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https://www.readbyqxmd.com/read/28884377/idh-mutation-status-trumps-the-pignatti-risk-score-as-a-prognostic-marker-in-low-grade-gliomas
#1
Olatz Etxaniz, Cristina Carrato, Itziar de Aguirre, Cristina Queralt, Ana Muñoz, José L Ramirez, Rafael Rosell, Salvador Villà, Rocio Diaz, Ana Estival, Pilar Teixidor, Alberto Indacochea, Sara Ahjal, Laia Vilà, Carme Balañá
Management of low-grade gliomas (LGG) is based on clinical and radiologic features, including the Pignatti prognostic scoring system, which classifies patients as low- or high-risk. To determine whether molecular data can offer advantages over these features, we have examined the prognostic impact of several molecular alterations in LGG. In a cohort of 58 patients with LGG, we have retrospectively analyzed clinical and molecular characteristics, including the Pignatti criteria, IDH mutations, TP53 mutations, the 1p/19q deletion, and MGMT methylation, and correlated our findings with progression-free survival (PFS) and overall survival (OS)...
September 7, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28869450/idh1-status-is-significantly-different-between-high-grade-thalamic-and-superficial-gliomas
#2
Mingrong Zuo, Mao Li, Ni Chen, Tianping Yu, Bing Kong, Ruofei Liang, Xiang Wang, Qing Mao, Yanhui Liu
BACKGROUND: While major progress has been made in diagnosis and treatment of gliomas based on molecules, molecular features of thalamic glioma have rarely been reported till now. OBJECTIVE: IDH1 mutation is important for prognosis of gliomas and represents a distinctive category of glioma. We intended to survey specific molecular abnormalities in high-grade thalamic gliomas (WHO III-IV). METHODS: We collected data of 50 and 93 newly diagnosed high-grade thalamic and superficial glioma patients respectively and conducted a comparative analysis of molecular characteristics between them...
August 23, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28856492/tumor-location-and-patient-age-predict-biological-signatures-of-high-grade-gliomas
#3
Roberto Altieri, Francesco Zenga, Alessandro Ducati, Antonio Melcarne, Fabio Cofano, Marco Mammi, Giuseppe Di Perna, Riccardo Savastano, Diego Garbossa
Prognostic factors for high-grade gliomas include patient age, IDH1 mutation, MGMT methylation, and Ki67 value. We assessed the predictive role of topographic location of gliomas for their biological signatures. Collecting all neuroradiological and histological data of patients with histologically proven HGG, we performed a retrospective monocentric study. A predictive value of frontal location for a lower Ki67 value (especially in the left hemisphere) and mutation of IDH1 (especially in the right hemisphere) was found...
August 31, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28851427/the-frequency-and-prognostic-effect-of-tert-promoter-mutation-in-diffuse-gliomas
#4
Yujin Lee, Jaemoon Koh, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Seung Hong Choi, Sung-Hye Park
Mutations in the telomerase reverse transcriptase gene promoter (TERTp) are common in glioblastomas (GBMs) and oligodendrogliomas (ODGs), and therefore, have a key role in tumorigenesis and may be of prognostic value. However, the extent of their prognostic importance in various gliomas is controversial. We studied 168 patients separated into five groups: Group 1: 65 patients with ODG carrying an IDH1 or IDH2 mutation (IDH-mutant) and 1p/19q-codeletion, Group 2: 23 patients with anaplastic astrocytoma (AA), IDH-mutant, Group 3: 13 patients with GBM, IDH-mutant, Group 4: 15 patients with AA, IDH-wildtype (WT), and Group 5: 52 patients with GBM, IDH-WT...
August 29, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28831025/lncrna-xist-interacts-with-mir-29c-to-modulate-the-chemoresistance-of-glioma-cell-to-tmz-through-dna-mismatch-repair-pathway
#5
Peng Du, Haiting Zhao, Renjun Peng, Qing Liu, Jian Yuan, Gang Peng, Yiwei Liao
Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However, growing resistance to TMZ remains a major challenge for clinicians. Recent evidence emphasizes the key regulatory roles of non-coding RNAs (lncRNAs and miRNAs) in tumor biology, including the chemoresistance of cancers. However, little is known about the role and regulation mechanisms of lncRNA cancer X-inactive specific transcripts (XIST) in glioma tumorigenesis and chemotherapy resistance. In the present study, higher XIST expression was observed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28823044/diagnostic-implications-of-tert-promoter-mutation-status-in-diffuse-gliomas-in-a-routine-clinical-setting
#6
Ekkehard Hewer, Nadine Prebil, Sabina Berezowska, Marielena Gutt-Will, Philippe Schucht, Matthias S Dettmer, Erik Vassella
IDH (isocitrate dehydrogenase) gene mutations are present in most diffuse low-grade gliomas and define the clinico-pathological core of the respective morphologically defined entities. Conversely, according to the 2016 WHO classification, the majority of glioblastomas belong to the IDH-wildtype category, which is defined by exclusion. TERT (telomerase reverse transcriptase gene) promoter mutations have been suggested as a molecular marker for primary glioblastomas. We analyzed molecular, histopathological, and clinical profiles of a series of 110 consecutive diffuse gliomas (WHO grades II-IV) diagnosed at our institution, in which TERT promoter mutation analysis had been performed as part of diagnostic work-up...
August 19, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28821714/gadd45a-plays-a-protective-role-against-temozolomide-treatment-in-glioblastoma-cells
#7
Hsiao-Han Wang, Tsuey-Yu Chang, Wei-Chen Lin, Kuo-Chen Wei, Jyh-Wei Shin
Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of GBM limits its application. Here, we found that TMZ inhibited the proliferation and induced the G2/M arrest of GBM cells. Therefore, we performed microarrays to identify the cell cycle- and apoptosis-related genes affected by TMZ...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801186/interim-results-from-the-catnon-trial-eortc-study-26053-22054-of-treatment-with-concurrent-and-adjuvant-temozolomide-for-1p-19q-non-co-deleted-anaplastic-glioma-a-phase-3-randomised-open-label-intergroup-study
#8
Martin J van den Bent, Brigitta Baumert, Sara C Erridge, Michael A Vogelbaum, Anna K Nowak, Marc Sanson, Alba Ariela Brandes, Paul M Clement, Jean Francais Baurain, Warren P Mason, Helen Wheeler, Olivier L Chinot, Sanjeev Gill, Matthew Griffin, David G Brachman, Walter Taal, Roberta Rudà, Michael Weller, Catherine McBain, Jaap Reijneveld, Roelien H Enting, Damien C Weber, Thierry Lesimple, Susan Clenton, Anja Gijtenbeek, Sarah Pascoe, Ulrich Herrlinger, Peter Hau, Frederic Dhermain, Irene van Heuvel, Roger Stupp, Ken Aldape, Robert B Jenkins, Hendrikus Jan Dubbink, Winand N M Dinjens, Pieter Wesseling, Sarah Nuyens, Vassilis Golfinopoulos, Thierry Gorlia, Wolfgang Wick, Johan M Kros
BACKGROUND: The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q co-deleted tumours, is unclear. We assessed the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas. METHODS: This was a phase 3, randomised, open-label study with a 2 × 2 factorial design. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with WHO performance status scores of 0-2...
August 8, 2017: Lancet
https://www.readbyqxmd.com/read/28791452/long-term-daily-temozolomide-with-dose-dependent-efficacy-in-mgmt-promotor-methylation-negative-recurrent-high-grade-astrocytoma
#9
Zhengqiu Zhou, Tracy A Howard, John L Villano
Temozolomide (TMZ) for malignant gliomas is traditionally dosed in 5 out of a 28-day cycle, however alternative regimens exist, including dose-dense. Continuous daily dosing is available, but the acceptable dose and duration of therapy is unknown. We document a 40-year-old male with recurrent anaplastic astrocytoma, IDH mutant and MGMT promotor methylation negative, who has well-tolerated continuous daily TMZ for 20 months at 100 mg per day for nearly the length of this period. A trial at 80 mg per day demonstrated disease progression with response upon return to 100 mg per day...
August 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28775233/genetic-and-immune-features-of-resectable-malignant-brainstem-gliomas
#10
Yang Zhang, Changcun Pan, Junmei Wang, Jingli Cao, Yuhan Liu, Yajie Wang, Liwei Zhang
We surveyed common genetic mutations (IDH1, H3F3A, PPM1D, and TP53) and immune features (PD-L1 expression and CD8+ T cell tumor infiltration) in a series of 62 malignant brainstem gliomas that were resected via microsurgery. IDH1 mutations were mutually exclusive with H3F3A mutations. IDH1 mutations appeared only in adults and occurred more frequently in tumors larger than 10cm3 (8/29 vs 1/32, Fisher's exact test, p=0.010). H3F3A mutations occurred more frequently in children and adolescent patients (19/24 vs 18/38, chi-square test, p=0...
July 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28755323/detection-of-the-alternative-lengthening-of-telomeres-pathway-in-malignant-gliomas-for-improved-molecular-diagnosis
#11
Anne Fogli, Marie-Véronique Demattei, Laetitia Corset, Catherine Vaurs-Barrière, Emmanuel Chautard, Julian Biau, Jean-Louis Kémény, Catherine Godfraind, Bruno Pereira, Toufik Khalil, Nathalie Grandin, Philippe Arnaud, Michel Charbonneau, Pierre Verrelle
Human malignant gliomas exhibit acquisition of either one of two telomere maintenance mechanisms, resulting from either reactivation of telomerase expression or activation of an alternative lengthening of telomeres (ALT) mechanism. In the present study, we analyzed 63 human malignant gliomas for the presence of ALT-specific extrachromosomal circles of telomeric DNA (C-circles) and measured telomerase expression, telomeric DNA content (Telo/Alu method), and telomeric repeat-containing RNAs (TERRA) levels. We also assessed histomolecular markers routinely used in clinical practice...
July 28, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28732379/integrative-analysis-of-novel-hypomethylation-and-gene-expression-signatures-in-glioblastomas
#12
Anan Yin, Amandine Etcheverry, Yalong He, Marc Aubry, Jill Barnholtz-Sloan, Luhua Zhang, Xinggang Mao, Weijun Chen, Bolin Liu, Wei Zhang, Jean Mosser, Xiang Zhang
Molecular and clinical heterogeneity critically hinders better treatment outcome for glioblastomas (GBMs); integrative analysis of genomic and epigenomic data may provide useful information for improving personalized medicine. By applying training-validation approach, we identified a novel hypomethylation signature comprising of three CpGs at non-CpG island (CGI) open sea regions for GBMs. The hypomethylation signature consistently predicted poor prognosis of GBMs in a series of discovery and validation datasets...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28696020/complete-durable-response-of-a-pediatric-anaplastic-oligodendroglioma-to-temozolomide-alone-case-report-and-review-of-literature
#13
Caryn Sorge, Rong Li, Sumit Singh, Alyssa T Reddy, David A Solomon, Arie Perry, Gregory K Friedman
Anaplastic oligodendroglioma (AO) is rare in children. Treatment typically consists of varying combinations of surgery, chemotherapy, and radiotherapy. We present a pediatric case of frontal lobe AO with periventricular subcallosal extension and local leptomeningeal involvement. The isocitrate dehydrogenase (IDH) wild-type tumor was MGMT methylated and contained an ATRX mutation, BRAF alteration, and 1p/19q co-deletion; a combination of alterations mostly encountered in pediatric oligodendrogliomas. The patient underwent a near total resection and had a complete, durable response to temozolomide alone, suggesting that conservative management without radiation may be appropriate in some cases...
July 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28693158/relationship-between-mgmt-gene-expression-and-treatment-effectiveness-and-prognosis-in-glioma
#14
Qiang Li, Jiang Guo, Weisheng Wang, Dingkun Wang
The expression of O(6)-methylguanine DNA methyltransferase (MGMT) in different grade gliomas were analyzed in relation to its therapeutic effect and impact on disease prognosis. In total, 62 patients with glioma, who were admitted by neurosurgery and received surgical treatment and postoperative conventional chemoradiation, were selected for this study. Expression of MGMT was greater with an increase in brain glioma grade. Gender, age, tumor size and Karnofsky performance status (KPS) score did not differ with MGMT expression (P>0...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28672945/o-6-methyl-guanine-dna-methyltransferase-methylation-and-idh1-2-mutation-in-small-cell-lung-cancer
#15
Hongyang Lu, Jing Qin, Haimiao Xu, Na Han, Fajun Xie, Weimin Mao
Small cell lung cancer (SCLC) is sensitive to first-line chemotherapy and radiotherapy, but frequently recurs. Temozolomide is a chemotherapeutic drug suitable for the treatment of relapsed SCLC, particularly when brain metastases are present. The response of SCLC to temozolomide may be associated with the methylation status of O(6)-methyl-guanine-DNA methyltransferase (MGMT). Isocitrate dehydrogenase (IDH) mutation is an independent prognostic factor of good outcome in gliomas and appears to be a significant marker of positive chemosensitivity in secondary glioblastoma...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28662073/apng-as-a-prognostic-marker-in-patients-with-glioblastoma
#16
Sigurd Fosmark, Sofie Hellwege, Rikke H Dahlrot, Kristian L Jensen, Helene Derand, Jesper Lohse, Mia D Sørensen, Steinbjørn Hansen, Bjarne W Kristensen
AIM: Expression of the base excision repair enzyme alkylpurine-DNA-N-glycosylase (APNG) has been correlated to temozolomide resistance. Our aim was to evaluate the prognostic value of APNG in a population-based cohort with 242 gliomas including 185 glioblastomas (GBMs). Cellular heterogeneity of GBMs was taken into account by excluding APNG expression in non-tumor cells from the analysis. METHODS: APNG expression was evaluated using automated image analysis and a novel quantitative immunohistochemical (IHC) assay (qIHC), where APNG protein expression was evaluated through countable dots...
2017: PloS One
https://www.readbyqxmd.com/read/28642179/analysis-of-outcomes-of-multidisciplinary-management-of-gliosarcoma-a-single-centre-study-2000-2013
#17
Abhinav Jain, Jason Correia, Patrick Schweder, Adele McMahon, Joseph Merola, Robert Aspoas
BACKGROUND: Gliosarcoma is a rare CNS tumour with a reported incidence of ∼2-8% of all gliomas. We reviewed the outcomes of patients treated at our institution over a 14-year period from 2000-2013 to characterize overall and progression free survival as well as to elucidate the additive effect of chemo-radiotherapy. METHODS: For the duration of 01/01/2000 to 31/12/2013, we retrospectively reviewed the clinical notes of all patients treated at our institution with a histopathological diagnosis of Gliosarcoma...
June 19, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28625978/the-alkylating-chemotherapeutic-temozolomide-induces-metabolic-stress-in-idh1-mutant-cancers-and-potentiates-nad-depletion-mediated-cytotoxicity
#18
Kensuke Tateishi, Fumi Higuchi, Julie J Miller, Mara V A Koerner, Nina Lelic, Ganesh M Shankar, Shota Tanaka, David E Fisher, Tracy T Batchelor, A John Iafrate, Hiroaki Wakimoto, Andrew S Chi, Daniel P Cahill
IDH1-mutant gliomas are dependent upon the canonical coenzyme NAD(+) for survival. It is known that PARP activation consumes NAD(+) during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD(+) biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide could potentiate NAD(+) depletion-mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of temozolomide on NAD(+) metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to temozolomide, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD(+) biosynthesis...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28581641/clk1-regulated-aerobic-glycolysis-is-involved-in-glioma-chemoresistance
#19
Li Zhang, Huicui Yang, Wenbin Zhang, Zhongqin Liang, Qiang Huang, Guoqiang Xu, Xuechu Zhen, Long Tai Zheng
Chemoresistance remains a major challenge for the treatment of glioma. In this study, we investigated the role of Clock 1 (Clk1), which encodes an enzyme that is necessary for ubiquinone biosynthesis in glioma chemoresistance in vitro. The results showed that Clk1 was highly expressed in GL261 mouse glioma cells which were most sensitive to 1,3Bis (2-chloroethyl) 1 nitrosourea (BCNU) while was low expressed in BCNU resistant cells such as glioma cancer stem cells, T98G, U87MG and U251 glioma cells. Knockdown of Clk1 in GL261 glioma cells significantly reduced BCNU- or cisplatin-induced cell apoptosis, whereas the proliferative activity and the expression of multidrug resistance-related genes including MDR1, O6-methylguanine-DNA methyltransferase, and GSTP1 were not changed...
August 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28575062/the-rs16906252-c-t-snp-is-not-associated-with-increased-overall-survival-or-temozolomide-response-in-a-han-chinese-glioma-cohort
#20
Kuo-Chen Wei, Chia-Yuan Chen, Li-Ying Feng, Wei-Tzu Huang, Chia-Hua Chen, Peng-Wei Hsu, Kai Wang, Leroy E Hood, Leslie Y Chen
The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST) and the response to temozolomide (TMZ) treatment. However, these findings haven't been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients...
2017: PloS One
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