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https://www.readbyqxmd.com/read/29141164/lomustine-and-bevacizumab-in-progressive-glioblastoma
#1
Wolfgang Wick, Thierry Gorlia, Martin Bendszus, Martin Taphoorn, Felix Sahm, Inga Harting, Alba A Brandes, Walter Taal, Julien Domont, Ahmed Idbaih, Mario Campone, Paul M Clement, Roger Stupp, Michel Fabbro, Emilie Le Rhun, Francois Dubois, Michael Weller, Andreas von Deimling, Vassilis Golfinopoulos, Jacoline C Bromberg, Michael Platten, Martin Klein, Martin J van den Bent
BACKGROUND: Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma. METHODS: We randomly assigned patients with progression after chemoradiation in a 2:1 ratio to receive lomustine plus bevacizumab (combination group, 288 patients) or lomustine alone (monotherapy group, 149 patients)...
November 16, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29140741/comparative-in-vitro-study-of-11-c-methionine-and-11-c-deuterodeprenyl-uptake-in-three-human-glioma-cell-lines
#2
Elena Vasilskis, Ingrid Kreimerman, Silvia Olivera, Eduardo Savio, Henry Engler
AIM: To compare the uptake of (11)C-deuterodeprenyl ((11)C-DED) and (11)C-methionine ((11)C-MET) in three human glioma cell lines and study the relationship with glial fibrillary acid protein (GFAP) and monoamine oxidase B (MAO B) expression. (11)C-DED is used in positron emission tomography imaging as a marker of astrocytosis in various central nervous system pathologies. It binds irreversibly to MAO B, a glial dimeric enzyme with increased activity in some neurological pathologies. MATERIALS AND METHODS: Binding and internalization studies of (11)C-MET and (11)C-DED were performed in astrocytoma grade III, glioblastoma grade IV, and radio-resistant glioblastoma grade IV cells...
November 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29139095/local-alkylating-chemotherapy-applied-immediately-after-5-ala-guided-resection-of-glioblastoma-does-not-provide-additional-benefit
#3
William Sage, Mathew Guilfoyle, Catriona Luney, Adam Young, Rohitashwa Sinha, Donatella Sgubin, Joseph H McAbee, Ruichong Ma, Sarah Jefferies, Rajesh Jena, Fiona Harris, Kieren Allinson, Tomasz Matys, Wendi Qian, Thomas Santarius, Stephen Price, Colin Watts
Grade IV glioma is the most common and aggressive primary brain tumour. Gross total resection with 5-aminolevulinic acid (5-ALA) guided surgery combined with local chemotherapy (carmustine wafers) is an attractive treatment strategy in these patients. No previous studies have examined the benefit carmustine wafers in a treatment programme of 5-ALA guided resection followed by a temozolomide-based chemoradiotherapy protocol. The objective of this study was to examine the benefit of carmustine wafers on survival in patients undergoing 5-ALA guided resection...
November 14, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29138945/glioblastoma-in-neurofibromatosis-1-patients-without-idh1-braf-v600e-and-tert-promoter-mutations
#4
Ichiyo Shibahara, Yukihiko Sonoda, Hiroyoshi Suzuki, Akifumi Mayama, Masayuki Kanamori, Ryuta Saito, Yasuhiro Suzuki, Shoji Mashiyama, Hiroshi Uenohara, Mika Watanabe, Toshihiro Kumabe, Teiji Tominaga
Pilocytic astrocytomas and low-grade gliomas are more common compared with glioblastomas in patients with neurofibromatosis 1 (NF1). A recent genome-wide analysis has shown frequent NF1 gene alterations in the mesenchymal subtype of a glioblastoma; however, little is known about clinicopathological features of glioblastomas in NF1 patients (NF1 glioblastomas). We analyzed four NF1 glioblastomas. Radiographical and intraoperative findings showed well-circumscribed tumors from surrounding brain. Pathological analysis presented a paucity of processes with an eosinophilic cytoplasm, bizarre nuclei, xanthomatous-like appearance, multinucleated giant cells, and histiocytoid appearance...
November 14, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/29138341/long-non-coding-rna-neat1-regulated-by-the-egfr-pathway-contributes-to-glioblastoma-progression-through-the-wnt-%C3%AE-catenin-pathway-by-scaffolding-ezh2
#5
Qun Chen, Jinquan Cai, Qixue Wang, Yunfei Wang, Mingyang Liu, Jingxuan Yang, Junhu Zhou, Chun-Sheng Kang, Min Li, Chuanlu Jiang
PURPOSE: Long noncoding RNAs have been implicated in gliomagenesis, but their mechanisms of action are mainly undocumented. Through public glioma mRNA expression datasets, we found that NEAT1 was a potential oncogene. We systematically analyzed the clinical significance and mechanism of NEAT1 in glioblastoma. EXPERIMENTAL DESIGN: Initially, we evaluated whether NEAT1 expression levels could be regulated by EGFR pathway activity. We subsequently evaluated the effect of NEAT1 on the WNT/β-Catenin pathway and its target binding gene...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29138078/is-there-an-indication-of-intraoperative-mri-in-subtotal-resection-of-glioblastoma-a-multicenter-retrospective-comparative-analysis
#6
Jan Coburger, Javier Segovia von Riehm, Oliver Ganslandt, Christian Rainer Wirtz, Mirjam Renovanz
INTRODUCTION: Surgery in patients with highly eloquent glioblastoma (GB) remains challenging. OBJECTIVE: To evaluate influence of use of iMRI on extent of resection (EoR), clinical outcome and survival in GB-patients with preoperatively intended subtotal resection (STR). METHODS: We performed a retrospective assessment in 3 neurosurgical centers(2008-2013). All patients with primary GB, unilocular growth, and adjuvant radiochemotherapy in whom a STR was intended were included...
November 11, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29138030/aspergillus-candidus-is-a-newly-recognized-source-of-sphaeropsidin-a-isolation-semi-synthetic-derivatization-and-anticancer-evaluation
#7
Yan Li, Robert Scott, Annie R Hooper, Geoffrey A Bartholomeusz, Alexander Kornienko, Gerald F Bills
This report details a search for alternative strains that produce the diterpenoid sphaeropsidin A (SphA) among A. candidus strains from the USDA Northern Regional Research Laboratories Culture Collection. We identified two strains that produced SphA using a limited set of test media. An initial scaled-up fermentation of NRRL 313 and isolation effort led to the procurement of sufficient quantities of SphA to prepare five semi-synthetic analogues (1-5) and evaluate their anticancer effects against glioblastoma cells D423 and Gli56 grown in 2D and 3D cultures...
November 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29137451/the-transcription-factor-atf5-role-in-cellular-differentiation-stress-responses-and-cancer
#8
REVIEW
Thomas K Sears, James M Angelastro
Activating transcription factor 5 (ATF5) is a cellular prosurvival transcription factor within the basic leucine zipper (bZip) family that is involved in cellular differentiation and promotes cellular adaptation to stress. Recent studies have characterized the oncogenic role of ATF5 in the development of several different types of cancer, notably glioblastoma. Preclinical assessment of a systemically deliverable dominant-negative ATF5 (dnATF5) biologic has found that targeting ATF5 results in tumor regression and tumor growth inhibition of glioblastoma xenografts in mouse models...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137258/aberrantly-activated-cox-2-and-wnt-signaling-interact-to-maintain-cancer-stem-cells-in-glioblastoma
#9
Megan Wu, Jennifer Guan, Chris Li, Simon Gunter, Labeeba Nusrat, Sheena Ng, Karan Dhand, Cindi Morshead, Albert Kim, Sunit Das
Glioblastoma recurrence after aggressive therapy typically occurs within six months, and patients inevitably succumb to their disease. Tumor recurrence is driven by a subpopulation of cancer stem cells in glioblastoma (glioblastoma stem-like cells, GSCs), which exhibit resistance to cytotoxic therapies, compared to their non-stem-cell counterparts. Here, we show that the Cox-2 and Wnt signaling pathways are aberrantly activated in GSCs and interact to maintain the cancer stem cell identity. Cox-2 stimulates GSC self-renewal and proliferation through prostaglandin E2 (PGE2), which in turn activates the Wnt signaling pathway...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136645/a-4-mirna-signature-to-predict-survival-in-glioblastomas
#10
Simon K Hermansen, Mia D Sørensen, Anker Hansen, Steen Knudsen, Alvaro G Alvarado, Justin D Lathia, Bjarne W Kristensen
Glioblastomas are among the most lethal cancers; however, recent advances in survival have increased the need for better prognostic markers. microRNAs (miRNAs) hold great prognostic potential being deregulated in glioblastomas and highly stable in stored tissue specimens. Moreover, miRNAs control multiple genes representing an additional level of gene regulation possibly more prognostically powerful than a single gene. The aim of the study was to identify a novel miRNA signature with the ability to separate patients into prognostic subgroups...
2017: PloS One
https://www.readbyqxmd.com/read/29136505/inhibition-of-trf1-telomere-protein-impairs-tumor-initiation-and-progression-in-glioblastoma-mouse-models-and-patient-derived-xenografts
#11
Leire Bejarano, Alberto J Schuhmacher, Marinela Méndez, Diego Megías, Carmen Blanco-Aparicio, Sonia Martínez, Joaquín Pastor, Massimo Squatrito, Maria A Blasco
Glioblastoma multiforme (GBM) is a deadly and common brain tumor. Poor prognosis is linked to high proliferation and cell heterogeneity, including glioma stem cells (GSCs). Telomere genes are frequently mutated. The telomere binding protein TRF1 is essential for telomere protection, and for adult and pluripotent stem cells. Here, we find TRF1 upregulation in mouse and human GBM. Brain-specific Trf1 genetic deletion in GBM mouse models inhibited GBM initiation and progression, increasing survival. Trf1 deletion increased telomeric DNA damage and reduced proliferation and stemness...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136455/lbh589-inhibits-glioblastoma-growth-and-angiogenesis-through-suppression-of-hif-1%C3%AE-expression
#12
Zhi-Gang Yao, Wen-Huan Li, Fang Hua, Hong-Xia Cheng, Miao-Qing Zhao, Xi-Chao Sun, Ye-Jun Qin, Jia-Mei Li
Glioblastoma (GBM) is an angiogenic malignancy with a highly unfavorable prognosis. Angiogenesis in GBM represents an adaptation to a hypoxic microenvironment and is correlated with tumor growth, invasion, clinical recurrence, and lethality. LBH589 (also called panobinostat) is a histone deacetylase (HDAC) inhibitor with potent antitumor activity. In the current study, we investigated the mechanism and effects of LBH589 on GBM growth and hypoxia-induced angiogenesis in vitro and in vivo. To determine the antitumor and angiogenesis activity and mechanism of LBH589, we used cell proliferations in vitro and GBM xenografts in vivo...
December 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29136334/identification-of-plasma-membrane-glycoproteins-specific-to-human-glioblastoma-multiforme-cells-using-lectin-arrays-and-lc-ms-ms
#13
YaeEun Park, Jeonghun Yeom, YoungSoo Kim, Hye Jin Lee, Ki-Cheol Han, SeungTaek Lee, Cheolju Lee, Ji Eun Lee
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant type of brain cancer and has poor prognosis with a median survival of less than one year. While the structural changes of tumor cell surface carbohydrates are known to be associated with invasive behavior of tumor cells, the cell surface glycoproteins to differentiate the low- and high-grade glioma cells can be potential diagnostic markers and therapeutic targets for GBMs. In the present study, lectin arrays consisting of eight lectins were employed to explore cell surface carbohydrate expression patterns on low-grade oligodendroglioma cells (Hs683) and GBM cells (T98G)...
November 14, 2017: Proteomics
https://www.readbyqxmd.com/read/29136244/a-molecular-cascade-modulates-map1b-and-confers-resistance-to-mtor-inhibition-in-human-glioblastoma
#14
Dan R Laks, Juan A Oses-Prieto, Alvaro G Alvarado, Jonathan Nakashima, Shreya Chand, Daniel B Azzam, Ankur A Gholkar, Jantzen Sperry, Kirsten Ludwig, Michael C Condro, Serli Nazarian, Anjelica Cardenas, Michelle Y S Shih, Robert Damoiseaux, Bryan France, Nicholas Orozco, Koppany Visnyei, Thomas J Crisman, Fuying Gao, Jorge Z Torres, Giovanni Coppola, Alma L Burlingame, Harley I Kornblum
Background: Clinical trials of therapies directed against nodes of the PI3K/AKT/mTOR signaling axis in Glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy. Methods: To determine mechanisms of resistance to chronic mTOR inhibition, we performed tandem screens on patient-derived GBM cultures. Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin and our analysis implicated a role for GSK3B attenuation in mediating resistance that was confirmed by functional studies...
November 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29135607/targeting-the-perivascular-niche-in-brain-tumors
#15
Giorgio Seano
PURPOSE OF REVIEW: Brain tumors are composed of primary tumors of the central nervous system, such us glioblastoma (GBM), and secondary metastatic tumors, such as melanoma, non-Hodgkin lymphoma as well as lung and breast cancers. Brain tumors are highly deadly, and unfortunately not many improvements have been achieved to improve the survival of patients with brain tumors. Chemoradiation resistance is one of the most clinically relevant challenges faced in patients with brain tumors. The perivascular niche is one of the most relevant microenvironment hubs in brain tumors...
November 14, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29135107/benefit-and-outcome-of-using-temozolomide-based-chemoradiotherapy-followed-by-temozolomide-alone-for-glioblastoma-in-clinical-practice
#16
Svetlana Salma, Igor Djan, Mladen Bjelan, Petar Vulekovic, Mico Novakovic, Vladimir Vidovic, Milos Lucic
PURPOSE: Temozolomide (TEM), an oral alkylating agent, has shown promising activity in the last 10 years in the treatment of glioblastoma multiforme (GBM). Our goal was to show the benefit of concomitant therapy involving 3D conformal radiotherapy and temozolomide in clinical practice. METHODS: This was a retrospective/prospective study and included a total of 113 patients with GBM diagnosis. Forty- seven patients received postoperative radiotherapy and 66 received concomitant temozolomide plus 3D conformal radiotherapy...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29135106/evidence-for-the-efficacy-of-disulfiram-and-copper-combination-in-glioblastoma-multiforme-a-propos-of-a-case
#17
Petros N Karamanakos, Dimitrios T Trafalis, Dionysios J Papachristou, Eleftheria S Panteli, Maria Papavasilopoulou, Andreas Karatzas, Dimitrios Kardamakis, Georgios Nasioulas, Marios Marselos
Glioblastoma multiforme (GBM) is the most common and aggressive malignancy of the central nervous system. Treatment usually involves a combination of surgical resection, chemotherapy, and radiotherapy, but ultimately this condition is incurable. Besides the dismal prognosis of GBM, financial factors have also presented challenges for advancing treatments. Taking into consideration the high cost of developing new anticancer drugs as well as the fact that GBM is a rare disease, thus further limiting financial incentive for drug development, it becomes obvious that there has been growing interest for repurposing candidates...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29135083/comparison-of-the-anticancer-properties-of-a-novel-valproic-acid-prodrug-to-leading-histone-deacetylase-inhibitors
#18
Nataly Tarasenko, Hanna Chekroun-Setti, Abraham Nudelman, Ada Rephaeli
The HDAC inhibitory activity of valproic acid (VPA) has led to on-going evaluation of it as an anticancer agent. The histone deacetylase (HDAC) inhibitor AN446, a prodrug of VPA, releases the acid upon metabolic degradation. AN446 is >60 fold more potent than VPA in killing cancer cells in vitro. Herein, we compare the activities of AN446, as an anticancer agent, to those of representative types from each of the four major classes of HDAC inhibitors (HDACIs): vorinostat, romidepsin, entinostat and VPA. AN446 exhibited the greatest selectivity and HDAC inhibitory activity against cancer cells...
November 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29134420/co-localization-and-interaction-of-pax5-with-iba1-in-brain-of-mice
#19
Shashank Kumar Maurya, Rajnikant Mishra
The Pax5, a B-cell-Specific Activator Protein (BSAP) and redox-sensitive transcription factor, is expressed in the immune-privileged brain, B-lymphocytes, lymph nodes and spleen. PAX5-mediated immune pathway has also been described in the progression of Glioblastoma multiforme. However, the status of Pax5 and its role in brain immunity are not yet elucidated. In silico analysis of Pax5 interacting proteins predicts its interaction with proteins of cell proliferation, differentiation of hematopoietic cells, neurogenesis and several cell signalling pathways...
November 13, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29133572/drug-repositioning-meets-precision-in-glioblastoma
#20
Wolfgang Wick, Tobias Kessler
Glioblastoma has a gigantic unmet medical need. Molecular knowledge has evolved substantially, including data on clonal selection with progression. Past trials for all-comers may have produced false negative results. Molecular precision at progression needs workup of new tissue and revisiting drugs with focus on brain tumor penetration may yield surprises.
November 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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