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Genetics and epigenetics of gliomas.
Abstract Gliomas are the most common primary intrinsic brain tumours. Their classification is based on phenotypic resemblance to normal glial cells (astrocytomas, oligodendrogliomas, mixed oligoastrocytomas) and pathological grading. Whereas this system is clinically relevant and has been the basis for our understanding of gliomas, systematic use of next-generation sequencing has transformed our knowledge of their pathogenesis and has uncovered genetic changes in an unanticipated number of genes and regulatory elements. In the past few years, in-depth analysis of low-grade astrocytomas and glioblastomas in both pae...
Source: Swiss Medical Weekly - October 31, 2014 Category: Journals (General) Authors: Suvà ML Tags: Swiss Med Wkly Source Type: research

Mixed glioma with molecular features of composite oligodendroglioma and astrocytoma: a true “oligoastrocytoma”?
(Source: Acta Neuropathologica)
Source: Acta Neuropathologica - October 31, 2014 Category: Neurology Source Type: research

MGMT promoter methylation and correlation with protein expression in primary central nervous system lymphoma
Abstract The O 6-methylguanine-DNA-methyltransferase (MGMT) gene encodes for a DNA repairing enzyme of which silencing by promoter methylation is involved in brain tumorigenesis. MGMT promoter methylation represents a favorable prognostic factor and has been associated with a better response to alkylating agents in glioma and systemic lymphoma. Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal malignant lymphoma. The current standard of care, based on high-dose methotrexate chemotherapy, has improved prognosis but outcome remains poor for a majority of patients. Therap...
Source: Virchows Archiv - October 30, 2014 Category: Pathology Source Type: research

MiR-133b Contributes to Arsenic-Induced Apoptosis in U251 Glioma Cells by Targeting the hERG Channel
Abstract Substantial evidence indicates that the human ether-a-go-go-related gene potassium channel (hERG, Kv11.1, KCNH2) is overexpressed in human glioblastoma multiforme (GBM) specimens and plays an essential role in the malignant proliferation of glioma cells. However, its upstream regulator in glioma cells is not fully elucidated. The present study was designed to determine whether the expression of hERG gene is regulated by miR-133b or miR-34a, thereby contributing to the anti-proliferation effect of arsenic trioxide (ATO) in U251 human glioma cells. Real-time polymerase chain reactions (qRT-PCR) and Western ...
Source: Journal of Molecular Neuroscience - October 30, 2014 Category: Neuroscience Source Type: research

Profile of MicroRNA Expression in Brain Tumors of Different Malignancy
The expression profiles of 10 mature microRNA (7, 10a, 17, 20a, 21, 23a, 26a, 137, 222) in biopsy specimens of gliomas of different malignancy were studied by the real time PCR with SYBR Green I fluorescent stain. The expression of microRNA-21 increased significantly, while that of microRNA-137 decreased, depending on the tumor malignancy. The expression of microRNA-9, −17, −20a, −23a, −26a was significantly higher, while that of microRNA-7 lower in the tumor vs. control tissue samples. New data on the molecular pathological mechanisms of gliomas related to their malignancy were obtained. Quantitative analysis of m...
Source: Bulletin of Experimental Biology and Medicine - October 29, 2014 Category: Biology Source Type: research

Revisiting TP53 Mutations and Immunohistochemistry—A Comparative Study in 157 Diffuse Gliomas
Abstract The association between p53 immunohistochemistry and TP53 mutation status has been controversial. The present study aims to re‐evaluate the efficacy of p53 immunohistochemistry to predict the mutational status of TP53. A total of 157 diffuse gliomas (World Health Organization grades II–IV) were assessed by exon‐by‐exon DNA sequencing from exon 4 through 10 of TP53 using frozen tissue samples. Immunohistochemistry with a p53 antibody (DO‐7) on paired formalin‐fixed paraffin‐embedded materials was assessed for the extent and intensity of reactivity in all cases. A total of 72 mutations were detected in...
Source: Brain Pathology - October 29, 2014 Category: Neurology Authors: Hirokazu Takami, Akihiko Yoshida, Shintaro Fukushima, Hideyuki Arita, Yuko Matsushita, Taishi Nakamura, Makoto Ohno, Yasuji Miyakita, Soichiro Shibui, Yoshitaka Narita, Koichi Ichimura Tags: Research Article Source Type: research

Spinal Cord Stimulation as Adjuvant During Chemotherapy and Reirradiation Treatment of Recurrent High-Grade Gliomas
Conclusions. Spinal cord stimulation during reirradiation and chemotherapy is feasible and well tolerated. In our study, spinal cord stimulation was associated with clinical improvement and longer survival than previously reported in recurrent anaplastic gliomas. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation in relapsed HGGs merits further research. (Source: Integrative Cancer Therapies)
Source: Integrative Cancer Therapies - October 29, 2014 Category: Cancer & Oncology Authors: Clavo, B., Robaina, F., Jorge, I. J., Cabrera, R., Ruiz-Egea, E., Szolna, A., Otermin, E., Llontop, P., Carames, M. A., Santana-Rodriguez, N., Sminia, P. Tags: Articles Source Type: research

Elimination of Cancer Stem-Like Side Population in Human Glioblastoma Cells Accompanied With Stemness Gene Suppression by Korean Herbal Recipe MSC500
Conclusion: Our results suggest the potential role of MSC500 as an integrative and complementary therapeutic for advanced or refractory high-grade glioma patients. (Source: Integrative Cancer Therapies)
Source: Integrative Cancer Therapies - October 29, 2014 Category: Cancer & Oncology Authors: Yao, C.-J., Han, T.-Y., Shih, P.-H., Yi, T.-Y., Lai, I.-C., Chang, K.-H., Lai, T.-Y., Chang, C.-L., Lai, G.-M. Tags: Articles Source Type: research

T1 in high‐grade glioma and the influence of different measurement strategies on parameter estimations in DCE‐MRI
ConclusionTemporal changes in the median kinetic parameters in tumor were equally well described using pixel‐wise and fixed T1(0) despite an increase in T1(0) over time, suggesting that T1 mapping is not generally required in DCE‐MRI based monitoring of glioma patients.J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc. (Source: Journal of Magnetic Resonance Imaging)
Source: Journal of Magnetic Resonance Imaging - October 28, 2014 Category: Radiology Authors: Christopher Larsson, Magne Kleppestø, Inge Grothe, Jonas Vardal, Atle Bjørnerud Tags: Original Research Source Type: research

New findings show that different brain tumors have the same origin
(Uppsala University) Glioma is a common name for serious brain tumors. Different types of glioma are usually diagnosed as separate diseases and have been considered to arise from different cell types in the brain. Now researchers at Uppsala University have shown that one and the same cell of origin can give rise to different types of glioma. This is important for the basic understanding of how these tumors are formed and can contribute to the development of more efficient and specific glioma therapies. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - October 28, 2014 Category: Global & Universal Source Type: news

Histologically Proven Radiation‐Induced Brainstem Glioma 93 Months After External Beam Radiotherapy for Pituitary Macroadenoma: Radiation Treatment Dose and Volume Correlation
ABSTRACT Patient is a 29‐year‐old with a history of recurrent growth hormone‐secreting pituitary macroadenoma diagnosed 12 years prior to presentation. Eight years prior to current presentation, the patient underwent re‐resection and received 50.4 Gy external beam radiotherapy (EBRT) in 28 fractions of 1.8 Gy each. Serial postradiation MRIs demonstrated regression in pituitary tumor size. Patient presented with new headaches 7.5 years after completing EBRT. Brain MRI demonstrated new FLAIR hyperintensity and contrast enhancement within the pons and medulla, corresponding to the 36 Gy isodose line of each radiation ...
Source: Journal of Neuroimaging - October 28, 2014 Category: Radiology Authors: Salim E. Abboud, Leo J. Wolansky, Sunil V. Manjila, Simon S. Lo, Baha M. Arafah, Warren R. Selman, Marta E. Couce, Lisa R. Rogers Tags: Case Report Source Type: research

Gene expression analyses to explore the biomarkers and therapeutic targets for gliomas
Abstract To improve treatment strategies of glioma, microarray data were applied to screen target molecules that were regulated by microRNAs (miRNAs). GSE31262 was downloaded from Gene Expression Omnibus, including five neural stem cells samples from normal human and nine stem cells samples from glioma patients. Differentially expressed genes (DEGs) were identified with Multtest package and Limma package of R language, and false discovery rate < 0.05 and |log2FC (fold change)| >1 were chosen as cut-off criterion. Hierarchical clustering and pathway enrichment analysis of DEGs were performed using pheatmap p...
Source: Neurological Sciences - October 28, 2014 Category: Neurology Source Type: research

Long-term proper name anomia after removal of the uncinate fasciculus.
We report a longer-term follow-up (9-12 months) in a selected group of 17 patients (six female, age range 27-64) who did not suffer any tumour recurrence in this timeframe. MRI and DTI were performed before and after surgery. While verbal fluency on categorical cue and object naming recovered to the same level as before surgery, proper naming remained significantly impaired even after 12 months (P = 0.032) in patients with uncinate removal, demonstrating this structure to be crucial for that function and supporting the hypothesis that subcortical connectivity is relevant to allow plasticity. We thus argued that the lef...
Source: Brain Structure and Function - October 28, 2014 Category: Neuroscience Authors: Papagno C, Casarotti A, Comi A, Pisoni A, Lucchelli F, Bizzi A, Riva M, Bello L Tags: Brain Struct Funct Source Type: research

3D Multimodal MRI Brain Glioma Tumor and Edema Segmentation: AGraph Cut Distribution Matching Approach
This study investigates a fast distribution-matching, data-driven algorithm for 3D multimodal MRI brain glioma tumor and edema segmentation in different modalities. From a very simple user input, we learn non-parametric model distributions which characterize the normal regions in the current data. Then, we state our segmentation problems as the optimization of several cost functions of the same form, each containing two terms: (i) a distribution matching prior, which evaluates a global similarity between distributions, and (ii) a smoothness prior to avoid the occurrence of small, isolated regions in the solution. (Source: ...
Source: Computerized Medical Imaging and Graphics - October 28, 2014 Category: Radiology Authors: Ines Njeh, Lamia sallemi, Ismail Ben ayed, Khalil Chtourou, Stephane Lehericy, Damien Galanaud, Ahmed Ben Hamida Source Type: research

Long-term proper name anomia after removal of the uncinate fasciculus
We report a longer-term follow-up (9–12 months) in a selected group of 17 patients (six female, age range 27–64) who did not suffer any tumour recurrence in this timeframe. MRI and DTI were performed before and after surgery. While verbal fluency on categorical cue and object naming recovered to the same level as before surgery, proper naming remained significantly impaired even after 12 months (P = 0.032) in patients with uncinate removal, demonstrating this structure to be crucial for that function and supporting the hypothesis that subcortical connectivity is relevant to allow plasticity. We thus argued that the...
Source: Anatomy and Embryology - October 27, 2014 Category: Anatomy Source Type: research

Case Western researchers awarded $250,000 to develop an effective treatment for childhood brain tumors
(Case Western Reserve University) Prayers from Maria Children's Glioma Cancer Foundation announced today that it will award its $250,000 Melana Matson Memorial Grant -- its third major research grant since 2010 -- to Case Western Reserve University, Case Comprehensive Cancer Center researchers James Basilion, Ph.D., Efstathis Karathanasis, Ph.D., and John Letterio, M.D., who are studying the use of nanotechnology to more effectively treat pediatric glioma brain tumors. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - October 27, 2014 Category: Cancer & Oncology Source Type: news

How Stemlike Are Sphere Cultures From Long-term Cancer Cell Lines? Lessons From Mouse Glioma Models
AbstractCancer stem cells may mediate therapy resistance and recurrence in various types of cancer, including glioblastoma. Cancer stemlike cells can be isolated from long-term cancer cell lines, including glioma lines. Using sphere formation as a model for cancer cell stemness in vitro, we derived sphere cultures from SMA-497, SMA-540, SMA-560, and GL-261 glioma cells. Gene expression and proteomics profiling demonstrated that sphere cultures uniformly showed an elevated expression of stemness-associated genes, notably including CD44. Differences in neural lineage marker expression between nonsphere and sphere cultures we...
Source: Journal of Neuropathology and Experimental Neurology - October 24, 2014 Category: Neurology Tags: Original Articles Source Type: research

Platelet-derived growth factor in glioblastoma-driver or biomarker?
In conclusion, a PDGF receptor profile may be a biomarker for a subgroup of GBM originating from a PDGF receptor-responsive cell. Although compelling experimental and clinical evidence supports the notion that the PDGF receptor pathway is a driver in GBM, formal proof is still missing. PMID: 25342206 [PubMed - as supplied by publisher] (Source: Upsala Journal of Medical Sciences)
Source: Upsala Journal of Medical Sciences - October 24, 2014 Category: Journals (General) Authors: Westermark B Tags: Ups J Med Sci Source Type: research

Glutamatergic neuron-targeted loss of LGI1 epilepsy gene results in seizures
Leucin-rich, glioma inactivated 1 (LGI1) is a secreted protein linked to human seizures of both genetic and autoimmune aetiology. Mutations in the LGI1 gene are responsible for autosomal dominant temporal lobe epilepsy with auditory features, whereas LGI1 autoantibodies are involved in limbic encephalitis, an acquired epileptic disorder associated with cognitive impairment. We and others previously reported that Lgi1-deficient mice have early-onset spontaneous seizures leading to premature death at 2–3 weeks of age. Yet, where and when Lgi1 deficiency causes epilepsy remains unknown. To address these questions, we ge...
Source: Brain - October 24, 2014 Category: Neurology Authors: Boillot, M., Huneau, C., Marsan, E., Lehongre, K., Navarro, V., Ishida, S., Dufresnois, B., Ozkaynak, E., Garrigue, J., Miles, R., Martin, B., Leguern, E., Anderson, M. P., Baulac, S. Tags: Original Articles Source Type: research

Decreased expression of the SPOP gene is associated with poor prognosis in glioma.
This study suggests that speckle-type POZ protein (SPOP) may be a tumor suppressor gene and its prognostic value in human glioma. Real-time quantitative RT-PCR (qRT‑PCR), western blotting, and immunohistochemical staining were used to examine SPOP expression in glioma tissues and normal brain (NB) tissues. The relationships between the SPOP expression levels, the clinicopathological factors, and patient survival were investigated. The molecular mechanisms of SPOP expression and its effects on cell viability, migration and invasion were also explored by MTT assay, wound-healing assays and Transwell assay. SPOP mRNA and pr...
Source: International Journal of Oncology - October 24, 2014 Category: Cancer & Oncology Authors: Ding D, Song T, Jun W, Tan Z, Fang J Tags: Int J Oncol Source Type: research

Reoperation for Recurrent High-Grade Glioma: A Current Perspective of the Literature
Optimal treatment for recurrent high-grade glioma continues to evolve. Currently, however, there is no consensus in the literature on the role of reoperation in the management of these patients. In this analysis, we reviewed the literature to examine the role of reoperation in patients with World Health Organization grade III or IV recurrent gliomas, focusing on how reoperation affects outcome, perioperative complications, and quality of life. An extensive literature review was performed through the use of the PubMed and Ovid Medline databases for January 1980 through August 2013. A total 31 studies were included in the fi...
Source: Neurosurgery - October 23, 2014 Category: Neurosurgery Tags: Review Source Type: research

End of life care in high-grade glioma patients in three European countries: a comparative study
This study aimed to (1) compare EOL care processes for high-grade glioma (HGG) patients in three European countries, (2) explore differences in perceived quality of care (QOC), and (3) identify aspects of good QOC in the EOL phase. We analyzed 207 questionnaires from relatives of deceased HGG patients, using a similar retrospective study design in three countries [The Netherlands (n = 83), Austria (n = 72) and the UK (n = 52)], and examined four subthemes: (1) organization of EOL care, (2) treatment preferences, (3) experiences with EOL care, (4) perceived QOC. Three months before death 75 % of patients were at home...
Source: Journal of Neuro-Oncology - October 23, 2014 Category: Cancer & Oncology Source Type: research

Antiepileptic drug prophylaxis in primary brain tumor patients: is current practice in agreement to the consensus?
Abstract The role of antiepileptic drugs (AED) prophylaxis in primary brain tumor (PBT) seizure-naïve patients remains unclear. Additionally, AED are associated with severe side effects, negative impact on cognition and drug interactions. Little is known about current practice regarding prophylactic AED use in PBT. We investigated its use in a tertiary care cancer center. We reviewed medical records of 260 patients registered in our center between 2008 and 2012, focusing on prophylactic AED use. A descriptive analysis was performed with SPSS IBM version 20.0. Median age was 44.5 years (11–83). Most patients h...
Source: Journal of Neuro-Oncology - October 23, 2014 Category: Cancer & Oncology Source Type: research

Venous thromboembolism in high grade glioma among surgical patients: results from a single center over a 10 year period
Abstract Patients with high-grade glioma are at elevated risk of venous thromboembolism (VTE). The relationship between VTE and survival in glioma patients remains unclear, as does the optimal protocol for chemoprophylaxis. The purpose of this study was to assessthe incidence of and risk factors associated with VTE in patients with high-grade glioma, and the correlation between VTE and survival in this population. Furthermore, we sought to define a protocol for perioperative DVT prophylaxis. This was a retrospective review of patients who underwent craniotomy for resection of high-grade glioma (WHO grade III ...
Source: Journal of Neuro-Oncology - October 23, 2014 Category: Cancer & Oncology Source Type: research

Diagnostic challenges, management and outcomes of midline low-grade gliomas
Conclusions Diagnosis of midline LGGs is complicated by both limitations of biopsy and imaging. Midline tumours have a poorer prognosis compared to lobar equivalents and survival differences are probably due to the absence of significant surgical intervention in midline locations. (Source: Journal of Neuro-Oncology)
Source: Journal of Neuro-Oncology - October 23, 2014 Category: Cancer & Oncology Source Type: research

Mechanisms involved in kinin-induced glioma cells proliferation: the role of ERK1/2 and PI3K/Akt pathways
This study investigated the role of kinin B1 and B2 receptors (B1R and B2R) on cell proliferation in human glioblastoma cell lineages. The mRNA expression of B1R and B2R was verified by RT-qPCR, whereas the effects of kinin agonists (des-Arg9-BK and BK) were analyzed by cell counting, MTT assay and annexin-V/PI determination. The PI3K/Akt and ERK1/2 signaling activation was assessed by flow cytometry. Our results demonstrated that both human glioblastoma cell lines U-138MG and U-251MG express functional B1R and B2R. The proliferative effects induced by the incubation of des-Arg9-BK and BK are likely related to the activati...
Source: Journal of Neuro-Oncology - October 23, 2014 Category: Cancer & Oncology Source Type: research

Olig2 labeling index is correlated with histological and molecular classifications in low-grade diffuse gliomas
In conclusion, Olig2 LI cannot be taken as a complete surrogate marker for molecular genotype, but could possibly provide some ancillary information when molecular assay is not availabe. (Source: Journal of Neuro-Oncology)
Source: Journal of Neuro-Oncology - October 23, 2014 Category: Cancer & Oncology Source Type: research

TERT promoter mutations and BRAF mutations are rare in sporadic, and TERT promoter mutations are absent in NF1-related malignant peripheral nerve sheath tumors
Abstract Hot spot mutations in the promoter region of telomerase reverse transcriptase (TERT promoter mutations) occur frequently in tumors of neuroectodermal origin such as melanoma and glioma. Many of these tumors are of neuroectodermal or ectomesenchymal origin which is suggestive of TERT promoter mutations playing a role in the development of malignant peripheral nerve sheath tumors (MPNSTs). In melanoma a correlation has been suggested between the occurrence of TERT promoter mutations and v-RAF murine sarcoma viral oncogene homolog B1 (BRAF) mutations. We investigated TERT promoter and BRAF mutation frequenc...
Source: Journal of Neuro-Oncology - October 23, 2014 Category: Cancer & Oncology Source Type: research

Vismodegib: A Review
Publication date: October 2014 Source:Actas Dermo-Sifiliográficas (English Edition), Volume 105, Issue 8 Author(s): V. Ruiz-Salas , M. Alegre , A. López-Ferrer , J.R. Garcés In January 2012, vismodegib (Erivedge, manufactured by Genentech) became the first selective inhibitor of the Hedgehog signaling pathway to be approved by the US Food and Drug Administration for the treatment of locally advanced and metastatic basal cell carcinoma. The drug selectively binds to Smoothened, a 7-helix transmembrane receptor, thereby inhibiting activation of transcription factors of the glioma-associated oncogene family and suppressi...
Source: Actas Dermo-Sifiliograficas - October 23, 2014 Category: Dermatology Source Type: research

Prospective therapies for high-grade glial tumours: A literature review
Publication date: September 2014 Source:Annals of Medicine and Surgery, Volume 3, Issue 3 Author(s): Sayed Samed Talibi , Sayed Samie Talibi , Bashaar Aweid , Osama Aweid After three decades of intensive research, cytoreductive surgery remains the gold standard of treatment of malignant gliomas. Survivorship at both 1-year and 5-years has not drastically changed in the UK. Concomitant chemo- and radiotherapy has enhanced the efficiency of surgery, enabling more aggressive tumour resection whilst also preserving the surrounding healthy brain parenchyma. More accurate imaging techniques have also played a role in tumour id...
Source: Annals of Medicine and Surgery - October 23, 2014 Category: Journals (General) Source Type: research

Successive distinct high-grade gliomas in L-2-hydroxyglutaric aciduria
Abstract Patients with L-2-hydroxyglutaric aciduria are at risk for developing cerebral neoplasms, particularly gliomas, as one of the optical isomers of the known oncometabolite, 2-hydroxyglutarate is produced in L-2-hydroxyglutaric aciduria. To illustrate the concept of sustained oncogenic potential in permanent exposure to L-2-hydroxyglutarate in brain tissue, we present the medical history of a patient with L-2-hydroxyglutaric aciduria who underwent surgery to remove a right temporal anaplastic astrocytoma and developed an anatomically distinct, but histopathologically similar, tumor in the left frontal region...
Source: Journal of Inherited Metabolic Disease - October 23, 2014 Category: Internal Medicine Source Type: research

Management of Elderly Patients With Gliomas.
Abstract The current progressive aging of the population is resulting in a continuous increase in the incidence of gliomas in elderly people, especially the most frequent subtype, glioblastoma (GBM). This sociohealth shift, known as the "silver tsunami," has prompted the neuro-oncology community to investigate the role of specific antitumor treatments, such as surgery, radiotherapy, chemotherapy, and other targeted therapies, for these traditionally undertreated patients. Advanced age, a widely recognized poor prognostic factor in both low-grade glioma (LGG) and high-grade glioma patients, should no longer be the s...
Source: The Oncologist - October 23, 2014 Category: Cancer & Oncology Authors: Gállego Pérez-Larraya J, Delattre JY Tags: Oncologist Source Type: research

Down Regulated Expression of Claudin-1 and Claudin-5 and Up Regulation of β-catenin Protein is Associated with Human Glioma Progression.
Abstract Glioblastoma multiforme is the most common form of intracranial malignancy in humans, and is characterized by aggressive tumor growth, tissue invasion and neurodegenerative properties. The present study investigated the expression status of tight junction associated Claudin 1 (CLDN1), Claudin 5 (CLDN5) and Adheren junction associated β-catenin genes in the light of their critical role in the progression of both low- and high-grade human gliomas. Using quantitative PCR and Western blot methods the mRNA and protein status of CLDN1, CLDN5 and β-catenin genes were studied in a total of 25 human gliomas of Wo...
Source: CNS and Neurological Disorders Drug Targets - October 23, 2014 Category: Drugs & Pharmacology Authors: Karnati HK, Panigrahi M, Shaik NA, Greig NH, Bagadi SA, Kapalavayi N Tags: CNS Neurol Disord Drug Targets Source Type: research

Erratum to "LRIG1 Enhances Chemosensitivity by Modulating BCL-2 Expression and Receptor Tyrosine Kinase Signaling in Glioma Cells" by Guo Z, et al. (Yonsei Med J 2014;55:1196-205.).
Authors: Abstract We would like to add the grant. PMID: 25323917 [PubMed - as supplied by publisher] (Source: Yonsei Medical Journal)
Source: Yonsei Medical Journal - October 22, 2014 Category: Universities & Medical Training Tags: Yonsei Med J Source Type: research

When should we consider transplantation in adult patients with sclerosing cholangitis due to multisystem Langerhans’ cell histiocytosis?
A 49-year-old male presented with jaundice and rapid general health impairment. For a decade, he was managed for hypopituitarism due to a pituitary stalk lesion, diagnosed as optic glioma. Physical examination revealed clinical signs of cirrhosis and purpuric scalp lesions. Laboratory tests showed cholestasis and inflammation. Skin biopsy showed large cell infiltrate, staining with S-100 protein and CD1a, confirming Langerhans cell histiocytosis (LCH). Magnetic resonance imaging with cholangiogram found moderate segmental intrahepatic biliary ductal dilatation and distortion, consistent with sclerosing cholangitis (SC, Sup...
Source: Digestive and Liver Disease - October 22, 2014 Category: Gastroenterology Authors: Julien Scanzi, Marion Goutte, Camille Teilhet, Armand Abergel Tags: Correspondence Source Type: research

The tumor suppressor prostate apoptosis response-4 (Par-4) is regulated by mutant IDH1 and kills glioma stem cells
Abstract Prostate apoptosis response-4 (Par-4) is an endogenous tumor suppressor that selectively induces apoptosis in a variety of cancers. Although it has been the subject of intensive research in other cancers, less is known about its significance in gliomas, including whether it is regulated by key driver mutations, has therapeutic potential against glioma stem cells (GSCs), and/or is a prognostic marker. We found that patient-derived gliomas with mutant isocitrate dehydrogenase 1 have markedly lower Par-4 expression (P < 0.0001), which was validated by The Cancer Genome Atlas dataset (P = 2.0 E-13). T...
Source: Acta Neuropathologica - October 21, 2014 Category: Neurology Source Type: research

Agios begins Phase I/II trial of AG-221 to treat advanced solid tumours
Agios Pharmaceuticals has started a Phase I/II multicentre trial of AG-221 in patients with advanced solid tumours, including gliomas, as well as angioimmunoblastic T-cell lymphoma (AITL) that carry an isocitrate dehydrogenase-2 (IDH2) mutation. (Source: Drug Development Technology)
Source: Drug Development Technology - October 21, 2014 Category: Pharmaceuticals Source Type: news

Inadvertent High-dose Therapy With Temozolomide in a Child With Recurrent Pontine Glioma Followed by a Rapid Clinical Response But Deteriorated After Substitution With Low-dose Therapy
We present a case of inadvertent high-dose therapy with temozolomide in a child with recurrent diffuse intrinsic pontine glioma followed by a rapid clinical response. The patient was a 7-year-old boy who initially presented with a history of left facial palsy, double vision, headache, and ataxia. His symptoms were completely resolved following radiotherapy but recurred 3 months after. Following recurrence, he received temozolomide in a dose >3 times higher than prescribed inadvertently but tolerated well with a rapid clinical response. He eventually deteriorated after he was substituted with a lower dose of temozolomide an...
Source: Journal of Pediatric Hematology Oncology - October 21, 2014 Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research

Resection of supratentorial gliomas: the need to merge microsurgical technical cornerstones with modern functional mapping concepts. An overview
Abstract Although surgery is not curative for the majority of intracranial gliomas, radical resection has been demonstrated to influence survival and delay tumor progression. Because gliomas are very frequently located in eloquent or more generally critical areas, surgeons must always balance the maximizing resection with the need to preserve neurological function. In this overview, we tried to summarize the recent literature and our personal experience about (1) the benefits and limits of using preoperative anatomical and functional neuroimaging (anatomical MRI, DTI fiber tracking, and functional MRI), (2) the is...
Source: Neurosurgical Review - October 21, 2014 Category: Neurosurgery Source Type: research

Menopausal hormone therapy and central nervous system tumor risk: Large UK prospective study and meta‐analysis
Abstract Female sex hormones are thought to affect women's risk of developing central nervous system (CNS) tumors. Some have reported an increased risk in users of menopausal hormone therapy (HT) but evidence is limited. In the UK General Practice Research Database we compared prospectively collected information on HT prescriptions in women aged 50‐79 years with CNS tumors diagnosed in 1987‐2011 with that in matched controls (four per case). Relative risks (RRs) in relation to prescribed HT were calculated overall and by CNS tumor subtype. A meta‐analysis was conducted, combining our results with those from other pub...
Source: International Journal of Cancer - October 21, 2014 Category: Cancer & Oncology Authors: Victoria S. Benson, Oksana Kirichek, Valerie Beral, Jane Green Tags: Epidemiology Source Type: research

Faciobrachial dystonic seizures and antibodies to Lgi1 in a 92-year-old patient: A case report
Faciobrachial dystonic seizures (FBDS) have recently been characterized as a distinctive type of seizures, which frequently precede the onset of limbic encephalitis and are associated with antibodies to the leucine-rich glioma inactivated-1 (Lgi1) protein [1]. We here report on a novel patient with FBDS and antibodies to Lgi1, who had a remarkably old age at first manifestation of the disease, but still showed a complete remission of FBDS following immunotherapy with intravenous immunoglobulins (IVIG). (Source: Journal of the Neurological Sciences)
Source: Journal of the Neurological Sciences - October 21, 2014 Category: Neurology Authors: Pawel Fidzinski, Sven Jarius, Christian Gaebler, Friedrich Boegner, Roland Nohr, Klemens Ruprecht Tags: Letter to the editor Source Type: research

Commentary on IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low‐grade gliomas
(Source: Epilepsia)
Source: Epilepsia - October 20, 2014 Category: Neurology Authors: Gianluca Marucci Tags: Letter Source Type: research

In response: IDH1 mutation expression is associated with seizures and protoplasmic subtype in patients with low‐grade glioma
(Source: Epilepsia)
Source: Epilepsia - October 20, 2014 Category: Neurology Authors: Andrew Morokoff, Simon Liubinas Tags: Letter Source Type: research

Angiocentric glioma: a rare intractable epilepsy-related tumour in children.
We present two teenage cases of the angiocentric variant of glioma: 1) a 15-year-old girl with a chronic and intractable partial epilepsy with cystic tumour located in the right temporal lobe and 2) a 14-year-old boy with intractable seizures and an extensive cortical lesion in the left parieto-occipital area. In both cases, the total tumours excision was performed. The histopathological findings revealed a characteristic angiocentric pattern that was composed of elongated cells arranging in pseudorosette-like structures around blood vessels. Moreover, schwannoma-like areas and subpial neoplastic infiltration with palisadi...
Source: Folia Neuropathologica - October 17, 2014 Category: Pathology Authors: Grajkowska W, Matyja E, Daszkiewicz P, Roszkowski M, Peregud-Pogorzelski J, Jurkiewicz E Tags: Folia Neuropathol Source Type: research

Abnormalities in the normal appearing white matter of the cerebral hemisphere contralateral to a malignant brain tumor detected by diffusion tensor imaging.
CONCLUSIONS: In patients with previously untreated anaplastic astrocytoma or glioblastoma, an increase of the ADC and a reduction of FA were found in the brain parenchyma of the hemisphere contralateral to the tumor localization. In the absence of visible MRI abnormalities, this may be an early indicator of microstructural changes of the NAWM attributed to malignant brain tumor. PMID: 25310733 [PubMed - in process] (Source: Folia Neuropathologica)
Source: Folia Neuropathologica - October 17, 2014 Category: Pathology Authors: Kallenberg K, Goldmann T, Menke J, Strik H, Bock HC, Mohr A, Buhk JH, Frahm J, Dechent P, Knauth M Tags: Folia Neuropathol Source Type: research

Specific monoclonal antibodies against IDH1/2 mutations as diagnostic tools for gliomas
Abstract Mutations of isocitrate dehydrogenase 1/2 (IDH1/2) have been reported in gliomas and other types of tumors, such as acute myeloid leukemias, cartilaginous tumors, intrahepatic cholangiocarcinomas, osteosarcomas, and giant cell tumors of bone. In gliomas, IDH mutations uniformly occur in the functionally critical arginine 132 residue (R132) of IDH1 and arginine 172 residue (R172) of IDH2. IDH1 and IDH2 catalyze the oxidative carboxylation of isocitrate to α-ketoglutarate (α-KG) in the cytosol and mitochondria, respectively. In contrast, mutated IDH1/2 proteins possess a neomorphic enzymatic function that...
Source: Brain Tumor Pathology - October 17, 2014 Category: Neurology Source Type: research

Anatomical localization of isocitrate dehydrogenase 1 mutation: a voxel‐based radiographic study of 146 low‐grade gliomas
ConclusionsLow‐grade gliomas with IDH1 mutation are region‐specific and preferentially located surrounding the rostral extension of the lateral ventricles. Furthermore, such mutations are associated with a favorable clinical outcome. (Source: European Journal of Neurology)
Source: European Journal of Neurology - October 16, 2014 Category: Neurology Authors: Y. Wang, T. Zhang, S. Li, X. Fan, J. Ma, L. Wang, T. Jiang Tags: Original Article Source Type: research

Drosophila oncogene Gas41 is RNAi modulator that intersects heterochromatin and siRNA pathway
Abstract Glioma amplified sequence41 (Gas41) is a highly conserved putative transcription factor that is frequently abundant in human gliomas. Gas41 shows oncogenic activity by promoting cell growth and viability. Here we show Gas41 is required for proper functioning of RNAi machinery in the nuclei, though three basic structural domains of RNAi components PAZ, PIWI and dsRNA binding are absent in the structural sequences. Variations of structural domains are highly conversed among prokaryotes and eukaryotes. Gas41 interacts with cytological RNase III enzyme Dicer1 both biochemically and genetically. However, Drosophila Gas...
Source: FEBS Journal - October 16, 2014 Category: Research Authors: Sumit G. Gandhi, Indira Bag, Saswati Sengupta, Manika Pal‐Bhadra, Utpal Bhadra Tags: Original Article Source Type: research

Attention dysfunction of postoperative patients with glioma
Conclusions: High-grade glioma patients suffer more severe attention impairment. In addition, the frontal and parietal lobe glioma patients suffer attention dysfunction in dissimilar manner. These findings will provide important guidance on the care of glioma patients after therapy. (Source: World Journal of Surgical Oncology)
Source: World Journal of Surgical Oncology - October 15, 2014 Category: Cancer & Oncology Authors: Dazhao FangJian JiangXiaoyang SunWeijie WangNan DongXianhua FuCong PangXingui ChenLianshu Ding Source Type: research

Alternative lengthening of telomeres is enriched in, and impacts survival of TP53 mutant pediatric malignant brain tumors
We examined the association of ALT with alterations in genes found to segregate with specific histological phenotypes and with clinical outcome. ALT was detected almost exclusively in malignant tumors (p = 0.001). ALT was highly enriched in primitive neuroectodermal tumors (12 %), choroid plexus carcinomas (23 %) and high-grade gliomas (22 %). Furthermore, in contrast to adult gliomas, pediatric low grade gliomas which progressed to high-grade tumors did not exhibit the ALT phenotype. Somatic but not germline TP53 mutations were highly associated with ALT (p = 1.01 × 10−8). Of the other alterations examined...
Source: Acta Neuropathologica - October 15, 2014 Category: Neurology Source Type: research