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https://www.readbyqxmd.com/read/27935819/a-novel-brain-tumour-model-in-zebrafish-reveals-the-role-of-yap-activation-in-mapk-pi3k-induced-malignant-growth
#1
Marie Mayrhofer, Victor Gourain, Markus Reischl, Pierre Affaticati, Arnim Jenett, Jean-Stephane Joly, Matteo Benelli, Francesca Demichelis, Pietro Luigi Poliani, Dirk Sieger, Marina Mione
Somatic mutations activating MAPK/PI3K signalling play a pivotal role in both tumours and brain developmental disorders. We developed a zebrafish model of brain tumour based on somatic expression of oncogenes that activate MAPK/PI3K signalling in neural progenitor cells. HRAS(V12) was the most effective in inducing both heterotopia and invasive tumours. Tumours, but not heterotopias, require persistent activation of phospho‑(p)ERK and express a gene signature similar to the mesenchymal glioblastoma subtype, with a strong YAP component...
November 24, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27935360/the-effect-of-postoperative-infection-on-survival-in-patients-with-glioblastoma
#2
Yi-Ren Chen, Beatrice Ugiliweneza, Eric Burton, Shiao Y Woo, Maxwell Boakye, Stephen Skirboll
OBJECTIVE Glioblastoma is a primary glial neoplasm with a median survival of approximately 1 year. There are anecdotal reports that postoperative infection may confer a survival advantage in patients with glioblastoma. However, only a few case reports in the literature, along with 2 retrospective cohort studies, show some potential link between infection and prolonged survival in patients with glioblastoma. The objective of this study was to evaluate the effect of postoperative infection in patients with glioblastoma using a large national database...
December 9, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27934912/bix01294-an-inhibitor-of-histone-methyltransferase-induces-autophagy-dependent-differentiation-of-glioma-stem-like-cells
#3
Iwona Anna Ciechomska, Piotr Przanowski, Judyta Jackl, Bartosz Wojtas, Bozena Kaminska
Glioblastoma (GBM) contains rare glioma stem-like cells (GSCs) with capacities of self-renewal, multi-lineage differentiation, and resistance to conventional therapy. Drug-induced differentiation of GSCs is recognized as a promising approach of anti-glioma therapy. Accumulating evidence suggests that unique properties of stem cells depend on autophagy. Here we demonstrate that BIX01294, an inhibitor of a G9a histone methyltransferase (introducing H3K9me2 and H3K27me3 repressive marks) triggers autophagy in human glioma cells...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27934135/cancer-cell-hyperactivity-and-membrane-dipolarity-monitoring-via-raman-mapping-of-interfaced-graphene-toward-non-invasive-cancer-diagnostics
#4
Bijentimala Keisham, Arron Cole, Phong Nguyen, Ankit Mehta, Vikas Berry
Ultrasensitive detection, mapping, and monitoring of the activity of cancer cells is critical for treatment evaluation and patient care. Here, we demonstrate that a cancer cell's glycolysis-induced hyperactivity and enhanced electronegative membrane (from sialic acid) can sensitively modify the second-order overtone of in-plane phonon vibration energies (2D) of interfaced graphene via a hole-doping mechanism. By leveraging ultrathin graphene's high quantum capacitance and responsive phononics, we sensitively differentiated the activity of interfaced Glioblastoma Multiforme (GBM) cells, a malignant brain tumor, from that of human astrocytes at a single-cell resolution...
December 7, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27932754/-overexpression-of-lentivirus-rfx1-and-its-inhibitory-effect-on-proliferation-of-glioblastoma-cells
#5
Kai Cheng, Haojie Sun, Mingzhi Zhang, Li Shen
To construct overexpression lentivirus vector for human regulatory factor X1 (RFX1) gene, and to explore its effect on proliferation of F98 cell line.
 Methods: Huamn RFX1 gene was amplified by polymerase reaction. Gene amplification products were inserted into lentivirus vector pITA, and the lentivirus vector pITA-RFX1 was constructed. The constructed vector was verified by agarose gel electrophoresis and DNA sequencing. Lentivirus vector pITA-RFX1 and virus packaging plasmids were cotransfected into 293T cells, and then transfected into F98 cells...
November 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/27932505/diagnostic-accuracy-of-t1-weighted-dynamic-contrast-enhanced-mri-and-dwi-adc-for-differentiation-of-glioblastoma-and-primary-cns-lymphoma
#6
X Lin, M Lee, O Buck, K M Woo, Z Zhang, V Hatzoglou, A Omuro, J Arevalo-Perez, A A Thomas, J Huse, K Peck, A I Holodny, R J Young
BACKGROUND AND PURPOSE: Glioblastoma and primary CNS lymphoma dictate different neurosurgical strategies; it is critical to distinguish them preoperatively. However, current imaging modalities do not effectively differentiate them. We aimed to examine the use of DWI and T1-weighted dynamic contrast-enhanced-MR imaging as potential discriminative tools. MATERIALS AND METHODS: We retrospectively reviewed 18 patients with primary CNS lymphoma and 36 matched patients with glioblastoma with pretreatment DWI and dynamic contrast-enhanced-MR imaging...
December 8, 2016: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/27932423/integrated-genomic-analysis-of-survival-outliers-in-glioblastoma
#7
Sen Peng, Harshil Dhurv, Brock Armstrong, Bodour Salhia, Christophe Legendre, Jeffrey Kiefer, Julianna Parks, Selene Virk, Andrew E Sloan, Quinn T Ostrom, Jill S Barnholtz-Sloan, Nhan L Tran, Michael E Berens
BACKGROUND: To elucidate molecular features associated with disproportionate survival of glioblastoma (GB) patients, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide); "GB outliers" were identified: long-term survivor of 33 months (LTS; n = 8) versus short-term survivor of 7 months (STS; n = 10). METHODS: We implemented exome, RNA, whole genome sequencing, and DNA methylation for collection of deep genomic data from STS and LTS GB patients...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27932422/significance-of-low-mtorc1-activity-in-defining-the-characteristics-of-brain-tumor-stem-cells
#8
Yi-Peng Han, Atsushi Enomoto, Yukihiro Shiraki, Shen-Qi Wang, Xiaoze Wang, Shinya Toyokuni, Naoya Asai, Kaori Ushida, Hosne Ara, Fumiharu Ohka, Toshihiko Wakabayashi, Jie Ma, Atsushi Natsume, Masahide Takahashi
BACKGROUND: The significance of mammalian target of rapamycin complex 1 (mTORC1) activity in the maintenance of cancer stem cells (CSCs) remains controversial. Previous findings showed that mTORC1 activation depleted the population of leukemia stem cells in leukemia, while maintaining the stemness in pancreatic CSCs. The purpose of this study was to examine the currently unknown role and significance of mTORC1 activity in brain tumor stem cells (BTSCs). METHODS: Basal mTORC1 activity and its kinetics were investigated in BTSC clones isolated from patients with glioblastoma and their differentiated progenies (DIFFs)...
December 8, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27930300/an-nad-dependent-transcriptional-program-governs-self-renewal-and-radiation-resistance-in-glioblastoma
#9
Amit D Gujar, Son Le, Diane D Mao, David Y A Dadey, Alice Turski, Yo Sasaki, Diane Aum, Jingqin Luo, Sonika Dahiya, Liya Yuan, Keith M Rich, Jeffrey Milbrandt, Dennis E Hallahan, Hiroko Yano, David D Tran, Albert H Kim
Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD(+)). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD(+) synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27930095/multi-omics-data-integration-and-mapping-of-altered-kinases-to-pathways-reveal-gonadotropin-hormone-signaling-in-glioblastoma
#10
Savita Jayaram, Manoj Kumar Gupta, Rajesh Raju, Poonam Gautam, Ravi Sirdeshmukh
Glioblastoma multiforme (GBM) is one of the most lethal brain tumors with an inadequately understood pathophysiology. Biomarkers that guide accurate diagnosis and treatment decisions would greatly support precision medicine for GBM. Previous studies of GBM have focused on signaling pathways such as epidermal growth factor receptor (EGFR), platelet-derived growth factor receptors (PDGFRs), notch, wnt, and others, identified with single omics technology platforms (genomics, transcriptomics, or proteomics), but not with their integrated use...
December 2016: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/27929413/exosome-proteome-of-u-87mg-glioblastoma-cells
#11
Sohyun Chun, Seunghyun Ahn, Chang-Hwan Yeom, Seyeon Park
Exosomes are small membrane vesicles between 30 and 100 nm in diameter secreted by many cell types, and are associated with a wide range of physiological and/or pathological processes. Exosomes containing proteins, lipids, mRNA, and microRNA contribute to cell-to-cell communication and cell-to-environment regulation, however, their biological functions are not yet fully understood. In this report, exosomes in the glioblastoma cell line, U-87MG, were isolated and the proteome was investigated. In addition, exosome proteome changes in U-87MG cells exposed to a low temperature were investigated to elucidate whether the exosome proteome could respond to an external stimulus...
December 6, 2016: Biology
https://www.readbyqxmd.com/read/27927130/p311-accelerates-skin-wound-reepithelialization-by-promoting-epidermal-stem-cell-migration-through-rho-a-and-rac1-activation
#12
Zhihui Yao, Haisheng Li, Weifeng He, Sisi Yang, Xiaorong Zhang, Rixing Zhan, Rui Xu, Jianglin Tan, Junyi Zhou, Jun Wu, Gaoxing Luo
P311 is a newly discovered functional gene, which has been proven to play a key role in blood pressure homeostasis, glioblastoma invasion, renal fibrosis, hypertrophic scar formation and others. In this study, we for the first time found that P311 could enhance reepithelialization during wound healing via promoting epidermal stem cell (EpSC) migration through Rho GTPases. P311 expression was highly increased in neo-epidermal cells during human and mouse skin wound healing, and P311was co-localized with BrdU positive label-retaining cells in a mouse superficial second degree burn wound model...
December 8, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27927027/primary-pineal-glioblastoma-multiforme-mimicking-a-germ-cell-tumour
#13
Syed Sameer Nadvi, Kritish Timatkia
Glioblastoma multiforme (GBM) is extremely rare in the pineal region, with only 19 previously reported cases. We report a unique case of a teenage girl with a pineal tumour with markedly raised beta-human chorionic gonadotropin (BHCG) levels, thought to be a germ-cell tumour. However, the raised BHCG was due to pregnancy, and biopsy revealed a pineal GBM.
December 7, 2016: British Journal of Neurosurgery
https://www.readbyqxmd.com/read/27927008/microrna-296-5p-promotes-invasiveness-through-downregulation-of-nerve-growth-factor-receptor-and-caspase-8
#14
Hong Lee, Chang Hoon Shin, Hye Ree Kim, Kyung Hee Choi, Hyeon Ho Kim
Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs posttranscriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells...
December 8, 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27926865/tenascin-c-orchestrates-glioblastoma-angiogenesis-by-modulation-of-pro-and-anti-angiogenic-signaling
#15
Tristan Rupp, Benoit Langlois, Maria M Koczorowska, Agata Radwanska, Zhen Sun, Thomas Hussenet, Olivier Lefebvre, Devadarssen Murdamoothoo, Christiane Arnold, Annick Klein, Martin L Biniossek, Vincent Hyenne, Elise Naudin, Ines Velazquez-Quesada, Oliver Schilling, Ellen Van Obberghen-Schilling, Gertraud Orend
High expression of the extracellular matrix component tenascin-C in the tumor microenvironment correlates with decreased patient survival. Tenascin-C promotes cancer progression and a disrupted tumor vasculature through an unclear mechanism. Here, we examine the angiomodulatory role of tenascin-C. We find that direct contact of endothelial cells with tenascin-C disrupts actin polymerization, resulting in cytoplasmic retention of the transcriptional coactivator YAP. Tenascin-C also downregulates YAP pro-angiogenic target genes, thus reducing endothelial cell survival, proliferation, and tubulogenesis...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926792/the-transcription-factor-pparalpha-is-overexpressed-and-is-associated-with-a-favourable-prognosis-in-idh-wildtype-primary-glioblastoma
#16
H R Haynes, P White, K M Hares, J Redondo, K C Kemp, W G B Singleton, C L Killick-Cole, J R Stevens, K Garadi, S Guglani, A Wilkins, K M Kurian
AIMS: PPARα agonists are in current clinical use as hypolipidaemic agents and show significant antineoplastic effects in human glioblastoma models. To date however, the expression of PPARα in large-scale glioblastoma data sets has not been examined. We aimed to investigate the expression of the transcription factor PPARα in primary glioblastoma, the relationship between PPARα expression and patients' clinicopathological features and other molecular markers associated with gliomagenesis...
December 7, 2016: Histopathology
https://www.readbyqxmd.com/read/27926485/axitinib-induces-senescence-associated-cell-death-and-necrosis-in-glioma-cell-lines-the-proteasome-inhibitor-bortezomib-potentiates-axitinib-induced-cytotoxicity-in-a-p21-waf-cip1-dependent-manner
#17
Maria Beatrice Morelli, Consuelo Amantini, Massimo Nabissi, Claudio Cardinali, Matteo Santoni, Giovanni Bernardini, Angela Santoni, Giorgio Santoni
Glioblastoma is associated with a poor overall survival despite new treatment advances. Antiangiogenic strategies targeting VEGF based on tyrosine kinase inhibitors (TKIs) are currently undergoing extensive research for the treatment of glioma.Herein we demonstrated that the TKI axitinib induces DNA damage response (DDR) characterized by γ-H2AX phosphorylation and Chk1 kinase activation leading to G2/M cell cycle arrest and mitotic catastrophe in U87, T98 and U251 glioma cell lines. Moreover, we found that p21(Waf1/Cip1) increased levels correlates with induction of ROS and senescence-associated cell death in U87 and T98 cell lines, which are reverted by N-acetyl cysteine pretreatment...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27924733/design-and-synthesis-of-1-4-dihydropyridine-derivatives-as-anti-cancer-agent
#18
Denish Viradiya, Sheefa Mirza, Faraz Shaikh, Rajesh Kakadiya, Anand Rathod, Nayan Jain, Rakesh Rawal, Anamik Shah
A series of 1,4-dihydropyridine based compounds bearing benzylpyridinium moiety have been designed and evaluated for in vitro anticancer activity against glioblastoma U87MG, lung cancer A549 and colorectal adenocarcinoma Caco-2 cell lines using the MTT assay. Among these compounds, 7b, 7d, 7e, and 7f exhibited potent anticancer activity against the cell lines tested. The cytotoxicity of the synthesized derivatives was compared to standard drugs (carboplatin, gemcitabine, and daunorubicin). Thus, synthesized 1,4-dihydropyridines can be considered as the encouraging molecules for further drug development as anticancer agents...
December 6, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27924163/highly-effective-auger-electron-therapy-in-an-orthotopic-glioblastoma-xenograft-model-using-convection-enhanced-delivery
#19
Helge Thisgaard, Bo Halle, Charlotte Aaberg-Jessen, Birgitte Brinkmann Olsen, Anne Sofie Nautrup Therkelsen, Johan Hygum Dam, Niels Langkjær, Sune Munthe, Kjell Någren, Poul Flemming Høilund-Carlsen, Bjarne Winther Kristensen
Glioblastoma, the most common and malignant primary brain tumor, always recurs after standard treatment. Therefore, promising new therapeutic approaches are needed. Short-range Auger-electron-emitters carry the ability of causing highly damaging radiation effects in cells. The aim of this study was to test the effect of [(125)I]5-Iodo-2'-deoxyuridine ((125)I-UdR, a radioactive Auger-electron-emitting thymidine analogue) Auger-therapy on immature glioblastoma spheroid cultures and orthotopic xenografted glioblastoma-bearing rats, the latter by means of convection-enhanced delivery (CED)...
2016: Theranostics
https://www.readbyqxmd.com/read/27924017/a-genome-integrated-massively-parallel-reporter-assay-reveals-dna-sequence-determinants-of-cis-regulatory-activity-in-neural-cells
#20
Brett B Maricque, Joseph D Dougherty, Barak A Cohen
Recent large-scale genomics efforts to characterize the cis-regulatory sequences that orchestrate genome-wide expression patterns have produced impressive catalogues of putative regulatory elements. Most of these sequences have not been functionally tested, and our limited understanding of the non-coding genome prevents us from predicting which sequences are bona fide cis-regulatory elements. Recently, massively parallel reporter assays (MPRAs) have been deployed to measure the activity of putative cis-regulatory sequences in several biological contexts, each with specific advantages and distinct limitations...
October 23, 2016: Nucleic Acids Research
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