leukemia. One IDH1R132H inhibitor (clomifene citrate) was found by virtual screening method, which can selectively suppress mutant enzyme activities in vitro and in vivo with a dose-dependent manner. The molecular docking indicated that clomifene occupied the allosteric site of the mutant IDH1. Enzymatic kinetics also demonstrated that clomifene inhibited mutant enzyme in a non-competitive manner...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28497806/management-of-diffuse-low-grade-gliomas-in-adults-use-of-molecular-diagnostics
#6
REVIEW
Jan Buckner, Caterina Giannini, Jeanette Eckel-Passow, Daniel Lachance, Ian Parney, Nadia Laack, Robert Jenkins
Diffuse WHO grade II gliomas are histologically and genetically heterogeneous. The 2016 WHO classification redefines grade II gliomas with respect to morphological and molecular tumour alterations: grade II oligodendrogliomas are defined by the presence of whole-arm codeletion in chromosomal arms 1p/19q, whereas isocitrate dehydrogenase (IDH) mutations define subclasses of astrocytoma. Although histological grade remains useful, the prognoses of patients with glioma are more tightly associated with molecular alterations than with grade, and chromosomal and gene array technologies are becoming increasingly beneficial in understanding tumour genetic heterogeneity...
May 12, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28488024/glioma-grading-and-determination-of-idh-mutation-status-and-atrx-loss-by-dce-and-asl-perfusion
#7
Cornelia Brendle, Johann-Martin Hempel, Jens Schittenhelm, Marco Skardelly, Ghazaleh Tabatabai, Benjamin Bender, Ulrike Ernemann, Uwe Klose
PURPOSE: To evaluate arterial spin labeling (ASL) perfusion and dynamic contrast-enhanced (DCE) perfusion in glioma grading according to the previous WHO classification of 2007, as well as concerning isocitrate dehydrogenase (IDH) mutation status and ATRX expression as required by the new WHO 2016 brain tumor classification. METHODS: The mean values of Ktrans, Kep, Ve, and Vp by DCE perfusion, and cerebral blood flow (CBF) by ASL perfusion were assessed retrospectively in 40 patients with initial glioma diagnosis...
May 9, 2017: Clinical Neuroradiology
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
#8
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/28474187/idh-mutant-and-1p-19q-co-deleted-oligodendrogliomas-tumor-grade-stratification-using-diffusion-susceptibility-and-perfusion-weighted-mri
#9
Yu Lin, Zhen Xing, Dejun She, Xiefeng Yang, Yingyan Zheng, Zebin Xiao, Xingfu Wang, Dairong Cao
PURPOSE: Currently, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion are proven diagnostic biomarkers for both grade II and III oligodendrogliomas (ODs). Non-invasive diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) are widely used to provide physiological information (cellularity, hemorrhage, calcifications, and angiogenesis) of neoplastic histology and tumor grade. However, it is unclear whether DWI, SWI, and DSC-PWI are able to stratify grades of IDH-mutant and 1p/19q co-deleted ODs...
May 4, 2017: Neuroradiology
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
#10
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/28470959/intra-dialytic-hypotension-identifying-patients-most-at-risk
#11
Nicholas Sangala, Venkat Gangaram, Katey Atkins, Graham Elliot, Robert Lewis
BACKGROUND: Intra-dialytic hypotension (IDH) remains a frequent but serious complication of haemodialysis. METHODS: We performed a retrospective observational analysis of our prevalent dialysis population extracting data from an online database. RESULTS: Four hundred and thirty-two patients underwent 21 consecutive outpatient dialysis sessions during the study period: Of the 9,072 dialysis sessions studied, 438 were complicated by episodes of IDH (4...
June 2017: Journal of Renal Care
https://www.readbyqxmd.com/read/28470431/radiogenomics-of-lower-grade-glioma-algorithmically-assessed-tumor-shape-is-associated-with-tumor-genomic-subtypes-and-patient-outcomes-in-a-multi-institutional-study-with-the-cancer-genome-atlas-data
#12
Maciej A Mazurowski, Kal Clark, Nicholas M Czarnek, Parisa Shamsesfandabadi, Katherine B Peters, Ashirbani Saha
Recent studies identified distinct genomic subtypes of lower-grade gliomas that could potentially be used to guide patient treatment. This study aims to determine whether there is an association between genomics of lower-grade glioma tumors and patient outcomes using algorithmic measurements of tumor shape in magnetic resonance imaging (MRI). We analyzed preoperative imaging and genomic subtype data from 110 patients with lower-grade gliomas (WHO grade II and III) from The Cancer Genome Atlas. Computer algorithms were applied to analyze the imaging data and provided five quantitative measurements of tumor shape in two and three dimensions...
May 3, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28469119/blood-pressure-variation-and-its-correlates-among-patients-undergoing-hemodialysis-for-renal-failure-in-benin-city-nigeria
#13
Enajite I Okaka, Chimezie G Okwuonu
BACKGROUND: Blood pressure (BP) variation is commonly encountered during hemodialysis (HD) procedure. Both intradialysis hypotension and hypertension have implications for outcome of treatment and overall morbidity and mortality of the patients. METHODOLOGY: A retrospective study was carried out in the dialysis unit of a tertiary health institution in Benin City among patients who had HD for acute kidney injury (AKI) or chronic kidney disease (CKD) over a 3-year period...
April 2017: Annals of African Medicine
https://www.readbyqxmd.com/read/28468611/clinical-association-analysis-of-ependymomas-and-pilocytic-astrocytomas-reveals-elevated-fgfr3-and-fgfr1-expression-in-aggressive-ependymomas
#14
Birgitta Lehtinen, Annina Raita, Juha Kesseli, Matti Annala, Kristiina Nordfors, Olli Yli-Harja, Wei Zhang, Tapio Visakorpi, Matti Nykter, Hannu Haapasalo, Kirsi J Granberg
BACKGROUND: Fibroblast growth factor receptors (FGFRs) are well-known proto-oncogenes in several human malignancies and are currently therapeutically targeted in clinical trials. Among glioma subtypes, activating FGFR1 alterations have been observed in a subpopulation of pilocytic astrocytomas while FGFR3 fusions occur in IDH wild-type diffuse gliomas, resulting in high FGFR3 protein expression. The purpose of this study was to associate FGFR1 and FGFR3 protein levels with clinical features and genetic alterations in ependymoma and pilocytic astrocytoma...
May 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28467778/somatostatin-receptor-2a-in-gliomas-association-with-oligodendrogliomas-and-favourable-outcome
#15
Aida Kiviniemi, Maria Gardberg, Katri Kivinen, Jussi P Posti, Ville Vuorinen, Jussi Sipilä, Melissa Rahi, Matti Sankinen, Heikki Minn
Somatostatin receptor subtype 2A (SSTR2A) is a potential therapeutic target in gliomas. Data on SSTR2A expression in different glioma entities, however, is particularly conflicting. Our objective was to characterize SSTR2A status and explore its impact on survival in gliomas classified according to the specific molecular signatures of the updated WHO classification. In total, 184 glioma samples were retrospectively analyzed for SSTR2A expression using immunohistochemistry with monoclonal antibody UMB-1. Double staining with CD68 was used to exclude microglia and macrophages from analyses...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465358/mutant-idh1-regulates-the-tumor-associated-immune-system-in-gliomas
#16
Nduka M Amankulor, Youngmi Kim, Sonali Arora, Julia Kargl, Frank Szulzewsky, Mark Hanke, Daciana H Margineantu, Aparna Rao, Hamid Bolouri, Jeff Delrow, David Hockenbery, A McGarry Houghton, Eric C Holland
Gliomas harboring mutations in isocitrate dehydrogenase 1/2 (IDH1/2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time than wild-type IDH1/2 (wtIDH1/2) tumors. Although there are many factors underlying the differences in survival between these two tumor types, immune-related differences in cell content are potentially important contributors. In order to investigate the role of IDH mutations in immune response, we created a syngeneic pair mouse model for mutant IDH1 (muIDH1) and wtIDH1 gliomas and demonstrated that muIDH1 mice showed many molecular and clinical similarities to muIDH1 human gliomas, including a 100-fold higher concentration of 2-hydroxygluratate (2-HG), longer survival time, and higher CpG methylation compared with wtIDH1...
May 2, 2017: Genes & Development
https://www.readbyqxmd.com/read/28450436/noninvasive-assessment-of-idh-mutational-status-in-world-health-organization-grade-ii-and-iii-astrocytomas-using-dwi-and-dsc-pwi-combined-with-conventional-mr-imaging
#17
Z Xing, X Yang, D She, Y Lin, Y Zhang, D Cao
BACKGROUND AND PURPOSE: Isocitrate dehydrogenase (IDH) has been shown to have both diagnostic and prognostic implications in gliomas. The purpose of this study was to examine whether DWI and DSC-PWI combined with conventional MR imaging could noninvasively predict IDH mutational status in World Health Organization grade II and III astrocytomas. MATERIALS AND METHODS: We retrospectively reviewed DWI, DSC-PWI, and conventional MR imaging in 42 patients with World Health Organization grade II and III astrocytomas...
April 27, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28447265/nadp-dependent-isocitrate-dehydrogenase-from-a-psychrophilic-bacterium-psychromonas-marina
#18
Ryo Hirota, Kango Tsubouchi, Yasuhiro Takada
The gene encoding NADP(+)-dependent isocitrate dehydrogenase (IDH; EC 1.1.1.42) of a psychrophilic bacterium, Psychromonas marina, was cloned and sequenced. The open reading frame of the gene encoding IDH of P. marina (PmIDH) was 2229 bp in length and corresponded to a polypeptide composed of 742 amino acids. The molecular mass of IDH was calculated as 80,426 Da. The deduced amino acid sequence of PmIDH exhibited high degrees of homology with the monomeric IDH from other bacteria such as Colwellia maris (62% identity) and Azotobacter vinelandii (AvIDH) (64%)...
April 26, 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/28444969/metabolic-reprogramming-and-epithelial-to-mesenchymal-transition-in-cancer
#19
REVIEW
Marco Sciacovelli, Christian Frezza
Several lines of evidence indicate that during transformation epithelial cancer cells can acquire mesenchymal features via a process called epithelial-to-mesenchymal transition (EMT). This process endows cancer cells with increased invasive and migratory capacity, enabling tumour dissemination and metastasis. EMT is associated with a complex metabolic reprogramming, orchestrated by EMT transcription factors, which support the energy requirements of increased motility and growth in harsh environmental conditions...
April 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28444336/intradialytic-hypotension-blood-pressure-changes-and-mortality-risk-in-incident-hemodialysis-patients
#20
Jason A Chou, Elani Streja, Danh V Nguyen, Connie M Rhee, Yoshitsugu Obi, Jula K Inrig, Alpesh Amin, Csaba P Kovesdy, John J Sim, Kamyar Kalantar-Zadeh
Background.: Intradialytic hypotension (IDH) occurs frequently in maintenance hemodialysis (HD) patients and may be associated with higher mortality. We hypothesize that nadir intradialytic systolic blood pressure (niSBP) is inversely related to death risk while iSBP change (Δ) and IDH frequency are incrementally associated with all-cause mortality. Methods.: In a US-based cohort of 112 013 incident HD patients over a 5-year period (2007-11), using niSBP, ΔiSBP (pre-HD SBP minus niSBP) and IDH frequency (proportion of HD treatments with niSBP <90 mmHg) within the first 91 days of HD, we examined mortality-predictability at 1, 2 and 5 years using Cox models and restricted cubic splines adjusted for case-mix, comorbidities and laboratory covariates...
April 21, 2017: Nephrology, Dialysis, Transplantation
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