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https://www.readbyqxmd.com/read/28737676/high-dose-ascorbate-causes-both-genotoxic-and-metabolic-stress-in-glioma-cells
#1
Maria Leticia Castro, Georgia M Carson, Melanie J McConnell, Patries M Herst
We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated by exposure to high dose ascorbate, radiation, ascorbate plus radiation and H₂O₂ in established and primary GBM cell lines. Genotoxic stress was measured as phosphorylation of the variant histone protein, H2AX, 8-oxo-7,8-dihydroguanine (8OH-dG) positive cells and cells with comet tails...
July 22, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28737508/targeting-nek2-attenuates-glioblastoma-growth-and-radioresistance-by-destabilizing-histone-methyltransferase-ezh2
#2
Jia Wang, Peng Cheng, Marat S Pavlyukov, Hai Yu, Zhuo Zhang, Sung-Hak Kim, Mutsuko Minata, Ahmed Mohyeldin, Wanfu Xie, Dongquan Chen, Violaine Goidts, Brendan Frett, Wenhao Hu, Hongyu Li, Yong Jae Shin, Yeri Lee, Do-Hyun Nam, Harley I Kornblum, Maode Wang, Ichiro Nakano
Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#3
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28735518/the-possible-prognostic-role-of-histone-deacetylase-and-transforming-growth-factor-%C3%AE-smad-signaling-in-high-grade-gliomas-treated-by-radio-chemotherapy-a-preliminary-immunohistochemical-study
#4
Roberta Sferra, Simona Pompili, Claudio Festuccia, Francesco Marampon, Giovanni L Gravina, Luca Ventura, Ernesto Di Cesare, Sara Cicchinelli, Eugenio Gaudio, Antonella Vetuschi
Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome...
May 16, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28735440/new-hypofractionation-radiation-strategies-for-glioblastoma
#5
REVIEW
Melissa Azoulay, Jennifer Shah, Erqi Pollom, Scott G Soltys
PURPOSE OF REVIEW: Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with a median survival of less than 2 years despite the standard of care treatment of 6 weeks of chemoradiotherapy. We review the data investigating hypofractionated radiotherapy (HFRT) in the treatment of newly diagnosed GBM. RECENT FINDINGS: Investigators have explored alternative radiotherapy strategies that shorten treatment duration with the goal of similar or improved survival while minimizing toxicity...
September 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28734730/multifaceted-c-x-c-chemokine-receptor-4-inhibition-interferes-with-anti-vascular-endothelial-growth-factor-therapy-induced-glioma-dissemination
#6
Jean-Pierre Gagner, Yasmeen Sarfraz, Valerio Ortenzi, Fawaz M Alotaibi, Luis A Chiriboga, Awab T Tayyib, Garry J Douglas, Eric Chevalier, Barbara Romagnoli, Gérald Tuffin, Michel Schmitt, Guillaume Lemercier, Klaus Dembowsky, David Zagzag
Resistance to antiangiogenic therapy glioblastoma (GBM) patients may involve hypoxia-induced expression of stromal cell-derived factor (SDF)-1α receptor C-X-C chemokine receptor 4 (CXCR4) on invading tumor, macrophage/microglial cells (MGCs), and glioma stem cells (GSCs). We determined whether antagonizing CXCR4 with peptide epitope mimetic POL5551 disrupts anti-vascular endothelial growth factor therapy-induced glioma growth and dissemination. Mice bearing orthotopic CT-2A or GL261 gliomas received POL5551 and/or anti-vascular endothelial growth factor antibody B20-4...
July 20, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28732340/vascular-regulation-of-glioma-stem-like-cells-a-balancing-act
#7
REVIEW
Lucy J Brooks, Simona Parrinello
Glioblastoma (GBM) are aggressive and therapy-resistant brain tumours driven by glioma stem-like cells (GSCs). GSC behaviour is controlled by the microenvironment, or niche, in which the cells reside. It is well-established that the vasculature is a key component of the GSC niche, which drives maintenance in the tumour bulk and invasion at the margin. Emerging evidence now indicates that the specific properties of the vasculature within these two regions impose different functional states on resident GSCs, generating distinct subpopulations...
July 18, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28730289/treatment-outcome-of-patients-with-recurrent-glioblastoma-multiforme-a-retrospective-multicenter-analysis
#8
Myra E van Linde, Cyrillo G Brahm, Philip C de Witt Hamer, Jaap C Reijneveld, Anna M E Bruynzeel, W Peter Vandertop, Peter M van de Ven, Michiel Wagemakers, Hiske L van der Weide, Roelien H Enting, Annemiek M E Walenkamp, Henk M W Verheul
Glioblastoma multiforme (GBM) universally recurs with dismal prognosis. We evaluated the efficacy of standard treatment strategies for patients with recurrent GBM (rGBM). From two centers in the Netherlands, 299 patients with rGBM after first-line treatment, diagnosed between 2005 and 2014, were retrospectively evaluated. Four different treatment strategies were defined: systemic treatment (SYST), re-irradiation (RT), re-resection followed by adjuvant treatment (SURG) and best supportive care (BSC). Median OS for all patients was 6...
July 20, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28730140/current-advances-in-checkpoint-inhibitors-lessons-from-non-central-nervous-system-cancers-and-potential-for-glioblastoma
#9
REVIEW
Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28729143/the-prognostic-impact-of-ventricular-opening-in-glioblastoma-surgery-a-retrospective-single-center-analysis
#10
Felix Behling, Marlene Kaltenstadler, Susan Noell, Jens Schittenhelm, Benjamin Bender, Franziska Eckert, Ghazaleh Tabatabai, Marcos Tatagiba, Marco Skardelly
OBJECTIVE: Ventricular opening during glioblastoma (GBM) resection is controversial. Sufficient evidence regarding its prognostic role is missing. We investigated the impact of ventricular opening on overall survival (OS), hydrocephalus development and postoperative morbidity in GBM patients. METHODS: Patients who underwent primary GBM resection between 2006 and 2013 were assessed retrospectively. Established predictors for overall survival (age, Karnofsky performance status, extent of resection (EOR), O-6-methylguanine-DNA methyltransferase promoter methylation status, isocitrate dehydrogenase mutation status) and further clinical data (postoperative status, further treatment, preoperative tumor volume, proximity to the ventricle) were included in univariate and multivariate analyses...
July 17, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28729027/micrornas-as-multifaceted-players-in-glioblastoma-multiforme
#11
Neri Mercatelli, Silvia Galardi, Silvia Anna Ciafrè
Glioblastoma multiforme (GBM) is the most common and inevitably lethal primary brain tumor, with a median survival rate of only 15 months from diagnosis. The current standard treatment involves maximal surgical resection flanked by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, even such aggressive treatment is never curative, and recurrent tumors always arise, commonly in more aggressive, chemo- and radio-resistant forms, leading to untreatable and deadly tumors. MicroRNAs, recognized major players in cancer, are deeply involved in GBM, as shown by more than a decade of studies...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28728846/the-effects-of-type-i-interferon-on-glioblastoma-cancer-stem-cells
#12
Ziyun Du, Chun Cai, Michelle Sims, Frederick A Boop, Andrew M Davidoff, Lawrence M Pfeffer
Glioblastomas (GBMs) are highly invasive brain tumors that are extremely deadly. The highly aggressive nature of GBM as well as its heterogeneity at the molecular and cellular levels has been attributed to a rare subpopulation of GBM stem-like cells (GSCs). Interferons (IFNs) are a family of endogenous antiviral proteins that have anticancer activity in vitro, and have been used clinically to treat GBM. IFN inhibits the proliferation of various established GBM cell lines, but the effects of IFNs on GSCs remain relatively unknown...
July 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28727297/parsel-parallel-selection-of-micro-rnas-for-survival-classification-in-cancers
#13
Debajyoti Sinha, Debarka Sengupta, Sanghamitra Bandyopadhyay
It is known that tumor micro-RNAs (miRNA) can define patient survival and treatment response. We present a framework to identify miRNAs which are predictive of cancer survival. The framework attempts to rank the miRNAs by exploring their collaborative role in gene regulation. Our approach tests a significantly large number of combinatorial cases leveraging parallel computation. We carefully avoided parametric assumptions involved in evaluations of miRNA expressions but used rigorous statistical computation to assign an importance score to a miRNA...
July 2017: Molecular Informatics
https://www.readbyqxmd.com/read/28727188/mir-21-a-key-player-in-glioblastoma-pathogenesis
#14
Mohammad Sadegh Masoudi, Emadodin Mehrabian, Hamed Mirzaei
Glioblastoma multiform (GBM) is one of common cancers worldwide which has high rate among various populations. Despite serious efforts worldwide, GBM remains a deadly disease which is associated with poor prognosis. Multiple lines evidence indicated that deregulation of a variety of cellular and molecular pathways are related with GBM pathogenesis. Among of various targets involved in GBM pathogenesis, microRNAs (miRNAs) have been emerged as targets which deregulation of them are related with various stages of GBM...
July 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28724615/glioblastoma-cellular-cross-talk-converges-on-nf-%C3%AE%C2%BAb-to-attenuate-egfr-inhibitor-sensitivity
#15
Ciro Zanca, Genaro R Villa, Jorge A Benitez, Amy Haseley Thorne, Tomoyuki Koga, Matteo D'Antonio, Shiro Ikegami, Jianhui Ma, Antonia D Boyer, Afsheen Banisadr, Nathan M Jameson, Alison D Parisian, Olesja V Eliseeva, Gabriela F Barnabe, Feng Liu, Sihan Wu, Huijun Yang, Jill Wykosky, Kelly A Frazer, Vladislav V Verkhusha, Maria G Isaguliants, William A Weiss, Timothy C Gahman, Andrew K Shiau, Clark C Chen, Paul S Mischel, Webster K Cavenee, Frank B Furnari
In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs)...
July 19, 2017: Genes & Development
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#16
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28720668/efficient-mitochondrial-glutamine-targeting-prevails-over-glioblastoma-metabolic-plasticity
#17
Kristell Oizel, Cynthia Chauvin, Lisa Oliver, Catherine Gratas, Fanny Geraldo, Ulrich Jarry, Emmanuel Scotet, Marion Rabe, Marie-Clotilde Alves-Guerra, Raluca Teusan, Fabien Gautier, Delphine Loussouarn, Vincent Compan, Jean-Claude Martinou, François M Vallette, Claire Pecqueur
Purpose Glioblastoma (GBM) is the most common and malignant form of primary human brain tumor in adults, with an average survival at diagnosis of 18 months. Metabolism is a new attractive therapeutic target in cancer, however, little is known about metabolic heterogeneity and plasticity within GBM tumors. We therefore aimed to investigate metabolic phenotyping of primary cultures in the context of molecular tumor heterogeneity to provide a proof-of concept for personalized metabolic targeting of GBM. <p> Experimental Design We have analyzed extensively several primary GBM cultures using transcriptomics, metabolic phenotyping assays and mitochondrial respirometry...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28720461/vaccine-preventable-anal-human-papillomavirus-in-australian-gay-and-bisexual-men
#18
I Mary Poynten, Sepehr N Tabrizi, Fengyi Jin, David J Templeton, Dorothy A Machalek, Alyssa Cornall, Samuel Phillips, Christopher K Fairley, Suzanne M Garland, Carmella Law, Andrew Carr, Richard J Hillman, Andrew E Grulich
OBJECTIVE: HPV causes ~90% of anal cancer and HPV16 is the type most commonly associated with anal cancer. Gay and bisexual men (GBM) are at greatly increased risk. We investigated patterns of vaccine-preventable anal HPV in older GBM. METHODS: The Study of the Prevention of Anal Cancer (SPANC) is an ongoing, prospective cohort study of HIV-positive and HIV-negative Australian GBM. Participants completed questionnaires and underwent an anal swab for HPV genotyping using Roche Linear Array...
June 2017: Papillomavirus Research
https://www.readbyqxmd.com/read/28718993/role-of-fdg-pet-mri-fdg-pet-ct-and-dynamic-susceptibility-contrast-perfusion-mri-in-differentiating-radiation-necrosis-from-tumor-recurrence-in-glioblastomas
#19
Mojgan Hojjati, Chaitra Badve, Vasant Garg, Curtis Tatsuoka, Lisa Rogers, Andrew Sloan, Peter Faulhaber, Pablo R Ros, Leo J Wolansky
BACKGROUND AND PURPOSE: To compare the utility of quantitative PET/MRI, dynamic susceptibility contrast (DSC) perfusion MRI (pMRI), and PET/CT in differentiating radiation necrosis (RN) from tumor recurrence (TR) in patients with treated glioblastoma multiforme (GBM). METHODS: The study included 24 patients with GBM treated with surgery, radiotherapy, and temozolomide who presented with progression on imaging follow-up. All patients underwent PET/MRI and pMRI during a single examination...
July 18, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28718668/olea-europaea-leaf-extract-improves-the-efficacy-of-temozolomide-therapy-by-inducing-mgmt-methylation-and-reducing-p53-expression-un-glioblastoma
#20
Gulcin Tezcan, Berrin Tunca, Hilal Demirci, Ahmet Bekar, Mevlut Ozgur Taskapilioglu, Hasan Kocaeli, Unal Egeli, Gulsah Cecener, Sahsine Tolunay, Ozgur Vatan
Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation...
July 18, 2017: Nutrition and Cancer
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