MedWorm: Glioma

Pilot study on evaluation of any correlation between MR perfusion (K(trans)) and diffusion (apparent diffusion coefficient) parameters in brain tumors at 3 Tesla.

Cancer Imaging — Wed, 08 Feb 2012 00:30:02 +0100

Conclusion: We found that irrespective of brain tumor type, there is an inverse correlation between ADC and K(trans). Our findings highlight an intricate relationship between vascular permeability and the tumor microenvironment, probably modulating and/or interacting with changes such as increased cellularity, ischemic insult and varying extracellular matrix composition. PMID: 22275724 [PubMed - in process] (Source: Cancer Imaging)

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CD97 gene expression and function correlate with WT1 protein expression and glioma invasiveness

EurekAlert! - Medicine and Health — Tue, 07 Feb 2012 05:00:00 +0100

(Journal of Neurosurgery Publishing Group) Researchers at Virginia Commonwealth University and Old Dominion University have discovered that suppression of Wilms tumor 1 protein (WT1) results in downregulation of CD97 gene expression in three glioblastoma cell lines and reduces the characteristic invasiveness exhibited by glial tumor cells. This finding is published online Feb. 7 in the Journal of Neurosurgery. Although further studies must be performed, the authors propose that CD97 may prove to be a new target for anti-glioma therapies. (Source: EurekAlert! - Medicine and Health)

Brain Tumor Eradication And Prolonged Survival

Health News from Medical News Today — Mon, 06 Feb 2012 09:00:00 +0100

Tocagen Inc. has announced the publication of data showing the company's investigational treatment for high grade glioma eradicates brain tumors and provides a dramatic survival benefit in mouse models of glioblastoma. Almost all mice receiving the top dose of Toca 511 followed by 5-FC were still alive at 180 days, which was the termination date for the experiment, whereas all control mice died by day 43. The article was published in the February issue of the Neuro-Oncology journal... (Source: Health News from Medical News Today)

CCND1 G870A Polymorphism with Altered Cyclin D1 Transcripts Expression Is Associated with the Risk of Glioma in a Chinese Population

DNA and Cell Biology — Sat, 04 Feb 2012 04:05:10 +0100

DNA and Cell Biology , Vol. 0, No. 0. (Source: DNA and Cell Biology)

Heparan sulfate sulfatase SULF2 regulates PDGFR{alpha} signaling and growth in human and mouse malignant glioma

Journal of Clinical Investigation — Fri, 03 Feb 2012 18:50:49 +0100

In this study, we demonstrated that the extracellular sulfatase, SULF2, an enzyme that regulates multiple HSPG-dependent RTK signaling pathways, was expressed in primary human GBM tumors and cell lines. Knockdown of SULF2 in human GBM cell lines and generation of gliomas from Sulf2–/– tumorigenic neurospheres resulted in decreased growth in vivo in mice. We found a striking SULF2 dependence in activity of PDGFRα, a major signaling pathway in GBM. Ablation of SULF2 resulted in decreased PDGFRα phosphorylation and decreased downstream MAPK signaling activity. Interestingly, in a survey of SULF2 levels in different subtypes of GBM, the proneural subtype, characterized by aberrations in PDGFRα, demonstrated the strongest SULF2 expression. Therefore, in a...

Dynamics of expression patterns of AQP4, dystroglycan, agrin and matrix metalloproteinases in human glioblastoma

Cell and Tissue Research — Fri, 03 Feb 2012 17:53:17 +0100

Abstract In human glioblastoma, the blood–brain barrier (BBB) is disturbed. According to our concept, the glio-vascular relationships and thus the control of the BBB are essentially dependent on the polarity of astroglial cells. This polarity is characterized by the uneven distribution of the water channel protein aquaporin-4 (AQP4), dystroglycan and other molecules. Recently, we were able to show that the extracellular matrix component agrin is important for the construction and localization of the so-called orthogonal arrays of particles (OAPs), which consist in AQP4. Here, combining freeze-fracture electron microscopy, immunohistochemistry and Western blotting, we describe alterations of expression and distribution of AQP4, dystroglycan, agrin and the matrix metallopr...

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Study published in Neuro-Oncology shows brain tumor eradication and prolonged survival

EurekAlert! - Biology — Fri, 03 Feb 2012 05:00:00 +0100

(Canale Communications) Tocagen Inc. today announced the publication of data showing the company's investigational treatment for high grade glioma eradicates brain tumors and provides a dramatic survival benefit in mouse models of glioblastoma. Almost all mice receiving the top dose of Toca 511 followed by 5-FC were still alive at 180 days, which was the termination date for the experiment, whereas all control mice died by day 43. The article was published today in the February issue of the Neuro-Oncology journal. (Source: EurekAlert! - Biology)

Sodium-dependent Migration and Proliferation in Glioma Cells [Molecular Bases of Disease]

Journal of Biological Chemistry — Fri, 03 Feb 2012 05:00:00 +0100

In this study, we have investigated the role of a glioma-specific cation channel assembled from subunits of the Deg/epithelial sodium channel (ENaC) superfamily, in the regulation of migration and cell cycle progression in glioma cells. Channel inhibition by psalmotoxin-1 (PcTX-1) significantly inhibited migration and proliferation of D54-MG glioma cells. Both PcTX-1 and benzamil, an amiloride analog, caused cell cycle arrest of D54-MG cells in G0/G1 phases (by 30 and 40%, respectively) and reduced cell accumulation in S and G2/M phases after 24 h of incubation. Both PcTX-1 and benzamil up-regulated expression of cyclin-dependent kinase inhibitor proteins p21Cip1 and p27Kip1. Similar results were obtained in U87MG and primary glioblastoma multiforme cells maintained in primary culture and ...

Del Mar Pharmaceuticals Granted U.S. Orphan Drug Designation For VAL-083 For The Treatment Of Glioma

Pharmaceutical Online News — Thu, 02 Feb 2012 10:36:00 +0100

DelMar Pharma today announced that the United States FDA Office of Orphan Products Development has granted orphan drug designation for VAL-083 for the treatment of glioma, including glioblastoma multiforme (GBM), the most common and aggressive form of brain cancer. (Source: Pharmaceutical Online News)

Early prediction of response to Vorinostat in an orthotopic rat glioma model

NMR in Biomedicine — Thu, 02 Feb 2012 05:00:00 +0100

Glioblastoma is the most common primary brain tumor and is uniformly fatal despite aggressive surgical and adjuvant therapy. As survival is short, it is critical to determine the value of therapy early on in treatment. Improved early predictive assessment would allow neuro‐oncologists to personalize and adjust or change treatment sooner to maximize the use of efficacious therapy. During carcinogenesis, tumor suppressor genes can be silenced by aberrant histone deacetylation. This epigenetic modification has become an important target for tumor therapy. Suberoylanilide hydroxamic acid (SAHA, Vorinostat, Zolinza) is an orally active, potent inhibitor of histone deacetylase (HDAC) activity. A major shortcoming of the use of HDAC inhibitors in the treatment of patients with brain tumors is t...

In silico Experimentation of Glioma Microenvironment Development and Anti-tumor Therapy

PLoS Computational Biology — Thu, 02 Feb 2012 05:00:00 +0100

by Yu Wu, Yao Lu, Weiqiang Chen, Jianping Fu, Rong Fan Tumor cells do not develop in isolation, but co-evolve with stromal cells and tumor-associated immune cells in a tumor microenvironment mediated by an array of soluble factors, forming a complex intercellular signaling network. Herein, we report an unbiased, generic model to integrate prior biochemical data and the constructed brain tumor microenvironment in silico as characterized by an intercellular signaling network comprising 5 types of cells, 15 cytokines, and 69 signaling pathways. The results show that glioma develops through three distinct phases: pre-tumor, rapid expansion, and saturation. We designed a microglia depletion therapy and observed significant benefit for virtual patients treated at the early stages but striki...

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Deletion of the SPARC acidic domain or EGF-like module reduces SPARC-induced migration and signaling through p38 MAPK/HSP27 in glioma

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

In conclusion, deletions of the acidic domain and EGF-like module have differential effects on cell surface binding and HSP27 protein stability; however, both regions regulate SPARC-induced migration and signaling through HSP27. Our data link the domains of SPARC with different functions and suggest one or both of the constructs as potential therapeutic agents to inhibit SPARC-induced migration. (Source: Carcinogenesis)

A dialog between glioma and microglia that promotes tumor invasiveness through the CCL2/CCR2/interleukin-6 axis

Carcinogenesis — Thu, 02 Feb 2012 05:00:00 +0100

This study has uncovered a mechanism by which glioma cells exploit microglia for increased invasiveness. Specifically, glioma-derived CCL2 acts upon CCR2-bearing microglia, which then produces IL-6 to stimulate gliomas. The CCL2/CCR2/IL-6 loop is a potential therapeutic target for the currently incurable malignant gliomas. (Source: Carcinogenesis)

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas

Investigational New Drugs — Wed, 01 Feb 2012 17:10:49 +0100

Summary L-Glutamate (Glu) plays a crucial role in the growth of malignant gliomas. We have established the feasibility of accelerating a naturally occurring brain to-blood Glu efflux by decreasing blood Glu levels with intravenous oxaloacetate, the respective Glu co-substrate of the blood resident enzyme humane glutamate–oxaloacetate transaminase (hGOT). We wished to demonstrate that blood Glu scavenging provides neuroprotection in the case of glioma. We now describe the neuroprotective effects of blood Glu scavenging in a fatal condition such as brain-implanted C6 glioma in rats and brain-implanted human U87 MG glioma in nude mice. Rat (C-6) or human (U87) glioma cells were grafted stereotactically in the brain of rats or mice. After development of tumors, the animals w...

Inhibition of sphingosine kinase 1 suppresses proliferation of glioma cells under hypoxia by attenuating activity of extracellular signal‐regulated kinase

Cell Proliferation — Wed, 01 Feb 2012 05:00:00 +0100

Conclusions: SphK1 and SphK2 are involved in proliferation of glioma cells in hypoxic conditions through distinct signalling pathways. SphK1, but not SphK2, promotes cell population expansion in hypoxic conditions by activating ERK. (Source: Cell Proliferation)

[News] Qiagen acquires new rights for personalised cancer care

The Lancet Oncology — Wed, 01 Feb 2012 05:00:00 +0100

As the push towards personalised healthcare in many developed and emerging economies continues, the race to develop quick and accurate companion diagnostic tests is hotting up, with cancer diagnostics at the forefront. In the past week Qiagen (Hilden, Germany) announced its acquisition of worldwide exclusive rights to develop a genetic test for the anaplastic lymphoma kinase (ALK) biomarker, which would potentially be used in conjunction with a new class of lung-cancer drugs, and similar rights to develop a test for mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), which have been implicated in low-grade gliomas, anaplastic gliomas, secondary glioblastoma, and acute myeloid leukaemia. (Source: The Lancet Oncology)

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Pseudotumoral form of neuroschistosomiasis: report of three cases in ganzi, china.

The American Journal of Tropical Medicine and Hygiene — Wed, 01 Feb 2012 05:00:00 +0100

Authors: Wan H, Masataka H, Zhang LP, Zheng DF Abstract Abstract. The authors report three rare cases of neuroschistosomiasis lacking extracranial involvement. No parasitic eggs were detected in the stool with the Kato-Katz thick smear methods. Computed tomography of the brains showed hypodense signals, and magnetic resonance imaging showed isointense signals on T1-weighted images, hyperintense signals on T2-weighted images, and intensely enhancing nodules in the brain after intravenous administration of gadolinium. High-grade gliomas were suspected, and operations or radiosurgery was performed. Cerebral schistosomiasis was confirmed in all cases by biopsy of the brain lesions, revealing granulomas containing embedded Schistosoma japonicum eggs. All cases were definitively diagnose...

Brain Tumors in Children- Current Therapies and Newer Directions

Indian Journal of Pediatrics — Tue, 31 Jan 2012 16:47:55 +0100

Abstract Brain tumors are the second most common malignancy and the major cause of cancer related mortality in children. Though significant advances in neuroimaging, neurosurgery, radiation therapy and chemotherapy have evolved over the years, overall survival rate remains less than 75%. Malignant gliomas, high risk medulloblastoma with recurrence and infant brain tumors continue to be a major cause of therapeutic frustration. Even today diffuse pontine gliomas are universally fatal. Though tumors like low grade glioma have an overall excellent survival, recurrences and progression in eloquent areas pose therapeutic challenges. As research continues to unravel the biology including key molecules and signaling pathways responsible for the oncogenesis of different childhood ...

Central nervous system lymphoma occurring in a patient with neurofibromatosis type 1 (von Recklinghausen disease)

Neurological Sciences — Tue, 31 Jan 2012 16:44:48 +0100

We report a case of CNS primitive lymphoma in an adult patient who resulted positive for NF1 at genetic testing. At present, only one case of CNS lymphoma in an adult patient displaying clinical criteria for NF1 diagnosis has been reported. Content Type Journal ArticleCategory Case ReportPages 1-5DOI 10.1007/s10072-011-0886-8Authors Marica Eoli, Fondazione I.R.C.C.S. Istituto Neurologico C. Besta, Unit of Molecular Neuro-Oncology, Milan, ItalyDonata Bianchessi, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyAnna Luisa Di Stefano, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyElena Prodi, Fondazione I.R.C.C.S. Istituto Neurologico Nazionale C. Mondino, Pavia, ItalyElena Anghileri, Fondazione I.R.C.C.S. Istituto Neurologic...

Classifying Human Brain Tumors by Lipid Imaging with Mass Spectrometry

Cancer Research — Tue, 31 Jan 2012 05:00:00 +0100

Brain tissue biopsies are required to histologically diagnose brain tumors, but current approaches are limited by tissue characterization at the time of surgery. Emerging technologies such as mass spectrometry imaging can enable a rapid direct analysis of cancerous tissue based on molecular composition. Here, we illustrate how gliomas can be rapidly classified by desorption electrospray ionization-mass spectrometry (DESI-MS) imaging, multivariate statistical analysis, and machine learning. DESI-MS imaging was carried out on 36 human glioma samples, including oligodendroglioma, astrocytoma, and oligoastrocytoma, all of different histologic grades and varied tumor cell concentration. Gray and white matter from glial tumors were readily discriminated and detailed diagnostic information could ...

New MRI Technique Helps Diagnose Gliomas

Diagnostic Imaging — Mon, 30 Jan 2012 09:30:01 +0100

A new magnetic resonance spectroscopy (MRS) technique provides a definitive diagnosis of brain cancer based on imaging of a protein associated with a mutated gene found in 80 percent of low- and intermediate-grade gliomas, according to a new study published January 26 in Nature Medicine. (Source: Diagnostic Imaging)

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Inhibition and eradication of human glioma with tumor-targeting Salmonella typhimurium in an orthotopic nude-mouse model.

Cell Cycle — Mon, 30 Jan 2012 08:36:30 +0100

In this study, we demonstrated that the Salmonella typhimurium A1-R tumor-targeting strain can inhibit and eradicate human glioma in an orthotopic nude-mouse model. S. typhimurium A1-R was administered by injection through a craniotomy open-window or intravenously in nude mice. To establish the model, 2 x 105 U87-RFP human glioma cells were injected stereotactically into the mouse brain through the craniotomy open window. Two weeks after glioma-cell implantation, mice were treated with S. typhimurium A1-R [2 x 10 ( 7) CFU/200 μl intravenous injection (i.v.) or 1 x 10 ( 6) CFU/1 μl intracranial injection (i.c.)] once a week for 3 weeks. Brain tumors were observed by fluorescence imaging through the craniotomy open window over time. S. typhimurium A1-R, administered i.c., inhibited brain t...

Aurora A is differentially expressed in gliomas, is associated with patient survival in glioblastoma and is a potential chemotherapeutic target in gliomas.

Cell Cycle — Mon, 30 Jan 2012 08:36:21 +0100

Authors: Lehman NL, O'Donnell JP, Whiteley LJ, Stapp RT, Lehman TD, Roszka KM, Schultz LR, Williams CJ, Mikkelsen T, Brown SL, Ecsedy JA, Poisson LM Abstract Aurora A is critical for mitosis and is overexpressed in several neoplasms. Its overexpression transforms cultured cells, and both its overexpression and knockdown cause genomic instability. In transgenic mice, Aurora A haploinsufficiency, not overexpression, leads to increased malignant tumor formation. Aurora A thus appears to have both tumor-promoting and tumor-suppressor functions. Here, we report that Aurora A protein, measured by quantitative protein gel blotting, is differentially expressed in major glioma types in lineage-specific patterns. Aurora A protein levels in WHO grade II oligodendrogliomas (n = 16) and grade I...

Patient Care Could Be Revolutionized By Diagnostic Brain Tumor Test

Health News from Medical News Today — Mon, 30 Jan 2012 08:00:00 +0100

Researchers at UT Southwestern Medical Center have developed what they believe to be the first clinical application of a new imaging technique to diagnose brain tumors. The unique test could preclude the need for surgery in patients whose tumors are located in areas of the brain too dangerous to biopsy. This new magnetic resonance spectroscopy (MRS) technique provides a definitive diagnosis of cancer based on imaging of a protein associated with a mutated gene found in 80 percent of low- and intermediate-grade gliomas. Presence of the mutation also means a better prognosis... (Source: Health News from Medical News Today)

A case of primary diffuse leptomeningeal gliomatosis predominantly involving the cervical spinal cord and mimicking chronic meningitis.

Turkish Neurosurgery — Mon, 30 Jan 2012 05:00:02 +0100

Authors: Heijink DS, Urgun K, Sav A, Seker A, Konya D Abstract Gliomas may rarely arise in the leptomeninges without any evidence of intraaxial involvement. A case of primary diffuse leptomeningeal gliomatosis (PDLG) histologically diagnosed as oligoastrocytoma is presented. A 50-year-old woman presented with nausea, vomiting and headache. Magnetic resonance imaging (MRI) of cranium and cervical region revealed dural thickening starting from the craniocervical junction to the level of C4 without any parenchymal lesions. CSF examination showed an increase in protein and decrease in glucose levels. There were neither any kind of atypical cells nor any kind of growth in bacterial cultures. The patient underwent biopsy at the level of C1 for diagnosis. The specimen wa...

Evaluation of novel combined carbogen USPIO (CUSPIO) imaging biomarkers in assessing the anti‐angiogenic effects of cediranib (AZD2171) in rat C6 gliomas

International Journal of Cancer — Mon, 30 Jan 2012 05:00:00 +0100

This study aimed to evaluate CUSPIO biomarkers for the assessment of tumour response to anti‐angiogenic therapy. CUSPIO imaging was performed in subcutaneous rat C6 gliomas before and 2 days after treatment with the potent VEGF signalling inhibitor cediranib (n=12), or vehicle (n=12). Histological validation of Hoechst 33342 uptake (perfusion), smooth muscle actin staining (maturation), pimonidazole adduct formation (hypoxia) and necrosis were sought. Following treatment, there was a significant decrease in fractional blood volume (‐43%, p<0.01) and a significant increase in haemodynamic vascular functionality (treatment altered ΔR2*carbogen from 1.2 to ‐0.2 s‐1, p<0.05). CUSPIO imaging revealed an overall significant decrease in plasma perfusion (‐27%, p<0.05) followin...

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Evaluation of biocompatibility and anti-glioma efficacy of doxorubicin and irinotecan drug-eluting bead suspensions in alginate

Clinical and Translational Oncology — Sat, 28 Jan 2012 16:53:16 +0100

Discussion We conclude that the alginate suspension of irinotecan DEBs can be considered safe and effective in a clinical setting. Content Type Journal ArticleCategory Research ArticlesPages 50-59DOI 10.1007/s12094-012-0761-yAuthors Silke Glage, Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, GermanyAndrew L. Lewis, Biocompatibles UK Ltd., Farnham Business Park Weydon Lane, Farnham, Surrey, GU9 8QL UKPatricia Mertens, International Neuroscience Institute, Rudolf-Pichlmayrstr. 4, 30625 Hannover, GermanySteffen Baltes, International Neuroscience Institute, Rudolf-Pichlmayrstr. 4, 30625 Hannover, GermanyPeter Geigle, CellMed AG, Industriestrasse 19, 63755 Alzenau, GermanyThomas Brinker, Inte...

Methylation status of O6-methylguanine-DNA-methyl transferase promoter region in non-small-cell lung cancer patients with brain metastasis

Clinical and Translational Oncology — Sat, 28 Jan 2012 16:53:10 +0100

Conclusions NSCLC patients with brain metastasis treated by brain surgery followed by radiotherapy may have a higher chance of relapse when the tumour has methylation of the MGMT promoter region. Content Type Journal ArticleCategory Research ArticlesPages 31-35DOI 10.1007/s12094-012-0758-6Authors Kenji Hashimoto, Neurosurgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanYoshitaka Narita, Neurosurgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanYuko Matsushita, Neurosurgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanYasuji Miyakita, Neurosurgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 JapanMakoto...

Diagnostic brain tumor test could revolutionize care of patients with low-grade gliomas

UT Southwestern Medical Center News — Sat, 28 Jan 2012 10:53:06 +0100

Researchers have developed what they believe to be the first clinical application of a new imaging technique to diagnose brain tumors. (Source: UT Southwestern Medical Center News)

Semantic memory is impaired in patients with unilateral anterior temporal lobe resection for temporal lobe epilepsy

Brain — Sat, 28 Jan 2012 05:00:00 +0100

In this study, therefore, we investigated the semantic performance of 20 patients with resection for chronic temporal lobe epilepsy with a full battery of semantic assessments, including more sensitive measures of semantic processing. The results provide a bridge between the current clinical observations about resection for temporal lobe epilepsy and the expectations from semantic dementia and other neuroscience findings. Specifically, we found that on simple semantic tasks, the patients’ accuracy fell in the normal range, with the exception that some patients with left resection for temporal lobe epilepsy had measurable anomia. Once the semantic assessments were made more challenging, by probing specific-level concepts, lower frequency/more abstract items or measuring reaction times...

MGMT promoter hypermethylation and its associations with genetic alterations in a series of 350 brain tumors

Journal of Neuro-Oncology — Fri, 27 Jan 2012 17:56:38 +0100

The objective of this study was to retrospectively investigate MGMT promoter hypermethylation status for a series of 350 human brain tumors, including 275 gliomas of different malignancy grade, 21 glioblastoma multiforme (GBM) cell lines, and 75 non-glial tumors. The analysis was performed by methylation-specific PCR and capillary electrophoresis. MGMT expression at the protein level was also evaluated by both immunohistochemistry (IHC) and western blotting analysis. Associations of MGMT hypermethylation with IDH1/IDH2 mutations, EGFR amplification, TP53 mutations, and 1p/19q co-deletion, and the prognostic significance of these, were investigated for the gliomas. MGMT promoter hypermethylation was identified in 37.8% of gliomas, but was not present in non-glial tumors, with the excepti...

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Study: MRS may provide diagnostic, prognostic biomarker for brain tumors

Health Imaging News — Fri, 27 Jan 2012 13:14:01 +0100

A new magnetic resonance spectroscopy (MRS) technique may offer a method to detect and track a protein associated with a genetic mutation in brain tumor cancer cells. The method could inform diagnosis of glioma and provide prognostic information, according to a study published online Jan. 26 in Nature Medicine. (Source: Health Imaging News)

Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma

Nature AOP — Fri, 27 Jan 2012 09:37:24 +0100

Authors: Jeremy Schwartzentruber, Andrey Korshunov, Xiao-Yang Liu, David T. W. Jones, Elke Pfaff, Karine Jacob, Dominik Sturm, Adam M. Fontebasso, Dong-Anh Khuong Quang, Martje Tönjes, Volker Hovestadt, Steffen Albrecht, Marcel Kool, Andre Nantel, Carolin Konermann, Anders Lindroth, Natalie Jäger, Tobias Rausch, Marina Ryzhova, Jan O. Korbel, Thomas Hielscher, Peter Hauser, Miklos Garami, Almos Klekner, Laszlo Bognar, Martin Ebinger, Martin U. Schuhmann, Wolfram Scheurlen, Arnulf Pekrun, Michael C. Frühwald, Wolfgang Roggendorf, Christoph Kramm, Matthias Dürken, Jeffrey Atkinson, Pierre Lepage, Alexandre Montpetit, Magdalena Zakrzewska, Krzystof Zakrzewski, Pawel P. Liberski, Zhifeng Dong, Peter Siegel, Andreas E. Kulozik, Marc Zapatka, Abhijit Guha, David Malkin, J...

Bevacizumab and irinotecan in children with recurrent or refractory brain tumors: Toxicity and efficacy trends

Pediatric Blood and Cancer — Fri, 27 Jan 2012 05:00:00 +0100

ConclusionBevacizumab‐related acute toxicity appears to be low in children, even in combination with irinotecan. Further prospective trials are required to confirm the hypothetical efficacy of bevacizumab and to assess the risk of long‐term toxicity especially in the youngest children. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

The regulation of cysteine cathepsins and cystatins in human gliomas

International Journal of Cancer — Fri, 27 Jan 2012 05:00:00 +0100

AbstractCysteine cathepsins play an important role in shaping the highly infiltrative growth pattern of human gliomas. We have previously demonstrated that the activity of cysteine cathepsins is elevated in invasive GBM cells in vitro, in part due to attenuation of their endogenous inhibitors, the cystatins. To investigate this relationship in vivo, we established U87‐MG xenografts in NOD/SCID‐eGFP mice. Here, tumour growth correlated with an elevated enzymatic activity of CatB both in the tumour core and at the periphery, whereas CatS and CatL levels were higher at the xenograft edge compared to the core. Reversely, StefB expression was detected in the tumour core, but it was generally absent in the tumour periphery, suggesting that down‐regulation of this inhibitor correlates with ...

In vivo intraoperative confocal microscopy for real-time histopathological imaging of brain tumors.

Journal of Neurosurgery — Fri, 27 Jan 2012 05:00:00 +0100

Conclusions Further study will be necessary for better definition of the role of intraoperative confocal microscopy as a routine adjunct for intraoperative brain tumor diagnosis. PMID: 22283191 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

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Efficacy of vincristine administered via convection-enhanced delivery in a rodent brainstem tumor model documented by bioluminescence imaging

Child's Nervous System — Thu, 26 Jan 2012 16:44:15 +0100

Conclusions VCR administered by CED was effective in reducing tumors and prolonging survival time. Content Type Journal ArticleCategory Original PaperPages 1-10DOI 10.1007/s00381-012-1690-3Authors Guifa Xi, Division of Pediatric Neurosurgery, Falk Brain Tumor Center, Children’s Memorial Hospital, Northwestern University, Feinberg School of Medicine, 2300 Children’s Plaza, 2430N Halsted St, Box # 28, Chicago, IL 60614, USAVeena Rajaram, Division of Anatomic Pathology, Children’s Memorial Hospital, 2300 Children’s Plaza, Box # 28, Chicago, IL 60614, USABabara Mania-Farnell, Department of Biological Sciences, Purdue University Calumet, 2200 169th Street, Hammond, IN 46323, USAChandra S. Mayanil, Department of Development Biology, Children’s Memorial Research Cent...

The challenge to remove diffuse low-grade gliomas while preserving brain functions

Acta Neurochirurgica — Thu, 26 Jan 2012 06:43:52 +0100

Abstract WHO grade II glioma, i.e. diffuse low-grade glioma, is a pre-malignant tumour, usually revealed by seizures in young patients with a normal life. This tumour has a constant growth, and will inescapably become anaplastic. Surgical resection significantly increases the overall survival by delaying the malignant transformation. Thus, the dilemma is to perform early surgery in order to optimise the extent of resection (and thus the median survival) by removing smaller tumours while preserving the quality of life. To this end, the new concept proposed in this review is to achieve surgical resection according to functional and not to oncological boundaries. In other words, the principle is to first understand the cerebral anatomo-functional organisation at the individua...

Comparison between intensity normalization techniques for dynamic susceptibility contrast (DSC)‐MRI estimates of cerebral blood volume (CBV) in human gliomas

Journal of Magnetic Resonance Imaging — Thu, 26 Jan 2012 05:00:00 +0100

Conclusion:The results suggest Gaussian normalization of leakage‐corrected CBV maps may be the best choice for image intensity correction for use in large‐scale, multicenter clinical trials where MR scanners and protocols vary widely due to ease of implementation, lowest variability, and highest tumor to normal tissue contrast. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc. (Source: Journal of Magnetic Resonance Imaging)

Pyruvate Protects the Brain Against Ischemia-Reperfusion Injury by Activating the Erythropoietin Signaling Pathway.

Stroke — Thu, 26 Jan 2012 05:00:00 +0100

CONCLUSIONS: Pyruvate activation of the hypoxia-inducible factor-1α-EPO signaling cascade in neurons and glia could protect the brain from ischemia-reperfusion injury. PMID: 22282883 [PubMed - as supplied by publisher] (Source: Stroke)

New Way Discovered To Image Brain Tumors And Predict Recurrence

Health News from Medical News Today — Wed, 25 Jan 2012 08:00:00 +0100

After people with low-grade glioma, a type of brain cancer, undergo neurosurgery to remove the tumors, they face variable odds of survival - depending largely on how rapidly the cancer recurs. Even though their doctors monitor the tumor closely with sophisticated imaging, it is difficult to determine with certainty whether cancer has returned in a more malignant state that requires aggressive treatment... (Source: Health News from Medical News Today)

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Protein and phosphoprotein levels in glioma and adenocarcinoma cell lines grown in normoxia and hypoxia in monolayer and three-dimensional cultures

Proteome Science — Wed, 25 Jan 2012 05:00:00 +0100

Conclusions: We identified subsets of proteins with clearly concordant/discordant behavior between gliomas and adenocarcinomas. In general, monolayer to 3D culture differences are clearer than normoxia to hypoxia differences, with anti-apoptotic, cytoskeletal rearrangement and cell survival pathways emphasized in the former and mTOR pathway, transcription, cell-cycle arrest modulation, and increased cell motility in the latter. (Source: Proteome Science)

A proteome comparison between physiological angiogenesis and angiogenesis in glioblastoma.

Molecular and Cellular Proteomics : MCP — Wed, 25 Jan 2012 05:00:00 +0100

Authors: Mustafa DA, Dekker LJ, Stingl C, Kremer A, Stoop M, Sillevis Smitt PA, Kros JM, Luider TM Abstract The molecular pathways involved in neovascularization of regenerating tissues and tumor angiogenesis resemble each other. However, the regulatory mechanisms of neovascularization under neoplastic circumstances are unbalanced leading to abnormal protein expression patterns resulting in the formation of defective and often abortive tumor vessels. Because gliomas are among the most vascularized tumors, we compared the protein expression profiles of proliferating vessels in glioblastoma with those in tissues in which physiological angiogenesis takes place. By using a combination of laser microdissection and LTQ Orbitrap mass spectrometry comparisons of protein profiles were made....

Lexical access speed is significantly correlated with the return to professional activities after awake surgery for low-grade gliomas

Journal of Neuro-Oncology — Tue, 24 Jan 2012 07:32:29 +0100

Abstract Awake surgery with intraoperative brain mapping is highly recommended for patients with diffuse low-grade gliomas in language areas, to maximise the extent of resection while preserving the integrity of functional networks and thus quality of life. The picture-naming test “DO.80” is the gold standard for language assessment before, during, and after surgery. Cognitive functioning is correlated with quality of life, itself linked with return to work. Our objective was to evaluate the significance of measuring naming speed, and its correlation with the return to professional activities. Two complementary studies are reported. In the first retrospective study, eleven patients were examined post-operatively. Five patients were selected because they were not able t...

The translocator protein ligand [18F]DPA-714 images glioma and activated microglia in vivo

European Journal of Nuclear Medicine and Molecular Imaging — Tue, 24 Jan 2012 07:19:32 +0100

Conclusion The TSPO radioligand [18F]DPA-714 can be used for PET imaging of intracranial 9L glioma in different rat strains. This preclinical study demonstrates the feasibility of employing [18F]DPA-714 as an alternative radiotracer to image human glioma. Content Type Journal ArticleCategory Original ArticlePages 1-13DOI 10.1007/s00259-011-2041-4Authors Alexandra Winkeler, Inserm, U1023, Laboratoire d’Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, FranceRaphael Boisgard, Inserm, U1023, Laboratoire d’Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, FranceAli R. Awde, Inserm, U1023, Laboratoire d’Imagerie Moléculaire Expérimentale, Université Paris Sud, Orsay, FranceAlbertine Dubois, Inserm, U1023, Laboratoire d’Imager...

Kinase activation of ClC-3 accelerates cytoplasmic condensation during mitotic cell rounding

AJP: Cell Physiology — Tue, 24 Jan 2012 05:00:00 +0100

"Mitotic cell rounding" describes the rounding of mammalian cells before dividing into two daughter cells. This shape change requires coordinated cytoskeletal contraction and changes in osmotic pressure. While considerable research has been devoted to understanding mechanisms underlying cytoskeletal contraction, little is known about how osmotic gradients are involved in cell division. Here we describe cytoplasmic condensation preceding cell division, termed "premitotic condensation" (PMC), which involves cells extruding osmotically active Cl– via ClC-3, a voltage-gated channel/transporter. This leads to a decrease in cytoplasmic volume during mitotic cell rounding and cell division. Using a combination of time-lapse microscopy and biophysical measurements, we demonstrate that PMC in...

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Epigenetically mediated down‐regulation of the differentiation‐promoting chaperon protein CRABP2 in astrocytic gliomas

International Journal of Cancer — Tue, 24 Jan 2012 05:00:00 +0100

AbstractImpairment of endogenous differentiation pathways like retinoic acid (RA) signaling seems to be a central pathogenetic event in astrocytic gliomas. Among others, expression of the differentiation‐promoting RA chaperon protein cellular retinoic acid binding protein 2 (CRABP2) is extenuated in high‐grade gliomas. Against this background, we aimed at identifying potential pathomechanisms underlying reduced CRABP2 expression in these tumors. Employing MassARRAY methylation analysis we detected extensive CpG methylation upstream of the CRABP2 gene locus in a study sample comprising 100 astrocytic gliomas of WHO grade II to IV. Compared to non‐tumorous control samples tumors revealed increased CpG methylation and methylation levels were inversely correlated to CRABP2 mRNA expressio...

Targeted Therapy for Brain Tumours: Role of PARP Inhibitors.

Current Cancer Drug Targets — Tue, 24 Jan 2012 05:00:00 +0100

Authors: Leonetti C, Biroccio A, Graziani G, Tentori L Abstract The prognosis of malignant glioma and metastatic brain tumours is still extremely poor, despite recent advances in therapeutic strategies with molecular-targeted agents. Poly(ADP-ribose) polymerase (PARP) inhibitors are a promising, novel class of anticancer drugs to be used either as single agents or in combination with chemotherapy and radiotherapy. PARP-1 and PARP-2 are the only PARP proteins that bind to DNA single strand breaks (SSBs), facilitating the repair process by the base excision repair. For this reason, PARPs have been extensively investigated as targets of novel drugs that may be used to enhance the antitumour activity of SSBs inducing agents, such as the methylating compound temozolomide, which is the d...

Team Finds New Way to Image Brain Tumors and Predict Recurrence

UCSF Medical Center — Mon, 23 Jan 2012 08:00:00 +0100

After people with low-grade glioma, a type of brain cancer, undergo neurosurgery to remove the tumors, they face variable odds of survival, depending largely on how rapidly the cancer recurs. Even though their doctors monitor the tumor closely with sophisticated imaging, it is difficult to determine with certainty whether cancer has returned in a more malignant state that requires aggressive treatment. (Source: UCSF Medical Center)

Team finds new way to image brain tumors and predict recurrence

EurekAlert! - Medicine and Health — Mon, 23 Jan 2012 05:00:00 +0100

(University of California - San Francisco) After people with low-grade glioma, a type of brain cancer, undergo neurosurgery to remove the tumors, they face variable odds of survival -- depending largely on how rapidly the cancer recurs. Even though their doctors monitor the tumor closely with sophisticated imaging, it is difficult to determine with certainty whether cancer has returned in a more malignant state that requires aggressive treatment. (Source: EurekAlert! - Medicine and Health)

Isolation and Cytotoxic Activity of Selaginellin Derivatives and Biflavonoids from Selaginella tamariscina

Planta Medica — Mon, 23 Jan 2012 05:00:00 +0100

Planta MedDOI: 10.1055/s-0031-1298175AbstractFive selaginellin derivatives, including two new selaginellins termed selaginellins M (1) and N (2), and three previously identified compounds, selaginellin (3), selaginellin A (4), and selaginellin C (5), were isolated from the Selaginella tamariscina (Beauv.) Spring plant. In addition, four known biflavonoids, namely neocryptomerin (6), hinokiflavone (7), pulvinatabiflavone (8), and 7′′-O-methylamentoflavone (9), were also isolated. The structures of new compounds 1 and 2 were elucidated by spectroscopic analysis. The cytotoxic activity of compounds 1-9 was evaluated against a small panel of human cancer cell lines, including U251 (human glioma cells), HeLa (human cervical carcinoma cells), and MCF-7 (human breast cancer cells). The two ne...

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Fourier transform infrared microspectroscopy identifies protein propionylation in histone deacetylase inhibitor treated glioma cells

Journal of Biophotonics — Sun, 22 Jan 2012 01:20:28 +0100

AbstractHistone deacetylase inhibitors (HDIs) have attracted considerable attention as potential drug molecules in tumour biology. In order to optimise chemotherapy, it is important to understand the mechanisms of regulation of histone deacetylase (HDAC) enzymes and modifications brought by various HDIs. In the present study, we have employed Fourier transform infrared microspectroscopy (FT‐IRMS) to evaluate modifications in cellular macromolecules subsequent to treatment with various HDIs. In addition to CH3 (methyl) stretching bands at 2872 and 2960 cm–1, which arises due to acetylation, we also found major changes in bands at 2851 and 2922 cm–1, which originates from stretching vibrations of CH2 (methylene) groups, in valproic acid treated cells. We further demonstrate that the ch...

Concurrent hypermethylation of DNMT1, MGMT and EGFR genes in progression of gliomas

Diagnostic Pathology — Fri, 20 Jan 2012 05:00:00 +0100

Conclusion: This study has provided further evidence that the histological transformation and progression of gliomas may be associated with the inactivation of the EGFR and MGMT genes. It seems that EGFR and MGMT promoter hypermethylations are early events in the clonal evolution of gliomas and this gene inactivation has proved to be stable even in tumour recurrence. However, the DNMT hypermethylation is a late part of glioma progression.Virtual slides: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1935054011612460 (Source: Diagnostic Pathology)

Correlation between low-level expression of the tumor suppressor gene TAp73 and the chemoresistance of human glioma stem cells

Cancer Chemotherapy and Pharmacology — Thu, 19 Jan 2012 06:53:40 +0100

Conclusion These findings indicate that TAp73 silencing is hallmark of GSC to maintain their chemoresistance phenotype. Thus, targeting TAp73 may provide a novel strategy to eradicating GSCs. Content Type Journal ArticleCategory Original ArticlePages 1-8DOI 10.1007/s00280-012-1823-0Authors Xiaogang Hu, Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaNan Wu, Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaPeiyuan Xia, Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaSicang Yu, Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, 400038 ChinaFengjun Sun, Department of Ph...

Quantitative volumetric analysis of gliomas with sequential MRI and 11C-methionine PET assessment: patterns of integration in therapy planning

European Journal of Nuclear Medicine and Molecular Imaging — Thu, 19 Jan 2012 06:51:13 +0100

Conclusion The metabolically active tumour volume observed in 11C-methionine PET differs from the volume of MRI by showing areas of infiltrative tumour and distinguishing from non-tumour lesions. Differences in 11C-methionine PET/MRI integration patterns can be assigned to tumour grades according to the WHO classification. This finding may improve tumour delineation and therapy planning for gliomas. Content Type Journal ArticleCategory Original ArticlePages 1-11DOI 10.1007/s00259-011-2049-9Authors Javier Arbizu, Department of Nuclear Medicine, Clinica Universidad de Navarra, Avenida Pio XII, 36, 31008 Pamplona, SpainS. Tejada, Department of Neurosurgery, Clinica Universidad de Navarra, Avenida Pio XII, 36, 31008 Pamplona, SpainJ. M. Marti-Climent, Department of Nucl...

Communication process in consultation of patients with incurable disease: a prospective study.

Bulletin du Cancer — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Marcoux I Abstract Patients wish to be fully informed about their health, but some information and its disclosure may pose special challenges depending on the severity of the illness. This prospective observational study investigates the content of information about the disease and treatment, as well as the process by which information is disclosed as part of 51 consultations with people with malignant gliomas. Patients and their relatives were fully informed of the diagnosis and treatments (types, risks, practical details), but disease progression with and without treatment, like the prognosis, was rarely addressed. Relatives were more likely than patients to ask questions related to the severity of the illness and the prognosis, leaving doctors in the difficult position...

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Induction of cell-cycle arrest and apoptosis in glioblastoma stem-like cells by WP1193, a novel small molecule inhibitor of the JAK2/STAT3 pathway

Journal of Neuro-Oncology — Tue, 17 Jan 2012 07:19:32 +0100

Abstract Glioma stem-like cells (GSCs) may be the initiating cells in glioblastoma (GBM) and contribute to the resistance of these tumors to conventional therapies. Development of novel chemotherapeutic agents and treatment approaches against GBM, especially those specifically targeting GSCs are thus necessary. In the present study, we found that a novel Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway inhibitor (WP1193) significantly decreased the proliferation of established glioma cell lines in vitro and inhibit the growth of glioma in vivo. To test the efficacy of WP1193 against GSCs, we then administrated WP1193 to GSCs isolated and expanded from multiple human GBM tumors. We revealed that WP1193 suppressed phosphorylation of JAK2...

Risk of ischemia in glioma surgery: comparison of first and repeat procedures

Journal of Neuro-Oncology — Tue, 17 Jan 2012 07:19:31 +0100

Abstract The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surgery than for first surgery, and sought to identify factors associated with the occurrence of postoperative infarction. Therefore, we searched our database to identify patients who were operated for primary or recurrent glial tumors between October 2007 and October 2010. We analyzed 177 procedures, of which 130 (73.4%) were first surgeries and 47 (26.5%) were repeat. Initial WHO grades, KPS scores, and age were evenly distributed between the groups. For...

The “go or grow” potential of gliomas is linked to the neuropeptide processing enzyme carboxypeptidase E and mediated by metabolic stress

Acta Neuropathologica — Tue, 17 Jan 2012 07:11:19 +0100

Abstract Glioblastoma (GBM), the most common malignant brain tumor, is among the most lethal neoplasms, with a median survival of approximately 1 year. Prognosis is poor since GBMs possess a strong migratory and highly invasive potential, making complete surgical resection impossible. Reduced expression of carboxypeptidase E (CPE), a neuropeptide-processing enzyme, in a cell death-resistant glioma cell line and lower CPE expression levels in the cohort of GBM samples of The Cancer Genome Atlas compared to normal brain control specimens prompted us to analyze the function of CPE as a putative tumor suppressor gene. In our samples, CPE was also reduced in GBM compared to normal brain with the strongest loss in cells surrounding hypoxic tumor areas as well as in most gli...

Temozolomide for Pediatric High-Grade Gliomas

Current Neurology and Neuroscience Reports — Tue, 17 Jan 2012 07:06:32 +0100

Content Type Journal ArticleCategory Clinical Trial ReportPages 1-3DOI 10.1007/s11910-012-0250-2Authors Roger J. Packer, Center for Neuroscience and Behavioral Medicine, Children’s National Medical Center, Gilbert Neurofibromatosis Institute, Brain Tumor Institute, 111 Michigan Avenue, NW, Washington, DC 20010, USA Journal Current Neurology and Neuroscience ReportsOnline ISSN 1534-6293Print ISSN 1528-4042 (Source: Current Neurology and Neuroscience Reports)

A call to researchers: The Cancer Genome Atlas

National Brain Tumor Society — Tue, 17 Jan 2012 06:00:00 +0100

TCGA is asking for researchers to help them collect low-grade glioma samples. (Source: National Brain Tumor Society)

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Attention Researchers: Help TCGA With Low-Grade Gliomas

National Brain Tumor Society — Tue, 17 Jan 2012 06:00:00 +0100

TCGA is asking for researchers to help them collect low-grade glioma samples. (Source: National Brain Tumor Society)

Eosinophils in glioblastoma biology

Journal of Neuroinflammation — Tue, 17 Jan 2012 05:00:00 +0100

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the e...

Characterization of 3'-untranslated region of the mouse GDNF gene

BMC Molecular Biology - Latest articles — Tue, 17 Jan 2012 05:00:00 +0100

Conclusions: Our study is the first characterization of the possible role of AREs and other suppressive regions in the 3'-UTR in regulating the amounts of GDNF mRNA in C6 cells. (Source: BMC Molecular Biology - Latest articles)

SUMO fusion system facilitates soluble expression and high production of bioactive human fibroblast growth factor 23 (FGF23).

Applied Microbiology and Biotechnology — Tue, 17 Jan 2012 05:00:00 +0100

Authors: Liu X, Chen Y, Wu X, Li H, Jiang C, Tian H, Tang L, Wang D, Yu T, Li X Abstract As a key humoral regulator of phosphate homeostasis and its involvement in the pathogenesis of human disease, human fibroblast growth factor 23 (hFGF23) has become a particularly attractive therapeutic target. To prepare soluble and bioactive recombinant human FGF23 to meet the increasing demand in its pharmacological application, small ubiquitin-related modifier (SUMO)-FGF23 fusion gene and FGF23 non-fusion gene were amplified by standard PCR methods and cloned into vector pET-22b and pET-3c, then transformed into Escherichia coli Rosetta (DE3) and BL21 (DE3). The best combination of plasmid and host strain was screened, and only Rosetta (DE3)/pET-SUMO-FGF23 was screened for rhFGF23 protein ex...

Spheres without Influence: Dissociating In Vitro Self-Renewal from Tumorigenic Potential in Glioma

Cancer Cell — Tue, 17 Jan 2012 00:00:00 +0100

Tracy-Ann Read, Robert J. Wechsler-Reya. The capacity for self-renewal is thought to be a critical property of tumor-initiating cells. This capacity is often associated with the ability to generate spheres in vitro. In this issue of C.... (Source: Cancer Cell)

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Self-Renewal Does Not Predict Tumor Growth Potential in Mouse Models of High-Grade Glioma

Cancer Cell — Tue, 17 Jan 2012 00:00:00 +0100

Lindy E. Barrett, Zvi Granot, Courtney Coker, Antonio Iavarone, Dolores Hambardzumyan, Eric C. Holland, Hyung-song Nam, Robert Benezra. Within high-grade gliomas, the precise identities and functional roles of stem-like cells remain unclear. In the normal neurogenic niche, ID (Inhibitor of DNA-binding) genes maintain.... (Source: Cancer Cell)

Complications of chemotherapy in neuro-oncology.

Herpes — Fri, 13 Jan 2012 11:30:16 +0100

Authors: Marosi C Abstract The persisting reservation against the use of chemotherapy in patients with malignant glioma was finally overcome by the breakthrough achieved with the use of the oral alkylating agent temozolomide (TMZ) as concomitant and adjuvant chemotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). The basic condition for an effective systemic drug therapy against malignant glioma is that the drug be able to cross the blood-brain barrier (BBB) and the brain-tumor barrier. Drugs crossing the BBB have to be nonpolar, small molecules with a molecular weight of less than 500Da, to bear no electrical charge, or to be able to use active transport mechanisms, as the BBB is functional in the peripheral growing areas of GBM. The prerequisite of liposolubi...

Sh3rf2/POSHER Antagonizes POSH-mediated JNK Signaling [Protein Synthesis and Degradation]

Journal of Biological Chemistry — Fri, 13 Jan 2012 05:00:00 +0100

We report that Sh3rf2, a homologue of the pro-apoptotic scaffold POSH (Plenty of SH3s), acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway. siRNA-mediated knockdown of Sh3rf2 promotes apoptosis of neuronal PC12 cells, cultured cortical neurons, and C6 glioma cells. This death appears to result from activation of JNK signaling. Loss of Sh3rf2 triggers activation of JNK and its target c-Jun. Also, apoptosis promoted by Sh3rf2 knockdown is inhibited by dominant-negative c-Jun as well as by a JNK inhibitor. Investigation of the mechanism by which Sh3rf2 regulates cell survival implicates POSH, a scaffold required for activation of pro-apoptotic JNK/c-Jun signaling. In cells lacking POSH, Sh3rf2 knockdown is unable to activate JNK. We further find that Sh3rf2 bind...

Space-time clustering of childhood central nervous system tumours in Yorkshire, UK

BMC Cancer — Fri, 13 Jan 2012 05:00:00 +0100

Conclusions: There was some evidence for a transient environmental component to the aetiology of PNETs. However, a possible role for chance cannot be excluded. (Source: BMC Cancer)

Use of (11)C-methionine PET parametric response map for monitoring WT1 immunotherapy response in recurrent malignant glioma.

Journal of Neurosurgery — Fri, 13 Jan 2012 05:00:00 +0100

Conclusions This study describes the limited value of Gd-enhanced MR imaging and highlights the potential of voxel-wise PRM analysis of MET-PET for monitoring treatment response in immunotherapy for malignant gliomas. Clinical trial registration no.: UMIN000002001. PMID: 22242671 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

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Characterization and outcomes of optic nerve gliomas: a population-based analysis

Journal of Neuro-Oncology — Thu, 12 Jan 2012 06:42:14 +0100

In conclusion, ONG are rare tumors seen predominantly in children. The overall prognosis of high-grade tumors remains poor in all age groups despite multi-modality treatment. Content Type Journal ArticleCategory Clinical StudyPages 1-7DOI 10.1007/s11060-011-0783-2Authors Mark V. Mishra, Department of Radiation Oncology, Jefferson Medical College, Philadelphia, PA, USADavid W. Andrews, Department of Neurosurgery, Jefferson Medical College, Philadelphia, PA, USAJon Glass, Department of Neurosurgery, Jefferson Medical College, Philadelphia, PA, USAJames J. Evans, Department of Neurosurgery, Jefferson Medical College, Philadelphia, PA, USAAdam P. Dicker, Department of Radiation Oncology, Jefferson Medical College, Philadelphia, PA, USAXinglei Shen, Department of Radiation Oncology, Jef...

MR Imaging Features of High-Grade Gliomas in Murine Models: How They Compare with Human Disease, Reflect Tumor Biology, and Play a Role in Preclinical Trials [RESEARCH PERSPECTIVES]

American Journal of Neuroradiology — Thu, 12 Jan 2012 05:00:00 +0100

SUMMARY: Murine models are the most commonly used and best investigated among the animal models of HGG. They constitute an important weapon in the development and testing of new anticancer drugs and have long been used in preclinical trials. Neuroimaging methods, particularly MR imaging, offer important advantages for the evaluation of treatment response: shorter and more reliable treatment end points and insight on tumor biology and physiology through the use of functional imaging DWI, PWI, BOLD, and MR spectroscopy. This functional information has been progressively consolidated as a surrogate marker of tumor biology and genetics and may play a pivotal role in the assessment of specifically targeted drugs, both in clinical and preclinical trials. The purpose of this Research Perspectives...

Correlations between Perfusion MR Imaging Cerebral Blood Volume, Microvessel Quantification, and Clinical Outcome Using Stereotactic Analysis in Recurrent High-Grade Glioma [BRAIN]

American Journal of Neuroradiology — Thu, 12 Jan 2012 05:00:00 +0100

CONCLUSIONS: rCBV provides a reliable estimation of tumor MVA as a biomarker of glioma outcome. rCBV poorly estimates MVD in the presence of vessel size heterogeneity inherent to human HGG. (Source: American Journal of Neuroradiology)

Neoplasms Associated with Germline and Somatic NF1 Gene Mutations.

The Oncologist — Thu, 12 Jan 2012 05:00:00 +0100

Conclusions. The lack of well-defined screening tests for early detection and the nonspecific clinical presentation contributes to a poorer outcome in malignancies associated with NF1. Small study group size, mixed patient population, and a lack of uniformity in reporting research results make comparison of treatment outcome for this group difficult. An International Consensus Meeting to address and recommend best practices for screening, diagnosis, management, and follow-up of malignancies associated with NF1 is needed. PMID: 22240541 [PubMed - as supplied by publisher] (Source: The Oncologist)

Metabolomics of Human Cerebrospinal Fluid Identifies Signatures of Malignant Glioma.

Molecular and Cellular Proteomics : MCP — Thu, 12 Jan 2012 05:00:00 +0100

Authors: Locasale JW, Melman T, Song S, Yang X, Swanson KD, Cantley LC, Wong ET, Asara JM Abstract Cerebrospinal fluid (CSF) is routinely collected for the diagnosis and monitoring of patients with gliomas and other neurological malignancies. However, little is known as to how its constituents may change in a patient when presented with a malignant brain tumor. Here, we used a targeted mass-spectrometry based metabolomics platform using selected reaction monitoring (SRM) with positive/negative switching and profiled the relative levels of over 124 polar metabolites present in patient CSF. We analyzed the metabolic profiles from 10 patients presenting malignant gliomas and 7 control patients that did not present malignancy to test whether a small sample size could provide statistica...

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Aphasia induced by gliomas growing in the ventrolateral frontal region: Assessment with diffusion MR tractography, functional MR imaging and neuropsychology

Cortex — Wed, 11 Jan 2012 05:00:00 +0100

Conclusions: Gliomas growing in the left VPCG are much more likely to cause speech deficits than gliomas infiltrating the IFG, including Broca’s area. Lesion extension to the AF connecting frontal to parietal and temporal regions is an important mechanism for the appearance of aphasia. (Source: Cortex)

Computational Studies on Translocator Protein (tspo) and its Ligands.

Current Topics in Medicinal Chemistry — Tue, 10 Jan 2012 19:55:13 +0100

Authors: Ortore G, Tuccinardi T, Martinelli A Abstract The Translocator Protein (18 kDa) (TSPO), previously known as the peripheral benzodiazepine receptor, is widely expressed in glial cells and in peripheral tissues and is involved in a variety of biological processes: steroidogenesis, cell growth and differentiation, apoptosis induction, etc. TSPO basal expression is up-regulated in a number of human pathologies, including a variety of tumors and neuropathologies, such as gliomas and neurodegenerative disorders (Huntington's and Alzheimer's diseases), as well as in various forms of brain injury and inflammation. Furthermore, changes in TSPO receptor levels have been found in anxiety and mood disorders. Nowadays, considerable efforts have been focused on the identification of new...

Knockdown of eukaryotic translation initiation factors 3B (EIF3B) inhibits proliferation and promotes apoptosis in glioblastoma cells

Neurological Sciences — Tue, 10 Jan 2012 16:57:06 +0100

In conclusion, EIF3B promotes the proliferation of U87 cells and may play an important role in human glioblastoma development. Content Type Journal ArticleCategory Original ArticlePages 1-6DOI 10.1007/s10072-011-0894-8Authors Hong Liang, Department of Neurosurgery, Daping Hospital of the Third Military Medical University, 400042 Chongqing, ChinaXuehua Ding, Department of Neurosurgery, Changzheng Hospital, Shanghai, ChinaChun Zhou, Department of Neurosurgery, Daping Hospital of the Third Military Medical University, 400042 Chongqing, ChinaYihua Zhang, Department of Neurosurgery, Daping Hospital of the Third Military Medical University, 400042 Chongqing, ChinaMinhui Xu, Department of Neurosurgery, Daping Hospital of the Third Military Medical University, 400042 Chongqing, ChinaChengq...

Low values of 5‐hydroxymethylcytosine (5hmC), the “sixth base”, are associated with anaplasia in human brain tumours

International Journal of Cancer — Tue, 10 Jan 2012 05:00:00 +0100

Abstract5‐Methylcytosine (5mC) in genomic DNA has important epigenetic functions in embryonic development and tumour biology. 5‐Hydroxymethylcytosine (5hmC) is generated from 5mC by the action of the TET (Ten‐Eleven‐Translocation) enzymes and may be an intermediate to further oxidation and finally demethylation of 5mC. We have used immunohistochemistry (IHC) and isotope‐based liquid chromatography mass spectrometry (LC‐MS) as to investigate the presence and distribution of 5hmC in human brain and brain tumours. In the normal adult brain IHC identified 61.5 % 5hmC positive cells in the cortex and 32.4 % 5hmC in white matter (WM) areas. In tumours, positive staining of cells ranged from 1.1 % in glioblastomas (WHO grade IV) to 8.9% in grade I gliomas (pilocytic astrocytomas). In ...

Overexpression of the long non‐coding RNA MEG3 impairs in vitro glioma cell proliferation

Journal of Cellular Biochemistry — Tue, 10 Jan 2012 05:00:00 +0100

AbstractGliomas are the most common type of primary brain tumor in the central nervous system of adults. Maternally Expressed Gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a non‐coding RNA associated with tumorigenesis. However, little is known about whether and how MEG3 regulates glioma development. In the present study we assayed the expression of MEG3 in glioma tissue samples by real‐time polymerase chain reaction assay, and defined the biological functions and target genes by CCK‐8 assay, flow cytometry and RNA immunoprecipitation. We firstly demonstrated that MEG3 expression was markedly decreased in glioma tissues compared with adjacent normal tissues. Moreover, ectopic expression of MEG3 inhibited cell proliferation and promoted cell apoptosis in U251 and U8...

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An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing

Journal of Neuro-Oncology — Mon, 09 Jan 2012 19:34:42 +0100

Abstract The prognosis for diffuse infiltrating pontine gliomas (DIPG) remains extremely poor, with the majority of patients surviving less than 2 years. Here, we have adapted standard xenograft techniques to study glioma growth in the mouse brainstem, and have utilized the mouse model for studying a relevant therapeutic for treating DIPGs. bioluminescence imaging monitoring revealed a progressive increase in signal following the injection of either of two tumor cell types into the brainstem. Mice with orthotopic GS2 tumors, and receiving a single 100 mg/kg dose of temozolomide showed a lengthy period of decreased tumor luminescence, with substantially increased survival relative to untreated mice (P < 0.001). A small molecule inhibitor that targets c...

Telomestatin impairs glioma stem cell survival and growth through the disruption of telomeric G-quadruplex and inhibition of the proto-oncogene, c-Myb.

Clinical Cancer Research — Mon, 09 Jan 2012 05:00:00 +0100

CONCLUSIONS: These data indicate that TMS potently eradicates GSCs through telomere disruption and c-Myb inhibition, and this study suggests a novel GSC-directed therapeutic strategy for GBM. PMID: 22230766 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Comparison between Acetazolamide Challenge and 10% Carbon Dioxide Challenge Perfusion CT in Rat C6 Glioma

Academic Radiology — Fri, 06 Jan 2012 11:08:02 +0100

Conclusions: The results of this study indicate that PCT with ACZ challenge is a more reliable technique compared to 10% CO2 challenge for the quantitative evaluation of microcirculation in gliomas. (Source: Academic Radiology)

Herpes simplex virus type 1 thymidine kinase-armed bovine herpesvirus type 4-based vector displays enhanced oncolytic properties in immunocompetent orthotopic syngenic mouse and rat glioma models.

Herpes — Fri, 06 Jan 2012 05:00:00 +0100

This article represents the result of a mutual interaction between human medical science and veterinary science, a combination of scientific knowledge often neglected. PMID: 22228853 [PubMed - as supplied by publisher] (Source: Herpes)

Novel brain tumor vaccine acts like bloodhound to locate cancer cells

ScienceDaily Headlines — Thu, 05 Jan 2012 19:24:24 +0100

A national U.S. clinical trial testing the efficacy of a novel brain tumor vaccine has begun. The vaccine will be tested in patients with newly diagnosed glioblastoma multiforme (GBM), the most aggressive and highest grade malignant glioma. (Source: ScienceDaily Headlines)

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Direct Inhibition of Myosin II Effectively Blocks Glioma Invasion In The Presence of Multiple Motogens.

Mol Biol Cell — Wed, 04 Jan 2012 05:00:00 +0100

In this study, we have investigated whether the molecular motor myosin II represents such a target, by examining glioma invasion in a series of increasingly complex models that are sensitive to PDGF, EGF, or both. Our results lead to two conclusions. First, malignant glioma cells are stimulated to invade brain through the activation of multiple signaling cascades that are not accounted for in simple in vitro assays. Second, even though there is a high degree of redundancy in pro-migratory signaling cascades in gliomas, blocking tumor invasion by directly targeting myosin II remains effective. Our results thus support our hypothesis that myosin II represents a point of convergence for signal transduction pathways that drive glioma invasion and that its inhibition cannot be overcome by other...

Inhibition of cyclooxygenase-2 enhances immunotherapy against experimental brain tumors

Cancer Immunology, Immunotherapy — Mon, 02 Jan 2012 16:46:34 +0100

In conclusion, we show that immunotherapy of experimental brain tumors is greatly potentiated when combined with COX-2 inhibition. Based on our results, the clinically available drug parecoxib may be added to immunotherapy against human brain tumors. Furthermore, the discovery that IFN-γ plasma levels can be used to determine the ongoing in vivo immune response has translational potential. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s00262-011-1196-yAuthors Sofia Eberstål, Glioma Immunotherapy Group, The Rausing Laboratory, BMC D14, Divison of Neurosurgery, Department of Clinical Sciences, Lund University, 221 84 Lund, SwedenWiaam Badn, Glioma Immunotherapy Group, The Rausing Laboratory, BMC D14, Divison of Neurosurgery, Department of Clinical Scie...

Enhanced therapeutic agent delivery through magnetic resonance imaging-monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status.

Neurosurgical Focus — Sun, 01 Jan 2012 05:00:00 +0100

Authors: Liu HL, Yang HW, Hua MY, Wei KC Abstract Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increas...

Delayed onset of paresis in rats with experimental intramedullary spinal cord gliosarcoma following intratumoral administration of the paclitaxel delivery system OncoGel.

Journal of Neurosurgery.Spine — Sun, 01 Jan 2012 05:00:00 +0100

Conclusions OncoGel is safe for intramedullary injection in rats in doses up to 5 μl of 3.0 mg/ml, prolongs median survival, and increases functional motor scores in rats challenged with an intramedullary gliosarcoma at the doses tested. This study suggests that locally delivered chemotherapeutic agents could be of temporary benefit in the treatment of malignant IMSCTs under experimental settings. PMID: 22208429 [PubMed - in process] (Source: Journal of Neurosurgery.Spine)

Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double strand breaks‐inducing agents by pharmacological inhibition of Ataxia Telangiectasia Mutated protein

Brain Pathology — Sun, 01 Jan 2012 05:00:00 +0100

In conclusion, pharmacological inhibition of ATM may specifically sensitize GSC to DSB‐inducing agents while sparing non‐stem cells. (Source: Brain Pathology)

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In vivo high‐resolution 3D Overhauser‐enhanced MRI in mice at 0.2 T

Contrast Media and Molecular Imaging — Sun, 01 Jan 2012 05:00:00 +0100

Overhauser‐enhanced MRI (OMRI) offers the potentiality of detecting low‐concentrated species generated by specific biological processes. However molecular imaging applications of OMRI need significant improvement in spatial localization. Here it is shown that 3D‐OMRI of a free radical injected in tumor‐bearing mice can be performed at high anatomical resolution at a constant field. A 30 mm cavity operating at 5.43 GHz was inserted in a C‐shaped magnet for proton MRI at 0.194 T. Nude mice with or without brain‐implanted C6 rat glioma were positioned in the cavity and injected with TOPCA (1‐oxyl‐2,2,5,5‐tetramethyl‐2,5‐dihydro‐1H‐pyrrole‐3‐carboxylic acid). OMRI was performed in 3D within several minutes in the brain region without high overheating of the ...

Fine‐mapping of a region of chromosome 5p15.33 (TERT‐CLPTM1L) suggests a novel locus in TERT and a CLPTM1L haplotype are associated with glioma susceptibility in a Chinese population

International Journal of Cancer — Sat, 31 Dec 2011 05:00:00 +0100

AbstractTwo genome wide association studies (GWAS) have identified 5p15.33 (TERT‐CLPTM1L) as one of the susceptible regions for glioma in European background. A replication research of our group highlighted the association signals in the TERT gene of this region in a Chinese Han population. To comprehensively explore the region of glioma association at 5p15.33 and to refine the potential causal variants to a smaller critical region, we conducted a fine‐mapping association study among 983 cases and 1024 controls in a Chinese Han population. Using Hapmap 3 datasets as a reference, we genotyped 16 tag SNPs across this 87.9kb region encompassing TERT. Significant association with glioma risk was observed for rs2853677 [GG vs GA: adjusted OR= 1.46, P= 5.51×10‐6, GG vs AA: adjusted OR= 1....

MiR-181d acts as a tumor suppressor in glioma by targeting K-ras and Bcl-2

Journal of Cancer Research and Clinical Oncology — Fri, 30 Dec 2011 06:49:27 +0100

Conclusion MiR-181d may act as a glioma suppressor by targeting K-ras and Bcl-2. Content Type Journal ArticleCategory Original PaperPages 1-12DOI 10.1007/s00432-011-1114-xAuthors Xie-Feng Wang, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 Jiangsu Province, People’s Republic of ChinaZhu-Mei Shi, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 Jiangsu Province, People’s Republic of ChinaXi-Rui Wang, Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 Jiangsu Province, People’s Republic of ChinaLei Cao, Department of Neurosurgery, The First ...

Potential of the gastric motility drug lorglumide in prostate cancer imaging.

European Journal of Pharmaceutical Sciences — Fri, 30 Dec 2011 05:00:00 +0100

Authors: Sturzu A, Sheikh S, Klose U, Echner H, Kalbacher H, Deeg M, Nägele T, Horger M, Schwentner C, Ernemann U, Heckl S Abstract The use of tissue-specific receptor ligands is a promising approach for cancer diagnostics and therapy. Lorglumide, a highly effective competitive ligand for the cholecystokinine-A receptor (CCKRA) was conjugated to a fluorescent dye and a magnetic resonance imaging (MRI) contrast agent to obtain a bifunctional marker for tissue with high CCKRA expression. An intermediate conjugate containing only lorglumide and a fluorescent dye was also produced. By performing CCKRA mRNA expression analysis on carcinoma cell lines we found that CCKRA is highly expressed in PC3 prostate carcinoma cells compared to U373 glioma and U2OS osteosarcoma cells. Uptake, spec...

Physiological and pathological functions of acid-sensing ion channels in the central nervous system.

Current Drug Targets — Thu, 29 Dec 2011 05:00:00 +0100

Authors: Chu XP, Xiong ZG Abstract Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain...

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Mesenchymal stem cells and glioma cells form a structural as well as a functional syncytium in vitro.

Experimental Neurology — Thu, 29 Dec 2011 05:00:00 +0100

Authors: Schichor C, Albrecht V, Korte B, Buchner A, Riesenberg R, Mysliwietz J, Paron I, Motaln H, Turnšek TL, Jürchott K, Selbig J, Tonn JC Abstract The interaction of human mesenchymal stem cells (hMSCs) and tumor cells has been investigated in various contexts. HMSCs are considered as cellular treatment vectors based on their capacity to migrate towards a malignant lesion. However, concerns about unpredictable behavior of transplanted hMSCs are accumulating. In malignant gliomas, the recruitment mechanism is driven by glioma-secreted factors which lead to accumulation of both, tissue specific stem cells as well as bone marrow derived hMSCs within the tumor. The aim of the present work was to study specific cellular interactions between hMSCs and glioma cells in vitro. We show...

Bay846, a new irreversible small molecule inhibitor of EGFR and Her2, is highly effective against malignant brain tumor models

Investigational New Drugs — Wed, 28 Dec 2011 06:53:28 +0100

Summary The epidermal growth factor receptor (EGFR) pathway is aberrantly activated in tumors and plays a key role in promoting tumor growth. Small molecule inhibitors which bind reversibly to EGFR have demonstrated limited clinical activity. Thus, there is a continued need to develop novel EGFR inhibitors with improved anti-tumor activity. Bay846 is a newly developed small molecule inhibitor that binds irreversibly to the tyrosine kinase domains of EGFR and Her2. The in vitro and in vivo efficacy of Bay846 was tested using a panel of nine human malignant brain tumor (glioma) models. Lapatinib, a reversible inhibitor of EGFR and Her2, was included for comparison. Six glioma cell lines were sensitive to Bay846 treatment. Bay846 strongly suppressed tumor cell growth in vitro ...

Regulation of Cdk7 activity through a phosphatidylinositol (3)-kinase/PKC-{iota}-mediated signaling cascade in glioblastoma

Carcinogenesis — Wed, 28 Dec 2011 05:00:00 +0100

The objective of this research was to study the potential function of protein kinase C (PKC)- in cell cycle progression and proliferation in glioblastoma. PKC- is highly overexpressed in human glioma and benign and malignant meningioma; however, little is understood about its role in regulating cell proliferation of glioblastoma. Several upstream molecular aberrations and/or loss of PTEN have been implicated to constitutively activate the phosphatidylinositol (PI) (3)-kinase pathway. PKC- is a targeted mediator in the PI (3)-kinase signal transduction repertoire. Results showed that PKC- was highly activated and overexpressed in glioma cells. PKC- directly associated and phosphorylated Cdk7 at T170 in a cell cycle-dependent manner, phosphorylating its downstream target, cdk2 at T160. Cdk2 ...

Association between ATM polymorphisms and cancer risk: a meta-analysis.

Molecular Biology Reports — Wed, 28 Dec 2011 05:00:00 +0100

In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk. PMID: 22203481 [PubMed - as supplied by publisher] (Source: Molecular Biology Reports)

Recent Advancements in Multimodality Treatment of GliomasRecent Advancements in Multimodality Treatment of Gliomas

Medscape Today Headlines — Wed, 28 Dec 2011 04:00:00 +0100

Find out more about the recent advancements in multimodality treatment of patients with gliomas, both in the primary and recurrent setting. Future Oncology (Source: Medscape Today Headlines)

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CD90 is identified as a marker for cancer stem cells in primary high-grade gliomas using tissue microarrays.

Molecular and Cellular Proteomics : MCP — Tue, 27 Dec 2011 05:00:00 +0100

Authors: He J, Liu Y, Zhu T, Zhu J, Dimeco F, Vescovi AL, Heth JA, Muraszko KM, Fan X, Lubman DM Abstract Although CD90 has been identified as a marker for various kinds of stem cells including liver cancer stem cells (CSCs) that are responsible for tumorigenesis, the potential role of CD90 as a marker for CSCs in gliomas has not been characterized. To address the issue, we investigated the expression of CD90 in tissue microarrays containing 15 glioblastoma multiformes (GBMs), 19 WHO grade III astrocytomas, 13 WHO grade II astrocytomas, 3 WHO grade I astrocytomas and 8 normal brain tissues. Immunohistochemical analysis showed that CD90 was expressed at a medium to high level in all tested high-grade gliomas (grade III and GBMs) while it was barely detectable in low-grade gliomas (g...

Imaging heterogeneity in gliomas using texture analysis.

Cancer Imaging — Mon, 26 Dec 2011 17:24:03 +0100

Conclusion: CTTA (e.g. TexRAD) has the potential to quantify tumour heterogeneity more so than size and thereby differentiate between high- and low-grade gliomas. PMID: 22186214 [PubMed - in process] (Source: Cancer Imaging)

Encapsulated therapeutic stem cells implanted in the tumor resection cavity induce cell death in gliomas

Nature Neuroscience — Sun, 25 Dec 2011 05:00:00 +0100

Authors: Timo M Kauer, Jose-Luiz Figueiredo, Shawn Hingtgen & Khalid Shah (Source: Nature Neuroscience)

Volumetric response evaluation after intensity modulated radiotherapy in patients with supratentorial gliomas.

Technology in Cancer Research and Treatment — Sat, 24 Dec 2011 16:49:00 +0100

Authors: Cho KH, Choi JH, Kim JY, Lee SH, Yoo H, Shin KH, Kim TH, Moon SH, Lee SH, Park HC Abstract Radiotherapy is frequently indicated to treat cerebral gliomas. Accurate response evaluation after radiotherapy is essential to determine the efficacy of treatment. We retrospectively analyzed the volumetric tumor response after simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in patients with gliomas. Thirty-five patients (Grade II, 7 patients; Grade III, 12; and Grade IV, 16) were treated with SIB-IMRT with a median total dose of 55.9 Gy/26 fractions for Grade II and 60 Gy/25 fractions for Grade III-IV tumors. Tumor responses were evaluated for enhancing volume on post-gadolinium T1-weighted images (Vgd) and hyper-intensity volume on T2-weighted FLAIR image...

A novel vaccine containing EphA2 epitope and LIGHT plasmid induces robust cellular immunity against glioma U251 cells.

Cellular Immunology — Sat, 24 Dec 2011 10:12:02 +0100

Authors: Chen H, Yuan B, Zheng Z, Liu Z, Wang S, Liu Y Abstract EphA2 is a receptor tyrosine kinase and can be acted as an attractive antigen for glioma vaccines. In addition, LIGHT plays an important role on enhancing T cell proliferation and cytokine production. To improve the CTL mediated immune response against glioma cells, we prepared the novel vaccine containing EphA2(883-891) peptide (TLADFDPRV) and LIGHT plasmid and utilized it to immunize the HLA-A2 transgenic HHD mice. In addition, trimera mice were immunized with the novel vaccine to elicit the antitumor immune response. The results demonstrated that the novel vaccine could induce robust cellular immunity against glioma U251 cells without lysing autologous lymphocytes. Moreover, the novel vaccine could significantly inh...

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Granulocyte-macrophage colony-stimulating factor as an autocrine survival-growth factor in human gliomas.

Cytokine — Sat, 24 Dec 2011 05:00:00 +0100

Authors: Revoltella RP, Menicagli M, Campani D Abstract We studied the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptors (GM-CSF.R) in 20 human brain gliomas with different tumor gradings and demonstrated constitutive high levels of both mRNA gene expression and protein production exclusively in the highest-grade tumors (WHO, III-IV grade). Five astrocytic cell lines were isolated in vitro from glioma cells, which had selectively adhered to plates pre-coated with rhGM-CSF. These cells were tumorigenic when xenografted to athymic mice, and produced GM-CSF constitutively in culture. Two lines, particularly lines AS1 and PG1, each from a patient with glioblastoma multiforme, constitutively over-expressed both GM-CSF and GM-CSF.R genes and secret...

Orbitofacial neurofibromatosis: clinical characteristics and treatment outcome

Eye — Fri, 23 Dec 2011 08:00:00 +0100

Authors: I A Chaudhry, J Morales, F A Shamsi, W Al-Rashed, E Elzaridi, Y O Arat, C Jacquemin, D T Oystreck & T M Bosley (Source: Eye)

PRMT5 Regulates Oligodendrocyte Differentiation [Gene Regulation]

Journal of Biological Chemistry — Fri, 23 Dec 2011 05:00:00 +0100

PRMT5 is a type II protein arginine methyltranferase that catalyzes monomethylation and symmetric dimethylation of arginine residues. PRMT5 is functionally involved in a variety of biological processes including embryo development and circadian clock regulation. However, the role of PRMT5 in oligodendrocyte differentiation and central nervous system myelination is unknown. Here we show that PRMT5 expression gradually increases throughout postnatal brain development, coinciding with the period of active myelination. PRMT5 expression was observed in neurons, astrocytes, and oligodendrocytes. siRNA-mediated depletion of PRMT5 in mouse primary oligodendrocyte progenitor cells abrogated oligodendrocyte differentiation. In addition, the PRMT5-depleted oligodendrocyte progenitor and C6 glioma cel...

Animal model of intramedullary spinal cord glioma using human glioblastoma multiforme neurospheres.

Journal of Neurosurgery.Spine — Fri, 23 Dec 2011 05:00:00 +0100

Conclusions The authors have established a novel animal model of spinal cord glioma using neurospheres derived from human GBM. When injected into the spinal cords of athymic nude rats, neurospheres gave rise to infiltrative, actively proliferating tumors that were histologically identical to spinal cord glioma in humans. On the basis of their results, the authors conclude that this is a reproducible animal model of high-grade spinal cord glioma based on a human GBM neurosphere line. This model represents an improvement over other models using nonhuman glioma cell lines. Novel therapeutic strategies can be readily evaluated using this model. PMID: 22195609 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery.Spine)

Effects of Irradiation on Brain Vasculature Using an In Situ Tumor Model

International Journal of Radiation Oncology * Biology * Physics — Fri, 23 Dec 2011 05:00:00 +0100

Conclusions: We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. (Source: International Journal of Radiation Oncology * Biology * Physics)

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Brain tumour risk linked to high blood pressure

NHS News Feed — Thu, 22 Dec 2011 17:30:00 +0100

Conclusion This large prospective cohort study comprising more than 500,000 people from Austria, Norway and Sweden suggested an association between high blood pressure and some types of brain tumour. It should be noted, however, that even among the group of people with highest blood pressure the overall incidence of brain cancers was low. Furthermore, there were several limitations to this study: Data was only available for the three types of tumour: meningioma and high- and low-grade glioma. Other types of tumour accounted for around 32% of the tumours in the study population. The researchers did not collect information on whether the participants had used medication, particularly on whether they were taking medication for lowering their blood pressure. These may have had an impact ...

Treatment-Related Change Versus Tumor Recurrence in High-Grade Gliomas: A Diagnostic Conundrum--Use of Dynamic Susceptibility Contrast-Enhanced (DSC) Perfusion MRI

American Journal of Roentgenology — Thu, 22 Dec 2011 05:00:00 +0100

CONCLUSION. Posttreatment imaging assessment of high-grade gliomas remains challenging. Familiarity with the expected MR imaging appearances of treatment-related change and tumor recurrence will help distinguish these entities allowing appropriate management. (Source: American Journal of Roentgenology)

DCE and DW‐MRI monitoring of vascular disruption following VEGF‐Trap treatment of a rat glioma model

NMR in Biomedicine — Thu, 22 Dec 2011 05:00:00 +0100

In conclusion, kinetic MRI parameters and change in ADC have been found to serve as sensitive and early biomarkers of VEGF‐Trap anti‐vascular targeted therapy. Copyright © 2011 John Wiley & Sons, Ltd.DCE‐MRI and MRI DW‐MRI were evaluated for detecting response of intracerebral 9L gliomas to the antivascular agent VEGF‐Trap. A significant drop in permeability parameters was observed 24 hours following the first dose of VEGF‐Trap accompanied by a decline in ADC values. VEGF‐Trap‐treated animals also required a significantly longer time for their tumors to reach 300% initial tumor volume compared to the untreated animals. (Source: NMR in Biomedicine)

Bioactivity‐guided Isolation of Cytotoxic Sesquiterpene Lactones of Gochnatia polymorpha ssp. floccosa

Phytotherapy Research — Thu, 22 Dec 2011 05:00:00 +0100

Phytochemical study of Gochnatia polymorpha (Less) Cabr. ssp. floccosa Cabr. trunk bark, guided by antiproliferative assays on 10 human cancer cell lines and the VERO cell line, yielded six known compounds identified as the triterpene bauerenyl acetate, the guaianolide 11α,13‐dihydrozaluzanin C and the dimeric guaianolides 10‐desoxygochnatiolide A, gochnatiolide A, 8‐hydroxi‐10‐desoxygochnatiolide A and 8‐hydroxigochnatiolide A. Extracts, fractions of extracts and isolated compounds were tested in vitro against a panel of human cancer cell lines, including U251 (glioma, CNS), UACC‐62 (melanoma), MCF‐7 (breast), NCI‐ADR/RES (drug‐resistant ovarian), 786.0 (kidney), NCI‐H460 (lung, no small cells), PC‐3 (prostate), OVCAR‐3 (ovarian), HT‐29 (colon), K562 (leukemia...

A Mathematical Model for the Glucose-Lactate Metabolism of in Vitro Cancer Cells.

Bulletin of Mathematical Biology — Thu, 22 Dec 2011 05:00:00 +0100

Authors: Mendoza-Juez B, Martínez-González A, Calvo GF, Pérez-García VM Abstract We propose a mathematical model of tumor cell nutrient uptake governed by the presence of two key biomolecular fuels: glucose and lactate. The model allows us to describe, in a remarkably simple way, different in vitro scenarios previously reported in experiments of tumor cell metabolism using distinct energy sources. The predictions of our model show good agreement with all the examined tumor cell lines (cervix, colon, and glioma) and provide a first step toward the development of more comprehensive frameworks accounting for in vivo cancer dynamics under complex spatial heterogeneities. PMID: 22190043 [PubMed - as supplied by publisher] (Source: Bulletin of Mathematical Biology)

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Activity of novel quinoxaline-derived chalcones on in vitro glioma cell proliferation.

European Journal of Medicinal Chemistry — Thu, 22 Dec 2011 05:00:00 +0100

Authors: Mielcke TR, Mascarello A, Filippi-Chiela E, Zanin RF, Lenz G, Leal PC, Chirardia LD, Yunes RA, Nunes RJ, Battastini AM, Morrone FB, Campos MM Abstract Gliomas are the most common and devastating tumors of the central nervous system (CNS). Many pieces of evidence point out the relevance of natural compounds for cancer therapy and prevention, including chalcones. In the present study, eight synthetic quinoxaline-derived chalcones, structurally based on the selective PI3Kγ inhibitor AS605240, were evaluated for anti-proliferative activity and viability inhibition using glioma cell lines from human and rat origin (U-138 MG and C6, respectively), at different time-periods of incubation and concentrations. The results revealed that four chalcones (compounds 1, 6, 7 and 8), whic...

Advances and Technical Standards in Neurosurgery

Springer Medicine titles — Thu, 22 Dec 2011 01:34:16 +0100

series:Advances and Technical Standards in NeurosurgeryAdvances: H. Duffau: Subpial dissection and subcortical mapping with vasculature and white matter pathways preservation in surgery for brain (low grade) gliomas. - F. Scholtes, G. Brook, D. Martin: Spinal cord injury and its treatment: current management and experimental perspectives. - M. Sindou, M. Messerer, J. Alvernia, G. Saint-Pierre: Percutaneous Biopsy through the Foramen Ovale for ... (Source: Springer Medicine titles)

Cell-Type-Dependent Thyroid Hormone Effects on Glioma Tumor Cell Lines

Clinical and Developmental Immunology — Wed, 21 Dec 2011 23:54:28 +0100

Conclusion. In conclusion, T3 can re-differentiate glioma tumor cells, whereas its effect on cell proliferation appears to be dependent on the type of tumor cell line with aggressive tumors being more sensitive to T3. TRα1 receptor may, at least in part, be implicated in this response. (Source: Clinical and Developmental Immunology)

Expression and distribution characteristics of human ortholog of mammalian enabled (hMena) in glioma

Chinese Journal of Cancer Research — Wed, 21 Dec 2011 19:52:11 +0100

Conclusion Our data suggested that the expression of hMena is closely related to malignant grade of glioma. hMena can label the migrating cells, and indicate the migrating path of glioma cells from the tumor to adjacent tissue along with the vascular basement membranes and tracts of white matter. Content Type Journal ArticleCategory Original ArticlePages 312-316DOI 10.1007/s11670-011-0312-zAuthors Xue-tao Dong, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Tianjin, 300052 ChinaXue-jun Yang, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Tianjin, 300052 ChinaHua-min Wang, Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin ...

The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma [Research Papers]

Genes and Development — Wed, 21 Dec 2011 05:00:00 +0100

Recent molecular classification of glioblastoma (GBM) has shown that patients with a mesenchymal (MES) gene expression signature exhibit poor overall survival and treatment resistance. Using regulatory network analysis of available expression microarray data sets of GBM, including The Cancer Genome Atlas (TCGA), we identified the transcriptional coactivator with PDZ-binding motif (TAZ), to be highly associated with the MES network. TAZ expression was lower in proneural (PN) GBMs and lower-grade gliomas, which correlated with CpG island hypermethylation of the TAZ promoter compared with MES GBMs. Silencing of TAZ in MES glioma stem cells (GSCs) decreased expression of MES markers, invasion, self-renewal, and tumor formation. Conversely, overexpression of TAZ in PN GSCs as well as murine neu...

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Cutoff Value of Choline Concentration Reliably Reveals High-Grade Brain Tumors among Other Contrast-Enhancing Brain Lesions

Zentralblatt fur Neurochirurgie - Central European Neurosurgery — Wed, 21 Dec 2011 05:00:00 +0100

Cen Eur NeurosurgDOI: 10.1055/s-0031-1291180To evaluate whether there is a cutoff value for a metabolite concentration measured by 1 H MR spectroscopy (MRS), which can be used to differentiate malignant brain tumors (high-grade gliomas, primary CNS lymphomas [PCNSL] and metastases) from other contrast-enhancing lesions like low-grade gliomas and non-neoplastic lesions.1 H MRS was performed in 252 consecutive patients with space-occupying brain lesions which were enhanced with application of a contrast agent. Concentrations of N-acetyl-aspartate, total creatine, choline containing metabolites (total choline, tCho), lipids, and lactate were evaluated from the contrast-enhancing part of the lesions and from the normal appearing brain tissue. Linear discriminant analysis was used to find t...

Diffuse Glioma: A Systemic Brain DiseaseDiffuse Glioma: A Systemic Brain Disease

Medscape Today Headlines — Tue, 20 Dec 2011 20:00:51 +0100

Medscape Medical News (Source: Medscape Today Headlines)

Epidemiology: allergy history, IgE, and cancer

Cancer Immunology, Immunotherapy — Tue, 20 Dec 2011 06:49:02 +0100

Abstract Numerous epidemiological studies have investigated potential associations between allergy history and cancer risk with strong inverse associations reported in studies of pancreatic cancer, glioma, and childhood leukemia. Recently, there has been a rapid expansion of the epidemiological literature both of studies evaluating self-reported allergy history in relation to cancer risk and of studies evaluating biological indicators of allergy history and immune function including levels of immunoglobulin (Ig) E. However, there are several potential methodological limitations associated with prior studies, and further research is required to clarify associations observed. This paper summarizes the recent epidemiological literature examining associations between allergy h...

Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions

Journal of Neuro-Oncology — Tue, 20 Dec 2011 06:47:31 +0100

In this study, we aimed to determine whether high micro-vessel density (MVD) expressed by RECK in glioma tissue is correlated with grades of glioma. We also compared RECK expression with that of the formerly known vessel marker, CD34, and vascular endothelial growth factor (VEGF). RECK, CD34, and VEGF immuno-reactivities of 72 glioma tissues were studied. RECK was seen in microvessels of glioma tissues. CD34 showed a similar pattern to RECK, whereas VEGF showed positive staining in cytoplasm of tumor cells and endothelial cells. Average MVD with RECK was 107.6 microvessels (range 7–290). RECK was positively correlated with grades of glioma. RECK and CD34 also showed a strong correlation (P = 0.001). Higher frequency of VEGF staining was also correlated with higher grade of...

Neuronal markers are expressed in human gliomas and NSE knockdown sensitizes glioblastoma cells to radiotherapy and temozolomide

BMC Cancer — Tue, 20 Dec 2011 05:00:00 +0100

Conclusions: Neuronal markers are aberrantly expressed in human GBMs, and NSE is consistently upregulated in different cellular stress conditions. Knockdown of NSE reduces the migration of GBM cells and sensitizes them to hypoxia, radiotherapy and chemotherapy. In addition, GBM patients with high NSE expression had significantly shorter survival than patients with low NSE expression. Collectively, these data suggest a role for NSE in the adaption to cellular stress, such as during treatment. (Source: BMC Cancer)

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Gene expression profiles of gliomas in formalin-fixed paraffin-embedded material

British Journal of Cancer AOP — Tue, 20 Dec 2011 05:00:00 +0100

Authors: L A M Gravendeel, J J de Rooi, P H C Eilers, M J van den Bent, P A E Sillevis Smitt & P J French (Source: British Journal of Cancer AOP)

Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma

Pediatric Blood and Cancer — Tue, 20 Dec 2011 05:00:00 +0100

AbstractDiffuse intrinsic pontine gliomas (DIPG) can not be cured with current treatment modalities. Targeted therapy in this disease would benefit from advanced technologies detecting relevant drugable mutations. Twenty patients with classic newly diagnosed DIPG underwent stereotactic biopsies and were analyzed for the presence of 983 different mutations in 115 oncogenes and tumor‐suppressor genes using OncoMap, a mass spectrometric method of allele detection. Our results identified oncogenic mutations in TP53 (40%), PI3KCA (15%), and ATM/MPL (5%) while none were identified in a large number of other genes commonly mutated in malignant gliomas. The identification of oncogenic mutations in the PI3K pathway offers the potential of a therapeutic target at initial diagnosis in this devastat...

The Zfx gene is expressed in human gliomas and is important in the proliferation and apoptosis of the human malignant glioma cell line U251

Journal of Experimental and Clinical Cancer Research — Tue, 20 Dec 2011 05:00:00 +0100

Conclusions: The results of our study demonstrate that the Zfx gene is highly expressed in glioma tissue and in glioma cell lines. Furthermore, Zfx may play a critical role in cell proliferation, cell cycle distribution, and apoptosis of human malignant glioma cells. (Source: Journal of Experimental and Clinical Cancer Research)

Pegylated interferon alpha-2b does not improve survival with pontine glioma

Modern Medicine — Tue, 20 Dec 2011 05:00:00 +0100

NEW YORK (Reuters Health) - Pegylated interferon alpha-2b (PEG-Intron) does not improve two-year survival in children with diffuse intrinsic pontine glioma (DIPG), according to a report in the November 15th online issue of Cancer. (Source: Modern Medicine)

Guanylate binding protein 1 is a novel effector of EGFR-driven invasion in glioblastoma

The Journal of Experimental Medicine — Mon, 19 Dec 2011 05:00:00 +0100

In this study, we show that EGFR activation promoted GBP1 expression in GBM cell lines through a signaling pathway involving Src and p38 mitogen-activated protein kinase. Moreover, we identified YY1 (Yin Yang 1) as the downstream transcriptional regulator regulating EGFR-driven GBP1 expression. GBP1 was required for EGFR-mediated MMP1 (matrix metalloproteinase 1) expression and glioma cell invasion in vitro. Although deregulation of GBP1 expression did not affect glioma cell proliferation, overexpression of GBP1 enhanced glioma cell invasion through MMP1 induction, which required its C-terminal helical domain and was independent of its GTPase activity. Reducing GBP1 levels by RNA interference in invasive GBM cells also markedly inhibited their ability to infiltrate the brain parenchyma of ...

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Childhood brain tumour risk and its association with wireless phones: a commentary

Environmental Health — Mon, 19 Dec 2011 05:00:00 +0100

Case-control studies on adults point to an increased risk of brain tumours (glioma and acoustic neuroma) associated with the long-term use of mobile phones. Recently, the first study on mobile phone use and the risk of brain tumours in children and adolescents, CEFALO, was published. It has been claimed that this relatively small study yielded reassuring results of no increased risk. We do not agree. We consider that the data contain several indications of increased risk, despite low exposure, short latency period, and limitations in the study design, analyses and interpretation. The information certainly cannot be used as reassuring evidence against an association, for reasons that we discuss in this commentary. (Source: Environmental Health)

RTOG Activates Study To Determine Best Treatment Strategies For Patients With Glioma Brain Tumors

Health News from Medical News Today — Fri, 16 Dec 2011 10:00:00 +0100

Treatment remains controversial for patients diagnosed with a low-risk, low-grade glioma (LGG) brain tumor. These patients have significantly better prognosis than patients diagnosed with more aggressive high-grade glioma, and their clinical care often involves ongoing observation for tumor changes with imaging studies. Because low-risk LGG are slow growing tumors, concerns about the potential adverse effects of early treatment on patients' neurocognitive function (NCF) and quality of life (QOL) may outweigh treatment benefits in patients who are frequently young and highly functional... (Source: Health News from Medical News Today)

Growth Hormone Secretion After Conformal Radiation Therapy in Pediatric Patients With Localized Brain Tumors [Pediatric Oncology]

Journal of Clinical Oncology — Fri, 16 Dec 2011 05:00:00 +0100

Conclusion GH secretion after CRT can be predicted on the basis of dose and time after irradiation in pediatric patients with localized brain tumors. These findings provide an objective radiation dose constraint for the hypothalamus. (Source: Journal of Clinical Oncology)

Postoperative radiation therapy for low‐grade glioma

Cancer — Fri, 16 Dec 2011 05:00:00 +0100

CONCLUSIONS:The use of PORT for patients with low‐grade glioma has declined in the period from 1998 to 2006 for both low‐risk and high‐risk patients. Cancer 2012;. © 2011 American Cancer Society. (Source: Cancer)

Alteration of endocannabinoid system in human gliomas

Journal of Neurochemistry — Fri, 16 Dec 2011 05:00:00 +0100

AbstractEndocannabinoids are neuromodulatory lipids that mediate the central and peripheral neural functions. Endocannabinoids have demonstrated their anti‐proliferative, anti‐angiogenic and pro‐apoptotic properties in a series of studies. In the present study, we investigated the levels of two major endocannabinoids, anandamide and 2‐arachidonylglycerol (2‐AG), and their receptors, CB1 and CB2, in human low grade glioma (WHO grade I‐II) tissues, high grade glioma (WHO grade III‐IV) tissues, and non‐tumor brain tissue controls. We also measured the expressions and activities of the enzymes responsible for anandamide and 2‐AG biosynthesis and degradation, i.e., N‐acylphosphatidylethanolamine‐hydrolysing phospholipase D (NAPE‐PLD), fatty acid amide hydrolase (FAAH), m...

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[Controversial aspects in WHO grade II gliomas management: review of recent literature].

Revista de Neurologia — Fri, 16 Dec 2011 05:00:00 +0100

CONCLUSIONS. There is growing scientific evidence against a 'wait-and-see' management of GIIG. Surgery is considered nowadays by most authors as the first step in the diagnosis and treatment of these tumors. PMID: 22127662 [PubMed - in process] (Source: Revista de Neurologia)

Clinical, radiological, and pathological features of 24 atypical intracranial epidermoid cysts.

Journal of Neurosurgery — Fri, 16 Dec 2011 05:00:00 +0100

Conclusions Radiologically, an atypical epidermoid cyst should be differentiated from dermoid cyst, teratoma, schwannoma, glioma, craniopharyngioma, and cavernous angioma. A tendency toward spontaneous hemorrhage is confirmed in atypical epidermoid cysts, and a hypothesis was proposed for spontaneously intracystic hemorrhage in atypical epidermoid cysts. Follow-up confirmed long-term survival of patients with atypical epidermoid cysts. PMID: 22175719 [PubMed - as supplied by publisher] (Source: Journal of Neurosurgery)

EGFR inhibitor enhances cisplatin sensitivity of human glioma cells

Journal of Huazhong University of Science and Technology -- Medical Sciences -- — Thu, 15 Dec 2011 16:45:05 +0100

This study was to examine the effect of an EGFR-tyrosine kinase inhibitor (AG1478) alone or in combination with cisplatin (CDDP) on the growth of glioma cells (U87). U87 glioma cells were treated with AG1478 (10 μmol/L) or CDDP (25 μmol/L) as a single agent or in combination for 24 or 48 h. The expression of EGFR and the components in its downstream signaling pathway [extracellular signal-regulated kinase (ERK), protein kinase B (AKT)] in U87 glioma cells was detected by Western blotting. Cell growth, cell cycle distribution and cell apoptosis were determined by MTT method and flow cytometry, respectively. The results showed that CDDP could induce the activation of EGFR and the components in its downstream signaling pathways in a concentration-dependent manner. The combined treatme...

Independent prognostic value of pre-treatment 18-FDG-PET in high-grade gliomas

Journal of Neuro-Oncology — Thu, 15 Dec 2011 06:43:55 +0100

Abstract The prognostic value of PET with (18F)-fluoro-2-deoxy-d-glucose (FDG) has been shown in high-grade gliomas (HGG), but not compared with consensual prognostic factors. We sought to evaluate the independent predictive value of pre-treatment FDG-PET on overall (OS) and event-free survival (EFS). We retrospectively analyzed 41 patients with histologically-confirmed HGG (31 glioblastomas and 10 anaplastic gliomas). The pre-treatment uptake of FDG was assessed qualitatively by five-step visual metabolic grading, and quantitatively by the ratio between the tumor and contralateral maximal standardized uptake value (T/CL). EFS and OS following PET were compared with FDG uptake by univariate analysis, and by two multivariate analyses: one including main consensual prognostic...

RTOG activates study to determine best treatment strategies for patients with glioma brain tumors

EurekAlert! - Medicine and Health — Thu, 15 Dec 2011 05:00:00 +0100

(American College of Radiology) The RTOG 0925 clinical trial seeks to determine if patients' neurocognitive changes caused by the tumor progression can help guide treatment decisions. (Source: EurekAlert! - Medicine and Health)

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Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: In Silico Modeling Integrates Imaging and Histology

Cancer Research — Thu, 15 Dec 2011 05:00:00 +0100

This study suggests that through the application of the proposed model for tumor–microenvironment interactions, predictable patterns of dynamic changes in glioma histology distinct from changes in cellular phenotype (e.g., proliferation and invasion rates) may be identified, thus providing a powerful clinical tool. Cancer Res; 71(24); 7366–75. ©2011 AACR. (Source: Cancer Research)

Genome-Wide High-Density SNP Linkage Search for Glioma Susceptibility Loci: Results from the Gliogene Consortium

Cancer Research — Thu, 15 Dec 2011 05:00:00 +0100

In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium single-nucleotide polymorphism, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P = 0.0005) at 17q12-21.32 and the Z-score of 4.20 (P = 0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P = 0.008) and the Z-score of 1.47 (P = 0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P = 0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susce...

GLIPR1 Suppresses Prostate Cancer Development through Targeted Oncoprotein Destruction

Cancer Research — Thu, 15 Dec 2011 05:00:00 +0100

Downregulation of the proapoptotic p53 target gene glioma pathogenesis-related protein 1 (GLIPR1) occurs frequently in prostate cancer, but the functional meaning of this event is obscure. Here, we report the discovery of functional relationship between GLIPR1 and c-Myc in prostate cancer where c-Myc is often upregulated. We found that the expression of GLIPR1 and c-Myc were inversely correlated in human prostate cancer. Restoration of GLIPR1 expression in prostate cancer cells downregulated c-myc levels, inhibiting cell-cycle progression. Downregulation was linked to a reduction in β-catenin/TCF4-mediated transcription of the c-myc gene, which was caused by GLIPR1-mediated redistribution of casein kinase 1α (CK1α) from the Golgi apparatus to the cytoplasm where CK1α could phosphorylat...

Bimodal Fluorescence and Magnetic Resonance Imaging Using Water-Soluble Hexagonal NaYF4:Ce,Tb,Gd Nanocrystals

Journal of Biophysics — Wed, 14 Dec 2011 15:17:29 +0100

The present study explored the feasibility of using hexagonal-phase NaYF4:Ce,Tb,Gd nanocrystals as bimodal probes for fluorescence and magnetic resonance (MR) imaging. Using a facile and user-friendly strategy, the NaYF4:Ce,Tb,Gd nanocrystals were synthesized with good water dispensability, high quantum yield (26%), and decent MR T1 relaxivity (r1=2.87 mM−1 s−1). The NaYF4:Ce,Tb,Gd NCs conjugated by folic acid presented great efficiency in fluorescence imaging of C6 glioma cells in vitro. Meanwhile, in in vivo MR experiments on rats, the NaYF4:Ce,Tb,Gd NCs also significantly increased T1 signal in the liver, spleen, and ...

MicroRNA-30e* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the NF-κB/IκB{alpha} negative feedback loop

Journal of Clinical Investigation — Wed, 14 Dec 2011 08:26:02 +0100

Constitutive activation of NF-κB is a frequent event in human cancers, playing important roles in cancer development and progression. In nontransformed cells, NF-κB activation is tightly controlled by IκBs. IκBs bind NF-κB in the cytoplasm, preventing it from translocating to the nucleus to modulate gene expression. Stimuli that activate NF-κB signaling trigger IκB degradation, enabling nuclear translocation of NF-κB. Among the genes regulated by NF-κB are those encoding the IκBs, providing a negative feedback loop that limits NF-κB activity. How transformed cells override this NF-κB/IκB negative feedback loop remains unclear. Here, we report in human glioma cell lines that microRNA-30e*...

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Alkylpurine-DNA-N-glycosylase confers resistance to temozolomide in xenograft models of glioblastoma multiforme and is associated with poor survival in patients

Journal of Clinical Investigation — Wed, 14 Dec 2011 08:26:02 +0100

Glioblastoma multiforme (GBM) is the most common and lethal of all gliomas. The current standard of care includes surgery followed by concomitant radiation and chemotherapy with the DNA alkylating agent temozolomide (TMZ). O6-methylguanine–DNA methyltransferase (MGMT) repairs the most cytotoxic of lesions generated by TMZ, O6-methylguanine. Methylation of the MGMT promoter in GBM correlates with increased therapeutic sensitivity to alkylating agent therapy. However, several aspects of TMZ sensitivity are not explained by MGMT promoter methylation. Here, we investigated our hypothesis that the base excision repair enzyme alkylpurine–DNA–N-glycosylase (APNG), which repairs the cytotoxic lesions N3-methyladenine and N7-methylguanine, may contribute to TMZ resistance. S...

Potent and selective inhibition of T-cell protein tyrosine phosphatase (TCPTP) by a dinuclear copper(II) complex

RSC - Chem. Commun. latest articles — Wed, 14 Dec 2011 07:28:18 +0100

Chem. Commun., 2012, Advance ArticleDOI: 10.1039/C2CC16818A, CommunicationCaixia Yuan, Miaoli Zhu, Qingming Wang, Liping Lu, Shu Xing, Xueqi Fu, Zheng Jiang, Shuo Zhang, Zongwei Li, Zhuoyu Li, Ruiting Zhu, Ling Ma, Liqing XuA dinuclear Cu(II) complex, [Cu2([small mu ]-IDA)(phen)3(NO3)]NO3[middle dot]4H2O, was found to potently and selectively inhibit T-cell protein tyrosine phosphatase, and lead to the anti-proliferation and apoptosis of C6 rat glioma cells.To cite this article before page numbers are assigned, use the DOI form of citation above.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Chem. Commun. latest articles)

Integration of adenovirus thymidine kinase suicide-gene therapy with surgery and radiation therapy for malignant glioma

Future Oncology — Tue, 13 Dec 2011 15:56:24 +0100

Future Oncology , January 2012, Vol. 8, No. 1, Pages 17-20. (Source: Future Oncology)

New similarity search based glioma grading

Neuroradiology — Tue, 13 Dec 2011 06:58:04 +0100

Conclusion Our findings indicate that integration of perfusion parameters and CE-T1w information in a semi-automatic similarity search based analysis improves the potential of MR-based glioma grading compared to CE-T1w data alone. Content Type Journal ArticleCategory Diagnostic NeuroradiologyPages 1-9DOI 10.1007/s00234-011-0988-2Authors Katrin Haegler, Department of Neuroradiology, Ludwig-Maximilians-University of Munich, Marchioninistrasse 15, 81377 Munich, GermanyMartin Wiesmann, Department of Neuroradiology, RWTH Aachen University, Aachen, GermanyChristian Böhm, Department of Computer Science, Ludwig-Maximilians-University of Munich, Munich, GermanyJessica Freiherr, Department of Neuroradiology, RWTH Aachen University, Aachen, GermanyOliver Schnell, Department of...