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https://www.readbyqxmd.com/read/28922853/a-rationale-for-targeting-extracellular-regulated-kinases-erk1-and-erk2-in-glioblastoma
#1
Ricarda Hannen, Maria Hauswald, Joerg Walter Bartsch
Glioblastoma (GBM) is the most common malignant primary brain tumor. It still carries a grim prognosis and new therapies are needed. This review summarizes the current status of mechanistic insights into the function of extracellular regulated kinase (ERK) and its potential as a therapeutic target for patients with GBM. Currently, some promising ERK inhibitors are in clinical trials in tumor entities other than GBM. Here, we provide a comprehensive overview on the functions of ERK1/2 in GBM and a rationale for treatment of GBM with ERK inhibitors...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28922847/germline-msh6-mutation-in-a-patient-with-two-independent-primary-glioblastomas
#2
Linda M Forsström, Koichiro Sumi, Markus J Mäkinen, Ji Eun Oh, Riitta Herva, Paul Kleihues, Hiroko Ohgaki, Lauri A Aaltonen
We previously reported a patient who had developed 2 glioblastomas at the age of 54 and 64 years, respectively. The first glioblastoma in the right frontal lobe was treated with surgery and radiotherapy. Ten years later, the patient developed a second, left frontal glioblastoma. Discordant patterns of TP53 and PTEN mutations suggested that the second tumor was not a recurrence but an independently developed glioblastoma. To determine the molecular mechanism underlying this enigmatic case with 10-year survival, we performed whole-exome sequencing...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28922732/physcion-8-o-%C3%AE-glucopyranosideregulates-cell-cycle-apoptosis-and-invasion-in-glioblastoma-cells-through-modulating-skp2
#3
Wen Li, Fuxia Li, Yanfang Zhu, Daqing Song
Glioblastoma multiforme (GBM) is the most common malignant glioma in the central nervous system. This study aimed to investigate the anti-tumor activity of physcion 8-O-β-glucopyranoside (PG) in GBM cells. This showed that PG could significantly block cell cycle progression, induce apoptosis, and suppress invasion in both model GBM cell lines (U87 and U251). At the molecular level, PG repressed the expression of S-phase kinase protein 2 (Skp2), which was responsible for the anti-tumor effect of PG in GBM cells...
September 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922698/survival-improvements-with-adjuvant-therapy-in-patients-with-glioblastoma
#4
Dasantha Jayamanne, Helen Wheeler, Raymond Cook, Charles Teo, David Brazier, Geoff Schembri, Marina Kastelan, Linxin Guo, Michael F Back
BACKGROUND: Evaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) protocol. METHODS: All patients with GBM managed between May 2007 and December 2014 with EORTC-NCIC protocol were entered into a prospective database...
September 18, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28922334/common-malignant-brain-tumors-can-18f-fdg-pet-ct-aid-in-differentiation
#5
Nilendu C Purandare, Ameya Puranik, Sneha Shah, Archi Agrawal, Tejpal Gupta, Aliasgar Moiyadi, Prakash Shetty, Epari Shridhar, Rakesh Jalali, Venkatesh Rangarajan
OBJECTIVES: The objectives of this study were to evalute the metabolic characteristics of common malignant space-occupying lesions (SOL) of the brain and to determine the utility of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in differentiating between the common types of malignant brain SOL. PATIENTS AND METHODS: All patients with brain SOL who were referred for an F-FDG PET/CT scan by a multidisciplinary team were included in this retrospective study. The metabolic characteristics of the brain lesions in the form of maximum standardized uptake value (SUVmax) along with tumor-to-background activity ratios were determined and differences were compared using nonparametric statistical tests...
September 15, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28921714/fetal-microchimerism-in-human-brain-tumors
#6
Lauren Broestl, Joshua B Rubin, Sonika Dahiya
Sex differences in cancer incidence and survival, including central nervous system tumors, are well documented. Multiple mechanisms contribute to sex differences in health and disease. Recently, the presence of fetal-in-maternal microchimeric cells has been shown to have prognostic significance in breast and colorectal cancers. The frequency and potential role of these cells has not been investigated in brain tumors. We therefore selected two common primary adult brain tumors for this purpose: meningioma, which is sex hormone responsive and has a higher incidence in women, and glioblastoma, which is sex hormone independent and occurs more commonly in men...
September 18, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28921565/the-impact-of-p-glycoprotein-and-breast-cancer-resistance-protein-on-the-brain-pharmacokinetics-and-pharmacodynamics-of-a-panel-of-mek-inhibitors
#7
Mark C de Gooijer, Ping Zhang, Ruud Weijer, Levi C M Buil, Jos H Beijnen, Olaf van Tellingen
Mitogen/extracellular signal-regulated kinase (MEK) inhibitors have been tested in clinical trials for treatment of intracranial neoplasms, including glioblastoma (GBM), but efficacy of these drugs has not yet been demonstrated. The blood-brain barrier (BBB) is a major impediment to adequate delivery of drugs into the brain and may thereby also limit the successful implementation of MEK inhibitors against intracranial malignancies. The BBB is equipped with a range of ATP-dependent efflux transport proteins, of which P-gp (ABCB1) and BCRP (ABCG2) are the two most dominant for drug efflux from the brain...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28919997/increased-infiltration-and-tolerised-antigen-specific-cd8-tem-cells-in-tumor-but-not-peripheral-blood-have-no-impact-on-survival-of-hcmv-glioblastoma-patients
#8
M Bahador, A Gras Navarro, M A Rahman, M Dominguez-Valentin, S Sarowar, E Ulvestad, G Njølstad, S A Lie, E K Kristoffersen, E Bratland, M Chekenya
Human cytomegalovirus (HCMV) antigens in glioblastoma (GBM) present opportunities for personalised immunotherapy. However, their presence in GBM tissue is still under debate, and evidence of their impact on functional immune responses and prognosis is sparse. Here, we investigated the presence of pp65 (UL83) and immediate early 1 (IE-1) HCMV antigens in a cohort of Norwegian GBM patients (n = 177), using qPCR, immunohistochemistry, and serology. HCMV status was then used to investigate whether viral antigens influenced immune cell phenotype, infiltration, activation and patient survival...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919992/molecular-and-clinical-characterization-of-tim-3-in-glioma-through-1-024-samples
#9
Guanzhang Li, Zheng Wang, Chuanbao Zhang, Xing Liu, Jinquan Cai, Zhiliang Wang, Huimin Hu, Fan Wu, Zhaoshi Bao, Yanwei Liu, Liang Zhao, Tingyu Liang, Fan Yang, Ruoyu Huang, Wei Zhang, Tao Jiang
Background: Researches on immunotherapy of glioma has been increasing exponentially in recent years. However, autoimmune-like side effects of current immune checkpoint blockade hindered the clinical application of immunotherapy in glioma. The discovery of the TIM-3, a tumor-specific immune checkpoint, has shed a new light on solution of this dilemma. We aimed at investigating the role of TIM-3 at transcriptome level and its relationship with clinical practice in glioma. Methods: A cohort of 325 glioma patients with RNA-seq data from Chinese Glioma Genome Atlas (CGGA project) was analyzed, and the results were well validated in TCGA RNA-seq data of 699 gliomas...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919569/spontaneous-hemorrhagic-glioblastoma-revealed-by-arterial-spin-labeling
#10
Sarah Fadili, Bruno Law Ye, Nadya Pyatigorskaya
We report a case of a haemorrhagic tumor early detected by pseudo-continuous arterial spin labeling sequence (pCASL) in the case where conventional MRI sequences where not contributive.
September 14, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28918420/computer-analysis-of-glioma-transcriptome-profiling-alternative-splicing-events
#11
Vladimir N Babenko, Natalya V Gubanova, Anatoly O Bragin, Irina V Chadaeva, Gennady V Vasiliev, Irina V Medvedeva, Alexey S Gaytan, Alexey L Krivoshapkin, Yuriy L Orlov
Here we present the analysis of alternative splicing events on an example of glioblastoma cell culture samples using a set of computer tools in combination with database integration. The gene expression profiles of glioblastoma were obtained from cell culture samples of primary glioblastoma which were isolated and processed for RNA extraction. Transcriptome profiling of normal brain samples and glioblastoma were done by Illumina sequencing. The significant differentially expressed exon-level probes and their corresponding genes were identified using a combination of the splicing index method...
September 18, 2017: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28918367/25-hydroxycholesterol-and-inflammation-in-lovastatin-deregulated-mevalonate-pathway
#12
Paola Maura Tricarico, Rossella Gratton, Luca Braga, Fulvio Celsi, Sergio Crovella
Mevalonate pathway deregulation has been observed in several diseases, including Mevalonate kinase deficiency (MKD). MKD is a hereditary auto-inflammatory disorder, due to mutations at mevalonate kinase gene (MVK), encoding mevalonate kinase (MK) enzyme. MVK mutations have been reported as associated with impairment of mevalonate pathway with consequent decrease of protein prenylation levels, defective autophagy and increase of IL-1β secretion, followed by cell death. Since 25-hydroxycholesterol (25-HC), a metabolite of cholesterol, can suppress IL-1β production, thus reducing inflammation, we evaluated the effect of 25-HC in an in vitro model of mevalonate pathway alteration, obtained using Lovastatin...
September 13, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28918048/mir-133a-promotes-trail-resistance-in-glioblastoma-via-suppressing-death-receptor-5-and-activating-nf-%C3%AE%C2%BAb-signaling
#13
Shan-Shan Wang, Lu Feng, Bao-Guang Hu, Ying-Fei Lu, Wei-Mao Wang, Wei Guo, Chun-Wai Suen, Bao-Hua Jiao, Jian-Xin Pang, Wei-Ming Fu, Jin-Fang Zhang
Recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), as a novel cancer therapeutic, is being tested in phase II and III clinical trials; however, TRAIL resistance remains a big obstacle preventing its clinical application. Considering that TRAIL-induced apoptosis through death receptors DR4 and DR5, their activation may be an alternative pathway to suppress TRAIL resistance. In this study, a negative correlation between DR5 expression and TRAIL resistance was observed, and miR-133a was predicted to be the most promising candidate to suppress DR5 expression...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917183/visualisation-of-an-nspef-induced-calcium-wave-using-the-genetically-encoded-calcium-indicator-gcamp-in-u87-human-glioblastoma-cells
#14
Lynn Carr, Sylvia M Bardet, Delia Arnaud-Cormos, Philippe Leveque, Rodney P O'Connor
Cytosolic, synthetic chemical calcium indicators are typically used to visualise the rapid increase in intracellular calcium ion concentration that follows nanosecond pulsed electric field (nsPEF) application. This study looks at the application of genetically encoded calcium indicators (GECIs) to investigate the spatiotemporal nature of nsPEF-induced calcium signals using fluorescent live cell imaging. Calcium responses to 44kV/cm, 10ns pulses were observed in U87-MG cells expressing either a plasma membrane targeted GECI (GCaMP5-G), or one cytosolically expressed (GCaMP6-S), and compared to the response of cells loaded with cytosolic or plasma membrane targeted chemical calcium indicators...
September 8, 2017: Bioelectrochemistry
https://www.readbyqxmd.com/read/28916747/hormetic-potential-of-methylglyoxal-a-side-product-of-glycolysis-in-switching-tumours-from-growth-to-death
#15
Marie-Julie Nokin, Florence Durieux, Justine Bellier, Olivier Peulen, Koji Uchida, David A Spiegel, James R Cochrane, Craig A Hutton, Vincent Castronovo, Akeila Bellahcène
Metabolic reprogramming toward aerobic glycolysis unavoidably favours methylglyoxal (MG) and advanced glycation end products (AGEs) formation in cancer cells. MG was initially considered a highly cytotoxic molecule with potential anti-cancer value. However, we have recently demonstrated that MG enhanced tumour growth and metastasis. In an attempt to understand this dual role, we explored MG-mediated dicarbonyl stress status in four breast and glioblastoma cancer cell lines in relation with their glycolytic phenotype and MG detoxifying capacity...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916736/silencing-of-urothelial-carcinoma-associated-1-inhibits-the-proliferation-and-migration-of-medulloblastoma-cells
#16
Xie Zhengyuan, Xiao Hu, Wang Qiang, Li Nanxiang, Cai Junbin, Zhang Wangming
BACKGROUND UCA1 is a long non-coding RNA that has been found to be aberrantly upregulated in various cancers. The aim of this study was to determine the expression level and function of UCA1 in medulloblastoma, the most common malignant brain tumor during childhood. MATERIAL AND METHODS Real-time PCR was used to detect the expression of UCA1 in medulloblastoma specimens and cell lines. Lentiviral-mediated expression of a short hairpin RNA (shRNA) targeting UCA1 or a negative control shRNA was also achieved with the medulloblastoma cell line, Daoy...
September 16, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28916645/correction-zika-virus-has-oncolytic-activity-against-glioblastoma-stem-cells
#17
Zhe Zhu, Matthew J Gorman, Lisa D McKenzie, Jiani N Chai, Christopher G Hubert, Briana C Prager, Estefania Fernandez, Justin M Richner, Rong Zhang, Chao Shan, Eric Tycksen, Xiuxing Wang, Pei-Yong Shi, Michael S Diamond, Jeremy N Rich, Milan G Chheda
No abstract text is available yet for this article.
September 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28916588/glioblastoma-stem-cell-clonal-dynamics-drive-intratumor-heterogeneity
#18
(no author information available yet)
GBM heterogeneity is primarily driven by the stochastic outcome of GBM stem cell hierarchical growth.
September 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28916189/phosphoinositide-5-phosphatase-activities-control-cell-motility-in-glioblastoma-two-phosphoinositides-pi-4-5-p2-and-pi-3-4-p2-are-involved
#19
REVIEW
Ana Raquel Ramos, William's Elong Edimo, Christophe Erneux
Inositol polyphosphate 5-phosphatases or phosphoinositide 5-phosphatases (PI 5-phosphatases) are enzymes that can act on soluble inositol phosphates and/or phosphoinositides (PIs). Several PI 5-phosphatases have been linked to human genetic diseases, in particular the Lowe protein or OCRL which is mutated in the Lowe syndrome. There are 10 different members of this family and 9 of them can use PIs as substrate. One of these substrates, PI(3,4,5)P3 binds to specific PH domains and recruits as effectors specific proteins to signaling complexes...
September 5, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28915860/anatomic-mapping-of-molecular-subtypes-in-diffuse-glioma
#20
Qisheng Tang, Yuxi Lian, Jinhua Yu, Yuanyuan Wang, Zhifeng Shi, Liang Chen
BACKGROUND: Tumor location served as an important prognostic factor in glioma patients was considered to postulate molecular features according to cell origin theory. However, anatomic distribution of unique molecular subtypes was not widely investigated. The relationship between molecular phenotype and histological subgroup were also vague based on tumor location. Our group focuses on the study of glioma anatomic location of distinctive molecular subgroups and histology subtypes, and explores the possibility of their consistency based on clinical background...
September 15, 2017: BMC Neurology
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