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MedWorm: Brain Tumor



MedWorm.com provides a medical RSS filtering service. Over 7000 RSS medical sources are combined and output via different filters. This feed contains the latest news and research in the Brain Tumor category.



Last Build Date: Tue, 22 Mar 2016 08:26:32 +0100

 



Driver or passenger effects of augmented c-Myc and Cdc20 in gliomagenesis.

Mon, 21 Mar 2016 05:47:03 +0100

CONCLUSIONS: These results suggest that the driver or passenger of oncogene signaling is dependent on cellular status. c-Myc is a driver when combined with kRas/Akt3 oncogenic signals in gliomagenesis, whereas Cdc20 overexpression is a passenger. Inhibition of cell differentiation of c-Myc may be a target for anti-glioma therapy. PMID: 26993778 [PubMed - as supplied by publisher] (Source: Oncotarget)

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Brain tumor modeling using the CRISPR/Cas9 system: state of the art and view to the future.

Mon, 21 Mar 2016 05:47:03 +0100

Authors: Mao XY, Dai JX, Zhou HH, Liu ZQ, Jin WL Abstract Although brain tumors have been known tremendously over the past decade, there are still many problems to be solved. The etiology of brain tumors is not well understood and the treatment remains modest. There is in great need to develop a suitable brain tumor models that faithfully mirror the etiology of human brain neoplasm and subsequently get more efficient therapeutic approaches for these disorders. In this review, we described the current status of animal models of brain tumors and analyzed their advantages and disadvantages. Additionally, prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), a versatile genome editing technology for investigating the function...



Evaluation of simple blood counts as inflammation markers for brain tumor patients

Mon, 21 Mar 2016 00:00:00 +0100

Conclusion Decreased MPV and increased RDW were both associated with brain tumor. However, prospective studies with larger sample sizes are needed to support the results and expose MPV and RDW variations between metastatic and primary brain tumors. (Source: Polish Journal of Neurology and Neurosurgery)



Neuronal antibodies in pediatric epilepsy: Clinical features and long‐term outcomes of a historical cohort not treated with immunotherapy

Mon, 21 Mar 2016 00:00:00 +0100

Summary ObjectiveIn autoimmune encephalitis the etiologic role of neuronal cell‐surface antibodies is clear; patients diagnosed and treated early have better outcomes. Neuronal antibodies have also been described in patients with pediatric epilepsy without encephalitis. The aim was to assess whether antibody presence had any effect on long‐term outcomes in these patients. MethodsPatients (n = 178) were recruited between 1988 and 1992 as part of the prospective Dutch Study of Epilepsy in Childhood; none received immunotherapy. Healthy age‐matched bone‐marrow donors served as controls (n = 112). All sera were tested for serum N‐methyl‐d‐aspartate receptor (NMDAR), alpha amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor, leucine rich glioma inactivated 1, c...



Molecules, Vol. 21, Pages 387: Synthesis and Biological Evaluation of an 18Fluorine-Labeled COX Inhibitor—[18F]Fluorooctyl Fenbufen Amide—For Imaging of Brain Tumors

Mon, 21 Mar 2016 00:00:00 +0100

Molecular imaging of brain tumors remains a great challenge, despite the advances made in imaging technology. An anti-inflammatory compound may be a useful tool for this purpose because there is evidence of inflammatory processes in brain tumor micro-environments. Fluorooctylfenbufen amide (FOFA) was prepared from 8-chlorooctanol via treatment with potassium phthalimide, tosylation with Ts2O, fluorination with KF under phase transfer catalyzed conditions, deprotection using aqueous hydrazine, and coupling with fenbufen. The corresponding radiofluoro product [18F]FOFA, had a final radiochemical yield of 2.81 mCi and was prepared from activated [18F]F− (212 mCi) via HPLC purification and concentration. The radiochemical purity was determined to be 99%, and the specific activity was shown t...



MMP‐9 in translation: from molecule to brain physiology, pathology, and therapy

Mon, 21 Mar 2016 00:00:00 +0100

This article is part of the 60th Anniversary special issue. MMP‐9, through cleavage of specific target proteins, plays a major role in synaptic plasticity and neuroinflammation, and by those virtues contributes to brain physiology and a host of neurological and psychiatric disorders. This article is part of the 60th Anniversary special issue. (Source: Journal of Neurochemistry)

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Multifunctional pDNA‐Conjugated Polycationic Au Nanorod‐Coated Fe3O4 Hierarchical Nanocomposites for Trimodal Imaging and Combined Photothermal/Gene Therapy

Mon, 21 Mar 2016 00:00:00 +0100

It is very desirable to design multifunctional nanocomposites for theranostic applications via flexible strategies. The synthesis of one new multifunctional polycationic Au nanorod (NR)‐coated Fe3O4 nanosphere (NS) hierarchical nanocomposite (Au@pDM/Fe3O4) based on the ternary assemblies of negatively charged Fe3O4 cores (Fe3O4‐PDA), polycation‐modified Au nanorods (Au NR‐pDM), and polycations is proposed. For such nanocomposites, the combined near‐infrared absorbance properties of Fe3O4‐PDA and Au NR‐pDM are applied to photoacoustic imaging and photothermal therapy. Besides, Fe3O4 and Au NR components allow the nanocomposites to serve as MRI and CT contrast agents. The prepared positively charged Au@pDM/Fe3O4 also can complex plasmid DNA into pDNA/Au@pDM/Fe3O4 and efficientl...



Diagnosis Disclosure Process in Patients With Malignant Brain Tumors.

Sun, 20 Mar 2016 05:19:02 +0100

This study was conducted prospectively during a one-year period. All patients were diagnosed with malignant brain tumors and received their diagnosis using the disclosure process. The communication between the provider and the patient during diagnosis disclosure was recorded for analysis, and patients completed a satisfaction survey. FINDINGS: Ninety-one patients with a brain tumor diagnosis participated in the study. Twenty-six were unable to complete the satisfaction survey because they were either deceased or close to the end of their lives. In total, 65 questionnaires were sent to patients and their families, and 43 responded. Patients were satisfied with the quality of the disclosure process regarding information given, psychological support, and communication with all healthcare ...



Intraoperative ultrasound and 5-ALA: the two faces of the same medal?

Sat, 19 Mar 2016 18:58:01 +0100

CONCLUSIONS: In our preliminary experience we observe that there are no significative advantages using IOUS plus 5-ALA. However we feel that IOUS is useful in first step of resection and fluorescence in the latest steps of operation. Therefore these two technologies could be considered the two faces of the same medal because they can help the surgeon to detect the tumor in all step of tumor removal. PMID: 26989904 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgical Sciences)



Epigenetic targeting of glioma stem cells: Short-term and long-term treatments with valproic acid modulate DNA methylation and differentiation behavior, but not temozolomide sensitivity.

Sat, 19 Mar 2016 17:53:03 +0100

Authors: Riva G, Butta V, Cilibrasi C, Baronchelli S, Redaelli S, Dalprà L, Lavitrano M, Bentivegna A Abstract Glioblastoma (GBM) is the most aggressive tumor of the central nervous system. GBM is a fatal tumor, incurable by conventional therapies. One of the factors underlying tumor recurrence and poor long-term survival is the presence of a cancer stem-like cell population, termed glioma stem cells (GSCs), which is particularly resistant to chemotherapy and radiotherapy and supports tumor self-renewal. The aim of the present study was to evaluate the impact and difference in effects of short-term and long‑term treatments with valproic acid (VPA), a histone deacetylase inhibitor, on seven GSC lines. We investigated for the first time the changes in the genome-wide DNA methylat...



Hypoxia-associated factor expression in low-grade and anaplastic gliomas: a marker of poor outcome.

Sat, 19 Mar 2016 17:51:03 +0100

Authors: Tchoghandjian A, Koh MY, Taieb D, Ganaha S, Powis G, Bialecki E, Graziani N, Figarella-Branger D, Metellus P Abstract Somatic mutations in isocitrate dehydrogenase (IDH) genes have recently been identified in a large proportion of glial tumors of the CNS and reported to be a strong prognostic factor in gliomas whatever the tumor grade. Few data are available in the literature regarding the relationship between IDH mutations and HIF expression in low-grade gliomas (LGGs), especially in a recently described aggressive molecular subtype: "triple negative" (IDH non mutated, 1p 19q non codeleted, p53 expression negative) gliomas. We analyzed clinical, radiological and molecular features of a series of 31 grade II/III gliomas. p53 expression, 1p19q deletion and IDH mutation stat...

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Patterns and Time-dependence of Unspecific Enhancement in Postoperative MRI After Glioblastoma Resection

Sat, 19 Mar 2016 00:00:00 +0100

Postoperative Magnetic Resoncance Imaging (MRI) is recommended soon after glioma surgery to avoid reactive non-neoplastic contrast enhancement indistinguishable from tumor. The purpose of this study was to analyze these patterns of postoperative contrast enhancement at 3T to define the optimal time frame for postoperative MRI. (Source: World Neurosurgery)



Electrocorticography is not necessary during awake brain surgery for gliomas

Sat, 19 Mar 2016 00:00:00 +0100

(Source: World Neurosurgery)



Physiologic MRI for assessment of response to therapy and prognosis in glioblastoma

Sat, 19 Mar 2016 00:00:00 +0100

Aside from bidimensional measurements from conventional contrast-enhanced MRI, there are no validated or FDA-qualified imaging biomarkers for high-grade gliomas. However, advanced functional MRI techniques, including perfusion- and diffusion-weighted MRI, have demonstrated much potential for determining prognosis, predicting therapeutic response, and assessing early treatment response. They may also prove useful for differentiating pseudoprogression from true progression after temozolomide chemoradiation and pseudoresponse from true response after anti-angiogenic therapy. This review will highlight recent developments using these techniques and emphasize the need for technical standardization and validation in prospective studies in order for these methods to become incorporated into stand...



A malignant cellular network in gliomas: potential clinical implications

Sat, 19 Mar 2016 00:00:00 +0100

The recent discovery of distinct, ultra-long, and highly functional membrane protrusions in gliomas, particularly in astrocytomas, extends our understanding of how these tumors progress in the brain and how they resist therapies. In this article, we will focus on ideas on how to target these membrane protrusions, for which we have suggested the term "tumor microtubes" (TMs), and the malignant multicellular network they form. First, we discuss TM-specific features and their differential biological functions known so far. Second, the connection between 1p/19q codeletion and the inability to form functional TMs via certain neurodevelopmental pathways is presented; this could provide an explanation for the distinct clinical features of oligodendrogliomas. Third, the role of TMs for primary and...



Glioma-derived extracellular vesicles selectively suppress immune responses

Sat, 19 Mar 2016 00:00:00 +0100

Conclusion The differential effects of high and low EV concentrations dictate modulatory effects on PBMCs. These data provide a role for EVs at high concentrations for inducing selective tolerance of an immune response in a tumor setting. This suggests that lymphocytes in patients’ circulation are not irreparably impaired, as previously thought, but can be rescued to augment antitumor responses. (Source: Neuro-Oncology)

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Tumor microenvironment tenascin-C promotes glioblastoma invasion and negatively regulates tumor proliferation

Sat, 19 Mar 2016 00:00:00 +0100

Conclusion Our findings suggest that detailed understanding of how TNC in the tumor microenvironment influences tumor behavior and the interactions between tumor cells and surrounding nontumor cells will benefit novel combinatory antitumor strategies to treat malignant brain tumors. (Source: Neuro-Oncology)



Combination viroimmunotherapy with checkpoint inhibition to treat glioma, based on location-specific tumor profiling

Sat, 19 Mar 2016 00:00:00 +0100

Conclusions Since different tumor types growing in the same location in the brain share a location-specific phenotype, we suggest that antigen-specific immunotherapies should be based upon expression of both histological type–specific tumor antigens and location-specific antigens. Our findings support clinical application of VSV-TAA therapy with checkpoint inhibition for aggressive brain tumors and highlight the importance of the intracranial microenvironment in sculpting a location-specific profile of tumor antigen expression. (Source: Neuro-Oncology)



Pathology concordance levels for meningioma classification and grading in NRG Oncology RTOG Trial 0539

Sat, 19 Mar 2016 00:00:00 +0100

Conclusion Our data suggest that current meningioma classification and grading are at least as objective and reproducible as for gliomas. Nevertheless, reproducibility remains suboptimal. Further improvements may be anticipated with education and clarification of subjective criteria, although development of biomarkers may be the most promising strategy. (Source: Neuro-Oncology)



Palliative and end-of-life care for children with diffuse intrinsic pontine glioma: results from a London cohort study and international survey

Sat, 19 Mar 2016 00:00:00 +0100

Conclusions This research assessed the current state of palliative and end-of-life care for children with DIPG. Our results show the variability and complexity of symptoms at end-stage disease and the current lack of disease-specific guidelines for this vulnerable group of patients. This first descriptive paper is intended to act as a solid basis for developing an international clinical trial and subsequent guideline to support high-quality palliative and end-of-life care. (Source: Neuro-Oncology)



Radiological features combined with IDH1 status for predicting the survival outcome of glioblastoma patients

Sat, 19 Mar 2016 00:00:00 +0100

Conclusions Combining the radiological features and IDH1 status of a tumor allows more accurate prediction of survival outcomes in glioblastoma patients. The complementary roles of genetic changes and radiological features of tumors should be considered in future studies. (Source: Neuro-Oncology)

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Hypothalamic–Optochiasmatic Pilocytic Astrocytoma Associated with Occipital and Sacral Spinal Cavernomas: A Mere Coincidence or a True Association?

Sat, 19 Mar 2016 00:00:00 +0100

The co-occurrence of cerebral gliomas and cavernous angiomas is rarely encountered in clinical practice. All reported cases with such association have occurred within the brain with none involving the spinal cord. (Source: World Neurosurgery)



Value of Early Postoperative FLAIR Volume Dynamic in Glioma With No or Minimal Enhancement

Sat, 19 Mar 2016 00:00:00 +0100

The evaluation of postoperative MRI in glioma with no or minimal enhancement is discussed controversially, because evaluation of residual tumor volume may be biased. Aim of this study was to clarify the value of early postoperative and 3-month MRI regarding its validity in predicting recurrent disease. (Source: World Neurosurgery)



IDH mutations in cancer and progress toward development of targeted therapeutics

Sat, 19 Mar 2016 00:00:00 +0100

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes, converting isocitrate to α-ketoglutarate (αKG). IDH1 and IDH2 mutations have been identified in multiple tumor types, including gliomas and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here we provide an overview of the function of normal and mutated IDH, discuss the role of IDH mutations in tumorigenesis and progression and review the key clinical considerations when treating IDH-mutated tumors based on emerging clinical data from mutant IDH1/2 inhibitor trials. IDH1 and IDH2 mutations confer neomorphic activity in the mutant protein, resulting in the conversion of αKG to the oncometabolite, D-2-hydroxyglutarate (2-HG). The subsequent accumulation...



Erratum.

Fri, 18 Mar 2016 13:42:01 +0100

Authors: Nicolai E. Savaskan, Zheng Fan, Thomas Broggini, Michael Buchfelder and Ilker Y. Eyüpoglu Abstract Due to an overlook on the author's side, the title with an error "Neurodegeneration and the Brain Tumor Microenviornment: Glutamate in the Limelight" by Dr. Nicolai E. Savaskan (Co-author) was published in the journal "Current Neuropharmacology" Volume 13, No 2, Page no 258-265. The correct title is as follows: Neurodegeneration and the Brain Tumor Microenviornment. Curr. Neuropharmacol., 2015, 13(2), 258 - 265. PMID: 26984019 [PubMed - as supplied by publisher] (Source: Current Neuropharmacology)



ABCG1 maintains high-grade glioma survival in vitro and in vivo.

Fri, 18 Mar 2016 05:56:02 +0100

Authors: Chen YH, Cimino PJ, Luo J, Dahiya S, Gutmann DH Abstract The overall survival for adults with malignant glioma (glioblastoma) remains poor despite advances in radiation and chemotherapy. One of the mechanisms by which cancer cells develop relative resistance to treatment is through de-regulation of endoplasmic reticulum (ER) homeostasis. We have recently shown that ABCG1, an ATP-binding cassette transporter, maintains ER homeostasis and suppresses ER stress-induced apoptosis in low-grade glioma. Herein, we demonstrate that ABCG1 expression is increased in human adult glioblastoma, where it correlates with poor survival in individuals with the mesenchymal subtype. Leveraging a mouse model of mesenchymal glioblastoma (NPcis), shRNA-mediated Abcg1 knockdown (KD) increased CHO...

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Evasion of Cell Senescence Leads to Medulloblastoma Progression

Fri, 18 Mar 2016 00:00:00 +0100

Publication date: Available online 17 March 2016 Source:Cell Reports Author(s): Lukas Tamayo-Orrego, Chia-Lun Wu, Nicolas Bouchard, Ahmed Khedher, Shannon M. Swikert, Marc Remke, Patryk Skowron, Michael D. Taylor, Frédéric Charron How brain tumors progress from precancerous lesions to advanced cancers is not well understood. Using Ptch1 +/− mice to study medulloblastoma progression, we found that Ptch1 loss of heterozygosity (LOH) is an early event that is associated with high levels of cell senescence in preneoplasia. In contrast, advanced tumors have evaded senescence. Remarkably, we discovered that the majority of advanced medulloblastomas display either spontaneous, somatic p53 mutations or Cdkn2a locus inactivation. Consistent with senescence evasion, these p53 mutat...



Risk of optic pathway glioma in children with neurofibromatosis type 1 and optic nerve tortuosity or nerve sheath thickening

Fri, 18 Mar 2016 00:00:00 +0100

Conclusions Optic nerve tortuosity at baseline is associated with OPG development among patients with NF-1, but does not predispose to aggressive OPG with associated vision loss. Neither nerve nor sheath thickening at baseline is associated with OPG development. (Source: British Journal of Ophthalmology)



De Novo Cerebellar Malignant Glioma: A Case Report

Fri, 18 Mar 2016 00:00:00 +0100

Conclusion When MRI detects a new, faint abnormality in the cerebellum, close follow-up of clinical symptoms and MRI on suspicion of glioma is warranted (Source: International Journal of Surgery Case Reports)



The Tumor-suppressive GTPase DiRas1 Binds SmgGDS [Signal Transduction]

Fri, 18 Mar 2016 00:00:00 +0100

In this study, we demonstrate that DiRas1 binds to SmgGDS, a protein that promotes the activation of several oncogenic GTPases. In silico docking studies predict that DiRas1 binds to SmgGDS in a manner similar to other small GTPases. SmgGDS is a guanine nucleotide exchange factor for RhoA, but we report here that SmgGDS does not mediate GDP/GTP exchange on DiRas1. Intriguingly, DiRas1 acts similarly to a dominant-negative small GTPase, binding to SmgGDS and inhibiting SmgGDS binding to other small GTPases, including K-Ras4B, RhoA, and Rap1A. DiRas1 is expressed in normal breast tissue, but its expression is decreased in most breast cancers, similar to its family member DiRas3 (ARHI). DiRas1 inhibits RhoA- and SmgGDS-mediated NF-κB transcriptional activity in HEK293T cells. We also report ...



Passive language mapping combining real-time oscillation analysis with cortico-cortical evoked potentials for awake craniotomy.

Fri, 18 Mar 2016 00:00:00 +0100

CONCLUSIONS The described technique allows for simple and quick functional brain mapping with higher sensitivity and specificity than ECS mapping. The authors believe that this could improve the reliability of functional brain mapping and facilitate rational and objective operations. Passive mapping also sheds light on the underlying physiological mechanisms of language in the human brain. PMID: 26991386 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

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Retraction Note to: TNF receptor-associated factor 6 regulates proliferation, apoptosis, and invasion of glioma cells.

Fri, 18 Mar 2016 00:00:00 +0100

Authors: Peng Z, Shuangzhu Y, Yongjie J, Xinjun Z, Ying L PMID: 26992906 [PubMed - as supplied by publisher] (Source: Molecular and Cellular Biochemistry)



ExRNA in Biofluids as Biomarkers for Brain Tumors.

Fri, 18 Mar 2016 00:00:00 +0100

Authors: Rennert RC, Hochberg FH, Carter BS Abstract Patients with high-grade gliomas and glioblastomas (GBMs) have poor survival despite optimal surgical and drug therapy. Minimally invasive diagnostic biomarkers would enable early diagnosis and tumor-specific treatments for 'personalized targeted' therapy, and would create the basis for response tracking in patients with GBM. Extracellular vesicles (EVs) isolated from cerebrospinal fluid and blood contain glioma-specific molecules, including tumor-derived EV RNAs that are detectable in small copy numbers in these biofluids. EV RNA mutations or expression changes are also detectable, the analysis of which gives rise to 'liquid biopsy' tumor profiling. PMID: 26993514 [PubMed - as supplied by publisher] (Source: Cellular and Mol...



Extracellular Vesicles in Brain Tumor Progression.

Fri, 18 Mar 2016 00:00:00 +0100

Authors: D'Asti E, Chennakrishnaiah S, Lee TH, Rak J Abstract Brain tumors can be viewed as multicellular 'ecosystems' with increasingly recognized cellular complexity and systemic impact. While the emerging diversity of malignant disease entities affecting brain tissues is often described in reference to their signature alterations within the cellular genome and epigenome, arguably these cell-intrinsic changes can be regarded as hardwired adaptations to a variety of cell-extrinsic microenvironmental circumstances. Conversely, oncogenic events influence the microenvironment through their impact on the cellular secretome, including emission of membranous structures known as extracellular vesicles (EVs). EVs serve as unique carriers of bioactive lipids, secretable and non-secretable ...



Father who thought he would be paralyzed walks daughter down the aisle at her wedding

Thu, 17 Mar 2016 19:43:33 +0100

Walter Thompson, a father from Oklahoma, was diagnosed with fist-sized, internal capsule glioma tumor in the middle of his brain just weeks before his daughter's wedding. (Source: the Mail online | Health)



Potential Diagnostic and Prognostic Value of Plasma Circulating MicroRNA-182 in Human Glioma.

Thu, 17 Mar 2016 05:44:02 +0100

CONCLUSIONS These results suggest that circulating miR-182 may be a potential noninvasive biomarker for the diagnosis and prognosis of human glioma. PMID: 26978735 [PubMed - in process] (Source: Medical Science Monitor)

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Multiple subsets of brain tumor initiating cells co‐exist in glioblastoma

Thu, 17 Mar 2016 00:00:00 +0100

This article is protected by copyright. All rights reserved. In this work we use single‐cell microfluidic profiling to test the fundamental hypothesis that multiple subsets of brain tumor‐initiating cells coexist, and underlie human glioblastoma molecular heterogeneity. (Source: Stem Cells)



Pharmacokinetics of high-dose methotrexate in infants aged less than 12 months treated for aggressive brain tumors

Thu, 17 Mar 2016 00:00:00 +0100

Conclusions Our data suggest that a higher dose of MTX for the treatment of aggressive brain tumors in early infants had an acceptable pharmacokinetic profile. Greater attention must be used in the treatment of children weighing less than 4 kg. (Source: Cancer Chemotherapy and Pharmacology)



Proton beam therapy

Thu, 17 Mar 2016 00:00:00 +0100

UK readers will remember a news story which gripped the headlines in 2014: a 5-year-old boy with medulloblastoma was removed from a paediatric oncology unit against medical advice by his parents who then fled to Europe, prompting a police search and their subsequent arrest. They were motivated by their desire for him to have proton beam therapy, unavailable in the UK, which he eventually underwent in the Czech Republic. In proton radiotherapy, as compared to conventional photon radiotherapy, the heavier subatomic particles are able to deliver their energy more precisely to the tumour, with less ‘scatter’ to surrounding tissues. This should result in fewer radiation-induced adverse effects, but hard evidence for this in paediatric brain tumour treatment has been scarce until now...



Exosomes as Tools to Suppress Primary Brain Tumor.

Thu, 17 Mar 2016 00:00:00 +0100

Authors: Katakowski M, Chopp M Abstract Exosomes are small microvesicles released by cells that efficiently transfer their molecular cargo to other cells, including tumor. Exosomes may pass the blood-brain barrier and have been demonstrated to deliver RNAs contained within to brain. As they are non-viable, the risk profile of exosomes is thought to be less than that of cellular therapies. Exosomes can be manufactured at scale in culture, and exosomes can be engineered to incorporate therapeutic miRNAs, siRNAs, or chemotherapeutic molecules. As natural biological delivery vehicles, interest in the use of exosomes as therapeutic delivery agents is growing. We previously demonstrated a novel treatment whereby mesenchymal stromal cells were employed to package tumor-suppressing miR-146...



Extracellular Vesicles and MicroRNAs: Their Role in Tumorigenicity and Therapy for Brain Tumors.

Thu, 17 Mar 2016 00:00:00 +0100

Authors: Bronisz A, Godlewski J, Chiocca EA Abstract MicroRNAs are small non-coding RNAs which mediate post-transcriptional gene regulation. Recently, microRNAs have also been found to be localized to the extracellular space, often encapsulated in secreted extracellular vesicles (EVs). This tandem of EVs and tissue-specific expressed/secreted microRNAs that can be taken up by neighboring or distant recipient cells, leading to changes in gene expression-suggests a cell-specialized role in physiological and pathological conditions. The complexity of solid tumors and their distinct pathophysiology relies on interactive communications between the various cell types in the neoplasm (tumor, endothelial, or macrophages, for instance). Understanding how such EV/microRNA-mediated communicat...

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Determining priority signs and symptoms for use as clinical outcomes assessments in trials including patients with malignant gliomas: Panel 1 Report

Thu, 17 Mar 2016 00:00:00 +0100

Patients with primary brain tumors such as malignant gliomas are highly symptomatic, often from the time of diagnosis. Signs and symptoms (signs/symptoms) can cause functional limitations that often worsen over the disease trajectory and may impact patient quality of life. It is recognized that standard measurements of tumor response do not adequately measure this impact or the impact that a therapy may have to mitigate these signs/symptoms and potentially have clinical benefit. Identifying a core set of signs/symptoms and functional limitations is important for understanding their clinical impact and is the first step to including clinical outcomes assessment in primary brain tumor clinical trials. (Source: Neuro-Oncology)



Clinical outcome assessment in malignant glioma trials: measuring signs, symptoms, and functional limitations

Thu, 17 Mar 2016 00:00:00 +0100

The shared goal of all parties developing therapeutics against malignant gliomas is to positively impact the lives of people affected by these cancers. Clinical outcome assessment (COA) tools, including measures of patient-reported outcome, performance outcome, clinician-reported outcome, and observer-reported outcome, allow patient-focused assessments to complement traditional efficacy measures such as overall survival and radiographic endpoints. This review examines the properties of various COA measures used in malignant glioma clinical trials to date and cross references their content to the priority signs, symptoms, and functional limitations defined through a community survey conducted by the National Brain Tumor Society. The overarching goal of this initiative is to identify COA mea...



Report of the Jumpstarting Brain Tumor Drug Development Coalition and FDA clinical trials clinical outcome assessment endpoints workshop (October 15, 2014, Bethesda MD)

Thu, 17 Mar 2016 00:00:00 +0100

This report summarizes the presentations and discussions of that workshop and the proposals that emerged to move the field forward and toward greater inclusion of these endpoints in future clinical trials for high-grade gliomas. (Source: Neuro-Oncology)



Atypical Teratoid Rhabdoid Tumor Diagnosis after Partial Resection of Dysembryoplastic Neuroepithelial Tumor: Case Report and Review of the Literature

Wed, 16 Mar 2016 19:34:06 +0100

This report adds to our knowledge about the poorly understood behavior and natural history of DNETs and emphasizes the importance of lifelong clinical and neuroimaging follow-up of these lesions.Pediatr Neurosurg (Source: Pediatric Neurosurgery)



Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging

Wed, 16 Mar 2016 13:57:30 +0100

ACS NanoDOI: 10.1021/acsnano.5b07573 (Source: ACS Nano)

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Kelsey’s transformation: From stroke survivor to motivational speaker

Wed, 16 Mar 2016 10:57:14 +0100

“When I woke up after my stroke, all I wanted was to be normal again,” recalls Kelsey Tainsh. Normal — as in a healthy teen athlete who could brush her teeth and shower on her own, who wasn’t wheelchair-bound, who wasn’t compelled to hide her paralyzed right hand in her pocket everywhere she went, one who hadn’t lost all of her high school friends except for her two triplet sisters. Now, this world-champion athlete not only learned to walk and talk again but also to embrace her differences. “Our hardest obstacles can be our biggest opportunities,” she says. Kelsey’s first taste of being different came at age 5. She was diagnosed with a brain tumor — an optic pathway pilocytic astrocytoma. Her parents brought her from their home in Winter Park, Florida, to Boston Childr...



Pushing the limits of structurally-diverse light-harvesting Ru(II) metal-organic chromophores for photodynamic therapy

Wed, 16 Mar 2016 00:00:00 +0100

Publication date: 15 May–1 June 2016 Source:Journal of Photochemistry and Photobiology A: Chemistry, Volumes 322–323 Author(s): Roberto Padilla, William A. Maza, Anthony J. Dominijanni, Brenda S.J. Winkel, Amanda J. Morris, Karen J. Brewer The synthesis of Ru(II) derivatives [(AnthbpyMe)(bpy)Ru(dpp)]2+ (2) and [(AnthbpyMe)2Ru(dpp)]2+ (3), and the analysis of their excited state properties as well as their photocytotoxicity against glioma cells are reported. Complexes 2 and 3 absorb visible light with metal-to-ligand charge transfer (MLCT) transitions at λ max =459nm (16,000M−1 cm−1) and λ max =461nm (21,000M−1 cm−1), respectively. The complexes exhibit bichromatic properties with the 3MLCT emission centered at λ em =661nm and λ em =663nm for 2 and 3, respectively, w...






In vivo detection of 2‐hydroxyglutarate in brain tumors by optimized point‐resolved spectroscopy (PRESS) at 7T

Wed, 16 Mar 2016 00:00:00 +0100

ConclusionData indicate that the optimized MRS provides good selectivity of 2HG from other metabolite signals and may confer reliable in vivo detection of 2HG at relatively low concentrations. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc. (Source: Magnetic Resonance in Medicine)



Neuroplastic Response following Radiotherapy for Pediatric Brain Tumors: A Pilot Study

Wed, 16 Mar 2016 00:00:00 +0100

Clinically effective measurement of cognitive toxicity from photon radiotherapy (XRT) should be accurate, sensitive, and specific. This pilot study tests translational findings on phasic changes in children’s memory systems that are sensitive and insensitive to toxic XRT effects, to identify a possible neuroplastic effect. (Source: International Journal of Radiation Oncology * Biology * Physics)

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Suppressing H19 Modulates Tumorigenicity and Stemness in U251 and U87MG Glioma Cells.

Wed, 16 Mar 2016 00:00:00 +0100

In this study, we discovered that the expression of H19 increased in GBM cell lines. H19 knocked down GBM cells also displayed decreased cellular proliferation and a higher apoptosis rate when induced by temozolomide. Interestingly, the GBM cell lines U87MG and U251 were found to express cancer stem cell markers CD133, NANOG, Oct4 and Sox2. Expression of these markers was downregulated in H19-deficient cells. Collectively, these data suggest a role for H19 in contributing to GBM malignancy and the maintenance of its stem cell properties. PMID: 26983719 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Neurobiology)



In vivo detection of 2-hydroxyglutarate in brain tumors by optimized point-resolved spectroscopy (PRESS) at 7T.

Wed, 16 Mar 2016 00:00:00 +0100

CONCLUSION: Data indicate that the optimized MRS provides good selectivity of 2HG from other metabolite signals and may confer reliable in vivo detection of 2HG at relatively low concentrations. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc. PMID: 26991680 [PubMed - as supplied by publisher] (Source: Magnetic Resonance in Medicine)



Educational program on fatigue for brain tumor patients: possibility strategy?

Tue, 15 Mar 2016 22:22:28 +0100

ABSTRACT Objective To evaluate the effectiveness of an educational program on improvement of fatigue and quality of life of patients with high-grade glioma during radiotherapy and chemotherapy treatment. Method This is a longitudinal, experimental study. Twenty-three patients with high-grade glioma were randomly assigned to one of two groups. Both groups completed the Functional Assessment of Cancer Therapy: Fatigue questionnaire and the Beck Depression Inventory, and one of the groups received the educational intervention. The groups did not show any change in quality of life and fatigue in this study, for this reason, the educational program did not present any significant difference. However, there was a significant difference in depressive symptoms during the educational program showin...



Cuba Has Made At Least 3 Major Medical Innovations That We Need

Tue, 15 Mar 2016 18:36:31 +0100

By most measures, the United States' business-friendly environment has proven to be fertile for medical innovation. Compared to other countries, America has filed the most patents in the life sciences, is conducting most of the world's clinical trials and has published the most biomedical research. That's what makes the medical prominence of Cuba all the more surprising to those who view a free market as an essential driver of scientific discovery. Cuba is very poor, and yet the country has some of the healthiest, most long-lived residents in the world -- as well as a medical invention or two that could run circles around U.S. therapies, thanks to government investment in scientific research and a preventive public health approach that views medical care as a birthright. The isla...



Toddler With Brain Cancer Gets Postcards From Across the Globe

Tue, 15 Mar 2016 15:16:56 +0100

Ellie Walton was diagnosed with a brain tumor at 4 months old. (Source: ABC News: Health)

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[Optic chiasm glioma in children: Endocrine disorders in 14 cases].

Tue, 15 Mar 2016 12:14:01 +0100

CONCLUSIONS: Children with optic chiasm gliomas may present endocrine disorders from the time of diagnosis of the tumor and, in particular as they develop on. The most common of these is precocious puberty. Pituitary deficits are associated with more aggressive tumours (those presenting with neuroophthalmological signs and symptoms before the age of five and requiring treatment). PMID: 26971985 [PubMed - as supplied by publisher] (Source: Medicina Clinica)



Neuroscientist receives Javits Award to study how brain tumors thwart immune system

Tue, 15 Mar 2016 04:00:00 +0100

(University of Michigan Health System) U-M neuroscientist Maria G. Castro, Ph.D., has been selected to receive the 2016 Javits Neuroscience Investigator Award, an honor that provides up to seven years of research funding for her brain tumor work. (Source: EurekAlert! - Cancer)



HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma

Tue, 15 Mar 2016 00:00:00 +0100

Publication date: 14 March 2016 Source:Cancer Cell, Volume 29, Issue 3 Author(s): Yanxin Pei, Kun-Wei Liu, Jun Wang, Alexandra Garancher, Ran Tao, Lourdes A. Esparza, Donna L. Maier, Yoko T. Udaka, Najiba Murad, Sorana Morrissy, Huriye Seker-Cin, Sebastian Brabetz, Lin Qi, Mari Kogiso, Simone Schubert, James M. Olson, Yoon-Jae Cho, Xiao-Nan Li, John R. Crawford, Michael L. Levy, Marcel Kool, Stefan M. Pfister, Michael D. Taylor, Robert J. Wechsler-Reya Medulloblastoma (MB) is a highly malignant pediatric brain tumor. Despite aggressive therapy, many patients succumb to the disease, and survivors experience severe side effects from treatment. MYC-driven MB has a particularly poor prognosis and would greatly benefit from more effective therapies. We used an...



Identification of novel FAK and S6K1 dual inhibitors from natural compounds via ADMET screening and molecular docking

Tue, 15 Mar 2016 00:00:00 +0100

In this study, the 3D structure of FAK (PDB ID: 2AL6) and S6K1 (3A60) were chosen for docking 60 natural compounds attempted to identify novel and specific inhibitors from them. The 30 selected molecules with high scores were further analyzed using DSSTox tools and DS 3.5 ADMET software. Based on a high docking score and energy interaction, 3 of the 9 candidate compounds, neferine B, neferine A, and antroquinonol D, were identified and the inhibitory activity of these compounds were subsequently validated in the C6 glioma cell line. All three selected compounds show potential effects on cell viability by MTT assay. Neferine B, neferine A, and antroquinonol D showed an IC50 value of 10-, 12-, and 16-μM, respectively. Moreover, these compounds decreased the p-FAk and p-S6k1 proteins in a do...



Nuclear unphosphorylated STAT3 correlates with a worse prognosis in human glioblastoma

Tue, 15 Mar 2016 00:00:00 +0100

In this study, expressions of STAT3, pSTAT3 (Y705), and pSTAT3 (S727) were evaluated using immunohistochemistry assays of tissue microarrays containing non-neoplastic tissue (NN, n=12), grade II astrocytomas (n=33), grade III astrocytomas (n=12), and GBM (n=85) specimens. In GBM specimens, STAT3 was overexpressed and exhibited greater nuclear localization compared with lower grade astrocytomas and NN. Conversely, nuclear localization of pSTAT3 (Y705) and pSTAT3 (S727) exhibited a similar phenotype in both GBMs and NNs. MET was also detected as a non-canonical pathway marker for STAT3. For tumors with higher levels of STAT3 nuclear localization, and not pSTAT3 (Y705) and pSTAT3 (S727), these specimens exhibited increased levels of MET expression. Thus, a non-canonical pathway may mediate a ...

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Quantitative measurement of blood flow in paediatric brain tumours - a comparative study of dynamic susceptibility contrast and multi time-point arterial spin labeled MRI.

Tue, 15 Mar 2016 00:00:00 +0100

CONCLUSIONS: Significant correlations between ASL-noVC and DSC measures in normal brain suggest that DSC is most sensitive to macrovascular blood flow. The absence of significant correlations within tumour ROI suggests that ASL is sensitive to different physiological mechanisms compared to DSC measures. Advances in knowledge: ASL provides comparable information to DSC in healthy tissue, but appears to reflect different physiology in tumour tissue. PMID: 26975495 [PubMed - as supplied by publisher] (Source: The British Journal of Radiology)



MGMT Hypermethylation—Missing Piece of the Puzzle in Primary Head and Neck Squamous Cell Carcinoma?

Tue, 15 Mar 2016 00:00:00 +0100

A secific mechanism explaining the higher chemoradiation responsiveness of human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) and the modulation of this effect by tobacco exposure remains unidentified. Promoter hypermethylation (HM) of the DNA-repair O6-Methylguanine (O6-MG)-DNA-methyl-transferase (MGMT) gene is an independent predictor of response to chemoradiation and survival in gliomas and lymphomas. We are investigating the role of MGMT in HNSCC in the context of tobacco exposure and HPV status. (Source: International Journal of Radiation Oncology * Biology * Physics)



Vaccine Therapies Against Gliomas: Prime Time Yet?

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Puduvalli VK PMID: 26984214 [PubMed - in process] (Source: Oncology (Williston Park, N.Y.))



Vaccine Therapy, Oncolytic Viruses, and Gliomas.

Tue, 15 Mar 2016 00:00:00 +0100

Authors: Desjardins A, Vlahovic G, Friedman HS Abstract After years of active research and refinement, vaccine therapy and oncolytic viruses are becoming part of the arsenal in the treatment of gliomas. In contrast to standard treatment with radiation therapy and chemotherapy, vaccines are more specific to the patient and the tumor. The majority of ongoing vaccine trials are investigating peptide, heat shock protein, and dendritic cell vaccines. The immunosuppression triggered by the tumor itself and by its treatment is a major obstacle to vaccine and oncolytic virus therapy. Thus, combination therapy with different agents that affect the immune system will probably be necessary. PMID: 26984213 [PubMed - in process] (Source: Oncology (Williston Park, N.Y.))



Outrunning Cancer

Mon, 14 Mar 2016 21:50:55 +0100

By: Yariv Kafri, Founder, Supportersize. Co-authors are Dr. Elizabeth K. O'Donnell and Dr. Jeffrey M. Peppercorn of Massachusetts General Hospital. I am in Colorado standing on top of Hope Pass, elevation 12,600 feet having hiked and ran up 3,400 feet of vertical gain since the morning as part of the TransRockies 58-mile staged trail race. For the next few minutes I appreciate the moment. Overcome with emotion, tears flood my eyes as I look back on the 18-month journey that began with an "out of the blue" stage IV lung cancer diagnosis followed by aggressive chemotherapy, radiation, surgery and the turmoil that immerses my wife and two young boys. Getting back on my feet, determined to continue and looking ahead, I return to the present, take deep breaths of the fresh, crisp (thin!) air...

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Prognostic Role of microRNA-21 Expression in Brain Tumors: a Meta-analysis

Mon, 14 Mar 2016 09:35:31 +0100

Abstract Many studies have shown that microRNAs have important roles in the development and progression of various cancers. Recent studies also showed that microRNA-21 expression may be associated with the prognosis of patients with several common cancers. However, there was still lack of evidence for the prognostic role of microRNA-21 expression in brain tumors. We performed a systemic review and meta-analysis of published and unpublished studies to assess the prognostic role of microRNA-21 expression in patients with brain tumors. PubMed, Embase, and Google Scholar databases were searched for eligible studies with data assessing the prognostic role of microRNA-21 expression in brain tumors. Pooled hazard ratios (HRs) of microRNA-21 expression for overall survival and 95 % conf...



2,3,7,8‐tetrachlorodibenzo‐p‐dioxin exposure influence the expression of glutamate transporter GLT‐1 in C6 glioma cells via the Ca2+/protein kinase C pathway

Mon, 14 Mar 2016 00:00:00 +0100

In this study, we investigated the role of TCDD in regulating the expression of glutamate transporter GLT‐1 in astrocytes. TCDD, at concentrations of 0.1–100 nm, had no significantly harmful effect on the viability of C6 glioma cells. However, the expression of GLT‐1 in C6 glioma cells was downregulated in a dose‐ and time‐dependent manner. TCDD also caused activation of protein kinase C (PKC), as TCDD induced translocation of the PKC from the cytoplasm or perinuclear to the membrane. The translocation of PKC was inhibited by one Ca2+ blocker, nifedipine, suggesting that the effects are triggered by the initial elevated intracellular concentration of free Ca2+. Finally, we showed that inhibition of the PKC activity reverses the TCDD‐triggered reduction of GLT‐1. In summary, o...



Overexpression of tissue microRNA10b may help predict glioma prognosis

Mon, 14 Mar 2016 00:00:00 +0100

Publication date: Available online 14 March 2016 Source:Journal of Clinical Neuroscience Author(s): Xinxin Zhang, Jian Cheng, Ling Fu, Qingshui Li We investigated the relationship between microRNA-10b (miR-10b) expression and prognosis in human glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to characterize the expression patterns of miR-10b in 128 glioma and 20 normal brain tissues. Clinical information – age, sex, Karnofsky Performance Status (KPS) and World Health Organization (WHO) grade – were also collected. The associations between miR-10b expression and the clinicopathological factors and outcome of glioma patients were statistically analyzed. Expression levels of miR-10b in glioma tissue were significantly higher than in norm...



SGEF Promotes Glioblastoma Cell Survival

Mon, 14 Mar 2016 00:00:00 +0100

Glioblastoma (GB) is the highest grade and most common form of primary adult brain tumors. Despite surgical removal followed by concomitant radiation and chemotherapy with the alkylating agent temozolomide, GB tumors develop treatment resistance and ultimately recur. Impaired response to treatment occurs rapidly, conferring a median survival of just fifteen months. Thus, it is necessary to identify the genetic and signaling mechanisms that promote tumor resistance to develop targeted therapies to combat this refractory disease. Previous observations indicated that SGEF (ARHGEF26), a RhoG-specific guanine nucleotide exchange factor (GEF), is overexpressed in GB tumors and plays a role in promoting TWEAK-Fn14–mediated glioma invasion. Here, further investigation revealed an important r...



Re: The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study) [letter]

Mon, 14 Mar 2016 00:00:00 +0100

(Source: American Journal of Neuroradiology)

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Contrast Leakage Patterns from Dynamic Susceptibility Contrast Perfusion MRI in the Grading of Primary Pediatric Brain Tumors [PEDIATRICS]

Mon, 14 Mar 2016 00:00:00 +0100

CONCLUSIONS: There was good interobserver agreement in the classification of DSC perfusion tissue signal-intensity time curves for pediatric brain tumors, particularly for T1-dominant leakage. Among patients with pediatric brain tumors, a T1-dominant leakage pattern is highly specific for a low-grade tumor and demonstrates high sensitivity and specificity for pilocytic or pilomyxoid astrocytomas. (Source: American Journal of Neuroradiology)



Histologically benign, clinically aggressive: Progressive non‐optic pathway pilocytic astrocytomas in adults with NF1

Mon, 14 Mar 2016 00:00:00 +0100

In conclusion, despite grade I histology, all three adult NF1 patients with progressive extra‐optic PAs suffered an aggressive clinical course which was not seen in pediatric patients. Clinicians should be aware of this clinico‐histologic discrepancy when counseling and managing adult NF1 patients with progressive extra‐optic PAs. © 2016 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A)



Inhibition of Autophagy by Chloroquine Enhances the Antitumor Efficacy of Sorafenib in Glioblastoma.

Mon, 14 Mar 2016 00:00:00 +0100

Authors: Liu X, Sun K, Wang H, Dai Y Abstract Glioblastoma multiforme (GBM) is the most aggressive and common brain tumor in adults. Sorafenib, a multi-kinase inhibitor, has been shown to inhibit cell proliferation and induce apoptosis through inhibition of STAT3 signaling in glioblastoma cells and in intracranial gliomas. However, sorafenib also induces cell autophagy. Due to the dual roles of autophagy in tumor cell survival and death, the therapeutic effect of sorafenib on glioblastoma is uncertain. Here, we combined sorafenib treatment in GBM cells (U373 and LN229) and tumors with the autophagy inhibitor chloroquine. We found that blockage of autophagy further inhibited cell proliferation and migration and induced cell apoptosis in vitro and in vivo. These findings suggest the ...



Ultrasound guided mini-invasive tailored approach and intraoperative neurophysiological monitoring. A synergistic strategy for the removal of tumours near the motor cortex. A preliminary experience.

Sun, 13 Mar 2016 19:15:02 +0100

CONCLUSIONS: The synergic strategy comprising intraoperative multimodal neurophysiological monitoring and the ultrasound sonography is feasible in all surgeries. Data are promising in terms of both clinical motor scores and extent of resection. This strategy represents an alternative approach to the treatment of supratentorial tumours, although further studies are necessary to confirm the long-term efficacy of this procedure. PMID: 26967717 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgical Sciences)



Loss of SOCS3 in myeloid cells prolongs survival in a syngeneic model of glioma.

Sun, 13 Mar 2016 18:08:02 +0100

Authors: McFarland BC, Marks MP, Rowse AL, Fehling SC, Gerigk M, Qin H, Benveniste EN Abstract In glioma, microglia and macrophages are the largest population of tumor-infiltrating cells, referred to as glioma associated macrophages (GAMs). Herein, we sought to determine the role of Suppressor of Cytokine Signaling 3 (SOCS3), a negative regulator of Signal Transducer and Activator of Transcription 3 (STAT3), in GAM functionality in glioma. We utilized a conditional model in which SOCS3 deletion is restricted to the myeloid cell population. We found that SOCS3-deficient bone marrow-derived macrophages display enhanced and prolonged expression of pro-inflammatory M1 cytokines when exposed to glioma tumor cell conditioned medium in vitro. Moreover, we found that deletion of SOCS3 in t...

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Metabolomics profiling in plasma samples from glioma patients correlates with tumor phenotypes.

Sun, 13 Mar 2016 18:08:02 +0100

CONCLUSION: Our findings identified metabolites and metabolic pathways that differentiated tumor phenotypes. These may be useful as host biomarker candidates to further help glioma molecular classification. PMID: 26967252 [PubMed - as supplied by publisher] (Source: Oncotarget)



The clinical value of aberrant epigenetic changes of DNA damage repair genes in human cancer.

Sun, 13 Mar 2016 18:08:02 +0100

Authors: Gao D, Herman JG, Guo M Abstract The stability and integrity of the human genome are maintained by the DNA damage repair (DDR) system. Unrepaired DNA damage is a major source of potentially mutagenic lesions that drive carcinogenesis. In addition to gene mutation, DNA methylation occurs more frequently in DDR genes in human cancer. Thus, DNA methylation may play more important roles in DNA damage repair genes to drive carcinogenesis. Aberrant methylation patterns in DNA damage repair genes may serve as predictive, diagnostic, prognostic and chemosensitive markers of human cancer. MGMT methylation is a marker for poor prognosis in human glioma, while, MGMT methylation is a sensitive marker of glioma cells to alkylating agents. Aberrant epigenetic changes in DNA damage repai...



Long-range and short-range tumor-stroma networks synergistically contribute to tumor-associated epilepsy.

Sun, 13 Mar 2016 18:08:02 +0100

Authors: Mao XY, Tokay T, Zhou HH, Jin WL Abstract Epileptic seizures are frequently caused by brain tumors. Traditional anti-epileptic treatments do not acquire satisfactory responses. Preoperative and postoperative seizures seriously influence the quality of life of patients. Thus, tumor-associated epilepsy (TAE) is an important subject of the current research. The delineation of the etiology of epileptogenesis in patients with primary brain tumor may help to find the novel and effective drug targets for treating this disease. In this review, we describe the current status of treatment of TAE. More importantly, we focus on the factors that are involved in the functional connectivity between tumors and stromal cells. We propose that there exist two modes, namely, long-range and sh...



PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma.

Sun, 13 Mar 2016 18:08:02 +0100

Authors: Li X, Wu C, Chen N, Gu H, Yen A, Cao L, Wang E, Wang L Abstract Glioblastoma multiform (GBM) is the most common malignant glioma of all the brain tumors and currently effective treatment options are still lacking. GBM is frequently accompanied with overexpression and/or mutation of epidermal growth factor receptor (EGFR), which subsequently leads to activation of many downstream signal pathways such as phosphatidylinositol 3-kinase (PI3K)/Akt/rapamycin-sensitive mTOR-complex (mTOR) pathway. Here we explored the reason why inhibition of the pathway may serve as a compelling therapeutic target for the disease, and provided an update data of EFGR and PI3K/Akt/mTOR inhibitors in clinical trials. PMID: 26967052 [PubMed - as supplied by publisher] (Source: Oncotarget)



Bacitracin Inhibits the Migration of U87-MG Glioma Cells via Interferences of the Integrin Outside-in Signaling Pathway.

Sat, 12 Mar 2016 07:19:02 +0100

CONCLUSION: Bacitracin, as a functional inhibitor of PDI, decreased the phosphorylated FAK and the secreted MMP-2, which are the downstream of integrin and play a major role in cell migration and invasion, might become one of the feasible therapeutic strategies for glioblastoma. PMID: 26962415 [PubMed] (Source: Journal of Korean Neurosurgical Society)

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Biological Significance of Mutant Isocitrate Dehydrogenase 1 and 2 in Gliomagenesis.

Sat, 12 Mar 2016 07:16:02 +0100

Authors: Ohba S, Hirose Y Abstract Mutations of the isocitrate dehydrogenase (IDH) genes are considered an important event that occurs at an early stage during gliomagenesis. The mutations often occur in grade 2 or 3 gliomas and secondary glioblastomas. Most IDH mutations are associated with codon 132 and 172 in IDH1 and IDH2 in gliomas, respectively. While IDH1 and IDH2 catalyze the oxidative decarboxylation of isocitrate to form α-ketoglutarate (α-KG), IDH1 and IDH2 mutations convert α-KG to 2-hydroxyglutarate (2-HG). The accumulation of oncometabolite 2-HG is believed to lead progenitor cells into gliomas, inhibiting several α-KG-dependent enzymes, including ten-eleven translocation enzymes, histone demethylases, and prolyl hydroxylases, although the mechanisms have not been...



MRI screening for glioma: a preliminary survey of healthy potential candidates

Sat, 12 Mar 2016 00:00:00 +0100

(Source: Acta Neurochirurgica)



A new cyclic RGD peptide dimer for integrin αvβ3 imaging.

Fri, 11 Mar 2016 11:56:03 +0100

CONCLUSIONS: These results suggest that the 131I-c(RGD)2 molecule may serve as a promising tracer for the detection of αvβ3-positive tumors. PMID: 26957261 [PubMed - in process] (Source: European Review for Medical and Pharmacological Sciences)



GLI2 Interacts with GCMa in Syncytialization [Signal Transduction]

Fri, 11 Mar 2016 00:00:00 +0100

Cell-cell fusion of human villous trophoblasts, referred to as a process of syncytialization, acts as a prerequisite for the proper development and functional maintenance of the human placenta. Given the fact that the main components of the Hedgehog signaling pathway are expressed predominantly in the syncytial layer of human placental villi, in this study, we investigated the potential roles and underlying mechanisms of Hedgehog signaling in trophoblastic fusion. Activation of Hedgehog signaling by a variety of approaches robustly induced cell fusion and the expression of syncytial markers, whereas suppression of Hedgehog signaling significantly attenuated cell fusion and the expression of syncytial markers in both human primary cytotrophoblasts and trophoblast-like BeWo cells. Moreover, ...



Interplay between GnT-III and ST6GAL1 in Regulating Cell Migration [Glycobiology and Extracellular Matrices]

Fri, 11 Mar 2016 00:00:00 +0100

N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. Overexpression of GnT-III inhibited migration in multiple types of tumor cells. However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. In detail, we show that overexpression of GnT-III significantly inhibits α2,3-sialylation but not α2,6-sialylation. The migratory ability of cells without or with a low level of α2,6-sialylation is consistently suppressed after GnT-III overexpression. In ...

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Carboplatin loaded Surface modified PLGA nanoparticles: Optimization, characterization, and in vivo brain targeting studies

Fri, 11 Mar 2016 00:00:00 +0100

Publication date: 1 June 2016 Source:Colloids and Surfaces B: Biointerfaces, Volume 142 Author(s): S. Jose, B.C. Juna, T.A. Cinu, H. Jyoti, N.A. Aleykutty The carboplatin (CP) loaded poly-lactide-co-glycolide (PLGA) nanoparticles (NPs) were formulated by modified solvent evaporation method. Its surface modification is done by 1% polysorbate80 (P80) to improve their entry into the brain after intraperitoneal administration (i.p) via receptor-mediated pathways. A formulation with maximum entrapment efficiency and minimal particle size was optimized by central composite design (CCD) based on mean particle size, and entrapment efficiencies as responses. The optimized formulation was characterized by mean particle size, entrapment efficiency, zeta potential, Fourier transform infrared (F...



Hydrophobic fractal surface from glycerol tripalmitate and the effects on C6 glioma cell growth

Fri, 11 Mar 2016 00:00:00 +0100

Publication date: 1 June 2016 Source:Colloids and Surfaces B: Biointerfaces, Volume 142 Author(s): Shanshan Zhang, Xuerui Chen, Jing Yu, Biyuan Hong, Qunfang Lei, Wenjun Fang To provide a biomimic environment for glial cell culture, glycerol tripalmitate (PPP) has been used as a raw material to prepare fractal surfaces with different degrees of hydrophobicity. The spontaneous formation of the hydrophobic fractal surfaces was monitored by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The surface morphologies were observed by a scanning electron microscope (SEM), and then the fractal dimension (FD) values of the surfaces were determined with the box-counting method. C6 glioma cells were cultured and compared on different hydrophobic PPP surfaces and poly-L-lysi...



Assessing the efficacy of coherent anti‐Stokes Raman scattering microscopy for the detection of infiltrating glioblastoma in fresh brain samples

Fri, 11 Mar 2016 00:00:00 +0100

Coherent anti‐Stokes Raman scattering (CARS) microscopy is an emerging technique for identification of brain tumors. However, tumor identification by CARS microscopy on bulk samples and in vivo has been so far verified retrospectively on histological sections, which only provide a gross reference for the interpretation of CARS images without matching at cellular level. Therefore, fluorescent labels were exploited for direct assessment of the interpretation of CARS images of solid and infiltrative tumors. Glioblastoma cells expressing green fluorescent protein (GFP) were used for induction of tumors in mice (n = 7). The neoplastic nature of cells imaged by CARS microscopy was unequivocally verified by addressing two‐photon fluorescence of GFP on fresh brain slices and in vivo. In fresh ...



Immunohistochemistry on IDH 1/2, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas

Fri, 11 Mar 2016 00:00:00 +0100

Abstract The molecular subgrouping of diffuse gliomas was recently found to stratify patients into prognostically distinct groups better than histological classification. Among several molecular parameters, the key molecules for the subtype diagnosis of diffuse gliomas are IDH mutation, 1p/19q co-deletion, and ATRX mutation; 1p/19q co-deletion is undetectable by immunohistochemistry, but is mutually exclusive with ATRX and p53 mutation in IDH mutant gliomas. Therefore, we applied ATRX and p53 immunohistochemistry instead of 1p/19q co-deletion analysis. The prognostic value of immunohistochemical diagnosis for Grade III gliomas was subsequently investigated. Then, the same immunohistochmical diagnostic approach was expanded for the evaluation of Grade II and IV diffuse glioma progn...



MicroRNA and extracellular vesicles in glioblastoma: small but powerful

Fri, 11 Mar 2016 00:00:00 +0100

Abstract To promote the tumor growth, angiogenesis, metabolism, and invasion, glioblastoma (GBM) cells subvert the surrounding microenvironment by influencing the endogenous activity of other brain cells including endothelial cells, macrophages, astrocytes, and microglia. Large number of studies indicates that the intra-cellular communication between the different cell types of the GBM microenvironment occurs through the functional transfer of oncogenic components such as proteins, non-coding RNAs, DNA and lipids via the release and uptake of extracellular vesicles (EVs). Unlike the communication through the secretion of chemokines and cytokines, the transfer and gene silencing activity of microRNAs through EVs is more complex as the biogenesis and proper packaging of microRNAs is...

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MR spectroscopy for in vivo assessment of the oncometabolite 2‐hydroxyglutarate and its effects on cellular metabolism in human brain gliomas at 9.4T

Fri, 11 Mar 2016 00:00:00 +0100

ConclusionWe demonstrate that MRS at 9.4T provides a noninvasive measure of 2HG in vivo, which may be used for therapy planning and prognostication, and may provide insights into related pathophysiologic metabolic alterations associated with IDH mutations. J. Magn. Reson. Imaging 2016. (Source: Journal of Magnetic Resonance Imaging)



No correlation between NF1 mutation position and risk of optic pathway glioma in 77 unrelated NF1 patients

Fri, 11 Mar 2016 00:00:00 +0100

Abstract Neurofibromatosis type 1 (NF1) is a common monogenic disorder whereby affected individuals are predisposed to developing CNS tumors, including optic pathway gliomas (OPGs, occurring in ~15 to 20 % of cases). So far, no definite genotype–phenotype correlation determining NF1 patients at risk for tumor formation has been described, although enrichment for mutations in the 5′ region of the NF1 gene in OPG patients has been suggested. We used whole exome sequencing, targeted sequencing, and copy number analysis to screen 77 unrelated NF1 patients with (n = 41) or without (n = 36; age ≥10 years) optic pathway glioma for germline NF1 alterations. We identified germline NF1 mutations in 69 of 77 patients (90 %), but no genotype–phenotype correlation was observed....



Bioinformatic analyses reveal a distinct Notch activation induced by STAT3 phosphorylation in the mesenchymal subtype of glioblastoma.

Fri, 11 Mar 2016 00:00:00 +0100

CONCLUSIONS These findings suggest a prominent role for STAT3 signaling in mesenchymal GBM and highlight the importance of identifying signaling pathways that contribute to specific cancer subtypes. PMID: 26967788 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)



Motor areas of the frontal cortex in patients with motor eloquent brain lesions.

Fri, 11 Mar 2016 00:00:00 +0100

CONCLUSIONS The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning. PMID: 26967780 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)



Prognostic role of STAT3 in solid tumors: a systematic review and meta-analysis.

Thu, 10 Mar 2016 18:18:02 +0100

In conclusion, elevated STAT3 expression is associated with poor survival in most solid tumors. STAT3 is a valuable biomarker for prognosis prediction and a promising therapeutic target in human solid tumors. PMID: 26959884 [PubMed - as supplied by publisher] (Source: Oncotarget)

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Knock-down of Hdj2/DNAJA1 co-chaperone results in an unexpected burst of tumorigenicity of C6 glioblastoma cells.

Thu, 10 Mar 2016 18:18:02 +0100

Authors: Meshalkina DA, Shevtsov MA, Dobrodumov AV, Komarova EY, Voronkina IV, Lazarev VF, Margulis BA, Guzhova IV Abstract The chaperone system based on Hsp70 and proteins of the DnaJ family is known to protect tumor cells from a variety of cytotoxic factors, including anti-tumor therapy. To analyze whether this also functions in a highly malignant brain tumor, we knocked down the expression of Hsp70 (HSPA1A) and its two most abundant co-chaperones, Hdj1 (DNAJB1) and Hdj2 (DNAJA1) in a C6 rat glioblastoma cell line. As expected, tumor depletion of Hsp70 caused a substantial reduction in its growth rate and increased the survival of tumor-bearing animals, whereas the reduction of Hdj1 expression had no effect. Unexpectedly, a reduction in the expression of Hdj2 led to the enhanced ...



Survival kinase genes present prognostic significance in glioblastoma.

Thu, 10 Mar 2016 18:18:02 +0100

Authors: Varghese RT, Liang Y, Guan T, Franck CT, Kelly DF, Sheng Z Abstract Cancer biomarkers with a strong predictive power for diagnosis/prognosis and a potential to be therapeutic targets have not yet been fully established. Here we employed a loss-of-function screen in glioblastoma (GBM), an infiltrative brain tumor with a dismal prognosis, and identified 20 survival kinase genes (SKGs). Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that the expression of CDCP1, CDKL5, CSNK1E, IRAK3, LATS2, PRKAA1, STK3, TBRG4, and ULK4 stratified GBM prognosis with or without temozolomide (TMZ) treatment as a covariate. For the first time, we found that GBM patients with a high level of NEK9 and PIK3CB had a greater chance of having recurrent tumors. The expression ...



Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas.

Thu, 10 Mar 2016 18:18:02 +0100

In conclusion, our findings indicate that autophagy in gliomas is rather driven by micro-environmental changes than by primary glioma-intrinsic features thus challenging the concept of exploitation of the autophago-lysosomal network (ALN) as a treatment approach in gliomas. PMID: 26956048 [PubMed - as supplied by publisher] (Source: Oncotarget)



Bilateral Thalamic Glioma: Case Report and Review.

Thu, 10 Mar 2016 14:05:02 +0100

We present the case of a 72 years old male suffering from the rapid deterioration of cognitive function to moderately severe dementia in a short period of time. Magnetic resonance studies demonstrated a bilateral thalamic glioma with a minimal focal gadolinium uptake in the left thalamus. Biopsy was performed and pathology report was of anaplastic astrocytoma, WHO grade III. Radiotherapy was proposed but was rejected by the patient's relatives. The patient deceased 57 days later. We performed an extensive review of the literature and by updating the previous described series we can state that to the best of our knowledge this is the 60th case described in the literature and the second eldest patient presented. Patients suffering from this disease present a poor prognosis, the longest survi...