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Neuro-oncology

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https://www.readbyqxmd.com/read/29771389/erratum
#1
(no author information available yet)
No abstract text is available yet for this article.
May 16, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#2
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29767783/timing-of-radiotherapy-in-newly-diagnosed-glioblastoma-no-need-to-rush
#3
M Geurts, M J van den Bent
No abstract text is available yet for this article.
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29762745/genome-wide-association-analysis-identifies-a-meningioma-risk-locus-at-11p15-5
#4
Elizabeth B Claus, Alex J Cornish, Peter Broderick, Joellen M Schildkraut, Sara E Dobbins, Amy Holroyd, Lisa Calvocoressi, Lingeng Lu, Helen M Hansen, Ivan Smirnov, Kyle M Walsh, Johannes Schramm, Per Hoffmann, Markus M Nöthen, Karl-Heinz Jöckel, Anthony Swerdlow, Signe Benzon Larsen, Christoffer Johansen, Matthias Simon, Melissa Bondy, Margaret Wrensch, Richard Houlston, Joseph L Wiemels
BACKGROUND: Meningioma are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31. METHODS: To identify a susceptibility locus for meningioma, we conducted a meta-analysis of two GWAS, imputed using a merged reference panel of 1,000 Genomes and UK10K data, with validation in two independent sample series totaling 2,138 cases and 12,081 controls...
May 12, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29762717/durable-complete-responses-in-some-recurrent-high-grade-glioma-patients-treated-with-toca-511-toca-fc
#5
Timothy F Cloughesy, Joseph Landolfi, Michael A Vogelbaum, Derek Ostertag, James B Elder, Stephen Bloomfield, Bob Carter, Clark C Chen, Steven N Kalkanis, Santosh Kesari, Albert Lai, Ian Y Lee, Linda M Liau, Tom Mikkelsen, Phioanh Nghiemphu, David Piccioni, William Accomando, Oscar R Diago, Daniel J Hogan, Dawn Gammon, Noriyuki Kasahara, Thian Kheoh, Douglas J Jolly, Harry E Gruber, Asha Das, Tobias Walbert
Background: Vocimagene amiretrorepvec (Toca 511) is an investigational gamma-retroviral replicating vector encoding cytosine deaminase that, when used in combination with extended-release 5-fluorocytosine (Toca FC), results preclinically in local production of 5-fluorouracil, depletion of immune-suppressive myeloid cells, and subsequent induction of anti-tumor immunity. Recurrent high grade glioma (rHGG) patients have a high unmet need for effective therapies that produce durable responses lasting more than 6 months...
May 12, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29750281/an-orthotopic-glioblastoma-animal-model-suitable-for-high-throughput-screenings
#6
Linda Pudelko, Steven Edwards, Mirela Balan, Daniel Nyqvist, Jonathan Al-Saadi, Johannes Dittmer, Ingrid Almlöf, Thomas Helleday, Lars Bräutigam
Background: Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies and clinically relevant orthotopic zebrafish models have been developed...
May 10, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29746665/blood-based-biomarkers-for-the-diagnosis-and-monitoring-of-gliomas
#7
Marcus Zachariah, Joao Paulo Oliveira-Costa, Bob Carter, Shannon L Stott, Brian V Nahed
No abstract text is available yet for this article.
May 9, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29741745/prospective-feasibility-and-safety-assessment-of-surgical-biopsy-for-patients-with-newly-diagnosed-diffuse-intrinsic-pontine-glioma
#8
Nalin Gupta, Liliana C Goumnerova, Peter Manley, Susan N Chi, Donna Neuberg, Maneka Puligandla, Jason Fangusaro, Stewart Goldman, Tadanori Tomita, Tord Alden, Arthur DiPatri, Joshua B Rubin, Karen Gauvain, David Limbrick, Jeffrey Leonard, J Russel Geyer, Sarah Leary, Samuel Browd, Zhihong Wang, Sandeep Sood, Anne Bendel, Mahmoud Nagib, Sharon Gardner, Matthias A Karajannis, David Harter, Kanyalakshmi Ayyanar, William Gump, Daniel C Bowers, Bradley Weprin, Tobey J MacDonald, Dolly Aguilera, Barunashish Brahma, Nathan J Robison, Erin Kiehna, Mark Krieger, Eric Sandler, Philipp Aldana, Ziad Khatib, John Ragheb, Sanjiv Bhatia, Sabine Mueller, Anu Banerjee, Amy-Lee Bredlau, Sri Gururangan, Herbert Fuchs, Kenneth J Cohen, George Jallo, Kathleen Dorris, Michael Handler, Melanie Comito, Mark Dias, Kellie Nazemi, Lissa Baird, Jeff Murray, Neal Lindeman, Jason L Hornick, Hayley Malkin, Claire Sinai, Lianne Greenspan, Karen D Wright, Michael Prados, Pratiti Bandopadhayay, Keith L Ligon, Mark W Kieran
Background: Diagnosis of diffuse intrinsic pontine gliomas (DIPG) has relied on imaging studies since the appearance is pathognomonic, and surgical risk was felt to be high and unlikely to affect therapy. The DIPG Biology and Treatment Study (DIPG-BATS) reported here incorporated a surgical biopsy at presentation and stratified subjects to receive FDA-approved agents chosen on the basis of specific biologic targets. Methods: Subjects were eligible for the trial if the clinical features and imaging appearance of a newly diagnosed tumor were consistent with a DIPG...
May 5, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29733389/temozolomide-for-immunomodulation-in-the-treatment-of-glioblastoma
#9
Aida Karachi, Farhad Dastmalchi, Duane Mitchell, Maryam Rahman
Temozolomide is the most widely used chemotherapy for patients with glioblastoma (GBM) despite the fact that approximately half of treated patients have temozolomide resistance and all patients eventually fail therapy. Due to the limited efficacy of existing therapies, immunotherapy is being widely investigated for patients with GBM. However, initial immunotherapy trials in GBM patients have had disappointing results as monotherapy. Therefore, combinatorial treatment strategies are being investigated. Temozolomide has several effects on the immune system that are dependent on mode of delivery and the dosing strategy that may have unpredicted effects on immunotherapy...
May 4, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29733378/assessing-the-predictability-of-idh-mutation-and-mgmt-methylation-status-in-glioma-patients-using-relaxation-compensated-multi-pool-cest-mri-at-7-0-tesla
#10
Daniel Paech, Johannes Windschuh, Johanna Oberhollenzer, Constantin Dreher, Felix Sahm, Jan-Eric Meissner, Steffen Goerke, Patrick Schuenke, Moritz Zaiss, Sebastian Regnery, Sebastian Bickelhaupt, Philipp Bäumer, Martin Bendszus, Wolfgang Wick, Andreas Unterberg, Peter Bachert, Mark Edward Ladd, Heinz-Peter Schlemmer, Alexander Radbruch
Background: Early identification of prognostic superior characteristics in glioma patients such as Isocitrate dehydrogenase(IDH)-mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promotor methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH-mutation status, MGMT promotor methylation, and differentiation of lower versus higher grade glioma (LGG vs. HGG) in newly-diagnosed patients employing relaxation-compensated multi-pool Chemical Exchange Saturation Transfer (CEST) magnetic resonance imaging (MRI) at 7...
May 4, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29718345/pi3k-activation-in-neural-stem-cells-drives-tumorigenesis-which-can-be-ameliorated-by-targeting-the-camp-response-element-binding-creb-protein
#11
Paul M Daniel, Gulay Filiz, Daniel V Brown, Michael Christie, Paul M Waring, Yi Zhang, John M Haynes, Colin Pouton, Dustin Flanagan, Elizabeth Vincan, Terrance G Johns, Karen Montgomery, Wayne A Phillips, Theo Mantamadiotis
Background: Hyperactivation of PI3K signaling is common in cancers but the precise role of the pathway in glioma biology remains to be determined. Some understanding of PI3K signaling mechanisms in brain cancer comes from studies on neural stem/progenitor cells, where signals transmitted via the PI3K pathway cooperate with other intracellular pathways and downstream transcription factors to regulate critical cell functions. Methods: To investigate the role for the PI3K pathway in glioma initiation and development, we generated a mouse model targeting the inducible expression of a PIK3CAH1047A oncogenic mutant and deletion of the PI3K negative regulator, PTEN, to neural stem/progenitor cells (NSPCs)...
April 30, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29718366/intratumoral-heterogeneity-of-oxygen-metabolism-and-neovascularization-uncovers-two-survival-relevant-subgroups-of-idh1-wild-type-glioblastoma
#12
Andreas Stadlbauer, Max Zimmermann, Arnd Doerfler, Stefan Oberndorfer, Michael Buchfelder, Roland Coras, Melitta Kitzwögerer, Karl Roessler
Background: The intratumoral heterogeneity of oxygen metabolism in combination with variable patterns of neovascularization (NV) as well as reprogramming of energy metabolism affects the landscape of tumor microenvironments (TMEs) in glioblastoma. Knowledge of the hypoxic and perivascular niches within the TME is essential for understanding treatment failure. Methods: Fifty-two patients with untreated glioblastoma (IDH1 wildtype) were examined with a physiological MRI protocol including a multiparametric quantitative blood-oxygen-level-dependent (qBOLD) approach and vascular architecture mapping (VAM)...
April 28, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29718344/association-of-plexiform-neurofibroma-volume-changes-and-development-of-clinical-morbidities-in-neurofibromatosis-1
#13
Andrea M Gross, Gurbani Singh, Srivandana Akshintala, Andrea Baldwin, Eva Dombi, Somto Ukwuani, Anne Goodwin, David J Liewehr, Seth M Steinberg, Brigitte C Widemann
Background: Plexiform neurofibromas (PN) in neurofibromatosis 1 (NF1) can cause substantial morbidities. Clinical trials targeting PN have recently described decreases in PN volumes. However, no previous study has assessed the association between changes in PN volumes and PN related morbidities. Our objective was to assess if increasing PN volume in NF1 is associated with increasing PN related morbidity. Methods: Retrospective review of patients enrolled on the NCI NF1 Natural History study with ≥ 7 years of data available...
April 28, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29660031/meningioma-transcription-factors-link-cell-lineage-with-systemic-metabolic-cues
#14
Ziming Du, Ryan Brewster, Parker H Merrill, Juliann Chmielecki, Josh Francis, Ayal Aizer, Malak Abedalthagafi, Lynette M Sholl, Lars Geffers, Brian Alexander, Sandro Santagata
Background: Tumor cells recapitulate cell-lineage transcriptional programs that are characteristic of normal tissues from which they arise. It is unclear why such lineage programs are fatefully maintained in tumors and if they contribute to cell proliferation and viability. Methods: Here, we used the most common brain tumor, meningioma, which is strongly associated with female gender and high body mass index (BMI), as a model system to address these questions. We screened expression profiling data to identify the transcription factor (TF) genes which are highly enriched in meningioma, and characterized the expression pattern of those TFs and downstream genes in clinical meningioma samples as well as normal brain tissues...
April 12, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29660022/molecular-ablation-of-tumor-blood-vessels-inhibits-therapeutic-effects-of-radiation-and-bevacizumab
#15
Viveka Nand Yadav, David Altshuler, Padma Kadiyala, Daniel Zamler, Andrea Comba, Henry Appelman, Patrick Dunn, Carl Koschmann, Maria G Castro, Pedro R Löwenstein
Background: Glioblastoma (GBM) is an aggressive and highly vascular tumor with median survival below 2 years. Despite advances in surgery, radiotherapy and chemotherapy survival has improved modestly. To combat glioma vascular proliferation anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) were introduced. Preclinically these agents were effective, yet they did not improve overall survival in Phase III trials. We tested the hypothesis that ganciclovir (GCV)-mediated killing of proliferating endothelial cells expressing HSV1-TK would have direct anti-tumor effects, and whether vessel ablation would affect the anti-tumor activity of anti-VEGF antibodies and radiotherapy...
April 12, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29660021/mapping-of-genomic-egfrviii-deletions-in-glioblastoma-insight-into-rearrangement-mechanisms-and-biomarker-development
#16
Tomoyuki Koga, Bin Li, Javier M Figueroa, Bing Ren, Clark C Chen, Bob S Carter, Frank B Furnari
Background: Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM) generated by deletion of exons two to seven of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron one, presenting significant challenges in terms of PCR-based mapping. Molecular mechanisms underlying these deletions remain unclear. Methods: We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative polymerase chain reaction (qPCR), arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS)...
April 12, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29648659/comment-on-trivalent-car-t-cells-overcome-interpatient-antigenic-variability-in-glioblastoma
#17
Hillary Caruso, Amy B Heimberger
No abstract text is available yet for this article.
April 10, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29660023/radiation-induces-age-dependent-deficits-in-cortical-synaptic-plasticity
#18
Die Zhang, Wei Zhou, Thanh Thai Lam, Connie Weng, Lawrence Bronk, Duo Ma, Qiang Wang, Joseph G Duman, Patrick M Dougherty, David R Grosshans
Background: Radiation-induced cognitive dysfunction is a significant side effect of cranial irradiation for brain tumors. Clinically, pediatric patients are more vulnerable than adults. However, the underlying mechanisms of dysfunction, including reasons for age dependence, are still largely unknown. Previous studies have focused on the loss of hippocampal neuronal precursor cells and deficits in memory. However, survivors may also experience deficits in attention, executive function, or other non-hippocampal-dependent cognitive domains...
April 6, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29660019/modeling-the-diffusion-of-d-2-hydroxyglutarate-from-idh1-mutant-gliomas-in-the-central-nervous-system
#19
Andreas Linninger, Grant A Hartung, Benjamin P Liu, Snezana Mirkov, Kevin Tangen, Rimas V Lukas, Dusten Unruh, C David James, Jann N Sarkaria, Craig Horbinski
Background: 20-30% of diffusely infiltrative gliomas in adults contain a point mutation in isocitrate dehydrogenase 1 (IDH1mut), which increases production of D-2-hydroxyglutarate (D2HG). This is so efficient that D2HG often reaches 30 mM within IDH1mut gliomas. Yet, while up to 100 µM D2HG can be detected in the circulating cerebrospinal fluid of IDH1mut glioma patients, the exposure of nonneoplastic cells within and surrounding an IDH1mut glioma to D2HG is unknown and difficult to measure directly...
April 5, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29660006/validation-of-post-operative-residual-contrast-enhancing-tumor-volume-as-an-independent-prognostic-factor-for-overall-survival-in-newly-diagnosed-glioblastoma
#20
Benjamin M Ellingson, Lauren E Abrey, Sarah J Nelson, Timothy J Kaufmann, Josep Garcia, Olivier Chinot, Frank Saran, Ryo Nishikawa, Roger Henriksson, Warren P Mason, Wolfgang Wick, Nicholas Butowski, Keith L Ligon, Elizabeth R Gerstner, Howard Colman, John de Groot, Susan Chang, Ingo Mellinghoff, Robert J Young, Brian M Alexander, Rivka Colen, Jennie W Taylor, Isabel Arrillaga-Romany, Arnav Mehta, Raymond Y Huang, Whitney B Pope, David Reardon, Tracy Batchelor, Michael Prados, Evanthia Galanis, Patrick Y Wen, Timothy F Cloughesy
Background: In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS). Methods: Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2)...
April 5, 2018: Neuro-oncology
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