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https://www.readbyqxmd.com/read/29301329/differential-characterization-of-temozolomide-resistant-human-glioma-cells
#1
Sheng-Wei Lai, Bor-Ren Huang, Yu-Shu Liu, Hsiao-Yun Lin, Chun-Chuan Chen, Cheng-Fang Tsai, Dah-Yuu Lu, Chingju Lin
Glioblastoma multiforme (GBM) is the most common type of primary and malignant tumor occurring in the adult central nervous system. Temozolomide (TMZ) has been considered to be one of the most effective chemotherapeutic agents to prolong the survival of patients with glioblastoma. Many glioma cells develop drug-resistance against TMZ that is mediated by increasing O-6-methylguanine-DNA methyltransferase (MGMT) levels. The expression of connexin 43 was increased in the resistant U251 subline compared with the parental U251 cells...
January 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29285383/effect-of-o6-methylguanine-dna-methyltransferase-methylation-in-medulloblastoma
#2
Tomoko Kurimoto, Akihide Kondo, Ikuko Ogino, Junya Fujimura, Atsushi Arakawa, Hajime Arai, Toshiaki Shimizu
Medulloblastoma is a highly malignant brain tumor that predominately affects children and requires multimodal treatment, including chemotherapy with alkylating agents. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that plays an important role in tumor resistance to alkylating agents. Recent studies demonstrated that MGMT promoter methylation suppresses the expression of MGMT and is associated with favorable outcomes of malignant glioma patients. However, the MGMT methylation status and its prognostic impact on medulloblastoma have not been fully elucidated to date...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29251333/efficacy-of-ribavirin-against-malignant-glioma-cell-lines-follow-up-study
#3
Yushi Ochiai, Emiko Sano, Yutaka Okamoto, Sodai Yoshimura, Kotaro Makita, Shun Yamamuro, Takashi Ohta, Akiyoshi Ogino, Hisashi Tadakuma, Takuya Ueda, Tomohiro Nakayama, Hiroyuki Hara, Atsuo Yoshino, Yoichi Katayama
Ribavirin, a nucleic acid analog, has been employed as an antiviral agent against RNA and DNA viruses and has become the standard agent used for chronic hepatitis C in combination with interferon-α2a. Furthermore, the potential antitumor efficacy of ribavirin has attracted increasing interest. Recently, we demonstrated a dose-dependent antitumor effect of ribavirin for seven types of malignant glioma cell lines. However, the mechanism underlying the antitumor effect of ribavirin has not yet been fully elucidated...
February 2018: Oncology Reports
https://www.readbyqxmd.com/read/29198811/preparation-of-pegylated-liposomes-incorporating-lipophilic-lomeguatrib-derivatives-for-the-sensitization-of-chemo-resistant-gliomas
#4
Rea D Signorell, Alexandros Papachristodoulou, Jiawen Xiao, Bianca Arpagaus, Tommaso Casalini, Joanes Grandjean, Jana Thamm, Frank Steiniger, Paola Luciani, Davide Brambilla, Beat Werner, Ernst Martin, Michael Weller, Patrick Roth, Jean-Christophe Leroux
Liposomal delivery is a well-established approach to increase the therapeutic index of drugs, mainly in the field of cancer chemotherapy. Here, we report the preparation and characterization of a new liposomal formulation of a derivative of lomeguatrib, a potent O6-methylguanine-DNA methyltransferase (MGMT) inactivator. The drug had been tested in clinical trials to revert chemoresistance, but was associated with a low therapeutic index. A series of lomeguatrib conjugates with distinct alkyl chain lengths - i...
November 30, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29196927/characteristics-of-cerebellar-glioblastomas-in-adults
#5
Thiébaud Picart, Marc Barritault, Julien Berthillier, David Meyronet, Alexandre Vasiljevic, Didier Frappaz, Jérôme Honnorat, Emmanuel Jouanneau, Delphine Poncet, François Ducray, Jacques Guyotat
Adult cerebellar glioblastomas (cGBM) are rare and their characteristics remain to be fully described. We analyzed the characteristics of 17 adult patients with cGBM and compared them to a series of 103 patients presenting a supra-tentorial glioblastoma (stGBM). The mean age at GBMc diagnosis was 53.4 years (range 28-77). A history of neurofibromatosis type I was noted in 3 patients. cGBM were hemispheric in 10 patients (58.8%), only vermian in 4 patients (23.5%), and both vermian and hemispheric in 3 patients (17...
December 1, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29170066/glioma-epigenetics-from-subclassification-to-novel-treatment-options
#6
REVIEW
Olga Gusyatiner, Monika E Hegi
Gliomas are the most common malignant primary brain tumors, of which glioblastoma is the most malignant form (WHO grade IV), and notorious for treatment resistance. Over the last decade mutations in epigenetic regulator genes have been identified as key drivers of subtypes of gliomas with distinct clinical features. Most characteristic are mutations in IDH1 or IDH2 in lower grade gliomas, and histone 3 mutations in pediatric high grade gliomas that are also associated with characteristic DNA methylation patterns...
November 20, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29164620/repair-gene-o6-methylguanine-dna-methyltransferase-is-controlled-by-sp1-and-up-regulated-by-glucocorticoids-but-not-by-temozolomide-and-radiation
#7
Dorthe Aasland, Thomas R Reich, Maja T Tomicic, Olivier J Switzeny, Bernd Kaina, Markus Christmann
Therapy of malignant glioma relies on treatment with the O6 -methylating agent temozolomide (TMZ) concomitant with ionizing radiation followed by adjuvant TMZ. For the treatment of recurrences, DNA chloroethylating drugs are also used. The main killing lesion induced by these drugs is O6 -alkylguanine. Since this damage is repaired by O6 -methylguanine-DNA methyltransferase (MGMT), the repair enzyme represents a most important factor of drug resistance, limiting the therapy of malignant high-grade gliomas. Although MGMT has been shown to be transcriptionally up-regulated in rodents following genotoxic stress, it is still unclear whether human MGMT is subject to up-regulation...
January 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29163774/integrative-analysis-of-novel-hypomethylation-and-gene-expression-signatures-in-glioblastomas
#8
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...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162646/nkg2d-dependent-anti-tumor-effects-of-chemotherapy-and-radiotherapy-against-glioblastoma
#9
Tobias Weiss, Hannah Schneider, Manuela Silginer, Alexander Steinle, Martin N Pruschy, Bojan Polic, Michael Weller, Patrick Roth
PURPOSE: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. EXPERIMENTAL DESIGN: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy...
November 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29159745/prognostic-value-of-tumor-volume-in-glioblastoma-patients-size-also-matters-for-patients-with-incomplete-resection
#10
Stefanie Bette, Melanie Barz, Benedikt Wiestler, Thomas Huber, Julia Gerhardt, Niels Buchmann, Stephanie E Combs, Friederike Schmidt-Graf, Claire Delbridge, Claus Zimmer, Jan S Kirschke, Bernhard Meyer, Yu-Mi Ryang, Florian Ringel, Jens Gempt
BACKGROUND: Incomplete resection of glioblastoma is discussed controversially in the era of combined radiochemotherapy. OBJECTIVE: The aim of this study was to analyze the benefit of subtotal tumor resection for glioblastoma patients as this was recently questioned in the era of radiochemotherapy. METHODS: Overall, 209 patients undergoing surgery for newly diagnosed WHO grade IV gliomas were retrospectively analyzed, and pre- and postoperative tumor volumes were manually segmented (cm(3))...
November 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29152101/functional-network-analysis-of-gene-phenotype-connectivity-associated-with-temozolomide
#11
Jia Shi, Bo Dong, Peng Zhou, Wei Guan, Ya Peng
Rationale: Glioma has a poor survival rate in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for treating glioma, but TMZ treatment consistently leads to high resistance. Aim: To investigate the underlying mechanisms of TMZ action with new therapeutic regimens in glioma. Methods and results: The biological effects of TMZ mainly depend on the three following DNA repair systems: methylguanine methyltransferase (MGMT), mismatch repair (MMR) and base excision repair (BER)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151909/bkm120-sensitizes-c6-glioma-cells-to-temozolomide-via-suppression-of-the-pi3k-akt-nf-%C3%AE%C2%BAb-mgmt-signaling-pathway
#12
Mao Li, Ruo Fei Liang, Xiang Wang, Qing Mao, Yan Hui Liu
Glioblastoma is the most common type of malignant intracranial tumor in adults. Temozolomide (TMZ), as the first-line chemotherapy agent used in patients with glioblastoma, has demonstrated different effects in patients due to the expression of O6-methylguanine-DNA methyltransferase (MGMT) which is able to repair the DNA lesions induced by TMZ. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is over-activated in glioblastoma and has been revealed to be potentially implicated in resistance to TMZ...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29137285/genetic-and-immune-features-of-resectable-malignant-brainstem-gliomas
#13
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 10cm(3) (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...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29110584/microrna-target-cross-talks-key-players-in-glioblastoma-multiforme
#14
Eman Ali Toraih, Nagwa Mahmoud Aly, Hoda Y Abdallah, Saeed Awad Al-Qahtani, Aly Am Shaalan, Mohammad Hosny Hussein, Manal Said Fawzy
The role of microRNAs in brain cancer is still naive. Some act as oncogene and others as tumor suppressors. Discovery of efficient biomarkers is mandatory to debate that aggressive disease. Bioinformatically selected microRNAs and their targets were investigated to evaluate their putative signature as diagnostic and prognostic biomarkers in primary glioblastoma multiforme. Expression of a panel of seven microRNAs (hsa-miR-34a, hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, hsa-miR-326, and hsa-miR-375) and seven target genes ( E2F3, PI3KCA, TOM34, WNT5A, PDCD4, DFFA, and EGFR) in 43 glioblastoma multiforme specimens were profiled compared to non-cancer tissues via quantitative reverse transcription-polymerase chain reaction...
November 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29103769/comparative-assessment-of-three-methods-to-analyze-mgmt-methylation-status-in-a-series-of-350-gliomas-and-gangliogliomas
#15
Leiming Wang, Zhuo Li, Cuicui Liu, Li Chen, Li Liu, Zeliang Hu, Lihong Zhao, Dehong Lu, Lianghong Teng
MGMT promoter methylation is considered as a prognostic and predictive biomarker indicating response to chemotherapy and radiotherapy in glioblastoma. A number of different methods and platforms including pyrosequencing (PSQ), quantitative methylation-specific PCR (qMSP) and immunohistochemistry (IHC), methylation-sensitive high resolution melting (MS-HRM) and NGS (Next Generation Sequencing) have been used to detect MGMT promoter methylation in gliomas. However, controversy remains about the most appropriate method to use for analyzing MGMT status...
October 10, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29100349/alu-hypomethylation-and-mgmt-hypermethylation-in-serum-as-biomarkers-of-glioma
#16
Mingjie Gong, Wei Shi, Jing Qi, Guoping Shao, Zhenghua Shi, Junxiang Wang, Jian Chen, Rongtao Chu
In order to improve prognosis of glioma patients, better tools are required for early diagnosis and treatment. Serum cell-free DNA methylation levels of Alu, MGMT, P16, RASSF1A from 124 glioma patients and 58 healthy controls were detected by the bisulfite sequencing. The median methylation level of Alu was 46.15% (IQR, 36.57%-54.00%) and 60.85% (IQR, 57.23%-65.68%) in glioma patients and healthy controls respectively. The median methylation level of MGMT in glioma samples was 64.65% (IQR, 54.87%-74.37%) compared to 38...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29098021/pyrrolidine-dithiocarbamate-sensitizes-u251-brain-glioma-cells-to-temozolomide-via-downregulation-of-mgmt-and-bcl-xl
#17
Jun-Hai Tang, Guo-Hao Huang, Ke-Jie Mou, Eric Erquan Zhang, Ningning Li, Lei Du, Xiao-Peng Zhu, Ling Chen, Hui Yang, Ke-Bin Zhang, Sheng-Qing Lv
The current study investigated the effect of pyrrolidine dithiocarbamate (PDTC) on the proliferation, apoptosis, cell cycle and sensitivity to temozolomide (TMZ) of the U251 glioma cell line. Proliferation, apoptosis and cell cycle analysis of U251 cells following treatment with PDTC and TMZ was determined by an MTT assay and flow cytometry, respectively. The mRNA and protein expression levels of O-6-methylguanine-DNA methyltransferase (MGMT), B-cell lymphoma extra-large (BCL-XL) and survivin were further determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting analysis...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29067692/glucocorticoids-promote-a-glioma-stem-cell-like-phenotype-and-resistance-to-chemotherapy-in-human-glioblastoma-primary-cells-biological-and-prognostic-significance
#18
Ourania N Kostopoulou, Abdul-Aleem Mohammad, Jiri Bartek, Julia Winter, Masany Jung, Giuseppe Stragliotto, Cecilia Söderberg-Nauclér, Natalia Landázuri
Glioma stem cells (GSCs) are glioblastoma (GBM) cells that are resistant to therapy and can give rise to recurrent tumors. The identification of patient-related factors that support GSCs is thus necessary to design effective therapies for GBM patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, which has been linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and GSCs...
October 25, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29053887/low-foxg1-and-high-olig-2-labelling-indices-define-a-prognostically-favorable-subset-in-idh-mutant-gliomas
#19
Sarah Schäfer, Felix Behling, Marco Skardelly, Marilin Koch, Ines Ott, Frank Paulsen, Ghazaleh Tabatabai, Jens Schittenhelm
AIMS: Previous data suggest that expression of transcription factors FoxG1 and Olig-2 can separate hotspot H3F3A-mutant tumors in pediatric glioma. We evaluated their prognostic potential and feasibility for identifying H3F3A-mutant tumors among IDH-mutant/wildtype gliomas. METHODS: Immunohistochemistry of FoxG1/Olig-2 and ATRX in 471 cases of diffuse gliomas and molecular determination of IDH, H3F3A, MGMT and 1p/19 codeletion status. RESULTS: Mean percentage of FoxG1 positive tumor cells increased from 17% in WHO grade II to over 21% in grade III to 37% in grade IV tumors, while mean Olig-2 indices decreased from 29% to 28% to 17% respectively...
October 20, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29031038/isocitrate-dehydrogenase-mutations-are-better-prognostic-marker-than-o6-methylguanine-dna-methyltransferase-promoter-methylation-in-glioblastomas-a-retrospective-single-centre-molecular-genetics-study-of-gliomas
#20
M Houdova Megova, J Drábek, Z Dwight, R Trojanec, V Koudeláková, J Vrbková, O Kalita, S Mlcochova, M Rabcanova, M Hajdúch
BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are a promising prognostic biomarker of gliomas. The purpose of our study was to examine the clinical prognostic properties of IDH1/2 mutations in a glioma patient cohort from the Czech Republic using an improved platform for simple and reliable IDH genotyping. MATERIAL AND METHODS: We retrospectively analyzed a group of 145 glioma patients by testing for the three most frequent IDH mutations, IDH1 R132H, IDH1 R132C, and IDH2 R172K, through the competitive amplification of differentially melting amplicons (CADMA) polymerase chain reaction (PCR)...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
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