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https://www.readbyqxmd.com/read/28092823/ph-lactate-and-hypoxia-reciprocity-in-regulating-high-affinity-monocarboxylate-transporter-expression-in-glioblastoma
#1
James P Caruso, Brandon J Koch, Philip D Benson, Elsa Varughese, Michael D Monterey, Amy E Lee, Ajal M Dave, Sam Kiousis, Andrew E Sloan, Saroj P Mathupala
Highly malignant brain tumors harbor the aberrant propensity for aerobic glycolysis, the excessive conversion of glucose to lactic acid even in the presence of ample tissue oxygen. Lactic acid is rapidly effluxed to the tumor microenvironment via a group of plasma-membrane transporters denoted monocarboxylate transporters (MCTs) to prevent "self-poisoning." One isoform, MCT2, has the highest affinity for lactate and thus should have the ability to respond to microenvironment conditions such as hypoxia, lactate, and pH to help maintain high glycolytic flux in the tumor...
January 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28091986/shift-of-microrna-profile-upon-glioma-cell-migration-using-patient-derived-spheroids-and-serum-free-conditions
#2
Sune Munthe, Bo Halle, Henning B Boldt, Helle Christiansen, Steffen Schmidt, Vivek Kaimal, Jessica Xu, Sonya Zabludoff, Jan Mollenhauer, Frantz R Poulsen, Bjarne W Kristensen
Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions...
January 13, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28089910/glioblastoma-cancer-stem-cells-evade-innate-immune-suppression-of-self-renewal-through-reduced-tlr4-expression
#3
Alvaro G Alvarado, Praveena S Thiagarajan, Erin E Mulkearns-Hubert, Daniel J Silver, James S Hale, Tyler J Alban, Soumya M Turaga, Awad Jarrar, Ofer Reizes, Michelle S Longworth, Michael A Vogelbaum, Justin D Lathia
Tumors contain hostile inflammatory signals generated by aberrant proliferation, necrosis, and hypoxia. These signals are sensed and acted upon acutely by the Toll-like receptors (TLRs) to halt proliferation and activate an immune response. Despite the presence of TLR ligands within the microenvironment, tumors progress, and the mechanisms that permit this growth remain largely unknown. We report that self-renewing cancer stem cells (CSCs) in glioblastoma have low TLR4 expression that allows them to survive by disregarding inflammatory signals...
December 27, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/28089821/the-role-of-stat3-in-glioblastoma-progression-through-dual-influences-on-tumor-cells-and-the-immune-microenvironment
#4
Nakho Chang, Sun Hee Ahn, Doo-Sik Kong, Hye Won Lee, Do-Hyun Nam
Glioblastoma multiforme (GBM) is the most aggressive form of cancer that begins within the brain; generally, the patient has a dismal prognosis and limited therapeutic options. Signal transducer and activator of transcription 3 (STAT3) is a critical mediator of tumorigenesis, tumor progression, and suppression of anti-tumor immunity in GBM. In a high percentage of GBM cells and tumor microenvironments, persistent activation of STAT3 induces cell proliferation, anti-apoptosis, glioma stem cell maintenance, tumor invasion, angiogenesis, and immune evasion...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28089804/multicentric-spinal-cord-glioblastoma
#5
Eibar Ernesto Cabrera-Aldana, Rafael De la Garza Ramos, Raúl Pichardo-Bahena
No abstract text is available yet for this article.
January 12, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28089418/distant-spread-of-a-supratentorial-glioblastoma-to-the-spinal-cord
#6
Krishnan Ravindran, Frank Gaillard, Arian Lasocki
Extracranial spread from a glioblastoma is rare. We present a case of a 48year-old man with a previously radiologically-stable left temporal lobe glioblastoma presenting with symptoms referrable to the spinal cord. MRI revealed a spinal cord lesion, with the differential including transverse myelitis and tumour. Open surgical biopsy revealed high-grade astrocytoma. Genetic analysis of both the supratentorial and spinal tumours revealed R132H IDH1 mutations, providing evidence that the spinal cord lesion had spread from the supratentorial tumour...
January 12, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28088078/genetically-tailored-magnetosomes-used-as-mri-probe-for-molecular-imaging-of-brain-tumor
#7
M Boucher, F Geffroy, S Prévéral, L Bellanger, E Selingue, G Adryanczyk-Perrier, M Péan, C T Lefèvre, D Pignol, N Ginet, S Mériaux
We investigate here the potential of single step production of genetically engineered magnetosomes, bacterial biogenic iron-oxide nanoparticles embedded in a lipid vesicle, as a new tailorable magnetic resonance molecular imaging probe. We demonstrate in vitro the specific binding and the significant internalization into U87 cells of magnetosomes decorated with RGD peptide. After injection at the tail vein of glioblastoma-bearing mice, we evidence in the first 2 h the rapid accumulation of both unlabeled and functionalized magnetosomes inside the tumor by Enhanced Permeability and Retention effects...
December 19, 2016: Biomaterials
https://www.readbyqxmd.com/read/28087981/humanized-chondroitinase-abc-sensitizes-glioblastoma-cells-to-temozolomide
#8
Alena Cristina Jaime-Ramirez, Nina Dmitrieva, Ji Young Yoo, Yeshavanth Banasavadi-Siddegowda, Jianying Zhang, Theresa Relation, Chelsea Bolyard-Blessing, Jeffrey Wojton, Balveen Kaur
INTRODUCTION: Malignant gliomas (GBMs) are extremely aggressive and have a median survival of approximately 15 months. Current treatment modalities, which include surgical resection, radiation and chemotherapy, have done little to prolong the lives of GBM patients. Chondroitin sulfate proteoglycans (CSPG) are critical for cell-cell and cell-extra cellular matrix (ECM) interactions and are implicated in glioma growth and invasion. Chondroitinase (Chase) ABC is a bacterial enzyme that cleaves chondroitin sulfate disaccharide chains from CSPGs in the tumor ECM...
January 14, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28087597/membrane-depolarizing-channel-blockers-induce-selective-glioma-cell-death-by-impairing-nutrient-transport-and-unfolded-protein-amino-acid-responses
#9
Mia Niklasson, Gianluca Maddalo, Zuzana Sramkova, Ercan Mutlu, Shimei Wee, Petra Sekyrova, Linnéa Schmidt, Nicolas Fritz, Ivar Dehnisch, Gregorios Kyriatzis, Michaela Krafcikova, Brittany B Carson, Jennifer Feenstra, Voichita D Marinescu, Anna Segerman, Martin Haraldsson, Anna-Lena Gustavsson, Lars Gj Hammarström, Annika Jenmalm-Jensen, Lene Uhrbom, A F Maarten Altelaar, Sten Linnarsson, Per Uhlén, Lukas Trantirek, C Theresa Vincent, Sven Nelander, Per Øyvind Enger, Michael Andäng
Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown...
January 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28081256/inhibition-of-acetyl-coa-carboxylase-1-acc1-and-2-acc2-reduces-proliferation-and-de-novo-lipogenesis-of-egfrviii-human-glioblastoma-cells
#10
Jessica E C Jones, William P Esler, Rushi Patel, Adhiraj Lanba, Nicholas B Vera, Jeffrey A Pfefferkorn, Cecile Vernochet
Tumor cell proliferation and migration processes are regulated by multiple metabolic pathways including glycolysis and de novo lipogenesis. Since acetyl-CoA carboxylase (ACC) is at the junction of lipids synthesis and oxidative metabolic pathways, we investigated whether use of a dual ACC inhibitor would provide a potential therapy against certain lipogenic cancers. The impact of dual ACC1/ACC2 inhibition was investigated using a dual ACC1/ACC2 inhibitor as well as dual siRNA knock down on the cellular viability and metabolism of two glioblastoma multiform cancer cell lines, U87 and a more aggressive form, U87 EGFRvIII...
2017: PloS One
https://www.readbyqxmd.com/read/28081224/resveratrol-impairs-glioma-stem-cells-proliferation-and-motility-by-modulating-the-wnt-signaling-pathway
#11
Chiara Cilibrasi, Gabriele Riva, Gabriele Romano, Massimiliano Cadamuro, Riccardo Bazzoni, Valentina Butta, Laura Paoletta, Leda Dalprà, Mario Strazzabosco, Marialuisa Lavitrano, Roberto Giovannoni, Angela Bentivegna
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12-15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits...
2017: PloS One
https://www.readbyqxmd.com/read/28079712/a-comprehensive-review-of-genomics-and-noncoding-rna-in-gliomas
#12
Ahmed Hassan, Jennifer Mosley, Sanjay Singh, Pascal Olivier Zinn
Glioblastoma (GBM) is the most malignant primary adult brain tumor. In spite of our greater understanding of the biology of GBMs, clinical outcome of GBM patients remains poor, as their median survival with best available treatment is 12 to 18 months. Recent efforts of The Cancer Genome Atlas (TCGA) have subgrouped patients into 4 molecular/transcriptional subgroups: proneural, neural, classical, and mesenchymal. Continuing efforts are underway to provide a comprehensive map of the heterogeneous makeup of GBM to include noncoding transcripts, genetic mutations, and their associations to clinical outcome...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28079711/cell-signaling-pathways-in-brain-tumors
#13
Rebecca A Harrison, John F de Groot
Primary brain tumors, particularly glioblastoma, are associated with significant morbidity and are often recalcitrant to standard therapies. In recent years, brain tumors have been the focus of large-scale genomic sequencing efforts, providing unprecedented insight into the genomic aberrations and cellular signaling mechanisms that drive these cancers. Discoveries from these efforts have translated into novel diagnostic algorithms, biomarkers, and therapeutic strategies in Neuro-Oncology. However, the cellular mechanisms that drive brain tumors are heterogeneous and complex: applying this new knowledge to improve patient outcomes remains a challenge...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28079702/radiomic-analysis-reveals-prognostic-information-in-t1-weighted-baseline-magnetic-resonance-imaging-in-patients-with-glioblastoma
#14
Michael Ingrisch, Moritz Jörg Schneider, Dominik Nörenberg, Giovanna Negrao de Figueiredo, Klaus Maier-Hein, Bogdana Suchorska, Ulrich Schüller, Nathalie Albert, Hartmut Brückmann, Maximilian Reiser, Jörg-Christian Tonn, Birgit Ertl-Wagner
OBJECTIVES: The aim of this study was to investigate whether radiomic analysis with random survival forests (RSFs) can predict overall survival from T1-weighted contrast-enhanced baseline magnetic resonance imaging (MRI) scans in a cohort of glioblastoma multiforme (GBM) patients with uniform treatment. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board and informed consent was waived. The MRI scans from 66 patients with newly diagnosed GBM from a previous prospective study were analyzed...
January 9, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28079349/interleukin-13-receptor-alpha-2-as-a-marker-of-poorer-prognosis-in-high-grade-astrocytomas
#15
Masahiko Wanibuchi, Yuko Kataoka-Sasaki, Masanori Sasaki, Shinichi Oka, Yayoi Otsuka, Miki Yamaguchi, Hirofumi Ohnishi, Shunya Ohtaki, Shouhei Noshiro, Satoshi Ookawa, Takeshi Mikami, Nobuhiro Mikuni, Osamu Honmou
BACKGROUND: Interleukin-13 receptor alpha 2 (IL13Rα2) is considered a prognostic marker for gliomas according to the World Health Organization (WHO) grade. However, the expression levels of the marker vary from case to case, even within the same grade. We investigated whether IL13Rα2 could serve as a predictor of poorer prognosis in gliomas. METHODS: mRNA expression of IL13Rα2 was measured using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 52 formalin-fixed paraffin-embedded glioma samples (4 pilocytic astrocytomas, 9 diffuse astrocytomas, 12 anaplastic astrocytomas, and 27 glioblastomas, grade IV)...
January 12, 2017: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/28078795/a-continuous-infusion-dynamic-mri-model-at-3-0-tesla-for-the-serial-quantitative-evaluation-of-microvascular-proliferation-in-an-animal-model-of-glioblastoma-multiforme
#16
Hunter R Underhill
PURPOSE: To develop a continuous-infusion dynamic MRI technique to characterize tumor-associated microvascular proliferation (MVP) in a rat brain model of glioblastoma multiforme. METHODS: The proposed model assumes effects due to tumor-associated MVP (eg, vascular permeability, K(trans) ; intravascular plasma fraction, vp ) cannot be individually separated and solves for a single parameter (k(vasc) ) that quantifies the T1 -weighted contrast enhancement from dynamic images acquired during continuous contrast agent (CA) infusion...
January 12, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28078681/synthesis-and-stability-studies-of-ga-67-labeled-phosphonium-salts
#17
Mingyue Kardashinsky, Nigel Lengkeek, Louis M Rendina
Delocalized lipophilic cations such as tri- and tetra-arylphosphonium are able to diffuse across the mitochondrial membrane, which allows them to selectively accumulate in cells with a high transmembrane potential (ΔΨm ). The mitochondrial membrane potential of cancer cells and cardiomyocytes has been reported to be significantly higher than that of normal epithelial cells. This feature can be exploited for the selective accumulation of phosphonium derivatives for the purposes of molecular imaging using radionuclides...
January 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28078484/the-effect-of-surface-charges-on-the-cellular-uptake-of-liposomes-investigated-by-live-cell-imaging
#18
Ji Hee Kang, Woo Young Jang, Young Tag Ko
PURPOSE: Liposomes have been developed as versatile nanocarriers for various pharmacological agents. The effect of surface charges on the cellular uptake of the liposomes has been studied by various methods using mainly fixed cells with inevitable limitations. Live cell imaging has been proposed as an alternative methods to overcome the limitations of the fixed cell-based analysis. In this study, we aimed to investigate the effects of surface charges on cellular association and internalization of the liposomes using live cell imaging...
January 11, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28076842/systemically-identifying-and-prioritizing-risk-lncrnas-through-integration-of-pan-cancer-phenotype-associations
#19
Chaohan Xu, Rui Qi, Yanyan Ping, Jie Li, Hongying Zhao, Li Wang, Michael Yifei Du, Yun Xiao, Xia Li
LncRNAs have emerged as a major class of regulatory molecules involved in normal cellular physiology and disease, our knowledge of lncRNAs is very limited and it has become a major research challenge in discovering novel disease-related lncRNAs in cancers. Based on the assumption that diverse diseases with similar phenotype associations show similar molecular mechanisms, we presented a pan-cancer network-based prioritization approach to systematically identify disease-specific risk lncRNAs by integrating disease phenotype associations...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28076826/identification-of-new-pyrrolo-2-3-d-pyrimidines-as-src-tyrosine-kinase-inhibitors-in%C3%A2-vitro-active-against-glioblastoma
#20
Francesca Musumeci, Anna Lucia Fallacara, Chiara Brullo, Giancarlo Grossi, Lorenzo Botta, Pierpaolo Calandro, Mario Chiariello, Miroslava Kissova, Emmanuele Crespan, Giovanni Maga, Silvia Schenone
In the last few years, several pyrrolo-pyrimidine derivatives have been either approved by the US FDA and in other countries for the treatment of different diseases or are currently in phase I/II clinical trials. Herein we present the synthesis and the characterization of a novel series of pyrrolo[2,3-d]pyrimidines, compounds 8a-j, and their activity against Glioblastoma multiforme (GBM). Docking studies and MM-GBSA analysis revealed the ability of such compounds to efficiently interact with the ATP binding site of Src...
December 19, 2016: European Journal of Medicinal Chemistry
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