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Adult-onset Alexander disease, associated with a mutation in an alternative GFAP transcript, may be phenotypically modulated by a non-neutral HDAC6 variant
Conclusions: Exome-NGS is an unbiased approach that not only helps identify new disease genes, but may also contribute to elucidate phenotypic expression. (Source: Orphanet Journal of Rare Diseases)
Source: Orphanet Journal of Rare Diseases - May 1, 2013 Category: Internal Medicine Authors: Laura MelchiondaMingyan FangHairong WangValeria FugnanesiMichela MorbinXuanzhu LiuWenyan LiIsabella CeccheriniLaura FarinaMario SavoiardoPio D¿AdamoJianguo ZhangAlfredo CostaSabrina RavagliaDaniele GhezziMassimo Zeviani Source Type: research

Molecular subtypes of glioma identified by genome‐wide methylation profiling
Recent studies have indicated a prognostic role for genome‐wide methylation in gliomas: Tumors that show an overall increase in DNA methylation at CpG sites (CIMP+; CpG island methylator phenotype) have a more favorable prognosis than CIMP− gliomas. Here, we have determined whether methylation profiling can identify more and clinically relevant molecular subtypes of glioma by performing genome‐wide methylation profiling on 138 glial brain tumors of all histological diagnosis. Hopach (Hierarchical ordered partitioning and collapsing hybrid) clustering using the 1,000 most variable CpGs identified three distinct glioma...
Source: Genes, Chromosomes and Cancer - April 30, 2013 Category: Cancer & Oncology Authors: Nanne K. Kloosterhof, Johan J. Rooi, Max Kros, Paul H. C. Eilers, Peter A. E. Sillevis Smitt, Martin J. Bent, Pim J. French Tags: Research Article Source Type: research

Breakpoint Analysis of Transcriptional and Genomic Profiles Uncovers Novel Gene Fusions Spanning Multiple Human Cancer Types
by Craig P. Giacomini, Steven Sun, Sushama Varma, A. Hunter Shain, Marilyn M. Giacomini, Jay Balagtas, Robert T. Sweeney, Everett Lai, Catherine A. Del Vecchio, Andrew D. Forster, Nicole Clarke, Kelli D. Montgomery, Shirley Zhu, Albert J. Wong, Matt van de Rijn, Robert B. West, Jonathan R. Pollack Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a “breakpoint analysis” pipeline to...
Source: PLoS Genetics - April 25, 2013 Category: Genetics & Stem Cells Authors: Craig P. Giacomini et al. Source Type: research

Effect of Bluetooth headset and mobile phone electromagnetic fields on the human auditory nerve
ConclusionsThe outcomes of the present study show that, contrary to the finding that the latency and amplitude of CNAPs are very sensitive to EMFs produced by the tested mobile phone, the EMFs produced by a common Bluetooth device do not induce any significant change in cochlear nerve activity. The conditions of exposure, therefore, differ from those of everyday life, in which various biological tissues may reduce the EMF affecting the cochlear nerve. Nevertheless, these novel findings may have important safety implications. Level of Evidence4. Laryngoscope, 2013 (Source: The Laryngoscope)
Source: The Laryngoscope - April 25, 2013 Category: ENT & OMF Authors: Marco Mandalà, Vittorio Colletti, Luca Sacchetto, Paolo Manganotti, Stefano Ramat, Alessandro Marcocci, Liliana Colletti Tags: Otology/Neurotology Source Type: research

Expression and clinical significance of the proliferation marker minichromosome maintenance protein 2 (Mcm2) in diffuse astrocytomas WHO grade II
Conclusions: In our hands Mcm2 immunostaining has no advantage over Ki67/MIB-1 in the evaluation ofgrade II astrocytomas. Larger studies are needed to fully clarify the prognostic role of thisbiomarker.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1715002791944037 (Source: Diagnostic Pathology)
Source: Diagnostic Pathology - April 24, 2013 Category: Pathology Authors: Tove Lind-LandströmRosilin VarugheseStein SundstrømSverre Torp Source Type: research

Multiple Neurofibromas as the Presenting Feature of Familial Atypical Multiple Malignant Melanoma (FAMMM) Syndrome
Abstract Mutations in the cyclin‐dependent kinase inhibitor‐2A (CDKN2A) gene have been associated with a number of malignancies, most notably cutaneous malignant melanoma (CMM). Mutations in this gene have also been associated with pancreatic cancer and breast cancer, as well as astrocytomas and other nervous system tumors (NST). Among NST, rare solitary internal neurofibromas have been reported, but multiple cutaneous neurofibromas have only been described in two families. In the first family, the affected individuals all carried a heterozygous G > C mutation at the splice acceptor site of intron 1 resulting in...
Source: American Journal of Medical Genetics Part A - April 23, 2013 Category: Genetics & Stem Cells Authors: Rachel Vanneste, Erika Smith, Gail Graham Tags: Clinical Report Source Type: research

Demystifying the molecular signature of glioblastoma multiforme arising in its rare morphological variants
I have read with interest the article by Joo et al cytogenetically analyzing glioblastoma multiforme (GBM) arising in granular cell astrocytoma (GCA) by performing high-resolution array comparative genomic hybridization; fluorescence in situ hybridization for Epidermal growth factor receptor (EGFR), CDKN2A, 1p (1p36); and 19q (19q13.3); mutational analysis for isocitrate dehydrogenase 1 and 2; and methylation-specific polymerase chain reaction for MGMT promoter methylation and comparing this to the recently established molecular subtypes of GBM. Their results indicate that the cytogenetic alterations of this variant are mo...
Source: Human Pathology - April 18, 2013 Category: Pathology Authors: Kirti Gupta Tags: Correspondence Source Type: research

AMPK Is Necessary to Maintain Glioblastoma Proliferation
In this study, we examined the role of AMPK in a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We also evaluated the activity and role of AMPK in human glioblastoma cells and xenografts. AMPK was constitutively activated in astrocytes expressing oncogenic H-RasV12 in parallel with high cell division rates. Genetic deletion of AMPK or attenuation of its activity in these cells was sufficient to reduce cell proliferation. The levels of pAMK were always related to the levels of phosph...
Source: Cancer Research - April 15, 2013 Category: Cancer & Oncology Authors: Rios, M., Foretz, M., Viollet, B., Prieto, A., Fraga, M., Costoya, J. A., Senaris, R. Tags: Tumor and Stem Cell Biology Source Type: research

[Correspondence] Everolimus for astrocytomas in tuberous sclerosis
David Franz and colleagues (Jan 12, p 125) present the results of EXIST-1, which shows that use of everolimus is associated with a significant reduction in tumour size, seizure frequency, and other adverse events relative to placebo in patients with tuberous sclerosis and associated subependymal giant cell astrocytoma (SEGA). Such results justifiably buoy some hope in the use of inhibitors of the mammalian target of rapamycin (mTOR) for the treatment of SEGAs, yet could relay an incomplete picture. (Source: LANCET)
Source: LANCET - April 13, 2013 Category: Journals (General) Authors: Debraj Mukherjee, J Manuel Sarmiento, Diana Ly, Miriam A Nuno, Chirag G Patil Tags: Correspondence Source Type: research

[Correspondence] Everolimus for astrocytomas in tuberous sclerosis – Author's reply
Debraj Mukherjee and colleagues raise a question about the development of hydrocephalus in the treatment group and the need for surgical intervention in our trial. They incorrectly state that “hydrocephalus was an inclusion criterion”, when, in fact, it was not. Critical hydrocephalus or clinical evidence of impending herniation was, however, an exclusion criterion. We state in the paper that “No cases of progression of subependymal giant cell astrocytomas were seen in the everolimus group; as a result, the duration of tumour response was censored for all everolimus-treated responders. (Source: LANCET)
Source: LANCET - April 13, 2013 Category: Journals (General) Authors: David Neal Franz Tags: Correspondence Source Type: research

Suppression of STIM1 inhibits human glioblastoma cell proliferation and induces G0/G1 phase arrest
Conclusion: Our findings confirm STIM1 as a rational therapeutic target in human glioblastoma, and also indicate that lentivirus-mediated STIM1 silencing is a promising therapeutic strategy for human glioblastoma. (Source: Journal of Experimental and Clinical Cancer Research)
Source: Journal of Experimental and Clinical Cancer Research - April 11, 2013 Category: Cancer & Oncology Authors: Guilin LiZhenxing ZhangRenzhi WangWenbin MaYing YangJunji WeiYanping Wei Source Type: research

Rim and Flame Signs: Postgadolinium MRI Findings Specific for Non-CNS Intramedullary Spinal Cord Metastases [SPINE]
CONCLUSIONS: The rim and flame signs are common in and specific for ISCM and are rare in primary spinal cord masses. (Source: American Journal of Neuroradiology)
Source: American Journal of Neuroradiology - April 10, 2013 Category: Radiology Authors: Rykken, J. B., Diehn, F. E., Hunt, C. H., Eckel, L. J., Schwartz, K. M., Kaufmann, T. J., Wald, J. T., Giannini, C., Wood, C. P. Tags: SPINE Source Type: research

RAF inhibitor targeting of BRAF fusions [Cell Biology]
Astrocytomas are the most common type of brain tumors in children. Activated BRAF protein kinase mutations are characteristic of pediatric astrocytomas with KIAA1549-BRAF fusion genes typifying low-grade astrocytomas and V600EBRAF alterations characterizing distinct or higher-grade tumors. Recently, BRAF-targeted therapies, such as vemurafenib, have shown great promise in treating V600E-dependent melanomas.... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - April 9, 2013 Category: Science Authors: Sievert, A. J., Lang, S.-S., Boucher, K. L., Madsen, P. J., Slaunwhite, E., Choudhari, N., Kellet, M., Storm, P. B., Resnick, A. C. Tags: Biological Sciences Source Type: research

Dysembryoplastic Neuroepithelial Tumors Share with Pleomorphic Xanthoastrocytomas and Gangliogliomas BRAFV600E Mutation and Expression
In conclusion, DNT shared with PXA and GG, BRAFV600E mutation and/or CD34 expression, which represent molecular markers for these tumors, and we recommend searching for CD34 expression and BRAFV600E mutation in all DNT, especially the non‐specific forms. (Source: Brain Pathology)
Source: Brain Pathology - March 20, 2013 Category: Neurology Authors: Céline Chappé, Laetitia Padovani, Didier Scavarda, Fabien Forest, Isabelle Nanni‐Metellus, Anderson Loundou, Sandy Mercurio, Frédéric Fina, Gabriel Lena, Carole Colin, Dominique Figarella‐Branger Tags: Research Article Source Type: research

An unbalanced translocation involving loss of 10q26.2 and gain of 11q25 in a pedigree with autism spectrum disorder and cerebellar juvenile pilocytic astrocytoma
We report on a pedigree with a pair of brothers each with minor anomalies, developmental delay, and autistic‐symptoms who share an unbalanced translocation (not detectable by karyotype). The unbalanced translocation involves a 7.1 Mb loss of the terminal portion of 10q, and a 4.2 Mb gain of 11q. One of the brothers also developed a cerebellar juvenile pilocytic astrocytoma. The father was found to be a balanced carrier and the couple had a previous miscarriage. We demonstrate that the breakpoint for the triplicated region from chromosome 11 is adjacent to two IgLON genes, namely Neurotrimin (NTM) and Opioid Binding P...
Source: American Journal of Medical Genetics Part A - March 12, 2013 Category: Genetics & Stem Cells Authors: Hassan M. Minhas, Matthew F. Pescosolido, Matthew Schwede, Justyna Piasecka, John Gaitanis, Umadevi Tantravahi, Eric M. Morrow Tags: Research Article Source Type: research

Choline Comparison with MRS and PET
In this study, we used the spontaneous murine astrocytoma model SMA560 injected intracranially into syngeneic VM/Dk mice, analyzing animals at various postimplantation time points using dynamic microPET imaging and CSI MRS. We observed an increase in tumor volume and 11C-choline uptake between days 5 and 18. Similarly, tCho levels decreased at days 5 to 18. We found a negative correlation between the tCho and PET results in the tumor and a positive correlation between the tCho tumor-to-brain ratio and choline uptake in the tumor. PCR results confirmed expected increases in expression levels for most of the transporters and...
Source: Cancer Research - March 3, 2013 Category: Cancer & Oncology Authors: Wehrl, H. F., Schwab, J., Hasenbach, K., Reischl, G., Tabatabai, G., Quintanilla-Martinez, L., Jiru, F., Chughtai, K., Kiss, A., Cay, F., Bukala, D., Heeren, R. M. A., Pichler, B. J., Sauter, A. W. Tags: Integrated Systems and Technologies Source Type: research

H3F3A K27M Mutation in Pediatric CNS Tumors: A Marker for Diffuse High-Grade Astrocytomas.
Abstract Brain tumors are one of the most common childhood malignancies. Diffuse high-grade gliomas represent approximately 10% of pediatric brain tumors. Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors. We performed a pyrosequencing-based analysis for the identification of H3F3A codon 27 and codon 34 mutations in 338 pediatric brain tumors. The K27M mutation...
Source: American Journal of Clinical Pathology - March 1, 2013 Category: Pathology Authors: Gielen GH, Gessi M, Hammes J, Kramm CM, Waha A, Pietsch T Tags: Am J Clin Pathol Source Type: research

Somatic neurofibromatosis type 1 (NF1) inactivation characterizes NF1-associated pilocytic astrocytoma [RESEARCH]
Low-grade brain tumors (pilocytic astrocytomas) arising in the neurofibromatosis type 1 (NF1) inherited cancer predisposition syndrome are hypothesized to result from a combination of germline and acquired somatic NF1 tumor suppressor gene mutations. However, genetically engineered mice (GEM) in which mono-allelic germline Nf1 gene loss is coupled with bi-allelic somatic (glial progenitor cell) Nf1 gene inactivation develop brain tumors that do not fully recapitulate the neuropathological features of the human condition. These observations raise the intriguing possibility that, while loss of neurofibromin function is neces...
Source: Genome Research - March 1, 2013 Category: Genetics & Stem Cells Authors: Gutmann, D. H., McLellan, M. D., Hussain, I., Wallis, J. W., Fulton, L. L., Fulton, R. S., Magrini, V., Demeter, R., Wylie, T., Kandoth, C., Leonard, J. R., Guha, A., Miller, C. A., Ding, L., Mardis, E. R. Tags: RESEARCH Source Type: research

Dysembryoplastic Neuroepithelial Tumours share with pleomorphic xanthoastrocytomas and gangliogliomas BRAFV600E mutation and expression
In conclusion, DNT shared with PXA and GG, BRAFV600E mutation and/or CD34 expression which represent molecular markers for these tumours and we recommend searching for CD34 expression and BRAFV600E mutation in all DNT, especially the non‐specific forms. (Source: Brain Pathology)
Source: Brain Pathology - February 26, 2013 Category: Neurology Authors: Céline Chappé, Laetitia Padovani, Didier Scavarda, Fabien Forest, Isabelle Nanni‐Metellus, Anderson Loundou, Sandy Mercurio, Frédéric Fina, Gabriel Lena, Carole Colin, Dominique Figarella‐Branger Tags: Research Article Source Type: research

Chromatin Remodeling Defects in Pediatric and Young Adult Glioblastoma: A Tale of a Variant Histone 3 Tail
Abstract Primary brain tumors occur in 8 out of 100 000 people and are the leading cause of cancer‐related death in children. Among brain tumors, high‐grade astrocytomas (HGAs) including glioblastoma multiforme (GBM) are aggressive and are lethal human cancers. Despite decades of concerted therapeutic efforts, HGAs remain essentially incurable in adults and children. Recent discoveries have revolutionized our understanding of these tumors in children and young adults. Recurrent somatic driver mutations in the tail of histone 3 variant 3 (H3.3), leading to amino acid substitutions at key residues, namely lysine (K) 27...
Source: Brain Pathology - February 25, 2013 Category: Neurology Authors: Adam M. Fontebasso, Xiao‐Yang Liu, Dominik Sturm, Nada Jabado Tags: MINI‐SYMPOSIUM: When Genetics Meets Epigenetics—A New Option for Therapeutic Intervention in Brain Tumors? Symposium Editor: Stefan M. Pfister, MD Source Type: research

Metabolic Modulation of Epigenetics in Gliomas
Abstract Cancer metabolism and epigenetics are two relatively new areas of cancer research. Recent years have seen an explosion of studies implicating either altered tumor metabolism or epigenetic mechanisms in the pathogenesis or maintenance of brain tumors. A new paradigm is emerging in cancer biology that represents a convergence of these themes, the metabolic regulation of epigenetics. We discuss this interrelationship in the context of two metabolic enzymes that can influence the pathogenesis of gliomas by altering the epigenetic state. The first of these enzymes is isocitrate dehydrogenase 1 (IDH1), which is mutated ...
Source: Brain Pathology - February 25, 2013 Category: Neurology Authors: Sriram Venneti, Craig B. Thompson Tags: MINI‐SYMPOSIUM: When Genetics Meets Epigenetics—A New Option for Therapeutic Intervention in Brain Tumors? Symposium Editor: Stefan M. Pfister, MD Source Type: research

PDGFRA amplification is common in pediatric and adult high‐grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma
Abstract High‐grade astrocytomas (HGAs), corresponding to WHO grades III (AA) and IV (GBM), are biologically aggressive and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non‐amplified (normal and polysomy) or amplified (low‐le...
Source: Brain Pathology - February 25, 2013 Category: Neurology Authors: Joanna J. Phillips, Derick Aranda, David W. Ellison, Alexander R. Judkins, Sidney E. Croul, Daniel J. Brat, Keith L. Ligon, Craig Horbinski, Sriram Venneti, Gelareh Zadeh, Mariarita Santi, Shengmei Zhou, Christina L. Appin, Stefano Sioletic, Lisa M. Sulli Tags: Research Article Source Type: research

ADC Values and Prognosis of Malignant Astrocytomas: Does Lower ADC Predict a Worse Prognosis Independent of Grade of Tumor?--A Meta-Analysis
CONCLUSION. Low ADC values correlate with poor survival in malignant astrocytomas independent of tumor grade. (Source: American Journal of Roentgenology)
Source: American Journal of Roentgenology - February 22, 2013 Category: Radiology Authors: Zulfiqar, M., Yousem, D. M., Lai, H. Tags: Neuroradiology/Head and Neck Imaging Source Type: research

Young Australian adults with NF1 have poor access to health care, high complication rates, and limited disease knowledge
Abstract Neurofibromatosis type 1 (NF1) is a multisystem disease associated with a lifelong risk of debilitating and potentially life‐limiting complications, however many adults with NF1 have no regular health surveillance. We interviewed and examined 17 young adults with NF1 between the ages of 25 and 33. Most had not been assessed for NF1‐related complications within the previous 8 years, including patients with known serious vascular complications, for example, renal artery stenosis. Acute and/or chronic pain, particularly back and plexiform‐related pain were common symptoms, and despite a significant impact on qu...
Source: American Journal of Medical Genetics Part A - February 20, 2013 Category: Genetics & Stem Cells Authors: Emily C. Oates, Jonathan M. Payne, Sheryl L. Foster, Nigel F. Clarke, Kathryn N. North Tags: Research Article Source Type: research

Brain and Neck Tumors Among Physicians Performing Interventional Procedures
In conclusion, these results raise additional concerns regarding brain cancer developing in physicians performing interventional procedures. Given that the brain is relatively unprotected and the left side of the head is known to be more exposed to radiation than the right, these findings of disproportionate reports of left-sided tumors suggest the possibility of a causal relation to occupational radiation exposure. (Source: The American Journal of Cardiology)
Source: The American Journal of Cardiology - February 18, 2013 Category: Cardiology Authors: Ariel Roguin, Jacob Goldstein, Olivier Bar, James A. Goldstein Tags: Miscellaneous Source Type: research

Nitrone-based Therapeutics for Neurodegenerative Diseases. Their use alone or in Combination with Lanthionines.
Abstract The possibility of free radical reactions occurring in biological processes led to the development and employment of novel methods and techniques focused on determining their existence and importance in normal and pathological conditions. For this reason the use of Nitrones for spin trapping free radicals came into widespread use in the 1970s and 1980s when surprisingly the first evidence of their potent biological properties was first noted. Since then wide-spread exploration and demonstration of the potent biological properties of phenyl-tert-butylnitrone (PBN) and derivatives were shown in preclinical m...
Source: Free Radical Biology and Medicine - February 15, 2013 Category: Biology Authors: Floyd RA, Castro Faria Neto HC, Zimmerman GA, Hensley K, Towner RA Tags: Free Radic Biol Med Source Type: research

Medical Management with mTOR Inhibitors vs. Surgical Resection: Comparison of Clinical Outcomes for Subependymal Giant Cell Astrocytoma (SEGA) in Tuberous Sclerosis Complex (TSC) (PL01.001)
CONCLUSIONS: Both surgical resection and medical treatment strategies can be effective for the management of SEGA in TSC, but neither is 100% effective or without complication or adverse side effect risk. In our cohort of patients, medical management with mTOR inhibitors offered better efficacy and reduced risk of serious complication when compared to surgical resection.Disclosure: Dr. Yoon has nothing to disclose. Dr. Ung has nothing to disclose. Dr. Mehta has nothing to disclose. Dr. Yang has nothing to disclose. Dr. Wu has received personal compensation for activities with Novartis. Dr. Krueger has received personal com...
Source: Neurology - February 14, 2013 Category: Neurology Authors: Yoon, S., Ung, N., Mehta, N., Yang, I., Wu, J., Krueger, D. Tags: PL01 Contemporary Clinical Issues Plenary Session Source Type: research

Effect of Everolimus on Subependymal Nodules (SENs) and Tubers in Patients with Subependymal Giant Cell Astrocytoma (SEGA) Associated with Tuberous Sclerosis Complex (TSC): Results from the EXIST-1 Trial (P01.049)
CONCLUSIONS: A possible trend towards shrinkage of SENs was observed with minimal change in tuber volume. No clear effect of everolimus on reducing the volumes of SENs and tubers was noted due to the high variability in percentage change observed for both treatment arms.Supported by: Novartis Pharmaceuticals Corporation.Disclosure: Dr. Franz has received personal compensation for activities with Novartis. Dr. Franz's institution has received research support from Novartis Pharmaceuticals. Dr Lam is an employee of Novartis Pharmaceuticals Corporation....... Dr. Cauwel has received personal compensation for activities with N...
Source: Neurology - February 14, 2013 Category: Neurology Authors: Franz, D., Lam, D., Cauwel, H., Jozwiak, S. Tags: P01 Neurologic Manifestations: Therapeutics Source Type: research

Treatment of Unresectable Adult Pilocytic Astrocytoma with Bevacizumab with or without Temozolomide (P01.097)
CONCLUSIONS: Bev when administered with or without TMZ is effective in unresectable adult PA and deserves a Phase II study.Disclosure: Dr. Green has nothing to disclose. Dr. Woyshner has nothing to disclose. Dr. Quan has nothing to disclose. Dr. Pope has received personal compensation for activities with Genentech and Hoffman-La Roche as a consultant. Dr. Cloughesy has received personal compensation for activities with Genentech, Inc., Hoffman-La Roche, Merck Serono, and Celgene as a consultant. (Source: Neurology)
Source: Neurology - February 14, 2013 Category: Neurology Authors: Green, R., Woyshner, E., Quan, J., Pope, W., Cloughesy, T. Tags: P01 Neuro-Oncology: Therapeutics Source Type: research

Astrocyte-Elevated Gene-1 (AEG-1) Is Induced by Hypoxia and Glucose Deprivation and Modulates the Glycolytic Phenotype in Glioblastoma (P02.160)
CONCLUSIONS: These findings identify a novel role for AEG-1 in the regulation of glycolysis in glioblastoma and indicate that anti-glycolytic therapies may be useful in treating malignancies that demonstrate AEG-1-overexpression.Disclosure: Dr. Noch has nothing to disclose. Dr. Pina-Oviedo has nothing to disclose. Dr. Perez-Liz has nothing to disclose. Dr. Bookland has nothing to disclose. Dr. Del Valle has nothing to disclose. Dr. Gordon has nothing to disclose. Dr. Khalili has nothing to disclose. (Source: Neurology)
Source: Neurology - February 14, 2013 Category: Neurology Authors: Noch, E., Pina-Oviedo, S., Perez-Liz, G., Bookland, M., Del Valle, L., Gordon, J., Khalili, K. Tags: P02 Neuro-Oncology: Basic Science Source Type: research

Tumors of the Central Nervous System, Volume 9
Lymphoma, Supratentorial Tumors, Glioneuronal Tumors, Gangliogliomas, Neuroblastoma in Adults, Astrocytomas, Ependymomas, Hemangiomas, and Craniopharyngiomasseries:Tumors of the Central Nervous SystemThe ninth volume in this essential series discusses key advances in our understanding of neoplasms in the human central nervous system. This publication deals with various aspects of nine separate types of brain tumors. With 70 contributors from 17 nations, this edition offers an unrivalled thoroughness and breadth of coverage that includes the very latest research results on the following ... (Source: Springer Biomedical Sciences titles)
Source: Springer Biomedical Sciences titles - February 12, 2013 Category: Biomedical Science Tags: Biomedicine (general) Source Type: news

Tumor blood flow from arterial spin labeling perfusion MRI: A key parameter in distinguishing high‐grade gliomas from primary cerebral lymphomas, and in predicting genetic biomarkers in high‐grade gliomas
Conclusion:pCASL imaging may facilitate differentiation of high‐grade gliomas from lymphomas and prediction of EGFR expression status in high‐grade gliomas. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc. (Source: Journal of Magnetic Resonance Imaging)
Source: Journal of Magnetic Resonance Imaging - February 6, 2013 Category: Radiology Authors: Roh‐Eul Yoo, Seung Hong Choi, Hye Rim Cho, Tae Min Kim, Se‐Hoon Lee, Chul‐Kee Park, Sung‐Hye Park, Il Han Kim, Tae Jin Yun, Ji‐Hoon Kim, Chul‐Ho Sohn, Moon Hee Han, Kee Hyun Chang Tags: Original Research Source Type: research

13-year-old tuberous sclerosis patient with renal cell carcinoma associated with multiple renal angiomyolipomas developing multifocal micronodular pneumocyte hyperplasia
Conclusion: Here we report a diagnostically challenging case of a 13-year-old patient with tuberous sclerosis and angiomyolipomas of the kidney who developed an unclassified renal cell carcinoma as well as multifocal micronodular pneumocyte hyperplasia. (Source: BioMed Central)
Source: BioMed Central - February 4, 2013 Category: Journals (General) Authors: Carl Ludwig BehnesGunther SchützeChristoph EngelkeFelix BremmerBastian GunawanHeinz-Joachim RadzunStefan Schweyer Source Type: research

Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma
Conclusion: Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA. Classification of evidence: This study provides Class III evidence that everolimus, titrated to trough serum levels of 5–15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months. (Source: Neurology)
Source: Neurology - February 4, 2013 Category: Neurology Authors: Krueger, D. A., Care, M. M., Agricola, K., Tudor, C., Mays, M., Franz, D. N. Tags: Primary brain tumor, All Pediatric, All Epilepsy/Seizures, Other neurocutaneous disorders ARTICLE Source Type: research

Management of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC): Clinical recommendations.
This report summarizes the clinical recommendations for the management of SEGA made by a panel of European experts in March 2012. Current treatment options and outstanding questions are outlined. PMID: 23391693 [PubMed - as supplied by publisher] (Source: European Journal of Paediatric Neurology)
Source: European Journal of Paediatric Neurology - February 4, 2013 Category: Neurology Authors: Jóźwiak S, Nabbout R, Curatolo P, On behalf of the participants of the TSC Consensus Meeting for SEGA and Epilepsy Management Tags: Eur J Paediatr Neurol Source Type: research

Surgery of highly eloquent gliomas primarily assessed as non-resectable: risks and benefits in a cohort study
Conclusions: In specialized centers, most highly eloquent gliomas are eligible for surgical resection with an acceptable rate of surgery-related deficits; therefore, they should be referred to specialized centers. (Source: BMC Cancer)
Source: BMC Cancer - February 2, 2013 Category: Cancer & Oncology Authors: Sandro KriegLea SchnurbusEhab ShibanDoris DroeseThomas ObermuellerNiels BuchmannJens GemptBernhard MeyerFlorian Ringel Source Type: research

[Clinico-pathological and molecular aspects of diagnostic and prognostic value in gliomas].
CONCLUSIONS. The study of proteomics and molecular biomarkers should complement the histopathological analysis and sometimes allows to determine direct or indirect predictive factors as well as the study of affected pathways which may become selective therapeutic targets. PMID: 23359078 [PubMed - in process] (Source: Revista de Neurologia)
Source: Revista de Neurologia - February 1, 2013 Category: Neurology Authors: Ortega-Aznar A, Jimenez-Leon P, Martinez E, Romero-Vidal FJ Tags: Rev Neurol Source Type: research

Molecular genetics of low-grade gliomas: genomic alterations guiding diagnosis and therapeutic intervention. 11th Annual Frye-Halloran Brain Tumor Symposium.
Conclusions The recent discovery of recurrent gene mutations in low-grade glioma has increased the understanding of the molecular mechanisms involved in a host of biological activities related to low-grade gliomas. Understanding the role these genetic alterations play in brain cancer initiation and progression will help lead to the development of novel treatment modalities than can be personalized to each patient, thereby helping transform this now often-fatal malignancy into a chronic or even curable disease. PMID: 23373454 [PubMed - in process] (Source: Neurosurgical Focus)
Source: Neurosurgical Focus - February 1, 2013 Category: Neurosurgery Authors: Jones PS, Dunn GP, Barker FG, Curry WT, Hochberg FH, Cahill DP Tags: Neurosurg Focus Source Type: research

The Cancer Genome Atlas expression profiles of low-grade gliomas.
Abstract Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of...
Source: Neurosurgical Focus - February 1, 2013 Category: Neurosurgery Authors: Gonda DD, Cheung VJ, Muller KA, Goyal A, Carter BS, Chen CC Tags: Neurosurg Focus Source Type: research

Improved survival in the largest national cohort of adults with cerebellar versus supratentorial low-grade astrocytomas.
Conclusions Taken together, adults with cerebellar WHO Grade I and II astrocytomas have a much more favorable survival curve than those with similar supratentorial tumors. Research demonstrates that the primary driver of this phenomenon is the improved survival in patients with cerebellar Grade II gliomas. PMID: 23373452 [PubMed - in process] (Source: Neurosurgical Focus)
Source: Neurosurgical Focus - February 1, 2013 Category: Neurosurgery Authors: Bagley JH, Babu R, Friedman AH, Adamson C Tags: Neurosurg Focus Source Type: research

The molecular biology of WHO Grade II gliomas.
Abstract The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the "low-grade gliomas," these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the ...
Source: Neurosurgical Focus - February 1, 2013 Category: Neurosurgery Authors: Marko NF, Weil RJ Tags: Neurosurg Focus Source Type: research

Malignancies in Chinese patients with neurofibromatosis type 1.
CONCLUSION. Chinese patients with neurofibromatosis type 1 are susceptible to different malignancies which contribute to mortality. These findings are similar to reports from overseas. Outcomes were unfavourable, except in patients having low-grade gliomas. Surveillance imaging may help early detection of deep-seated malignancies but the benefits accruing from such monitoring warrants prospective evaluation. PMID: 23378354 [PubMed - in process] (Source: Hong Kong Med J)
Source: Hong Kong Med J - February 1, 2013 Category: Journals (General) Authors: Cheuk DK, Chiang AK, Ha SY, Chan GC Tags: Hong Kong Med J Source Type: research

Anaplastic astrocytomas with abundant Rosenthal fibers in elderly patients: A diagnostic pitfall of high‐grade gliomas
To investigate the clinicopathological features of anaplastic astrocytoma (AA) with abundant Rosenthal fibers (RFs), this study assessed four cases of AA (elderly patients; age ≥70 years). Histologically, these tumors were composed of diffusely infiltrating astrocytomas with brightly eosinophilic cytoplasmic granules or cork‐screw or beaded bundles. Tumor cells showed pleomorphism, bizarre giant cells, and mitotic activity, but no necrosis. The cytoplasmic granules showed negativity on PAS staining. Immunohistochemically, the tumor cells with cytoplasmic granular cells showed a positive reaction for GFAP. The cytoplasm...
Source: Neuropathology - February 1, 2013 Category: Neurology Authors: Yasuo Sugita, Shinji Nakashima, Koichi Ohshima, Mizuhiko Terasaki, Motohiro Morioka Tags: Original Article Source Type: research

PI3K/Akt and Stat3 signaling regulated by PTEN control of the cancer stem cell population, proliferation and senescence in a glioblastoma cell line.
PI3K/Akt and Stat3 signaling regulated by PTEN control of the cancer stem cell population, proliferation and senescence in a glioblastoma cell line. Int J Oncol. 2013 Mar;42(3):921-8 Authors: Moon SH, Kim DK, Cha Y, Jeon I, Song J, Park KS Abstract Malignant gliomas are the most common primary brain tumor in adults. A number of genes have been implicated in glioblastoma including mutation and deletion of PTEN. PTEN is a regulator of PI3K-mediated Akt signaling pathways and has been recognized as a therapeutic target in glioblastoma. To achieve potent therapeutic inhibition of t...
Source: International Journal of Oncology - January 31, 2013 Category: Cancer & Oncology Authors: Moon SH, Kim DK, Cha Y, Jeon I, Song J, Park KS Tags: Int J Oncol Source Type: research

Immunohistochemical expression of IDH1 in gliomas: A tissue microarray-based approach
Conclusion : Monoclonal antibody to IDH1 (R132) is a useful and less-labor-intensive method to detect mutations in gliomas. IDH1 is a useful immunohistochemical marker to differentiate reactive gliosis from low-grade astrocytoma, has potential as an independent prognostic marker and also helps in distinguishing primary from secondary GBM. Its sensitivity and specificity need to be assessed by simultaneous sequencing and its validation on clinically annotated samples. (Source: Journal of Cancer Research and Therapeutics)
Source: Journal of Cancer Research and Therapeutics - January 29, 2013 Category: Cancer & Oncology Authors: Varuna SipayyaIra SharmaKC SharmaAvninder Singh Source Type: research

Characterization of microglia/macrophages in gliomas developed in S‐100β‐v‐erbB transgenic rats
In conclusion, S‐100β‐v‐erbB TG rats may serve as a useful animal model for further analysis of TAMs in terms of tumor cell proliferation, microvascular proliferation and phagocytosis, and as a tool for therapeutic use in malignant gliomas, although it should be noted that the polarization of TAMs toward the M2 phenotype remains unclear. (Source: Neuropathology)
Source: Neuropathology - January 20, 2013 Category: Neurology Authors: Atsushi Sasaki, Hideaki Yokoo, Yuko Tanaka, Taku Homma, Yoichi Nakazato, Hiroko Ohgaki Tags: Original Article Source Type: research

Promoter methylation of WNT inhibitory factor-1 and expression pattern of WNT/β-catenin pathway in human astrocytoma: pathologic and prognostic correlations
Promoter methylation of WNT inhibitory factor-1 and expression pattern of WNT/β-catenin pathway in human astrocytoma: pathologic and prognostic correlations Modern Pathology advance online publication, January 18 2013. doi:10.1038/modpathol.2012.215 Authors: Sun A Kim, Jihye Kwak, Hae Yun Nam, Sung Min Chun, Byoung Wook Lee, Hyang Ju Lee, Shin Kwang Khang & Seong Who Kim (Source: Modern Pathology AOP)
Source: Modern Pathology AOP - January 18, 2013 Category: Pathology Authors: Sun A KimJihye KwakHae Yun NamSung Min ChunByoung Wook LeeHyang Ju LeeShin Kwang KhangSeong Who Kim Tags: astrocytoma β-catenin glioblastoma promoter methylation WNT inhibitory factor-1 WNT pathway Source Type: research

IDH1-WT Disruption Suppresses D-2HG in IDH1-Mutated Gliomas
Point mutations at Arg132 of the cytoplasmic NADP+-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the “oncometabolite” D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually associated with a wild-type IDH1 allele (heterozygous) in cancer. Here, we identify 2 gliomas that underwent loss of the wild-type IDH1 allele but retained the mutant IDH1 allele following tumor progression from World Health Organization (WHO) grade III anaplastic astrocytomas to WHO grade IV glioblastomas. Intratumoral D-2HG was 14-fold lower in the glioblastomas lackin...
Source: Cancer Research - January 16, 2013 Category: Cancer & Oncology Authors: Jin, G., Reitman, Z. J., Duncan, C. G., Spasojevic, I., Gooden, D. M., Rasheed, B. A., Yang, R., Lopez, G. Y., He, Y., McLendon, R. E., Bigner, D. D., Yan, H. Tags: Priority Reports Source Type: research

Inhibition of formyl peptide receptor in high-grade astrocytoma by CHemotaxis Inhibitory Protein of S. aureus
jp & A M E Walenkamp (Source: British Journal of Cancer AOP)
Source: British Journal of Cancer AOP - January 15, 2013 Category: Cancer & Oncology Authors: J C BoerU M DomanskaH Timmer-BosschaI G J BoerC J C de HaasJ V JosephF A E KruytE G E de VriesW F A den DunnenJ A G van StrijpA M E Walenkamp Tags: FPR1 CHIPS astrocytoma mitochondrial peptides migration Source Type: research