WorldWideScience

Sample records for intrinsic pontine glioma

  1. Functionally-defined Therapeutic Targets in Diffuse Intrinsic Pontine Glioma

    Science.gov (United States)

    Grasso, Catherine S.; Tang, Yujie; Truffaux, Nathalene; Berlow, Noah E.; Liu, Lining; Debily, Marie-Anne; Quist, Michael J.; Davis, Lara E.; Huang, Elaine C.; Woo, Pamelyn J; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa B.; Sun, Wenchao; Kogiso, Mari; Du, Yuchen; Lin, Qi; Huang, Yulun; Hütt-Cabezas, Marianne; Warren, Katherine E.; Dret, Ludivine Le; Meltzer, Paul S.; Mao, Hua; Quezado, Martha; van Vuurden, Dannis G.; Abraham, Jinu; Fouladi, Maryam; Svalina, Matthew N.; Wang, Nicholas; Hawkins, Cynthia; Nazarian, Javad; Alonso, Marta M.; Raabe, Eric; Hulleman, Esther; Spellman, Paul T.; Li, Xiao-Nan; Keller, Charles; Pal, Ranadip; Grill, Jacques; Monje, Michelle

    2015-01-01

    Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNAseq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated efficacy in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat with histone demethylase inhibitor GSKJ4 revealed synergy. Together, these data suggest a promising therapeutic strategy for DIPG. PMID:25939062

  2. Pre-Clinical Models of Diffuse Intrinsic Pontine Glioma

    Directory of Open Access Journals (Sweden)

    Oren J Becher

    2015-07-01

    Full Text Available Diffuse Intrinsic Pontine Glioma (DIPG is a rare and incurable brain tumor that arises in the brainstem of children predominantly between the ages of six and eight. Its intricate morphology and involvement of normal pons tissue precludes surgical resection, and the standard of care today remains fractionated radiation alone. In the past 30 years, there have been no significant advances made in the treatment of DIPG. This is largely because we lack good models of DIPG and therefore have little biological basis for treatment. In recent years however, due to increased biopsy and acquisition of autopsy specimens, research is beginning to unravel the genetic and epigenetic drivers of DIPG. Insight gleaned from these studies has led to improvements in approaches to both model these tumors in the lab, as well as to potentially treat them in the clinic. This review will detail the initial strides towards modeling DIPG in animals, which included allograft and xenograft rodent models using non-DIPG glioma cells. Important advances in the field came with the development of in vitro cell and in vivo xenograft models derived directly from autopsy material of DIPG patients or from human embryonic stem cells. Lastly, we will summarize the progress made in the development of genetically engineered mouse models of DIPG. Cooperation of studies incorporating all of these modeling systems to both investigate the unique mechanisms of gliomagenesis in the brainstem and to test potential novel therapeutic agents in a preclinical setting will result in improvement in treatments for DIPG patients.

  3. Rapid and fulminant leptomeningeal spread following radiotherapy in diffuse intrinsic pontine glioma.

    Science.gov (United States)

    Tinkle, Christopher L; Orr, Brent A; Lucas, John T; Klimo, Paul; Patay, Zoltan; Baker, Suzanne J; Broniscer, Alberto; Qaddoumi, Ibrahim

    2017-01-13

    A 4-year-old male presented with rapid-onset cranial nerve palsy and ataxia. Brain magnetic resonance imaging (MRI) revealed a pontine mass lesion with discordant conventional and advanced imaging. A stereotactic core biopsy revealed glioblastoma with immunostaining suggestive of histone H3K27M and TP53 mutation, consistent with diffuse intrinsic pontine glioma. MRI 3 months after radiotherapy revealed extensive new leptomeningeal metastatic disease involving both the supra- and infratentorial brain, as well as the imaged portion of the spine. Tissue procured at the time of needle biopsy has undergone striking in vivo expansion as an orthotopic xenograft.

  4. Bevacizumab Targeting Diffuse Intrinsic Pontine Glioma: Results of 89Zr-Bevacizumab PET Imaging in Brain Tumor Models

    NARCIS (Netherlands)

    Jansen, M.H.; Lagerweij, T.; Sewing, A.C.; Vugts, D.J.; Vuurden, D.G. van; Molthoff, C.F.; Caretti, V.; Veringa, S.J.; Petersen, N.; Carcaboso, A.M.; Noske, D.P.; Vandertop, W.P.; Wesseling, P.; Dongen, G.A. van; Kaspers, G.J.; Hulleman, E.

    2016-01-01

    The role of the VEGF inhibitor bevacizumab in the treatment of diffuse intrinsic pontine glioma (DIPG) is unclear. We aim to study the biodistribution and uptake of zirconium-89 ((89)Zr)-labeled bevacizumab in DIPG mouse models. Human E98-FM, U251-FM glioma cells, and HSJD-DIPG-007-FLUC primary DIPG

  5. Hypofractionation vs Conventional Radiation Therapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Matched-Cohort Analysis

    NARCIS (Netherlands)

    Janssens, G.O.R.J.; Jansen, M.H.; Lauwers, S.J.; Nowak, P.J.; Oldenburger, F.R.; Bouffet, E.; Saran, F.; Kamphuis-van Ulzen, K.; Lindert, E.J. van; Schieving, J.H.; Boterberg, T.; Kaspers, G.J.L.; Span, P.N.; Kaanders, J.H.A.M.; Gidding, C.E.M.; Hargrave, D.

    2013-01-01

    PURPOSE: Despite conventional radiation therapy, 54 Gy in single doses of 1.8 Gy (54/1.8 Gy) over 6 weeks, most children with diffuse intrinsic pontine glioma (DIPG) will die within 1 year after diagnosis. To reduce patient burden, we investigated the role of hypofractionation radiation therapy give

  6. A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells

    Directory of Open Access Journals (Sweden)

    Katherine L. Misuraca

    2016-01-01

    Full Text Available Diffuse intrinsic pontine glioma (DIPG is a rare and incurable brain tumor that arises predominately in children and involves the pons, a structure that along with the midbrain and medulla makes up the brainstem. We have previously developed genetically engineered mouse models of brainstem glioma using the RCAS/Tv-a system by targeting PDGF-B overexpression, p53 loss, and H3.3K27M mutation to Nestin-expressing brainstem progenitor cells of the neonatal mouse. Here we describe a novel mouse model targeting these same genetic alterations to Pax3-expressing cells, which in the neonatal mouse pons consist of a Pax3+/Nestin+/Sox2+ population lining the fourth ventricle and a Pax3+/NeuN+ parenchymal population. Injection of RCAS-PDGF-B into the brainstem of Pax3-Tv-a mice at postnatal day 3 results in 40% of mice developing asymptomatic low-grade glioma. A mixture of low- and high-grade glioma results from injection of Pax3-Tv-a;p53fl/fl mice with RCAS-PDGF-B and RCAS-Cre, with or without RCAS-H3.3K27M. These tumors are Ki67+, Nestin+, Olig2+, and largely GFAP− and can arise anywhere within the brainstem, including the classic DIPG location of the ventral pons. Expression of the H3.3K27M mutation reduces overall H3K27me3 as compared with tumors without the mutation, similar to what has been previously shown in human and mouse tumors. Thus, we have generated a novel genetically engineered mouse model of DIPG, which faithfully recapitulates the human disease and represents a novel platform with which to study the biology and treatment of this deadly disease.

  7. Diffuse intrinsic pontine glioma: is MRI surveillance improved by region of interest volumetry?

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Garan T. [University Hospital of North Tees, Department of General Radiology, North Tees and Hartlepool NHS Foundation Trust, Stockton-on-Tees, Cleveland (United Kingdom); Armitage, Paul A.; Griffiths, Paul D. [University of Sheffield, Academic Unit of Radiology, Sheffield (United Kingdom); Batty, Ruth; Connolly, Daniel J.A. [Sheffield Children' s NHS Foundation Trust, Department of Radiology, Sheffield (United Kingdom); Lee, Vicki [Sheffield Children' s NHS Foundation Trust, Department of Oncology, Sheffield (United Kingdom); McMullan, John [Sheffield Children' s NHS Foundation Trust, Department of Neurosurgery, Sheffield (United Kingdom)

    2014-08-21

    Paediatric diffuse intrinsic pontine glioma (DIPG) is noteworthy for its fibrillary infiltration through neuroparenchyma and its resultant irregular shape. Conventional volumetry methods aim to approximate such irregular tumours to a regular ellipse, which could be less accurate when assessing treatment response on surveillance MRI. Region-of-interest (ROI) volumetry methods, using manually traced tumour profiles on contiguous imaging slices and subsequent computer-aided calculations, may prove more reliable. To evaluate whether the reliability of MRI surveillance of DIPGs can be improved by the use of ROI-based volumetry. We investigated the use of ROI- and ellipsoid-based methods of volumetry for paediatric DIPGs in a retrospective review of 22 MRI examinations. We assessed the inter- and intraobserver variability of the two methods when performed by four observers. ROI- and ellipsoid-based methods strongly correlated for all four observers. The ROI-based volumes showed slightly better agreement both between and within observers than the ellipsoid-based volumes (inter-[intra-]observer agreement 89.8% [92.3%] and 83.1% [88.2%], respectively). Bland-Altman plots show tighter limits of agreement for the ROI-based method. Both methods are reproducible and transferrable among observers. ROI-based volumetry appears to perform better with greater intra- and interobserver agreement for complex-shaped DIPG. (orig.)

  8. Diffuse intrinsic pontine gliomas in children: Interest of robotic frameless assisted biopsy. A technical note.

    Science.gov (United States)

    Coca, H A; Cebula, H; Benmekhbi, M; Chenard, M P; Entz-Werle, N; Proust, F

    2016-12-01

    Diffuse intrinsic pontine gliomas (DIPG) constitute 10-15% of all brain tumors in the pediatric population; currently prognosis remains poor, with an overall survival of 7-14 months. Recently the indication of DIPG biopsy has been enlarged due to the development of molecular biology and various ongoing clinical and therapeutic trials. Classically a biopsy is performed using a stereotactic frame assisted procedure but the workflow may sometimes be heavy and more complex especially in children. In this study the authors present their experience with frameless robotic-guided biopsy of DIPG in a pediatric population. Retrospective study on a series of five consecutive pediatric patients harboring DIPG treated over a 4-year period. All patients underwent frameless robotic-guided biopsy via a transcerebellar approach. Among the 5 patients studied 3 were male and 2 female with a median age of 8.6 years [range 5 to 13 years]. Clinical presentation included ataxia, hemiparesis and cranial nerve palsy in all patients. MRI imaging of the lesion showed typical DIPG features (3 of them located in the pons) with hypo-intensity on T1 and hyper-intensity signal on T2 sequences and diffuse gadolinium enhancement. The mean procedure time was 56minutes (range 45 to 67minutes). No new postoperative neurological deficits were recorded. Histological diagnosis was achieved in all cases as follows: two anaplastic astrocytomas (grade III), two glioblastomas, and one diffuse astrocytoma (grade III). Frameless robotic assisted biopsy of DIPG in pediatric population is an easier, effective, safe and highly accurate method to achieve diagnosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Single- and Multivoxel Proton Spectroscopy in Pediatric Patients With Diffuse Intrinsic Pontine Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Steffen-Smith, Emilie A. [Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Venzon, David J. [Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Bent, Robyn S. [Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Hipp, Sean J. [Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Department of Pediatrics, Walter Reed National Military Medical Center, Bethesda, Maryland (United States); Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Warren, Katherine E., E-mail: warrenk@mail.nih.gov [Pediatric Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States)

    2012-11-01

    Purpose: To determine the feasibility of two magnetic resonance spectroscopy (MRS) techniques for treating pediatric patients with diffuse intrinsic pontine gliomas (DIPGs) and to evaluate the relationship of metabolic profiles determined by each technique. Utility of each technique for improving patient management is also discussed. Methods and Materials: Children with DIPG (n = 36) were evaluated using single-voxel spectroscopy (SVS) and magnetic resonance spectroscopic imaging (MRSI) during the same imaging session. Patients were followed longitudinally (n = 150 total studies). Technical feasibility was defined by sufficient water and lipid suppression for detection of metabolites. Correlation of metabolic data obtained by SVS and MRSI was determined using the Spearman rank method. Metabolite ratios, including choline:N-acetyl-aspartate (Cho:NAA) and Cho:creatine (Cho:Cr), were obtained from SVS and MRSI. Results: SVS and MRSI acquisitions were feasible in >90% of studies. Maximum Cho:NAA and Cho:Cr from MRSI analysis were strongly associated with Cho:NAA and Cho:Cr obtained by SVS (r = 0.67 and 0.76, respectively). MRSI Cho:NAA values were more heterogeneous than Cho:Cr values within the same lesion, and a strong linear relationship between the range and maximum Cho:NAA values was observed. Conclusions: SVS and MRSI acquisitions were feasible, with a strong correlation in metabolic data. Both techniques may improve diagnostic evaluation and management of DIPG. SVS is recommended for global assessment of tumor metabolism before and after therapy. MRSI showed heterogeneous patterns of metabolic activity within these tumors and is recommended for planning and monitoring targeted therapies and evaluating nearby tissue for tumor invasion.

  10. Role of Early Postradiation Magnetic Resonance Imaging Scans in Children With Diffuse Intrinsic Pontine Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Christine [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Kaushal, Aradhana, E-mail: kaushala@mail.nih.gov [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Hammoud, Dima A. [Radiology and Imaging Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Steffen-Smith, Emilie A.; Bent, Robyn [Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Citrin, Deborah; Camphausen, Kevin [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States); Warren, Katherine E. [Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)

    2012-07-15

    Purpose: To determine optimal timing of assessing postradiation radiographic response on magnetic resonance imaging (MRI) scans in pediatric patients with diffuse intrinsic pontine glioma (DIPG). Methods and Materials: Patients were treated on a prospective study at the National Cancer Institute (Protocol no. 06-C-0219) evaluating the effects of radiotherapy (RT). Standard RT was administered in standard fractionation over 6 weeks. Postradiation MRI scans were performed at 2 and 6-8 weeks. Results: Eleven patients with DIPG were evaluated. Median age was 6 years (range, 4-13 years). Patients were treated with external-beam RT to 55.8 Gy (n = 10) or 54 Gy (n = 1), with a gross tumor volume to planning target volume expansion of 1.8-2.0 cm. All patients received prescribed dose and underwent posttreatment MRI scans at 2 and 6-8 weeks. Pretreatment imaging revealed compression of fourth ventricle (n = 11); basilar artery encasement (n = 9); tumor extension outside the pons (n = 11); and tumor hemorrhage (n = 2). At the 2-week scan, basilar artery encasement improved in 7 of 9 patients, and extent of tumor was reduced in 5 of 11 patients. Fourth ventricle compression improved in 6 of 11 patients but worsened in 3 of 11 patients. Presumed necrosis was observed in 5 of 11 patients at 2 weeks and in 1 additional patient at 6-8 weeks. There was no significant difference in mean anteroposterior and transverse diameters of tumor between the 2- and 6-8-week time points. Six of 11 patients had increasing ventricular size, with no evidence of obstruction. Conclusions: There is no significant difference in tumor size of DIPG patients who have received standard RT when measured at 2 weeks vs. 6-8 weeks after RT. The majority of patients had the largest change in tumor size at the 2-week post-RT scan, with evolving changes documented on the 6-8-week scan. Six of 11 patients had progressive ventriculomegaly without obstruction, suggestive of communicating hydrocephalus. To the best

  11. In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma.

    Directory of Open Access Journals (Sweden)

    Susanna J E Veringa

    Full Text Available Pediatric high-grade gliomas (pHGG, including diffuse intrinsic pontine gliomas (DIPG, are the leading cause of cancer-related death in children. While it is clear that surgery (if possible, and radiotherapy are beneficial for treatment, the role of chemotherapy for these tumors is still unclear. Therefore, we performed an in vitro drug screen on primary glioma cells, including three DIPG cultures, to determine drug sensitivity of these tumours, without the possible confounding effect of insufficient drug delivery. This screen revealed a high in vitro cytotoxicity for melphalan, doxorubicine, mitoxantrone, and BCNU, and for the novel, targeted agents vandetanib and bortezomib in pHGG and DIPG cells. We subsequently determined the expression of the drug efflux transporters P-gp, BCRP1, and MRP1 in glioma cultures and their corresponding tumor tissues. Results indicate the presence of P-gp, MRP1 and BCRP1 in the tumor vasculature, and expression of MRP1 in the glioma cells themselves. Our results show that pediatric glioma and DIPG tumors per se are not resistant to chemotherapy. Treatment failure observed in clinical trials, may rather be contributed to the presence of drug efflux transporters that constitute a first line of drug resistance located at the blood-brain barrier or other resistance mechanism. As such, we suggest that alternative ways of drug delivery may offer new possibilities for the treatment of pediatric high-grade glioma patients, and DIPG in particular.

  12. Proceedings of the diffuse intrinsic pontine glioma (DIPG) Toronto Think Tank: advancing basic and translational research and cooperation in DIPG.

    Science.gov (United States)

    Bartels, Ute; Hawkins, Cynthia; Vézina, Gilbert; Kun, Larry; Souweidane, Mark; Bouffet, Eric

    2011-10-01

    Diffuse intrinsic pontine glioma (DIPG) nearly exclusively affects children. The prognosis of DIPGs has remained grim despite more than three decades of clinical research and numerous clinical trials. More than 90% of the children with DIPG will succumb within 2 years of diagnosis. The tumor's incidence is still undefined, but data suggest 100-150 affected children annually in the US. The single proven effective treatment modality in DIPG remains radiation therapy. For the majority of patients however this treatment is only of transient effectiveness. Recent breakthroughs in the understanding of the molecular biology of DIPG have raised new hope and opened new avenues for therapeutic options. The advancement of basic and translational research and cooperation was the objective of the Toronto Think Tank, as new approaches are urgently needed.

  13. Motexafin-Gadolinium and Involved Field Radiation Therapy for Intrinsic Pontine Glioma of Childhood: A Children's Oncology Group Phase 2 Study

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, Kristin A., E-mail: bradley@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Zhou Tianni [Department of Preventive Medicine, University of Southern California, Los Angeles, California (United States); McNall-Knapp, Rene Y. [Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Jakacki, Regina I. [Division of Pediatric Hematology/Oncology, Children' s Hospital of Pittsburgh, Pittsburgh, Pennsylvania (United States); Levy, Adam S. [Division of Pediatric Hematology/Oncology, Children' s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, New York (United States); Vezina, Gilbert [Department of Radiology, Children' s National Medical Center, George Washington University School of Medicine, Washington, DC (United States); Pollack, Ian F. [Department of Neurosurgery, Children' s Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States)

    2013-01-01

    Purpose: To evaluate the effects on 1-year event-free survival (EFS) and overall survival (OS) of combining motexafin and gadolinium (MGd), a potent radiosensitizer, with daily fractionated radiation therapy in children with newly diagnosed intrinsic pontine gliomas. Methods and Materials: Patients with newly diagnosed intrinsic pontine glioma were treated with MGd daily for 5 consecutive days each week, for a total of 30 doses. Patients received a 5- to 10-min intravenous bolus of MGd, 4.4 mg/kg/day, given 2 to 5 h prior to standard dose irradiation. Radiation therapy was administered at a daily dose of 1.8 Gy for 30 treatments over 6 weeks. The total dose was 54 Gy. Results: Sixty eligible children received MGd daily, concurrent with 6 weeks of radiation therapy. The estimated 1-year EFS was 18% {+-} 5%, and the estimated 1-year OS was 53% {+-} 6.5%. The most common grade 3 to 4 toxicities were lymphopenia, transient elevation of liver transaminases, and hypertension. Conclusions: Compared to historical controls, the addition of MGd to a standard 6-week course of radiation did not improve the survival of pediatric patients with newly diagnosed intrinsic pontine gliomas.

  14. Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas.

    Directory of Open Access Journals (Sweden)

    Stephanie Puget

    Full Text Available Diffuse intrinsic pontine glioma (DIPG is one of the most frequent malignant pediatric brain tumor and its prognosis is universaly fatal. No significant improvement has been made in last thirty years over the standard treatment with radiotherapy. To address the paucity of understanding of DIPGs, we have carried out integrated molecular profiling of a large series of samples obtained with stereotactic biopsy at diagnosis. While chromosomal imbalances did not distinguish DIPG and supratentorial tumors on CGHarrays, gene expression profiling revealed clear differences between them, with brainstem gliomas resembling midline/thalamic tumours, indicating a closely-related origin. Two distinct subgroups of DIPG were identified. The first subgroup displayed mesenchymal and pro-angiogenic characteristics, with stem cell markers enrichment consistent with the possibility to grow tumor stem cells from these biopsies. The other subgroup displayed oligodendroglial features, and appeared largely driven by PDGFRA, in particular through amplification and/or novel missense mutations in the extracellular domain. Patients in this later group had a significantly worse outcome with an hazard ratio for early deaths, ie before 10 months, 8 fold greater that the ones in the other subgroup (p = 0.041, Cox regression model. The worse outcome of patients with the oligodendroglial type of tumors was confirmed on a series of 55 paraffin-embedded biopsy samples at diagnosis (median OS of 7.73 versus 12.37 months, p = 0.045, log-rank test. Two distinct transcriptional subclasses of DIPG with specific genomic alterations can be defined at diagnosis by oligodendroglial differentiation or mesenchymal transition, respectively. Classifying these tumors by signal transduction pathway activation and by mutation in pathway member genes may be particularily valuable for the development of targeted therapies.

  15. Preclinical evaluation of convection-enhanced delivery of liposomal doxorubicin to treat pediatric diffuse intrinsic pontine glioma and thalamic high-grade glioma.

    Science.gov (United States)

    Sewing, A Charlotte P; Lagerweij, Tonny; van Vuurden, Dannis G; Meel, Michaël H; Veringa, Susanna J E; Carcaboso, Angel M; Gaillard, Pieter J; Peter Vandertop, W; Wesseling, Pieter; Noske, David; Kaspers, Gertjan J L; Hulleman, Esther

    2017-05-01

    OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models. METHODS The sensitivity of primary pHGG cell lines to a range of anthracyclines was tested in vitro. Preclinical CED of free doxorubicin and pegylated liposomal doxorubicin (PLD) to the brainstem and thalamus of naïve nude mice was performed. The maximum tolerated dose (MTD) was determined based on the observation of clinical symptoms, and brains were analyzed after H & E staining. Efficacy of the MTD was tested in adult glioma E98-FM-DIPG and E98-FM-thalamus models and in the HSJD-DIPG-007-Fluc primary DIPG model. RESULTS Both pHGG and DIPG cells were sensitive to anthracyclines in vitro. Doxorubicin was selected for further preclinical evaluation. Convection-enhanced delivery of the MTD of free doxorubicin and PLD in the pons was 0.02 mg/ml, and the dose tolerated in the thalamus was 10 times higher (0.2 mg/ml). Free doxorubicin or PLD via CED was ineffective against E98-FM-DIPG or HSJD-DIPG-007-Fluc in the brainstem; however, when applied in the thalamus, 0.2 mg/ml of PLD slowed down tumor growth and increased survival in a subset of animals with small tumors. CONCLUSIONS Local delivery of doxorubicin to the brainstem causes severe toxicity, even at doxorubicin concentrations that are safe in the thalamus. As a consequence, the authors could not establish a therapeutic

  16. Hypofractionation vs Conventional Radiation Therapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Matched-Cohort Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Jansen, Marc H. [Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam (Netherlands); Lauwers, Selmer J. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Nowak, Peter J. [Department of Radiation Oncology, Erasmus Medical Centre, Rotterdam (Netherlands); Oldenburger, Foppe R. [Department of Radiation Oncology, Academic Medical Centre, Amsterdam (Netherlands); Bouffet, Eric [Department of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto (Canada); Saran, Frank [Department of Pediatric Oncology, The Royal Marsden NHS Foundation Trust, Sutton (United Kingdom); Kamphuis-van Ulzen, Karin [Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Lindert, Erik J. van [Department of Neurosurgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Schieving, Jolanda H. [Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Boterberg, Tom [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Kaspers, Gertjan J. [Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam (Netherlands); Span, Paul N.; Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Gidding, Corrie E. [Department of Pediatric Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Hargrave, Darren [Department of Oncology, Great Ormond Street Hospital, London (United Kingdom)

    2013-02-01

    Purpose: Despite conventional radiation therapy, 54 Gy in single doses of 1.8 Gy (54/1.8 Gy) over 6 weeks, most children with diffuse intrinsic pontine glioma (DIPG) will die within 1 year after diagnosis. To reduce patient burden, we investigated the role of hypofractionation radiation therapy given over 3 to 4 weeks. A 1:1 matched-cohort analysis with conventional radiation therapy was performed to assess response and survival. Methods and Materials: Twenty-seven children, aged 3 to 14, were treated according to 1 of 2 hypofractionation regimens over 3 to 4 weeks (39/3 Gy, n=16 or 44.8/2.8 Gy, n=11). All patients had symptoms for {<=}3 months, {>=}2 signs of the neurologic triad (cranial nerve deficit, ataxia, long tract signs), and characteristic features of DIPG on magnetic resonance imaging. Twenty-seven patients fulfilling the same diagnostic criteria and receiving at least 50/1.8 to 2.0 Gy were eligible for the matched-cohort analysis. Results: With hypofractionation radiation therapy, the overall survival at 6, 9, and 12 months was 74%, 44%, and 22%, respectively. Progression-free survival at 3, 6, and 9 months was 77%, 43%, and 12%, respectively. Temporary discontinuation of steroids was observed in 21 of 27 (78%) patients. No significant difference in median overall survival (9.0 vs 9.4 months; P=.84) and time to progression (5.0 vs 7.6 months; P=.24) was observed between hypofractionation vs conventional radiation therapy, respectively. Conclusions: For patients with newly diagnosed DIPG, a hypofractionation regimen, given over 3 to 4 weeks, offers equal overall survival with less treatment burden compared with a conventional regimen of 6 weeks.

  17. Discrepant longitudinal volumetric and metabolic evolution of diffuse intrinsic Pontine gliomas during treatment: implications for current response assessment strategies

    Energy Technology Data Exchange (ETDEWEB)

    Loebel, U. [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); St. Jude Children' s Research Hospital, Department of Diagnostic Imaging, Memphis, TN (United States); Hwang, S.; Edwards, A.; Patay, Z. [St. Jude Children' s Research Hospital, Department of Diagnostic Imaging, Memphis, TN (United States); Li, Y.; Li, X. [St. Jude Children' s Research Hospital, Department of Biostatistics, Memphis, TN (United States); Broniscer, A. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Science Center, Department of Pediatrics, Memphis, TN (United States)

    2016-10-15

    Based on clinical observations, we hypothesized that in infiltrative high-grade brainstem neoplasms, such as diffuse intrinsic pontine glioma (DIPG), longitudinal metabolic evaluation of the tumor by magnetic resonance spectroscopy (MRS) may be more accurate than volumetric data for monitoring the tumor's biological evolution during standard treatment. We evaluated longitudinal MRS data and corresponding tumor volumes of 31 children with DIPG. We statistically analyzed correlations between tumor volume and ratios of Cho/NAA, Cho/Cr, and NAA/Cr at key time points during the course of the disease through the end of the progression-free survival period. By the end of RT, tumor volume had significantly decreased from the baseline (P <.0001) and remained decreased through the last available follow-up magnetic resonance imaging study (P =.007632). However, the metabolic profile of the tumor tissue (Cho/Cr, NAA/Cr, and Cho/NAA ratios) did not change significantly over time. Our data show that longitudinal tumor volume and metabolic profile changes are dissociated in patients with DIPG during progression-free survival. Volume changes, therefore, may not accurately reflect treatment-related changes in tumor burden. This study adds to the existing body of evidence that the value of conventional MRI metrics, including volumetric data, needs to be reevaluated critically and, in infiltrative tumors in particular, may not be useful as study end-points in clinical trials. We submit that advanced quantitative MRI data, including robust, MRS-based metabolic ratios and diffusion and perfusion metrics, may be better surrogate markers of key end-points in clinical trials. (orig.)

  18. Implementation of a multi-institutional diffuse intrinsic pontine glioma autopsy protocol and characterization of a primary cell culture.

    Science.gov (United States)

    Caretti, V; Jansen, M H A; van Vuurden, D G; Lagerweij, T; Bugiani, M; Horsman, I; Wessels, H; van der Valk, P; Cloos, J; Noske, D P; Vandertop, W P; Wesseling, P; Wurdinger, T; Hulleman, E; Kaspers, G J L

    2013-06-01

    Diffuse intrinsic pontine glioma (DIPG) is a fatal paediatric malignancy. Tumour resection is not possible without serious morbidity and biopsies are rarely performed. The resulting lack of primary DIPG material has made preclinical research practically impossible and has hindered the development of new therapies for this disease. The aim of the current study was to address the lack of primary DIPG material and preclinical models by developing a multi-institutional autopsy protocol. An autopsy protocol was implemented in the Netherlands to obtain tumour material within a brief post mortem interval. A team of neuropathologists and researchers was available at any time to perform the autopsy and process the material harvested. Whole brain autopsy was performed and primary DIPG material and healthy tissue were collected from all affected brain areas. Finally, the study included systematic evaluation by parents. Five autopsies were performed. The mean time interval between death and time of autopsy was 3 h (range 2-4). All tumours were graded as glioblastoma. None of the parents regretted their choice to participate, and they all derived comfort in donating tissue of their child in the hope to help future DIPG patients. In addition, we developed and characterized one of the first DIPG cell cultures from post mortem material. Here we show that obtaining post mortem DIPG tumour tissue for research purposes is feasible with short delay, and that the autopsy procedure is satisfying for participating parents and can be suitable for the development of preclinical DIPG models. © 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.

  19. Human pontine glioma cells can induce murine tumors

    NARCIS (Netherlands)

    Caretti, V.; Sewing, A.C.; Lagerweij, T.; Schellen, P.; Bugiani, M.; Jansen, M.H.; Vuurden, D.G. van; Navis, A.C.; Horsman, I.; Vandertop, W.P.; Noske, D.P.; Wesseling, P.; Kaspers, G.J.L.; Nazarian, J.; Vogel, H.; Hulleman, E.; Monje, M.; Wurdinger, T.

    2014-01-01

    Diffuse intrinsic pontine glioma (DIPG), with a median survival of only 9 months, is the leading cause of pediatric brain cancer mortality. Dearth of tumor tissue for research has limited progress in this disease until recently. New experimental models for DIPG research are now emerging. To develop

  20. ''Occult'' post-contrast signal enhancement in pediatric diffuse intrinsic pontine glioma is the MRI marker of angiogenesis?

    Energy Technology Data Exchange (ETDEWEB)

    Conway, Ashley E.; Reddick, Wilburn E.; Li, Yimei; Yuan, Ying; Glass, John O.; Baker, Justin N.; Kun, Larry E.; Broniscer, Alberto; Patay, Zoltan [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States)

    2014-05-15

    In diffuse intrinsic pontine gliomas (DIPG), subtracting pre-contrast from post-contrast T1-weighted images (T1WI) occasionally reveals subtle, ''occult'' enhancement. We hypothesized that this represents intravascular enhancement related to angiogenesis and hence that these tumors should have greater blood volume fractions than do non-enhancing tumors. We retrospectively screened MR images of 66 patients initially diagnosed with DIPG and analyzed pretreatment conventional and dynamic susceptibility contrast (DSC) perfusion MRI studies of 61 patients. To determine the incidence of occult enhancement, cerebral blood volume (CBV) values were compared in areas of occult enhancement (OcE), no enhancement (NE), and normal-appearing deep cerebellar white matter (DCWM). Tumors of 10 patients (16.4 %) had occult enhancement; those of 6 patients (9.8 %) had no enhancement at all. The average CBV in areas of occult enhancement was significantly higher than that in non-enhancing areas of the same tumor (P =.03), within DCWM in the same patient (P =.03), and when compared to anatomically paired/similar regions of interest (ROI) in patients with non-enhancing tumors (P =.005). Areas of OcE correspond to areas of higher CBV in DIPG, which may be an MRI marker for angiogenesis, but larger scale studies may be needed to determine its potential relevance to grading by imaging, treatment stratification, biopsy guidance, and evaluation of response to targeted therapy. (orig.)

  1. Craniospinal irradiation with concurrent temozolomide for primary metastatic pediatric high-grade or diffuse intrinsic pontine gliomas. A first report from the GPOH-HIT-HGG Study Group

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, K.; Schlamann, A.; Pietschmann, S.; Kortmann, R.D. [University Medical Center Leipzig, Department of Radiation Oncology, Leipzig (Germany); Guckenberger, M. [University Medical Center Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Warmuth-Metz, M. [University Medical Center Wuerzburg, Department of Neuroradiology, Wuerzburg (Germany); Glueck, A. [Clinic for Radiation Oncology Schwabing, Muenchen (Germany); Wawer, A. [University Medical Center Muenchen Schwabing, Department of Pediatric Hematology and Oncology, Muenchen (Germany); Kramm, C.; Bueren, A.O. von [University Medical Center Goettingen, Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Goettingen (Germany)

    2014-04-15

    High-grade (HGG) and diffuse intrinsic pontine gliomas (DIPG) with primary metastatic spread are extremely rare and have a dismal prognosis. Analogous to simultaneous radiochemotherapy in non-metastatic HGG and DIPG, concurrent craniospinal irradiation (CSI) and metronomic temozolomide (metroTMZ) may represent a reasonable therapeutic approach. However, the antitumor efficacy and toxicity of this treatment still have to be investigated. Between March 2007 and December 2012, six children with primary metastatic HGG (n=4) or DIPG (n=2) received CSI and concurrent metroTMZ based on individual treatment recommendations and, in some cases, within the HIT-HGG 2007 multicenter trial. Outcome and treatment-related toxicities were evaluated. All patients received irradiation to the entire craniospinal axis (35.2 Gy, n=5; 36 Gy, n=1:) and 5 received a local boost to macroscopic tumor deposits. Simultaneously, metroTMZ (75 mg/m{sup 2}/day, n=5; 60 mg/m{sup 2}/day, n=1) was administered. Additionally, 1 patient received nimotuzumab once per week. Within a median follow-up of 10.0 months (range 6.5-18.7 months), all patients experienced disease progression and 5 patients died. Median progression-free survival was 4.0±0.8 months (range 2.4-10.7 months) and median overall survival was 7.6±3.5 months (range 4.0-17.6 months). Acute myelosuppression most severely limited application of this aggressive treatment strategy. Severe hematotoxicities (= grade 3) occurred in all patients and metroTMZ had to be interrupted or discontinued in 4 out of 6 cases. Concurrent CSI and metroTMZ might represent a feasible treatment approach for primary metastatic HGG and DIPG. On the basis of our experience, severe but manageable acute hematotoxicity has to be expected. An international effort is warranted to reassess the efficacy and toxicity of this approach within a prospective study. (orig.)

  2. Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy--results of a United Kingdom phase II trial (CNS 2007 04).

    Science.gov (United States)

    Bailey, S; Howman, A; Wheatley, K; Wherton, D; Boota, N; Pizer, B; Fisher, D; Kearns, P; Picton, S; Saran, F; Gibson, M; Glaser, A; Connolly, D J A; Hargrave, D

    2013-12-01

    Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28d) of temozolomide was studied with the aim of overcoming O(6)-methylguanine methyltransferase (MGMT) mediated resistance. Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75 mg/m(2)) after which up to 12 courses of 21d of adjuvant temozolomide (75-100mg/m(2)) were given 4 weekly. The trial used a 2-stage design and passed interim analysis. At diagnosis median age was 8 years (2-20 years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10-100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9 months, 35% (21%, 49%) at 1 year and 17% (7%, 30%) at 2 years. Median survival was 9.5 months (range 7.5-11.4 months). There were five 2-year survivors with a median age of 13.6 years at diagnosis. This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration.

  3. Dual Inhibition of PI3K/AKT and MEK/ERK Pathways Induces Synergistic Antitumor Effects in Diffuse Intrinsic Pontine Glioma Cells

    Directory of Open Access Journals (Sweden)

    Y. Linda Wu

    2017-04-01

    Full Text Available Diffuse intrinsic pontine glioma (DIPG is a devastating disease with an extremely poor prognosis. Recent studies have shown that platelet-derived growth factor receptor (PDGFR and its downstream effector pathway, PI3K/AKT/mTOR, are frequently amplified in DIPG, and potential therapies targeting this pathway have emerged. However, the addition of targeted single agents has not been found to improve clinical outcomes in DIPG, and targeting this pathway alone has produced insufficient clinical responses in multiple malignancies investigated, including lung, endometrial, and bladder cancers. Acquired resistance also seems inevitable. Activation of the Ras/Raf/MEK/ERK pathway, which shares many nodes of cross talk with the PI3K/AKT pathway, has been implicated in the development of resistance. In the present study, perifosine, a PI3K/AKT pathway inhibitor, and trametinib, a MEK inhibitor, were combined, and their therapeutic efficacy on DIPG cells was assessed. Growth delay assays were performed with each drug individually or in combination. Here, we show that dual inhibition of PI3K/AKT and MEK/ERK pathways synergistically reduced cell viability. We also reveal that trametinib induced AKT phosphorylation in DIPG cells that could not be effectively attenuated by the addition of perifosine, likely due to the activation of other compensatory mechanisms. The synergistic reduction in cell viability was through the pronounced induction of apoptosis, with some effect from cell cycle arrest. We conclude that the concurrent inhibition of the PI3K/AKT and MEK/ERK pathways may be a potential therapeutic strategy for DIPG.

  4. Pontine glioma extending to the ipsilateral cavernous sinus and Meckel's cave: MR appearance.

    Science.gov (United States)

    Yuh, W T; Nguyen, H D; Mayr, N A; Follett, K A

    1992-01-01

    The authors describe an exophytic glioma of the pons that grew into the Meckel's cave and cavernous sinus in a 75-year-old man. Pontine gliomas should be included in the differential diagnosis of a hyperintense, complex cystic mass seen along the distribution of cranial nerve V.

  5. Correlation of (18)F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

    Science.gov (United States)

    Zukotynski, Katherine A; Vajapeyam, Sridhar; Fahey, Frederic H; Kocak, Mehmet; Brown, Douglas; Ricci, Kelsey I; Onar-Thomas, Arzu; Fouladi, Maryam; Poussaint, Tina Young

    2017-08-01

    The purpose of this study was to describe baseline (18)F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain (18)F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. (18)F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and (18)F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher

  6. [Xanthofibrogranulomatosis, pontine glioma, multiple nevocytic nevi and albinism (authors transl)].

    Science.gov (United States)

    Martin, U; Cremer, H; Klein, D; Kutzner, M

    1975-05-23

    A case of retroperitoneal fibrosis with ureter compression is reported. Clinical picture and course were determined by the presence of an additional tumor (astrospongoblastoma) of the pons. Extraretroperitoneal tissue changes found at post mortem examination were shown histologically to be foreign tissues of the same type deposited in the retroperitoneal space (disseminated xanthofibrogranuloma). Possible connections between the disseminated xanthofibrogranuloma, the pontine tumor and an albinism also present and multiple nevocytic nevi of the skin are discussed.

  7. Focal pontine lesions provide evidence that intrinsic functional connectivity reflects polysynaptic anatomical pathways.

    Science.gov (United States)

    Lu, Jie; Liu, Hesheng; Zhang, Miao; Wang, Danhong; Cao, Yanxiang; Ma, Qingfeng; Rong, Dongdong; Wang, Xiaoyi; Buckner, Randy L; Li, Kuncheng

    2011-10-19

    Intrinsic functional connectivity detected by functional MRI (fMRI) provides a useful but indirect approach to study the organization of human brain systems. An unresolved question is whether functional connectivity measured by resting-state fMRI reflects anatomical connections. In this study, we used the well-characterized anatomy of cerebrocerebellar circuits to directly test whether intrinsic functional connectivity is associated with an anatomic pathway. Eleven first-episode stroke patients were scanned five times during a period of 6 months, and 11 healthy control subjects were scanned three times within 1 month. In patients with right pontine strokes, the functional connectivity between the right motor cortex and the left cerebellum was selectively reduced. This connectivity pattern was reversed in patients with left pontine strokes. Although factors beyond anatomical connectivity contribute to fMRI measures of functional correlation, these results provide direct evidence that functional connectivity depends on intact connections within a specific polysynaptic pathway.

  8. Detection of Histone H3 mutations in cerebrospinal fluid-derived tumor DNA from children with diffuse midline glioma

    National Research Council Canada - National Science Library

    Tina Y Huang; Andrea Piunti; Rishi R Lulla; Jin Qi; Craig M Horbinski; Tadanori Tomita; C David James; Ali Shilatifard; Amanda M Saratsis

    2017-01-01

    Diffuse midline gliomas (including diffuse intrinsic pontine glioma, DIPG) are highly morbid glial neoplasms of the thalamus or brainstem that typically arise in young children and are not surgically resectable...

  9. Veliparib, Radiation Therapy, and Temozolomide in Treating Younger Patients With Newly Diagnosed Diffuse Pontine Gliomas

    Science.gov (United States)

    2016-10-05

    Childhood Mixed Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliosarcoma

  10. Genetically Engineered Mouse Model of Diffuse Intrinsic Pontine Glioma as a Preclinical Tool

    Science.gov (United States)

    2014-11-01

    sagittal orientation. Sections were rehydrated in PBS-T (0.1% Triton-X100) and blocked in PBS-T with 10% normal goat serum . Pri- mary antibodies were...acquired from previously published data [4,9,11,48]. Human BSG and CG samples with expression data available from Necker- Sick Children [5] were...100 units/mL penicillin and 100 μg/mL streptomycin at 37°C and 5% CO2, and pas- saged a maximum of 3 times for experiments. Cells were plated in clear 6

  11. The role of hypofractionation radiotherapy for diffuse intrinsic brainstem glioma in children: a pilot study.

    NARCIS (Netherlands)

    Janssens, G.O.; Gidding, C.E.M.; Lindert, E.J. van; Oldenburger, F.R.; Erasmus, C.E.; Schouten-Meeteren, A.Y.; Kaanders, J.H.A.M.

    2009-01-01

    PURPOSE: Most children with a diffuse intrinsic brainstem glioma will die within 1 year after diagnosis. To reduce patient burden, we investigated the feasibility of a radical hypofractionation radiotherapy schedule, given over 3 weeks, as an alternative to the standard regimen (30 fractions over 6

  12. Gliomas

    OpenAIRE

    Berger, M.; Weller, M.

    2016-01-01

    Key Features •Synthesizes widely dispersed information on the management of gliomas into one comprehensive resource •Chapters written by international authors who are preeminent researchers in the field •Fully explores the therapeutic options for patient care, from chemotherapy to radiotherapy to personalized approaches Description Researchers’ knowledge of gliomas continues to advance rapidly at both the basic and translational levels, and Gliomas provides a thorough overview ...

  13. Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment.

    Science.gov (United States)

    Wang, Qianghu; Hu, Baoli; Hu, Xin; Kim, Hoon; Squatrito, Massimo; Scarpace, Lisa; deCarvalho, Ana C; Lyu, Sali; Li, Pengping; Li, Yan; Barthel, Floris; Cho, Hee Jin; Lin, Yu-Hsi; Satani, Nikunj; Martinez-Ledesma, Emmanuel; Zheng, Siyuan; Chang, Edward; Sauvé, Charles-Etienne Gabriel; Olar, Adriana; Lan, Zheng D; Finocchiaro, Gaetano; Phillips, Joanna J; Berger, Mitchel S; Gabrusiewicz, Konrad R; Wang, Guocan; Eskilsson, Eskil; Hu, Jian; Mikkelsen, Tom; DePinho, Ronald A; Muller, Florian; Heimberger, Amy B; Sulman, Erik P; Nam, Do-Hyun; Verhaak, Roel G W

    2017-07-10

    We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single-cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4(+) T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Longitudinal transcriptome analysis showed that expression subtype is retained in 55% of cases. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence associated with CD8(+) T cell enrichment. Frequency of M2 macrophages detection associated with short-term relapse after radiation therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Implementation of a multi-institutional diffuse intrinsic pontine glioma autopsy protocol and characterization of a primary cell culture

    NARCIS (Netherlands)

    Caretti, V.; Jansen, M.H.; Vuurden, D.G. van; Lagerweij, T.; Bugiani, M.; Horsman, I.; Wessels, H.; Valk, P. van der; Cloos, J.; Noske, D.P.; Vandertop, W.P.; Wesseling, P.; Wurdinger, T.; Hulleman, E.; Kaspers, G.J.L.

    2013-01-01

    V. Caretti, M. H. A. Jansen, D. G. van Vuurden, T. Lagerweij, M. Bugiani, I. Horsman, H. Wessels, P. van der Valk, J. Cloos, D. P. Noske, W. P. Vandertop, P. Wesseling, T. Wurdinger, E. Hulleman and G. J. L. Kaspers (2013) Neuropathology and Applied Neurobiology39, 426-436 Implementation of a

  15. Glioma cell death induced by irradiation or alkylating agent chemotherapy is independent of the intrinsic ceramide pathway.

    Directory of Open Access Journals (Sweden)

    Dorothee Gramatzki

    Full Text Available BACKGROUND/AIMS: Resistance to genotoxic therapy is a characteristic feature of glioma cells. Acid sphingomyelinase (ASM hydrolyzes sphingomyelin to ceramide and glucosylceramide synthase (GCS catalyzes ceramide metabolism. Increased ceramide levels have been suggested to enhance chemotherapy-induced death of cancer cells. METHODS: Microarray and clinical data for ASM and GCS in astrocytomas WHO grade II-IV were acquired from the Rembrandt database. Moreover, the glioblastoma database of the Cancer Genome Atlas network (TCGA was used for survival data of glioblastoma patients. For in vitro studies, increases in ceramide levels were achieved either by ASM overexpression or by the GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP in human glioma cell lines. Combinations of alkylating chemotherapy or irradiation and ASM overexpression, PPMP or exogenous ceramide were applied in parental cells. The anti-glioma effects were investigated by assessing proliferation, metabolic activity, viability and clonogenicity. Finally, viability and clonogenicity were assessed in temozolomide (TMZ-resistant cells upon treatment with PPMP, exogenous ceramide, alkylating chemotherapy, irradiation or their combinations. RESULTS: Interrogations from the Rembrandt and TCGA database showed a better survival of glioblastoma patients with low expression of ASM or GCS. ASM overexpression or PPMP treatment alone led to ceramide accumulation but did not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PPMP or exogenous ceramide induced acute cytotoxicity in glioblastoma cells. Combined treatments with chemotherapy or irradiation led to additive, but not synergistic effects. Finally, no synergy was found when TMZ-resistant cells were treated with exogenous ceramide or PPMP alone or in combination with TMZ or irradiation. CONCLUSION: Modulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS

  16. Diffuse pontine astrocytoma with lipocytic differentiation.

    Science.gov (United States)

    Craver, Randall; Arcement, Christopher; Chrisentery Singleton, Tammuella

    2012-01-01

    A 7-year-old boy was treated with radiation and chemotherapy for a diffuse pontine glioma. At autopsy, 8 months after diagnosis, the tumor was a diffuse grade II fibrillary astrocytoma with prominent lipocytic differentiation. Literature review suggests that lipocytic differentiation in low-grade astrocytomas occurs in a variety of patient ages, anatomic sites, grades, and astrocytic subtypes. Although the majority of low-grade lipoastrocytomas have behaved benignly, this child's lipoastrocytoma was the underlying cause of death. This outcome suggests that the outcomes of low-grade lipoastrocytic tumors may be expected to be the same as the underlying tumor subtype.

  17. Optic glioma

    Science.gov (United States)

    Glioma - optic; Optic nerve glioma; Juvenile pilocytic astrocytoma; Brain cancer - optic glioma ... Optic gliomas are rare. The cause of optic gliomas is unknown. Most optic gliomas are slow-growing ...

  18. Hypertensive Encephalopathy: Isolated Pons Involvement Mimicking Central Pontine Myelinolysis

    Energy Technology Data Exchange (ETDEWEB)

    Gamanagatti, S.; Subramanian, S. [India Institute of Medical Sciences, New Delhi (India)

    2006-09-15

    MRI of the brain was performed, and it demonstrated an isolated high signal on the T2 weighted and fluid attenuated inversion recovery sequences that involved only the central pons with sparing the periphery. There was no restricted diffusion on diffusion weighted imaging. The differential diagnosis included posterior reversible syndrome and central pontine myelinolysis; however, the blood sodium on admission was normal. The pathogenesis of HE is that the auto-regulatory mechanisms that control the cerebral blood flow are exceeded, resulting in hyper-perfusion. The consequent over-distension of the cerebral vessels, the breakdown of the blood brain barrier and ultimately, the extravasation of fluid into the interstitium all cause vasogenic edema. In most cases, the changes of hypertensive encephalopathy represent reversible vasogenic edema, which can be seen on T2-weighted images, and restricted diffusion is not seen on the diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) maps. Hypertensive encephalopathy that manifests as a reversible increased signal isolated to the pons on T2-weighted images is extremely uncommon. The differential diagnosis for such pontine T2 hyperintensity includes pontine glioma, ischemic and radiation changes (generally irreversible conditions), as well as central pontine myelinolysis (CPM) and demyelinating disorders such as multiple sclerosis, acute disseminated encephalomyelitis and rhomb-encephalitis. In CPM electrolyte imbalances provide a clue for the diagnosis, where as for glioma, there will be an expansion and mass effect. In conclusion, clinical recognition of brainstem HE may be difficult. The features of a lack of correlation between the severity of the radiological abnormality and the clinical status, combined with the rapid resolution following antihypertensive treatment, should suggest the diagnosis. It is important for the radiologist to be familiar with the imaging abnormalities of this life

  19. Central Pontine Myelinolysis: Report of Four Cases

    Directory of Open Access Journals (Sweden)

    Handan Akar

    2010-09-01

    Full Text Available Central pontine myelinolysis is a neurological disorder characterized by loss of myelin in the central pons as well as in the other parts of the brain like basal ganglia, lateral geniculate bodies, external and internal capsules, and cerebellum. We report the clinical and radiological findings of three patients with central pontine myelinolysis and one patient with both pontine and extrapontine myelinolysis.

  20. Multiple Gliomas

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Multiple gliomas are well-recognized but uncommon tumors. The incidence of multiple gliomas according to some reports ranges from 0.5% to 20% of all gliomas diagnosed. Multiple gliomas can be divided into two categories. One is by location of the lesions (multifocal and multicentric). The second type is by the time of the lesions occur (synchronous and metachronous). The lesions generally show hypo, or isodensity on CT; a hypo- or isointense signal on T1-weighted images, and a hyperintense signal on T2-weighted images. Glioblastoma is the most frequent histotype. The prognosis of multiple gliomas remains unfavorable. The treatment of multiple gliomas includes surgery, radiotherapy and chemotherapy. Distinction between multicentric and multifocal gliomas is difficult. This report reviews in detail the aspects of multiple gliomas mentioned above.

  1. Asymptomatic pontine and extra-pontine lesions in a patient with end-stage renal disease

    Directory of Open Access Journals (Sweden)

    Raj Kanwar Yadav

    2016-01-01

    Full Text Available Osmotic demyelination syndrome leading to central pontine/extra-pontine myelinolysis (CPM/EPM occurs mainly in patients with history of alcohol abuse, malnourishment, following liver transplantation and less commonly, in association with other systemic diseases. Asymptomatic CPM/EPM is rare. Patients with end-stage renal disease (ESRD who develop CPM/EPM are usually symptomatic with florid neurologic manifestations. Herein, we present a patient with ESRD on maintenance hemodialysis who was incidentally detected to have pontine and extra-pontine lesions suggestive of myelinolysis without any neurologic signs or symptoms.

  2. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1.

    Science.gov (United States)

    Josupeit, Rafael; Bender, Sebastian; Kern, Sonja; Leuchs, Barbara; Hielscher, Thomas; Herold-Mende, Christel; Schlehofer, Jörg R; Dinsart, Christiane; Witt, Olaf; Rommelaere, Jean; Lacroix, Jeannine

    2016-05-19

    Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG). A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV) in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6), including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Cytotoxic effects induced by the virus have been observed in all HGG neurospheres at half maximal inhibitory concentration (IC50) doses of input virus between 1 and 10 plaque forming units per cell. H-1PV infection at this dose range was able to prevent tumorigenicity of NCH421k glioblastoma multiforme (GBM) "stem-like" cells in NOD/SCID mice. Interestingly NCH421R, an isogenic subclone with equal capacity of xenograft formation, but resistant to H-1PV infection could be isolated from the parental NCH421k culture. To reveal changes in gene expression associated with H-1PV resistance we performed a comparative gene expression analysis in these subclones. Several dysregulated genes encoding receptor proteins, endocytosis factors or regulators innate antiviral responses were identified and represent intriguing candidates for to further study molecular mechanisms of H-1PV resistance.

  3. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1

    Directory of Open Access Journals (Sweden)

    Rafael Josupeit

    2016-05-01

    Full Text Available Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG. A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6, including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Cytotoxic effects induced by the virus have been observed in all HGG neurospheres at half maximal inhibitory concentration (IC50 doses of input virus between 1 and 10 plaque forming units per cell. H-1PV infection at this dose range was able to prevent tumorigenicity of NCH421k glioblastoma multiforme (GBM “stem-like” cells in NOD/SCID mice. Interestingly NCH421R, an isogenic subclone with equal capacity of xenograft formation, but resistant to H-1PV infection could be isolated from the parental NCH421k culture. To reveal changes in gene expression associated with H-1PV resistance we performed a comparative gene expression analysis in these subclones. Several dysregulated genes encoding receptor proteins, endocytosis factors or regulators innate antiviral responses were identified and represent intriguing candidates for to further study molecular mechanisms of H-1PV resistance.

  4. Predictors of Dysphagia in Acute Pontine Infarction.

    Science.gov (United States)

    Lapa, Sriramya; Luger, Sebastian; Pfeilschifter, Waltraud; Henke, Christian; Wagner, Marlies; Foerch, Christian

    2017-05-01

    Little is known about the frequency and the clinical characteristics of neurogenic dysphagia in pontine strokes. In this study, we sought to identify predictors for dysphagia in a cohort of patients with isolated pontine infarctions. We included all patients admitted to our department between 2008 and 2014 having an acute (dysphagia was the primary end point of the study and was assessed by a Speech-Language Pathologist according to defined criteria. The study recruited 59 patients, 14 with and 45 without dysphagia. Median (interquartile range) stroke severity (in terms of National Institutes of Health Stroke Scale values) was higher in the dysphagic group as compared with patients without dysphagia (8.5 [6-12] versus 2 [1-5]; Pdysphagia. Dysphagia occurs frequently in patients with isolated pontine infarctions. Clinical and imaging predictors of dysphagia may help to provide optimal screening, to prevent complications and to improve long-term prognosis. © 2017 American Heart Association, Inc.

  5. Central Pontine and Extrapontine Myelinolysis in Encephalitis

    Directory of Open Access Journals (Sweden)

    Suvrendu Sankar Kar

    2013-08-01

    Full Text Available A 15 years male presented with fever, convulsion, unconsciousness and dystonia of acute onset. He was investigated and treated. MRI brain shows central pontine and extrapontine myelinolysis. Osmotic injury, Wilson's disease and other possibilities were excluded by clinical findings with supportive investigations. Patient was improved satisfactorily with treatment. [Natl J Med Res 2013; 3(4.000: 420-421

  6. Musical hallucinations associated with pontine lacunar lesions.

    Science.gov (United States)

    Serby, Michael J; Hagiwara, Mari; O'Connor, Lisa; Lalwani, Anil K

    2013-01-01

    Three elderly patients experienced musical hallucinations (MH) in the context of hearing loss. In at least two of the cases, the onset was sudden. All three patients had pontine T2/FLAIR hyperintense foci on MR scan after the onset of the MH.

  7. Pontine hemorrhage in a patient with pheochromocytoma.

    Science.gov (United States)

    Scardigli, K; Biller, J; Brooks, M H; Cespedes, L E; Posniak, H V

    1985-02-01

    A 24-year-old woman with a two-year history of hypertension was hospitalized for coma and quadriplegia secondary to pontine hemorrhage. A seven-year history of intermittent severe headaches, diaphoresis, and anxiety together with persistent severe hypertension led to the diagnosis of pheochromocytoma. This unusual but devastating manifestation of pheochromocytoma illustrates the importance of excluding remedial forms of hypertension in young patients before initiating antihypertensive therapy.

  8. Imaging of adult brainstem gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Purohit, Bela, E-mail: purohitbela@yahoo.co.in; Kamli, Ali A.; Kollias, Spyros S.

    2015-04-15

    Highlights: •BSG are classified on MRI into diffuse low-grade, malignant, focal tectal and exophytic subtypes. •Their prognosis and treatment is variable and is almost similar to adult supratentorial gliomas. •This article illustrates the imaging of adult BSGs on MRI and FET-PET. •We also describe prognostic factors and the treatment options of these tumours. -- Abstract: Brainstem gliomas (BSGs) are uncommon in adults accounting for about 2% of all intracranial neoplasms. They are often phenotypically low-grade as compared to their more common paediatric counterparts. Since brainstem biopsies are rarely performed, these tumours are commonly classified according to their MR imaging characteristics into 4 subgroups: (a) diffuse intrinsic low-grade gliomas, (b) enhancing malignant gliomas, (c) focal tectal gliomas and (d) exophytic gliomas/other subtypes. The prognosis and treatment is variable for the different types and is almost similar to adult supratentorial gliomas. Radiotherapy (RT) with adjuvant chemotherapy is the standard treatment of diffuse low-grade and malignant BSGs, whereas, surgical resection is limited to the exophytic subtypes. Review of previous literature shows that the detailed imaging of adult BSGs has not received significant attention. This review illustrates in detail the imaging features of adult BSGs using conventional and advanced MR techniques like diffusion weighted imaging (DWI), diffusion tensor imaging (DTI), MR perfusion weighted imaging (PWI), MR spectroscopy (MRS), as well as {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography ({sup 18}F-FET/PET). We have discussed the pertinent differences between childhood and adult BSGs, imaging mimics, prognostic factors and briefly reviewed the treatment options of these tumours.

  9. Central pontine myelinolysis after liver transplantation.

    Science.gov (United States)

    Estol, C J; Faris, A A; Martinez, A J; Ahdab-Barmada, M

    1989-04-01

    Eight adults and 3 children out of 85 patients who had neuropathologic examination after death following orthotopic liver transplantation showed central pontine myelinolysis (CPM). Four patients also had extrapontine myelinolysis. Eight patients had significant serum sodium changes. In 5, the fluctuation occurred perioperatively and 4 had a clinical picture consistent with CPM, although no patient had this as an antemortem diagnosis. We emphasize the role of hepatic dysfunction as a cause of CPM and recommend careful monitoring of electrolytes in the perioperative period of patients undergoing liver transplantation.

  10. Control of breathing by interacting pontine and pulmonary feedback loops

    Directory of Open Access Journals (Sweden)

    Yaroslav I Molkov

    2013-02-01

    Full Text Available The medullary respiratory network generates respiratory rhythm via sequential phase switching, which in turn is controlled by multiple feedbacks including those from the pons and nucleus tractus solitarii; the latter mediates pulmonary afferent feedback to the medullary circuits. It is hypothesized that both pontine and pulmonary feedback pathways operate via activation of medullary respiratory neurons that are critically involved in phase switching. Moreover, the pontine and pulmonary control loops interact, so that pulmonary afferents control the gain of pontine influence of the respiratory pattern. We used an established computational model of the respiratory network (Smith et al. J. Neurophysiol. 2007 and extended it by incorporating pontine circuits and pulmonary feedback. In the extended model, the pontine neurons receive phasic excitatory activation from, and provide feedback to, medullary respiratory neurons responsible for the onset and termination of inspiration. The model was used to study the effects of: (1 vagotomy (removal of pulmonary feedback, (2 suppression of pontine activity attenuating pontine feedback, and (3 these perturbations applied together on the respiratory pattern and durations of inspiration (TI and expiration (TE. In our model: (a the simulated vagotomy resulted in increases of both TI and TE, (b the suppression of pontine-medullary interactions led to the prolongation of TI at relatively constant, but variable TE, and (c these perturbations applied together resulted in apneusis, characterized by a significantly prolonged TI. The results of modeling were compared with, and provided a reasonable explanation for, multiple experimental data. The characteristic changes in TI and TE demonstrated with the model may represent characteristic changes in the balance between the pontine and pulmonary feedback control mechanisms that may reflect specific cardio-respiratory disorders and diseases.

  11. Primary cerebello-pontine angle malignant melanoma : a case report.

    Directory of Open Access Journals (Sweden)

    Desai K

    2001-04-01

    Full Text Available A rare case of primary malignant melanoma in the cerebello-pontine angle, in a 17 year old girl is presented. The patient presented with one month history of headache, diplopia, facial asymmetry and ataxia. The computerised tomography (CT scan and magnetic resonance imaging (MRI revealed a large cerebello-pontine angle mass with features suggestive of a melanoma. The typical black coloured, solid and vascular melanoma was excised completely. Cerebello-pontine angle melanoma are extremely rare tumours with dismal long term outcome in majority of these cases.

  12. Lenalidomide and Radiation for Children with Brain Cancers

    Science.gov (United States)

    n this trial, patients up to age 18 who are newly diagnosed with diffuse intrinsic pontine gliomas (DIPG) or who have other incompletely resected high-grade gliomas will undergo radiation therapy and receive oral lenalidomide, followed by lenalidomide.

  13. Targeted Radiolabeled Compounds in Glioma Therapy.

    Science.gov (United States)

    Cordier, Dominik; Krolicki, Leszek; Morgenstern, Alfred; Merlo, Adrian

    2016-05-01

    Malignant gliomas of World Health Organization (WHO) grades II-IV represent the largest entity within the group of intrinsic brain tumors and are graded according to their pathophysiological features with survival times between more than 10 years (WHO II) and only several months (WHO IV). Gliomas arise from astrocytic or oligodendrocytic precursor cells and exhibit an infiltrative growth pattern lacking a clearly identifiable tumor border. The development of effective treatment strategies of the invasive tumor cell front represents the main challenge in glioma therapy. The therapeutic standard consists of surgical resection and, depending on the extent of resection and WHO grade, adjuvant external beam radiotherapy or systemic chemotherapy. Within the last decades, there has been no major improvement of the prognosis of patients with glioma. The consistent overexpression of neurokinin type 1 receptors in gliomas WHO grades II-IV has been used to develop a therapeutic substance P-based targeting system. A substance P-analogue conjugated to the DOTA or DOTAGA chelator has been labeled with different alpha-particle or beta-particle emitting radionuclides for targeted glioma therapy. The radiopharmaceutical has been locally injected into the tumors or the resection cavity. In several clinical studies, the methodology has been examined in adjuvant and neoadjuvant clinical settings. Although no large controlled series have so far been generated, the results of radiolabeled substance P-based targeted glioma therapy compare favorably with standard therapy. Recently, labeling with the alpha particle emitting Bi-213 has been found to be promising due to the high linear energy transfer and the very short tissue range of 0.08 mm. Further development needs to focus on the improvement of the stability of the compound and the application by dedicated catheter systems to improve the intratumoral distribution of the radiopharmaceutical within the prognostically critical

  14. Primary pontine hemorrhage. A clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Jun; Kagimoto, Hiroshi; Maeda, Masanobu; Soda, Takao [Shimane Prefectural Central Hospital, Izumo (Japan)

    2002-07-01

    We studied the relationship between outcome and clinical symptoms or CT findings of 34 cases with primary pontine hemorrhage diagnosed by CT scan from April 1994 to March 1999. This series comprised 19 males and 15 females ranging in age from 45 to 89 years with a mean of 67.1 years. According to their outcome at discharge, the cases were divided into 6 groups. Sixteen cases died within 2 weeks after onset (group AD), 4 cases died with complication in the chronic phase (group D), 3 cases were severely disabled to bed-ridden state (group C), 2 cases recovered to a daily life with wheelchair (group B), 4 cases recovered to a daily life with partial assistance (group A), and 5 cases showed a full recovery (group J). The factors significantly correlated with bed outcome are as follows: young age, consciousness disturbance, respiratory disturbance, tachycardia over 90 beats per minute, hyperthermia over 39 deg C, abnormal pupils, loss of oculocephalic reflex, tetraplegia, decerebrate rigidity, bilateral extension or over 30 mm transverse diameter of the hematoma. (author)

  15. Pontine tegmentum hematoma: report of a case with pure hemiplegia

    Directory of Open Access Journals (Sweden)

    MILAGRES ANTONIO CARLOS DE PÁDUA

    1998-01-01

    Full Text Available The authors report the case of a 50 year-old hypertensive male patient with a pontine hematoma. The clinical presentation was characterized by pure pyramidal deficit signs (no other signs or symptoms were present. A pure hemiplegia syndrome, although common in supratentorial lesions, is considered to be a rare event in pontine vascular lesions. The pathophysiologic mechanisms of these neurological findings are unclear. The exclusive involvement of the pyramidal tract in this case is likely due to a variation in the vascular anatomy of the pons but, in some cases, a vascular malformation may be the cause.

  16. Alcoholism with central pontine demyelination: a case report

    Directory of Open Access Journals (Sweden)

    Rohit Arora

    2014-02-01

    Full Text Available Central pontine myelinolysis is a non-inflammatory demyelinating disease characterized by loss of myelin with relative neuron sparing, associated with rapid correction of hyponatremia and sometimes hypernatremia or chronic alcoholism. We are reporting a case of 52 year old male patient who was chronic alcoholic from past 20 years, presented to us with complaints of altered sensorium and dysarthria of 5 days duration .He was investigated and diagnosed as case of central pontine myelinosis associated with chronic alcoholism. [Int J Basic Clin Pharmacol 2014; 3(1.000: 230-232

  17. Epidemiology of gliomas.

    Science.gov (United States)

    Ostrom, Quinn T; Gittleman, Haley; Stetson, Lindsay; Virk, Selene M; Barnholtz-Sloan, Jill S

    2015-01-01

    Gliomas are the most common type of primary intracranial tumors. Some glioma subtypes cause significant mortality and morbidity that are disproportionate to their relatively rare incidence. A very small proportion of glioma cases can be attributed to inherited genetic disorders. Many potential risk factors for glioma have been studied to date, but few provide explanation for the number of brain tumors identified. The most significant of these factors includes increased risk due to exposure to ionizing radiation, and decreased risk with history of allergy or atopic disease. The potential effect of exposure to cellular phones has been studied extensively, but the results remain inconclusive. Recent genomic analyses, using the genome-wide association study (GWAS) design, have identified several inherited risk variants that are associated with increased glioma risk. The following chapter provides an overview of the current state of research in the epidemiology of intracranial glioma.

  18. Morphine-sensitive paroxysmal sympathetic storm in pontine intracerebral hemorrhage.

    Science.gov (United States)

    Ko, Sang-Bae; Kim, Chi Kyung; Lee, Seung-Hoon; Bae, Hee-Joon; Yoon, Byung-Woo

    2010-11-01

    Paroxysmal sympathetic storm (PSS) is a rare complication of severe traumatic brain injury or cerebrovascular disease. Various medications have been tried in patients with PSS, but the clinical responses of the patients were variable. We report a classic case of PSS after spontaneous pontine hemorrhage in which the patient's fluctuating blood pressure and body temperature were dramatically stabilized using morphine.

  19. Cerebellar diaschisis in pontine infractions: a report of five cases

    Energy Technology Data Exchange (ETDEWEB)

    Tsuda, Yoshiyasu [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Ayada, Yoshihide [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Izumi, Yoshinari [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Ichihara, Sin-Ichiro [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Hosomi, Naohisa [Kagawa Medical School (Japan). Second Dept. of Internal Medicine; Ohkawa, Motoomi [Kagawa Medical School (Japan). Dept. of Radiology; Matsuo, Hirohide [Kagawa Medical School (Japan). Second Dept. of Internal Medicine

    1995-05-01

    We evaluate regional cerebral and cerebellar perfusion to prove the occurrence and follow the persistence of crossed cerebellar diaschisis in infratentorial pontine infarction. Six consecutive patients exhibiting mild hemiparetic symptoms or a heavy feeling in the head (mean age 65 years; four women, two men) and diagnosed as having pontine infarction by magnetic resonance imaging were sugjected to evaluation. Lesions due to infarction were located at the upper basis pontis in five partients and the upper tegmentum pontis in one, and medially at the paramedian portion in four and laterally in two. Regional cerebral and cerebellar perfusion was evaluated semiquantitatively by iodine-123 N-isopropyl-p-iodoamphetamine (IMP) single-photon emission tomography (SPET); this was done during the acute stage in five cases (mean time after onset: 0.7 months) and during the chronic stage in three (mean time after onset: 14.8 months) Significant asymmetry in cerebellar perfusion, which was reduced in the contralateral or ipsilateral cerebellar hemisphere, was demonstrated semiquantitatively in four cases during the acute stage and in one during the chronic stage, as compared with normal controls. This asymmetry continued to the chronic stage (6.5 and 33.0 months) in two cases, while no patient showed any significant asymmetries in cerebral perdusion in any region of interest in either SPET study. The pontine lesion may damage the pyramidal tract and corticocerebellar pathway, and interruption of the cerebrocerebellar pontine circuits may be regarded as the cause of the crossed cerebellar diaschisis observed in five of the six reported patients with pontine infarction. (orig.)

  20. [Surgical treatment of chiasmal gliomas in children].

    Science.gov (United States)

    Helcl, F

    1997-03-01

    Chiasmal gliomas are rare brain tumors occurring especially in children. Their proper treatment is still controversial and consists of surgery, radiotherapy and chemotherapy. Surgical removal of these tumors can usually be only partial or subtotal and radiotherapy frequently follows. There are supporters of surgical approach, as well as its enemies. The author has been engaged in problems of optimal treatment of this entity for more than 10 years. He is offering a review of knowledge from the literature concerning surgical treatment of this disease in children. The great majority of articles in the literature are dealing with retrospective analysis of relatively small series of patients usually treated in single neurosurgical department and the surgical treatment is enclosed like a part of combined therapy. Articles dealing only with surgical treatment of chiasmal gliomas are few and reviews determining the contemporary role of surgery of this entity are also lacking. This was the main impulse for writing this compilation. The short history of surgical therapy is reviewed. Some new trends of this therapy are also mentioned (microsurgery, Cavitron Ultrasonic Surgical Aspirator and peroperative use of visual evoked potentials). Up to date criteria for surgical treatment of chiasmal gliomas in children are given-exploration of chiasmal region and performing a biopsy in all cases, radical surgery only in extrinsic gliomas of the chiasmal region and conservative surgical approach to intrinsic chiasmal gliomas. It is emphasized that the significance of obstructive hydrocephalus in this entity has not been fully estimated till now, as well as the role of shunting procedures. Surgical treatment remains, nevertheless, an important armamentarium in the management of chiasmal gliomas in children. (Ref. 20.)

  1. Optical intrinsic signal imaging and neuromonitoring mapping for surgery of glioma near the central sulcus%电生理监测及光学成像定位显微手术切除中央沟区脑胶质瘤

    Institute of Scientific and Technical Information of China (English)

    蒋宇钢; 周倩; 张明铭

    2011-01-01

    目的 探讨中央沟区手术中应用电生理监测及光学成像技术定位脑运动及感觉功能区的方法及意义.方法 5例中央沟区脑胶质瘤患者术中首先利用电生理监测技术定位中央沟及中央前回运动功能区,然后通过光学成像定位中央后回感觉功能区.根据术中的定位,选择显微手术对肿瘤切除,最后进行功能情况评估.结果 临床应用5例,均成功定位中央沟及相应的感觉、运动功能区.术后24 h内复查MRI显示均达到肿瘤全切除.术后随访3~12个月,5例患者的感觉、运动功能基本恢复正常.结论 联合使用术中电生理监测技术及光学成像技术定位患者的躯体运动和感觉功能区是显微手术切除中央沟区脑胶质瘤的一种安全与有效的方法.%Objective To study the methods and significance of motor and sensory areas mapping by optical intrinsic signal imaging (IOSI) and neuromonitoring (IOM) during the operation on the lesions near the central sulcus. Methods Intraoperative neuromonitoring were firstly used to map the central sulcus and motor cortex in 5 patients with glioma undergoing surgery. Then, intrinsic optical signals imaging were used to locate the postcentral gyrus. According to the results of mapping, microsurgical operation was chosen for the resection of glioma and postoperative functional results were evaluated. Results All the patients acquired accurate location of central sulcus, motor cortex and somatosensory cortex. The enhanced MRI performed within 24 hours postsurgery showed total resection in 5 cases. The motor and somatosensory function of 5 patients returned to normal after 3-12 months. Conclusion Intraoperative location of the somatosensory area and motor area by optical intrinsic signal imaging and neuromonitoring is a reliable and safe method.

  2. What drives progressive motor deficits in patients with acute pontine infarction?

    Directory of Open Access Journals (Sweden)

    Jue-bao Li

    2015-01-01

    Full Text Available Progressive motor deficits are relatively common in acute pontine infarction and frequently associated with increased functional disability. However, the factors that affect the progression of clinical motor weakness are largely unknown. Previous studies have suggested that pontine infarctions are caused mainly by basilar artery stenosis and penetrating artery disease. Recently, lower pons lesions in patients with acute pontine infarctions have been reported to be related to progressive motor deficits, and ensuing that damage to the corticospinal tracts may be responsible for the worsening of neurological symptoms. Here, we review studies on motor weakness progression in pontine infarction and discuss the mechanisms that may underlie the neurologic worsening.

  3. Gasperini syndrome as clinical manifestation of pontine demyelination

    Directory of Open Access Journals (Sweden)

    Krasnianski M

    2009-09-01

    Full Text Available Abstract The Gasperini syndrome is a very rare brainstem disease characterized by the typical combination of ipsilateral lesions of the cranial nerves V-VII and dissociated contralateral hemihypesthesia, whereas both contralateral and ipsilateral hypacusis was described. Since the first description in 1912, only a few cases of this crossed brainstem syndrome were published so far. Pontine infarction and bleedings were the reported causes of the syndrome. Here we report a 44-year-old man with the classical Gasperini syndrome due to pontine demyelination in multiple sclerosis. The clinical findings were correlated with changes on MRI. The present case shows that classical crossed brainstem syndromes are topological terms not invariably associated with brainstem ischemia in particular vascular areas and may contribute to the differential diagnosis of peripheral facial nerve palsy.

  4. Right Sensory Alien Hand Phenomenon from a Left Pontine Hemorrhage

    OpenAIRE

    Rafiei, Nastaran; Chang, Gregory Youngnam

    2009-01-01

    Background Acute onset of a sensory alien hand phenomenon has been observed only from a supratentorial lesion involving the non-dominant hand, mostly from a right posterior cerebral artery infarction. A single acute vascular lesion resulting in a dominant hand sensory alien hand syndrome has not been previously documented. Case Report A 78-year old right-handed woman exhibited right sensory alien hand phenomenon from a left pontine hemorrhage. Disturbance of proprioceptive input and visuospat...

  5. MR imaging of pontine infarction within 2 weeks after ictus

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Hata, Hirofumi; Ohno, Masato (Kyushu Rosai Hospital, Fukuoka (Japan))

    1991-08-01

    Magnetic resonance (MR) images of 10 patients with pontine infarction were reviewed. A total of 17 examinations were performed on a 1.5 Tesla high-field scanner (GE) within two weeks after ictus. The infarcted area was detected by MR as early as 20 hours after stroke in one case. However, MR images obtained in two cases three and nine hours after onset were unremarkable. It is therefore suggested that follow-up study should be performed when initial MR images within 20 hours postictus are normal. T{sub 1}-weighted images at four, nine and twelve days after ictus were interpreted as normal. In two of these three examinations, the infarcted areas were clearly demonstrated as hyperintense lesions on T{sub 2}-weighted images. In the other examination, however, an area of mildly increased signal intensity was seen on T{sub 2}-weighted images. This case suggests that the fogging effect is also observed on MR imaging and that a small pontine infarction may be overlooked during the subacute stage. Basilar artery occlusion was detected as an absence-of-flow void in three of the ten patients. In conclusion, MR imaging proved to be a relatively useful diagnostic modality for evaluating acute and subacute pontine infarction. (author).

  6. Temozolomide in malignant glioma

    OpenAIRE

    Gregor Dresemann

    2010-01-01

    Gregor DresemannCenter for Neurooncology at Aerztehaus Velen, Velen, GermanyAbstract: Glioblastoma multiforme WHO grade IV (GBM) is the most aggressive ­malignant glioma and the most frequent primary tumor of the central nervous system. The median ­survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with ­temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional ...

  7. Genetic Alterations in Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Bralten, Linda B. C.; French, Pim J., E-mail: p.french@erasmusmc.nl [Department of Neurology, Erasmus University Medical Center, Erasmus University Rotterdam, Dr Molewaterplein 50, 3000 CA, Rotterdam (Netherlands)

    2011-03-07

    Gliomas are the most common type of primary brain tumor and have a dismal prognosis. Understanding the genetic alterations that drive glioma formation and progression may help improve patient prognosis by identification of novel treatment targets. Recently, two major studies have performed in-depth mutation analysis of glioblastomas (the most common and aggressive subtype of glioma). This systematic approach revealed three major pathways that are affected in glioblastomas: The receptor tyrosine kinase signaling pathway, the TP53 pathway and the pRB pathway. Apart from frequent mutations in the IDH1/2 gene, much less is known about the causal genetic changes of grade II and III (anaplastic) gliomas. Exceptions include TP53 mutations and fusion genes involving the BRAF gene in astrocytic and pilocytic glioma subtypes, respectively. In this review, we provide an update on all common events involved in the initiation and/or progression across the different subtypes of glioma and provide future directions for research into the genetic changes.

  8. Pontine Stimulation Overcomes Developmental Limitations in the Neural Mechanisms of Eyeblink Conditioning

    Science.gov (United States)

    Freeman, John H., Jr; Rabinak, Christine A.; Campolattaro, Matthew M.

    2005-01-01

    Pontine neuronal activation during auditory stimuli increases ontogenetically between postnatal days (P) P17 and P24 in rats. Pontine neurons are an essential component of the conditioned stimulus (CS) pathway for eyeblink conditioning, providing mossy fiber input to the cerebellum. Here we examined whether the developmental limitation in pontine…

  9. Image findings in central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM); Bildgebung bei zentraler pontiner Myelinolyse (CPM) und extrapontiner Myelinolyse (EPM)

    Energy Technology Data Exchange (ETDEWEB)

    Oergel, Anja; Hauser, Till-Karsten; Naegele, T.; Horger, Marius [Univ. Hospital Tuebingen (Germany). Dept. of Radiology

    2017-02-15

    CT and NMR Image findings in central pontine myelinolysis (CPM) and extrapontine myelinolysis were compared with histological results. The clinical appearance and diagnosis using CT and NMR imaging are related to therapy decisions and outcome.

  10. Solitary Fibrous Tumor of the Cerebello-Pontine Angle

    Science.gov (United States)

    Biggs, Nigel D.; Fagan, Paul A.; Turner, Jennifer J.; Doust, Bruce

    1999-01-01

    A case is presented of solitary fibrous tumor occurring in the cerebello-pontine angle. There have been only two other reported cases of a solitary fibrous tumors in this region. Imaging studies showed the tumor to be characteristic in shape and position of an acoustic tumor. However, at surgery the tumor was found to have a “rock hard” consistency. Solitary fibrous tumor differs from acoustic schwannoma and meningioma in its histopathological features and in this case, regrowth, after incomplete excision, was extremely rapid. ImagesFigure 2Figure 3Figure 4Figure 5Figure 6 PMID:17171119

  11. [Pontine cavernous angioma (cavernoma) with initial ENT manifestations].

    Science.gov (United States)

    Pino Rivero, V; González Palomino, A; Pantoja Hernández, C G; Trinidad Ruíz, G; Marqués Rebollo, L; Blasco Huelva, A

    2006-01-01

    We report the case of a 22 years old female who consulted us for facial parestesias, hearing loss in right ear and sudden tinnitus. Her audiometry showed an unilateral discreet sensorineural hipoacusia and the cranial IRM, a mass of 20 mm diameter in right pontine region and bulbus informed as cavernous angioma with signs of recent bleeding. The patient was sent to Neurosurgery but she refused the intervention. The risk of hemorrhage in the cavernomas is estimated at 0.25% to 1.6% per year and represents the main reason to advise a surgical treatment.

  12. Cognitive and Emotional Dysfunction after Central Pontine Myelinolysis

    Directory of Open Access Journals (Sweden)

    Tatia M. C. Lee

    2003-01-01

    Full Text Available The case of a 67-year-old right-handed Chinese man with Central Pontine Myelinolysis [CPM] is described to illustrate the resulting cognitive and emotional disturbances. A comparison of the data in this report with that in published studies suggests that ethnicity does not seem to have much effect on the symptoms of CPM. Possible underlying neural-pathological mechanisms are discussed. This case further substantiates the speculation that the brainstem plays a role in higher cognitive processes and emotional regulation.

  13. Malignant melanoma of the cerebello-pontine angle region

    Directory of Open Access Journals (Sweden)

    F. Menezes Braga

    1989-12-01

    Full Text Available A case of malignant melanoma in the cerebello-pontine angle region is presented in a 72 years old female patient, who had neurological examination and CT scan suggestive of acoustic neuroma. The surgical finding and the histological examination provided the diagnosis. As a primary focus was not found on clinical examination and although autopsy was not carried out, there is a possibility of the diagnosis being a primary malignant melanoma in CNS. This specific location for this kind of tumor was found to be rare when literature is looked up.

  14. Tegmental pontine hemorrhages: clinical features and prognostic factors.

    Science.gov (United States)

    Lancman, M; Norscini, J; Mesropian, H; Bardeci, C; Bauso, T; Granillo, R

    1992-05-01

    We report six patients with partial, predominantly paramedian, tegmental pontine hemorrhages. Constant clinical manifestations consisted of: ipsilateral miosis, horizontal gaze paresis, lower motor neuron facial paresis, contralateral hemisensory loss and mild and transitory hemiparesis, dysarthria and mild or no compromise of consciousness. Five out of six were hypertensive. All patients survived with mild sequelae, oculomotor disturbances being the most persistent deficit. We found in our patients that a transverse diameter of less than 17 mm, unilaterality of the injury and absence of coma were the major indicators of a favorable outcome.

  15. German flooding of the Pontine Marshes in World War II.

    Science.gov (United States)

    Geissler, Erhard; Guillemin, Jeanne

    2010-03-01

    The German army's 1943 flooding of the Pontine Marshes south of Rome, which later caused a sharp rise in malaria cases among Italian civilians, has recently been described by historian Frank Snowden as a unique instance of biological warfare and bioterrorism in the European theater of war and, consequently, as a violation of the 1925 Geneva Protocol prohibiting chemical and biological warfare. We argue that archival documents fail to support this allegation, on several counts. As a matter of historical record, Hitler prohibited German biological weapons (BW) development and consistently adhered to the Geneva Protocol. Rather than biological warfare against civilians, the Wehrmacht used flooding, land mines, and the destruction of vital infrastructure to obstruct the Allied advance. To protect its own troops in the area, the German army sought to contain the increased mosquito breeding likely to be caused by the flooding. Italians returning to the Pontine Marshes after the German retreat in 1944 suffered malaria as a result of environmental destruction, which was banned by the 1899 and 1907 Hague Conventions and by subsequent treaties. In contrast, a state's violation of the Geneva Protocol, whether past or present, involves the use of germ weapons and, by inference, a state-level capability. Any allegation of such a serious violation demands credible evidence that meets high scientific and legal standards of proof.

  16. Galectin-1-mediated biochemical controls of melanoma and glioma aggressive behavior

    Institute of Scientific and Technical Information of China (English)

    Florence; Lefranc; Véronique; Mathieu; Robert; Kiss

    2011-01-01

    Gliomas and melanomas are associated with dismal prognosis because of their marked intrinsic resistance to proapoptotic stimuli,such as conventional chemotherapy and radiotherapy,as well as their ability to escape immune cell attacks.In addition,gliomas and melanomas display pronounced neoangiogenesis.Galectin-1 is a hypoxia-sensitive protein,which is abundantly secreted by glioma and melanoma cells,which displays marked proangiogenic effects.It also provides immune tolerogenic environments to melanoma and glioma cells through the killing of activated T cells that attack these tumor cells.Galectin-1 protects glioma and melanoma cells against cytotoxic insults(including chemotherapy and radiotherapy) through a direct role in the unfolded protein response.Altogether,these facts clearly point to galectin-1 as an important target to be combated in gliomas and melanomas in order to:(1) weaken the defenses of these two types of cancers against radiotherapy,chemotherapy and immunotherapy/vaccine therapy;and(2) reinforce antiangiogenic therapies.In the present article,we review the biochemical and molecular biology-related pathways controlled by galectin-1,which are actually beneficial for melanoma and glioma cells,and therefore detrimental for melanoma and glioma patients.

  17. Molecular Profiling of Gliomas

    NARCIS (Netherlands)

    A.M. Gravendeel (Lonneke)

    2012-01-01

    textabstractGliomas are the most common type of primary brain tumors in adults with an incidence rate of 5.27 per 100.000 patients every year 1-2. In 1926, Bailey and Cushing suggested a classification model based on distinct histological morphologies 3, which forms the basis of the currently used W

  18. Can pontine trigeminal T2-hyperintensity suggest herpetic etiology of trigeminal neuralgia?

    Science.gov (United States)

    Russo, Carmela; Ugga, Lorenzo; Mazio, Federica; Capone, Elisa; D’Arco, Felice; Mankad, Kshitij; Caranci, Ferdinando; Marano, Enrico; Brunetti, Arturo

    2016-01-01

    Background Trigeminal neuralgia (TN) is usually classified into two different categories: idiopathic and secondary. We have investigated the frequency of brainstem pontine lesions in patients with idiopathic TN without multiple sclerosis (MS) or stroke, and their association with herpes zoster (HZ) infection. Methods Brain magnetic resonance imaging (MRI) studies of 28 patients with TN were retrospectively reviewed. Results We found seven patients with clinical suspicion of HZ infection and pontine T2 hyperintense lesions, associated with nerve atrophy in one case. Fifteen patients had a neurovascular conflict (NVC) without brainstem involvement, two of them associated with trigeminal atrophy, while four patients had only volumetric reduction of the nerve. In all patients MRI findings were ipsilateral to the side of TN. Conclusions Pontine T2 hyperintensities could be considered as a MRI sign of TN in patients without NVCs. This “trigeminal pontine sign” (TPS) is frequently found in association with herpetic infections. PMID:27942467

  19. [Alcoholism and possible consequences for the central nerval system - pontine and extrapontine myelinolysis].

    Science.gov (United States)

    Niemann, T; Iranyi, A; Ott, H W

    2009-06-10

    The central pontine and extrapontine myelinolysis is an important entity in the neurology disorders in the context with alcohol abuse. Though often first based on clinical characteristics, the diagnosis can be often supported with radiologic imaging.

  20. Pontine abscess with initial treatment failure following infectious endocarditis with Streptococcus salivarius

    National Research Council Canada - National Science Library

    Knudtzen, Fredrikke Christie; Lynge, Maja; Gaini, Shahin

    2015-01-01

    .... A cerebral MRI revealed a 17×30 mm pontine abscess with surrounding oedema. The patient had, 2 months prior to admission, been treated for Streptococcus salivarius aortic valve endocarditis...

  1. Central Pontine Myelinolysis Induced by Alcohol Withdrawal: A Case Report

    Science.gov (United States)

    2017-01-01

    Central pontine myelinolysis (CPM) is a demyelinating disorder characterized by the loss of myelin in the center of the basis pons, and is mainly caused by the rapid correction of hyponatremia. We report the case of a young woman who presented with gait disturbance and alcohol withdrawal, and who was eventually diagnosed with CPM. Generally, the cause and pathogenesis of CPM in chronic alcoholics remain unclear. In this cases, the CPM may be unrelated to hyponatremia or its correction. However, it is possible that the osmotic pressure changes due to refeeding syndrome after alcohol withdrawal was the likely cause in this case. This case illustrates the need for avoiding hasty, and possibly incomplete diagnoses, and performing more intensive test procedures to ensure a correct diagnosis.

  2. Human gliomas contain morphine

    DEFF Research Database (Denmark)

    Olsen, Peter; Rasmussen, Mads; Zhu, Wei

    2005-01-01

    morphine via high pressure liquid chromatography (HPLC). The HPLC peak corresponding to an authentic morphine standard had its morphine level determined via radioimmune assay. The identity of this material was established by Q-TOF-MS analysis. RESULTS: Each glioma exhibited an endogenous morphine presence....... Tumor extractions demonstrated a molecular mass of 286.14 da, identical to authentic morphine. Subsequent fragmentation analysis of this molecule revealed fragment masses of 129.01 da, 183.09 da and 201.07 da, corresponding to authentic morphine fragments. This material was not found in any......BACKGROUND: Morphine has been found in cancer cell lines originating from human and animal cells. Thus, it became important to demonstrate whether or not actual tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were biochemically treated to isolate and separate endogenous...

  3. Gene Therapy for Gliomas

    OpenAIRE

    Nanda, Dharminderkoemar

    2008-01-01

    textabstractThe overall median survival in glioblastoma multiforme (GBM) patients is less than one year and fewer than 5% of patients survive more than 5 years. The current standard of care for GBM patients involves neurosurgical resection of the tumor followed by radiotherapy with concomitant and adjuvant temozolomide chemotherapy. After initial treatment, all malignant gliomas eventually recur, mostly within a 2-3 cm margin of the original tumor on CT/MRI. The poor prognosis warrants resear...

  4. Incontinência do choro e infarto protuberancial unilateral Incontinence of crying and unilateral pontine infarct

    Directory of Open Access Journals (Sweden)

    Ricardo de Oliveira-Souza

    1995-09-01

    Full Text Available O presente estudo trata do caso de um paciente que apresentou incontinência do choro e hemiplegia direita por infarto ventroprotuberancial paramediano detectado pela RNM. O caráter circunscrito da lesão foi endossado pela normalidade dos potenciais evocados sômato-sensitivos e auditivos de curta-latência. Os episódios de choro desapareceram poucos dias depois do início do tratamento com doses baixas de imipramina. Discutimos o choro e riso patológicos como forma de incontinência da mímica resultante de desconexão límbico-motora, enfatizando a impropriedade de incluí-los na síndrome pseudobulbar, uma vez que dependem de correlatos anatômicos e funcionais distintos.A 64-year-old man presented with pathologic crying and right hemiplegia due to a unilateral pontine infarct from probable branch disease of the basilar artery. The circumscribed nature of the lesion was supported by MRI and short-latency evoked potentials. The weeping spells ceased after a few days of imipramine in low doses. Pathologic laughing and crying can be viewed as a limbic-motor disconnection syndrome, in which the faciovocal motor system is released from forebrain afferents carrying information of emotional content. The inclusion of pathologic laughing and crying in the syndrome pseudobulbar palsy is inaccurate and misleading, since each is related to distinct functional and anatomic systems intrinsic to the human brainstem.

  5. A quantitative evaluation of pontine atrophy by MR imaging in patients with spinocerebellar degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Hirotomo; Tsukamoto, Hiroshi; Kawaguchi, Hiroshi [St. Marianna Univ., Kawasaki, Kanagawa (Japan). School of Medicine

    2000-04-01

    The purpose of this study is to evaluate if pontine measurement on MR images is capable of diagnosing spinocerebellar degeneration (SCD). The study population consists of 68 cases with SCD (34 males and 34 females with a mean age of 57.8 years ranging from 28 to 82 years) and 240 controls (120 males and 120 females with a mean age of 49.3 years ranging from 20 to 78 years). Patients with SCD were classified into three groups. Type I includes 23 cases with olivopontocerebellar atrophy (OPCA), 7 with spinocerebellar ataxia 2 (SCA2), one with SCA3, 3 with multiple system atrophy (MSA), and one with dentate-rubro-pallido-luysian atrophy (DRPLA) (total of 35 cases). Type II consists of 12 cases with late cortical cerebellar atrophy (LCCA) and 3 with SCA6 (total of 15 cases). The last group includes 18 cases with unclassified SCD. The pontine index was calculated using the following equation; transverse distance between bilateral trigeminal nerve root x AP distance of the pons between the pontine basilar sulcus and the median sulcus of the fourth ventricle. Measurement was performed at the level of the trigeminal nerve root on axial T1-weighted images. Pontine indexes were 699{+-}77.19 for the controls and 455{+-}134.23 for SCD groups (pERROR [Basic syntax error] in: <0ERROR [Basic syntax error] in:.0001; t-test). For SCD patients the pontine indexes were significantly Small for Type I in contrast to Type II (pERROR [Basic syntax error] in:<0ERROR [Basic syntax error] in:.001; t-test). Sensitivity of the Pontine indexes for SCD was 70.6% with a cutoff value of 540 (mean-2SD of controls). In agreement with the findings of the study it is proposed that the pontine index may be useful in diagnosis of SCD and OPCA in particular. (author)

  6. Vesicular acetylcholine transporter-immunoreactive axon terminals enriched in the pontine nuclei of the mouse.

    Science.gov (United States)

    Tsutsumi, T; Houtani, T; Toida, K; Kase, M; Yamashita, T; Ishimura, K; Sugimoto, T

    2007-06-08

    Information to the cerebellum enters via many afferent sources collectively known as precerebellar nuclei. We investigated the distribution of cholinergic terminal-like structures in the mouse precerebellar nuclei by immunohistochemistry for vesicular acetylcholine transporter (VAChT). VAChT is involved in acetylcholine transport into synaptic vesicles and is regarded as a reliable marker for cholinergic terminals and preterminal axons. In adult male mice, brains were perfusion-fixed. Polyclonal antibodies for VAChT, immunoglobulin G-peroxidase and diaminobenzidine were used for immunostaining. In the mouse brain, immunoreactivity was seen in almost all major cholinergic cell groups including brainstem motoneurons. In precerebellar nuclei, the signal could be detected as diffusely beaded terminal-like structures. It was seen heaviest in the pontine nuclei and moderate in the pontine reticulotegmental nucleus; however, it was seen less in the medial solitary nucleus, red nucleus, lateral reticular nucleus, inferior olivary nucleus, external cuneate nucleus and vestibular nuclear complex. In particular, VAChT-immunoreactive varicose fibers were so dense in the pontine nuclei that detailed distribution was studied using three-dimensional reconstruction of the pontine nuclei. VAChT-like immunoreactivity clustered predominantly in the medial and ventral regions suggesting a unique regional difference of the cholinergic input. Electron microscopic observation in the pontine nuclei disclosed ultrastructural features of VAChT-immunoreactive varicosities. The labeled bouton makes a symmetrical synapse with unlabeled dendrites and contains pleomorphic synaptic vesicles. To clarify the neurons of origin of VAChT-immunoreactive terminals, VAChT immunostaining combined with wheat germ agglutinin-conjugated horseradish peroxidase retrograde labeling was conducted by injecting a retrograde tracer into the right pontine nuclei. Double-labeled neurons were seen bilaterally in the

  7. Temozolomide in malignant glioma

    Directory of Open Access Journals (Sweden)

    Gregor Dresemann

    2010-07-01

    Full Text Available Gregor DresemannCenter for Neurooncology at Aerztehaus Velen, Velen, GermanyAbstract: Glioblastoma multiforme WHO grade IV (GBM is the most aggressive ­malignant glioma and the most frequent primary tumor of the central nervous system. The median ­survival of newly diagnosed GBM patients was between 9 to 12 months prior to treatment with ­temozolomide being introduced. Primary resection that is as complete as possible is recommended for malignant glioma. Conventional fractionated irradiation 55 to 60 gy with concomitant temozolomide followed by standard temozolomide 6 cycles (5/28 (EORTC/NCIC-regime published by R Stupp in 2005 is the standard of care for newly diagnosed GBM after surgery, independent of the methylation status of the MGM-T gene promoter. Age is no ­contraindication for treatment with temozolomide, although comorbidity and performance status have to be ­considered. For temozolomide naive GBM and astrocytoma grade III patients with disease progression, temozolomide is still the treatment of choice outside of clinical studies. A ­general consensus regarding the schedule of choice has not yet been achieved; so far the 5 out of 28 days regimen (5/28 is the standard of care in most countries. Patients with disease progression after standard temozolomide (5/28 are candidates for clinical studies. Outside of clinical ­studies, dose-dense (7/7, prolonged (21/28, or metronomic (28/28 temozolomide, or alternatively a nitrosourea-based regimen can be an option. The excellent toxicity profile of ­temozolomide allows for various combinations with antitumor agents. None of these ­combinations, however, have been demonstrated to be statistically significantly superior compared to temozolomide alone. The role of lower dosed, dose-dense, or continuous regimen with or without drug combination and the role of temozolomide for newly diagnosed astrocytoma grade III and low grade glioma still has to be determined.Keywords: glioblastoma

  8. Pontine infarction with pure motor hemiparesis or hemiplegia: A prospective study

    Science.gov (United States)

    Ling, Li; Zhu, Liangfu; Zeng, Jinsheng; Liao, Songjie; Zhang, Suping; Yu, Jian; Yang, Zhiyun

    2009-01-01

    Background The study aimed to prospectively observe the clinical and neuroimaging features of pontine infarction with pure motor hemiparesis (PMH) or hemiplegia at early stage. Methods In 118 consecutive selected patients with the first-ever ischemic stroke within 6 hours after onset, fifty of them presented with PMH or hemiplegia and had negative acute computed tomography (CT) scans, then magnetic resonance imaging (MRI) confirmed the corresponding infarcts in pons or cerebrum. The clinical and neuroimaging features of the pontine infarctions were compared with those of cerebral infarctions. Results The pontine infarction with PMH or hemiplegia accounted for 10.2% (12/118) of all first-ever ischemic stroke patients and 24% (12/50) of the patients with both PMH or hemiplegia and acute negative CT scans. Compared to the patients with cerebral infarction, the patients with pontine infarction had more frequency of diabetes mellitus (50.0% vs 5.3%, P = 0.001), nonvertiginous dizziness at onset (58.3% vs 21.1%, P = 0.036) and a progressive course (33.3% vs 2.6%, P = 0.011). Conclusion The pontine infarction may present as PMH or hemiplegia with more frequency of nonvertiginous dizziness, a progressive course and diabetes mellitus. MRI can confirm the infarct location in the basal pons at early stage after stroke onset. PMID:19527495

  9. Patient with pontine warning syndrome and bilateral posterior internuclear ophthalmoplegia: case report

    Directory of Open Access Journals (Sweden)

    Su Li

    2010-06-01

    Full Text Available Abstract Background Capsular warning syndrome was first described in 1993, featured with repetitive episodes of motor and/or sensory dysfunction without cortical signs. Recently, it has been demonstrated that clinically typical capsular warning syndrome can be associated with pontine infarct and the term “pontine warning syndrome� was coined. Case Presentation A 54-year-old woman with a history of hypertension was seen with profound left-sided hemiplegia. She had had 3 episodes of left-sided weakness before complete hemiplegia. Her speech was slurred. Left central facial palsy and hemiglossoplegia were presented. Her left plantar response was extensor and bilateral posterior internuclear ophthalmoplegia was seen on neurologic examination. Biochemical tests revealed hyperglycemia and dyslipidemia on the next day. MRI demonstrated an acute right paramedian pontine infarct. The patient was commenced on oral clopidogrel, atorvastatin and acarbose. After 23 days of hospitalization, she was discharged with severe left hemiplegia. Conclusions 1 Pontine warning syndrome may be underestimated and understudied. 2 Posterior internuclear ophthalmoplegia is a rare clinical sign in cerebrovascular diseases, while it can help to locate a brainstem lesion rather than an internal capsular one. 3 Blood pressure lowing administration may be improper for patients with pontine warning syndrome.

  10. Reduced thalamic and pontine connectivity in Kleine-Levin syndrome

    Directory of Open Access Journals (Sweden)

    Maria eEngström

    2014-04-01

    Full Text Available The Kleine-Levin syndrome is a rare sleep disorder, characterized by exceptionally long sleep episodes. The neuropathology of the syndrome is unknown and treatment is often inadequate. The aim of the study was to improve understanding of the underlying neuropathology, related to cerebral networks, in Kleine-Levin syndrome during sleep episodes. One patient with Kleine-Levin syndrome and congenital nystagmus, was investigated by resting state functional Magnetic Resonance Imaging during both asymptomatic and hypersomnic periods. Fourteen healthy subjects were also investigated as control samples. Functional connectivity was assessed from seed regions of interest in the thalamus and the dorsal pons. Thalamic connectivity was normal in the asymptomatic patient whereas the connectivity between the brain stem, including dorsal pons, and the thalamus was diminished during hypersomnia. These results suggest that the patient’s nystagmus and hypersomnia might have their pathological origin in adjacent dorsal pontine regions. This finding provides additional knowledge of the cerebral networks involved in the neuropathology of this disabling disorder. Furthermore, these findings regarding a rare syndrome have broad implications and results could be of interest to researchers and clinicians in the whole field of sleep medicine.

  11. Central pontine myelinolysis secondary to hypokalaemic nephrogenic diabetes insipidus.

    LENUS (Irish Health Repository)

    Davenport, C

    2010-01-01

    Central pontine myelinolysis (CPM) has been described in alcoholic patients and in the aftermath of rapid correction of chronic hyponatraemia. We describe a case of CPM occurring secondary to nephrogenic diabetes insipidus (DI), which developed as a consequence of severe hypokalaemia. A 63-year-old man with alcohol dependence was admitted to hospital with severe pulmonary sepsis and type 1 respiratory failure. On admission, he had euvolaemic hyponatraemia of 127 mmol\\/L, consistent with a syndrome of inappropriate antidiuretic hormone secondary to his pneumonia. Following admission, his plasma potassium dropped from 3.2 to a nadir of 2.3 mmol\\/L. Mineralocorticoid excess, ectopic adrenocorticotrophic hormone production and other causes of hypokalaemia were excluded. The hypokalaemia provoked significant hypotonic polyuria and a slow rise in plasma sodium to 161 mmol\\/L over several days. Plasma glucose, calcium and creatinine were normal. The polyuria did not respond to desmopressin, and subsequent correction of his polyuria and hypernatraemia after normalization of plasma potassium confirmed the diagnosis of nephrogenic DI due to hypokalaemia. The patient remained obtunded, and the clinical suspicion of osmotic demyelination was confirmed on magnetic resonance imaging. The patient remained comatose and passed away 10 days later. This is the first reported case of nephrogenic DI resulting in the development of CPM, despite a relatively slow rise in plasma sodium of less than 12 mmol\\/L\\/24 h. Coexisting alcohol abuse, hypoxaemia and hypokalaemia may have contributed significantly to the development of CPM in this patient.

  12. Central pontine myelinolysis secondary to hypokalaemic nephrogenic diabetes insipidus.

    Science.gov (United States)

    Davenport, C; Liew, A; Vic Lau, P; Smith, D; Thompson, C J; Kearns, G; Agha, A

    2010-01-01

    Central pontine myelinolysis (CPM) has been described in alcoholic patients and in the aftermath of rapid correction of chronic hyponatraemia. We describe a case of CPM occurring secondary to nephrogenic diabetes insipidus (DI), which developed as a consequence of severe hypokalaemia. A 63-year-old man with alcohol dependence was admitted to hospital with severe pulmonary sepsis and type 1 respiratory failure. On admission, he had euvolaemic hyponatraemia of 127 mmol/L, consistent with a syndrome of inappropriate antidiuretic hormone secondary to his pneumonia. Following admission, his plasma potassium dropped from 3.2 to a nadir of 2.3 mmol/L. Mineralocorticoid excess, ectopic adrenocorticotrophic hormone production and other causes of hypokalaemia were excluded. The hypokalaemia provoked significant hypotonic polyuria and a slow rise in plasma sodium to 161 mmol/L over several days. Plasma glucose, calcium and creatinine were normal. The polyuria did not respond to desmopressin, and subsequent correction of his polyuria and hypernatraemia after normalization of plasma potassium confirmed the diagnosis of nephrogenic DI due to hypokalaemia. The patient remained obtunded, and the clinical suspicion of osmotic demyelination was confirmed on magnetic resonance imaging. The patient remained comatose and passed away 10 days later. This is the first reported case of nephrogenic DI resulting in the development of CPM, despite a relatively slow rise in plasma sodium of less than 12 mmol/L/24 h. Coexisting alcohol abuse, hypoxaemia and hypokalaemia may have contributed significantly to the development of CPM in this patient.

  13. Post-surgical management of pontine hemorrhage with Ayurvedic treatment

    Directory of Open Access Journals (Sweden)

    Areekkat Manojkumar

    2013-01-01

    Full Text Available A female aged 30 years, consulted the Govt. Ayurveda Hospital, Perinthalmanna with complaints of left side of the body totally paralysed along with severe shivering of the right hand and head and the patient was bedridden for 1½ years. She was diagnosed earlier with spontaneous pontine hematoma (on 10 th Nov 2007 and had undergone midline sub occipital craniectomy (on 13 th Nov 2007 as an emergency treatment. She developed neurotrophic ulcer in the right eye with lagophthalmos post-surgery. The patient showed no improvement to treatment but further developed stromal abscess and hence paramedian tarsorraphy (4 th Jan 2008 was done. The deficits in the right eye led to diminution of vision of that eye after Allopathy treatment. The patient sought Ayurvedic treatment for a better prognosis. The patient was under Ayurvedic treatment from 5 th Mar 2009 to 24 th Nov 2009. During that period Ayurvedic treatment such as abhyaṅga (oil massage, patra poṭṭalī sveda (use of poultices and mṛdu virecana (purgation was also done. After a period of 8 months of internal medication and treatment, the shivering of the right hand and head resolved. She could move the left leg and left hand and started walking without support. There was gradual loss of vision during the course of Ayurvedic treatment. At present, the patient is able to move around and do household works on her own.

  14. Acute Psychosis as Main Manifestation of Central Pontine Myelinolysis

    Directory of Open Access Journals (Sweden)

    Mangala Gopal

    2017-01-01

    Full Text Available Central pontine myelinolysis (CPM is an acute demyelinating neurological disorder affecting primarily the central pons and is frequently associated with rapid correction of hyponatremia. Common clinical manifestations of CPM include spastic quadriparesis, dysarthria, pseudobulbar palsy, and encephalopathy of various degrees; however, coma, “locked-in” syndrome, or death can occur in most severe cases. Rarely, CPM presents with neuropsychiatric manifestations, such as personality changes, acute psychosis, paranoia, hallucinations, or catatonia, typically associated with additional injury to the brain, described as extrapontine myelinolysis (EPM. We present a patient with primarily neuropsychiatric manifestations of CPM, in the absence of focal neurologic deficits or radiographic extrapontine involvement. A 51-year-old female without significant medical history presented with dizziness, frequent falls, diarrhea, generalized weakness, and weight loss. Physical examination showed no focal neurological deficits. Laboratory data showed severe hyponatremia, which was corrected rather rapidly. Subsequently, the patient developed symptoms of an acute psychotic illness. Initial brain magnetic resonance imaging (MRI was unremarkable, although a repeat MRI two weeks later revealed changes compatible with CPM. This case demonstrates that acute psychosis might represent the main manifestation of CPM, especially in early stages of the disease, which should be taken into consideration when assessing patients with acute abnormalities of sodium metabolism.

  15. Acute Psychosis as Main Manifestation of Central Pontine Myelinolysis

    Science.gov (United States)

    Gopal, Mangala; Patel, Harsh

    2017-01-01

    Central pontine myelinolysis (CPM) is an acute demyelinating neurological disorder affecting primarily the central pons and is frequently associated with rapid correction of hyponatremia. Common clinical manifestations of CPM include spastic quadriparesis, dysarthria, pseudobulbar palsy, and encephalopathy of various degrees; however, coma, “locked-in” syndrome, or death can occur in most severe cases. Rarely, CPM presents with neuropsychiatric manifestations, such as personality changes, acute psychosis, paranoia, hallucinations, or catatonia, typically associated with additional injury to the brain, described as extrapontine myelinolysis (EPM). We present a patient with primarily neuropsychiatric manifestations of CPM, in the absence of focal neurologic deficits or radiographic extrapontine involvement. A 51-year-old female without significant medical history presented with dizziness, frequent falls, diarrhea, generalized weakness, and weight loss. Physical examination showed no focal neurological deficits. Laboratory data showed severe hyponatremia, which was corrected rather rapidly. Subsequently, the patient developed symptoms of an acute psychotic illness. Initial brain magnetic resonance imaging (MRI) was unremarkable, although a repeat MRI two weeks later revealed changes compatible with CPM. This case demonstrates that acute psychosis might represent the main manifestation of CPM, especially in early stages of the disease, which should be taken into consideration when assessing patients with acute abnormalities of sodium metabolism.

  16. Tricyclic Neovibsanin Scaffold Inhibits Glioma by Targeting Glioma ...

    African Journals Online (AJOL)

    formation capacity and induction of apoptosis in glioma cells. Methods: ... present in plants and possess polyfunctional structures ... the ethics and review committee for the animal studies at .... adhered and started to differentiate forming U138.

  17. Therapy of central pontine myelinolysis following living donor liver transplantation: Report of three cases

    Institute of Scientific and Technical Information of China (English)

    Zhong-Wei Zhang; Yan Kang; Li-Jing Deng; Chuan-Xing Luo; Yan Zhou; Xin-Sheng Xue; Dong Wang; Wan-Hong Yin

    2009-01-01

    We analyzed the clinical manifestations and experiences of diagnosing and treating central pontine myelinolysis following living donor liver transplantation. The clinical data of three patients with central pontine myelinolysis following living donor liver transplantation from January 2005 to November 2007 were retrospectively analyzed at the West China Hospital, Sichuan University, China.The three patients developed hyponatremia prior to surgery. Case 1 suffered locked-in syndrome following surgery, and received a large dose of gamma globulin,and subsequently recovered. Case 2 was in a coma for three days, and received hyperbaric chamber treatment.This patient remained in a mild coma for six months following surgery. Case 3 developed consciousness disturbances, gradually went into a coma following surgery, and died due to pulmonary infection. Central pontine myelinolysis is a severe complication in patients following living donor liver transplantation. Largedose gamma globulin treatment, as well as hyperbaric oxygen, might be effective therapeutic methods.

  18. Causative factors of high intensity areas identified by MRI in the pontine base

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira [Nagoya Univ. (Japan). Faculty of Medicine; Arahata, Yutaka; Motegi, Yoshimasa

    1994-08-01

    High intensity areas in the pontine base were found more frequently in patients of group A who had multiple supratentorial high intensity areas smaller than 15 mm in size and of group B whose vertebral arteries were asymmetric on MR angiography, as compared to those who had none of the above findings of MRI and MR angiography. The high intensity areas of group A were often found bilaterally in the upper pons and those of group B were present unilaterally in the lower pons. Pontine high intensity areas were found frequently on the same side as the smaller vertebral artery in group B. Periventricular hyperintensity was more severe in group A than than in group B. These results suggest that high intensity lesions in the pontine base may conform with the following conditions: (1) multiple small high intensity areas in the supratentorium due to diffuse arteriosclerosis, and (2) asymmetry of the vertebral arteries inducing hemodynamic disorders. (author).

  19. Central pontine myelinolysis in advanced HIV infection with tuberculosis and multicentric Castleman's disease.

    Science.gov (United States)

    Katchanov, J; Branding, G; Stocker, H

    2013-07-01

    We present a case of central pontine myelinolysis (CPM) in a patient with advanced HIV infection and miliary tuberculosis. While hospitalized the patient developed an unusual ataxic variant of CPM with full clinical recovery. Follow-up imaging revealed resolution of pontine lesions. To our knowledge, this is the first report of a clinical and radiological recovery from CPM in advanced HIV disease. Our report extends our knowledge of neurological presentations in patients with advanced HIV infection. It highlights the importance of considering CPM in patients with advanced HIV disease presenting with an ataxic syndrome, even in the absence of an electrolyte derangement.

  20. Magnetic resonance imaging of sequelae of central pontine myelinolysis in chronic alcohol abusers

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Kudo, Sho [Department of Radiology, Saga Medical School, 5-1-1 Nabeshima, 849-8501, Saga (Japan); Yuzuriha, Takefumi; Murakami, Masaru; Endoh, Koichi; Hiejima, Shigeto; Koga, Hiroshi [Center for Emotional and Behavional Disorders, Hizen National Hospital, 160 Mitsu, Higashisefuri, Kanzaki, 842-0192, Saga (Japan)

    2003-12-01

    Central pontine myelinolysis (CPM) is one of the serious neurological complications of alcoholism. This study evaluated magnetic resonance images of sequelae of CPM. Approximately 600 alcoholic patients were examined by a 1.0-T magnetic resonance imaging device, and 11 patients were retrospectively found to have a central pontine lesion, a presumed sequela of CPM. The lesions had various shapes and most were cavitary. In 3 of the 11 patients bilateral symmetrical oval lesions were faintly visible in the middle cerebellar peduncles. These middle cerebellar peduncular lesions were diagnosed as having Wallerian degeneration of the pontocerebellar tract secondary to CPM. (orig.)

  1. Central Pontine and Extrapontine Myelinolysis: The Great Masquerader—An Autopsy Case Report

    Directory of Open Access Journals (Sweden)

    Sajish Jacob

    2014-01-01

    Full Text Available Central pontine myelinolysis is a demyelinating disorder characterized by the loss of myelin in the center of the basis pontis usually caused by rapid correction of chronic hyponatremia. The clinical features vary depending on the extent of involvement. Demyelination can occur outside the pons as well and diagnosis can be challenging if both pontine and extrapontine areas are involved. We herein report a case of myelinolysis involving pons, lateral geniculate bodies, subependymal region, and spinal cord. To the best of our knowledge, this case represents the second case of spinal cord involvement in osmotic demyelination syndrome and the first case of involvement of thoracic region of spinal cord.

  2. [Controversy on treatments for gliomas].

    Science.gov (United States)

    Nomura, K

    1998-09-01

    Gliomas are representative primary malignant brain tumors, and with such tumors it is difficult to define the advanced stage. If the advanced stage indicates no curability by surgery alone, most gliomas would belong to this criterion because of their poor prognosis without any completely effective treatment. In this sense, no one could show a standard therapy to treat these unfortunate patients, for example, patients with glioblastoma, they could permit only 1 year survived even they had any applicable treatments to the lesions, these days. Treatment for low-grade gliomas has been most controversial for a long time, and no standard treatments have been determined so far. In this paper, as the treatment of low-grade gliomas it was intended to report what must be done for this patient and the present results of opinion survey for the treatment of gliomas which was done to professors of 80 institutes, from schools of medicine at all universities and medical colleges in Japan. For high-grade gliomas, some effectiveness of radiation therapy was disclosed as well as chemotherapy from recent papers. Gene therapy was also discussed briefly, its present status and future.

  3. Atypical presentation of central pontine myelinolysis in hyperglycemia

    Directory of Open Access Journals (Sweden)

    Swapna Talluri

    2017-09-01

    Full Text Available Central pontine myelinolysis (CPM usually occurs with rapid correction of severe chronic hyponatremia. Despite the pronounced fluctuations in serum osmolality, CPM is rarely seen in diabetics. This is a case report of CPM associated with hyperglycemia. A 45-year-old non-smoking and non-alcoholic African American male with past medical history of type 2 diabetes, hypertension, stage V chronic kidney disease and hypothyroidism presented with a two-week history of intermittent episodes of gait imbalance, slurred speech and inappropriate laughter. Physical examination including complete neurological assessment and fundoscopic examination were unremarkable. Laboratory evaluation was significant for serum sodium: 140 mmol/L, potassium: 3.9 mmol/L, serum glucose: 178 mg/dL and serum osmolality: 317 mosmol/kg. His ambulatory blood sugars fluctuated between 100 and 600 mg/dL in the six weeks prior to presentation, without any significant or rapid changes in his corrected serum sodium or other electrolyte levels. MRI brain demonstrated a symmetric lesion in the central pons with increased signal intensity on T2- and diffusion-weighted images. After neurological consultation and MRI confirmation, the patient was diagnosed with CPM secondary to hyperosmolar hyperglycemia. Eight-week follow-up with neurology was notable for near-complete resolution of symptoms. This case report highlights the importance of adequate blood glucose control in diabetics. Physicians should be aware of complications like CPM, which can present atypically in diabetics and is only diagnosed in the presence of a high index of clinical suspicion.

  4. Cerebellar and pontine tegmental hypermetabolism in miller-fisher syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyrong; Kim, Ji Soo; Lee, Won Woo; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    Miller Fisher syndrome (MFS) has been considered as a variant of Guillain-Barre syndrome (GBS), a type of acute immune neuropathies involving peripheral nerve system. Unlike GBS, presence of cerebellar type ataxia and supranuclear ophthalmioplesia in MFS suggests additional involvement of the central nervous system. To determine involvement of the central nervous system in MFS, we investigated the cerebral metabolic abnormalities in patients with MFS using FDG PET. Nine patients who were diagnosed as MFS based on acute ophthalmoplegia, ataxia, and areflexia without other identifiable causes participated in this study. In six patients, serum antibodies possibly related with symptom of MFS (anti- GQ1b or anti-GM1) were detected at the time of the study. With the interval of 25 26 days (range: 3-83 days) from the symptom on set, brain FDG PET were underwent in patients and compared with those from healthy controls. In group analysis comparing with healthy controls, FDG PET of patients revealed increased metabolism in the bilateral cerebellar hemispheres and vermis, and the thalamus. In contrast, the occipital cortex showed decreased metabolism. Individual analyses disclosed hypermetabolism in the cerebellar vermis or hemispheres in 5, and in the pontine tegmentum in 2 of the 9 patients. We also found that the cerebellar vermian hypermetabolism was inversely correlated with the interval between from the symptom on set to PET study. Moreover, follow-up PET of a patient demonstrated that cerebellar hypermetabolism decreased markedly with an improvement of the ophthalmoplegia and ataxia. These findings indicate an involvement of the central nervous system in MFS and suggest an antibody-associated acute inflammatory process as a mechanism of this disorder.

  5. Gamma-aminobutyric acid-mediated neurotransmission in the pontine reticular formation modulates hypnosis, immobility, and breathing during isoflurane anesthesia.

    Science.gov (United States)

    Vanini, Giancarlo; Watson, Christopher J; Lydic, Ralph; Baghdoyan, Helen A

    2008-12-01

    Many general anesthetics are thought to produce a loss of wakefulness, in part, by enhancing gamma-aminobutyric acid (GABA) neurotransmission. However, GABAergic neurotransmission in the pontine reticular formation promotes wakefulness. This study tested the hypotheses that (1) relative to wakefulness, isoflurane decreases GABA levels in the pontine reticular formation; and (2) pontine reticular formation administration of drugs that increase or decrease GABA levels increases or decreases, respectively, isoflurane induction time. To test hypothesis 1, cats (n = 5) received a craniotomy and permanent electrodes for recording the electroencephalogram and electromyogram. Dialysis samples were collected from the pontine reticular formation during isoflurane anesthesia and wakefulness. GABA levels were quantified using high-performance liquid chromatography. For hypothesis 2, rats (n = 10) were implanted with a guide cannula aimed for the pontine reticular formation. Each rat received microinjections of Ringer's (vehicle control), the GABA uptake inhibitor nipecotic acid, and the GABA synthesis inhibitor 3-mercaptopropionic acid. Rats were then anesthetized with isoflurane, and induction time was quantified as loss of righting reflex. Breathing rate was also measured. Relative to wakefulness, GABA levels were significantly decreased by isoflurane. Increased power in the electroencephalogram and decreased activity in the electromyogram caused by isoflurane covaried with pontine reticular formation GABA levels. Nipecotic acid and 3-mercaptopropionic acid significantly increased and decreased, respectively, isoflurane induction time. Nipecotic acid also increased breathing rate. Decreasing pontine reticular formation GABA levels comprises one mechanism by which isoflurane causes loss of consciousness, altered cortical excitability, muscular hypotonia, and decreased respiratory rate.

  6. Notch Promotes Radioresistance of Glioma Stem Cells

    OpenAIRE

    Wang, Jialiang; Wakeman, Timothy P.; Latha, Justin D.; Hjelmeland, Anita B.; Wang, Xiao-Fan; White, Rebekah R.; Rich, Jeremy N.; Sullenger, Bruce A.

    2010-01-01

    Radiotherapy represents the most effective nonsurgical treatments for gliomas. Yet, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we showed that inhibition of Notch pathway with gamma-secretase inhibitors (GSIs) rendered the glioma st...

  7. Use of statins and risk of glioma

    DEFF Research Database (Denmark)

    Gaist, David; Andersen, L; Hallas, Jesper;

    2013-01-01

    Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting.......Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting....

  8. Repetitive firing properties of medial pontine reticular formation neurones of the rat recorded in vitro.

    Science.gov (United States)

    Gerber, U; Greene, R W; McCarley, R W

    1989-03-01

    1. Intracellularly recorded neurones in nucleus reticularis pontis caudalis of the medial pontine reticular formation (mPRF) in the in vitro slice preparation were analysed for repetitive firing properties in response to intracellularly applied constant-current pulses. 2. Three neuronal classes were defined by this procedure: (1) non-burst neurones, which had only a non-burst firing pattern; (2) low-threshold burst neurones, which had either a low-threshold burst pattern or a non-burst pattern; (3) high-threshold burst neurones, which had either a high-threshold burst pattern or a non-burst pattern. 3. Histological characterization of electrophysiologically identified mPRF neurones with carboxyfluorescein showed no definite morphological difference between the first two classes. There was a trend for low-threshold burst neurones to have larger somata. 4. The low-threshold burst was generated by a slow calcium-dependent low-threshold spike, revealed in the presence of tetrodotoxin. The size of the low-threshold spike and thus the number of fast action potentials in the low-threshold burst was controlled by at least five factors including: activation; inactivation; amplitude of low-threshold conductance available to be activated; delayed outward conductance; and early transient outward conductance. 5. The non-burst pattern examined in both non-burst and low-threshold burst neurones appeared to be controlled primarily by one or more calcium-dependent potassium conductances sensitive to the removal of calcium and tetraethyl-ammonium. In the presence of tetrodotoxin (TTX), the addition of antagonists to calcium-dependent potassium current revealed a slow high-threshold calcium spike which was distinguished from the low-threshold spike by its threshold, lack of inactivation (at potentials negative to -40 mV) and insensitivity to Mg2+. A long-duration after-hyperpolarization (greater than 0.5 s) was not observed in any of these cells. 6. An early transient outward

  9. Rehabilitation for a Patient with Hemiplegia, Ataxia, and Cognitive Dysfunction Caused by Pontine Hemorrhage

    Directory of Open Access Journals (Sweden)

    Tetsuya Tsunoda

    2015-10-01

    Full Text Available Patients with pontine hemorrhage usually experience severe disturbances of consciousness, pupillary abnormalities, quadriparesis, and respiratory failure. However, little is known regarding cognitive dysfunction in patients with pontine hemorrhage. We report the case of a rehabilitation patient presenting with hemiplegia, ataxia, and cognitive dysfunction caused by a pontine hemorrhage. A 55-year-old, right-handed male suffered sudden onset of vertigo, dysarthria, and hemiplegia on the right side. He was diagnosed with brain stem hemorrhage, and conservative treatment was administered. The vertigo improved, but dysarthria, ataxia, hemiplegia, and gait disorder persisted. He was disoriented with respect to time and place and showed a poor attention span, impaired executive function, and reduced volition. A computed tomography revealed hematomas across the pons on both sides, but no lesions were obvious in the cerebellum and cerebrum. Single-photon emission tomography showed decreased perfusion in the brain stem, bilateral basal ganglia, and frontal and parietal lobes in the left hemisphere. The patient received exercise therapy and cognitive rehabilitation, and home modifications were performed to allow him to continue living at home under the supervision of his family. His symptoms improved, along with enhanced regional cerebral blood flow to the frontal and temporal lobes. These findings suggest that the pontine hemorrhage caused diaschisis resulting in secondary reduction of activity in the cerebral hemisphere and the occurrence of cortical symptoms. Therefore, rehabilitation is necessary, along with active instructions for the family members of patients with severe neurological deficits.

  10. A neurotological study of patients with pontine hyperintense lesions on T2 weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Toru; Tominaga, Satoru; Yukimasa, Akiko; Oku, Masaya; Sakagami, Masafumi [Hyogo Coll. of Medicine, Nishinomiya (Japan)

    2002-03-01

    Pontine hyperintense lesions seen on T2-weighted MRI were thought to be related to disequilibrium. Some of these lesions have a low signal on T1-weighted imaging, while others have an iso-signal. The purpose of this study was to clarify the relationship between neurological findings and pontine lesions detected by MRI. The subjects were 11 patients (6 males, 5 females; age range: 30 to 83 years [mean: 64.1 years]) with pontine hyperintense lesions identified on T2-weighted MRI. We compared the clinical signs and the MRI findings. Six of the patients had low-intensity areas on T1-weighted images, and the other 5 had iso-intensity areas. Six patients complained of vertigo, and 5 complained of dizziness. Eight complained of positionaly evoked disequilibrium. Positional nystagmus was seen in 4 patients. In 9 patients, abnormalities were found on the ENG test, including the saccadic eye movement test, ETT, and OKP. Numbness on the lips occurred in 2 patients, and cerebellar signs were present in 4. None of the patients had facial paralysis. Disequilibrium originating in the central nervous system was suggested in 10 patients. Clinical examinations revealed similar findings in patients with a low signal on T1-weighted MRI and those with an iso-signal. Our results indicate that pontine lesions identified by T2-weighted MRI cause vertigo or dizziness, and, in most cases, these lesions cause abnormal neurological or neurological abnormalities. (author)

  11. Clinical significance of pontine high signals identified on magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

    1993-07-01

    Spin-echo magnetic resonance imaging (MRI) was evaluated to 530 cases in order to investigate the clinical significance of pontine high signals. The subjects comprised 109 cases of pontine infarction with high signal on T[sub 2]-weighted image and low signal on T[sub 1]-weighted image (PI group), 145 of pontine high signal with high signal on T[sub 2]-weighted image but normal signal on T[sub 1]-weighted image (PH group) and 276 of age-matched control without abnormality either on T[sub 1] or T[sub 2]-weighted images (AC group). Subjective complaints such as vertigo-dizziness were more frequent in the PH group than in the PI group. In both PI and groups, periventricular hyperintensity as well as subcortical high signals in the supratentorium were more severe than in the AC group. These degrees were higher in the PI group than in the PH group. In conclusion, PH as well as PI may result from diffuse arteriosclerosis and PH is considered to be an early finding of pontine ischemia. (author).

  12. Rehabilitation for a Patient with Hemiplegia, Ataxia, and Cognitive Dysfunction Caused by Pontine Hemorrhage.

    Science.gov (United States)

    Tsunoda, Tetsuya; Maeshima, Shinichiro; Watanabe, Makoto; Nagai, Ayako; Ueno, Yoshiya; Ozeki, Yasunori; Okamoto, Sayaka; Mizuno, Shiho; Sonoda, Shigeru

    2015-01-01

    Patients with pontine hemorrhage usually experience severe disturbances of consciousness, pupillary abnormalities, quadriparesis, and respiratory failure. However, little is known regarding cognitive dysfunction in patients with pontine hemorrhage. We report the case of a rehabilitation patient presenting with hemiplegia, ataxia, and cognitive dysfunction caused by a pontine hemorrhage. A 55-year-old, right-handed male suffered sudden onset of vertigo, dysarthria, and hemiplegia on the right side. He was diagnosed with brain stem hemorrhage, and conservative treatment was administered. The vertigo improved, but dysarthria, ataxia, hemiplegia, and gait disorder persisted. He was disoriented with respect to time and place and showed a poor attention span, impaired executive function, and reduced volition. A computed tomography revealed hematomas across the pons on both sides, but no lesions were obvious in the cerebellum and cerebrum. Single-photon emission tomography showed decreased perfusion in the brain stem, bilateral basal ganglia, and frontal and parietal lobes in the left hemisphere. The patient received exercise therapy and cognitive rehabilitation, and home modifications were performed to allow him to continue living at home under the supervision of his family. His symptoms improved, along with enhanced regional cerebral blood flow to the frontal and temporal lobes. These findings suggest that the pontine hemorrhage caused diaschisis resulting in secondary reduction of activity in the cerebral hemisphere and the occurrence of cortical symptoms. Therefore, rehabilitation is necessary, along with active instructions for the family members of patients with severe neurological deficits.

  13. An extended chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids phenotype

    OpenAIRE

    Lane, Chris; Phadke, Rahul; Howard, Robin

    2014-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described central nervous system inflammatory condition. In this case report we describe a patient initially with features consistent with this syndrome, who represented with seizures (not previously reported in this syndrome) and corresponding prominent cortical involvement on imaging (also not previously noted). Owing to diagnostic uncertainty, cerebral biopsy was performed...

  14. Wernicke′s encephalopathy and central pontine myelinolysis in hyperemesis gravidarum

    Directory of Open Access Journals (Sweden)

    Panee Sutamnartpong

    2013-01-01

    Full Text Available A pregnant woman, who had been suffering from hyperemesis gravidarum, presented with alteration of consciousness, ocular nystagmus and ataxia. Magnetic Resonance Imaging of the brain showed typical findings of Wernicke′s encephalopathy and central pontine myelinolysis. The clinical features responded dramatically to thiamine supplementation.

  15. Possible causes of central pontine myelinolysis after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Jun Yu; Shu-Sen Zheng; Ting-Bo Liang; Yan Shen; Wei-Lin Wang; Qing-Hong Ke

    2004-01-01

    AIM: To sum up the clinical characteristics of patients with central pontine myelinolysis (CPM) after orthotopic liver transplantation (OLT) and to document the possible causes of CPM.METHODS: Data of 142 patients undergoing OLT between January 1999 to May 2003 were analyzed retrospectively.Following risk factors during perioperation were analyzed in patients with and without CPM: primary liver disease,preoperative serum sodium level, magnesium level and plasma osmolality, fluctuation degree of serum sodium concentration, and immunosuppressive drug level, etc.RESULTS: A total of 13 (9.2%) neurologic symptoms appeared in 142 patients post-operation including 5 cases (3.5%) with CPM and 8 cases (5.6%) with cerebral hemorrhage or infarct. Two patients developing CPM after OLT had a hyponatremia history before operation (serum sodium<130 mmol/L), their mean serum sodium level was 130.6±5.54 mmol/L. The serum sodium level was significantly lower in CPM patients than in patients without neurologic complications or with cerebral hemorrhage/infarct (P<0.05).The increase in serum sodiumduring perioperative 48 h after OLT in patients with CPM was significantly greater than that in patients with cerebral hemorrhage/infarct but without neurologic complications (19.5±6.54 mmol/L, 10.1±6.43 mmol/L,4.5±4.34 mmol/L, respectively, P<0.05). Plasma osmolality was greatly increased postoperation in patients with CPM.Hypomagnesemia was noted in all patients perioperation,but there were no significant differences between groups.The duration of operation on patients with CPM was longer than that on others (492±190.05 min, P<0.05). Cyclosporin A (CsA) levels were normal in all patients, but there were significant differences between patients with or without neurologic complications (P<0.05).CONCLUSION: CPM may be more prevalent following liver transplantation. Although the diagnosis of CPM after OLT can be made by overall neurologic evaluations including magnetic resonance

  16. Isocitrate dehydrogenase mutations in gliomas.

    Science.gov (United States)

    Waitkus, Matthew S; Diplas, Bill H; Yan, Hai

    2016-01-01

    Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg(132) of IDH1 and Arg(172) of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy.

  17. Rehabilitation of patients with glioma.

    Science.gov (United States)

    Vargo, Mary; Henriksson, Roger; Salander, Pär

    2016-01-01

    Disabling sequelae occur in a majority of patients diagnosed with brain tumor, including glioma, such as cognitive deficits, weakness, and visual perceptual changes. Often, multiple impairments are present concurrently. Healthcare staff must be aware of the "biographic disruption" the patient with glioma has experienced. While prognostic considerations factor into rehabilitation goals and expectations, regardless of prognosis the treatment team must offer cohesive support, facilitating hope, function, and quality of life. Awareness of family and caregiver concerns plays an important role in the overall care. Inpatient rehabilitation, especially after surgical resection, has been shown to result in functional improvement and homegoing rates on a par with individuals with other neurologic conditions, such as stroke or traumatic brain injury. Community integration comprises a significant element of life satisfaction, as has been shown in childhood glioma survivors. Employment is often affected by the glioma diagnosis, but may be ameliorated, when appropriate, by addressing modifiable factors such as depression, fatigue, or sleep disturbance, or by workplace accommodations. Further research is needed into many facets of rehabilitation in the setting of glioma, including establishing better care models for consistently identifying and addressing functional limitations in this population, measuring outcomes of various levels of rehabilitation care, identifying optimal physical activity strategies, delineating the long-term effects of rehabilitation interventions, and exploring impact of rehabilitation interventions on caregiver burden. The effective elements of cognitive rehabilitation, including transition of cognitive strategies to everyday living, need to be better defined.

  18. Paediatric and adult malignant glioma

    DEFF Research Database (Denmark)

    Jones, Chris; Perryman, Lara; Hargrave, Darren

    2012-01-01

    Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome...... to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between...... the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric...

  19. Immunotherapy for malignant glioma

    Directory of Open Access Journals (Sweden)

    Carter M Suryadevara

    2015-01-01

    Full Text Available Malignant gliomas (MG are the most common type of primary malignant brain tumor. Most patients diagnosed with glioblastoma (GBM, the most common and malignant glial tumor, die within 12-15 months. Moreover, conventional treatment, which includes surgery followed by radiation and chemotherapy, can be highly toxic by causing nonspecific damage to healthy brain and other tissues. The shortcomings of standard-of-care have thus created a stimulus for the development of novel therapies that can target central nervous system (CNS-based tumors specifically and efficiently, while minimizing off-target collateral damage to normal brain. Immunotherapy represents an investigational avenue with the promise of meeting this need, already having demonstrated its potential against B-cell malignancy and solid tumors in clinical trials. T-cell engineering with tumor-specific chimeric antigen receptors (CARs is one proven approach that aims to redirect autologous patient T-cells to sites of tumor. This platform has evolved dramatically over the past two decades to include an improved construct design, and these modern CARs have only recently been translated into the clinic for brain tumors. We review here emerging immunotherapeutic platforms for the treatment of MG, focusing on the development and application of a CAR-based strategy against GBM.

  20. Frequent Nek1 overexpression in human gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Jun [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Cai, Yu, E-mail: aihaozuqiu22@163.com [School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai (China); Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China); Liu, Pin [Med-X Research Institute, Shanghai Jiao Tong University, Shanghai (China); Zhao, Weiguo [Neurosurgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai (China)

    2016-08-05

    Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

  1. Neuronavigator-guided glioma surgery

    Institute of Scientific and Technical Information of China (English)

    杜固宏; 周良辅; 毛颖

    2003-01-01

    Objective To evaluate the effectiveness of neuronavigator-guided surgery for the resection of gliomas. Methods A total of 80 patients with gliomas underwent surgical treatment under the StealthStation neuronavigator to estimate the extent of the tumors. In 27 cases, the measurements of brain shifts at the dura, cortical surface and lesion margin were recorded during the operations. A technique termed "micro-catheter fence post" was used in superficial gliomas to compensate for brain shift.Results Mean fiducial error and predicted accuracy in the 80 cases were 2.03 mm±0.89 mm and 2.43 mm±0.99 mm, respectively. The shifts at the dura, cortical surface and lesion margin were 3.44 mm±2.39 mm, 7.58 mm±3.75 mm, and 6.55 mm±3.19 mm, respectively. Although neuronavigation revealed residual tumors, operations were discontinued in 5 cases of deep-seated gliomas. In the other 75 cases, total tumor removals were achieved in 62 (82.7%), and subtotal removals were achieved in 13 (17.3%). Post-operation, neurological symptoms were improved or unchanged in 68 cases (85.0%), and worsened in 12 (15.0%). No deaths occurred during the operations and post-operations. Conclusions Intraoperative brain shifts mainly contribute to the fail of spatial accuracy during neuronavigator-guided glioma surgery. The "micro-catheter fence post" technique used for glioma surgery is shown to be useful for compensating for intraoperative brain shifts. This technique, thus, contributes to an increase in total tumor removal and a decrease in surgical complications.

  2. Pediatric gliomas as neurodevelopmental disorders.

    Science.gov (United States)

    Baker, Suzanne J; Ellison, David W; Gutmann, David H

    2016-06-01

    Brain tumors represent the most common solid tumor of childhood, with gliomas comprising the largest fraction of these cancers. Several features distinguish them from their adult counterparts, including their natural history, causative genetic mutations, and brain locations. These unique properties suggest that the cellular and molecular etiologies that underlie their development and maintenance might be different from those that govern adult gliomagenesis and growth. In this review, we discuss the genetic basis for pediatric low-grade and high-grade glioma in the context of developmental neurobiology, and highlight the differences between histologically-similar tumors arising in children and adults.

  3. p53 mutant human glioma cells are sensitive to UV-C-induced apoptosis due to impaired cyclobutane pyrimidine dimer removal.

    Science.gov (United States)

    Batista, Luis F Z; Roos, Wynand P; Kaina, Bernd; Menck, Carlos F M

    2009-02-01

    The p53 protein is a key regulator of cell responses to DNA damage, and it has been shown that it sensitizes glioma cells to the alkylating agent temozolomide by up-regulating the extrinsic apoptotic pathway, whereas it increases the resistance to chloroethylating agents, such as ACNU and BCNU, probably by enhancing the efficiency of DNA repair. However, because these agents induce a wide variety of distinct DNA lesions, the direct importance of DNA repair is hard to access. Here, it is shown that the induction of photoproducts by UV light (UV-C) significantly induces apoptosis in a p53-mutated glioma background. This is caused by a reduced level of photoproduct repair, resulting in the persistence of DNA lesions in p53-mutated glioma cells. UV-C-induced apoptosis in p53 mutant glioma cells is preceded by strong transcription and replication inhibition due to blockage by unrepaired photolesions. Moreover, the results indicate that UV-C-induced apoptosis of p53 mutant glioma cells is executed through the intrinsic apoptotic pathway, with Bcl-2 degradation and sustained Bax and Bak up-regulation. Collectively, the data indicate that unrepaired DNA lesions induce apoptosis in p53 mutant gliomas despite the resistance of these gliomas to temozolomide, suggesting that efficiency of treatment of p53 mutant gliomas might be higher with agents that induce the formation of DNA lesions whose global genomic repair is dependent on p53.

  4. Wild rodents of Pontine Islands as bioindicators of environmental quality / I Roditori selvatici delle isole Pontine come bioindicatori della qualità ambientale

    Directory of Open Access Journals (Sweden)

    Luisa Anna Ieradi

    1992-07-01

    Full Text Available Abstract An investigation was performed in Pontine Islands (Ponza, Palmarola, Zannone within the researches performed in the Latium region aimed at locating risk and control areas using wild Rodents as bioindicators. Serological analyses and mutagenetic tests were applied on collected animals (Mus domesticus, Rattus norvegicus, Rattus rattus. Serological examinations show: positive sera (17.6% against Leptospira icterohaemorrhagiae only in mice and rats from Ponza; positive sera versus Rickettsia mooseri (7%, Toxoplasma gondii (7% and Leishmania donovani (12.5%; no antibodies against Hantaviruses were detected. Results obtained by the micronucleus test show that rodent populations from Pontine Islands may be considered as control for the environmental mutagenesis studies. Riassunto Il lavoro fa parte di un progetto di ricerca che ha lo scopo di individuare aree esposte a rischio e aree di controllo attraverso l'applicazione di un sistema integrato di indagini su Roditori selvatici utilizzati come bioindicatori. Test sierologici e di mutagenesi sono stati effettuati su Murini infestanti, raccolti nelle isole Pontine (Ponza, Palmarola, Zannone individuate come presumibili aree di controllo. Il test di agglutinazione microscopica (MAT ha evidenziato sieropositività nel 17% dei Murini raccolti a Ponza. Il test di immunofluorescenza indiretta per la ricerca delle agglutinine IgG per Hantaan virus, risultato negativo in tutti gli animali esaminati, è indicativo dell'assenza del virus nel territorio. I1 test di fissazione del complemento per la ricerca di anticorpi contro le Rickettsie ha mostrato una positività solo per Rickettsia mooseri in 2 R. norvegicus e 1 R. rattus di Ponza e 2 R. rattus di Palmarola. I risultati ottenuti con il test dei micronuclei evidenziano che nelle tre specie esaminate la frequenza media

  5. Central pontine and extrapontine myelinolysis that developed during alcohol withdrawal, without hyponatremia, in a chronic alcoholic.

    Science.gov (United States)

    An, Jae Young; Park, Sung Kyung; Han, Si Ryung; Song, In Uk

    2010-01-01

    Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) are osmotic demyelination syndrome. A 45-year-old man with a history of alcoholism visited the ER with dysarthria and dysphagia for 2 days. These symptoms occurred 3 days after he had stopped drinking alcohol. The neurological symptoms progressed to anarthria, pseudobulbar palsy and gait disturbance. During admission, the electrolyte studies were within the normal range. Diffusion-weighted images revealed high signal intensities in the pons, thalamus and basal ganglia. Apparent diffusion coefficient image showed low signal intensities in the pontine lesion, but isosignal intensities in the extrapontine lesion. The symptoms gradually improved after 1 month with only conservative treatment. The 1 month-follow-up MRI showed significant reduction of the previous extrapontine lesions. These findings suggest that cytotoxic edema is central to the pathogenesis of CPM, but vasogenic edema plays an important role in the pathogenesis of EPM occurring during alcohol withdrawal.

  6. Neurofibromatosis type 1 associated with vertebrobasilar dolichoectasia and pontine ischemic stroke.

    Science.gov (United States)

    Giannantoni, Nadia Mariagrazia; Broccolini, Aldobrando; Frisullo, Giovanni; Pilato, Fabio; Profice, Paolo; Morosetti, Roberta; Di Lella, Giuseppe; Zampino, Giuseppe; Della Marca, Giacomo

    2015-01-01

    Neurofibromatosis type 1 (NF1) is a heterogeneous, common, neurocutaneous disorder presenting different complications during a life span, including cerebrovascular dysplasia. To our knowledge this is the first reported case of NF1 associated with vertebrobasilar dolichoectasia and pontine ischemic stroke. We describe a 57-year-old man with NF1 who presented an acute onset right-sided facial palsy and hemiplegia, dysarthria, and gait imbalance. Magnetic resonance imaging showed an acute left paramedian pontine infarct and a hypoplastic right vertebral artery. Brain Computed Tomography Angiography revealed the occurrence of vertebrobasilar dolichoectasia. Co-occurrence of VBD and NF1 might not be merely casual and it may significantly heighten the mortality rate in this multisystem disorder. We suggest a possible role of VBD in the genesis of our patient's clinical-radiological features and prompt the early detection of asymptomatic arteriopathy in individuals with NF1 in order to ameliorate patients' quality of life and life expectancy.

  7. Atypical supernumerary phantom limb and phantom limb pain in two patients with pontine hemorrhage.

    Science.gov (United States)

    Yoo, Seung Don; Kim, Dong Hwan; Jeong, Yong Seol; Chon, Jinmann; Bark, Jihea

    2011-06-01

    Phantom limbs are usually observed after amputation of extremities. In patients after a stroke, a similar but rarely occurring phenomenon consisting of the patient experiencing the presence of an additional limb has been described. This phenomenon, generally called supernumerary phantom limb (SPL), may be caused by lesions in the right or left cerebral hemisphere, but has been predominantly reported in patients who have had a right hemispheric stroke. We report two cases of atypical SPL and phantom limb pain (PLP) after pontine hemorrhage. The patients were treated conservatively and their symptoms lasted more than 1 month. This is the first report of SPLs after left pontine hemorrhage, and phantom perception and pain lasted longer than those in previously observed cases. Our results indicate that SPL may be more common than reported; therefore, thorough examinations are essential for the care of stroke patients.

  8. Visual hallucinations and pontine demyelination in a child: possible REM dissociation?

    Science.gov (United States)

    Vita, Maria Gabriella; Batocchi, Anna Paola; Dittoni, Serena; Losurdo, Anna; Cianfoni, Alessandro; Stefanini, Maria Chiara; Vollono, Catello; Della Marca, Giacomo; Mariotti, Paolo

    2008-12-15

    An 11 year-old-boy acutely developed complex visual and acoustic hallucinations. Hallucinations, consisting of visions of a threatening, evil character of the Harry Potter saga, persisted for 3 days. Neurological and psychiatric examinations were normal. Ictal EEG was negative. MRI documented 3 small areas of hyperintense signal in the brainstem, along the paramedian and lateral portions of pontine tegmentum, one of which showed post-contrast enhancement. These lesions were likely of inflammatory origin, and treatment with immunoglobulins was started. Polysomnography was normal, multiple sleep latency test showed a mean sleep latency of 8 minutes, with one sleep-onset REM period. The pontine tegmentum is responsible for REM sleep regulation, and contains definite "REM-on" and "REM-off" regions. The anatomical distribution of the lesions permits us to hypothesize that hallucinations in this boy were consequent to a transient impairment of REM sleep inhibitory mechanisms, with the appearance of dream-like hallucinations during wake.

  9. Endoscopic endonasal transclival resection of a ventral pontine cavernous malformation: technical case report.

    Science.gov (United States)

    Gómez-Amador, Juan Luis; Ortega-Porcayo, Luis Alberto; Palacios-Ortíz, Isaac Jair; Perdomo-Pantoja, Alexander; Nares-López, Felipe Eduardo; Vega-Alarcón, Alfredo

    2016-10-21

    Brainstem cavernous malformations are challenging due to the critical anatomy and potential surgical risks. Anterolateral, lateral, and dorsal surgical approaches provide limited ventral exposure of the brainstem. The authors present a case of a midline ventral pontine cavernous malformation resected through an endoscopic endonasal transclival approach based on minimal brainstem transection, negligible cranial nerve manipulation, and a straightforward trajectory. Technical and reconstruction technique advances in endoscopic endonasal skull base surgery provide a direct, safe, and effective corridor to the brainstem.

  10. The Role of Pontin and Reptin in Cellular Physiology and Cancer Etiology

    Directory of Open Access Journals (Sweden)

    Yu-Qian Mao

    2017-08-01

    Full Text Available Pontin (RUVBL1, TIP49, TIP49a, Rvb1 and Reptin (RUVBL2, TIP48, TIP49b, Rvb2 are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities superfamily and are involved in various cellular processes that are important for oncogenesis. First identified as being upregulated in hepatocellular carcinoma and colorectal cancer, their overexpression has since been shown in multiple cancer types such as breast, lung, gastric, esophageal, pancreatic, kidney, bladder as well as lymphatic, and leukemic cancers. However, their exact functions are still quite unknown as they interact with many molecular complexes with vastly different downstream effectors. Within the nucleus, Pontin and Reptin participate in the TIP60 and INO80 complexes important for chromatin remodeling. Although not transcription factors themselves, Pontin and Reptin modulate the transcriptional activities of bona fide proto-oncogenes such as MYC and β-catenin. They associate with proteins involved in DNA damage repair such as PIKK complexes as well as with the core complex of Fanconi anemia pathway. They have also been shown to be important for cell cycle progression, being involved in assembly of telomerase, mitotic spindle, RNA polymerase II, and snoRNPs. When the two ATPases localize to the cytoplasm, they were reported to promote cancer cell invasion and metastasis. Due to their various roles in carcinogenesis, it is not surprising that Pontin and Reptin are proving to be important biomarkers for diagnosis and prognosis of various cancers. They are also current targets for the development of new therapeutic anticancer drugs.

  11. Pontine stroke presenting as isolated facial nerve palsy mimicking Bell's palsy: a case report

    OpenAIRE

    Saluja Paramveer; Manandhar Lochana; Agarwal Rishi; Grandhi Bala

    2011-01-01

    Abstract Introduction Isolated facial nerve palsy usually manifests as Bell's palsy. Lacunar infarct involving the lower pons is a rare cause of solitary infranuclear facial paralysis. The present unusual case is one in which the patient appeared to have Bell's palsy but turned out to have a pontine infarct. Case presentation A 47-year-old Asian Indian man with a medical history of hypertension presented to our institution with nausea, vomiting, generalized weakness, facial droop, and slurred...

  12. Pontine Reticulospinal Projections in the Neonatal Mouse: Internal Organization and Axon Trajectories

    OpenAIRE

    Sivertsen, Magne Sand; Perreault, Marie-Claude; Glover, Joel C.

    2015-01-01

    We recently characterized physiologically a pontine reticulospinal (pRS) projection in the neonatal mouse that mediates synaptic effects on spinal motoneurons via parallel uncrossed and crossed pathways (Sivertsen et al. [2014] J Neurophysiol 112:1628–1643). Here we characterize the origins, anatomical organization, and supraspinal axon trajectories of these pathways via retrograde tracing from the high cervical spinal cord. The two pathways derive from segregated populations of ipsilaterally...

  13. [Pure motor hemiplegia with ipsilateral lingual palsy caused by pontine infarction].

    Science.gov (United States)

    Aidi, S; el Alaoui Faris, M; Essalhi, M; Jiddane, M; Chkili, T

    1996-12-01

    A 36 year old diabetic man developed a pure motor hemiplegia (PMH) associated with an ipsilateral lingual palsy. Magnetic resonance imaging revealed a pontine infarct. Lingual palsies have never been reported in patients with PMH so far, but may be associated with other lacunar syndromes such as the "dysarthria-clumsy hand syndrome". This observation supports the hypothesis that corticohypoglossal pathways may have bilateral and assymetrical projections.

  14. Central pontine myelinolysis (CPM and extrapontine myelinolysis (EPM following concurrent chemoradiotherapy for nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Chen-Hui Chong

    2016-06-01

    Full Text Available Central pontine myelinolysis (CPM is a disease that may present with coma, quadriplegia, or no symptoms at all. It is an iatrogenic demyelinating disease caused most frequently by overzealous correction of chronic hyponatremia and excessive swings in serum osmolality. Lesions can also occur outside the pons as extrapontine myelinolysis (EPM. Herein we have reported a case of CPM and EPM in a patient after chemoradiotherapy for recurrent nasopharyngeal carcinoma.

  15. Sleep Duration Varies as a Function of Glutamate and GABA in Rat Pontine Reticular Formation

    OpenAIRE

    Watson, Christopher J.; Lydic, Ralph; Baghdoyan, Helen A.

    2011-01-01

    The oral part of the pontine reticular formation (PnO) is a component of the ascending reticular activating system and plays a role in the regulation of sleep and wakefulness. The PnO receives glutamatergic and GABAergic projections from many brain regions that regulate behavioral state. Indirect, pharmacological evidence has suggested that glutamatergic and GABAergic signaling within the PnO alters traits that characterize wakefulness and sleep. No previous studies have simultaneously measur...

  16. Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling.

    Directory of Open Access Journals (Sweden)

    Marc J Geisen

    2008-06-01

    Full Text Available The pontine neurons (PN represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both the anteroposterior (AP and dorsoventral (DV axes. Unlike DV migration, which is controlled by the Netrin-1/Dcc attractive pathway, little is known about the molecular mechanisms guiding PN migration along the AP axis. Here, we show that Hoxa2 and Hoxb2 are required both intrinsically and extrinsically to maintain normal AP migration of subsets of PN, by preventing their premature ventral attraction towards the midline. Moreover, the migration defects observed in Hoxa2 and Hoxb2 mutant mice were phenocopied in compound Robo1;Robo2, Slit1;Slit2, and Robo2;Slit2 knockout animals, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using chromatin immunoprecipitation assays, we further demonstrated that Robo2 is a direct target of Hoxa2 in vivo and that maintenance of high Robo and Slit expression levels was impaired in Hoxa2 mutant mice. Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent premature ventral migration of PN. These findings provide novel insights into the molecular control of neuronal migration from transcription factor to regulation of guidance receptor and ligand expression. Specifically, they address the question of how exposure to multiple guidance cues along the AP and DV axes is regulated at the transcriptional level and in turn translated into stereotyped migratory responses during tangential migration of neurons in the developing mammalian brain.

  17. MicroRNA in Human Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mengfeng, E-mail: limf@mail.sysu.edu.cn [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Li, Jun [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Liu, Lei; Li, Wei [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Yang, Yi [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080 (China); Yuan, Jie [Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Chinese Ministry of Education, Guangzhou 510080 (China); Key Laboratory of Functional Molecules from Oceanic Microorganisms (Sun Yat-sen University), Department of Education of Guangdong Province, Guangzhou 510080 (China)

    2013-10-23

    Glioma represents a serious health problem worldwide. Despite advances in surgery, radiotherapy, chemotherapy, and targeting therapy, the disease remains one of the most lethal malignancies in humans, and new approaches to improvement of the efficacy of anti-glioma treatments are urgently needed. Thus, new therapeutic targets and tools should be developed based on a better understanding of the molecular pathogenesis of glioma. In this context, microRNAs (miRNAs), a class of small, non-coding RNAs, play a pivotal role in the development of the malignant phenotype of glioma cells, including cell survival, proliferation, differentiation, tumor angiogenesis, and stem cell generation. This review will discuss the biological functions of miRNAs in human glioma and their implications in improving clinical diagnosis, prediction of prognosis, and anti-glioma therapy.

  18. One-and-a-half syndrome in pontine infarcts: MRI correlates

    Energy Technology Data Exchange (ETDEWEB)

    Seze, J. de; Lucas, C.; Vermersch, P.; Leys, D. [Department of Neurology, Stroke Unit, Hopital R. Salengro, CHRU de Lille (France); Leclerc, X.; Sahli, A. [Department of Neuroradiology, Lille University Hospital, Lille (France)

    1999-09-01

    The one-and-a-half syndrome is characterised by a lateral gaze palsy in one direction and internuclear ophthalmoplegia in the other. It is due to a unilateral lesion of the dorsal pontine tegmentum, involving the ipsilateral paramedian pontine reticular formation, internuclear fibres of the ipsilateral medical longitudinal fasciculus and, usually, the abducens nucleus. The main causes of this rare syndrome are stroke and multiple sclerosis. Few cases have been reported since the introduction of MRI. Our aim was to examine clinicoradiological correlations in six patients with a one-and-a-half syndrome due to a stroke. Ophthalmological symptoms were diplopia, oscillopsia or blurred vision. Four patients had an associated facial nerve palsy, three a hemiparesis and one a unilateral hemihypoaesthesia. MRI revealed an infarct in the pons in all patients. The cause of the infarct was a basilar artery dissection in one patient, bilateral vertebral artery dissection in a second and unknown in the other four. All patients recovered within 2 days to 8 weeks. This study showed a good correlation between the site of the lesion (superior, inferior or extensive pontine ischaemia) and clinical deficits. (orig.)

  19. Tegmental-type primary pontine hemorrhage with mesencephalic extension. Clinico-CT-anatomic correlations

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Noboru; Ishikawa, Hiroshi; Kaneko, Mitsuo; Tanaka, Keisei

    1983-06-01

    In nine autopsy cases of tegmental-type primary pontine hemorrhage, two cases with a mesencephalic extension which was not accurately diagnosed symptomatologically, but which was clearly detected on CT films, were found. Correlative clinico-CT-anatomic reports on this kind of pontine hemorrhage have not been included in the literature. The two patients were both females, 73 and 53 years old. Both were hypertensive and under medical care. They showed disturbances of consciousness and respiration, pin-point pupils, fixed eyes in the midposition, right hemiplegia, right extensor plantar response, etc., but both responded well to painful stimuli on the left half of the body. CT examinations detected a continuous high-density area in the left-sided tegmentum of the pons and midbrain. They died 9 and 21 days later respectively. With the help of an electronic image analyser, a great volume of hematoma was measured in the postmortem brainstem in these cases (17 ml and 14 ml). Precise analyses of the correlations among clinical symptomatology, CT, and anatomical findings, and histological examinations were carried out in an attempt to find the pathogenesis of this disease. In the diagnosis of tegmental-type primary pontine hemorrhage, attention should be paid to a possible mesencephalic involvement as one of the modes of hematoma extension, although it may be rather rare.

  20. Evaluating the evidence surrounding pontine cholinergic involvement in REM sleep generation

    Directory of Open Access Journals (Sweden)

    Kevin P Grace

    2015-09-01

    Full Text Available Rapid eye movement (REM sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of rapid eye movement (REM sleep generation posited that induction of the state required activation of the ‘pontine REM sleep generator’ by cholinergic inputs. Here we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii loss-of-function studies show that endogenous cholinergic input to the PFT is not required for REM sleep generation, and (iv Cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.

  1. Case of primary pontine hemorrhage of the young adult followed by CT scan

    Energy Technology Data Exchange (ETDEWEB)

    Mashiyama, Shoji; Higuchi, Hiroshi; Takahashi, Akira

    1985-01-01

    A case of primary pontine hemorrhage of the young was reported. He was 22 years of age, who did not have the history of hypertension. He suddenly noticed disturbance of skilled act of his right hand and speech disturbance. He was admitted to our clinic two days after the onset. Neurological examination revealed right facial palsy, disturbance of delicate movement of his right hand and slight dysarthria. Lumbar puncture, after six days from the onset, yielded watery clear cerebrospinal fluid containing 6/3 cells/mm/sup 3/, 27mg/dl of protein and 65.1 mg/dl of sugar. An opening pressure was 75 mmH/sub 2/O. The vertebral angiography revealed no evidence of mass lesion and vascular anomalies. CT scan demonstrated a pontine hematoma, the size of this hematoma sequentially enlarged in follow-up CT scan. His clinical symptoms were gradually aggravated, i.e. cerebellar sign, urinary disturbance and involuntary movement. Conservative therapy was performed and his symptoms gradually improved. The size of hematoma was reduced in follow-up CT scan. The genesis, diagnosis and treatment of primary pontine hemorrhage of the young were discussed. (author).

  2. Evaluating the Evidence Surrounding Pontine Cholinergic Involvement in REM Sleep Generation.

    Science.gov (United States)

    Grace, Kevin P; Horner, Richard L

    2015-01-01

    Rapid eye movement (REM) sleep - characterized by vivid dreaming, motor paralysis, and heightened neural activity - is one of the fundamental states of the mammalian central nervous system. Initial theories of REM sleep generation posited that induction of the state required activation of the "pontine REM sleep generator" by cholinergic inputs. Here, we review and evaluate the evidence surrounding cholinergic involvement in REM sleep generation. We submit that: (i) the capacity of pontine cholinergic neurotransmission to generate REM sleep has been firmly established by gain-of-function experiments, (ii) the function of endogenous cholinergic input to REM sleep generating sites cannot be determined by gain-of-function experiments; rather, loss-of-function studies are required, (iii) loss-of-function studies show that endogenous cholinergic input to the PTF is not required for REM sleep generation, and (iv) cholinergic input to the pontine REM sleep generating sites serve an accessory role in REM sleep generation: reinforcing non-REM-to-REM sleep transitions making them quicker and less likely to fail.

  3. The Glioma International Case-Control Study

    DEFF Research Database (Denmark)

    Amirian, E. Susan; Armstrong, Georgina N; Zhou, Renke

    2016-01-01

    Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly...... describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen...

  4. The pathobiology of glioma tumors.

    Science.gov (United States)

    Gladson, Candece L; Prayson, Richard A; Liu, Wei Michael

    2010-01-01

    The ongoing characterization of the genetic and epigenetic alterations in the gliomas has already improved the classification of these heterogeneous tumors and enabled the development of rodent models for analysis of the molecular pathways underlying their proliferative and invasive behavior. Effective application of the targeted therapies that are now in development will depend on pathologists' ability to provide accurate information regarding the genetic alterations and the expression of key receptors and ligands in the tumors. Here we review the mechanisms that have been implicated in the pathogenesis of the gliomas and provide examples of the cooperative nature of the pathways involved, which may influence the initial therapeutic response and the potential for development of resistance.

  5. Tumor Metabolism of Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  6. Tumor Metabolism of Malignant Gliomas

    Directory of Open Access Journals (Sweden)

    Deliang Guo

    2013-11-01

    Full Text Available Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  7. The Pathobiology of Glioma Tumors

    OpenAIRE

    Gladson, Candece L.; Prayson, Richard A.; LIU Wei

    2010-01-01

    The ongoing characterization of the genetic and epigenetic alterations in the gliomas has already improved the classification of these heterogeneous tumors and enabled the development of rodent models for analysis of the molecular pathways underlying their proliferative and invasive behavior. Effective application of the targeted therapies that are now in development will depend on pathologists’ ability to provide accurate information regarding the genetic alterations and the expression of ke...

  8. The proneural molecular signature is enriched in oligodendrogliomas and predicts improved survival among diffuse gliomas.

    Directory of Open Access Journals (Sweden)

    Lee A D Cooper

    Full Text Available The Cancer Genome Atlas Project (TCGA has produced an extensive collection of '-omic' data on glioblastoma (GBM, resulting in several key insights on expression signatures. Despite the richness of TCGA GBM data, the absence of lower grade gliomas in this data set prevents analysis genes related to progression and the uncovering of predictive signatures. A complementary dataset exists in the form of the NCI Repository for Molecular Brain Neoplasia Data (Rembrandt, which contains molecular and clinical data for diffuse gliomas across the full spectrum of histologic class and grade. Here we present an investigation of the significance of the TCGA consortium's expression classification when applied to Rembrandt gliomas. We demonstrate that the proneural signature predicts improved clinical outcome among 176 Rembrandt gliomas that includes all histologies and grades, including GBMs (log rank test p = 1.16e-6, but also among 75 grade II and grade III samples (p  =  2.65e-4. This gene expression signature was enriched in tumors with oligodendroglioma histology and also predicted improved survival in this tumor type (n =  43, p  =  1.25e-4. Thus, expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for lower grade oligodendrogliomas, and likely represent important differences in tumor biology with implications for treatment and therapy. Integrated DNA and RNA analysis of low-grade and high-grade proneural gliomas identified increased expression and gene amplification of several genes including GLIS3, TGFB2, TNC, AURKA, and VEGFA in proneural GBMs, with corresponding loss of DLL3 and HEY2. Pathway analysis highlights the importance of the Notch and Hedgehog pathways in the proneural subtype. This demonstrates that the expression signatures identified in the TCGA analysis of GBMs also have intrinsic prognostic value for low-grade oligodendrogliomas, and likely represent important differences in tumor

  9. Current treatment of low grade gliomas

    NARCIS (Netherlands)

    M.J. van den Bent (Martin); T.A.B. Snijders (Tom); J.E.C. Bromberg (Jacolien)

    2012-01-01

    textabstractLow grade gliomas affect predominantly young adults, and have a relatively favorable prognosis compared to grade III and grade IV gliomas. The challenge for an optimal management of these patients is to find the balance between an optimal survival and the preservation of neurological fun

  10. TAZ promotes temozolomide resistance by upregulating MCL-1 in human glioma cells.

    Science.gov (United States)

    Tian, Tian; Li, Aimin; Lu, Hong; Luo, Ran; Zhang, Mingzhi; Li, Zhaoming

    2015-08-07

    Temozolomide is a novel cytotoxic agent currently used as first-line chemotherapy for glioblastoma multiforme (GBM). However, intrinsic or acquired chemoresistance to temozolomide remains the greatest obstacle to the successful treatment of human GBM. The principal mechanism responsible for this resistance is largely unknown. In the present study, we showed that expression of transcriptional co-activator with PDZ-binding motif (TAZ) in glioma cells correlated with temozolomide chemoresistance in human glioma cells. Overexpression of TAZ promoted temozolomide resistance in U-87MG cells, whereas knockdown of TAZ expression sensitized temozolomide-resistant U-251MG cells to temozolomide. Further, TAZ inhibits temozolomide induced apoptosis via upregulation of MCL-1 (myeloid cell leukemia 1) and high expression of TAZ predicts a poor prognosis for GBM patients. In conclusion, our results suggest that TAZ had a critical role in the resistance to temozolomide in glioma cells, and it may provide a promising target for improving the therapeutic outcome of temozolomide-resistant gliomas.

  11. PP2A Inhibitor PME-1 Drives Kinase Inhibitor Resistance in Glioma Cells.

    Science.gov (United States)

    Kaur, Amanpreet; Denisova, Oxana V; Qiao, Xi; Jumppanen, Mikael; Peuhu, Emilia; Ahmed, Shafiq U; Raheem, Olayinka; Haapasalo, Hannu; Eriksson, John; Chalmers, Anthony J; Laakkonen, Pirjo; Westermarck, Jukka

    2016-12-01

    Glioblastoma multiforme lacks effective therapy options. Although deregulated kinase pathways are drivers of malignant progression in glioblastoma multiforme, glioma cells exhibit intrinsic resistance toward many kinase inhibitors, and the molecular basis of this resistance remains poorly understood. Here, we show that overexpression of the protein phosphatase 2A (PP2A) inhibitor protein PME-1 drives resistance of glioma cells to various multikinase inhibitors. The PME-1-elicited resistance was dependent on specific PP2A complexes and was mediated by a decrease in cytoplasmic HDAC4 activity. Importantly, both PME-1 and HDAC4 associated with human glioma progression, supporting clinical relevance of the identified mechanism. Synthetic lethality induced by both PME-1 and HDAC4 inhibition was dependent on the coexpression of proapoptotic protein BAD. Thus, PME-1-mediated PP2A inhibition is a novel mechanistic explanation for multikinase inhibitor resistance in glioma cells. Clinically, these results may inform patient stratification strategies for future clinical trials with selected kinase inhibitors in glioblastoma multiforme. Cancer Res; 76(23); 7001-11. ©2016 AACR.

  12. Pontine stroke presenting as isolated facial nerve palsy mimicking Bell's palsy: a case report

    Directory of Open Access Journals (Sweden)

    Saluja Paramveer

    2011-07-01

    Full Text Available Abstract Introduction Isolated facial nerve palsy usually manifests as Bell's palsy. Lacunar infarct involving the lower pons is a rare cause of solitary infranuclear facial paralysis. The present unusual case is one in which the patient appeared to have Bell's palsy but turned out to have a pontine infarct. Case presentation A 47-year-old Asian Indian man with a medical history of hypertension presented to our institution with nausea, vomiting, generalized weakness, facial droop, and slurred speech of 14 hours' duration. His physical examination revealed that he was conscious, lethargic, and had mildly slurred speech. His blood pressure was 216/142 mmHg. His neurologic examination showed that he had loss of left-sided forehead creases, inability to close his left eye, left facial muscle weakness, rightward deviation of the angle of the mouth on smiling, and loss of the left nasolabial fold. Afferent corneal reflexes were present bilaterally. MRI of the head was initially read as negative for acute stroke. Bell's palsy appeared less likely because of the acuity of his presentation, encephalopathy-like imaging, and hypertension. The MRI was re-evaluated with a neurologist's assistance, which revealed a tiny 4 mm infarct involving the left dorsal aspect of the pons. The final diagnosis was isolated facial nerve palsy due to lacunar infarct of dorsal pons and hypertensive encephalopathy. Conclusion The facial nerve has a predominant motor component which supplies all muscles concerned with unilateral facial expression. Anatomic knowledge is crucial for clinical localization. Bell's palsy accounts for around 72% of facial palsies. Other causes such as tumors and pontine infarcts can also present as facial palsy. Isolated dorsal infarct presenting as isolated facial palsy is very rare. Our case emphasizes that isolated facial palsy should not always be attributed to Bell's palsy. It can be a presentation of a rare dorsal pontine infarct as observed

  13. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

    Science.gov (United States)

    Pittock, Sean J; Debruyne, Jan; Krecke, Karl N; Giannini, Caterina; van den Ameele, Jelle; De Herdt, Veerle; McKeon, Andrew; Fealey, Robert D; Weinshenker, Brian G; Aksamit, Allen J; Krueger, Bruce R; Shuster, Elizabeth A; Keegan, B Mark

    2010-09-01

    The classification and pathological mechanisms of many central nervous system inflammatory diseases remain uncertain. In this article we report eight patients with a clinically and radiologically distinct pontine-predominant encephalomyelitis we have named 'chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids' (CLIPPERS). The patients were assessed clinically, radiologically and pathologically at Mayo Clinic, USA and Ghent University Hospital, Belgium from 1999 to 2009. Median follow-up duration from clinical onset was 22 months (range 7-144 months). Patients underwent extensive laboratory (serum and cerebrospinal fluid), radiological and pathological testing (conjunctival, transbronchial and brain biopsies) to search for causes of an inflammatory central nervous system disorder. All eight patients (five female, three male) presented with episodic diplopia or facial paresthesias with subsequent brainstem and occasionally myelopathic symptoms and had a favourable initial response to high dose glucocorticosteroids. All patients had symmetric curvilinear gadolinium enhancement peppering the pons and extending variably into the medulla, brachium pontis, cerebellum, midbrain and occasionally spinal cord. Radiological improvement accompanied clinical response to glucocorticosteroids. Patients routinely worsened following glucocorticosteroid taper and required chronic glucocorticosteroid or other immunosuppressive therapy. Neuropathology of biopsy material from four patients demonstrated white matter perivascular, predominantly T lymphocytic, infiltrate without granulomas, infection, lymphoma or vasculitis. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a definable, chronic inflammatory central nervous system disorder amenable to immunosuppressive treatment. The T cell predominant inflammatory pathology in affected central nervous system lesions and the clinical and radiological

  14. Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome.

    Science.gov (United States)

    Hunt, Nicholas J; Waters, Karen A; Rodriguez, Michael L; Machaalani, Rita

    2015-08-01

    Infants at risk of sudden infant death syndrome (SIDS) have been shown to have dysfunctional sleep and poor arousal thresholds. In animal studies, both these attributes have been linked to impaired signalling of the neuropeptide orexin. This study examined the immunoreactivity of orexin (OxA and OxB) in the tuberal hypothalamus (n = 27) and the pons (n = 15) of infants (1-10 months) who died from SIDS compared to age-matched non-SIDS infants. The percentage of orexin immunoreactive neurons and the total number of neurons were quantified in the dorsomedial, perifornical and lateral hypothalamus at three levels of the tuberal hypothalamus. In the pons, the area of orexin immunoreactive fibres were quantified in the locus coeruleus (LC), dorsal raphe (DR), laterodorsal tegmental (LDT), medial parabrachial, dorsal tegmental (DTg) and pontine nuclei (Pn) using automated methods. OxA and OxB were co-expressed in all hypothalamic and pontine nuclei examined. In SIDS infants, orexin immunoreactivity was decreased by up to 21 % within each of the three levels of the hypothalamus compared to non-SIDS (p ≤ 0.050). In the pons, a 40-50 % decrease in OxA occurred in the all pontine nuclei, while a similar decrease in OxB immunoreactivity was observed in the LC, LDT, DTg and Pn (p ≤ 0.025). No correlations were found between the decreased orexin immunoreactivity and previously identified risk factors for SIDS, including prone sleeping position and cigarette smoke exposure. This finding of reduced orexin immunoreactivity in SIDS infants may be associated with sleep dysfunction and impaired arousal.

  15. A case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in East Asia.

    Science.gov (United States)

    Tohge, Rie; Nagao, Masahiro; Yagishita, Akira; Matsubara, Shiro

    2012-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a clinically and radiologically distinct pontine-predominant perivascular neuroinflammation showing T lymphocyte infiltration. It is assumed to have an autoimmune or other inflammatory mediated pathogenesis. We report the first known case of CLIPPERS in East Asia, characterized by multiple punctate enhancement of the brainstem extending to the bilateral posterior limb of the internal capsule and caudal to the spinal cord conus. The patient had elevated IgE levels and a history of allergies, suggesting that lesions may arise from neuroinflammation in response to T lymphocyte infiltration into perivascular spaces.

  16. Symptomatic ependymal cysts of the perimesencephalic and cerebello-pontine angle cisterns.

    Science.gov (United States)

    Sharma, R R; Pawar, S J; Kharangate, P P; Delmendo, A

    2000-11-01

    Primary intracranial ependymal cysts are extremely rare. These are congenital, benign ependyma lined, commonly intraparenchymal and uncommonly extraparenchymal cysts in leptomeningeal location of variable size seen in the adult life. The authors report two cases of symptomatic ependymal cysts: one in the perimesencephalic cistern in a 10-month-old infant presenting with delayed mile stones and another in the cerebello-pontine cistern in a morbidly obese 35-year-old woman with known benign intracranial hypertension now presenting with hemifacial spasm. Neurosurgical intervention was curative in both cases. Interesting clinical, radiological and histological features are presented and discussed.

  17. [CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids)].

    Science.gov (United States)

    Kan, Shinichi

    2016-09-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) has been recently identified as an inflammatory central nervous system (CNS) disorder. Punctate and curvilinear gadolinium enhancement (peppering) the pons is a characteristic magnetic resonance imaging (MRI) feature of CLIPPERS. Pathogenesis of this disorder remains unknown. A specific serum or cerebrospinal fluid biomarker for this disorder is currently unknown. Whether CLIPPERS is an actual new disease or just represents overlapping symptoms from multiple diseases is still debated. Many differential diagnoses exist even when using imaging as a tool. Pre-lymphoma states, such as grade I LYG (lymphomatoid granulomatosis) and sentinel lesions of primary CNS lymphoma are the most difficult to distinguish.

  18. An extended chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids phenotype.

    Science.gov (United States)

    Lane, Chris; Phadke, Rahul; Howard, Robin

    2014-06-25

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described central nervous system inflammatory condition. In this case report we describe a patient initially with features consistent with this syndrome, who represented with seizures (not previously reported in this syndrome) and corresponding prominent cortical involvement on imaging (also not previously noted). Owing to diagnostic uncertainty, cerebral biopsy was performed revealing histology consistent with CLIPPERS, excluding other differentials. Following a further brainstem relapse, this patient was treated with high-dose steroids, subsequently switched to a tapering oral regime and now, azathioprine, a steroid-sparing agent. She remains well on this.

  19. Primary pontine gliobastoma multiforme: A case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Baik, Ji Yeon; Baek, Hye Jin [Dept. of Radiology, Inje University College of Medicine, Haeundae Paik Hospital, Busan (Korea, Republic of); Moon, Jin Il; Cho, Soo Buem; Choi, Bo Hwa; Bae, Kyung Soo; Jeon, Kyung Nyeo [Dept. of Radiology, Gyeongsang National University School of Medicine, Gyeongsang National University Changwon Hospital, Changwon (Korea, Republic of); Choi, Dae Seob; Shin, Hwa Seon [Dept. of Radiology, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju (Korea, Republic of)

    2016-08-15

    Glioblastoma multiforme (GBM) most commonly occurs in the pons while it is rare in the brainstem. However, diagnosis of brainstem GBM can be difficult due to its rarity and nonspecific clinical manifestations. Herein, we presented a case of a 47-year-old female patient confirmed as primary pontine GBM by histopathological examination. This case highlights that GBM should be considered in the differential diagnosis of patients with a space-occupying lesion in the brainstem as well as the importance of a meticulous radiological review with clinical suspicion.

  20. Silencing of MGMT with small interference RNA reversed resistance in human BCUN-resistant glioma cell lines

    Institute of Scientific and Technical Information of China (English)

    XIE Si-ming; FANG Mao; GUO Hui; ZHONG Xue-yun

    2011-01-01

    Background Our previous study had cloned two glioma cell lines SWOZ1 and SWOZ2 isolated from parental glioma cell line SWO38.The 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance of SWOZ1 was higher than that of SWOZ2.Since O6-methylguanine-DNA methyltransferase (MGMT) was thought to be closely related to BCNU resistance in glioma,this study aimed to explore the function of MGMT in glioma resistant to BCNU.Methods A BCNU resistant glioma cell line SWOZ2-BCNU was established.The expression of MGMT was detected in SWOZ1,SWOZ2 and SWOZ2-BCNU.Small interferencing RNA targeting MGMT was used to silence the expression of MGMT in resistant cell lines SWOZ1 and SWOZ2-BCNU.The cytotoxicity of BCNU to these cells was measured using the cell counting kit-8 assay.Statistical analysis was carried out by one-way analysis of variance in statistical package SPSS 13.0.Results The resistance of SWOZ1 and SWOZ2-BCNU against BCNU was 4.9-fold and 5.3-fold higher than that of SWOZ2.The results of quantitative RT-PCR and Western blotting confirmed that MGMT was both significantly increased in SWOZ1 and SWOZ2-BCNU compared to SOWZ2.After transfection with small interferencing RNA targeting MGMT,a decreased level of MGMT mRNA expression in SWOZ1 and SWOZ2-BCNU for more than 75% compared to negative control was found and confirmed by Western blotting.As a result,the resistance against BCNU was reversed for about 50% both in the BCNU-resistant cell lines SWOZ1 and SWOZ2-BCNU.Conclusions Silencing MGMT with specific small interferencing RNA can reverse the BCNU resistant phenotype in these glioma cell lines.MGMT may play an important role both in intrinsic and acquired BCNU-resistance in glioma.

  1. Magnetic paclitaxel nanoparticles inhibit glioma growth and improve the survival of rats bearing glioma xenografts.

    Science.gov (United States)

    Zhao, Ming; Liang, Chao; Li, Anmin; Chang, Jin; Wang, Hanjie; Yan, Runmin; Zhang, Jiajing; Tai, Junli

    2010-06-01

    Paclitaxel has fared poorly in clinical trials against brain glioma. We hypothesized that superparamagnetic nanocarriers may enhance its bioactivities by delivering it into the brain. The magnetic paclitaxel nanoparticles (MPNPs) were fabricated and their cytotoxicity against glioma was tested both in vitro and in glioma-bearing rats. MPNPs exhibited superparamagnetism and produced an extended release of paclitaxel over 15 days in vitro. They were easily internalized into glioma cells and exerted remarkable toxicity, as free paclitaxel did. Furthermore, after intravenous injection of MPNPs to glioma-bearing rats and magnetic targeting with a 0.5 T magnet, drug content increased for 6- to 14-fold in implanted glioma and 4.6- to 12.1-fold in the normal brain compared to free paclitaxel. The survival of glioma-bearing rats was significantly prolonged after magnetic targeting therapy with MPNPs. MPNPs efficiently delivered paclitaxel into brain glioma by magnetic targeting and enhance its antitumor activity. They are promising for local chemotherapy for malignant glioma.

  2. Pontine tegmental cap dysplasia: developmental and cognitive outcome in three adolescent patients

    Directory of Open Access Journals (Sweden)

    Tortorella Gaetano

    2011-06-01

    Full Text Available Abstract Pontine Tegmental Cap Dysplasia (PTCD is a recently described, rare disorder characterized by a peculiar cerebellar and brainstem malformation. Nineteen patients have been reported to date, of which only one in the adolescent age, and data on the clinical, cognitive and behavioural outcome of this syndrome are scarce. Here we describe three adolescent patients with PTCD. All presented bilateral deafness and multiple cranial neuropathies, variably associated with skeletal, cardiac and gastro-intestinal malformations. Feeding and swallowing difficulties, that are often causative of recurrent aspiration pneumonias and death in the first years of life, completely resolved with age in all three patients. Neuropsychological assessment showed borderline to moderate cognitive impairment, with delay in adaptive functioning, visual-spatial and language deficits. Two of three patients also showed mild behavioural problems, although their overall socialization abilities were well preserved. Cochlear implantation in two patients significantly improved their relational and learning abilities. Fibre tractography confirmed the abnormal bundle of transversely oriented fibres forming the typical pontine "tegmental cap" and absence of decussation of the superior cerebellar peduncles, supporting the hypothesis that PTCD results from abnormal axonal guidance and/or migration. These data indicate that PTCD may have a favourable long-term outcome, with borderline cognitive deficit or even normal cognition and partially preserved speech.

  3. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A case report and review of literature

    OpenAIRE

    Soma Madhan Reddy; Rahul Lath; Meenakshi Swain; Alok Ranjan

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of central nervous system with distinct clinical and radiological features. The etiopathogenesis of this rare entity remains to be understood. The histopathological findings closely resemble chronic inflammatory diseases like sarcoidosis and malignancies like lymphoma. With advancements in serology, immunopathology and radiology CLIPPERS is iden...

  4. Chronic hepatitis B infection presenting with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report

    OpenAIRE

    Weng, Ching-Fu; Chan, Ding-Cheng; Chen, Ya-Fang; Liu, Fei-Chih; Liou, Horng-Huei

    2015-01-01

    Introduction Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a brainstem disorder characterized by perivascular pathologic reaction with lymphocyte infiltration and leading to diplopia, facial palsy, dysarthria, and gait ataxia. It was thought to be an autoimmune disorder without distinct pathogenesis. Chronic hepatitis B virus infection has been proposed in correlation with autoimmune diseases, including central nervous system demyelinating di...

  5. NF1 germline mutation differentially dictates optic glioma formation and growth in neurofibromatosis-1.

    Science.gov (United States)

    Toonen, Joseph A; Anastasaki, Corina; Smithson, Laura J; Gianino, Scott M; Li, Kairong; Kesterson, Robert A; Gutmann, David H

    2016-05-01

    Neurofibromatosis type 1 (NF1) is a common neurogenetic condition characterized by significant clinical heterogeneity. A major barrier to developing precision medicine approaches for NF1 is an incomplete understanding of the factors that underlie its inherent variability. To determine the impact of the germline NF1 gene mutation on the optic gliomas frequently encountered in children with NF1, we developed genetically engineered mice harboring two representative NF1-patient-derived Nf1 gene mutations (c.2542G>C;p.G848R and c.2041C>T;p.R681X). We found that each germline Nf1 gene mutation resulted in different levels of neurofibromin expression. Importantly, only R681X(CKO) but not G848R(CKO), mice develop optic gliomas with increased optic nerve volumes, glial fibrillary acid protein immunoreactivity, proliferation and retinal ganglion cell death, similar to Nf1 conditional knockout mice harboring a neomycin insertion (neo) as the germline Nf1 gene mutation. These differences in optic glioma phenotypes reflect both cell-autonomous and stromal effects of the germline Nf1 gene mutation. In this regard, primary astrocytes harboring the R681X germline Nf1 gene mutation exhibit increased basal astrocyte proliferation (BrdU incorporation) indistinguishable from neo(CKO) astrocytes, whereas astrocytes with the G848R mutation have lower levels of proliferation. Evidence for paracrine effects from the tumor microenvironment were revealed when R681X(CKO) mice were compared with conventional neo(CKO) mice. Relative to neo(CKO) mice, the optic gliomas from R681X(CKO) mice had more microglia infiltration and JNK(Thr183/Tyr185) activation, microglia-produced Ccl5, and glial AKT(Thr308) activation. Collectively, these studies establish that the germline Nf1 gene mutation is a major determinant of optic glioma development and growth through by both tumor cell-intrinsic and stromal effects.

  6. ALA-PDT of glioma cell micro-clusters in BD-IX rat brain

    Science.gov (United States)

    Madsen, Steen J.; Angell-Petersen, Even; Spetalen, Signe; Carper, Stephen W.; Ziegler, Sarah A.; Hirschberg, Henry

    2006-02-01

    A significant contributory factor to the poor prognosis of patients with glioblastoma multiforme is the inability of conventional treatments to eradicate infiltrating glioma cells. A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. The intrinsic sensitivity of rat glioma cells to PDT was investigated by exposing ALA-incubated cells to a range of radiant exposures and irradiances using 635 nm light. Biodistribution studies were undertaken on tumor-bearing animals in order to determine the tumor selectivity of the photosensitizer following systemic administration (i.p.) of ALA. Effects of ALA-PDT on normal brain and gross tumor were evaluated using histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 h after tumor cell implantation: a time when the micro-clusters of cells are protected by an intact blood-brain-barrier (BBB). Rat glioma cells in monolayer are susceptible to ALA-PDT - lower irradiances are more effective than higher ones. Fluorescence microscopy of frozen tissue sections showed that photosensitizer is produced with better than 200:1 tumor-to-normal tissue selectivity following i.p. ALA administration. ALA-PDT resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells compared to non-treated controls if the drug was delivered either i.p. or directly into the brain. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT.

  7. Adult high-grade malignant gliomas

    Directory of Open Access Journals (Sweden)

    Fable Zustovich

    2011-12-01

    Full Text Available Central nervous system (CNS malignant gliomas are relatively rare diseases. Prognosis is poor but has improved over recent years due to the improvement in the multi-disciplinary treatment: surgery, radiotherapy and chemotherapy...

  8. Targeting immune checkpoints in malignant glioma

    Science.gov (United States)

    Li, Tete; Liu, Yong-Jun; Chen, Wei; Chen, Jingtao

    2017-01-01

    Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the bodys anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered immune privileged and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma. In this review, we focus on immune checkpoint inhibitors, specifically, antagonizing monoclonal antibodies for programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO). We discuss advances in the working mechanisms of these immune checkpoint molecules, their status in malignant glioma, and current preclinical and clinical trials targeting these molecules in malignant glioma. PMID:27756892

  9. The Art of Intraoperative Glioma Identification

    Directory of Open Access Journals (Sweden)

    Zoe Z Zhang

    2015-07-01

    Full Text Available A major dilemma in brain tumor surgery is the identification of tumor boundaries to maximize tumor excision and minimize postoperative neurological damage. Gliomas, especially low-grade tumors, and normal brain have a similar color and texture which poses a challenge to the neurosurgeon. Advances in glioma resection techniques combine the experience of the neurosurgeon and various advanced technologies. Intraoperative methods to delineate gliomas from normal tissue consist of 1 image-based navigation, 2 intraoperative sampling, 3 electrophysiological monitoring, and 4 enhanced visual tumor demarcation. The advantages and disadvantages of each technique are discussed. A combination of these methods is becoming widely accepted in routine glioma surgery. Gross total resection in conjunction with radiation, chemotherapy, or immune/gene therapy may increase the rates of cure in this devastating disease.

  10. Post Traumatic Glioma – An association questioned

    Directory of Open Access Journals (Sweden)

    Chaurasia I.D.

    2015-03-01

    Full Text Available Post traumatic glioma has been a matter of debate. Few reports favor its occurrence in previous head injury scar, subsequently developing into glioma. Here we report a case of young patient presented with headache, seizures and gradual loss of vision. On investigation found to have brain tumor. Patient had head injury occurred 3 yrs back. It fulfills all the criteria required to establish traumatic origin, further supporting the association.

  11. Suppression of glioma progression by Egln3.

    Directory of Open Access Journals (Sweden)

    Vicki A Sciorra

    Full Text Available Grade IV astrocytoma or glioblastoma has a poor clinical outcome that can be linked to hypoxia, invasiveness and active vascular remodeling. It has recently been suggested that hypoxia-inducible factors, Hifs, increase glioma growth and aggressiveness [1], [2], [3]. Here, we tested the hypothesis that Egl 9 homolog 3 (Egln3, a prolyl-hydroxylase that promotes Hif degradation, suppresses tumor progression of human and rodent glioma models. Through intracranial tumorigenesis and in vitro assays, we demonstrate for the first time that Egln3 was sufficient to decrease the kinetics of tumor progression and increase survival. We also find that Klf5, a transcription factor important to vascular remodeling, was regulated by hypoxia in glioma. An analysis of the tumor vasculature revealed that elevated Egln3 normalized glioma capillary architecture, consistent with a role for Egln3 in eliciting decreases in the production of Hif-regulated, angiogenic factors. We also find that the hydroxylase-deficient mutant, Egln3(H196A partially maintained tumor suppressive activity. These results highlight a bifurcation of Egln3 signaling and suggest that Egln3 has a non-hydroxylase-dependent function in glioma. We conclude that Egln3 is a critical determinant of glioma formation and tumor vascular functionality.

  12. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

    Directory of Open Access Journals (Sweden)

    Fine Howard A

    2010-07-01

    Full Text Available Abstract Background Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. Results We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. Conclusions GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  13. Microglia-glioma cross-talk: a two way approach to new strategies against glioma.

    Science.gov (United States)

    Arcuri, Cataldo; Fioretti, Bernard; Bianchi, Roberta; Mecca, Carmen; Tubaro, Claudia; Beccari, Tommaso; Franciolini, Fabio; Giambanco, Ileana; Donato, Rosario

    2017-01-01

    Glioblastoma (GBM) is the most malignant and aggressive among primary brain tumors, characterized by very low life expectancy. In vivo, glioma and glioblastoma in particular contain large numbers of immune cells (myeloid cells) such as microglia and tumour-infiltrating macrophages (or glioma associated macrophages). These glioma-infiltrating myeloid cells comprise up to 30% of total tumor mass and have been suggested to play several roles in glioma progression including proliferation, survival, motility and immunosuppression. Although tumor microglia and macrophages can acquire proinflammatory (M1) phenotype being capable of releasing proinflammatory cytokines, phagocytosing and presenting antigens, their effector immune function in gliomas appears to be suppressed by the acquisition of an anti-inflammatory (M2) phenotype. In the present work we review the microglia-glioma interactions to highlight the close relationship between the two cell types and the factors that can influence their properties (chemokines, cytokines, S100B protein). A future therapeutic possibility might be to simultaneously targeting, for example with nanomedicine, glioma cells and microglia to push the microglia towards an antitumor phenotype (M1) and/or prevent glioma cells from "conditioning" by microglia.

  14. Known glioma risk loci are associated with glioma with a family history of brain tumours

    DEFF Research Database (Denmark)

    Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika

    2013-01-01

    Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive...

  15. Molecular Diagnostics of Gliomas Using Next Generation Sequencing of a Glioma-Tailored Gene Panel.

    Science.gov (United States)

    Zacher, Angela; Kaulich, Kerstin; Stepanow, Stefanie; Wolter, Marietta; Köhrer, Karl; Felsberg, Jörg; Malzkorn, Bastian; Reifenberger, Guido

    2017-03-01

    Current classification of gliomas is based on histological criteria according to the World Health Organization (WHO) classification of tumors of the central nervous system. Over the past years, characteristic genetic profiles have been identified in various glioma types. These can refine tumor diagnostics and provide important prognostic and predictive information. We report on the establishment and validation of gene panel next generation sequencing (NGS) for the molecular diagnostics of gliomas. We designed a glioma-tailored gene panel covering 660 amplicons derived from 20 genes frequently aberrant in different glioma types. Sensitivity and specificity of glioma gene panel NGS for detection of DNA sequence variants and copy number changes were validated by single gene analyses. NGS-based mutation detection was optimized for application on formalin-fixed paraffin-embedded tissue specimens including small stereotactic biopsy samples. NGS data obtained in a retrospective analysis of 121 gliomas allowed for their molecular classification into distinct biological groups, including (i) isocitrate dehydrogenase gene (IDH) 1 or 2 mutant astrocytic gliomas with frequent α-thalassemia/mental retardation syndrome X-linked (ATRX) and tumor protein p53 (TP53) gene mutations, (ii) IDH mutant oligodendroglial tumors with 1p/19q codeletion, telomerase reverse transcriptase (TERT) promoter mutation and frequent Drosophila homolog of capicua (CIC) gene mutation, as well as (iii) IDH wildtype glioblastomas with frequent TERT promoter mutation, phosphatase and tensin homolog (PTEN) mutation and/or epidermal growth factor receptor (EGFR) amplification. Oligoastrocytic gliomas were genetically assigned to either of these groups. Our findings implicate gene panel NGS as a promising diagnostic technique that may facilitate integrated histological and molecular glioma classification.

  16. A clinico-radiological study on 254 cases of pontine high signals on magnetic resonance imaging in relation to brain stem semiology

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

    1993-11-01

    A total of 254 patients who were proved to have pontine high intensity areas on T[sub 2]-weighted magnetic resonance imaging (MRI) were analyzed in relation to brain stem semiology. A comparative study on MRI and MR angiography was made between 254 patients with pontine high signals and 276 control cases showing no abnormality either on T[sub 1] or T[sub 2]-weighted images. Of the 254 patients, 62 had transient subjective complaints such as vertigo-dizziness. Supratentorial high signals, basilar artery tortuousness and vertebral artery asymmetry on MR angiography were seen more frequently in patients with pontine high signals than in the controls. In conclusion, pontine high signals may result from diffuse arteriosclerosis and MR angiography is considered to be a useful screening method. (author).

  17. Intrinsic-Density Functionals

    CERN Document Server

    Engel, J

    2006-01-01

    The Hohenberg-Kohn theorem and Kohn-Sham procedure are extended to functionals of the localized intrinsic density of a self-bound system such as a nucleus. After defining the intrinsic-density functional, we modify the usual Kohn-Sham procedure slightly to evaluate the mean-field approximation to the functional, and carefully describe the construction of the leading corrections for a system of fermions in one dimension with a spin-degeneracy equal to the number of particles N. Despite the fact that the corrections are complicated and nonlocal, we are able to construct a local Skyrme-like intrinsic-density functional that, while different from the exact functional, shares with it a minimum value equal to the exact ground-state energy at the exact ground-state intrinsic density, to next-to-leading order in 1/N. We briefly discuss implications for real Skyrme functionals.

  18. A Case of Central Pontine Myelinolysis Caused by Hypophosphatemia Secondary to Refeeding Syndrome.

    Science.gov (United States)

    Yamashita, Chikara; Shigeto, Hiroshi; Maeda, Norihisa; Torii, Takako; Ohyagi, Yasumasa; Kira, Jun-Ichi

    2015-01-01

    Central pontine myelinolysis (CPM), which was originally considered to be the result of rapid correction of chronic hyponatremia, is not necessarily accompanied by hyponatremia or drastic changes in serum sodium level. Here, we report a case of an anorexic 55-year-old male with a history of pharyngo-laryngo-esophagogastrectomy, initially hospitalized with status epilepticus. Although his consciousness gradually recovered as we were controlling his convulsion, it deteriorated again with new onset of anisocoria, and magnetic resonance imaging (MRI) at this point revealed CPM. Rapid change of serum sodium or osmolarity, which is often associated with CPM, had not been apparent throughout his hospitalization. Instead, a review of the serum biochemistry test results showed that serum phosphate had drastically declined the day before the MRI first detected CPM. In this case, we suspect that hypophosphatemia induced by refeeding syndrome greatly contributed to the occurrence of CPM.

  19. A Case of Central Pontine Myelinolysis Caused by Hypophosphatemia Secondary to Refeeding Syndrome

    Directory of Open Access Journals (Sweden)

    Chikara Yamashita

    2015-10-01

    Full Text Available Central pontine myelinolysis (CPM, which was originally considered to be the result of rapid correction of chronic hyponatremia, is not necessarily accompanied by hyponatremia or drastic changes in serum sodium level. Here, we report a case of an anorexic 55-year-old male with a history of pharyngo-laryngo-esophagogastrectomy, initially hospitalized with status epilepticus. Although his consciousness gradually recovered as we were controlling his convulsion, it deteriorated again with new onset of anisocoria, and magnetic resonance imaging (MRI at this point revealed CPM. Rapid change of serum sodium or osmolarity, which is often associated with CPM, had not been apparent throughout his hospitalization. Instead, a review of the serum biochemistry test results showed that serum phosphate had drastically declined the day before the MRI first detected CPM. In this case, we suspect that hypophosphatemia induced by refeeding syndrome greatly contributed to the occurrence of CPM.

  20. Central pontine myelinolysis presenting as isolated sixth nerve palsy in third trimester of pregnancy

    Directory of Open Access Journals (Sweden)

    Tushar Divakar Gosavi

    2015-01-01

    Full Text Available A 30-year-old primigravida presented with isolated left sixth nerve palsy at 38 weeks gestation. Her MRI showed a lesion consistent with central pontine myelinolysis (CPM. Extensive investigations did not reveal any secondary cause for the CPM. She recovered spontaneously in 2 weeks with complete resolution of her MRI changes. To our knowledge, this is the first report of CPM occurring in third trimester in the absence of identifiable secondary causes and of CPM presenting as an isolated sixth nerve palsy. We discuss the reported causes of CPM in pregnancy, possible pathophysiologic mechanisms involved and the anatomic basis of the unique clinical presentation of sixth nerve palsy in our case.

  1. Clinical Evolution of Central Pontine Myelinolysis in a Patient with Alcohol Withdrawal: A Blurred Clinical Horizon

    Directory of Open Access Journals (Sweden)

    Abdul S. Mohammed

    2016-01-01

    Full Text Available Central pontine myelinolysis (CPM, a potentially fatal and debilitating neurological condition, was first described in 1959 in a study on alcoholic and malnourished patients. It is a condition most frequently related to rapid correction of hyponatremia. Chronic alcoholism associated CPM tends to be benign with a favorable prognosis compared to CPM secondary to rapid correction of hyponatremia. We describe a normonatremic, alcoholic patient who presented with CPM after a rapid rise in his sodium levels. Our case illustrates the fact that CPM can manifest even in patients who are normonatremic at baseline. Rapid rises in sodium levels should be promptly reversed before clinical symptoms manifest in patient with risk factors for CPM irrespective of their baseline sodium levels. Furthermore, clinical evolution of CPM can be difficult to discern from the natural course of alcohol withdrawal delirium, requiring astuteness and maintenance of a high degree of clinical suspicion on the part of the physician.

  2. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) after treatment for Hodgkin's lymphoma.

    Science.gov (United States)

    Mashima, Kyoko; Suzuki, Shigeaki; Mori, Takehiko; Shimizu, Toshihiko; Yamada, Satoshi; Hirose, Shigemichi; Okamoto, Shinichiro; Suzuki, Norihiro

    2015-12-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system (CNS) disorder with distinct radiological features. However, CLIPPERS may mimic CNS lymphoma, and several cases in which CLIPPERS occurred premonitory to CNS lymphoma have been reported. We report a 31-year-old man presenting with progressive gait ataxia and the characteristic MRI features of CLIPPERS. He was diagnosed with stage II Hodgkin's lymphoma at the age of 15, and we considered the possibility of newly emerged CNS lymphoma occurring in the immunosuppressive condition after the treatment of Hodgkin's lymphoma. Histological findings showed no evidence of CNS lymphoma and the neurological symptoms were resolved by steroids. Although CLIPPERS developed in the reverse order in this case, CLIPPERS should be considered in different diagnosis for CNS lymphoma.

  3. Isolated extra pontine myelinolysis – a rare imaging appearance of osmotic demyelination syndrome

    Directory of Open Access Journals (Sweden)

    D. Rajitha

    2014-01-01

    Full Text Available Rapid correction of hyponatraemia leads to serious neurological complications, like osmotic demyelination syndrome (ODS. In ODS, magnetic resonance imaging (MRI often reveals features of pontine myelinolysis, that may occur in isolation or may, sometimes be associated with extrapontine myelinolysis. Isolated extrapontine myelinolysis is rare. We report the case of a 53-year-old lady brought to the emergency service with vomitings, and altered sensorium. She was found to have profound hyponatraemia (serum sodium 110 meq/L. Correction of hyponatremia was done with slow intravenous infusion of 3% sodium chloride. However, inadvertant, concomitant oral administration of salt led to overcorrection with serum sodium going upto 150 meq/L. She developed quadriplegia, depressed level of consciousness and respiratory failure and required ventilatory support. MRI brain showed features of isolated extrapontine myelinolysis.

  4. Projections from the oral pontine reticular nucleus to the spinal cord of the mouse.

    Science.gov (United States)

    Liang, Huazheng; Watson, Charles; Paxinos, George

    2015-01-01

    The present study investigated projections of the mouse oral pontine reticular nucleus (PnO) to the spinal cord by (a) injecting a retrograde tracer fluoro-gold (FG) to the lumbar cord and (b) an anterograde tracer biotinylated dextran amine (BDA) to PnO. We found that PnO projects to the entire spinal cord with an ipsilateral predominance. PnO fibers mainly travel in the ipsilateral ventral funiculus in the entire cord, terminating in laminae 7-10 with a lower density of fibers and boutons in lower segments. A small number of fibers travel in the contralateral ventral funiculus in the cervical cord with a similar terminating pattern to the ipsilateral counterpart. The present study is the first demonstration of PnO fiber terminals in the mouse spinal cord. This pathway might be responsible for muscle atonia during REM sleep, but needs physiological research to confirm this.

  5. New similarity search based glioma grading

    Energy Technology Data Exchange (ETDEWEB)

    Haegler, Katrin; Brueckmann, Hartmut; Linn, Jennifer [Ludwig-Maximilians-University of Munich, Department of Neuroradiology, Munich (Germany); Wiesmann, Martin; Freiherr, Jessica [RWTH Aachen University, Department of Neuroradiology, Aachen (Germany); Boehm, Christian [Ludwig-Maximilians-University of Munich, Department of Computer Science, Munich (Germany); Schnell, Oliver; Tonn, Joerg-Christian [Ludwig-Maximilians-University of Munich, Department of Neurosurgery, Munich (Germany)

    2012-08-15

    MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading. We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences. For each patient, a so-called tumor feature vector (= probability-based classifier) was defined and used for grading. Biopsy was used as gold standard, and similarity based grading was compared to grading solely based on CE-T1w. Accuracy, sensitivity, and specificity of pure CE-T1w based glioma grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor grading allowed differentiation between low-grade (I or II) and high-grade (III) gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and 87.0%. 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. (orig.)

  6. Immunoglobulin genes implicated in glioma risk.

    Science.gov (United States)

    Pandey, Janardan P; Kaur, Navtej; Costa, Sandra; Amorim, Julia; Nabico, Rui; Linhares, Paulo; Vaz, Rui; Viana-Pereira, Marta; Reis, Rui M

    2014-01-01

    Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped the IGHG locus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus.

  7. A case of mistaken identity: alcohol withdrawal, schizophrenia, or central pontine myelinolysis?

    Directory of Open Access Journals (Sweden)

    Schneider P

    2012-02-01

    Full Text Available Paul Schneider1, Vicki A Nejtek2,3, Cheryl Hurd2,31Green Oaks Behavioral Health Care Services, Dallas, 2University of North Texas Health Science Center, Fort Worth, 3John Peter Smith Health Network, Fort Worth, Texas, USAAbstract: Demyelination is a hallmark of central pontine myelinolysis (CPM. Neuropsychiatric manifestations of this condition include weakness, quadriplegia, pseudobulbar palsy, mood changes, psychosis, and cognitive disturbances. These psychiatric symptoms are also associated with schizophrenia and alcohol withdrawal. Thus, it is clinically relevant to differentiate between CPM, schizophrenia, and alcohol withdrawal as the treatment and prognostic outcomes for each diagnosis are distinct. We present a series of events that led to a misdiagnosis of a patient admitted to the medical emergency center presenting with confusion, psychomotor agitation, and delirium who was first diagnosed with schizophrenia and alcohol withdrawal by emergency medical physicians and later discovered by the psychiatric consult team to have CPM. With a thorough psychiatric evaluation, a review of the laboratory results first showing mild hyponatremia (127 mmol/L, subsequent hypernatremia (154 mmol/L, and magnetic resonance brain imaging, psychiatrists concluded that CPM was the primary diagnosis underlying the observed neuropsychopathology. This patient has mild impairments in mood, cognition, and motor skills that remain 12 months after her emergency-center admission. This case report reminds emergency clinicians that abnormal sodium metabolism can have long-term and devastating psychopathological and neurological consequences. Differentiating between CPM, schizophrenia, and alcohol withdrawal using neuroimaging techniques and preventing the risks for CPM using slow sodium correction are paramount.Keywords: MRI, alcohol, schizophrenia, central pontine myelinolysis, hyponatremia

  8. Pontine reticulospinal projections in the neonatal mouse: Internal organization and axon trajectories.

    Science.gov (United States)

    Sivertsen, Magne S; Perreault, Marie-Claude; Glover, Joel C

    2016-04-15

    We recently characterized physiologically a pontine reticulospinal (pRS) projection in the neonatal mouse that mediates synaptic effects on spinal motoneurons via parallel uncrossed and crossed pathways (Sivertsen et al. [2014] J Neurophysiol 112:1628-1643). Here we characterize the origins, anatomical organization, and supraspinal axon trajectories of these pathways via retrograde tracing from the high cervical spinal cord. The two pathways derive from segregated populations of ipsilaterally and contralaterally projecting pRS neurons with characteristic locations within the pontine reticular formation (PRF). We obtained estimates of relative neuron numbers by counting from sections, digitally generated neuron position maps, and 3D reconstructions. Ipsilateral pRS neurons outnumber contralateral pRS neurons by threefold and are distributed about equally in rostral and caudal regions of the PRF, whereas contralateral pRS neurons are concentrated in the rostral PRF. Ipsilateral pRS neuron somata are on average larger than contralateral. No pRS neurons are positive in transgenic mice that report the expression of GAD, suggesting that they are predominantly excitatory. Putative GABAergic interneurons are interspersed among the pRS neurons, however. Ipsilateral and contralateral pRS axons have distinctly different trajectories within the brainstem. Their initial spinal funicular trajectories also differ, with ipsilateral and contralateral pRS axons more highly concentrated medially and laterally, respectively. The larger size and greater number of ipsilateral vs. contralateral pRS neurons is compatible with our previous finding that the uncrossed projection transmits more reliably to spinal motoneurons. The information about supraspinal and initial spinal pRS axon trajectories should facilitate future physiological assessment of synaptic connections between pRS neurons and spinal neurons.

  9. New insights on the petrology of submarine volcanics from the Western Pontine Archipelago (Tyrrhenian Sea, Italy)

    Science.gov (United States)

    Conte, A. M.; Perinelli, C.; Bianchini, G.; Natali, C.; Martorelli, E.; Chiocci, F. L.

    2016-11-01

    The Pontine Islands form a volcanic archipelago in the Tyrrhenian Sea. It consists of two edifices, the islands of Ponza, Palmarola and Zannone and the islands of Ventotene and Santo Stefano, respectively. The Archipelago developed during two main volcanic cycles in the Plio-Pleistocene: 1) the Pliocene episode erupted subalkaline, silica-rich volcanic units, which constitute the dominant products in the western edifice (Ponza and Zannone Islands); 2) the Pleistocene episode erupted more alkaline products, represented by evolved rocks (trachytes to peralkaline rhyolites) in the islands of Ponza and Palmarola and by basic to intermediate rocks in the eastern edifice (Ventotene and Santo Stefano Islands). In this paper we present new geochemical and petrological data from submarine rock samples collected in two oceanographic cruises and a scuba diving survey. The main result is the recovery of relatively undifferentiated lithotypes that provide further insights on the magmatic spectrum existing in the Pontine Archipelago, allowing modelling of the whole suite of rocks by fractional crystallization processes. New major and trace element data and thermodynamic constrains (by the software PELE) indicate the existence of three distinct evolutionary trends corresponding to a HK calcalkaline series in the Pliocene, followed by a transitional and then by a shoshonite series in the Pleistocene. In particular, the transitional series, so far overlooked in the literature, is required in order to explain the genesis of several peralkaline felsic rocks recognized in the Archipelago. On the whole, the new geochemical data i) confirm the orogenic signature of the suites, ii) allow to rule out an anatectic origin for both subalkaline and peralkaline rhyolites and iii) indicate highly heterogeneous mantle sources, due to crustal components variously recycled in the mantle via subduction.

  10. Molecular Therapeutic Targets for Glioma Angiogenesis

    Directory of Open Access Journals (Sweden)

    Shingo Takano

    2010-01-01

    Full Text Available Due to the prominent angiogenesis that occurs in malignant glioma, antiangiogenic therapy has been attempted. There have been several molecular targets that are specific to malignant gliomas, as well as more broadly in systemic cancers. In this review, I will focus on some topics related to molecular therapeutic targets for glioma angiogenesis. First, important angiogenic factors that could be considered molecular targets are VEGF, VEGF-induced proteins on endothelial cells, tissue factor, osteopontin, v3 integrin, and thymidine phosphorylase as well as endogenous inhibitors, soluble Flt1, and thrombospondin 1. Second, hypoxic areas are also decreased by metronomic CPT11 treatment as well as temozolomide. Third, glioma-derived endothelial cells that are genetically and functionally distinct from normal endothelial cells should be targeted, for example, with SDF-1 and CXCR7 chemokine. Fourth, endothelial progenitor cells (EPCs likely contribute towards glioma angiogenesis in the brain and could be useful as a drug delivery tool. Finally, blockade of delta-like 4 (Dll4 results in a nonfunctioning vasculature and could be another important target distinct from VEGF.

  11. Genetic characterization of adult infratentorial gliomas.

    Science.gov (United States)

    Miwa, Tomoru; Hirose, Yuichi; Sasaki, Hikaru; Ikeda, Eiji; Yoshida, Kazunari; Kawase, Takeshi

    2009-02-01

    Adult infratentorial gliomas are rare and have not been well studied. We therefore conducted genetic analysis of those tumors to see if there was any characteristic that could be relevant in clinical management and understanding of tumorigenesis. Nineteen adult infratentorial gliomas were analyzed for chromosomal aberration by comparative genomic hybridization, and for expression of p53 and epidermal growth factor receptor (EGFR) by immunohistochemistry. The most frequent chromosomal aberration was the gain of 7p, and five of the seven cerebellar or fourth ventricle malignant gliomas had that aberration. However, the gain of 7q, the characteristic abnormality of supratentorial astrocytomas commonly associated with the gaining of 7p, was observed only in 1 of 11 adult infratentorial astrocytic tumors. Combined losses of 1p and 19q, the genetic hallmark of oligodendroglioma, were not observed. Results of immunohistochemistry of p53 and EGFR were comparable to those reported in supratentorial gliomas. Our findings might suggest the presence of distinct tumorigenic pathway in adult infratentorial gliomas.

  12. Sensitivity of Interstitial combined Chemotherapy against Glioma

    Institute of Scientific and Technical Information of China (English)

    WANG Ming-sheng; LIN Jian-ying; ZHOU Guo-sheng; ZHANG Xin-zhong

    2006-01-01

    Objective To investigate the inhibitory effects of combination chemotherapy of Carboplatin(CBP) ,Teniposide (Vm-26) ,Methasquin(MTX),and Nimodipine(NIM) on glioma,and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells,and to compare the sensitivity of glioma cells to administration of CBP,Vm-26, MTX, and NIM with that of the administration of CBP + NIM, Vm-26 + NIM, MTX + NIM, CBP + Vm-26 + MTX, or CBP + Vm-26 + MTX + NIM respectively. Results The inhibition rate of CBP + Vm-26 + MTX + NIM combination administration against glioma cells was 96.64%,which was higher than that of CBP + NIM (69.03%), Vm-26 + NIM (71.53%), MTX + NIM (52. 75% ), CBP + Vm-26 + MTX(78.59%)(P<0.01),and the dosage of CBP,Vm-26,and MTX was declined to 1/10 ~ 1/100 that of respective use of CBP,Vm-26,and MTX. Conclusions The curative effects of combination administration of CBP,Vm-26, MTX, and NIM was much better than that of respective administration,suggesting a higher inhibition rate and a lower dosage use.

  13. [Chemotherapy of chiasmal gliomas in children].

    Science.gov (United States)

    Helcl, F

    1995-04-01

    Chiasmal gliomas are rare tumors occurring predominantly in childhood. Their optimal treatment is still controversial. In the past only neurosurgeons (performing partial or subtotal removal of the tumor, biopsy or shunting procedure in hydrocephalus) and radiotherapeutists participated in their treatment. In the middle of the eighties there was only a single article dealing with chemotherapy of these tumors (Rosenstock, 1985). Since that time there was an increased number of articles about harmful effects of radiotherapy on the developing child's brain. Neurosurgeons are aware that they will not solve this problem alone. During the past 7 years we have observed gradual retreat from radiotherapy and an inclination to combined chemotherapy of the chiasmal gliomas in children. The author has been engaged in the research of this clinical entity for more than 10 years and he offers to readers a summary of the contemporary knowledge about chemotherapy of chiasmal gliomas in children. Despite the fact that there is lacking experience with long-term survivors after chemotherapy, which is extremely important especially in this disease, the preliminary short-term results of combined chemotherapy of chiasmal gliomas in children are promising. Rapid development of chemistry and pharmacology in the last few years is promising for the discovery of further, more effective anti-tumor drugs. Their new combinations could improve present non-satisfactory results of treatment of chiasmal gliomas in children. (Ref. 25.)

  14. Modeling Glioma Growth and Invasion in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Hanna Teresa Witte

    2009-09-01

    Full Text Available Glioblastoma is the most common and most malignant intrinsic human brain tumor, characterized by extensive invasion and proliferation of glial (astrocytic tumor cells, frequent activation of tyrosine kinase receptor signaling pathways, relative resistance to chemotherapy and radiotherapy, and poor prognosis. Using the Gal4-UAS system, we have produced glioma models in Drosophila by overexpressing homologs of human tyrosine kinase receptors under control of the glia-specific promoter reversed polarity (repo. Glial overexpression of activated epidermal growth factor receptor (EGFR resulted in enhanced proliferation and migration of larval glial cells with increased numbers in the eye imaginal disc, diffuse tumor-like enlargement of the optic stalk, and marked ectopic invasion of glial cells along the optic nerve. Glial overexpression of the downstream kinase PI3K showed similar pathology. Overexpression of activated pvr (platelet-derived growth factor receptor/vascular endothelial growth factor receptor homolog led to migration of glial cells along the optic nerve, whereas expression of activated htl (fibroblast growth factor receptor 1 homolog and INR (insulin receptor showed markedly elevated numbers of glial cells in the optic stalk. The EGFR/phosphatidylinositol 3-phosphate kinase (PI3K phenotype was partly reverted by the administration of the EGFR tyrosine kinase inhibitor gefitinib and completely rescued by the PI3K inhibitor wortmannin and the Akt inhibitor triciribine. We suggest that Drosophila models will be useful for deciphering signaling cascades underlying abnormal behavior of glioma cells for genetic screens to reveal interacting genes involved in gliomagenesis and for experimental therapy approaches.

  15. Glioma cells on the run – the migratory transcriptome of 10 human glioma cell lines

    Directory of Open Access Journals (Sweden)

    Holz David

    2008-01-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is the most common primary intracranial tumor and despite recent advances in treatment regimens, prognosis for affected patients remains poor. Active cell migration and invasion of GBM cells ultimately lead to ubiquitous tumor recurrence and patient death. To further understand the genetic mechanisms underlying the ability of glioma cells to migrate, we compared the matched transcriptional profiles of migratory and stationary populations of human glioma cells. Using a monolayer radial migration assay, motile and stationary cell populations from seven human long term glioma cell lines and three primary GBM cultures were isolated and prepared for expression analysis. Results Gene expression signatures of stationary and migratory populations across all cell lines were identified using a pattern recognition approach that integrates a priori knowledge with expression data. Principal component analysis (PCA revealed two discriminating patterns between migrating and stationary glioma cells: i global down-regulation and ii global up-regulation profiles that were used in a proband-based rule function implemented in GABRIEL to find subsets of genes having similar expression patterns. Genes with up-regulation pattern in migrating glioma cells were found to be overexpressed in 75% of human GBM biopsy specimens compared to normal brain. A 22 gene signature capable of classifying glioma cultures based on their migration rate was developed. Fidelity of this discovery algorithm was assessed by validation of the invasion candidate gene, connective tissue growth factor (CTGF. siRNA mediated knockdown yielded reduced in vitro migration and ex vivo invasion; immunohistochemistry on glioma invasion tissue microarray confirmed up-regulation of CTGF in invasive glioma cells. Conclusion Gene expression profiling of migratory glioma cells induced to disperse in vitro affords discovery of genomic signatures; selected

  16. Restoration of sensitivity in chemo-resistant glioma cells by cold atmospheric plasma.

    Science.gov (United States)

    Köritzer, Julia; Boxhammer, Veronika; Schäfer, Andrea; Shimizu, Tetsuji; Klämpfl, Tobias G; Li, Yang-Fang; Welz, Christian; Schwenk-Zieger, Sabina; Morfill, Gregor E; Zimmermann, Julia L; Schlegel, Jürgen

    2013-01-01

    Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. Despite multimodal treatments including surgery, chemotherapy and radiotherapy the prognosis remains poor and relapse occurs regularly. The alkylating agent temozolomide (TMZ) has been shown to improve the overall survival in patients with malignant gliomas, especially in tumors with methylated promoter of the O6-methylguanine-DNA-methyltransferase (MGMT) gene. However, intrinsic and acquired resistance towards TMZ makes it crucial to find new therapeutic strategies aimed at improving the prognosis of patients suffering from malignant gliomas. Cold atmospheric plasma is a new auspicious candidate in cancer treatment. In the present study we demonstrate the anti-cancer properties of different dosages of cold atmospheric plasma (CAP) both in TMZ-sensitive and TMZ-resistant cells by proliferation assay, immunoblotting, cell cycle analysis, and clonogenicity assay. Importantly, CAP treatment restored the responsiveness of resistant glioma cells towards TMZ therapy. Concomitant treatment with CAP and TMZ led to inhibition of cell growth and cell cycle arrest, thus CAP might be a promising candidate for combination therapy especially for patients suffering from GBMs showing an unfavorable MGMT status and TMZ resistance.

  17. Restoration of sensitivity in chemo-resistant glioma cells by cold atmospheric plasma.

    Directory of Open Access Journals (Sweden)

    Julia Köritzer

    Full Text Available Glioblastoma (GBM is the most common and aggressive brain tumor in adults. Despite multimodal treatments including surgery, chemotherapy and radiotherapy the prognosis remains poor and relapse occurs regularly. The alkylating agent temozolomide (TMZ has been shown to improve the overall survival in patients with malignant gliomas, especially in tumors with methylated promoter of the O6-methylguanine-DNA-methyltransferase (MGMT gene. However, intrinsic and acquired resistance towards TMZ makes it crucial to find new therapeutic strategies aimed at improving the prognosis of patients suffering from malignant gliomas. Cold atmospheric plasma is a new auspicious candidate in cancer treatment. In the present study we demonstrate the anti-cancer properties of different dosages of cold atmospheric plasma (CAP both in TMZ-sensitive and TMZ-resistant cells by proliferation assay, immunoblotting, cell cycle analysis, and clonogenicity assay. Importantly, CAP treatment restored the responsiveness of resistant glioma cells towards TMZ therapy. Concomitant treatment with CAP and TMZ led to inhibition of cell growth and cell cycle arrest, thus CAP might be a promising candidate for combination therapy especially for patients suffering from GBMs showing an unfavorable MGMT status and TMZ resistance.

  18. Treatment of malignant glioma using hyperthermia*

    Institute of Scientific and Technical Information of China (English)

    Jiahang Sun; Mian Guo; Hengyuan Pang; Jingtao Qi; Jinwei Zhang; Yunlong Ge

    2013-01-01

    Thirty pathological y diagnosed patients with grade III-IV primary or recurrent malignant glioma (tumor diameter 3-7 cm) were randomly divided into two groups. The control group underwent conventional radiotherapy and chemotherapy. In the hyperthermia group, primary cases received hyperthermia treatment, and patients with recurrent tumors were treated with hyperthermia in com-bination with radiotherapy and chemotherapy. Hyperthermia treatment was administered using a 13.56-MHz radio frequency hyperthermia device. Electrodes were inserted into the tumor with the aid of a CT-guided stereotactic apparatus and heat was applied for 1 hour. During 3 months after hyperthermia, patients were evaluated with head CT or MRI every month. Gliomas in the hyper-thermia group exhibited growth retardation or growth termination. Necrosis was evident in 80%of the heated tumor tissue and there was a decrease in tumor diameter. Our findings indicate that ra-dio frequency hyperthermia has a beneficial effect in the treatment of malignant glioma.

  19. Characteristics of gliomas in patients with somatic IDH mosaicism.

    Science.gov (United States)

    Bonnet, Charlotte; Thomas, Laure; Psimaras, Dimitri; Bielle, Franck; Vauléon, Elodie; Loiseau, Hugues; Cartalat-Carel, Stéphanie; Meyronet, David; Dehais, Caroline; Honnorat, Jérôme; Sanson, Marc; Ducray, François

    2016-03-31

    IDH mutations are found in the majority of adult, diffuse, low-grade and anaplastic gliomas and are also frequently found in cartilaginous tumors. Ollier disease and Maffucci syndrome are two enchondromatosis syndromes characterized by the development of multiple benign cartilaginous tumors due to post-zygotic acquisition of IDH mutations. In addition to skeletal tumors, enchondromatosis patients sometimes develop gliomas. The aim of the present study was to determine whether gliomas in enchondromatosis patients might also result from somatic IDH mosaicism and whether their characteristics are similar to those of sporadic IDH-mutated gliomas. For this purpose, we analyzed the characteristics of 6 newly diagnosed and 32 previously reported cases of enchondromatosis patients who developed gliomas and compared them to those of a consecutive series of 159 patients with sporadic IDH-mutated gliomas. As was the case with sporadic IDH mutated gliomas, enchondromatosis gliomas were frequently located in the frontal lobe (54 %) and consisted of diffuse low-grade (73 %) or anaplastic gliomas (21 %). However, they were diagnosed at an earlier age (25.6 years versus 44 years, p mosaicism and that the timing of IDH mutation acquisition might affect the location and molecular characteristics of gliomas. Early acquisition of IDH mutations could shift gliomagenesis towards the brainstem thereby mimicking the regional preference of histone mutated gliomas.

  20. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels

    OpenAIRE

    Fujisawa, Naoaki; Oya, Soichi; Mori, Harushi; Matsui, Toru

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to expe...

  1. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) with intracranial Epstein–Barr virus infection

    OpenAIRE

    Ma, Yue; Sun, Xiaolong; Li, Wen; Li, Yi; Kang, Tao; Yang, Xiai; Jiang, Wen

    2016-01-01

    Abstract Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological features. The pathophysiology of CLIPPERS still remains unclear and the reports are quite few. Although the radiological lesions were reported to be located predominantly in the pons, brachium pontis, and cerebellum, other adjacent structures such as t...

  2. Difusion weighted imaging characteristics differentiate acute symptomatic cerebral microbleeds from silent microbleeds: An acute pontine microhemorrhage case presentation

    Directory of Open Access Journals (Sweden)

    Arda Yılmaz

    2015-04-01

    Full Text Available Cerebral microbleeds (CMBs on susceptibility weighted imaging (SWI have generally been considered to be silent. Recent reports indicated that, albeit it is a rarity, CMBs can cause acute focal neurological symptoms. Herein we present a patient who was admitted with cheiro-oral syndrome due to an acute izolated pontine microbleed. Combination of diffusion weighted imaging and SWI can be useful in the differentiation of acute symptomatic cerebral microbleeds from chronic ones.

  3. Lorentz invariant intrinsic decoherence

    CERN Document Server

    Milburn, G J

    2003-01-01

    Quantum decoherence can arise due to classical fluctuations in the parameters which define the dynamics of the system. In this case decoherence, and complementary noise, is manifest when data from repeated measurement trials are combined. Recently a number of authors have suggested that fluctuations in the space-time metric arising from quantum gravity effects would correspond to a source of intrinsic noise, which would necessarily be accompanied by intrinsic decoherence. This work extends a previous heuristic modification of Schr\\"{o}dinger dynamics based on discrete time intervals with an intrinsic uncertainty. The extension uses unital semigroup representations of space and time translations rather than the more usual unitary representation, and does the least violence to physically important invariance principles. Physical consequences include a modification of the uncertainty principle and a modification of field dispersion relations, in a way consistent with other modifications suggested by quantum grav...

  4. Molecular Alterations of KIT Oncogene in Gliomas

    Directory of Open Access Journals (Sweden)

    Ana L. Gomes

    2007-01-01

    Full Text Available Gliomas are the most common and devastating primary brain tumours. Despite therapeutic advances, the majority of gliomas do not respond either to chemo or radiotherapy. KIT, a class III receptor tyrosine kinase (RTK, is frequently involved in tumourigenic processes. Currently, KIT constitutes an attractive therapeutic target. In the present study we assessed the frequency of KIT overexpression in gliomas and investigated the genetic mechanisms underlying KIT overexpression. KIT (CD117 immunohistochemistry was performed in a series of 179 gliomas of various grades. KIT activating gene mutations (exons 9, 11, 13 and 17 and gene amplification analysis, as defined by chromogenic in situ hybridization (CISH and quantitative real-time PCR (qRT-PCR were performed in CD117 positive cases. Tumour cell immunopositivity was detected in 15.6% (28/179 of cases, namely in 25% (1/4 of pilocytic astrocytomas, 25% (5/20 of diffuse astrocytomas, 20% (1/5 of anaplastic astrocytomas, 19.5% (15/77 of glioblastomas and one third (3/9 of anaplastic oligoastrocytomas. Only 5.7% (2/35 of anaplastic oligodendrogliomas showed CD117 immunoreactivity. No association was found between tumour CD117 overexpression and patient survival. In addition, we also observed CD117 overexpression in endothelial cells, which varied from 0–22.2% of cases, being more frequent in high-grade lesions. No KIT activating mutations were identified. Interestingly, CISH and/or qRT-PCR analysis revealed the presence of KIT gene amplification in 6 glioblastomas and 2 anaplastic oligoastrocytomas, corresponding to 33% (8/24 of CD117 positive cases. In conclusion, our results demonstrate that KIT gene amplification rather than gene mutation is a common genetic mechanism underlying KIT expression in subset of malignant gliomas. Further studies are warranted to determine whether glioma patients exhibiting KIT overexpression and KIT gene amplification may benefit from therapy with anti-KIT RTK

  5. Isocitrate dehydrogenase status and molecular subclasses of glioma and glioblastoma.

    Science.gov (United States)

    Agnihotri, Sameer; Aldape, Kenneth D; Zadeh, Gelareh

    2014-12-01

    Diffuse gliomas and secondary glioblastomas (GBMs) that develop from low-grade gliomas are a common and incurable class of brain tumor. Mutations in the metabolic enzyme glioblastomas (IDH1) represent a distinguishing feature of low-grade gliomas and secondary GBMs. IDH1 mutations are one of the most common and earliest detectable genetic alterations in low-grade diffuse gliomas, and evidence supports this mutation as a driver of gliomagenesis. Here, the authors highlight the biological consequences of IDH1 mutations in gliomas, the clinical and therapeutic/diagnostic implications, and the molecular subtypes of these tumors. They also explore, in brief, the non-IDH1-mutated gliomas, including primary GBMs, and the molecular subtypes and drivers of these tumors. A fundamental understanding of the diversity of GBMs and lower-grade gliomas will ultimately allow for more effective treatments and predictors of survival.

  6. Intrinsic Time Quantum Geometrodynamics

    CERN Document Server

    Ita, Eyo Eyo; Yu, Hoi-Lai

    2015-01-01

    Quantum Geometrodynamics with intrinsic time development and momentric variables is presented. An underlying SU(3) group structure at each spatial point regulates the theory. The intrinsic time behavior of the theory is analyzed, together with its ground state and primordial quantum fluctuations. Cotton-York potential dominates at early times when the universe was small; the ground state naturally resolves Penrose's Weyl Curvature Hypothesis, and thermodynamic and gravitational `arrows of time' point in the same direction. Ricci scalar potential corresponding to Einstein's General Relativity emerges as a zero-point energy contribution. A new set of fundamental canonical commutation relations without Planck's constant emerges from the unification of Gravitation and Quantum Mechanics.

  7. Central pontine myelinolysis in a chronic alcoholic: A clinical and brain magnetic resonance imaging follow-up

    Directory of Open Access Journals (Sweden)

    Dujmović Irena

    2013-01-01

    Full Text Available Introduction. Central pontine myelinolysis (CPM is a noninflammatory, demyelinating lesion usually localised in the basis pontis. Chronic alcoholism is frequently associated with this condition which may have a variable clinical outcome. Until now, brain magnetic resonance imaging (MRI follow-up in alcoholic CPM cases after alcohol withdrawal has been rarely described. Case report. We reported a 30- year-old male with a 12-year history of alcohol abuse, who presented with inability to stand and walk, nausea, vomiting and somnolence. Neurological examination revealed: impared fixation on lateral gaze, dysarthria, mild spastic quadriparesis, truncal and extremity ataxia, sock-like hypesthesia and moderate decrease in vibration sense in legs. Brain MRI showed a trident-shaped non-enhancing pontine lesion highly suggestive of CPM. After an eight-month alcoholfree follow-up period, the patient’s clinical status significantly improved, while the extent of MRI pontine lesion was merely slightly reduced. Conclusion. The presented case demonstrates that CPM in chronic alcoholics may have a benign clinical course after alcohol withdrawal, which is not necessarily associated with the reduction of lesions on brain MRI. [Projekat Ministarstva nauke Republike Srbije, br. 175031

  8. Molecular targeting for malignant gliomas (Review).

    Science.gov (United States)

    Kondo, Yasuko; Hollingsworth, Emporia F; Kondo, Seiji

    2004-05-01

    With tendency to invade rapidly in the brain, malignant gliomas are very resistant to conventional therapies including radiation and chemotherapy. Recent advances in genetic and molecular techniques have made it possible to define characteristic molecular profiles of malignant gliomas. Based on the list of the molecules closely related to glioblastoma tissues, we reviewed strategies targeting them. Target molecules extensively studied include EGFR, PTEN, telomerase and signal pathway modulators for Ras/Raf/MAPK and PI3K/Akt/mTOR pathways. Therapies targeting specific molecules may result in killing tumor cells effectively while keeping normal cells intact.

  9. Using bioluminescence imaging in glioma research.

    Science.gov (United States)

    Luwor, Rodney B; Stylli, Stanley S; Kaye, Andrew H

    2015-05-01

    Glioblastoma multiforme (GBM) is the most common malignant brain tumour and has the worst prognosis. Over the last decade, the use of bioluminescence imaging technology has rapidly become widespread to further understand the mechanisms that drive GBM development and progression. Pre-clinical evaluation and optimisation of therapeutic efficacy in GBM research has also utilised this simple non-invasive technology. Here we summarise recent advances made in glioma biology and therapeutic intervention using bioluminescence imaging. This review also describes the current knowledge regarding the use of luciferase-based reporters in examining the role of specific cancer signalling cascades that promote glioma progression.

  10. Intrinsic contractures of the hand.

    Science.gov (United States)

    Paksima, Nader; Besh, Basil R

    2012-02-01

    Contractures of the intrinsic muscles of the fingers disrupt the delicate and complex balance of intrinsic and extrinsic muscles, which allows the hand to be so versatile and functional. The loss of muscle function primarily affects the interphalangeal joints but also may affect etacarpophalangeal joints. The resulting clinical picture is often termed, intrinsic contracture or intrinsic-plus hand. Disruption of the balance between intrinsic and extrinsic muscles has many causes and may be secondary to changes within the intrinsic musculature or the tendon unit. This article reviews diagnosis, etiology, and treatment algorithms in the management of intrinsic contractures of the fingers. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Gefitinib induces apoptosis in human glioma cells by targeting Bad phosphorylation.

    Science.gov (United States)

    Chang, Cheng-Yi; Shen, Chiung-Chyi; Su, Hong-Lin; Chen, Chun-Jung

    2011-12-01

    Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is under clinical testing and use in cancer patients, including glioma. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma remain largely uncharacterized. Gefitinib inhibits cell growth and induces apoptosis in human glioma cells. Gefitinib also induces death of H4 cells with characteristics of the intrinsic apoptotic pathway, including Bax mitochondrial translocation, mitochondrial outer membrane permeabilization, cytochrome c cytosolic release, and caspase-9/caspase-3 activation. The importance of Bax in mediating gefitinib-induced apoptosis was confirmed by the attenuation of apoptosis by Bax siRNA and Bax channel blocker. Gefitinib caused Bad dephosphorylation, particularly in serine-112, and increased its binding preference to Bcl-2 and Bcl-xL. The dephosphorylation of Bad in gefitinib-treated cells was accompanied by reduced intracellular cyclic AMP content and protein kinase A (PKA) activity. Adenylyl cyclase activator forskolin attenuated, but PKA inhibitor H89 augmented, gefitinib-induced Bad dephosphorylation, Bax mitochondrial translocation, caspase-9/caspase-3 activation, and viability loss. Intriguingly, a nonselective protein phosphatase inhibitor okadaic acid alleviated gefitinib-induced alterations, except Bad dephosphorylation. In parallel with the higher basal PKA activity, response of U87 cells to gefitinib treatment was delayed and relatively resistant compared with that of H4 and T98G cells. Inactivation of PKA sensitized H4, T98G, and U87 cells to gefitinib cytotoxicity, Bad dephosphorylation in serine-112, and caspase-9/caspase-3 activation. Our findings suggest the involvement of the Bad/Bax signaling pathway in gefitinib-induced glioma apoptosis. Furthermore, the inactivation of PKA was shown to play a role in triggering the proapoptotic function of Bad.

  12. Lymphoid Cell-Glioma Cell Interaction Enhances Cell Coat Production by Human Gliomas: Novel Suppressor Mechanism

    Science.gov (United States)

    Dick, Steven J.; Macchi, Beatrice; Papazoglou, Savvas; Oldfield, Edward H.; Kornblith, Paul L.; Smith, Barry H.; Gately, Maurice K.

    1983-05-01

    Certain human glioma lines produce mucopolysaccharide coats that impair the generation of cytolytic lymphocytes in response to these lines in vitro. Coat production is substantially enhanced by the interaction of glioma cells with a macromolecular factor released by human peripheral blood mononuclear cells in culture. This interaction thus constitutes an unusual mechanism by which inflammatory cells may nonspecifically suppress the cellular immune response to at least one class of solid tumors in humans.

  13. Predicting Intrinsic Motivation

    Science.gov (United States)

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the extent to…

  14. The Association between Some Nutrients and Adult Gliomas: A Case-Control Study of Adult Gliomas

    Directory of Open Access Journals (Sweden)

    M Shayanfar

    2014-02-01

    Full Text Available Abestract Background & aim: It has been estimated that about 30–40 percent of all cancers could be prevented by diet and lifestyle. In the present study, associations between food groups and some nutrients were studied in adult glioma. Methods: In the present hospital-based case-control study which took place in Tehran, Iran, from 2010 to 2012, socio-economic information, demographics, lifestyle factors, health and dietary intakes of 128 patients with glioma as cases, and 256 healthy controls, were collected through interviews and questionnaires. Logistic regression was used to estimate odds ratios. SPSS version 19 was used for all statistical analyses. Results: After adjusting for potential confounders, inverse associations between calcium intake and adult glioma and vitamin C were observed. (Highest tertile versus lowest: OR = 0.20, 95% CI = 0.87-0.46, P for trend = 0.001 and vitamin C (OR = 0.34, 95% CI = 0.15-0.76, P for trend = 0.002. In addition, we observed elevated ORs for highest vs. lowest tertile of cholesterol intake (OR = 2.78, 95% CI = 1.29-5.99, P for trend = 0.061. We observed no significant associations with adult glioma for intakes of total fat, carbohydrate, protein, vitamin A, vitamin E and beta carotene. Conclusion: the results showed that intake of calcium and vitamin C may possibly prevent glioma in adults. Key words: Gliomas, Adult, Ca, Vitamin C

  15. Kynurenic acid synthesis by human glioma

    DEFF Research Database (Denmark)

    Vezzani, A; Gramsbergen, J B; Versari, P;

    1990-01-01

    Biopsy material from human gliomas obtained during neurosurgery was used to investigate whether pathological human brain tissue is capable of producing kynurenic acid (KYNA), a natural brain metabolite which can act as an antagonist at excitatory amino acid receptors. Upon in vitro exposure to 40...

  16. Genetics and pharmacogenomics of diffuse gliomas

    NARCIS (Netherlands)

    Thuijl, H.F. van; Ylstra, B.; Wurdinger, T.; Nieuwenhuizen, D. van; Heimans, J.J.; Wesseling, P.; Reijneveld, J.C.

    2013-01-01

    Rapidly evolving techniques for analysis of the genome provide new opportunities for cancer therapy. For diffuse gliomas this has resulted in molecular markers with potential for personalized therapy. Some drugs that utilize pharmacogenomics are currently being tested in clinical trials. In melanoma

  17. Mean Diffusional Kurtosis in Patients with Glioma

    DEFF Research Database (Denmark)

    Tietze, A.; Hansen, Mikkel Bo; Østergaard, Leif

    2015-01-01

    , and the contralateral normal appearing white and grey matter of 34 patients (22 high-grade, 12 low-grade gliomas). MK’ and MD in different grades were compared using a Wilcoxon rank-sum test. Receiver Operating Characteristic curves and the area under the curve were calculated to determine the diagnostic accuracy of MK...

  18. Changing incidence and improved survival of gliomas

    NARCIS (Netherlands)

    Ho, Vincent K. Y.; Reijneveld, Jaap C.; Enting, Roeline; Bienfait, Henri P.; Robe, Pierre; Baumert, Brigitta G.; Visser, Otto

    2014-01-01

    BACKGROUND: Tumours of the central nervous system (CNS) represent a relatively rare but serious health burden. This study provides insight into the incidence and survival patterns of gliomas in the Netherlands diagnosed in adult patients during the time period 1989-2010, with a focus on glioblastoma

  19. Neuromyelitis Optica Lesion Mimicking Brainstem Glioma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-12-01

    Full Text Available A 12-year-old girl who presented with weakness of the left extremities and right sided sixth cranial nerve palsy had neuromyelitis optica (NMO mistaken for brainstem glioma on MRI, in a report from Brain Research Institute, Yonsei University College of Medicine,Seoul, Republic of KoreaNeuromyelitis Optica, Optic-Spinal Syndrome, Spectroscopy.

  20. Hormone replacement therapy and risk of glioma

    DEFF Research Database (Denmark)

    Andersen, Lene; Friis, Søren; Hallas, Jesper;

    2013-01-01

    Aim: Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored. We investigated the influence of HRT use on the risk of glioma...

  1. Surgical strategies for glioma involving language areas

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong; JIANG Tao; XIE Jian; LIU Fu-sheng; LI Shou-wei; QIAO Hui; WANG Zhong-cheng

    2008-01-01

    Background Successful treatment of gliomas in or adjacent to language areas constitutes a major challenge to neurosurgery. The present study was performed to evaluate the procedure of language mapping via intraoperative direct cortical electrical stimulation under awake anaesthesia when performed prior to resective glioma surgery.Methods Thirty patients with gliomas and left-hemisphere dominance and, who underwent language mapping via intraoperative direct cortical electrical stimulation under awake anaesthesia before resective glioma surgery, were analyzed retrospectively. All patients had tumors in or adjacent to cortical language areas. The brain lesions were removed according to anatomic-functional boundaries with preservation of areas of language function. Both preoperative and postoperative functional findings were evaluated.Results Intraoperative language areas were detected in 20 patients but not in four patients. Language mapping failure for reasons attributable to the anaesthesia or to an intraoperative increase in intracranial pressure occurred in six cases.Seven patients presented with moderate or severe language deficits after six months of follow-up. Total resection was achieved in 14 cases, near-total resection in 12 cases and subtotal resection in four cases.Conclusions Intraoperative cortical electrical stimulation is an accurate and safe approach to identification of the language cortex. Awake craniotomy intraoperative cortical electrical stimulation, in combination with presurgical neurological functional imaging to identify the anatomic-functional boundaries of tumor resection, permits extensive tumor excision while preserving normal language function and minimizing the risk of postoperative language deficits.

  2. The mechanism of noradrenergic alpha 1 excitatory modulation of pontine reticular formation neurons.

    Science.gov (United States)

    Stevens, D R; McCarley, R W; Greene, R W

    1994-11-01

    The alpha 1 adrenergic receptor occurs in all major divisions of the CNS and is thought to play a role in all behaviors influenced by norepinephrine (NE). In the medial pontine reticular formation (mPRF), the proposed site of adrenergic enhancement of startle responses (Davis, 1984), alpha 1 agonists excite most neurons (Gerber et al., 1990). We here report that alpha 1 excitation results from a reduction of a voltage- and calcium-dependent potassium current, not previously recognized as ligand-modulated. The calcium sensitivity is suggested by its antagonism with Mg2+, Cd2+, Ba2+, low concentrations of tetraethylammonium, and charybdotoxin. The voltage sensitivity of this conductance falls within the membrane potential range critical to action potential generation. Based on this voltage sensitivity, the change in repetitive firing characteristics may be predicted according to a mathematical model of the mPRF neuronal electrophysiology. The predicted response to a 50% decrease in the phenylephrine (PE)-sensitive conductance is similar to the observed responses, with respect to both the current response under voltage-clamp conditions and alterations of the AHP and frequency/current curve. In contrast, modeling a reduction of a voltage-insensitive leak current predicts none of these changes. Thus, the noradrenergic reduction of this current depolarizes the membrane, increases the likelihood of an initial response to depolarizing input, and increases firing rate during sustained depolarization in a manner consistent with an NE role as an excitatory neuromodulator of the mPRF.

  3. Central pontine and extrapontine myelinolysis: from epileptic and other manifestations to cognitive prognosis.

    Science.gov (United States)

    Odier, Céline; Nguyen, Dang Khoa; Panisset, Michel

    2010-07-01

    The objective of this study is to review the presentation, outcome and aetiology of central pontine and extrapontine myelinolysis (CPEPM) in a tertiary hospital center. The study method is a case series and included identification of patients from University of Montreal Health Centre archives database (1995-2007). All diagnoses were confirmed by neuroimaging or brain autopsy. Twelve individuals (25-66 years old) presented heterogeneous manifestations. Co-morbidities included diabetes insipidus (n = 2), haemodialysis (n = 1), cirrhosis (n = 3), gastroenteritis (n = 2) and potomania (n = 1). Aetiologies included rapid correction of severe hyponatremia (n = 6)/acute hypernatremia (n = 1); immediate (n = 2) or remote (n = 1 with recurrent cirrhosis) orthotopic liver transplantation (OLT) with tacrolimus-induced immunosuppression (n = 3); and chronic alcoholism (n = 4, two with hyponatremia). Four individuals died acutely. Two were lost to follow-up. Six had good motor or cerebellar recovery. Neuropsychological evaluations (n = 5/6) revealed a subcortical/frontal dysfunction. Cognitive impairment represented the major remaining lasting sequel (n = 4). Three salient clinical syndromes were observed: (1) predominant cerebellar presentation in individuals with alcoholism (n = 4); (2) significant alteration of consciousness at presentation (n = 4), all resulting in death (OLT, n = 3); (3) seizures persisting after natremia correction (n = 2). Clinical presentation of CPEPM is heterogeneous and can even include seizures. Cognitive impairment should be screened as it is a significant factor limiting return to normal life.

  4. Severe hyponatraemia secondary to beer potomania complicated by central pontine myelinolysis.

    Science.gov (United States)

    Kelly, J; Wassif, W; Mitchard, J; Gardner, W N

    1998-01-01

    A case of severe hyponatraemia in a 56-year-old male alcohol misuser secondary to beer potomania is presented. In view of severe volume depletion and the patient's inability to drink, normal saline was cautiously infused. Despite initial improvement, he subsequently deteriorated neurologically. Magnetic resonance imaging demonstrated the classical lesion of central pontine myelinolysis (CPM). The rate of correction of plasma sodium was within limits normally considered safe. Beer potomania should be considered as a cause of hyponatraemia in alcohol misusers. Recognition is important as the electrolyte imbalance repairs simply with cessation of alcohol intake and institution of normal diet. Correction of chronic hyponatraemia by infusion of normal or hypertonic saline should not be attempted unless life-threatening neurological complications supervene. When the balance of risks favours correction, caution should be exercised, as CPM may occur. Although a rate of correction of plasma sodium of up to 10 mM per 24-hour period has been associated with a low risk of precipitating CPM, this case illustrates that a completely safe rate of correction probably cannot be defined.

  5. Incidence and mechanism of central pontine myelinolysis based on analysis of MRI images and risk factors

    Energy Technology Data Exchange (ETDEWEB)

    Kondo, Masato [Akita Univ. (Japan). School of Medicine

    2000-02-01

    In this study, the incidence of central pontine myelinolysis (CPM)-like lesions on MRI images was studied in 1917 subjects, 1,500 of which were psychiatric patients and 417 were patients attending a brain health examination. The CPM-like lesions were first classified into four groups based on the characteristics of their MRI images: group 1 showed symmetrical lesions on both T1 low and T2 high images and were considered to be typical CPM; group 2 showed symmetrical high intensity lesions only on T2 images; group 3 had asymmetrical lesions only on T2 images; and group 4 had asymmetrical lesions on both T1 low and T2 high images. Furthermore, the relationships of each group with particular risk factors, such as alcoholism, hypertension, hyperlipidemia were statistically analysed. The cause of CPM-like features in the MRI images were discussed. Among our subjects, the incidence of CPM-like lesions was 3.8%, and that of group 1 was 1.2%. Significant correlations between group 1 and alcoholism, and group 3 and 4 with brain ischemic lesions were observed. A previous hypothesis that group 2 may be a premature state of CPM is not supported by our results. (author)

  6. A case of bronchiectasis needing lung isolation for cerebello pontine angle tumor excision: Anesthetic challenges

    Directory of Open Access Journals (Sweden)

    C Srinivasan

    2016-01-01

    Full Text Available The main goals of neuroanesthesia are the maintenance of adequate cerebral perfusion pressure, avoidance of hypercarbia, hypoxemia, and to provide better brain relaxation. Providing anesthesia for a patient with bronchiectasis needing lung isolation for craniotomy can be challenging. A 56-year-old male patient, case of right lung bronchiectasis with a right cerebello pontine angle tumor underwent excision in the left lateral position. Since he had severe bronchiectasis of the right lung, we had isolated the right lung using right-sided double lumen tube to avoid spillage. Intraoperative split lung test was performed to assess the right lung contribution on carbon dioxide (CO 2 elimination and found that there was a significant contribution from the right lung. Hence, both lungs were ventilated to control CO 2 . The importance of lung isolation to prevent spillage and avoidance of one lung ventilation to control the arterial CO 2 are highlighted in this case report. By providing a balanced anesthetic keeping both, the neurosurgical and thoracic concerns are important for better postoperative outcome.

  7. Pontine abscess with initial treatment failure following infectious endocarditis with Streptococcus salivarius.

    Science.gov (United States)

    Knudtzen, Fredrikke Christie; Lynge, Maja; Gaini, Shahin

    2015-07-02

    We present a case report of a 65-year-old man admitted to the department of infectious diseases on suspicion of meningitis with headache, fever and double vision. A cerebral MRI revealed a 17×30 mm pontine abscess with surrounding oedema. The patient had, 2 months prior to admission, been treated for Streptococcus salivarius aortic valve endocarditis. The abscess was not suitable for surgery, and the patient received multidrug antibiotic treatment for 4 weeks. The patient initially responded well clinically, but was readmitted 4 weeks after discontinuation of treatment, with headache and dizziness. A new cerebral MRI showed progression of the abscess. He received an additional 8 weeks of broad spectrum antibiotic treatment, followed by 12 weeks of oral treatment with pivampicillin. His symptoms resolved and a cerebral MRI at discontinuation of treatment showed regression of the abscess to 7.5 mm. 2015 BMJ Publishing Group Ltd.

  8. Sleep duration varies as a function of glutamate and GABA in rat pontine reticular formation.

    Science.gov (United States)

    Watson, Christopher J; Lydic, Ralph; Baghdoyan, Helen A

    2011-08-01

    The oral part of the pontine reticular formation (PnO) is a component of the ascending reticular activating system and plays a role in the regulation of sleep and wakefulness. The PnO receives glutamatergic and GABAergic projections from many brain regions that regulate behavioral state. Indirect, pharmacological evidence has suggested that glutamatergic and GABAergic signaling within the PnO alters traits that characterize wakefulness and sleep. No previous studies have simultaneously measured endogenous glutamate and GABA from rat PnO in relation to sleep and wakefulness. The present study utilized in vivo microdialysis coupled on-line to capillary electrophoresis with laser-induced fluorescence to test the hypothesis that concentrations of glutamate and GABA in the PnO vary across the sleep/wake cycle. Concentrations of glutamate and GABA were significantly higher during wakefulness than during non-rapid eye movement sleep and rapid eye movement sleep. Regression analysis revealed that decreases in glutamate and GABA accounted for a significant portion of the variance in the duration of non-rapid eye movement sleep and rapid eye movement sleep episodes. These data provide novel support for the hypothesis that endogenous glutamate and GABA in the PnO contribute to the regulation of sleep duration.

  9. A dual functional fluorescent probe for glioma imaging mediated by blood-brain barrier penetration and glioma cell targeting.

    Science.gov (United States)

    Ma, Hongwei; Gao, Zhiyong; Yu, Panfeng; Shen, Shun; Liu, Yongmei; Xu, Bainan

    2014-06-20

    Glioma is a huge threat for human being because it was hard to be completely removed owing to both the infiltrating growth of glioma cells and integrity of blood brain barrier. Thus effectively imaging the glioma cells may pave a way for surgical removing of glioma. In this study, a fluorescent probe, Cy3, was anchored onto the terminal of AS1411, a glioma cell targeting aptamer, and then TGN, a BBB targeting peptide, was conjugated with Cy3-AS1411 through a PEG linker. The production, named AsT, was characterized by gel electrophoresis, (1)H NMR and FTIR. In vitro cellular uptake and glioma spheroid uptake demonstrated the AsT could not only be uptaken by both glioma and endothelial cells, but also penetrate through endothelial cell monolayer and uptake by glioma spheroids. In vivo, AsT could effectively target to glioma with high intensity. In conclusion, AsT could be used as an effective glioma imaging probe.

  10. Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Bin [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Hu, Zhiqiang, E-mail: zhiqhutg@126.com [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Huang, Hui; Zhu, Guangtong; Xiao, Zhiyong [Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038 (China); Wan, Weiqing; Zhang, Peng; Jia, Wang; Zhang, Liwei [Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100050 (China)

    2014-11-07

    Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

  11. IL-13Ra2- and glioma stem cell-pulsed dendritic cells induce glioma cell death in vitro

    Institute of Scientific and Technical Information of China (English)

    Ying Wang; Ruifan Xie; Hongquan Niu; Ting Lei

    2016-01-01

    Objective Gliomas are the most common malignant tumors in the central nervous system. Despite mul-tiple therapies including surgery, chemotherapy, and radiotherapy, the prognosis of patients remains poor. Immunotherapy is an alternative method of treating glioma, and the use of dendritic cel vaccines is one of the promising treatment options. However, there is no specific tumor cel antigen that can trigger dendritic cel s (DCs). IL-13Ra2 is a specific antigen expressed in glioma cel s; in the current study, we have at-tempted to explore whether IL-13Ra2 could be the antigen that triggers DCs and to envisage its application as potential therapy for glioma. Methods The expression of IL-13Ra2 was detected in U251 glioma cel lines and primary glioma tissues using dif erent methods. DCs from human blood were isolated and pulsed with recombinant IL-13Ra2, fol-lowing which the cytotoxicity of these DCs on glioma cel s was detected and analyzed. Results About 55.9% human glioma tissue cel s expressed IL-13Ra2, while normal brain tissue cel s did not show any expression. DC vaccines loaded with IL-13Ra2, glioma cel antigen, and brain tumor stem cel (BTSC) antigen could significantly stimulate the proliferation of T lymphocytes and induce cel death in the glioma tissue. Compared to other groups, DC vaccines loaded with BTSC antigen showed the strongest ability to activate cytotoxic T lymphocytes (CTLs), while the glioma cel antigen group showed no significant dif erence. Conclusion IL-13Ra2, which is expressed in gliomas and by glioma stem cel s, as wel as IL-13Ra2 could prove to be potential antigens for DC vaccine-based immunotherapy.

  12. Receptor-Mediated Drug Delivery Systems Targeting to Glioma

    Directory of Open Access Journals (Sweden)

    Shanshan Wang

    2015-12-01

    Full Text Available Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS. The complexity of glioma, especially the existence of the blood-brain barrier (BBB, makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications.

  13. BMPs as Therapeutic Targets and Biomarkers in Astrocytic Glioma

    Directory of Open Access Journals (Sweden)

    Pilar González-Gómez

    2014-01-01

    Full Text Available Astrocytic glioma is the most common brain tumor. The glioma initiating cell (GIC fraction of the tumor is considered as highly chemoresistant, suggesting that GICs are responsible for glioma relapse. A potential treatment for glioma is to induce differentiation of GICs to a more benign and/or druggable cell type. Given BMPs are among the most potent inducers of GIC differentiation, they have been considered as noncytotoxic therapeutic compounds that may be of use to prevent growth and recurrence of glioma. We herein summarize advances made in the understanding of the role of BMP signaling in astrocytic glioma, with a particular emphasis on the effects exerted on GICs. We discuss the prognostic value of BMP signaling components and the implications of BMPs in the differentiation of GICs and in their sensitization to alkylating drugs and oncolytic therapy/chemotherapy. This mechanistic insight may provide new opportunities for therapeutic intervention of brain cancer.

  14. Slit2/Robo1 signaling in glioma migration and invasion.

    Science.gov (United States)

    Xu, Yun; Li, Wen-Liang; Fu, Li; Gu, Feng; Ma, Yong-Jie

    2010-12-01

    Slit2/Robo1 is a conserved ligand-receptor system, which greatly affects the distribution, migration, axon guidance and branching of neuron cells. Slit2 and its transmembrane receptor Robo1 have different distribution patterns in gliomas. The expression of Slit2 is at very low levels in pilocytic astrocytoma, fibrillary astrocytoma and glioblastoma, while Robo1 is highly expressed in different grades of gliomas at both mRNA and protein levels. Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Although the specific mechanisms of tumor-suppressive effect of Slit2/Robo1 have not been elucidated, it has been proved that Slit2/Robo1 signaling inhibits glioma cell migration and invasion by inactivation of Cdc42-GTP. With the research development on the molecular mechanisms of Slit2/Robo1 signaling in glioma invasion and migration, Slit2/Robo1 signaling may become a potential target for glioma prevention and treatment.

  15. MICrocephaly, disproportionate pontine and cerebellar hypoplasia syndrome: A clinico-radiologic phenotype linked to calcium/calmodulin-dependent serine protein kinase gene mutation

    Directory of Open Access Journals (Sweden)

    Rashid Saleem

    2013-01-01

    Full Text Available MICrocephaly, disproportionate pontine and cerebellar hypoplasia (MICPCH syndrome, a rare X-linked disorder, generally seen in girls, is characterized by neurodevelopmental delay, microcephaly, and disproportionate pontine and cerebellar hypoplasia. It is caused by inactivating calcium/calmodulin-dependent serine protein kinase (CASK gene mutations. We report a 2-year-old girl with severe neurodevelopmental delay, microcephaly, minimal pontine hypoplasia, cerebellar hypoplasia, and normal looking corpus callosum, with whom the conventional cytogenetic studies turned out to be normal, and an array-comparative genomic hybridization (a-CGH analysis showed CASK gene duplication at Xp11.4. Our case highlights the importance of using clinico-radiologic phenotype to guide genetic investigation and it also confirms the role of a-CGH analysis in establishing the genetic diagnosis of MICPCH syndrome, when conventional cytogenetic studies are inconclusive.

  16. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

    with an AFM (2).    The intuitive explanation for the depletion based on "hydrophobic mismatch" between the obviously hydrophilic bulk phase of water next to the hydrophobic polymer. It would thus be an intrinsic property of all interfaces between non-matching materials. The detailed physical interaction path......  The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...

  17. GABAergic Transmission in Rat Pontine Reticular Formation Regulates the Induction Phase of Anesthesia and Modulates Hyperalgesia Caused by Sleep Deprivation

    OpenAIRE

    Vanini, Giancarlo; Nemanis, Kriste; Baghdoyan, Helen A.; Lydic, Ralph

    2014-01-01

    The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia, and pain. The role of PnO GABA in modulating these states remains incompletely understood. The present study used time to Loss and time to Resumption of Righting Response (LoRR and RoRR) as surrogate measures of loss and resumption of consciousness. This study tested three hypotheses: (1) pharmacologically manipulating GABA levels in rat PnO alters LoRR, RoRR, and nociception; (2) propof...

  18. Living and dead benthic foraminiferal assemblages from bathyal environment in the Pontine Archipelago (Tyrrhenian Sea, Italy)

    Science.gov (United States)

    Di Bella, Letizia; Frezza, Virgilio; Ingrassia, Michela; Latino Chiocci, Francesco; Martorelli, Eleonora

    2016-04-01

    The western Pontine Archipelago (Tyrrhenian Sea, Italy), located about 30 km away from the Italian Peninsula, is composed of three volcanic islands (Ponza, Palmarola and Zannone). Sedimentological and micropaleontological characterization of the infralittoral and circalittoral zones in the Pontine Archipelago was already been studied, whereas it is lacking for deeper environments. The present study shows the preliminary micropaleontological results carried out on samples collected in the bathyal zone (at 500 mwd) in the Ventotene basin. Sediment samples, high resolution multibeam bathymetry, biological and video data were acquired in order to characterise both the morphological and biological features of study area, during the research cruise "BOLLE 2014" carried out on June 2014 aboard to the R/V Urania. Sediment samples were collected with a multi-corer, that allowed sampling of the upper decimetre of the sediments column. Successively, each core was sliced horizontally every 1 cm from the top to the bottom. For micropaleontological analyses, all samples were stained with Rose Bengal to distinguish living and dead assemblages. For each interval of the core all living specimens and 200 dead benthic foraminifera were classified and counted. Diversity index (α-Fisher, Shannon indices) and Faunal Density (specimens/gr) were calculated to define the structure of the assemblage. A variable number of living benthic foraminifera (Rose Bengal-stained) were found in all core-intervals (7-155 tests), with the Faunal Density ranging from 3 to 82 specimens/gr. A total of 77 species are recognised from living benthic foraminiferal assemblages, with a range of 4-31 species found in each core-interval. The α-Fisher index ranges between 3.88 and 43.45, whereas Shannon index shows a more limited variability (1.28-2.92). Among the living foraminifera, calcareous imperforate tests are very abundant, with percentages ranging between 33.3 and 100%; perforate species are subordinate

  19. Activity of lysosomal exoglycosidases in human gliomas.

    Science.gov (United States)

    Wielgat, P; Walczuk, U; Szajda, S; Bień, M; Zimnoch, L; Mariak, Z; Zwierz, K

    2006-12-01

    There is a lot of data suggesting that modifications of cell glycoconjugates may be important in progression of cancer. In the present work we studied activities of lysosomal exoglycosidases: beta-hexosaminidase and its isoenzymes A and B, beta-galactosidase and alpha-mannosidase, in human gliomas. Enzyme activity was determined spectrophotometrically based on the release of p-nitrophenol from p-nitrophenyl-derivative of appropriate sugars. The activities of the exoglycosidases tested were significantly higher in malignant glial tumors than in control tissue (normal brain tissue) and non-glial tumors. The highest activities of exoglycosidases were observed in high-grade gliomas, and a positive correlation of enzyme activities and degree of malignancy was noted. Our results suggest that lysosomal exoglycosidases may participate in the progression and dynamical development of glial tumors.

  20. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

    Science.gov (United States)

    Datta, Subimal; O'Malley, Matthew W .

    2013-01-01

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

  1. Neuronal Correlates of Cross-Modal Transfer in the Cerebellum and Pontine Nuclei

    Science.gov (United States)

    Campolattaro, Matthew M.; Kashef, Alireza; Lee, Inah; Freeman, John H.

    2011-01-01

    Cross-modal transfer occurs when learning established with a stimulus from one sensory modality facilitates subsequent learning with a new stimulus from a different sensory modality. The current study examined neuronal correlates of cross-modal transfer of Pavlovian eyeblink conditioning in rats. Neuronal activity was recorded from tetrodes within the anterior interpositus nucleus (IPN) of the cerebellum and basilar pontine nucleus (PN) during different phases of training. After stimulus pre-exposure and unpaired training sessions with a tone conditioned stimulus (CS), light CS, and periorbital stimulation unconditioned stimulus (US), rats received associative training with one of the CSs and the US (CS1-US). Training then continued on the same day with the other CS to assess cross-modal transfer (CS2-US). The final training session included associative training with both CSs on separate trials to establish stronger cross-modal transfer (CS1/CS2). Neurons in the IPN and PN showed primarily unimodal responses during pre-training sessions. Learning-related facilitation of activity correlated with the conditioned response (CR) developed in the IPN and PN during CS1-US training. Subsequent CS2-US training resulted in acquisition of CRs and learning-related neuronal activity in the IPN but substantially less little learning-related activity in the PN. Additional CS1/CS2 training increased CRs and learning-related activity in the IPN and PN during CS2-US trials. The findings suggest that cross-modal neuronal plasticity in the PN is driven by excitatory feedback from the IPN to the PN. Interacting plasticity mechanisms in the IPN and PN may underlie behavioral cross-modal transfer in eyeblink conditioning. PMID:21411647

  2. Off the beaten path: drug addiction and the pontine laterodorsal tegmentum.

    Science.gov (United States)

    Kohlmeier, Kristi A

    2013-01-01

    Drug addiction is a multileveled behavior controlled by interactions among many diverse neuronal groups involving several neurotransmitter systems. The involvement of brainstem-sourced, cholinergic neurotransmission in the development of addiction and in the persistent physiological processes that drive this maladaptive behavior has not been widely investigated. The major cholinergic input to neurons in the midbrain which are instrumental in assessment of reward and assignment of salience to stimuli, including drugs of abuse, sources from acetylcholine- (ACh-) containing pontine neurons of the laterodorsal tegmentum (LDT). Excitatory LDT input, likely cholinergic, is critical in allowing behaviorally relevant neuronal firing patterns within midbrain reward circuitry. Via this control, the LDT is positioned to be importantly involved in development of compulsive, addictive patterns of behavior. The goal of this review is to present the anatomical, physiological, and behavioral evidence suggesting a role of the LDT in the neurobiology underlying addiction to drugs of abuse. Although focus is directed on the evidence supporting a vital participation of the cholinergic neurons of the LDT, data indicating a contribution of noncholinergic LDT neurons to processes underlying addiction are also reviewed. While sparse, available information of actions of drugs of abuse on LDT cells and the output of these neurons as well as their influence on addiction-related behavior are also presented. Taken together, data from studies presented in this review strongly support the position that the LDT is a major player in the neurobiology of drug addiction. Accordingly, the LDT may serve as a future treatment target for efficacious pharmaceutical combat of drug addiction.

  3. Fear extinction memory consolidation requires potentiation of pontine-wave activity during REM sleep.

    Science.gov (United States)

    Datta, Subimal; O'Malley, Matthew W

    2013-03-06

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction.

  4. Intrinsically Disordered Energy Landscapes

    Science.gov (United States)

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-05-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium.

  5. Musical hallucinations following insular glioma resection.

    Science.gov (United States)

    Isolan, Gustavo Rassier; Bianchin, Marino Muxfeldt; Bragatti, José Augusto; Torres, Carolina; Schwartsmann, Gilberto

    2010-02-01

    Hallucinations can be auditory, visual, tactile, gustatory, or olfactory, and can be caused by psychiatric (such as schizophrenia and depression), neurological (such as cerebrovascular accidents, neoplasia, and infection), or endocrine and metabolic disorders. Musical hallucinations related to neurological disorders are rare. The authors present a case of a patient with a right insular glioma who developed transient musical hallucinations after microsurgical resection of the tumor.

  6. CURRENT APPROACHES TO CHEMORADIOTHERAPY FOR MALIGNANT GLIOMAS

    Directory of Open Access Journals (Sweden)

    Ye. L. Choinzonov

    2014-01-01

    Full Text Available High-grade malignant gliomas (WHO grade G III–IV account for more than 50% of all primary brain tumors. Despite aggressive treatment, survival rates are still very low with a median reported survival of no more than 1.5 years.Radiation therapy is an integral part of the combined treatment, but often does not influence lethally on resistant tumor cells. Thereby, in recent decades there has been an active search for novel approaches to the treatment of malignant gliomas (chemotherapeutic drugs, biological modifiers, local hyperthermia. Experimental data showed that the effect of high temperatures has both a direct damaging effect on tumor cells and a sensitizing effect. Significant advantages are achieved when the complex treatment of different malignant tumorsincludes local hyperthermia. However data on the treatment of patients with primary and recurrent gliomas G III–IV using local hyperthermia are scarce.The literature review is given in the article provides an overview of the existing treatment methods for brain tumors.

  7. Value of MRI for the diagnosis of pontine infarction%磁共振成像在脑桥梗死诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    殷雁; 金钰; 孙庆华; 尹琳

    2012-01-01

    目的 探讨脑桥梗死的临床与MRI特征.方法 回顾性分析96例脑桥梗死患者的临床资料,评估危险因素,分析临床与MRI特点.结果 首发临床表现复杂多样,96例患者中,头晕或眩晕79例(82.29%),肢体活动不便76例(79.17%),构音障碍54例(56.25%),中枢性面瘫49例(51.04%),感觉障碍31例(32.29%),中枢性舌瘫25例(26.04%)等表现最常见;多表现为病灶对侧的中枢性面瘫和(或)舌瘫合并肢体瘫和(或)无感觉障碍,而经典脑桥综合征3例(3.13%);病灶在脑桥上段21例(21.88%),中段62例(64.58%),下段13例(13.54%);腹内侧41例(42.71%),腹外侧22例(22.92%),中部16例(16.67%),背内侧11例(11.46%),背外侧6例(6.25%).结论 脑桥梗死常见临床表现为头晕或眩晕,肢体活动受限,构音障碍,中枢性面瘫,感觉障碍,中枢性舌瘫.交叉症状或体征在脑桥梗死患者中并不常见,经典的脑桥综合征病例少见.脑桥梗死以中段最常见,尤其是腹内侧.MRI对脑桥梗死的诊断有极其重要的意义.%Objective To study the clinical and MRI features of pontine infarction. Methods The clinical data about 96 patients with pontine infarction were retrospectively analyzed. Its risk factors were assessed. Clinical and MRI features of pontine infarction were analyzed. Results Among the 96 patients with different clinical manifestations, dizziness or vertigo was found in 79 (82. 29%),limb paralysis in 76(79. 17%) , barylalia in 54 (56. 25%) , central facial palsy in 49 (51. 04%), sensory disturbance in 31(32. 29%),central tongue palsy in 25(26.04%) respectively. Pontine infarction was usually manifested as contralateral central facial and/or tongue palsy accompanying limb paralysis and/or sensory disturbance. Three patients were diagnosed with classical pontine syndrome. Lesions were found in the upper,middle and lower pontine of 21(21. 88%) , 62(64. 58%) and 13(13. 54%)patients, respectively,and in the ventral

  8. Gaussian Intrinsic Entanglement

    Science.gov (United States)

    Mišta, Ladislav; Tatham, Richard

    2016-12-01

    We introduce a cryptographically motivated quantifier of entanglement in bipartite Gaussian systems called Gaussian intrinsic entanglement (GIE). The GIE is defined as the optimized mutual information of a Gaussian distribution of outcomes of measurements on parts of a system, conditioned on the outcomes of a measurement on a purifying subsystem. We show that GIE vanishes only on separable states and exhibits monotonicity under Gaussian local trace-preserving operations and classical communication. In the two-mode case, we compute GIE for all pure states as well as for several important classes of symmetric and asymmetric mixed states. Surprisingly, in all of these cases, GIE is equal to Gaussian Rényi-2 entanglement. As GIE is operationally associated with the secret-key agreement protocol and can be computed for several important classes of states, it offers a compromise between computable and physically meaningful entanglement quantifiers.

  9. Intrinsic Time Quantum Gravity

    CERN Document Server

    Yu, Hoi Lai

    2016-01-01

    Correct identification of the true gauge symmetry of General Relativity being 3d spatial diffeomorphism invariant(3dDI) (not the conventional infinite tensor product group with principle fibre bundle structure), together with intrinsic time extracted from clean decomposition of the canonical structure yields a self-consistent theory of quantum gravity. A new set of fundamental commutation relations is also presented. The basic variables are the eight components of the unimodular part of the spatial dreibein and eight SU(3) generators which correspond to Klauder's momentric variables that characterize a free theory of quantum gravity. The commutation relations are not canonical, but have well defined group theoretical meanings. All fundamental entities are dimensionless; and the quantum wave functionals are preferentially in the dreibein representation. The successful quantum theory of gravity involves only broad spectrum of knowledge and deep insights but no exotic idea.

  10. Conditioned medium from neural stem cells inhibits glioma cell growth.

    Science.gov (United States)

    Li, Z; Zhong, Q; Liu, H; Liu, P; Wu, J; Ma, D; Chen, X; Yang, X

    2016-10-31

    Malignant glioma is one of the most common brain tumors in the central nervous system. Although the significant progress has been made in recent years, the mortality is still high and 5-year survival rate is still very low. One of the leading causes to the high mortality for glioma patients is metastasis and invasion. An efficient method to control the tumor metastasis is a promising way to treat the glioma. Previous reports indicated that neural stem cells (NSCs) were served as a delivery vector to the anti-glioma therapy. Here, we used the conditioned medium from rat NSCs (NSC-CM) to culture the human glioblastoma cell lines. We found that NSC-CM could inhibit the glioma cell growth, invasion and migration in vitro and attenuate the tumor growth in vivo. Furthermore, this anti-glioma effect was mediated by the inactivation of mitogen activated protein kinase (MAPK) pathway. Above all, this study provided the direct evidence to put forward a simple and efficient method in the inhibition of glioma cells/tumor growth, potentially advancing the anti-glioma therapy.

  11. Expression and prognostic value of JAM-A in gliomas

    DEFF Research Database (Denmark)

    Rosager, Ann Mari; Sørensen, Mia D; Dahlrot, Rikke H

    2017-01-01

    in WHO grade II and III gliomas. JAM-A protein expression was evaluated by immunohistochemistry and advanced quantitative image analysis with continuous estimates of staining intensity. The JAM-A antibody stained tumor cell membranes and cytoplasm to various extent in different glioma subtypes...

  12. Repeating hemorrhage after radiotherapy for glioma. Radiological and histological observations

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Hirokazu [Miyakonojo Medical Association Hospital, Miyazaki (Japan); Wakisaka, Shinichiro; Kubota, Toshihiko; Hosotani, Kazuo

    1998-02-01

    A case of radiation necrosis which was observed six years after radiotherapy for a glioma in the right parietal lobe is reported. This patient developed hemiparesis, and radiological examinations showed similar findings consisted with recurrent glioma. Histological examination disclosed that the lesion is correspond to the radiation necrosis. (author)

  13. A role for ion channels in perivascular glioma invasion.

    Science.gov (United States)

    Thompson, Emily G; Sontheimer, Harald

    2016-10-01

    Malignant gliomas are devastating tumors, frequently killing those diagnosed in little over a year. The profuse infiltration of glioma cells into healthy tissue surrounding the main tumor mass is one of the major obstacles limiting the improvement of patient survival. Migration along the abluminal side of blood vessels is one of the salient features of glioma cell invasion. Invading glioma cells are attracted to the vascular network, in part by the neuropeptide bradykinin, where glioma cells actively modify the gliovascular interface and undergo volumetric alterations to navigate the confined space. Critical to these volume modifications is a proposed hydrodynamic model that involves the flux of ions in and out of the cell, followed by osmotically obligated water. Ion and water channels expressed by the glioma cell are essential in this model of invasion and make opportune therapeutic targets. Lastly, there is growing evidence that vascular-associated glioma cells are able to control the vascular tone, presumably to free up space for invasion and growth. The unique mechanisms that enable perivascular glioma invasion may offer critical targets for therapeutic intervention in this devastating disease. Indeed, a chloride channel-blocking peptide has already been successfully tested in human clinical trials.

  14. Vasculogenic mimicry:a novel target for glioma therapy

    Institute of Scientific and Technical Information of China (English)

    Yin-Sheng Chen; Zhong-Ping Chen

    2014-01-01

    Anti-angiogenic therapy has shown promising but insufficient efficacy on gliomas. Recent studies suggest that vasculogenic mimicry (VM), or the formation of non-endothelial, tumor-cel-lined microvascular channels, occurs in aggressive tumors, including gliomas. There is also evidence of a physiological connection between the endothelial-lined vasculature and VM channels. Tumor cels, by virtue of their high plasticity, can form vessel-like structures themselves, which may function as blood supply networks. Our previous study on gliomas showed that microvessel density was comparably less in VM-positive tumors than in VM-negative tumors. Thus, VM may act as a complement to ensure tumor blood supply, especialy in regions with less microvessel density. Patients with VM-positive gliomas survived a shorter period of time than did patients with VM-negative gliomas. Although the detailed molecular mechanisms for VM are not fuly understood, glioma stem cels might play a key role, since they are involved in tumor tissue remodeling and contribute to neovascularization via transdifferentiation. In the future, successful treatment of gliomas should involve targeting both VM and angiogenesis. In this review, we summarize the progress and chalenges of VM in gliomas.

  15. Interaction between 5 genetic variants and allergy in glioma risk

    DEFF Research Database (Denmark)

    Schoemaker, Minouk J; Robertson, Lindsay; Wigertz, Annette

    2010-01-01

    The etiology of glioma is barely known. Epidemiologic studies have provided evidence for an inverse relation between glioma risk and allergic disease. Genome-wide association data have identified common genetic variants at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756...

  16. The AAA+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors.

    Science.gov (United States)

    Matias, Pedro M; Baek, Sung Hee; Bandeiras, Tiago M; Dutta, Anindya; Houry, Walid A; Llorca, Oscar; Rosenbaum, Jean

    2015-01-01

    Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10-12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models.

  17. The AAA+ proteins Pontin and Reptin enter adult age: From understanding their basic biology to the identification of selective inhibitors

    Directory of Open Access Journals (Sweden)

    Pedro M Matias

    2015-05-01

    Full Text Available Pontin and Reptin are related partner proteins belonging to the AAA+ (ATPases Associated with various cellular Activities family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10-12, 2014, and reported significant new advances on the mechanisms of action of these two AAA+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models.

  18. Recurrent Hemorrhagic Venous Infarctions Caused by Thrombosis of a Pontine Developmental Venous Anomaly and Protein S Mutation.

    Science.gov (United States)

    Nakamura, Yuri; Takase, Kei-Ichiro; Matsushita, Takuya; Yoshimura, Satoshi; Yamasaki, Ryo; Murai, Hiroyuki; Kikuchi, Kazufumi; Kira, Jun-Ichi

    2016-11-01

    A 34-year-old man presented with an acute onset of upbeat nystagmus, slurred speech, and limb and truncal ataxias. The patient had a history of limb ataxia and gait disturbance previously treated as brainstem encephalitis with corticosteroids 3 years previously. Brain magnetic resonance imaging showed pontine developmental venous anomaly (DVA) and hemorrhagic infarction within the drainage territory of the DVA. Three months later, the patient exhibited recurrent limb ataxia, double vision, and numbness of the left side of the body. The brain magnetic resonance imaging revealed recurrent hemorrhagic venous infarction within the same territory of the pontine DVA. Laboratory tests disclosed a hypercoagulable state owing to a decrease of protein S activity despite the normal antigen level. Genetic testing indicated that the patient was a homozygous carrier of protein S Tokushima. The patient's severe disability remained unchanged in spite of treatment with anticoagulation therapy using warfarin. We propose that further research on hereditary coagulopathy be carried out in patients with recurrent episodes of DVA-related infarction.

  19. Complete clinical recovery of a central pontine and extrapontine myelinolysis delayed onset in a child with acute myeloblastic leukemia.

    Science.gov (United States)

    Yilmaz, D; Karapinar, B; Balkan, C; Ay, Y; Kavakli, K

    2011-02-01

    Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with the demyelination of extrapontine areas of the central nervous system. It typically occurs 0.5-7 days after a rapid increment in serum Na level in hyponatremic patients and may lead to death. A 2.5-year-old child with a diagnosis of acute myeloblastic leukemia developed febril neutropenia, diarrhea, gastrointestinal hemorrhage followed by pulmonary aspergillosis. He could not tolerate enteral nutrition. He was given broad spectrum antibiotics and antifungal treatment. Laboratory tests showed electrolyte abnormalities including hyponatremia, hypokalemia and hypophosphatemia in a chronic course. Twenty three days after a rapid correction of hyponatremia (16 mEq/L/24 h) he revealed flask quadriparesis, disphagia, mutism, irregular respiratory pattern and loss of cough and gag reflex. Cranial magnetic resonance showed central pontine and extrapontine myelinolysis. He required mechanical ventilation and then he regained his neurologic functions. He completed chemotherapy protocol and underwent hematopoietic stem cell transplantation. After 2.5 years of the occurrence of CPM he is in completely normal physical and neurological status. CPM is a very severe but rare disorder in children with underlying disease. In the presence of multiple etiologic factors it may reveal a delayed onset and optimum outcome can be seen even in the severe clinical presentation with adequate intensive support.

  20. Glioma Association and Balancing Selection of ZFPM2.

    Directory of Open Access Journals (Sweden)

    Shui-Ying Tsang

    Full Text Available ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain, uterus and smooth muscles, plays important roles in cardiac and gonadal development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has been reported but hitherto its genetic association with cancer and effects on gliomas have not been studied. In the present study, the hexamer insertion-deletion polymorphism rs71305152, located within a large haplotype block spanning intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n = 350, non-glioma cancer (n = 354 and healthy control (n = 463 by direct sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression in glioma tissues (n = 69 of different grades was quantified by real-time RT-PCR. Moreover, potential natural selection pressure acting on the gene was investigated. Disease-association analysis showed that the overall genotype of rs71305152 was significantly associated with gliomas (P = 0.016, and the heterozygous genotype compared to the combined homozygous genotypes was less frequent in gliomas than in controls (P = 0.005 or non-glioma cancers (P = 0.020. ZFPM2 mRNA expression was negatively correlated with the grades of gliomas (P = 0.002, with higher expression levels in the low-grade gliomas. In the astrocytoma subtype, higher ZFPM2 expression was also correlated with the rs71305152 heterozygous genotype (P = 0.028. In addition, summary statistics tests gave highly positive values, demonstrating that the gene is under the influence of balancing selection. These findings suggest that ZFPM2 is a glioma susceptibility gene, its genotype and expression showing associations with incidence and severity, respectively. Moreover, the balancing selection acting on ZFPM2 may be related to the important roles it has to play in multiple organ development or associated disease etiology.

  1. Clinical significance of vasculogenic mimicry in human gliomas.

    Science.gov (United States)

    Liu, Xiao-mei; Zhang, Qing-ping; Mu, Yong-gao; Zhang, Xiang-hen; Sai, Ke; Pang, Jesse Chung-Sean; Ng, Ho-Keung; Chen, Zhong-ping

    2011-11-01

    Vasculogenic mimicry (VM) is known as non-endothelial tumor cell-lined microvascular channels in aggressive tumors. We have previously found the presence of VM in high-grade gliomas. In this study, we aimed to identify VM patterns in gliomas and to explore their clinical significance. Tumor samples as well as their detailed clinical/prognostic data were collected from 101 patients. Vasculogenic mimicry in the glioma samples was determined by dual staining for endothelial marker CD34 and periodic acid-Schiff (PAS). Tumor samples were also immunohistochemically stained for Ki-67, VEGF, COX-2 and MMP-9. The association between VM and the clinical characteristics of the patients were analyzed. A Kaplan-Meier survival analysis and log-rank tests were performed to compare survival times of the patients. Vasculogenic mimicry was present in 13 out of 101 samples. The higher grade gliomas had a higher incidence of VM than that of lower grade gliomas (P = 0.006). Vasculogenic mimicry channels were associated with the expression of COX-2 and MMP-9 (P age and preoperative epilepsy of the patients, or expression of Ki-67 and VEGF. However, patients with VM-positive gliomas survived a shorter period of time than those with VM negative gliomas (P = 0.027). Interestingly, in high-grade gliomas, the level of microvascular density was lower in VM positive tumors than those VM negative tumors (P = 0.039). Our results suggest that VM channels in gliomas correlate with increasing malignancy and higher aggressiveness, and may provide a complementation to the tumor's blood supply, especially in less vascularized regions, which may aid in the identification of glioma patients with a poorer prognosis.

  2. Morbidity profile following aggressive resection of parietal lobe gliomas.

    Science.gov (United States)

    Sanai, Nader; Martino, Juan; Berger, Mitchel S

    2012-06-01

    The impact of parietal lobe gliomas is typically studied in the context of parietal lobe syndromes. However, critical language pathways traverse the parietal lobe and are susceptible during tumor resection. The authors of this study reviewed their experience with parietal gliomas to characterize the impact of resection and the morbidity associated with language. The study population included adults who had undergone resection of parietal gliomas of all grades. Tumor location was identified according to a proposed classification system for parietal region gliomas. Low- and high-grade tumors were volumetrically analyzed using FLAIR and T1-weighted contrast-enhanced MR imaging. One hundred nineteen patients with parietal gliomas were identified--34 with low-grade gliomas and 85 with high-grade gliomas. The median patient age was 45 years, and most patients (53) presented with seizures, whereas only 4 patients had an appreciable parietal lobe syndrome. The median preoperative tumor volume was 31.3 cm(3), the median extent of resection was 96%, and the median postoperative tumor volume was 0.9 cm(3). Surprisingly, the most common early postoperative neurological deficit was dysphasia (16 patients), not weakness (12 patients), sensory deficits (14 patients), or parietal lobe syndrome (10 patients). A proposed parietal glioma classification system, based on surgical anatomy, was predictive of language deficits. This is the largest reported experience with parietal lobe gliomas. The findings suggested that parietal language pathways are compromised at a surprisingly high rate. The proposed parietal glioma classification system is predictive of postoperative morbidity associated with language and can assist with preoperative planning. Taken together, these data emphasize the value of identifying language pathways when operating within the parietal lobe.

  3. Cognitive impairments in patients with low grade gliomas and high grade gliomas

    Directory of Open Access Journals (Sweden)

    Eliane C. Miotto

    2011-08-01

    Full Text Available OBJECTIVE: The relationship between brain tumors and cognitive deficits is well established in the literature. However, studies investigating the cognitive status in low and high-grade gliomas patients are scarce, particularly in patients with average or lower educational level. This study aimed at investigating the cognitive functioning in a sample of patients with low and high-grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19 and high-grade glioma (G2, n=8 patients underwent a detailed neuropsychological assessment of memory, executive functions, visuo-perceptive and visuo-spatial abilities, intellectual level and language. RESULTS: There was a significant impairment on verbal and visual episodic memory, executive functions including mental flexibility, nominal and categorical verbal fluency and speed of information processing in G2. G1 showed only specific deficits on verbal and visual memory recall, mental flexibility and processing speed. CONCLUSION: These findings demonstrated different levels of impairments in the executive and memory domains in patients with low and high grade gliomas.

  4. Neurofibromatosis type 1 associated low grade gliomas : A comparison with sporadic low grade gliomas

    NARCIS (Netherlands)

    Helfferich, Jelte; Nijmeijer, Ronald; Brouwer, Oebele F.; Boon, Maartje; Fock, Annemarie; Hoving, Eelco W.; Meijer, Lisethe; den Dunnen, Wilfred F. A.; de Bont, Eveline S. J. M.

    2016-01-01

    Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, associated with a variable clinical phenotype including cafe-au-lait spots, intertriginous freckling, Lisch nodules, neurofibromas, optic pathway gliomas and distinctive bony lesions. NF1 is caused by a mutation in the NF1 gene, which

  5. Role of MRI in the management of children with diffuse pontine tumors: a study of 15 patients and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Kornreich, Liora; Schwarz, Michael; Karmazyn, Boaz; Horev, Gadi [Schneider Children' s Medical Center of Israel, Department of Imaging, Petah Tiqva (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Cohen, Ian J.; Shuper, Avinoam; Yaniv, Issac [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Schneider Children' s Medical Center of Israel, Department of Hematology-Oncology, Petah Tiqva (Israel); Michovitz, Shalom [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Schneider Children' s Medical Center of Israel, Department of Neurosurgery, Petah Tiqva (Israel); Fenig, Eyal [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Rabin Medical Center,Beilinson Campus, Institute of Oncology, Radiotherapy Unit, Petah Tiqva (Israel)

    2005-09-01

    Pontine tumors carry the worst prognosis of all brain tumors. In most cases, the diagnosis is based solely on MR imaging, without biopsy. To describe the MR findings of pontine tumors at diagnosis and during follow-up and correlate those with prognosis and to assess the value of MR imaging in patient management compared to clinical evaluation. Ninety-one MR scans of 15 children with diffuse pontine tumors were reviewed at diagnosis and during follow-up. The parameters analyzed were as follows: tumor extent, area, and volume; encasement of the basilar artery; presence of exophytic component; necrosis; cysts; hydrocephalus; and intensity and enhancement. Findings were correlated to length of progression-free and overall survival. Trends of amelioration or worsening on imaging were compared with the clinical findings. Median length of progression-free survival was 10 months, and median survival was 20 months. Only hydrocephalus at presentation was associated with shorter progression-free survival (P=0.02). On the last examination of each patient, the craniocaudal diameter was significantly greater than at diagnosis (P=0.03). The concordance between the imaging and the clinical findings was good. MR is the mainstay for the diagnosis and management of pontine tumors. Cranial growth seems to be an ominous sign. However, the prognostic value of MR is limited. MR findings correlate well with the clinical examination. (orig.)

  6. The ascending reticular activating system from pontine reticular formation to the hypothalamus in the human brain: a diffusion tensor imaging study.

    Science.gov (United States)

    Jang, Sung Ho; Kwon, Hyeok Gyu

    2015-03-17

    The ascending reticular activating system (ARAS) is responsible for regulation of consciousness. Precise evaluation of the ARAS is important for diagnosis and management of patients with impaired consciousness. In the current study, we attempted to reconstruct the portion of the ARAS from the pontine reticular formation (RF) to the hypothalamus in normal subjects, using diffusion tensor imaging (DTI). A total of 31 healthy subjects were recruited for this study. DTI scanning was performed using 1.5-T, and the ARAS from the pontine RF to the hypothalamus was reconstructed. Values of fractional anisotropy, mean diffusivity, and tract volume of the ARAS from the pontine RF to the hypothalamus were measured. In all subjects, the ARAS from the pontine RF to the hypothalamus originated from the RF at the level of the mid-pons, where the trigeminal nerve could be seen, ascended through the periaqueductal gray matter of the midbrain anterolaterally to the anterior commissure level, and then terminated into the hypothalamus. No significant differences in DTI parameters were observed between the left and right hemispheres and between males and females (phypothalamus in normal subjects using DTI. We believe that the reconstruction methodology and the results of this study would be useful to clinicians involved in the care of patients with impaired consciousness and researchers in studies of the ARAS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Reconstructing production technology and distribution, using thin section petrography: A pilot study of Roman pottery production in the Pontine region, Central Italy

    NARCIS (Netherlands)

    Borgers, B.; Tol, G.; de Haas, T.

    2016-01-01

    This paper explores aspects of production and distribution of local Roman pottery from the Pontine region, Central Italy, based on ceramics recovered in surveys carried out within the ‘Minor Centres’ project. The aim of this project was to investigate the role of minor centres in local economies of

  8. Intraoperative optical biopsy for brain tumors using spectro-lifetime properties of intrinsic fluorophores

    Science.gov (United States)

    Vasefi, Fartash; Kittle, David S.; Nie, Zhaojun; Falcone, Christina; Patil, Chirag G.; Chu, Ray M.; Mamelak, Adam N.; Black, Keith L.; Butte, Pramod V.

    2016-04-01

    We have developed and tested a system for real-time intra-operative optical identification and classification of brain tissues using time-resolved fluorescence spectroscopy (TRFS). A supervised learning algorithm using linear discriminant analysis (LDA) employing selected intrinsic fluorescence decay temporal points in 6 spectral bands was employed to maximize statistical significance difference between training groups. The linear discriminant analysis on in vivo human tissues obtained by TRFS measurements (N = 35) were validated by histopathologic analysis and neuronavigation correlation to pre-operative MRI images. These results demonstrate that TRFS can differentiate between normal cortex, white matter and glioma.

  9. REM sleep modulation by perifornical orexinergic inputs to the pedunculo-pontine tegmental neurons in rats.

    Science.gov (United States)

    Khanday, M A; Mallick, B N

    2015-11-12

    Rapid eye movement sleep (REMS) is regulated by the interaction of the REM-ON and REM-OFF neurons located in the pedunculo-pontine-tegmentum (PPT) and the locus coeruleus (LC), respectively. Many other brain areas, particularly those controlling non-REMS (NREMS) and waking, modulate REMS by modulating these REMS-related neurons. Perifornical (PeF) orexin (Ox)-ergic neurons are reported to increase waking and reduce NREMS as well as REMS; dysfunction of the PeF neurons are related to REMS loss-associated disorders. Hence, we were interested in understanding the neural mechanism of PeF-induced REMS modulation. As a first step we have recently reported that PeF Ox-ergic neurons modulate REMS by influencing the LC neurons (site for REM-OFF neurons). Thereafter, in this in vivo study we have explored the role of PeF inputs on the PPT neurons (site for REM-ON neurons) for the regulation of REMS. Chronic male rats were surgically prepared with implanted bilateral cannulae in PeF and PPT and electrodes for recording sleep-waking patterns. After post-surgical recovery sleep-waking-REMS were recorded when bilateral PeF neurons were stimulated by glutamate and simultaneously bilateral PPT neurons were infused with either saline or orexin receptor1 (OX1R) antagonist. It was observed that PeF stimulation increased waking and decreased NREMS as well as REMS, which were prevented by OX1R antagonist into the PPT. We conclude that the PeF stimulation-induced reduction in REMS was likely to be due to inhibition of REM-ON neurons in the PPT. As waking and NREMS are inversely related, subject to confirmation, the reduction in NREMS could be due to increased waking or vice versa. Based on our findings from this and earlier studies we have proposed a model showing connections between PeF- and PPT-neurons for REMS regulation.

  10. PCR-Based Simple Subgrouping Is Validated for Classification of Gliomas and Defines Negative Prognostic Copy Number Aberrations in IDH Mutant Gliomas.

    Directory of Open Access Journals (Sweden)

    Shunsuke Nakae

    Full Text Available Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1 mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS and overall survival (OS of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, -9p, and -11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas.

  11. A review of the role of stem cells in the development and treatment of glioma.

    Science.gov (United States)

    Heywood, Richard M; Marcus, Hani J; Ryan, David J; Piccirillo, Sara G M; Al-Mayhani, Talal M Fael; Watts, Colin

    2012-06-01

    The neurosurgical management of patients with intrinsic glial cancers is one of the most rapidly evolving areas of practice. This has been fuelled by advances in surgical technique not only in cytoreduction but also in drug delivery. Further innovation will depend on a deeper understanding of the biology of the disease and an appreciation of the limitations of current knowledge. Here we review the controversial topic of cancer stem cells applied to glioma to provide neurosurgeons with a working overview. It is now recognised that the adult human brain contains regionally specified cell populations capable of self-renewal that may contribute to tumour growth and maintenance following accumulated mutational change. Tumour cells adapted to maintain growth demonstrate some stem-like characteristics and as such constitute a legitimate therapeutic target. Cellular reprogramming technologies raise the potential of developing stem cells as novel surgical tools to target disease and possibly ameliorate some of the consequences of treatment. Achieving these goals remains a significant challenge to neurosurgical oncologists, not least in challenging how we think about treating brain cancer. This review will briefly examine our understanding of adult stem cells within the brain, the evidence that they contribute to the development of brain tumours as tumour-initiating cells, and the potential implications for therapy. It will also look at the role stem cells may play in the future management of glioma.

  12. Intrinsic Angular Momentum of Light.

    Science.gov (United States)

    Santarelli, Vincent

    1979-01-01

    Derives a familiar torque-angular momentum theorem for the electromagnetic field, and includes the intrinsic torques exerted by the fields on the polarized medium. This inclusion leads to the expressions for the intrinsic angular momentum carried by the radiation traveling through a charge-free medium. (Author/MA)

  13. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  14. Identification of molecular pathways facilitating glioma cell invasion in situ.

    Directory of Open Access Journals (Sweden)

    Ido Nevo

    Full Text Available Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC xenograft model to explore gene expression changes in situ in Invading Glioma Cells (IGCs compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. IGCs were found to have reduced expression of genes within the extracellular matrix compartment, and genes involved in cell adhesion, cell polarity and epithelial to mesenchymal transition (EMT processes. The infiltrated microenvironment showed activation of wound repair and tissue remodeling networks. We confirmed by protein analysis the downregulation of EMT and polarity related genes such as CD44 and PARD3 in IGCs, and EFNB3, a tissue-remodeling agent enriched at the infiltrated microenvironment. OLIG2, a proliferation regulator and glioma progenitor cell marker upregulated in IGCs was found to function in enhancing migration and stemness of GSCs. Overall, our results unveiled a more comprehensive picture of the complex and dynamic cell autonomous and tumor-host interactive pathways of glioma invasion than has been previously demonstrated. This suggests targeting of multiple pathways at the junction of invading tumor and microenvironment as a viable option for glioma therapy.

  15. PRG3 induces Ras-dependent oncogenic cooperation in gliomas

    Science.gov (United States)

    Yakubov, Eduard; Chen, Daishi; Broggini, Thomas; Sehm, Tina; Majernik, Gökce Hatipoglu; Hock, Stefan W.; Schwarz, Marc; Engelhorn, Tobias; Doerfler, Arnd; Buchfelder, Michael; Eyupoglu, Ilker Y.; Savaskan, Nicolai E.

    2016-01-01

    Malignant gliomas are one of the most devastating cancers in humans. One characteristic hallmark of malignant gliomas is their cellular heterogeneity with frequent genetic lesions and disturbed gene expression levels conferring selective growth advantage. Here, we report on the neuronal-associated growth promoting gene PRG3 executing oncogenic cooperation in gliomas. We have identified perturbed PRG3 levels in human malignant brain tumors displaying either elevated or down-regulated PRG3 levels compared to non-transformed specimens. Further, imbalanced PRG3 levels in gliomas foster Ras-driven oncogenic amplification with increased proliferation and cell migration although angiogenesis was unaffected. Hence, PRG3 interacts with RasGEF1 (RasGRF1/CDC25), undergoes Ras-induced challenges, whereas deletion of the C-terminal domain of PRG3 (PRG3ΔCT) inhibits Ras. Moreover PRG3 silencing makes gliomas resistant to Ras inhibition. In vivo disequilibrated PRG3 gliomas show aggravated proliferation, invasion, and deteriorate clinical outcome. Thus, our data show that the interference with PRG3 homeostasis amplifies oncogenic properties and foster the malignancy potential in gliomas. PMID:27058420

  16. Glioma epidemiology in the central Tunisian population: 1993-2012.

    Science.gov (United States)

    Trabelsi, Saoussen; Brahim, Dorra H'mida-Ben; Ladib, Mohamed; Mama, Nadia; Harrabi, Imed; Tlili, Kalthoum; Yacoubi, Mohamed Tahar; Krifa, Hedi; Hmissa, Sihem; Saad, Ali; Mokni, Moncef

    2014-01-01

    Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.

  17. Effects of Photodynamic Therapy on the Ultrastructure of Glioma Cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To study the change in ultrastructure of C6 glioma cells after photodynamic therapy (PDT), to compare morphological differences in necrosis and apoptosis before and after PDT treatment, and to evaluate the effect of photodynamic therapy on the blood brain tumor barrier (BTB) of C6 glioma. Methods The model was produced by transplanting C6 glioma cells cultured in vitro using Peterson method into the caudate nuclei of Wister rats. The experiment group received PDT for two weeks after the operation. The sub-cellular structure, blood-brain-barrier (BBB) and BTB in both groups were observed under electron microscope. Results Apoptosis in different phases and necrosis could be observed in some C6 glioma cells.Swelling occurred on the ultrastructure of cellular organs such as mitochondria and endoplasmic reticulum in most of the cells.Damage to the BTB, reduction of the number of cellular organs in endothelial cells of the capillary blood vessels, stretch of the tight junction, and enlargement of the gaps between endothelial cells were also seen in the experiment group. Meanwhile,limited impact on the normal sub-cellular structures and BBB was observed. Conclusion PDT could induce apoptosis and necrosis of C6 glioma cells due to the damage to the ultrastructure of mitochondria and endoplasmic reticulum. The weakened function of C6 glioma BTB initiated by PDT makes it possible to perform a combined therapy of PDT and chemotherapy for glioma.

  18. Long noncoding RNA profiles reveal three molecular subtypes in glioma.

    Science.gov (United States)

    Li, Rui; Qian, Jin; Wang, Ying-Yi; Zhang, Jun-Xia; You, Yong-Ping

    2014-04-01

    Gliomas are the most lethal type of primary brain tumor in adult. Long noncoding RNAs (lncRNAs), which are involved in the progression of various cancers, may offer a potential gene therapy target in glioma. We first classified gliomas into three molecular subtypes (namely LncR1, LncR2 and LncR3) in Rembrandt dataset using consensus clustering. Survival analysis indicated that LncR3 had the best prognosis, while the LncR1 subtype showed the poorest overall survival rate. The results were further validated in an independent glioma dataset GSE16011. Additionally, we collected and merged data of the two databases (Rembrandt and GSE16011 dataset) and analyzed prognosis of each subtype in WHO II, III and IV gliomas. The similar results were obtained. Gene Set Variation Analysis (GSVA) demonstrated that LncR1 subtype enriched cultured astroglia's gene signature, while LncR2 subtype was characterized by neuronal gene signature. Oligodendrocytic was rich in LncR3. In addition, IDH1 mutation and 1p/19q LOH were found rich with LncR3, and EGFR amplification showed high percentage in LncR1 in GSE16011 dataset. We report a novel molecular classification of glioma based on lncRNA expression profiles and believe that it would provide a potential platform for future studies on gene treatment for glioma and lead to more individualized therapies to improve survival rates. © 2014 John Wiley & Sons Ltd.

  19. Telomere maintenance and the etiology of adult glioma.

    Science.gov (United States)

    Walsh, Kyle M; Wiencke, John K; Lachance, Daniel H; Wiemels, Joseph L; Molinaro, Annette M; Eckel-Passow, Jeanette E; Jenkins, Robert B; Wrensch, Margaret R

    2015-11-01

    A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk has remained elusive. Recent data address this question and are reviewed here. Common inherited variants near the telomerase-component genes TERC and TERT are associated both with longer telomere length and increased risk of glioma. Exome sequencing of glioma patients from families with multiple affected members has identified rare inherited mutations in POT1 (protection of telomeres protein 1) as high-penetrance glioma risk factors. These heritable POT1 mutations are also associated with increased telomere length in leukocytes. Tumor sequencing studies further indicate that acquired somatic mutations of TERT and ATRX are among the most frequent alterations found in adult gliomas. These mutations facilitate telomere lengthening, thus bypassing a critical mechanism of apoptosis. Although future research is needed, mounting evidence suggests that glioma is, at least in part, a disease of telomere dysregulation. Specifically, several inherited and acquired variants underlying gliomagenesis affect telomere pathways and are also associated with increased telomere length.

  20. Time generated by intrinsic observers

    CERN Document Server

    Svozil, Karl

    2009-01-01

    We shortly review the construction of knowledge by intrinsic observers. Intrinsic observers are embedded in a system and are inseparable parts thereof. The intrinsic viewpoint has to be contrasted with an extrinsic, "God's eye" viewpoint, from which the system can be observed externally without in any way changing it. This epistemological distinction has concrete, formalizable consequences. One consequence is the emergence of "complementarity" for intrinsic observers, even if the underlying system is totally deterministic (computable). Another consequence is the appearence of time and inertial frames for intrinsic observers. The necessary operational techniques are developed in the context of Cellular Automata. We finish with a somewhat speculative question. Given space-time frames generated by clocks which use sound waves for synchronization; why could supersonic travel not cause time paradoxes?

  1. Selective Targeting to Glioma with Nucleic Acid Aptamers.

    Directory of Open Access Journals (Sweden)

    Shraddha Aptekar

    Full Text Available Malignant glioma is characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue; hence, diagnosis and treatment is difficult and patient survival is poor. Aptamers contribute a promising and unique technology for the in vitro imaging of live cells and tissues, with a potentially bright future in clinical diagnostics and therapeutics for malignant glioma. The binding selectivity, uptake capacity and binding target of two DNA aptamers, SA43 and SA44, were investigated in glioma cells and patient tissues. The binding assay showed that SA43 and SA44 bound with strong affinity (Kd, 21.56 ± 4.60 nM and Kd, 21.11 ± 3.30 nM respectively to the target U87MG cells. Quantitative analysis by flow cytometry showed that the aptamers were able to actively internalise in U87MG and 1321N1 glioma cells compared to the non-cancerous and non-glioma cell types. Confocal microscopy confirmed staining in the cytoplasm, and co-localisation studies with endoplasmic reticulum, Golgi apparatus and lysosomal markers suggested internalisation and compartmentalisation within the endomembrane system. Both aptamers selectively bound to Ku 70 and Ku 80 DNA repair proteins as determined by aptoprecipitation (AP followed by mass spectrometry analysis and confirmation by Western blot. In addition, aptohistochemical (AHC staining on paraffin embedded, formalin fixed patient tissues revealed that the binding selectivity was significantly higher for SA43 aptamer in glioma tissues (grade I, II, III and IV compared to the non-cancerous tissues, whereas SA44 did not show selectivity towards glioma tissues. The results indicate that SA43 aptamer can differentiate between glioma and non-cancerous cells and tissues and therefore, shows promise for histological diagnosis of glioma.

  2. Current status of cerebral glioma surgery in China

    Institute of Scientific and Technical Information of China (English)

    WU Jin-song; ZHANG Jie; ZHUANG Dong-xiao; YAO Cheng-jun; QIU Tian-ming; LU Jun-feng; ZHU Feng-ping; MAO Ying; ZHOU Liang-fu

    2011-01-01

    The treatment of gliomas is highly individualized.Surgery for gliomas is essentially for histological diagnosis,to alleviate mass effect,and most importantly,to favor longer survival expectancy.During the past two decades,many surgical techniques and adjuvants have been applied to glioma surgery in China,which lead to a rapid development in the field of cerebral glioma surgery.This article broadly and critically reviewed the existing studies on cerebral glioma surgery and to portrait the current status of glioma surgery in China.A literature search was conducted covering major innovative surgical techniques and adjuvants for glioma surgery in China.The following databases were searched:the Pubmed (January 1995 to date);China Knowledge Resource Integrated Database (January 1995 to date) and VIP Database for Chinese Technical Periodicals (January 1995 to date).A selection criterion was established to exclude duplicates and irrelevant studies.The outcome measures were extracted from included studies.A total of 3307 articles were initially searched.After excluded by abstracts and full texts,69 studies conducted in the mainland of China were included and went through further analysis.The philosophy of surgical strategies for cerebral gliomas in China is undergoing tremendous change.Nowadays Chinese neurosurgeons pay more attention to the postoperative neurofunctional status of the patients.The aim of the glioma surgery is not only the more extensive tumor resection but also the maximal safety of intervention.The well balance of longer overall survival and higher quality of life should be judged with respect to each individual patient.

  3. Surgical considerations for ′intrinsic′ brainstem gliomas: Proposal of a modification in classification

    Directory of Open Access Journals (Sweden)

    Mehta V

    2009-01-01

    Full Text Available Background: Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unclear Objective: To evaluate the clinical, radiological and surgical outcome of 40 focal ′intrinsic′ brainstem gliomas and propose a surgical strategy-oriented classification. Materials and Methods: A total of 40 focal ′intrinsic′ ("expanding variety" tumors have been operated over a period of 8.5-years (January 1998-June 2007. Our criteria included patients with (1 well-defined gadolinium enhancing tumor; (2 relatively long duration of symptoms (> six months and (3 good neurological functional status and independent for all activities of daily living. The cutoff size of 2 cm was not rigidly adhered to. Results: The ′intrinsic′ brainstem tumors were classified into three types: Expanding, diffuse infiltrative and pure ventral varieties. Only patients with expanding variety of brainstem gliomas were subjected to surgery, mean age 19.2 years (range 4-55 years and male to female ration mean: 3:2. The tumor location included pons (n=19, midbrain (n=13 and medulla (n=8. Surgical approaches included midline suboccipital (n=28, retromastoid (n=7, subtemporal (n=3 and supracerebellar-infratentorial (n=2. Thirty-two cases with ′diffuse infiltrative′ and ′pure ventral′ variety were given radiotherapy only. Histology pathology revealed pilocytic variety (n=10, Grade II (n=17 and Grade III (n=13. There was one death in the surgical series (due to aspiration. Complications included meningitis (n=2, wound infection (n=1, chest infection (n=5 and transient mutism (n=1. Follow-up ranged from 3-68 months. Overall, 36 improved /remained same and three worsened in their clinical status at the time of discharge. Conclusion: The surgical management of intrinsic brainstem tumors presents a surgical challenge; radical

  4. Central pontine myelinolysis with a hyperintense lesion in diffusion weighted MRI: overview by means of a case report; Zentrale pontine Myelinolyse mit hyperintenser Laesion im diffusionsgewichteten MRT: Uebersicht anhand eines Fallberichtes

    Energy Technology Data Exchange (ETDEWEB)

    Kuhn, J.; Bewermeyer, H. [Neurologische Klinik, Kliniken der Stadt Koeln gGmbH, Krankenhaus Merheim, Koeln (Germany); Harzheim, A. [Radiologische Klinik, Kliniken der Stadt Koeln gGmbH, Krankenhaus Merheim, Koeln (Germany)

    2005-07-01

    Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with demyelination of other areas of the central nervous system (CNS). The etiology and pathogenesis of this disorder are still not fully understood. However, almost all cases of CPM are related to severe diseases or chronic alcoholism and occur in the setting of rapidly corrected serum hyponatremia and hypotonicity respectively. Depending on the involvement of other CNS structures, the clinical picture can vary considerably. Magnetic resonance imaging is the most sensitive investigation for the antemortem diagnosis of CPM, although the radiological findings lag behind and do not necessarily correlate with the clinical picture. Quite obviously diffusion-weighted imaging can be useful in the rapid diagnosis of CPM. This short review summarizes the current knowledge on the pathogenesis, clinical presentation, radiological findings, prognosis and therapeutic approaches of CPM. Characteristical clinical features and MR-findings including hyperintensity on diffusion-weighted images are illustrated by a typical case. (orig.)

  5. Season of Birth and Risk for Adult Onset Glioma

    Directory of Open Access Journals (Sweden)

    Jimmy T. Efird

    2010-04-01

    Full Text Available Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive.

  6. Noscapine inhibits tumor growth in TMZ-resistant gliomas.

    Science.gov (United States)

    Jhaveri, Niyati; Cho, Heeyeon; Torres, Shering; Wang, Weijun; Schönthal, Axel H; Petasis, Nicos A; Louie, Stan G; Hofman, Florence M; Chen, Thomas C

    2011-12-22

    Noscapine, a common oral antitussive agent, has been shown to have potent antitumor activity in a variety of cancers. Treatment of glioblastoma multiforme (GBM) with temozolomide (TMZ), its current standard of care, is problematic because the tumor generally recurs and is then resistant to this drug. We therefore investigated the effects of noscapine on human TMZ-resistant GBM tumors. We found that noscapine significantly decreased TMZ-resistant glioma cell growth and invasion. Using the intracranial xenograft model, we showed that noscapine increased survival of animals with TMZ-resistant gliomas. Thus noscapine can provide an alternative therapeutic approach for the treatment of TMZ-resistant gliomas.

  7. Notch Signaling Enhances Nestin Expression in Gliomas

    Directory of Open Access Journals (Sweden)

    Alan H. Shih

    2006-12-01

    Full Text Available Recent findings suggest that Notch signaling is active in brain tumors and stem cells, and that stem cells or cells with progenitor characteristics contribute to brain tumor formation. These stem cells are marked by expression of several markers, including nestin, an intermediate filament protein. We have studied how the Notch signaling pathway affects nestin expression in brain tumors. We find that Notch receptors and ligands are expressed in vitro and in human samples of glioblastomas, the highest grade of malignant gliomas. In culture, Notch activity activates the nestin promoter. Activation of the Notch pathway also occurs in a glioblastoma multiforme mouse model induced by Kras, with translational regulation playing a role in Notch expression. Combined activation of Notch and Kras in wild-type nestin-expressing cells leads to their expansion within the subventricular zone and retention of proliferation and nestin expression. However, activation of Notch alone is unable to induce this cellular expansion. These data suggest that Notch may have a contributing role in the stem-like character of glioma cells.

  8. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Soma Madhan Reddy

    2015-01-01

    Full Text Available Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS is a recently described inflammatory disease of central nervous system with distinct clinical and radiological features. The etiopathogenesis of this rare entity remains to be understood. The histopathological findings closely resemble chronic inflammatory diseases like sarcoidosis and malignancies like lymphoma. With advancements in serology, immunopathology and radiology CLIPPERS is identified as a distinct entity that differs considerably in its clinical presentation, immunopathology, radiological findings and response to steroids. We describe a case that presented to us with progressive quadriparesis and lower cranial nerve deficits whose radiological and pathological findings were consistent with CLIPPERS. The patient had a good outcome with long term immunosuppression.

  9. Vasoactive intestinal polypeptide excites medial pontine reticular formation neurons in the brainstem rapid eye movement sleep-induction zone

    DEFF Research Database (Denmark)

    Kohlmeier, Kristi Anne; Reiner, P B

    1999-01-01

    Although it has long been known that microinjection of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) induces a state that resembles rapid eye movement (REM) sleep, it is likely that other transmitters contribute to mPRF regulation of behavioral states. A key...... candidate is the peptide vasoactive intestinal polypeptide (VIP), which innervates the mPRF and induces REM sleep when injected into this region of the brainstem. To begin understanding the cellular mechanisms underlying this phenomenon, we examined the effects of VIP on mPRF cells using whole-cell patch...... conclude that VIP excites mPRF neurons by activation of a sodium current. This effect is mediated at least in part by G-protein stimulation of adenylyl cyclase, cAMP, and protein kinase A. These data suggest that VIP may play a physiological role in REM induction by its actions on mPRF neurons....

  10. Reptin and Pontin function antagonistically with PcG and TrxG complexes to mediate Hox gene control

    Science.gov (United States)

    Diop, Soda Balla; Bertaux, Karine; Vasanthi, Dasari; Sarkeshik, Ali; Goirand, Benjamin; Aragnol, Denise; Tolwinski, Nicholas S; Cole, Michael D; Pradel, Jacques; Yates, John R; Mishra, Rakesh K; Graba, Yacine; Saurin, Andrew J

    2008-01-01

    Pontin (Pont) and Reptin (Rept) are paralogous ATPases that are evolutionarily conserved from yeast to human. They are recruited in multiprotein complexes that function in various aspects of DNA metabolism. They are essential for viability and have antagonistic roles in tissue growth, cell signalling and regulation of the tumour metastasis suppressor gene, KAI1, indicating that the balance of Pont and Rept regulates epigenetic programmes critical for development and cancer progression. Here, we describe Pont and Rept as antagonistic mediators of Drosophila Hox gene transcription, functioning with Polycomb group (PcG) and Trithorax group proteins to maintain correct patterns of expression. We show that Rept is a component of the PRC1 PcG complex, whereas Pont purifies with the Brahma complex. Furthermore, the enzymatic functions of Rept and Pont are indispensable for maintaining Hox gene expression states, highlighting the importance of these two antagonistic factors in transcriptional output. PMID:18259215

  11. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A case report and review of literature.

    Science.gov (United States)

    Reddy, Soma Madhan; Lath, Rahul; Swain, Meenakshi; Ranjan, Alok

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of central nervous system with distinct clinical and radiological features. The etiopathogenesis of this rare entity remains to be understood. The histopathological findings closely resemble chronic inflammatory diseases like sarcoidosis and malignancies like lymphoma. With advancements in serology, immunopathology and radiology CLIPPERS is identified as a distinct entity that differs considerably in its clinical presentation, immunopathology, radiological findings and response to steroids. We describe a case that presented to us with progressive quadriparesis and lower cranial nerve deficits whose radiological and pathological findings were consistent with CLIPPERS. The patient had a good outcome with long term immunosuppression.

  12. Idiopathic pontine Streptococcus salivarius abscess in an immunocompetent patient: management lessons through case illustration and literature review.

    Science.gov (United States)

    Mandapat, Aimee Luna; Eddleman, Christopher S; Bissonnette, Mei Lin; Batjer, H Hunt; Zembower, Teresa R

    2011-12-01

    A 55-y-old woman with no previous medical history presented with a 3-day history of progressive headache, nausea, emesis, right-sided facial numbness, and right-sided extremity weakness. Serial magnetic resonance imaging demonstrated rapid enlargement of a left-sided ring-enhancing dorsal pontine lesion with an exophytic portion, raising concern for an abscess. A stereotactically guided left-sided retrosigmoid craniotomy for abscess incision and decompression was performed given the rapid progression of her neurological deficits. Streptococcus salivarius was isolated from the intra-operative samples. After an extensive evaluation, no source for the S. salivarius was identified. Solitary brainstem abscesses are uncommon intracranial infections with high morbidity and mortality. Patients can present with non-specific symptoms and often have no previous medical history. Since 1974, 40 patients with solitary brainstem abscess have survived to hospital discharge. We outline management strategies for solitary brainstem abscess based on a literature review of survivors.

  13. Recent progress on intrinsic charm

    Science.gov (United States)

    Hobbs, T. J.

    2017-03-01

    Over the past ˜10 years, the topic of the nucleon's nonperturbative or intrinsic charm (IC) content has enjoyed something of a renaissance, largely motivated by theoretical developments involving quark modelers and PDF-fitters. In this talk I will briefly describe the importance of intrinsic charm to various issues in high-energy phenomenology, and survey recent progress in constraining its overall normalization and contribution to the momentum sum rule of the nucleon. I end with the conclusion that progress on the side of calculation has now placed the onus on experiment to unambiguously resolve the proton's intrinsic charm component.

  14. Intrinsic time geometrodynamics: explicit examples

    CERN Document Server

    Lin, Huei-Chen

    2016-01-01

    Intrinsic time quantum geometrodynamics resolved `the problem of time' and bridged the deep divide between quantum mechanics and canonical quantum gravity with a Schrodinger equation which describes evolution in intrinsic time variable. In this formalism, Einstein's general relativity is a particular realization of a wider class of theories. Explicit classical black hole and cosmological solutions and the motion of test particles are derived and analyzed in this work in the context of constant three-curvature solutions in intrinsic time geometrodynamics; and we exemplify how this formalism yields results which agree with the predictions of Einstein's theory.

  15. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) with intracranial Epstein–Barr virus infection

    Science.gov (United States)

    Ma, Yue; Sun, Xiaolong; Li, Wen; Li, Yi; Kang, Tao; Yang, Xiai; Jiang, Wen

    2016-01-01

    Abstract Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological features. The pathophysiology of CLIPPERS still remains unclear and the reports are quite few. Although the radiological lesions were reported to be located predominantly in the pons, brachium pontis, and cerebellum, other adjacent structures such as the white matter and spinal cord were very recently reported as involved regions in CLIPPERS. In this study, we report a case of CLIPPERS presenting with intracranial Epstein–Barr virus (EBV) infection and diffuse white matter involvement. Case summary: A 37-year-old male was diagnosed with mediastinal Hodgkin's lymphoma (lymphocyte predominance type) at the age of 26, and then obtained complete remission after treatment and remained free of relapse for 11 years. He was admitted with 7 months’ history of mental disorder, and 20 days’ history of gait and limb ataxia, dysphagia, and cough. The diagnosis of CLIPPERS was established based on the findings of punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the mid-brain, the pontine brachium, and diffuse white matter in magnetic resonance imaging (MRI), together with CD3+ T-lymphocytic inflammatory infiltration in perivascular and parenchymal area revealed by bilateral parietal lobe brain biopsy. Also, our patient exhibited a good response to steroid therapy and remained free of relapse for 5 months. Importantly, we found intracranial Epstein–Barr virus infection in this patient. Conclusion: CLIPPERS might be an autoimmune disorder, and intracranial EBV-infection raises the possibility that EBV-associated autoimmunity is associated with CLIPPERS pathogenesis. PMID:27861371

  16. Terbium-doped manganese carbonate nanoparticles with intrinsic photoluminescence and magnetic resonance imaging capacity.

    Science.gov (United States)

    Liu, Kang; Shi, Xin; Wang, Tingjian; Ai, Penghui; Gu, Wei; Ye, Ling

    2017-01-01

    Herein, we present the first example of manganese carbonate (MnCO3) nanoparticles (NPs) featuring intrinsic photoluminescence (PL) and magnetic resonance (MR) imaging capacity by Terbium (Tb) doping. The Tb-doped MnCO3 NPs were prepared by one-step thermal decomposition of Mn-oleate precursor in the presence of Tb-oleate. The oleate capped Tb-doped MnCO3 NPs are in rhombohedral shape with an average size of about 13nm. When endowed with high water-dispersible via replacing oleate with carboxylic silane, the Tb-doped MnCO3 NPs exhibit distinct intrinsic PL originated from the doped Tb(3+) ions. Meanwhile, the MR imaging capacity of Tb-doped MnCO3 NPs is well retained, as demonstrated by a high r1 relaxivity of 4.0428mM(-1)s(-1) and a significant MR contrast enhancement effect towards tiny brain glioma in mice.

  17. Alpinetin targets glioma stem cells by suppressing Notch pathway.

    Science.gov (United States)

    Wang, Jianpeng; Yan, Zhiyong; Liu, Xia; Che, Shusheng; Wang, Chao; Yao, Weicheng

    2016-07-01

    Glioma is among the most common human malignancies with poor prognosis. Glioma stem cells (GSCs) are the culprit of glioma, suggesting that GSCs are potential therapeutic targets. Notch signaling pathway plays a pivotal role for the function of GSCs, implying that suppression of Notch pathway may be an effective strategy for GSC-targeting therapy. In this study, we found that alpinetin, a natural compound, can suppress the proliferation and invasiveness of GSCs and induce apoptosis in GSCs. Immunoblot analysis and luciferase assay revealed that Notch signaling was suppressed by alpinetin. Furthermore, restoration of Notch signaling activity rescued the effect of alpinetin on GSC's function. The anti-tumor activity of alpinetin was further confirmed in an animal model. Collectively, targeting of GSC by alpinetin is an effective strategy for glioma therapy.

  18. The functional role of Notch signaling in human gliomas

    DEFF Research Database (Denmark)

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2010-01-01

    have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now......Gliomas are among the most devastating adult tumors for which there is currently no cure. The tumors are derived from brain glial tissue and comprise several diverse tumor forms and grades. Recent reports highlight the importance of cancer-initiating cells in the malignancy of gliomas. These cells...... firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC. In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic...

  19. Epileptic seizures in patients with glioma: A single centrebased ...

    African Journals Online (AJOL)

    Epileptic seizures in patients with glioma: A single centrebased study in China. ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL ... Fisher's exact and Chi square tests were used for analysis of seizure ...

  20. Salinomycin inhibits the tumor growth of glioma stem cells by selectively suppressing glioma-initiating cells.

    Science.gov (United States)

    Chen, Tunan; Yi, Liang; Li, Fei; Hu, Rong; Hu, Shengli; Yin, Yi; Lan, Chuan; Li, Zhao; Fu, Chuhua; Cao, Liu; Chen, Zhi; Xian, Jishu; Feng, Hua

    2015-04-01

    Glioma‑initiating cells are a small population of cells that have the ability to undergo self‑renewal and initiate tumorigenesis. In the present study, the potential role of salinomycin, a polyether antibiotic, on the suppression of glioma cell growth was investigated. GL261 glioma cells were maintained in a stem‑cell‑like status [GL261 neurospheres (GL261‑NS)] or induced for differentiation [GL261 adherent cells (GL261‑AC)]. It was demonstrated that salinomycin significantly reduced the cell viability of GL261‑NS and GL261‑AC cells in a dose‑dependent manner, with a more substantial inhibition of GL261‑NS proliferation (Psalinomycin on cell growth was more effective than that of 1‑(4‑amino‑2‑methyl‑5‑pyrimid l)‑methyl‑3‑(2‑chloroethyl)‑3‑nitrosourea hydrochloride and vincristine (PSalinomycin depleted GL261‑NS from tumorspheres and induced cell apoptosis. In addition, salinomycin prolonged the median survival time of glioma‑bearing mice (Psalinomycin may preferentially inhibit glioma‑initiated cell growth by inducing apoptosis, suggesting that salinomycin may provide a valuable therapeutic strategy for the treatment of malignant glioma.

  1. Glioma-Associated Antigen HEATR1 Induces Functional Cytotoxic T Lymphocytes in Patients with Glioma

    Directory of Open Access Journals (Sweden)

    Zhe Bao Wu

    2014-01-01

    Full Text Available A2B5+ glioblastoma (GBM cells have glioma stem-like cell (GSC properties that are crucial to chemotherapy resistance and GBM relapse. T-cell-based antigens derived from A2B5+ GBM cells provide important information for immunotherapy. Here, we show that HEAT repeat containing 1 (HEATR1 expression in GBM tissues was significantly higher than that in control brain tissues. Furthermore, HEATR1 expression in A2B5+ U87 cells was higher than that in A2B5−U87 cells (P=0.016. Six peptides of HEATR1 presented by HLA-A*02 were selected for testing of their ability to induce T-cell responses in patients with GBM. When peripheral blood mononuclear cells from healthy donors (n=6 and patients with glioma (n=33 were stimulated with the peptide mixture, eight patients with malignant gliomas had positive reactivity with a significantly increased number of responding T-cells. The peptides HEATR1682–690, HEATR11126–1134, and HEATR1757–765 had high affinity for binding to HLA-A*02:01 and a strong capacity to induce CTL response. CTLs against HEATR1 peptides were capable of recognizing and lysing GBM cells and GSCs. These data are the first to demonstrate that HEATR1 could induce specific CTL responses targeting both GBM cells and GSCs, implicating that HEATR1 peptide-based immunotherapy could be a novel promising strategy for treating patients with GBM.

  2. Intrinsic motivation and learning dynamics

    CERN Document Server

    Zgonnikov, Arkady

    2013-01-01

    We investigate the effects of intrinsic motivation on the dynamics of learning processes. We construct a simple model of a single agent adapting to unknown environment. Performing a repeated choice between a number of initially unexplored alternatives, the agent gains rewards for each selected alternative and in doing so gradually comprehends the environment. In our model the agent choice is governed by two stimuli. The traditional extrinsic motive inclines the agent to maximize the cumulative payoff throughout the process, while the second, intrinsic one, biases the agent towards the novel options that she inherently likes. We show that the intrinsic motivation can induce an instability and periodic dynamics of the learning process which is always stationary in the case of selfish, rational agent. Interestingly, the opposite effect can arise as well: when the impact of intrinsic motivation on the agent choice is strong, the equiprobable choice equilibrium strategy becomes stable. Based on the presented resul...

  3. Harmonic structures and intrinsic torsion

    DEFF Research Database (Denmark)

    Conti, Diego; Madsen, Thomas Bruun

    2015-01-01

    We discuss the construction of Sp(2)Sp(1)-structures whose fundamental form is closed. In particular, we find 10 new examples of 8-dimensional nilmanifolds that admit an invariant closed 4-form with stabiliser Sp(2) Sp(1). Our constructions entail the notion of SO(4)-structures on 7-manifolds. We...... present a thorough investigation of the intrinsic torsion of such structures, leading to the construction of explicit Lie group examples with invariant intrinsic torsion....

  4. Harmonic structures and intrinsic torsion

    DEFF Research Database (Denmark)

    Conti, Diego; Madsen, Thomas Bruun

    We discuss the construction of 8-manifolds with harmonic Sp(2)Sp(1)-structures. In particular, we find 10 new examples of nilmanifolds that admit a closed 4-form Omega whose stabiliser is Sp(2)Sp(1). Our constructions entail the notion of SO(4)-structures on 7-manifolds. We present a thorough inv...... investigation of the intrinsic torsion of such structures; in addition to the construction of harmonic structures, this analysis leads to explicit Lie group examples with invariant intrinsic torsion....

  5. UNUSUAL PRESENTATION OF BRAINSTEM GLIOMA AS PROGRESSIVE BULBAR PALSY

    Directory of Open Access Journals (Sweden)

    Suma

    2015-04-01

    Full Text Available Brain stem gliomas/astrocytomas are slowly growing tumors affecting children and young adults. They usually present with unilateral cranial nerve palsies followed by long tract signs. Here we present a case report of a 42 year old male patient, who initially presented with thyrotoxicosis and slowly progressing dysphagia, dysarthria and dysphonia with no other long tract signs, and was later found to have brain stem glioma.

  6. Gene expression of manganese superoxide dismutase in human glioma cells

    Directory of Open Access Journals (Sweden)

    Novi S. Hardiany

    2010-02-01

    Full Text Available Aim This study analyze the MnSOD gene expression as endogenous antioxidant in human glioma cells compared with leucocyte cells as control.Methods MnSOD gene expression of 20 glioma patients was analyzed by measuring the relative expression of mRNA and enzyme activity of MnSOD in brain and leucocyte cells. The relative expression of mRNA MnSOD was determined by using quantitative Real Time RT-PCR and the enzyme activity of MnSOD using biochemical kit assay (xantine oxidase inhibition. Statistic analysis for mRNA and enzyme activity of MnSOD was performed using Kruskal Wallis test.Results mRNA of MnSOD in glioma cells of 70% sample was 0.015–0.627 lower, 10% was 1.002-1.059 and 20% was 1.409-6.915 higher than in leucocyte cells. Also the specific activity of MnSOD enzyme in glioma cells of 80% sample showed 0,064-0,506 lower and 20% sample was 1.249-2.718 higher than in leucocyte cells.Conclusion MnSOD gene expression in human glioma cells are significantly lower than its expression in leucocytes cells. (Med J Indones 2010; 19:21-5Keywords : MnSOD, glioma, gene expression

  7. Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

    Directory of Open Access Journals (Sweden)

    Sadahiro Kaneko

    2016-01-01

    Full Text Available Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD. Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD.

  8. Role of MicroRNAs in Malignant Glioma

    Institute of Scientific and Technical Information of China (English)

    Bao-Cheng Wang; Jie Ma

    2015-01-01

    Objective:This overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant glioma.Data Sources:Using the keyword terms "glioma" and "miRNA," we performed the literature search in PubMed,Ovid,and web.metstr.com databases from their inception to October 2014.Study Selection:In screening out the quality of the articles,factors such as clinical setting of the study,the size of clinical samples were taken into consideration.Animal studied for verification and reviews article were also included in our data collection.Results:Despite many advance in miRNA for malignant glioma,further studies were still required to focus on the following aspects:(i) Improving the understanding about biogenesis of miRNA and up-down regulation;(ii) utilizing high-throughput miRNA expression analysis to screen out the core miRNA for glioma;(iii) Focusing related miRNAs on the signal transduction pathways that regulate the proliferation and growth of glioma.Conclusions:We discussed the most promising miRNA,correlative signaling pathway and their relation with gliomas in the way of prompting miRNA target into being a clinical therapeutic strategy.

  9. Ion channel gene expression predicts survival in glioma patients.

    Science.gov (United States)

    Wang, Rong; Gurguis, Christopher I; Gu, Wanjun; Ko, Eun A; Lim, Inja; Bang, Hyoweon; Zhou, Tong; Ko, Jae-Hong

    2015-08-03

    Ion channels are important regulators in cell proliferation, migration, and apoptosis. The malfunction and/or aberrant expression of ion channels may disrupt these important biological processes and influence cancer progression. In this study, we investigate the expression pattern of ion channel genes in glioma. We designate 18 ion channel genes that are differentially expressed in high-grade glioma as a prognostic molecular signature. This ion channel gene expression based signature predicts glioma outcome in three independent validation cohorts. Interestingly, 16 of these 18 genes were down-regulated in high-grade glioma. This signature is independent of traditional clinical, molecular, and histological factors. Resampling tests indicate that the prognostic power of the signature outperforms random gene sets selected from human genome in all the validation cohorts. More importantly, this signature performs better than the random gene signatures selected from glioma-associated genes in two out of three validation datasets. This study implicates ion channels in brain cancer, thus expanding on knowledge of their roles in other cancers. Individualized profiling of ion channel gene expression serves as a superior and independent prognostic tool for glioma patients.

  10. EXPRESSION AND SWITCHING OF TH 1/TH2 TYPE CYTOKINES GENE IN HUMAN GLIOMAS

    Institute of Scientific and Technical Information of China (English)

    Yong-sheng Hu; Xin-gang Li; Qing-lin Zhang; Dong-hai Wang; Song-feng Gong

    2005-01-01

    Objective To study the expression and switching of Th1/Th2 cytokines gene in hman gliomas and its effects on occurring and developing of human gliomas.Methods Interleukin(IL)-2 and intefferon-γ represent Th1 type cytokines. IL-4, IL-6, IL-10, and IL-13 represent Th2 type cytokines. The gene expressions of Th1/Th2 cytokines in human glioma cells, glioma infiltrating lymphocytes,and glioma cell lines were detected by reverse transcription polymerase chain reaction (RT-PCR). The biological activity of cytokines in the supematant of glioma cell lines was assayed by enzyme-linked immunosorbent assay (ELISA)method.Results The total positive rates of Th1 and Th2 type cytokines gene in human glioma cells were 14.77% and 75%. The total positive rates of Thl and Th2 type cytokines gene in glioma infiltrating lymphocytes were 22.73% and 68.17%. There was obviously predominant expression of Th2 type cytokines in human glioma tissues, glioma infiltrating lymphocytes, and glioma cell lines. There was no unbalanced expression of Th1/Th2 cytokines in normal brain tissues.Conclusion There is a predominant expression of Th2 type cytokines in human glioma cells. The switching of Th1/Th2 cytokines gene may play an important role in the occurring and developing of human gliomas.

  11. [Surgical resection of gliomas in 2008].

    Science.gov (United States)

    Carpentier, A C

    2008-11-01

    Surgical resection of gliomas is a well-established treatment. It allows a histo-genetic diagnosis, a mass effect reduction, an intracranial hypertension treatment, a recovery of an eventual neurological deficit induced by the mass effect, but mostly brings a significant survival. New imaging sequences are optimizing the surgical management of brain tumors by bringing precisions on the tumor morphology, on cortical/subcortical eloquent areas (functional and diffusion MRI), on histology (spectroscopic MR). If the tumor is located in eloquent area, surgery is performed under electrostimulation control to take into account cerebral plasticity and to avoid postoperative functional deficits. Neuronavigation, per-operative echography, and per-operative MRI are recognized tools for optimizing the tumor resection. Ongoing researches concern the adjunction of local treatments within the surgical field (photodynamic therapy, chemotherapy, convection immunotherapy...), but also the development of minimal invasive procedures (radiosurgery, high intensity focalized ultrasounds, laser interstitial thermal therapy).

  12. Intraoperative radiation therapy for malignant glioma

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Noboru; Yamada, Hiromu; Andoh, Takashi; Takada, Mitsuaki; Hirata, Toshifumi; Funakoshi, Takashi; Doi, Hidetaka; Yanagawa, Shigeo (Gifu Univ. (Japan). Faculty of Medicine)

    1989-04-01

    Intraoperative radiation therapy (IOR) is an ideal means of exterminating residual tumor after surgical resection. In this study, the clinical results of IOR using a Scanditronix Microtron MM-22 were evaluated in 14 patients with malignant glioma, five of whom had recurrent tumors. Between July, 1985 and October, 1986, 11 patients with glioblastoma multiforme (GB) were irradiated 18 times (mean, 1.6 times/case), and three with astrocytoma (Kernohan grade III) underwent IOR once each. The target-absorbed dose at 1 to 2 cm deeper than the tumor resection surface was 15 to 50 Gy. During irradiation, a cotton bolus was placed in the dead space after over 91% of the tumor had been resected. As a rule, external irradiation therapy was also given postoperatively at a dose of 30 to 52 Gy. One patient died of pneumonia and disseminated intravascular coagulation syndrome 1 month postoperatively. The 1- and 2-year survival rates of the ramaining 13 patients were 84.6% and 61.5%, respectively; among the 10 with GB, they were 80% and 50%. Generally, the smaller the tumor size, the better the results. There were no adverse effects, despite the dose 15 to 50 Gy applied temporally to the tumor bed. IOR was especially effective against small, localized tumors, but was not always beneficial in cases of large tumors, particularly those with a contralateral focus. The improved survival rate in this series demonstrates that IOR is significantly effective in the 'induction of remission' following surgical excision of malignant gliomas. (author).

  13. Pontine-to-midbrain ratio indexes ocular-motor function and illness stage in adult Niemann-Pick disease type C.

    Science.gov (United States)

    Walterfang, M; Macfarlane, M D; Looi, J C L; Abel, L; Bowman, E; Fahey, M C; Desmond, P; Velakoulis, D

    2012-03-01

    Niemann-Pick disease type C (NPC) is a progressive neurovisceral disorder associated with dystonia, ataxia and a characteristic gaze palsy. Neuropathological studies have demonstrated brainstem atrophy associated with neuronal inclusions and loss, and neurofibrillary tangles, although it is not known whether this pathology can be detected in vivo or how these changes relate to illness variables, particularly ocular-motor changes. Our aim was to utilize a method for brainstem atrophy, validated in progressive supranuclear palsy (PSP), in a group of adult patients with NPC, and explore its relationship to illness variables and ocular-motor functioning. We calculated the midbrain and pontine area, and pontine-to-midbrain ratio (PMR) from midsagittal images of 10 adult patients with NPC and 27 age- and gender-matched controls. Measures were correlated with illness variables, and measures of horizontal saccadic functioning. Pontine-to-midbrain ratio was 14% higher in the NPC group, but this difference was not significant. However, PMR showed a significant positive correlation with duration of illness and a measure of illness severity. Furthermore, PMR was significantly negatively correlated with saccadic peak velocity and gain, and self-paced saccadic performance. Pontine-to-midbrain ratio was increased in adult patients with NPC compared to controls, although not to the same degree as previously described in PSP, which also presents with significant gaze palsy. These changes were driven predominantly by progressive midbrain atrophy. The strong correlation with illness and ocular-motor variables suggests that it may be a useful marker for illness progression in NPC. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

  14. SLEEP AND GABA LEVELS IN THE ORAL PART OF RAT PONTINE RETICULAR FORMATION ARE DECREASED BY LOCAL AND SYSTEMIC ADMINISTRATION OF MORPHINE

    OpenAIRE

    Watson, Christopher J.; Lydic, Ralph; Baghdoyan, Helen A.

    2006-01-01

    Morphine, a μ-opioid receptor agonist, is a commonly prescribed treatment for pain. Although highly efficacious, morphine has many unwanted side effects including disruption of sleep and obtundation of wakefulness. One mechanism by which morphine alters sleep and wakefulness may be by modulating GABAergic signaling in brain regions regulating arousal, including the oral pontine reticular formation (PnO). This study used in vivo microdialysis in unanesthetized Sprague-Dawley rat to test the hy...

  15. Effects of endostatin on C6 glioma-induced edema

    Institute of Scientific and Technical Information of China (English)

    YANG Li-juan; LIN Zhi-xiong; KANG De-zhi; WENG Shen-mei; LIN Jian-hua; HUANG Qiang; ZHANG Peng-fei

    2011-01-01

    Background Glioma-induced edema is considered as one of the most pathological characteristics of glioma and a significant source of morbidity and mortality.New strategies are needed for the treatment of peritumoral edema in glioma.Endostatin has been proven to be beneficial as an anti-angiogenic agent in experimental gliomas,but the effects are unclear.This study aimed to investigate the effects of endostatin on C6 glioma-induced edema.Methods Tumorigenic mice were established by subcutaneous injection of three glioma cell lines,C6-null cells and stable transfected-C6 cells overexpressing mock vector (C6-mock cells) and endostatin (C6-endo cells).Endostatin expression in xenograft C6 glioma was determined by immunostaining and Western blotting.Glioma-induced edema and tumor vessel permeability were assayed.The effect of endostatin on vascular enodothelial growth factor (VEGF) expression in vivo was analyzed by quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA).The number of vesiculo-vascuolar organelles (VVOs) formed in tumor endothelia was calculated using electron microscopy.Data were analyzed by using one-way analysis of variance (ANOVA) followed by Dunnett's post hoc test for multiple comparisons to the control groups.Results Overexpression of endostatin (C6-endo cells) significantly suppressed tumor growth and reduced tumor edema and vessel permeability.ELISA analysis showed that the level of VEGF protein was markedly decreased in tumor from C6-endo cells compared with tumor from C6-null cells and C6-mock cells.Similar results were obtained by Q-PCR.Furthermore,the number of VVOs observed in tumor from C6-endo mice was significantly reduced compared with tumor from C6-null cells or C6-mock cells.Conclusions Our data provide primary evidence that endostatin reduces glioma-induced edema and vascular permeability.Using endostatin may be an effective strategy for treating glioma edema.

  16. DELETION AND 5'CPG ISLAND METHYLATION OF p15 GENE IN BRAIN GLIOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the abnormality of p15 gene in brain glioma and the correlation of it with occurrence or malignant progression of brain glioma. Methods: Deletion and 5'CPG island methylation of p15 gene were detected by the methods of PCR and PCR-based methylation in 56 cases of brain glioma. Results: Out of 43 cases of high grade glioma, 14 cases were found to have homozygous deletion of p15E1, while none of the 13 cases of low grade glioma was found to have deletion of p15E1 (P<0.05). Methylation of 5'CPG Island of p15 gene was found only in four cases of glioma. Conclusion: Abnormality of p15 gene may involved in the occurrence and malignant progression of brain glioma. Homozygous deletion of gene is the major mechanism of inactivation for p15 gene in brain glioma.

  17. Changing paradigms - An update on the multidisciplinary management of malignant glioma

    NARCIS (Netherlands)

    R. Stupp (Roger); M.E. Hegi (Monika); M.J. van den Bent (Martin); W.P. Mason (Warren); M. Weller (Michael); R.O. Mirimanoff; J.G. Cairncross (Gregory)

    2006-01-01

    textabstractTreatment of malignant glioma requires a multidisciplinary team. Treatment includes surgery, radiotherapy, and chemotherapy. Recently developed agents have demonstrated activity against recurrent malignant glioma and efficacy if given concurrently with radiotherapy in the upfront setting

  18. Long-Term Outcome of Endonasal Transsphenoidal Approach for the Treatment of Pontine Cavernous Malformation: Case Report with 11 Years of Follow-Up.

    Science.gov (United States)

    Banczerowski, Péter; Czigléczki, Gábor; Gádor, Ildikó; Nyáry, István

    2016-05-01

    Ventromedial localized cavernous malformations in the pons pose a difficult problem because of their surgical access and the high risk of deleterious consequences due to damage of the surrounding tissues. We report an endonasal transsphenoidal approach for the treatment of ventromedial pontine cavernomas that also follows principles of optimal access known as the "two-point method" for the resection of cavernous malformations. A 31-year-old woman presented with sudden left hemiparesis, nausea, and headache. Radiologic findings demonstrated a ventral pontine cavernous malformation in the midline slightly extending to the right, together with signs of acute hemorrhage. Surgical intervention was performed, and the cavernoma was completely resected via a transnasal transsphenoidal approach. Cerebrospinal fluid (CSF) rhinorrhea that ensued postoperatively needed an additional reconstructive surgery using the same approach. No further CSF leakage was evident, and an 11-year follow-up examination revealed neither signs of neurologic deficit nor recurrence of the resected pontine cavernoma. The long-term outcome proves the effectiveness and safety of this novel surgical route in the treatment of ventromedial cavernous malformations in the pons.

  19. Treating malignant glioma in Chinese patients: update on temozolomide

    Directory of Open Access Journals (Sweden)

    Chang L

    2014-02-01

    Full Text Available Liang Chang,1 Jun Su,1 Xiuzhi Jia,2,3 Huan Ren2,3 1Department of Neurosurgery, The Tumor Hospital of Harbin Medical University, 2Department of Immunology, Harbin Medical University, 3Key Lab Infection and Immunity, Heilongjiang Province, Harbin, People's Republic of China Abstract: Malignant glioma, ie, anaplastic astrocytoma and glioblastoma, is the most common type of primary malignant brain tumor in the People's Republic of China, and is particularly aggressive. The median survival of patients with newly diagnosed glioblastoma is only 12–14 months despite advanced therapeutic strategies. Treatment of malignant glioma consists mainly of surgical resection followed by adjuvant radiation and chemotherapy. Temozolomide (TMZ, a second-generation oral alkylating agent, is playing an increasingly important role in the treatment of malignant glioma in Chinese patients. Since the publication of a study by Stupp et al in 2005, which used a protocol of conventional fractionated irradiation with concomitant TMZ followed by standard TMZ for six cycles, many clinical studies in the People's Republic of China have demonstrated that such a treatment strategy has significantly improved efficacy with limited side effects for newly diagnosed glioblastoma after surgery as compared with strategies that do not contain TMZ. However, as a relatively new agent, the history and development of TMZ for malignant glioma is not well documented in Chinese patients. Multicenter, randomized controlled trials including appropriately sized patient populations investigating multiple aspects of TMZ therapy and related combination therapies are warranted in patients with malignant glioma. This review provides an update on the efficacy, mechanism of action, adverse reactions, and clinical role of TMZ in the treatment of malignant glioma in Chinese patients. Keywords: malignant glioma, chemotherapy, temozolomide, efficacy, side effect, People's Republic of China

  20. IDH1 mutation detection by droplet digital PCR in glioma.

    Science.gov (United States)

    Wang, Jing; Zhao, Yi-ying; Li, Jian-feng; Guo, Cheng-cheng; Chen, Fu-rong; Su, Hong-kai; Zhao, Hua-fu; Long, Ya-kang; Shao, Jian-yong; To, Shing shun Tony; Chen, Zhong-ping

    2015-11-24

    Glioma is the most frequent central nervous system tumor in adults. The overall survival of glioma patients is disappointing, mostly due to the poor prognosis of glioblastoma (Grade IV glioma). Isocitrate dehydrogenase (IDH) is a key factor in metabolism and catalyzes the oxidative decarboxylation of isocitrate. Mutations in IDH genes are observed in over 70% of low-grade gliomas and some cases of glioblastoma. As the most frequent mutation, IDH1(R132H) has been served as a predictive marker of glioma patients. The recently developed droplet digital PCR (ddPCR) technique generates a large amount of nanoliter-sized droplets, each of which carries out a PCR reaction on one template. Therefore, ddPCR provides high precision and absolute quantification of the nucleic acid target, with wide applications for both research and clinical diagnosis. In the current study, we collected 62 glioma tissue samples (Grade II to IV) and detected IDH1 mutations by Sanger direct sequencing, ddPCR, and quantitative real-time PCR (qRT-PCR). With the results from Sanger direct sequencing as the standard, the characteristics of ddPCR were compared with qRT-PCR. The data indicated that ddPCR was much more sensitive and much easier to interpret than qRT-PCR. Thus, we demonstrated that ddPCR is a reliable and sensitive method for screening the IDH mutation. Therefore, ddPCR is able to applied clinically in predicting patient prognosis and selecting effective therapeutic strategies. Our data also supported that the prognosis of Grade II and III glioma was better in patients with an IDH mutation than in those without mutation.

  1. Surgical Outcomes of High-Grade Spinal Cord Gliomas

    Science.gov (United States)

    Hida, Kazutoshi; Yano, Syunsuke; Aoyama, Takeshi; Koyanagi, Izumi; Houkin, Kiyohiro

    2015-01-01

    Study Design A retrospective study. Purpose The purpose of this study was to obtain useful information for establishing the guidelines for treating high-grade spinal cord gliomas. Overview of Literature The optimal management of high-grade spinal cord gliomas remains controversial. We report the outcomes of the surgical management of 14 high-grade spinal glioma. Methods We analyzed the outcomes of 14 patients with high-grade spinal cord gliomas who were surgically treated between 1989 and 2012. Survival was charted with the Kaplan-Meier plots and comparisons were made with the log-rank test. Results None of the patients with high-grade spinal cord gliomas underwent total resection. Subtotal resection was performed in two patients, partial resection was performed in nine patients, and open biopsy was performed in three patients. All patients underwent postoperative radiotherapy and six patients further underwent radiation cordotomy. The median survival time for patients with high-grade spinal cord gliomas was 15 months, with a 5-year survival rate of 22.2%. The median survival time for patients with World Health Organization grade III tumors was 25.5 months, whereas the median survival time for patients with glioblastoma multiforme was 12.5 months. Both univariate and multivariate Cox proportional hazards models demonstrated a significant effect only in the group that did not include cervical cord lesion as a factor associated with survival (p=0.04 and 0.03). Conclusions The surgical outcome of patients diagnosed with high-grade spinal cord gliomas remains poor. Notably, only the model which excluded cervical cord lesions as a factor significantly predicted survival. PMID:26713128

  2. Extracellular diffusion quantified by magnetic resonance imaging during rat C6 glioma cell progression

    Directory of Open Access Journals (Sweden)

    G. Song

    Full Text Available Solution reflux and edema hamper the convection-enhanced delivery of the standard treatment for glioma. Therefore, a real-time magnetic resonance imaging (MRI method was developed to monitor the dosing process, but a quantitative analysis of local diffusion and clearance parameters has not been assessed. The objective of this study was to compare diffusion into the extracellular space (ECS at different stages of rat C6 gliomas, and analyze the effects of the extracellular matrix (ECM on the diffusion process. At 10 and 20 days, after successful glioma modeling, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA was introduced into the ECS of rat C6 gliomas. Diffusion parameters and half-life of the reagent were then detected using MRI, and quantified according to the mathematical model of diffusion. The main ECM components [chondroitin sulfate proteoglycans (CSPGs, collagen IV, and tenascin C] were detected by immunohistochemical and immunoblot analyses. In 20-day gliomas, Gd-DTPA diffused more slowly and derived higher tortuosity, with lower clearance rate and longer half-life compared to 10-day gliomas. The increased glioma ECM was associated with different diffusion and clearance parameters in 20-day rat gliomas compared to 10-day gliomas. ECS parameters were altered with C6 glioma progression from increased ECM content. Our study might help better understand the glioma microenvironment and provide benefits for interstitial drug delivery to treat brain gliomas.

  3. Description of selected characteristics of familial glioma patients – Results from the Gliogene Consortium

    DEFF Research Database (Denmark)

    Sadetzki, Siegal; Bruchim, Revital; Oberman, Bernice

    2013-01-01

    While certain inherited syndromes (e.g. Neurofibromatosis or Li-Fraumeni) are associated with an increased risk of glioma, most familial gliomas are non-syndromic. This study describes the demographic and clinical characteristics of the largest series of non-syndromic glioma families ascertained...

  4. [18F]-fluoro-l-thymidine PET and advanced MRI for preoperative grading of gliomas

    Directory of Open Access Journals (Sweden)

    S. Collet

    2015-01-01

    Conclusion: Whereas advanced MRI parameters give indications for the grading of gliomas, the addition of [18F]-FLT-PET could be of interest for the accurate preoperative classification of diffuse gliomas, particularly for identification of doubtful grade III and IV gliomas.

  5. Intrinsic energy partition in fission

    Directory of Open Access Journals (Sweden)

    Mirea M.

    2013-03-01

    Full Text Available The intrinsic energy partition between two complementary fission fragments is investigated microscopically. The intrinsic excitation energy of fission fragments is dynamically evaluated in terms of the time-dependent pairing equations. These equations are corroborated with two conditions. One of them fixes the number of particles and the other separates the pairing active spaces associated to the two fragments in the vicinity of the scission configuration. The excitation energy in a wide distribution of fission fragments is calculated for the 234U parent nucleus.

  6. Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma

    Directory of Open Access Journals (Sweden)

    Fujita Mitsugu

    2007-12-01

    Full Text Available Abstract Background In patients with high grade glioma, little is known regarding existence of naturally occurring adaptive T cell reactivity against glioma-associated antigens (GAAs. In this report, we characterized GAA-specific CD8+ T cells and innate immune cells in a patient who has survived with anaplastic astrocytoma (AA for over 12 years without recurrence. Methods Peripheral blood mononuclear cells (PBMCs derived from the long term survivor with AA were evaluated for the frequency, cytotoxic T lymphocyte (CTL activity and differentiation status of CD8+ cells recognizing GAA-derived epitopes as well as relative numbers of other immune cell subsets. This patient's AA tissue was evaluated for expression of two GAAs EphA2 and interleukin-13 receptor α2 subunit (IL-13Rα2 by immunohistochemistry. Results The patient's tumor expressed both EphA2 and IL-13Rα2, and in vitro stimulated PBMC demonstrated superior EphA2883–891 and IL-13Rα2345–353-specific CTL reactivity compared to PBMC samples from two other patients with progressing malignant glioma. Unstimulated EphA2883–891-reactive CD8+ T cells contained high numbers of CD45RA-/CCR7- late effector and CD45RA-/CCR7+ central memory cells. Among other leukocyte subsets, elevated numbers of NK-T cells were found. Conclusion To our knowledge, the current study is one of the first demonstrating the presence of antigen-experienced, GAA-reactive CD8+ T cells in a patient who has survived with AA for over 12 years without recurrence. Further studies are warranted to determine whether the status of GAA-reactive CD8+ T cells dictates survival of patients and/or response to therapeutic vaccines.

  7. Facing Contrast-Enhancing Gliomas: Perfusion MRI in Grade III and Grade IV Gliomas according to Tumor Area

    Directory of Open Access Journals (Sweden)

    Anna Luisa Di Stefano

    2014-01-01

    Full Text Available Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV, calculated with Dynamic Susceptibility Contrast (DSC Perfusion-Weighted Imaging (PWI, allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal rCBV with a Region of Interest (ROI approach in three tumor areas—the contrast-enhancing area, the nonenhancing tumor, and the high perfusion area on CBV map—in patients affected by contrast-enhancing glioma (grades III and IV. Twenty-one patients were included: 15 were affected by grade IV and 6 by grade III glioma. Maximal rCBV values for each patient were averaged according to glioma grade. Although rCBV from contrast-enhancement and from nonenhancing tumor areas was higher in grade IV glioma than in grade III (5.58 and 2.68; 3.01 and 2.2, resp., the differences were not significant. Instead, rCBV recorded in the high perfusion area on CBV map, independently of tumor compartment, was significantly higher in grade IV glioma than in grade III (7.51 versus 3.78, P=0.036. In conclusion, neoangiogenesis encompasses different tumor compartments and CBV maps appear capable of best characterizing the degree of neovascularization. Facing contrast-enhancing brain tumors, areas of high perfusion on CBV maps should be considered as the reference areas to be targeted for glioma grading.

  8. Topoisomerase I inhibitors, shikonin and topotecan, inhibit growth and induce apoptosis of glioma cells and glioma stem cells.

    Directory of Open Access Journals (Sweden)

    Feng-Lei Zhang

    Full Text Available Gliomas, the most malignant form of brain tumors, contain a small subpopulation of glioma stem cells (GSCs that are implicated in therapeutic resistance and tumor recurrence. Topoisomerase I inhibitors, shikonin and topotecan, play a crucial role in anti-cancer therapies. After isolated and identified the GSCs from glioma cells successfully, U251, U87, GSCs-U251 and GSCs-U87 cells were administrated with various concentrations of shikonin or topotecan at different time points to seek for the optimal administration concentration and time point. The cell viability, cell cycle and apoptosis were detected using cell counting kit-8 and flow cytometer to observe the inhibitory effects on glioma cells and GSCs. We demonstrated that shikonin and topotecan obviously inhibited proliferation of not only human glioma cells but also GSCs in a dose- and time-dependent manner. According to the IC50 values at 24 h, 2 μmol/L of shikonin and 3 μmol/L of topotecan were selected as the optimal administration concentration. In addition, shikonin and topotecan induced cell cycle arrest in G0/G1 and S phases and promoted apoptosis. The down-regulation of Bcl-2 expression with the activation of caspase 9/3-dependent pathway was involved in the apoptosis process. Therefore, the above results showed that topoisomerase I inhibitors, shikonin and topotecan, inhibited growth and induced apoptosis of GSCs as well as glioma cells, which suggested that they might be the potential anticancer agents targeting gliomas to provide a novel therapeutic strategy.

  9. Efficacy of ribavirin against malignant glioma cell lines

    Science.gov (United States)

    OGINO, AKIYOSHI; SANO, EMIKO; OCHIAI, YUSHI; YAMAMURO, SHUN; TASHIRO, SHINYA; YACHI, KAZUNARI; OHTA, TAKASHI; FUKUSHIMA, TAKAO; OKAMOTO, YUTAKA; TSUMOTO, KOUHEI; UEDA, TAKUYA; YOSHINO, ATSUO; KATAYAMA, YOICHI

    2014-01-01

    Ribavirin (1-β-D-ribofuranosy-1,2,4-triazole-3-carboxamide) has been widely administered as an antiviral agent against RNA and DNA viruses. Ribavirin, in combination with interferon, has predominantly been applied in the treatment of the hepatitis C virus infection and its potential antitumor efficacy has recently become a point of interest. The aim of the present study was to evaluate the effect of ribavirin on the growth of malignant glioma cells, to identify novel predictive genes in malignant glioma cells (by analyzing gene expression profiles) and to assess the influence of ribavirin on the cell cycle of malignant glioma cells. The present study evaluated the antitumor efficacy of ribavirin against various malignant glioma cell lines (A-172, AM-38, T98G, U-87MG, U-138MG, U-251MG and YH-13). After culturing the cells in ribavirin-containing culture medium (final concentration, 0–1,000 μM) for 72 h, the viable proliferated cells were harvested and counted. The half maximal inhibitory concentration of ribavirin, with regard to the growth of the malignant glioma cell lines, was determined from the concentration of ribavirin required for 50% growth inhibition in comparison to the untreated control cells. Furthermore, the current study identified the genes in which the gene expression levels correlated with the ribavirin sensitivity of the malignant glioma cells lines, using a high-density oligonucleotide array. Finally, cell cycle analysis was performed on the U-87MG cell line. It was identified that ribavirin inhibited the growth of all of the malignant glioma cell lines in a dose-dependent manner, although the ribavirin sensitivity varied between each cell line. Of the extracted genes, PDGFRA demonstrated the strongest positive correlation between gene expression level and ribavirin sensitivity. Cell cycle analysis of the U-87MG cell line demonstrated that ribavirin treatment induces G0/G1 arrest and thus may be an effective agent for inhibiting malignant

  10. Isocitrate dehydrogenase 1 and 2 mutations in gliomas.

    Science.gov (United States)

    Megova, Magdalena; Drabek, Jiri; Koudelakova, Vladimira; Trojanec, Radek; Kalita, Ondrej; Hajduch, Marian

    2014-12-01

    Over the past few years, new biomarkers have allowed a deeper insight into gliomagenesis and facilitated the identification of possible targets for glioma therapy. Isocitrate dehydrogenase (IDH) 1 and IDH2 mutations have been shown to be promising biomarkers for monitoring disease prognosis and predicting the response to treatment. This review summarizes recent findings in this field. Web of Science, Science Direct, and PubMed online databases were used to search for publications investigating the role of IDH in glioma. References were identified by searching for the keywords "IDH1 or IDH2 and glioma and diagnostic or predictive or prognostic" in papers published from January, 2008, to April, 2014. Only papers in English were reviewed. Publications available only as an abstract were not included. IDH1/2 mutations are tightly associated with grade II and III gliomas and secondary glioblastomas, with better prognosis and production of a recently described oncometabolite, 2-hydroxyglutarate (2HG). Although the contradictory positive effect of IDH mutation on prognosis and negative role of 2HG in tumor transformation remain unresolved, the future direction of personalized treatment strategies targeted to glioma development is likely to focus on IDH1/2 mutations.

  11. Possible novel therapy for malignant gliomas with secretable trimeric TRAIL.

    Directory of Open Access Journals (Sweden)

    Moonsup Jeong

    Full Text Available Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and many novel therapeutic approaches, average survival for the patients with malignant gliomas is only about 1 year. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL has shown potent and cancer-selective killing activity and drawn considerable attention as a promising therapy for cancers, but concerns over delivery and toxicity have limited progress. We have developed a secretable trimeric TRAIL (stTRAIL and here evaluated the therapeutic potential of this stTRAIL-based gene therapy in brain tumors. An adenovirus (Ad-stTRAIL delivering stTRAIL was injected into intra-cranial human glioma tumors established in nude mice and tumor growth monitored using the magnetic resonance imaging (MRI. Ad-stTRAIL gene therapy showed potent tumor suppressor activity with no toxic side effects at therapeutically effective doses. When compared with 1, 3-bis(2-chloroethyl-1-nitrosourea (BCNU, a conventional therapy for malignant gliomas, Ad-stTRAIL suppressed tumor growth more potently. The combination of Ad-stTRAIL and BCNU significantly increased survival compared to the control mice or mice receiving Ad-stTRAIL alone. Our data indicate that Ad-stTRAIL, either alone or combined with BCNU, has promise as a novel therapy for malignant gliomas.

  12. Cannabinoids as potential new therapy for the treatment of gliomas.

    Science.gov (United States)

    Parolaro, Daniela; Massi, Paola

    2008-01-01

    Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin) for their treatment are only palliative and survival diagnosis is normally 6-12 months. The development of new therapeutic strategies for the management of gliomas is therefore essential. Interestingly, cannabinoids have been shown to exert antiproliferative effects on a wide spectrum of cells in culture. Of interest, cannabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models, curbing the growth of xenografts generated by subcutaneous or intratecal injection of glioma cells in immune-deficient mice. Moreover, cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of nontransformed counterparts. A pilot clinical trial on patients with glioblastoma multiforme demonstrated their good safety profile together and remarkable antitumor effects, and may set the basis for further studies aimed at better evaluating the potential anticancer activity of cannabinoids.

  13. Impact of Temozolomide on Immune Response during Malignant Glioma Chemotherapy

    Directory of Open Access Journals (Sweden)

    Sadhak Sengupta

    2012-01-01

    Full Text Available Malignant glioma, or glioblastoma, is the most common and lethal form of brain tumor with a median survival time of 15 months. The established therapeutic regimen includes a tripartite therapy of surgical resection followed by radiation and temozolomide (TMZ chemotherapy, concurrently with radiation and then as an adjuvant. TMZ, a DNA alkylating agent, is the most successful antiglioma drug and has added several months to the life expectancy of malignant glioma patients. However, TMZ is also responsible for inducing lymphopenia and myelosuppression in malignant glioma patients undergoing chemotherapy. Although TMZ-induced lymphopenia has been attributed to facilitate antitumor vaccination studies by inducing passive immune response, in general lymphopenic conditions have been associated with poor immune surveillance leading to opportunistic infections in glioma patients, as well as disrupting active antiglioma immune response by depleting both T and NK cells. Deletion of O6-methylguanine-DNA-methyltransferase (MGMT activity, a DNA repair enzyme, by temozolomide has been determined to be the cause of lymphopenia. Drug-resistant mutation of the MGMT protein has been shown to render chemoprotection against TMZ. The immune modulating role of TMZ during glioma chemotherapy and possible mechanisms to establish a strong TMZ-resistant immune response have been discussed.

  14. Clinicopathologic implications of NF1 gene alterations in diffuse gliomas.

    Science.gov (United States)

    Vizcaíno, M Adelita; Shah, Smit; Eberhart, Charles G; Rodriguez, Fausto J

    2015-09-01

    Recent studies have identified somatic alterations in the gene encoding for neurofibromin (NF1) in a subset of glioblastoma (GBM), usually associated with the mesenchymal molecular subtype. To understand the significance of NF1 genetic alterations in diffuse gliomas in general, we evaluated public databases and tested for NF1 copy number alterations in a cohort using fluorescence in situ hybridization. NF1 genetic loss (homozygous NF1 deletions or mutations with predicted functional consequences) was present in 30 (of 281) (11%) GBM and 21 (of 286) (7%) lower-grade gliomas in The Cancer Genome Atlas data. Furthermore, NF1 loss was associated with worse overall and disease-specific survival in the lower-grade glioma, but not GBM, Group in The Cancer Genome Atlas cohort. IDH1 or 2 mutations co-existed in lower-grade gliomas with NF1 loss (36%) but not in GBM. In our cohort studied by fluorescence in situ hybridization, NF1/17q (n = 2) or whole Ch17 (n = 3) losses were only identified in the GBM group (5/86 [6%]). Tumors with NF1/Ch17 loss were predominantly adult GBM (4/5); lacked EGFR amplification (0/4), strong p53 immunolabeling (1/5), or IDH1 (R132H) protein expression (0/5); but expressed the mesenchymal marker podoplanin in 4/5. NF1 genetic loss occurs in a subset of diffuse gliomas, and its significance deserves further exploration.

  15. A graphic method for identification of novel glioma related genes.

    Science.gov (United States)

    Gao, Yu-Fei; Shu, Yang; Yang, Lei; He, Yi-Chun; Li, Li-Peng; Huang, GuaHua; Li, Hai-Peng; Jiang, Yang

    2014-01-01

    Glioma, as the most common and lethal intracranial tumor, is a serious disease that causes many deaths every year. Good comprehension of the mechanism underlying this disease is very helpful to design effective treatments. However, up to now, the knowledge of this disease is still limited. It is an important step to understand the mechanism underlying this disease by uncovering its related genes. In this study, a graphic method was proposed to identify novel glioma related genes based on known glioma related genes. A weighted graph was constructed according to the protein-protein interaction information retrieved from STRING and the well-known shortest path algorithm was employed to discover novel genes. The following analysis suggests that some of them are related to the biological process of glioma, proving that our method was effective in identifying novel glioma related genes. We hope that the proposed method would be applied to study other diseases and provide useful information to medical workers, thereby designing effective treatments of different diseases.

  16. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Ryabova, A. I., E-mail: ranigor@mail.ru; Novikov, V. A.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Choinzonov, E. L. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Siberian State Medical University, Tomsk, 634050 (Russian Federation); Gribova, O. V. [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Baranova, A. V. [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  17. The molecular biology of WHO grade II gliomas.

    Science.gov (United States)

    Marko, Nicholas F; Weil, Robert J

    2013-02-01

    The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the "low-grade gliomas," these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.

  18. Epo is involved in angiogenesis in human glioma.

    Science.gov (United States)

    Nico, Beatrice; Annese, Tiziana; Guidolin, Diego; Finato, Nicoletta; Crivellato, Enrico; Ribatti, Domenico

    2011-03-01

    In this study, the extent of angiogenesis, evaluated as microvascular density, and the immunoreactivity of tumor cells to erythropoietin (Epo) and of endothelial cells to Epo receptor (EpoR) have been correlated in human glioma specimens, and the effect of anti-Epo antibody on glioma-induced angiogenesis in vivo in the chick embryo chorioallantoic membrane (CAM) has been investigated. Results show that: (1) Epo/EpoR expression correlates with angiogenesis, (2) in the CAM assay, tumor bioptic specimens induce a strong angiogenic response, comparable to that induced by VEGF, and (3) an anti-Epo antibody co-administered with tumor bioptic specimens significantly inhibits the angiogenic response. These findings suggest the presence of a loop in the Epo/EpoR system, i.e. Epo is secreted by glioma tumor cells and it affects glioma vascular endothelial cells via its receptor and promotes angiogenesis in a paracrine manner. Moreover, as demonstrated by in vivo experiments, Epo is responsible for the strong angiogenic response induced by human glioma bioptic specimens, because an anti-Epo antibody is able to significantly inhibit this response.

  19. A Graphic Method for Identification of Novel Glioma Related Genes

    Directory of Open Access Journals (Sweden)

    Yu-Fei Gao

    2014-01-01

    Full Text Available Glioma, as the most common and lethal intracranial tumor, is a serious disease that causes many deaths every year. Good comprehension of the mechanism underlying this disease is very helpful to design effective treatments. However, up to now, the knowledge of this disease is still limited. It is an important step to understand the mechanism underlying this disease by uncovering its related genes. In this study, a graphic method was proposed to identify novel glioma related genes based on known glioma related genes. A weighted graph was constructed according to the protein-protein interaction information retrieved from STRING and the well-known shortest path algorithm was employed to discover novel genes. The following analysis suggests that some of them are related to the biological process of glioma, proving that our method was effective in identifying novel glioma related genes. We hope that the proposed method would be applied to study other diseases and provide useful information to medical workers, thereby designing effective treatments of different diseases.

  20. Targeting the erythropoietin receptor on glioma cells reduces tumour growth

    Energy Technology Data Exchange (ETDEWEB)

    Peres, Elodie A.; Valable, Samuel [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Guillamo, Jean-Sebastien [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Departement de Neurologie, CHU de Caen (France); Marteau, Lena [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Bernaudin, Jean-Francois [Service d' Histologie-Biologie Tumorale, ER2UPMC, Universite Paris 6, Hopital Tenon, Paris (France); Roussel, Simon [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Lechapt-Zalcman, Emmanuele [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Service d' Anatomie Pathologique, CHU de Caen (France); Bernaudin, Myriam [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France); Petit, Edwige, E-mail: epetit@cyceron.fr [CERVOxy team ' Hypoxia and cerebrovascular pathophysiology' , UMR 6232 CI-NAPS, Universite de Caen Basse-Normandie, Universite Paris-Descartes, CNRS, CEA. G.I.P. CYCERON, Caen (France)

    2011-10-01

    Hypoxia has been shown to be one of the major events involved in EPO expression. Accordingly, EPO might be expressed by cerebral neoplastic cells, especially in glioblastoma, known to be highly hypoxic tumours. The expression of EPOR has been described in glioma cells. However, data from the literature remain descriptive and controversial. On the basis of an endogenous source of EPO in the brain, we have focused on a potential role of EPOR in brain tumour growth. In the present study, with complementary approaches to target EPO/EPOR signalling, we demonstrate the presence of a functional EPO/EPOR system on glioma cells leading to the activation of the ERK pathway. This EPO/EPOR system is involved in glioma cell proliferation in vitro. In vivo, we show that the down-regulation of EPOR expression on glioma cells reduces tumour growth and enhances animal survival. Our results support the hypothesis that EPOR signalling in tumour cells is involved in the control of glioma growth.

  1. Concurrent thermochemoradiotherapy for brain high-grade glioma

    Science.gov (United States)

    Ryabova, A. I.; Novikov, V. A.; Choinzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Bober, E. E.; Frolova, I. G.; Baranova, A. V.

    2016-08-01

    Despite the achievements in the current strategies for treatment, the prognosis in malignant glioma patients remains unsatisfactory. Hyperthermia is currently considered to be the most effective and universal modifier of radiotherapy and chemotherapy. Preliminary treatment outcomes for 28 patients with newly diagnosed (23) and recurrent (5) high-grade gliomas were presented. All the patients received multimodality treatment including surgery, thermoche-moradiotherapy followed by 4 cycles of adjuvant chemotherapy. All the patients endured thermochemoradiotherapy well. A complication, limited skin burn (II stage), was diagnosed in two cases and treated conservatively without treatment interruption. A month after thermochemoradiotherapy the results were as follows: complete regression was achieved in 4 cases, partial regression in 4 cases, stable disease in 14 cases and disease progression in 6 cases (one of them is pseudo-progression). After completing the adjuvant chemotherapy 2 more patients demonstrated complete response and 1 patient had disease progression. Introduction of local hyperthermia in multimodal therapy of malignant glioma does not impair the combined modality treatment tolerability of patients with malignant gliomas. A small number of studied patients and short follow-up time do not allow making reliable conclusions about the impact of local hyperthermia on the treatment outcomes; however, there is a tendency towards the increase in disease-free survival in the patients with newly diagnosed malignant gliomas.

  2. Intrinsic Motivation in Physical Education

    Science.gov (United States)

    Davies, Benjamin; Nambiar, Nathan; Hemphill, Caroline; Devietti, Elizabeth; Massengale, Alexandra; McCredie, Patrick

    2015-01-01

    This article describes ways in which educators can use Harter's perceived competence motivation theory, the achievement goal theory, and self-determination theory to develop students' intrinsic motivation to maintain physical fitness, as demonstrated by the Sound Body Sound Mind curriculum and proven effective by the 2013 University of…

  3. Relapse of herpes encephalitis induced by temozolomide-based chemoradiation in a patient with malignant glioma.

    Science.gov (United States)

    Okada, Masaki; Miyake, Keisuke; Shinomiya, Aya; Kawai, Nobuyuki; Tamiya, Takashi

    2013-02-01

    The authors report on a case of concurrent herpes simplex encephalitis (HSE) and malignant glioma. The co-occurrence of HSE and malignant glioma is very rare, but it can occur during glioma treatment. Both radiotherapy and chemoradiation with temozolomide can induce viral reactivation, leading to HSE relapse. Careful observation for HSE is necessary when administering chemoradiation to patients with a history of HSE. Antiviral therapy for HSE must be initiated immediately, and the chemoradiation for glioma should be stopped; however, it is not clear what antitumor therapy is optimal when HSE co-occurs during the treatment of glioma.

  4. In Vivo Imaging of Hypoxia-Inducible Factor Regulation in a Subcutaneous and Orthotopic GL261 Glioma Tumor Model Using a Reporter Gene Assay

    Directory of Open Access Journals (Sweden)

    Sandra Bürgi

    2014-11-01

    Full Text Available Intratumoral hypoxia changes the metabolism of gliomas, leading to a more aggressive phenotype with increased resistance to radio- and chemotherapy. Hypoxia triggers a signaling cascade with hypoxia-inducible factor (HIF as a key regulator. We monitored activation of the HIF pathway longitudinally in murine glioma tumors. GL261 cells, stably transfected with a luciferase reporter driven under the control of a promoter comprising the HIF target gene motive hypoxia response element, were implanted either subcutaneously or orthotopically. In vivo experiments were carried out using bioluminescence imaging. Tumors were subsequently analyzed using immunofluorescence staining for hypoxia, endothelial cells, tumor perfusion, and glucose transporter expression. Transient upregulation of the HIF signaling was observed in both subcutaneous and orthotopic gliomas. Immunofluorescence staining confirmed hypoxic regions in subcutaneous and, to a lesser extent, intracranial tumors. Subcutaneous tumors showed substantial necrosis, which might contribute to the decreased bioluminescence output observed toward the end of the experiment. Orthotopic tumors were less hypoxic than subcutaneous ones and did not develop extensive necrotic areas. Although this may be the result of the overall smaller size of orthotopic tumors, it might also reflect differences in the local environment, such as the better intrinsic vascularization of brain tissue compared to the subcutaneous tissue compartment.

  5. Morphologic Relationship between the Pontine Micturition Center and the Sympathetic Center in the Spinal Cord of the Rat

    Institute of Scientific and Technical Information of China (English)

    WU Xinhong; XIAO Chuanguo

    2005-01-01

    Summary: To study whether the sympathetic nerves coordinate with the parasympathetic nerves during micturition in the rat. We used antegrade neural tracing with biotinylated dextran amine (BDA) injected into the pontine micturition center (PMC) to label the terminals in the L6-S1 cord. Preganglionic parasympathetic neurons (PPNs) in the L6-S1 segment were labelled by retrograde transport of Fluorogold (FG) from the major pelvic ganglion (MPG).We detected retrograde neurons in L6-S1 using retrograde transport of horseradish peroxidase (HRP) from the intermediolateral cell column (IML) of the L1-L2 segment where sympathetic preganglionic neurons (SPNs) are located. Immunohistochemical methods showed that PPNs were identified to be choline acetyltransferase-immunoreactive (ChAT-IR). HRP-labelled neurons were not ChAT-IR and located dorsal to PPNs. BDA-labelled terminals were located mainly in the bilateral IML of L6-S1, some of which had synaptic contact with the HRP-labelled neurons. In addition, there were some wheat germ agglutinin-horseradish peroxidase (WGA-HRP) labelled terminals in the ipsilateral IML of the L1-L2 segment after WGA-HRP was microinjected into SPN. We conclude that PMC may control the preganglionic neurons of sympathetic nerves through the interneurons located dorsal to PPNs.

  6. Chemical Topography of Efferent Projections from the Median Preoptic Nucleus to Pontine Monoaminergic Cell Groups in the Rat

    Science.gov (United States)

    Zardetto-Smith, Andrea M.; Johnson, Alan Kim

    1995-01-01

    This study examined efferent output from the median preoptic nucleus (MNPO) to pontine noradrenergic and serotonergic cell groups using an anterograde tracing technique (Phaseolus vulgaris leucoagglutinin, PHA-L) combined with glucose oxidase immunocytochemistry to serotonin (5-HT) or to dopamine-beta-hydroxylase (DBH). Injections of PHA-L into the ventral MNPO resulted in moderate axonal labeling within the region of the B7 and B8 serotonergic groups in the dorsal raphe. PHA-L labeled fibers and punctate processes were observed in close apposition to many of the 5-HT immunoreactive neurons in these regions. In contrast, sparse terminal labeling was found within the B5 group in the raphe pontis nucleus, and only trace fiber labeling observed in the B3 and B6 groups. Efferents from the MNPO also provided moderate innervation to the A6 and A7 noradrenergic groups. PHA-L labeled punctate processes were found most frequently in close apposition to DBH-immunoreactive neurons at mid- to caudal levels of the locus coeruleus. Some labeled axons were also present within the A7 and A5 groups. Additionally, a close apposition between labeled MNPO efferents and 5-HT fibers within the lateral parabrachial nucleus was observed. The results indicate the MNPO provides a topographic innervation of monoaminergic groups in the upper brainstem.

  7. Pudendal but not tibial nerve stimulation inhibits bladder contractions induced by stimulation of pontine micturition center in cats.

    Science.gov (United States)

    Lyon, Timothy D; Ferroni, Matthew C; Kadow, Brian T; Slater, Richard C; Zhang, Zhaocun; Chang, Victor; Lamm, Vladimir; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2016-02-15

    This study examined the possibility that pudendal nerve stimulation (PNS) or tibial nerve stimulation (TNS) inhibits the excitatory pathway from the pontine micturition center (PMC) to the urinary bladder. In decerebrate cats under α-chloralose anesthesia, electrical stimulation of the PMC (40 Hz frequency, 0.2-ms pulse width, 10-25 s duration) using a microelectrode induced bladder contractions >20 cmH2O amplitude when the bladder was filled to 60-70% capacity. PNS or TNS (5 Hz, 0.2 ms) at two and four times the threshold (2T and 4T) to induce anal or toe twitch was applied to inhibit the PMC stimulation-induced bladder contractions. Propranolol, a nonselective β-adrenergic receptor antagonist, was administered intravenously (1 mg/kg i.v.) to determine the role of sympathetic pathways in PNS/TNS inhibition. PNS at both 2T and 4T significantly (P contractions induced by PMC stimulation, while TNS at 4T facilitated the bladder contractions. Propranolol completely eliminated PNS inhibition and TNS facilitation. This study indicates that PNS, but not TNS, inhibits PMC stimulation-induced bladder contractions via a β-adrenergic mechanism that may occur in the detrusor muscle as a result of reflex activity in lumbar sympathetic nerves. Neither PNS nor TNS activated a central inhibitory pathway with synaptic connections to the sacral parasympathetic neurons that innervate the bladder. Understanding the site of action involved in bladder neuromodulation is important for developing new therapies for bladder disorders.

  8. Expanding the clinical, radiological and neuropathological phenotype of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

    Science.gov (United States)

    Simon, Neil G; Parratt, John D; Barnett, Michael H; Buckland, Michael E; Gupta, Ruta; Hayes, Michael W; Masters, Lynette T; Reddel, Stephen W

    2012-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of the CNS with a predilection for the hindbrain and responsive to immunotherapy. Five further cases are described with detailed pathology and long term evaluation. CLIPPERS does not represent a benign condition, and without chronic immunosuppression the disease may relapse. The radiological distribution is focused not only in the pons but also in the brachium ponti and cerebellum. Pontocerebellar atrophy occurred early, even in cases treated promptly. Significant cognitive impairment was seen in some cases and was associated with additional cerebral atrophy. The pathology included distinctive histiocytic as well as lymphocytic components and evidence of neuro-axonal injury. Additional subclinical systemic findings on investigation were identified. Relapse was associated with withdrawal of corticosteroids, and disability was least marked in cases where both the presentation and relapses were treated promptly. We propose that the title of the syndrome be amended to chronic lymphocytic inflammation with pontocerebellar perivascular enhancement responsive to steroids to more accurately reflect the distribution of the radiological findings.

  9. [Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) associated with swelling in the brainstem: a case report].

    Science.gov (United States)

    Tani, Hiroki; Nakajima, Hideto; Yamane, Kazushi; Ohnishi, Hiroyuki; Kimura, Fumiharu; Hanafusa, Toshiaki

    2014-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a rare central nervous system inflammatory disease characterized by the punctate gadolinium enhancement peppering the pons and the cerebellar peduncles as neuroimaging. We report the case of a 66-year-old woman who presented with CLIPPERS associated with swelling in the brainstem. She was hospitalized because of gait ataxia and consciousness disturbance. MRI of the brain showed FLAIR hyperintense lesions in the pons, cerebellar peduncles, cerebellum and the subcortical white matter lesion in the right occipital lobe with significant swelling in the brainstem. Diffusion-weighted MRI did not show an abnormal signal, indicating vasogenic edema. Post-contrast T1-weighted MRI showed enhanced area in the right occipital lobe and panctate gadolinium enhancement peppering brainstem. Treatment with steroids led to rapid improvement. However, she showed exacerbation of clinical and radiological findings during the tapering schedule of steroid. The biopsy from the occipital lobe revealed intense perivascular and parenchymal lymphocytic infiltrates composed of primarily T cells, B cells and macrophages. The patient was diagnosed with CLIPPERS, and treatment with increased dose of corticosteroid induced a clinical improvement. Previous reports well described a characteristic MRI finding of punctate enhancement peppering the pons. In addition, the pons and cerebellar peduncles swelling can occur in this disorder.

  10. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels.

    Science.gov (United States)

    Fujisawa, Naoaki; Oya, Soichi; Mori, Harushi; Matsui, Toru

    2015-11-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of β-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different.

  11. Central amygdala lesions inhibit pontine nuclei acoustic reactivity and retard delay eyeblink conditioning acquisition in adult rats.

    Science.gov (United States)

    Pochiro, Joseph M; Lindquist, Derick H

    2016-06-01

    In delay eyeblink conditioning (EBC) a neutral conditioned stimulus (CS; tone) is repeatedly paired with a mildly aversive unconditioned stimulus (US; periorbital electrical shock). Over training, subjects learn to produce an anticipatory eyeblink conditioned response (CR) during the CS, prior to US onset. While cerebellar synaptic plasticity is necessary for successful EBC, the amygdala is proposed to enhance eyeblink CR acquisition. In the current study, adult Long-Evans rats received bilateral sham or neurotoxic lesions of the central nucleus of the amygdala (CEA) followed by 1 or 4 EBC sessions. Fear-evoked freezing behavior, CS-mediated enhancement of the unconditioned response (UR), and eyeblink CR acquisition were all impaired in the CEA lesion rats relative to sham controls. There were also significantly fewer c-Fos immunoreactive cells in the pontine nuclei (PN)-major relays of acoustic information to the cerebellum-following the first and fourth EBC session in lesion rats. In sham rats, freezing behavior decreased from session 1 to 4, commensurate with nucleus-specific reductions in amygdala Fos+ cell counts. Results suggest delay EBC proceeds through three stages: in stage one the amygdala rapidly excites diffuse fear responses and PN acoustic reactivity, facilitating cerebellar synaptic plasticity and the development of eyeblink CRs in stage two, leading, in stage three, to a diminution or stabilization of conditioned fear responding.

  12. Glioma-initiating cells and molecular pathology: implications for therapy.

    Science.gov (United States)

    Natsume, Atsushi; Kinjo, Sayano; Yuki, Kanako; Kato, Takenori; Ohno, Masasuke; Motomura, Kazuya; Iwami, Kenichiro; Wakabayashi, Toshihiko

    2011-02-01

    There is now compelling evidence that gliomas harbor a small population of cells, termed glioma-initiating cells (GICs), characterized by their ability to undergo self-renewal and initiate tumorigenesis. The development of therapeutic strategies targeted toward GIC signaling may improve the treatment of malignant gliomas. The characterization of GICs provides a clue to elucidating histological heterogeneity and treatment failure. The role of the stem cell marker CD133 in the initiation and progression of brain tumors is still uncertain. Here, we review some of the signaling mechanisms involved in GIC biology, such as phosphatase and tensin homolog (PTEN), sonic hedgehog, Notch, and WNT signaling pathways, maternal embryonic leucine-zipper kinase (MELK), BMI1, and Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling. In addition, we discuss the role of microRNAs in GICs by focusing on microRNA-21 regulation by type I interferon.

  13. Targeting autophagy to sensitive glioma to temozolomide treatment.

    Science.gov (United States)

    Yan, Yuanliang; Xu, Zhijie; Dai, Shuang; Qian, Long; Sun, Lunquan; Gong, Zhicheng

    2016-02-02

    Temozolomide (TMZ), an alkylating agent, is widely used for treating primary and recurrent high-grade gliomas. However, the efficacy of TMZ is often limited by the development of resistance. Recently, studies have found that TMZ treatment could induce autophagy, which contributes to therapy resistance in glioma. To enhance the benefit of TMZ in the treatment of glioblastomas, effective combination strategies are needed to sensitize glioblastoma cells to TMZ. In this regard, as autophagy could promote cell survival or autophagic cell death, modulating autophagy using a pharmacological inhibitor, such as chloroquine, or an inducer, such as rapamycin, has received considerably more attention. To understand the effectiveness of regulating autophagy in glioblastoma treatment, this review summarizes reports on glioblastoma treatments with TMZ and autophagic modulators from in vitro and in vivo studies, as well as clinical trials. Additionally, we discuss the possibility of using autophagy regulatory compounds that can sensitive TMZ treatment as a chemotherapy for glioma treatment.

  14. Boldine: a potential new antiproliferative drug against glioma cell lines.

    Science.gov (United States)

    Gerhardt, Daniéli; Horn, Ana Paula; Gaelzer, Mariana Maier; Frozza, Rudimar Luiz; Delgado-Cañedo, Andrés; Pelegrini, Alessandra Luiza; Henriques, Amélia T; Lenz, Guido; Salbego, Christianne

    2009-12-01

    Malignant gliomas are the most common and devastating primary tumors of the central nervous system. Currently no efficient treatment is available. This study evaluated the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on glioma proliferation and cell death. Boldine decreased the cell number of U138-MG, U87-MG and C6 glioma lines at concentrations of 80, 250 and 500 muM. We observed that cell death caused by boldine was cell-type specific and dose-dependent. Exposure to boldine for 24 h did not activate key mediators of apoptosis. However, it induced alterations in the cell cycle suggesting a G(2)/M arrest in U138-MG cells. Boldine had no toxic effect on non-tumor cells when used at the same concentrations as those used on tumor cells. Based on these results, we speculate that boldine may be a promising compound for evaluation as an anti-cancer agent.

  15. Silver nanoparticles: a novel radiation sensitizer for glioma?

    Science.gov (United States)

    Liu, Peidang; Huang, Zhihai; Chen, Zhongwen; Xu, Ruizhi; Wu, Hao; Zang, Fengchao; Wang, Cailian; Gu, Ning

    2013-11-01

    Malignant gliomas are the most common primary intracranial tumors with a dismal prognosis. Previous investigations by our group demonstrated the radiosensitizing effect of silver nanoparticles (AgNPs) on glioma cells in vitro. The goal of the present study was to evaluate the efficacy of intratumoral administration of AgNPs in combination with a single dose of ionizing radiation at clinically relevant MV energies for the treatment of C6 glioma-bearing rats. AgNPs (10 or 20 μg/10 μl) were stereotactically administered on day 8 after tumor implantation. One day after AgNP injection, rats bearing glioma received 10 Gy radiation. The mean survival times were 100.5 and 98 days, the corresponding percent increase in life spans was 513.2% and 497.7%, and the cure rates were 41.7 and 38.5% at 200 days for the 10 and 20 μg AgNPs and radiation combination groups, respectively. In contrast, the mean survival times for irradiated controls, 10 and 20 μg AgNPs alone, and untreated controls were 24.5, 16.1, 19.4, and 16.4 days, respectively. Furthermore, a cooperative antiproliferative and proapoptotic effect was obtained when gliomas were treated with AgNPs followed by radiotherapy. Our results showed the therapeutic efficacy of AgNPs in combination with radiotherapy without apparent systemic toxicity, suggesting the clinical potential of AgNPs in improving the outcome of malignant glioma radiotherapy.Malignant gliomas are the most common primary intracranial tumors with a dismal prognosis. Previous investigations by our group demonstrated the radiosensitizing effect of silver nanoparticles (AgNPs) on glioma cells in vitro. The goal of the present study was to evaluate the efficacy of intratumoral administration of AgNPs in combination with a single dose of ionizing radiation at clinically relevant MV energies for the treatment of C6 glioma-bearing rats. AgNPs (10 or 20 μg/10 μl) were stereotactically administered on day 8 after tumor implantation. One day after Ag

  16. MR imaging of optic chiasmatic glioma

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seong Sook; Lee, Ho Kyu; Kim, Hyun Jin; Ryu, Meung Sun; Goo, Hyun Woo; Yoon, Chong Hyun; Choi, Choong Gon; Suh, Dae Chul; Ra, Young Shin; Khang, Shin Kwang [University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2002-08-01

    To evaluate the MR findings of optic chiasmatic glioma (OCG). MR images were reviewed in 14 patients with histologically proven OCGs and one with neurofibromatosis type 1 (male: female=8:7, mean age=8.5 years.) Tumors were evaluated retrospectively with respect to their size, involvement of the optic pathway, transverse/vertical diameter ratio based on the coronal plane, signal intensities, enhancement pattern, and the presence of a cyst or calcification. Tumors was measured 1.7-5.5 (mean, 3.3) cm in maximum diameter. In ten patients, the optic tracts were involved, and in three, the optic nerves. In 12 patients, tumors had a transverse/vertical diameter ratio of over one, and showed iso (n=5) or low signal intensity (n=10) compared with gray matter at T1-weighted imaging and high signal intensity (n=15) at T2-weighted imaging. Cyst formations were ween in eight patients, and tumors were enhanced strongly and homogeneously in nine and peripherally in four. In seven three was associated hydrocephalus, and in one, calcification. OCG is a suprasellar tumor which can extend into the optic pathway, has a transverse/vertical diameter ratio of more than one, and shows strong and homogeneous enhancement. These MR imaging findings are useful for the differentiation of OCG from other suprasellar tumors.

  17. Epigenetic aberrations and therapeutic implications in gliomas.

    Science.gov (United States)

    Natsume, Atsushi; Kondo, Yutaka; Ito, Motokazu; Motomura, Kazuya; Wakabayashi, Toshihiko; Yoshida, Jun

    2010-06-01

    Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor-suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing - a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY-ESO-1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia.

  18. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Cheng-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 406, Taiwan (China); Kuan, Yu-Hsiang [Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Ou, Yen-Chuan; Li, Jian-Ri [Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Wu, Chih-Cheng [Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan (China); Pan, Pin-Ho [Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 435, Taiwan (China); Chen, Wen-Ying [Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Huang, Hsuan-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Chen, Chun-Jung, E-mail: cjchen@vghtc.gov.tw [Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan (China); Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Center for General Education, Tunghai University, Taichung 407, Taiwan (China); Department of Nursing, HungKuang University, Taichung 433, Taiwan (China)

    2014-09-10

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK.

  19. Molecular subtypes of glioblastoma are relevant to lower grade glioma.

    Directory of Open Access Journals (Sweden)

    Xiaowei Guan

    Full Text Available Gliomas are the most common primary malignant brain tumors in adults with great heterogeneity in histopathology and clinical course. The intent was to evaluate the relevance of known glioblastoma (GBM expression and methylation based subtypes to grade II and III gliomas (ie. lower grade gliomas.Gene expression array, single nucleotide polymorphism (SNP array and clinical data were obtained for 228 GBMs and 176 grade II/II gliomas (GII/III from the publically available Rembrandt dataset. Two additional datasets with IDH1 mutation status were utilized as validation datasets (one publicly available dataset and one newly generated dataset from MD Anderson. Unsupervised clustering was performed and compared to gene expression subtypes assigned using the Verhaak et al 840-gene classifier. The glioma-CpG Island Methylator Phenotype (G-CIMP was assigned using prediction models by Fine et al.Unsupervised clustering by gene expression aligned with the Verhaak 840-gene subtype group assignments. GII/IIIs were preferentially assigned to the proneural subtype with IDH1 mutation and G-CIMP. GBMs were evenly distributed among the four subtypes. Proneural, IDH1 mutant, G-CIMP GII/III s had significantly better survival than other molecular subtypes. Only 6% of GBMs were proneural and had either IDH1 mutation or G-CIMP but these tumors had significantly better survival than other GBMs. Copy number changes in chromosomes 1p and 19q were associated with GII/IIIs, while these changes in CDKN2A, PTEN and EGFR were more commonly associated with GBMs.GBM gene-expression and methylation based subtypes are relevant for GII/III s and associate with overall survival differences. A better understanding of the association between these subtypes and GII/IIIs could further knowledge regarding prognosis and mechanisms of glioma progression.

  20. Progress of temozolomide in the treatment of recurrent high-grade gliomas

    Directory of Open Access Journals (Sweden)

    LI Jin-duo

    2013-12-01

    Full Text Available High-grade gliomas are central nervous system malignancies which are difficult to treat. Surgery, temozolomide combined with radiotherapy postoperatively and adjuvant chemotherapy with temozolomide have been established as the standard treatment options for high-grade gliomas. Nevertheless, the prognosis of patients with high-grade gliomas remains poor. At present, there is no standard therapy for recurrent or relapsed high-grade gliomas. Temozolomide is still an effective drug for the treatment of recurrent high-grade gliomas. According to the characteristics of patients, there have been many kinds of temozolomide administration and other treatments in combination. Individual therapy were paid more attention, so that the patients with high-grade gliomas recurrence could get greater survival benefit. This paper aims to introduce the progress of temozolomide in the treatment of recurrent high-grade gliomas in recent years.

  1. CREB1 regulates glucose transport of glioma cell line U87 by targeting GLUT1.

    Science.gov (United States)

    Chen, Jiaying; Zhang, Can; Mi, Yang; Chen, Fuxue; Du, Dongshu

    2017-06-23

    Glioma is stemmed from the glial cells in the brain, which is accounted for about 45% of all intracranial tumors. The characteristic of glioma is invasive growth, as well as there is no obvious boundary between normal brain tissue and glioma tissue, so it is difficult to resect completely with worst prognosis. The metabolism of glioma is following the Warburg effect. Previous researches have shown that GLUT1, as a glucose transporter carrier, affected the Warburg effect, but the molecular mechanism is not very clear. CREB1 (cAMP responsive element-binding protein1) is involved in various biological processes, and relevant studies confirmed that CREB1 protein regulated the expression of GLUT1, thus mediating glucose transport in cells. Our experiments mainly reveal that the CREB1 could affect glucose transport in glioma cells by regulating the expression of GLUT1, which controlled the metabolism of glioma and affected the progression of glioma.

  2. [Arteriovenous malformation-glioma association: study of four cases].

    Science.gov (United States)

    Borges, Lia Raquel R; Malheiros, Suzana M F; Pelaez, Maria Paula; Stávale, João Norberto; Santos, Adrialdo J; Carrete, Henrique; Nogueira, Roberto Gomes; Ferraz, Fernando A P; Gabbai, Alberto A

    2003-06-01

    We reviewed the clinical presentation, imaging and histopathologic findings in 4 patients with the diagnosis of arteriovenous malformation associated with glioma that were operated on from 1991 to 2000 in our institution. Four patients (2 males; age between 15 and 52 years) presented with progressive headache with clinical evidence of intracranial hypertension (in 3) and partial seizures (in 1). CT scan showed a brain tumor without any detectable pathologic vessels. Histologic examination revealed astrocytic tumors associated with arteriovenous malformation. No patient presented the vascular component intermixed with the tumor. The arteriovenous-glioma association is rare and must be identified by a clear demarcation between the malformation and the tumor.

  3. Diagnostic and prognostic value of IDH1 mutation in gliomas

    Directory of Open Access Journals (Sweden)

    YANG Yan-wu

    2012-12-01

    Full Text Available Objective To discuss the significance of IDH1 mutation for diagnosis and prognosis of gliomas through detecting of IDH1 mutation in supratentorial glioma cells. Methods IDH1 genes of postoperative pathological samples obtained from 315 patients with supratentorial gliomas (3 cases of WHO Ⅰ, 95 cases of WHO Ⅱ, 37 cases of WHO Ⅲ and 180 cases of WHO Ⅳ were collected for DNA extraction, on which PCR amplification and direct sequencing were done. At the same time, multiple-factor analysis was used on those patients' age, sex, tumor location, excision extension, Karnofsky Performance Status (KPS and progression-free survival time or median survival time, to investigate the influence of IDH1 mutation on the prognosis of patients. Results A total of 112 gene mutations among 315 cases (35.56% were found and they were all R132H type of mutations. Mutation rates in WHOⅡ, Ⅲ and Ⅳ gliomas were 72.63% (69/95, 24.32% (9/37 and 18.89% (34/180 respectively, which were significantly different (P = 0.000, for all. Among patients with IDH1 mutations in WHOⅣ gliomas, there were 18 cases of primary glioblastoma and 16 cases of secondary glioblastoma, the mutation rates of which were 11.39% (18/158 and 72.73% (16/22, respectively. The latter was much higher than the former and the difference was statistically significant ( χ 2 = 23.654,P = 0.001. Survival analysis revealed that IDH1 mutation presented notable effect on the prognosis of patients with gliomas. Conclusion IDH1 mutation can happen in WHO Ⅱ, Ⅲ and Ⅳ gliomas, and the mutation rates of WHOⅡ gliomas and secondary glioblastomas of WHO Ⅳ are higher than others. The survival time of patients are remarkably influenced by IDH1 mutation, and the prognosis of patient with IDH1 mutation is good, which may suggest that IDH1 mutation is an important diagnostic and prognostic biomarker in different grades of gliomas.

  4. Ionizing radiation augments glioma tropism of mesenchymal stem cells.

    Science.gov (United States)

    Thomas, Jonathan G; Parker Kerrigan, Brittany C; Hossain, Anwar; Gumin, Joy; Shinojima, Naoki; Nwajei, Felix; Ezhilarasan, Ravesanker; Love, Patrice; Sulman, Erik P; Lang, Frederick F

    2017-03-31

    OBJECTIVE Mesenchymal stem cells (MSCs) have been shown to localize to gliomas after intravascular delivery. Because these cells home to areas of tissue injury, the authors hypothesized that the administration of ionizing radiation (IR) to tumor would enhance the tropism of MSCs to gliomas. Additionally, they sought to identify which radiation-induced factors might attract MSCs. METHODS To assess the effect of IR on MSC migration in vitro, transwell assays using conditioned medium (CM) from an irradiated commercially available glioma cell line (U87) and from irradiated patient-derived glioma stem-like cells (GSCs; GSC7-2 and GSC11) were employed. For in vivo testing, green fluorescent protein (GFP)-labeled MSCs were injected into the carotid artery of nude mice harboring orthotopic U87, GSC7-2, or GSC17 xenografts that were treated with either 0 or 10 Gy of IR, and brain sections were quantitatively analyzed by immunofluorescence for GFP-positive cells. These GSCs were used because GSC7-2 is a weak attractor of MSCs at baseline, whereas GSC17 is a strong attractor. To determine the factors implicated in IR-induced tropism, CM from irradiated GSC7-2 and from GSC11 was assayed with a cytokine array and quantitative ELISA. RESULTS Transwell migration assays revealed statistically significant enhanced MSC migration to CM from irradiated U87, GSC7-2, and GSC11 compared with nonirradiated controls and in a dose-dependent manner. After their intravascular delivery into nude mice harboring orthotopic gliomas, MSCs engrafted more successfully in irradiated U87 (p = 0.036), compared with nonirradiated controls. IR also significantly increased the tropism of MSCs to GSC7-2 xenografts (p = 0.043), which are known to attract MSCs only poorly at baseline (weak-attractor GSCs). Ionizing radiation also increased the engraftment of MSCs in strong-attractor GSC17 xenografts, but these increases did not reach statistical significance. The chemokine CCL2 was released by GSC7-2 and GSC

  5. The functional role of Notch signaling in human gliomas

    DEFF Research Database (Denmark)

    Stockhausen, Marie-Thérése; Kristoffersen, Karina; Poulsen, Hans Skovgaard

    2010-01-01

    have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now...... firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC. In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic...

  6. Glioma Stem Cells but Not Bulk Glioma Cells Upregulate IL-6 Secretion in Microglia/Brain Macrophages via Toll-like Receptor 4 Signaling.

    Science.gov (United States)

    a Dzaye, Omar Dildar; Hu, Feng; Derkow, Katja; Haage, Verena; Euskirchen, Philipp; Harms, Christoph; Lehnardt, Seija; Synowitz, Michael; Wolf, Susanne A; Kettenmann, Helmut

    2016-05-01

    Peripheral macrophages and resident microglia constitute the dominant glioma-infiltrating cells. The tumor induces an immunosuppressive and tumor-supportive phenotype in these glioma-associated microglia/brain macrophages (GAMs). A subpopulation of glioma cells acts as glioma stem cells (GSCs). We explored the interaction between GSCs and GAMs. Using CD133 as a marker of stemness, we enriched for or deprived the mouse glioma cell line GL261 of GSCs by fluorescence-activated cell sorting (FACS). Over the same period of time, 100 CD133(+ )GSCs had the capacity to form a tumor of comparable size to the ones formed by 10,000 CD133(-) GL261 cells. In IL-6(-/-) mice, only tumors formed by CD133(+ )cells were smaller compared with wild type. After stimulation of primary cultured microglia with medium from CD133-enriched GL261 glioma cells, we observed an selective upregulation in microglial IL-6 secretion dependent on Toll-like receptor (TLR) 4. Our results show that GSCs, but not the bulk glioma cells, initiate microglial IL-6 secretion via TLR4 signaling and that IL-6 regulates glioma growth by supporting GSCs. Using human glioma tissue, we could confirm the finding that GAMs are the major source of IL-6 in the tumor context.

  7. Immunotherapeutic targeting of shared melanoma-associated antigens in a murine glioma model.

    Science.gov (United States)

    Prins, Robert M; Odesa, Sylvia K; Liau, Linda M

    2003-12-01

    Immune-based treatments for central nervous system gliomas have traditionally lagged behind those of more immunogenic tumors such as melanoma. The relative paucity of defined glioma-associated antigens that can be targeted by the immune system may partially account for this situation. Antigens present on melanomas have been extensively characterized, both in humans and in murine preclinical models. Melanocytes and astrocytes are both derived embryologically from the neural ectoderm. Their neoplastic counterparts, malignant melanomas and gliomas, have been shown in humans to share common antigens at the RNA level. However, little is known concerning whether gliomas can be targeted by immune-based strategies that prime T cells to epitopes from melanoma-associated antigens (MAAs). In this study, we provide evidence that two common murine glioma cell lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related protein 2 (TRP-2). To understand the immunogenicity of murine gliomas to CD8(+) T cells, we examined the ability of a MAA-specific CTL cell line to lyse the glioma cells, as well as the in vivo expansion of MAA-specific CD8(+) T cells in animals harboring gliomas. Both glioma cell lines were lysed by a human gp100-specific CTL cell line in vitro. Mice harboring s.c. GL26 gliomas possessed TRP-2-specific CD8(+) T cells, providing further evidence that these gliomas express the protein products in the context of MHC class I. Furthermore, MAA peptide-pulsed dendritic cells could prime T cells that specifically recognize GL26 glioma cells in vitro. Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed dendritic cells had significantly extended survival when challenged with tumor cells in the brain, resulting in >50% long-term survival. These results suggest that shared MAAs on gliomas can be targeted immunotherapeutically, pointing the way to a new potential treatment option for patients with malignant gliomas.

  8. Dissection of mitogenic and neurodegenerative actions of cystine and glutamate in malignant gliomas.

    Science.gov (United States)

    Savaskan, N E; Seufert, S; Hauke, J; Tränkle, C; Eyüpoglu, I Y; Hahnen, E

    2011-01-06

    Malignant glioma represents one of the most aggressive and lethal human neoplasias. A hallmark of gliomas is their rapid proliferation and destruction of vital brain tissue, a process in which excessive glutamate release by glioma cells takes center stage. Pharmacologic antagonism with glutamate signaling through ionotropic glutamate receptors attenuates glioma progression in vivo, indicating that glutamate release by glioma cells is a prerequisite for rapid glioma growth. Glutamate has been suggested to promote glioma cell proliferation in an autocrine or paracrine manner, in particular by activation of the (RS)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrate (AMPA) subtype of glutamate receptors. Here, we dissect the effects of glutamate secretion on glioma progression. Glioma cells release glutamate through the amino-acid antiporter system X(c)(-), a process that is mechanistically linked with cystine incorporation. We show that disrupting glutamate secretion by interfering with the system X(c)(-) activity attenuates glioma cell proliferation solely cystine dependently, whereas glutamate itself does not augment glioma cell growth in vitro. Neither AMPA receptor agonism nor antagonism affects glioma growth in vitro. On a molecular level, AMPA insensitivity is concordant with a pronounced transcriptional downregulation of AMPA receptor subunits or overexpression of the fully edited GluR2 subunit, both of which block receptor activity. Strikingly, AMPA receptor inhibition in tumor-implanted brain slices resulted in markedly reduced tumor progression associated with alleviated neuronal cell death, suggesting that the ability of glutamate to promote glioma progression strictly requires the tumor microenvironment. Concerning a potential pharmacotherapy, targeting system X(c)(-) activity disrupts two major pathophysiological properties of glioma cells, that is, the induction of excitotoxic neuronal cell death and incorporation of cystine required for

  9. Immunohistochemical evaluation of tissue factor, fibrin/fibrinogen and D-dimers in canine gliomas.

    Science.gov (United States)

    de la Fuente, Cristian; Pumarola, Martí; Blasco, Ester; Fernández, Francisco; Viu, Judit; Añor, Sònia

    2014-06-01

    In human gliomas, tissue factor (TF) is overexpressed, associated with the grade of malignancy and influences tumour biology. Intra-tumoural fibrin/fibrinogen deposition and activation of the fibrinolytic system also play a role in tumour cell proliferation and angiogenesis. The first aim of the present study was to investigate TF expression and the presence of fibrin/fibrinogen and D-dimers in canine glioma biopsies, graded according to the World Health Organization (WHO) classification of tumours of the central nervous system. The second aim was to investigate the occurrence of intravascular thrombosis (IVT) in canine gliomas, as a potential histological marker of glioma type or grade of malignancy. An immunohistochemical study using antibodies against TF, fibrin/fibrinogen and D-dimers was performed with 24 glioma samples, including 15 oligodendrogliomas, 6 astrocytomas and 3 mixed gliomas. Immunohistochemical data were statistically analysed to determine whether there was any relationship between glioma type and grade of malignancy. All gliomas were moderate to strongly positive for TF and the staining score was significantly higher (P = 0.04) in high-grade (III or IV) than in low-grade (II) gliomas. Intra-tumoural fibrin/fibrinogen deposition was detected in all tumour biopsies assessed, and D-dimers were detected in 17/24 gliomas. IVT was a frequent finding, but was not linked to a specific glioma type or malignancy grade. TF expression, fibrin/fibrinogen deposition, extravascular fibrinolytic system activation and IVT occur in canine gliomas. Canine glioma might be a suitable model for studying coagulation and fibrinolysis as potential therapeutic targets for human gliomas.

  10. Harmonic structures and intrinsic torsion

    DEFF Research Database (Denmark)

    Conti, Diego; Madsen, Thomas Bruun

    We discuss the construction of 8-manifolds with harmonic Sp(2)Sp(1)-structures. In particular, we find 10 new examples of nilmanifolds that admit a closed 4-form Omega whose stabiliser is Sp(2)Sp(1). Our constructions entail the notion of SO(4)-structures on 7-manifolds. We present a thorough inv...... investigation of the intrinsic torsion of such structures; in addition to the construction of harmonic structures, this analysis leads to explicit Lie group examples with invariant intrinsic torsion.......We discuss the construction of 8-manifolds with harmonic Sp(2)Sp(1)-structures. In particular, we find 10 new examples of nilmanifolds that admit a closed 4-form Omega whose stabiliser is Sp(2)Sp(1). Our constructions entail the notion of SO(4)-structures on 7-manifolds. We present a thorough...

  11. Harmonic structures and intrinsic torsion

    DEFF Research Database (Denmark)

    Conti, Diego; Madsen, Thomas Bruun

    2015-01-01

    We discuss the construction of Sp(2)Sp(1)-structures whose fundamental form is closed. In particular, we find 10 new examples of 8-dimensional nilmanifolds that admit an invariant closed 4-form with stabiliser Sp(2) Sp(1). Our constructions entail the notion of SO(4)-structures on 7-manifolds. We...... present a thorough investigation of the intrinsic torsion of such structures, leading to the construction of explicit Lie group examples with invariant intrinsic torsion.......We discuss the construction of Sp(2)Sp(1)-structures whose fundamental form is closed. In particular, we find 10 new examples of 8-dimensional nilmanifolds that admit an invariant closed 4-form with stabiliser Sp(2) Sp(1). Our constructions entail the notion of SO(4)-structures on 7-manifolds. We...

  12. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    Directory of Open Access Journals (Sweden)

    Mueller-Klieser Wolfgang

    2011-07-01

    Full Text Available Abstract Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2, 3-oxoacid-CoA transferase 1 (OXCT1 and acetyl-CoA acetyltransferase 1 (ACAT1 were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic

  13. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    Science.gov (United States)

    2011-01-01

    Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently

  14. Intrinsic Patterns of Human Activity

    Science.gov (United States)

    Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

    2003-03-01

    Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly

  15. [The re-introduction of malaria in the Pontine Marshes and the Cassino district during the end of World War II. Biological warfare or global war tactics?].

    Science.gov (United States)

    Sabbatani, Sergio; Fiorino, Sirio; Manfredi, Roberto

    2013-12-01

    After the fall of the Fascist regime on September 8, 1943, Italy was split into two parts: (i) the Southern regions where the King Victor Emanuel III and the military general staff escaped was under the control of English-American allied armies, and (ii) the northern regions comprising Lazio, Tuscany, Umbria, and Marche still under the control of the Germans. The German Wehrmacht, after suffering several defeats on Southern lines, established a new strengthened line of defence called the Gustav line, located south of Rome and crossing in the western portion the recently-drained Pontine Marshes. In his book published in 2006, Frank Snowden hypothesised that occupying German armies in 1943 had initiated a programme of re-flooding the Pontine plain as a biological warfare strategy to re-introduce malaria infection in the territories south of Rome, Such a plan was intended (i) to slow down the advance of English-American forces, and (ii) to punish Italians who abandoned their former allies. Other authors, including Annibale Folchi, Erhard Geissler, and Jeanne Guillemin, have disputed this hypothesis based on an analysis of recently-uncovered archive documents. What is not disputed is that the flooding of the Pontine and Roman plains in 1943 contributed to a severe malaria epidemic in 1944, which was associated with exceptionally high morbidity and mortality rates in the afflicted populations. Herein, we critically evaluate the evidence and arguments of whether the Wehrmacht specifically aimed to spread malaria as a novel biological warfare strategy in Italy during the Second World War. In our opinion, evidence for specific orders to deliberately spread malaria by the German army is lacking, although the strategy itself may have been considered by Nazis during the waning years of the war.

  16. Job assignments, intrinsic motivation and explicit incentives

    OpenAIRE

    Nafziger, Julia

    2008-01-01

    This paper considers the interplay of job assignments with the intrinsic and extrinsic motivation of an agent. Job assignments influence the self confidence of the agent, and thereby his intrinsic motivation. Monetary reward allow the principal to complement intrinsic motivation with extrinsic incentives. The main result is that the principal chooses an inefficient job assignment rule to enhance the agent's intrinsic motivation even though she can motivate him with monetary rewards. This show...

  17. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A lymphocytic reactive response of the central nervous system? A case report.

    Science.gov (United States)

    Wang, Xiaolin; Huang, Dehui; Huang, Xusheng; Zhang, Jiatang; Ran, Ye; Lou, Xin; Gui, Qiuping; Yu, Shengyuan

    2017-04-15

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroid (CLIPPERS) was first described in 2010. The characteristic clinical picture, radiological distribution and steroid response have been well-described in previous reports. However, the underlying pathogenesis and nosological position of CLIPPERS in the CNS require further investigation for the primary CNS lymphoma have been identified by autopsy subsequently. Here, we report a 51-year-old woman who was diagnosed with CLIPPERS but progressed to primary CNS lymphomatoid granulomatosis, which supports that CLIPPERS is not just an inflammatory CNS disorder.

  18. Sodium-reduced continuous venovenous hemodiafiltration (CVVHDF) for the prevention of central pontine myelinolysis (CPM) in hyponatremic patients scheduled for orthotopic liver transplantation.

    Science.gov (United States)

    Lenk, Marcus R; Kaspar, Michael

    2012-08-01

    Two patients in end-stage hepatic failure presented for orthotopic liver transplantation with longstanding severe hyponatremia (121 and 122 mmol/L). Both patients underwent liver transplantation with the concomitant use of continuous venovenous hemodiafiltration. Replacement and dialysate solutions were prepared individually to contain a sodium level that was individually considered safe with regard to the development of central pontine myelinolysis. The sodium increase in both patients was within the expected and planned limits despite a situation of mass transfusion. Both patients did well postoperatively and neither patient suffered neurological deficits.

  19. Critical Neural Networks in Awake Surgery for Gliomas

    Science.gov (United States)

    KINOSHITA, Masashi; MIYASHITA, Katsuyoshi; TSUTSUI, Taishi; FURUTA, Takuya; NAKADA, Mitsutoshi

    2016-01-01

    From the embarrassing character commonly infiltrating eloquent brain regions, the surgical resection of glioma remains challenging. Owing to the recent development of in vivo visualization techniques for the human brain, white matter regions can be delineated using diffusion tensor imaging (DTI) as a routine clinical practice in neurosurgery. In confirmation of the results of DTI tractography, a direct electrical stimulation (DES) substantially influences the investigation of cortico-subcortical networks, which can be identified via specific symptoms elicited in the concerned white matter tracts (eg., the arcuate fascicle, superior longitudinal fascicles, inferior fronto-occipital fascicle, inferior longitudinal fascicle, frontal aslant tract, sensori-motor tracts, optic radiation, and so forth). During awake surgery for glioma using DES, it is important to identify the anatomo-functional structure of white matter tracts to identify the surgical boundaries of brain regions not only to achieve maximal resection of the glioma but also to maximally preserve quality of life. However, the risk exists that neurosurgeons may be misled by the inability of DTI to visualize the actual anatomy of the white matter fibers, resulting in inappropriate decisions regarding surgical boundaries. This review article provides information of the critical neuronal network that is necessary to identify and understand in awake surgery for glioma, with special references to white matter tracts and the author’s experiences. PMID:27250817

  20. The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma.

    Science.gov (United States)

    Bhat, Krishna P L; Salazar, Katrina L; Balasubramaniyan, Veerakumar; Wani, Khalida; Heathcock, Lindsey; Hollingsworth, Faith; James, Johanna D; Gumin, Joy; Diefes, Kristin L; Kim, Se Hoon; Turski, Alice; Azodi, Yasaman; Yang, Yuhui; Doucette, Tiffany; Colman, Howard; Sulman, Erik P; Lang, Frederick F; Rao, Ganesh; Copray, Sjef; Vaillant, Brian D; Aldape, Kenneth D

    2011-12-15

    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 neural stem cells (NSCs) induced MES marker expression and aberrant osteoblastic and chondrocytic differentiation in a TEAD-dependent fashion. Using chromatin immunoprecipitation (ChIP), we show that TAZ is directly recruited to a majority of MES gene promoters in a complex with TEAD2. The coexpression of TAZ, but not a mutated form of TAZ that lacks TEAD binding, with platelet-derived growth factor-B (PDGF-B) resulted in high-grade tumors with MES features in a murine model of glioma. Our studies uncover a direct role for TAZ and TEAD in driving the MES differentiation of malignant glioma.

  1. Mutant tristetraprolin: a potent inhibitor of malignant glioma cell growth

    Science.gov (United States)

    Malignant gliomas rely on the production of certain critical growth factors including VEGF, interleukin (IL)-6 and IL-8, to fuel rapid tumor growth, angiogenesis, and treatment resistance. Post-transcriptional regulation through adenine and uridine-rich elements of the 3' untranslated region is one ...

  2. Levetiracetam improves verbal memory in high-grade glioma patients

    NARCIS (Netherlands)

    de Groot, Marjolein; Douw, Linda; Sizoo, Eefje M; Bosma, Ingeborg; Froklage, Femke E; Heimans, Jan J; Postma, Tjeerd J; Klein, Martin; Reijneveld, Jaap C

    2013-01-01

    BACKGROUND: Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of

  3. Targeted therapies for malignant gliomas: novel agents, same barrier

    NARCIS (Netherlands)

    Lin, F.

    2013-01-01

    Malignant gliomas are common and devastating brain malignancies. Despite this extensive treatment the mean overall survival is still only 14.6 months and more effective treatments are urgently needed. Targeted therapy holds the promise for the new generation of chemotherapy due to the selectively ta

  4. Glioma surgery in eloquent areas : can we preserve cognition?

    NARCIS (Netherlands)

    Satoer, Djaina; Visch-Brink, Evy; Dirven, Clemens; Vincent, Arnaud

    2015-01-01

    BACKGROUND: Cognitive preservation is crucial in glioma surgery, as it is an important aspect of daily life functioning. Several studies claimed that surgery in eloquent areas is possible without causing severe cognitive damage. However, this conclusion was relatively ungrounded due to the lack of e

  5. Glioma surgery in eloquent areas: can we preserve cognition?

    NARCIS (Netherlands)

    D.D. Satoer (Djaina); E.G. Visch-Brink (Evy); C.M.F. Dirven (Clemens); A. Vincent (Audrey)

    2016-01-01

    textabstractBackground: Cognitive preservation is crucial in glioma surgery, as it is an important aspect of daily life functioning. Several studies claimed that surgery in eloquent areas is possible without causing severe cognitive damage. However, this conclusion was relatively ungrounded due to t

  6. Gliomas and the vascular fragility of the blood brain barrier

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo eDubois

    2014-12-01

    Full Text Available Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB. By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM, characterized by a highly heterogeneous cell population (including tumor stem cells, extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the blood brain barrier and the concerns that arise when this barrier is affected.

  7. An unusual cystic appearance of disseminated low-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Huang, T.; Zimmerman, R.A. [Dept. of Radiology, Children' s Hospital of Philadelphia, PA (United States); Perilongo, G. [Dipt. di Pediatria, Univ. di Padova (Italy); Kaufman, B.A. [Dept. of Neurosurgery, St Louis Children' s Hospital, St Louis, MO (United States); Holden, K.R. [Division of Pediatric Neurology, Room 511, Children' s Hospital, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425-2232 (United States); Carollo, C. [Division of Neuroradiology, Regione Veneto, Azienda Ospedalieri di Padova, Universita di Padova, Via Giustiniani 3, 35 128 Padua (Italy); Kling Chong, W.K. [Dept. of Radiology, Great Ormond Street Hospital for Children, London (United Kingdom)

    2001-10-01

    We report five cases of pediatric disseminated low-grade gliomas of the brainstem or spinal cord that exhibited an unusual, cystic pattern. Leptomeningeal disease was present in three of these at diagnosis, and was detected shortly afterwards in the other two. Four patients are alive up to 5 years later, following minimal to no intervention, while one is dead. (orig.)

  8. Glioma surgery in eloquent areas : can we preserve cognition?

    NARCIS (Netherlands)

    Satoer, Djaina; Visch-Brink, Evy; Dirven, Clemens; Vincent, Arnaud

    2015-01-01

    BACKGROUND: Cognitive preservation is crucial in glioma surgery, as it is an important aspect of daily life functioning. Several studies claimed that surgery in eloquent areas is possible without causing severe cognitive damage. However, this conclusion was relatively ungrounded due to the lack of

  9. Glioma surgery in eloquent areas: can we preserve cognition?

    NARCIS (Netherlands)

    D.D. Satoer (Djaina); E.G. Visch-Brink (Evy); C.M.F. Dirven (Clemens); A. Vincent (Audrey)

    2016-01-01

    markdownabstract__Background:__ Cognitive preservation is crucial in glioma surgery, as it is an important aspect of daily life functioning. Several studies claimed that surgery in eloquent areas is possible without causing severe cognitive damage. However, this conclusion was relatively ungrounded

  10. Prognostic Marker before Treatment of Patients with Malignant Glioma

    Directory of Open Access Journals (Sweden)

    Norbert Galldiks

    2012-11-01

    Full Text Available The purpose of this positron emission tomography (PET study was to compare the prognostic value of pretreatment volume of [11C] methionine (MET uptake and semiquantitative MET uptake ratio in patients with malignant glioma. The study population comprised 40 patients with malignant glioma. Pretreatment magnetic resonance imaging (MRI and MET-PET imaging were performed before the initiation of glioma treatment in all patients. The pretreatment MET uptake ratios and volumes were assessed. To create prognostically homogeneous subgroups, patients′ pretreatment prognostic factors were stratified according to the six classes of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA. Univariate and multivariate analyses were performed to determine significant prognostic factors. Survival analyses identified the pretreatment volume of MET uptake and a higher RTOG RPA class as significant predictors. In contrast, pretreatment maximum areas of contrast enhancement on MRI and semiquantitative MET uptake ratios could not be identified as significant prognostic factors. The patients′ outcomes and Karnofsky Performance Scale scores were significantly correlated with pretreatment volume of MET uptake but not with semiquantitative MET uptake ratio. The data suggest that pretreatment volumetry of MET uptake but not the semiquantitative MET uptake ratio is a useful biologic prognostic marker in patients with malignant glioma.

  11. Growth hormone and cancer: GH production and action in glioma?

    Science.gov (United States)

    Lea, Robert W; Dawson, Timothy; Martinez-Moreno, Carlos G; El-Abry, Nasra; Harvey, Steve

    2015-09-01

    The hypersecretion of pituitary growth hormone (GH) is associated with an increased risk of cancer, while reducing pituitary GH signaling reduces this risk. Roles for pituitary GH in cancer are therefore well established. The expression of the GH gene is, however, not confined to the pituitary gland and it is now known to occur in many extrapituitary tissues, in which it has local autocrine or paracrine actions, rather than endocrine function. It is, for instance, expressed in cancers of the prostate, lung, skin, endometrium and colon. The oncogenicity of autocrine GH may also be greater than that induced by endocrine or exogenous GH, as higher concentrations of GHR antagonists are required to inhibit its actions. This may reflect the fact that autocrine GH is thought to act at intracellular receptors directly after synthesis, in compartments not readily accessible to endocrine (or exogenous) GH. The roles and actions of extrapituitary GH in cancer may therefore differ from those of pituitary GH. The possibility that GH may be expressed and act in glioma tumors was therefore examined by immunohistochemistry. These results demonstrate, for the first time, the presence of abundant GH- and GH receptor (GHR-) immunoreactivity in glioma, in which they were co-localized in cytoplasmic but not nuclear compartments. These results demonstrate that glioma differs from most cancers in lacking nuclear GHRs, but GH is nevertheless likely to have autocrine or paracrine actions in the induction and progression of glioma.

  12. Convection-enhanced Delivery of Therapeutics for Malignant Gliomas

    Science.gov (United States)

    SAITO, Ryuta; TOMINAGA, Teiji

    2017-01-01

    Convection-enhanced delivery (CED) circumvents the blood–brain barrier by delivering agents directly into the tumor and surrounding parenchyma. CED can achieve large volumes of distribution by continuous positive-pressure infusion. Although promising as an effective drug delivery method in concept, the administration of therapeutic agents via CED is not without challenges. Limitations of distribution remain a problem in large brains, such as those of humans. Accurate and consistent delivery of an agent is another challenge associated with CED. Similar to the difficulties caused by immunosuppressive environments associated with gliomas, there are several mechanisms that make effective local drug distribution difficult in malignant gliomas. In this review, methods for local drug application targeting gliomas are discussed with special emphasis on CED. Although early clinical trials have failed to demonstrate the efficacy of CED against gliomas, CED potentially can be a platform for translating the molecular understanding of glioblastomas achieved in the laboratory into effective clinical treatments. Several clinical studies using CED of chemotherapeutic agents are ongoing. Successful delivery of effective agents should prove the efficacy of CED in the near future. PMID:27980285

  13. Gliomas and the vascular fragility of the blood brain barrier

    Science.gov (United States)

    Dubois, Luiz Gustavo; Campanati, Loraine; Righy, Cassia; D’Andrea-Meira, Isabella; Spohr, Tania Cristina Leite de Sampaio e; Porto-Carreiro, Isabel; Pereira, Claudia Maria; Balça-Silva, Joana; Kahn, Suzana Assad; DosSantos, Marcos F.; Oliveira, Marcela de Almeida Rabello; Ximenes-da-Silva, Adriana; Lopes, Maria Celeste; Faveret, Eduardo; Gasparetto, Emerson Leandro; Moura-Neto, Vivaldo

    2014-01-01

    Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB). By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM), characterized by a highly heterogeneous cell population (including tumor stem cells), extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the BBB and the concerns that arise when this barrier is affected. PMID:25565956

  14. A Neuroblastoma × Glioma Hybrid Cell Line with Morphine Receptors

    Science.gov (United States)

    Klee, Werner A.; Nirenberg, Marshall

    1974-01-01

    A neuroblastoma × glioma hybrid cell line with well-developed neural properties was found that has high-affinity morphine receptors. The average cell contains approximately 3 × 106 receptors. In contrast, parent cells and other neuroblastoma or hybrid cell lines tested had few or no morphine receptors. PMID:4530316

  15. Pediatric glioma stem cells: biologic strategies for oncolytic HSV virotherapy

    Directory of Open Access Journals (Sweden)

    Gregory K Friedman

    2013-02-01

    Full Text Available While glioblastoma multiforme (GBM is the most common adult malignant brain tumor, GBMs in childhood represent less than 10% of pediatric malignant brain tumors and are phenotypically and molecularly distinct from adult GBMs. Similar to adult patients, outcomes for children with high-grade gliomas (HGGs remain poor. Furthermore, the significant morbidity and mortality yielded by pediatric GBM is compounded by neurotoxicity for the developing brain caused by current therapies. Poor outcomes have been attributed to a subpopulation of chemotherapy and radiotherapy resistant cells, termed ‘glioma stem cells’ (GSCs, ‘glioma progenitor cells’, or ‘glioma-initiating cells', which have the ability to initiate and maintain the tumor and to repopulate the recurring tumor after conventional therapy. Future innovative therapies for pediatric HGGs must be able to eradicate these therapy-resistant GSCs. Oncolytic herpes simplex viruses, genetically engineered to be safe for normal cells and to express diverse foreign anti-tumor therapeutic genes, have been demonstrated in preclinical studies to infect and kill GSCs and tumor cells equally while sparing normal brain cells. In this review, we discuss the unique aspects of pediatric GSCs, including markers to identify them, the microenvironment they reside in, signaling pathways that regulate them, mechanisms of cellular resistance, and approaches to target GSCs, with a focus on the promising therapeutic, genetically engineered oncolytic herpes simplex virus (HSV.

  16. Epileptic seizures in patients with glioma: A single centre- based ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights ... Results: Preoperative seizures were noted in 33.8 % of glioma patients. ..... adverse effects and in any case, it is important to ... data or proper documentation. .... brain tumour-related epilepsy: seizure control, safety,.

  17. Senescence from glioma stem cell differentiation promotes tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Ouchi, Rie [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Okabe, Sachiko; Migita, Toshiro [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Nakano, Ichiro [Department of Neurosurgery, Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, AL 35233 (United States); Seimiya, Hiroyuki, E-mail: hseimiya@jfcr.or.jp [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan)

    2016-02-05

    Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such as IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM in part via paracrine effects of the secreted proteins. - Highlights: • Non-stem glioma cells (NSGCs) lose telomerase and eventually become senescent. • Senescent NSGCs secrete pro-angiogenic proteins, such as VEGFs, IL-6, and IL-8. • Senescent NSGCs enhance the growth of brain microvascular endothelial cells. • Senescent NSGCs enhance the tumorigenic potential of glioma stem cells in vivo.

  18. [Gliomas and BRCA genes mutations: fortuitous association or imputability?].

    Science.gov (United States)

    Girardstein-Boccara, Laura; Mari, Véronique; Met-Domestici, Marie; Burel-Vandenbos, Fanny; Berthet, Pascaline; Paquis, Philippe; Frenay, Marc Paul; Lebrun-Frenay, Christine

    2014-09-01

    BRCA is a tumor suppressor gene implicated in the major mechanisms of cellular stability in every type of cell. Its mutations are described in numerous cancers, mainly breast and ovarian in women. It was also found an increase of lifetime risk of pancreas, colon, prostate cancer or lymphoma in men carriers. We report the cases of two female patients aged 40 and 58-years-old female patients and one 35-years-old male patient, with brain or medullar gliomas, carriers of a germline mutation of BRCA gene. Those gliomas were particularly aggressive and were not responding to the standard treatment, with chemo and radiotherapy. The very unusual characteristics in location and evolutive profile of these central nervous system tumors raise the question of a genetical underlying mechanism, maybe linked to the BRCA gene mutation that carry these patients. In addition, a non-fortuitous association between germline mutation of BRCA and occurrence of a glioma can be evoked according to the embryological, epidemiological and biomolecular findings noted in the literature. Other clinical and experimental studies are necessary to precise the physiopathological link existing between BRCA mutations and the occurrence of a glioma; this could have therapeutical and clinical implications in the future.

  19. Levetiracetam improves verbal memory in high-grade glioma patients

    NARCIS (Netherlands)

    de Groot, Marjolein; Douw, Linda; Sizoo, Eefje M; Bosma, Ingeborg; Froklage, Femke E; Heimans, Jan J; Postma, Tjeerd J; Klein, Martin; Reijneveld, Jaap C

    BACKGROUND: Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of

  20. Expression and Prognostic Significance of p53 in Glioma Patients: A Meta-analysis.

    Science.gov (United States)

    Jin, Yueling; Xiao, Weizhong; Song, Tingting; Feng, Guangjia; Dai, Zhensheng

    2016-07-01

    Glioma is a brain tumor deriving from the neoplastic glial cells or neuroglia. Due to its resistance to anticancer drugs and different disease progress of individuals, patients with high-grade glioma are difficult to completely cure, leading to a poor prognosis and low overall survival. Therefore, there is an urgent need to look for prognostic and diagnostic indicators that can predict glioma grades. P53 is one of the widely studied biomarkers in human glioma. The purpose of this study was to comprehensively evaluate the significance of p53 expression in glioma grades and overall survival. We searched commonly used electronic databases to retrieve related articles of p53 expression in glioma. Overall, a total of 21 studies including 1322 glioma patients were finally screened out. We observed that the frequency of p53 immuno-positivity was higher in high-grade patients than that in low-grade category (63.8 vs. 41.6 %), and our statistic analysis indicated that p53 expression was associated with pathological grade of glioma (OR 2.93, 95 % CI 1.87-4.60, P p53 expression in patients with glioma. In conclusion, our results suggested that p53 immunohistochemical expression might have an effective usefulness in predicting the prognosis in patients with glioma.

  1. In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model

    Directory of Open Access Journals (Sweden)

    Meurer Luise

    2006-09-01

    Full Text Available Abstract Background ATP is an important signalling molecule in the peripheral and central nervous system. Both glioma growth and tumor resection induces cell death, thus liberating nucleotides to the extracellular medium. Nucleotides are hydrolyzed very slowly by gliomas when compared with astrocytes and induce neuronal cell death and glioma proliferation. The objective of the present study was to test the involvement of extracellular ATP in glioblastoma growth in a rat glioma model. Methods To deplete the extracellular ATP, the enzyme apyrase was tested on the treatment of gliomas implanted in the rats CNS. One million glioma C6 cells in 3 microliters of DMEM/FCS were injected in the right striata of male Wistar rats, 250–270 g. After 20 days, the rats were decapitated and the brain sectioning and stained with hematoxylin and eosine. We performed immunohistochemical experiments with Ki67, CD31 and VEGF. Total RNA was isolated from cultured glioma C6 cells and the cDNA was analyzed by Real Time-PCR with primers for the NTPDase family. Results C6 glioma cells effectively have a low expression of all NTPDases investigated, in comparison with normal astrocytes. The implanted glioma co-injected with apyrase had a significant reduction in the tumor size (p Conclusion These results indicate that the participation of extracellular ATP and the ecto-nucleotidases may be associated with the development of this type of brain tumor in an in vivo glioma model.

  2. Stochastic Intrinsic Kriging for Simulation Metamodelling

    NARCIS (Netherlands)

    Mehdad, E.; Kleijnen, Jack P.C.

    2014-01-01

    We derive intrinsic Kriging, using Matherons intrinsic random functions which eliminate the trend in classic Kriging. We formulate this intrinsic Kriging as a metamodel in deterministic and random simulation models. For random simulation we derive an experimental design that also specifies the numbe

  3. Plaques of Nonstenotic Basilar Arteries with Isolated Pontine Infarction on Three-dimensional High Isotropic Resolution Magnetic Resonance Imaging

    Institute of Scientific and Technical Information of China (English)

    Xian-Jin Zhu; Wei-Jian Jiang; Lei Liu; Li-Bin Hu; Wu Wang; Zun-Jing Liu

    2015-01-01

    Background:There are few studies for evaluating plaque characteristics of nonstenotic basilar arteries (BA).Our aim was to determine entire BA plaques with a three-dimensional volumetric isotropic turbo spin-echo acquisition (VISTA) and investigate the differences between the patients with and without isolated pontine infarction (IPI).Methods:Twenty-four consecutive symptomatic patients with nonstenotic BA on time of flight magnetic resonance angiography (TOF MRA) were enrolled from China-Japan Friendship Hospital between January 2014 and December 2014.BA was classified as "normal" or"irregular" based on TOF MRA,and "normal wall","slight wall-thickening",and "plaque" based on three-dimensional VISTA images.Outcomes from MRA and VISTA were compared.Patients were categorized as IPI and non-IPI groups based on the diffusion-weighted imaging.Clinical and plaque characteristics were compared between the two groups.Results:A total of 1024 image slices including 311 (30.37%) plaque slices,427 (41.70%) slight wall-thickening slices,and 286 (27.93%) normal wall slices for the entire BA from 23 patients were finally included for analysis.VISTA images detected plaques in all the 9 (100%) irregular MRA patients and 7 of 14 (50%) normal MRA patients.IPI was found in 1 1 (47.83%) patients.Compared to non-IPI group,the IPI group had a higher percentage of plaque slices (P =0.001) and lower percentage of normal wall slices (P =0.014) than non-IPI group.Conclusions:Three-dimensional VISTA images enable detection of BA plaques not visualized by MRA.BA plaques could be found in both the IPI and non-IPI group.However,IPI group showed plaques more extensively in BA than the non-IPI group.

  4. GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation.

    Science.gov (United States)

    Vanini, Giancarlo; Nemanis, Kriste; Baghdoyan, Helen A; Lydic, Ralph

    2014-07-01

    The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia and pain. The role of PnO γ-aminobutyric acid (GABA) in modulating these states remains incompletely understood. The present study used time to loss and time to resumption of righting response (LoRR and RoRR) as surrogate measures of loss and resumption of consciousness. This study tested three hypotheses: (i) pharmacologically manipulating GABA levels in rat PnO alters LoRR, RoRR and nociception; (ii) propofol decreases GABA levels in the PnO; and (iii) inhibiting GABA synthesis in the PnO blocks hyperalgesia caused by sleep deprivation. Administering a GABA synthesis inhibitor [3-mercaptopropionic acid (3-MPA)] or a GABA uptake inhibitor [nipecotic acid (NPA)] into rat PnO significantly altered LoRR caused by propofol. 3-MPA significantly decreased LoRR for propofol (-18%). NPA significantly increased LoRR during administration of propofol (36%). Neither 3-MPA nor NPA altered RoRR following cessation of propofol or isoflurane delivery. The finding that LoRR was decreased by 3-MPA and increased by NPA is consistent with measures showing that extracellular GABA levels in the PnO were decreased (41%) by propofol. Thermal nociception was significantly decreased by 3-MPA and increased by NPA, and 3-MPA blocked the hyperalgesia caused by sleep deprivation. The results demonstrate that GABA levels in the PnO regulate the time for loss of consciousness caused by propofol, extend the concept that anesthetic induction and emergence are not inverse processes, and suggest that GABAergic transmission in the PnO mediates hyperalgesia caused by sleep loss.

  5. Three-year prognosis of first-ever primary pontine hemorrhage in a hospital-based registry.

    Science.gov (United States)

    Ye, Zusen; Huang, Xiaoya; Han, Zhao; Shao, Bei; Cheng, Jianhua; Wang, Zhen; Zhang, Zheng; Xiao, Meijuan

    2015-07-01

    Our aim was to evaluate the mortality rate of primary pontine hemorrhage (PPH) and to determine the factors related to the prognosis. Limited data exist on the long-term prognosis and determinants of death in patients with PPH in China. Our study analyzed consecutive cases of first-ever PPH from April 2007 to March 2011 in a hospital-based stroke registry. Mortality rates during 30 day and 3 year follow-ups were analyzed. We used the Kaplan-Meier method to estimate the event rates and binary logistic regression analysis, and Cox proportional hazard regression analysis to identify predictors of short-term and long-term prognosis, respectively. A total of 76 patients were identified, 44 (57.89%) were men. Both 30 day and 3 year overall mortalities in men were higher than women but this different was not statistically significant. Coma on admission, hematoma ⩾ 4 mL and a massive hemorrhage were significantly related to 30 day mortality of PPH. Multivariate Cox proportional hazard regression revealed that coma on admission (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.16-4.13; p = 0.02) and hematoma ⩾ 4 mL (HR 2.23; 95% CI 1.25-3.96; p = 0.01) were independent predictors of 3 year mortality. In conclusion, the short-term mortality rate and factors related to the prognosis of Chinese patients with PPH are similar to those reported for other populations. A low Glasgow coma scale score on admission and a large hematoma volume may be related to poor 3 year prognosis after PPH.

  6. Endogenous cholinergic input to the pontine REM sleep generator is not required for REM sleep to occur.

    Science.gov (United States)

    Grace, Kevin P; Vanstone, Lindsay E; Horner, Richard L

    2014-10-22

    Initial theories of rapid eye movement (REM) sleep generation posited that induction of the state required activation of the pontine subceruleus (SubC) by cholinergic inputs. Although the capacity of cholinergic neurotransmission to contribute to REM sleep generation has been established, the role of cholinergic inputs in the generation of REM sleep is ultimately undetermined as the critical test of this hypothesis (local blockade of SubC acetylcholine receptors) has not been rigorously performed. We used bilateral microdialysis in freely behaving rats (n = 32), instrumented for electroencephalographic and electromyographic recording, to locally manipulate neurotransmission in the SubC with select drugs. As predicted, combined microperfusion of D-AP5 (glutamate receptor antagonist) and muscimol (GABAA receptor agonist) in the SubC virtually eliminated REM sleep. However, REM sleep was not reduced by scopolamine microperfusion in this same region, at a concentration capable of blocking the effects of cholinergic receptor stimulation. This result suggests that transmission of REM sleep drive to the SubC is acetylcholine-independent. Although SubC cholinergic inputs are not majorly involved in REM sleep generation, they may perform a minor function in the reinforcement of transitions into REM sleep, as evidenced by increases in non-REM-to-REM sleep transition duration and failure rate during cholinergic receptor blockade. Cholinergic receptor antagonism also attenuated the normal increase in hippocampal θ oscillations that characterize REM sleep. Using computational modeling, we show that our in vivo results are consistent with a mutually excitatory interaction between the SubC and cholinergic neurons where, importantly, cholinergic neuron activation is gated by SubC activity.

  7. Upregulation of B23 promotes tumor cell proliferation and predicts poor prognosis in glioma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jianguo [Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province (China); Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province (China); Sun, Jie; Yang, Liu; Yan, Yaohua; Shi, Wei; Shi, Jinlong; Huang, Qingfeng; Chen, Jian [Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province (China); Lan, Qing, E-mail: lanqingsj@163.com [Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu Province (China)

    2015-10-09

    B23 (also known as Nucleophosmin, NPM, numatrin or NO38) is a ubiquitously expressed phosphoprotein belonging to the nucleoplasmin family of chaperones. In this study we intended to investigate the clinical significance of B23 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that B23 was overexpressed in glioma tissues and glioma cell lines. In addition, the expression level of B23 was positively correlated with glioma pathological grade and Ki-67 expression. Kaplan–Meier analysis revealed that a higher B23 expression in patients with glioma was associated with a poorer prognosis. In vitro, after the release of glioma cell lines from serum starvation, the expression of B23 was upregulated, as well as PCNA (Proliferating Cell Nuclear Antigen) and cyclin A. In addition, knockdown of B23 by small interfering RNA transfection diminished the expression of PCNA, cyclin D1 and arrested cell growth at G1 phase. Taken together, our results implied that B23 could be a candidate prognostic biomarker as well as a potential therapeutical target of glioma. - Highlights: • B23 expression increased as the malignant degree of glioma increased, which was consistent with Ki-67 expression. • High expression of B23 could be a strong determinant of poor prognosis in glioma. • B23 may be involved in the proliferation of glioma in a cell-cycle-dependent pathway. • Knockdown of B23 expression by siRNA could affect the progression of glioma. • B23 may be a potential prognosis biomarker and a possible therapeutic target for glioma.

  8. Slit2 inhibits glioma cell invasion in the brain by suppression of Cdc42 activity.

    Science.gov (United States)

    Yiin, Jia-Jean; Hu, Bo; Jarzynka, Michael J; Feng, Haizhong; Liu, Kui-Wei; Wu, Jane Y; Ma, Hsin-I; Cheng, Shi-Yuan

    2009-12-01

    Acquisition of insidious invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Slit2, a chemorepulsive factor, controls cell migration of neuronal and glial cells during development and inhibits chemotaxic migration of various types of cells in vitro. However, the role of Slit2 in vitro remains controversial, and the biological significance of Slit2 expression in cancer cell invasion in vivo has not yet been determined. In the present study, we characterized the effects of Slit2 expression on the migration and invasion of invasive glioma cells in vitro and in vivo. By reverse transcriptase polymerase chain reaction (PCR) analyses, Slit2 was found to be expressed at lower levels in primary glioma specimens and invasive glioma cells compared with normal human brain cells and astrocytes. Ectopic expression of Slit2 or treatment with recombinant Slit2 on glioma cells attenuates cell migration and invasion through inhibition of Cdc42 activity in vitro. Cellular depletion of Robo1, a cognate receptor for Slit2, prevented Slit2 inhibition of Cdc42 activity and glioma cell migration. In vivo, expression of Slit2 by invasive SNB19 glioma cells markedly inhibited glioma cell infiltration into the brain of mice. Moreover, impediment of glioma cell invasion by Slit2 did not affect the expression of N-cadherin and beta-catenin in glioma cells. These results provide the first evidence demonstrating that Slit2-Robo1 inhibits glioma invasion through attenuating Cdc42 activity in vitro and in the brain. Understanding the mechanisms of Slit2-Robo1 inhibition of glioma cell invasion will foster new treatments for malignant gliomas.

  9. Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma.

    Directory of Open Access Journals (Sweden)

    Judith Schwartzbaum

    Full Text Available Allergy is inversely related to glioma risk. To determine whether prediagnostic allergy-related serum proteins are associated with glioma, we conducted a nested case-control study of seven cytokines (IL4, IL13, IL5, IL6, IL10, IFNG, TGFB2, two soluble cytokine receptors (sIL4RA, sIL13RA2 and three allergy-related transcription factors (FOXP3, STAT3, STAT6 using serum specimens from the Janus Serum Bank Cohort in Oslo, Norway. Blood donors subsequently diagnosed with glioma (n = 487 were matched to controls (n = 487 on age and date of blood draw and sex. We first estimated individual effects of the 12 serum proteins and then interactions between IL4 and IL13 and their receptors using conditional logistic regression. We next tested equality of case-control inter-correlations among the 12 serum proteins. We found that TGFB2 is inversely related to glioblastoma (Odds Ratio (OR = 0.87, 95% Confidence Interval (CI = 0.76, 0.98. In addition, ≤ 5 years before diagnosis, we observed associations between IL4 (OR = 0.82, 95% CI = 0.66, 1.01, sIL4RA (OR = 0.80, 95% CI = 0.65, 1.00, their interaction (OR = 1.06, 95% CI = 1.01, 1.12 and glioblastoma. This interaction was apparent > 20 years before diagnosis (IL4-sIL4RA OR = 1.20, 95% CI = 1.05, 1.37. Findings for glioma were similar. Case correlations were different from control correlations stratified on time before diagnosis. Five years or less before diagnosis, correlations among case serum proteins were weaker than were those among controls. Our findings suggest that IL4 and sIL4RA reduce glioma risk long before diagnosis and early gliomagenesis affects circulating immune function proteins.

  10. ECHOGRAPHIC PICTURE OF OPTIC NERVE GLIOMA IN NEUROFIBROMATOSIS TYPE-1

    Directory of Open Access Journals (Sweden)

    Biljana Kuzmanović

    2002-12-01

    Full Text Available Background. Authors want to present echographic picture of orbital part of low-grade pilocytic astrocytoma involving the optic nerve and/or chiasm and optic tract (optic pathway glioma or visual pathway glioma.Methods. 4 children with neurofibromatosis type-1 complicated with optic pathway glioma diagnosed earlier with magnetic resonance were examined by ultrasound. Standardised A-scan technique was used for optic nerve width measurement. The 30° test and B-scan (axial, transverse and longitudinal sections of both eyes and orbits were performed as well.Results. The optic nerve diameter in our cases ranged from 4.48 to 8.5 mm. Two children had the left side optic pathway glioma, one boy had the right side optic pathway glioma and in one tumour was bilateral. The transversal section of the nerve revealed dark oval and in more perpendicular sections round void of the nerve. As the beam is swept towards the orbital apex void becomes more fusiform. The nerve and its sheaths are markedly widened. An abnormal increase in reflectivity and irregularity of the spike’s pattern is exhibited as well. No calcification along the sheaths is noticed. The transverse section of the tumour demonstrated an »inverse doughnut« sign. The outer whiter outline of the widened sheaths surrounds an inner darker circle. The longitudinal section revealed the optic nerve head continuing into the widened optic nerve. The 30° test was negative. The differential diagnosis of meningeoma, optic neuritis and orbital cysticercosis should be considered.Conclusions. Ultrasound as a cheap, safe, easily repeatable imaging method should become a method of choice for screening optic nerve tumours in neurofibromatosis type-1, especially in children, as well as for follow-up after treatment.

  11. Establishment of intramedullary spinal cord glioma model in rats

    Institute of Scientific and Technical Information of China (English)

    REN Tian-jian; WANG Zhong-cheng; ZHANG Ya-zhuo; LI Dan; WANG Hong-yun; LI Zhen-zong

    2010-01-01

    Background Treating intramedullary spinal cord gliomas is a big challenge because of limited options, high recurrence rate and poor prognosis. An intramedullary glioma model is prerequisite for testing new treatments. This paper describes the establishment of a rodent intramedullary glioma model and presents functional progression, neuroimaging and histopathological characterization of the tumour model.Methods Fischer344 rats (n=24) were randomized into two groups. Group 1 (n=16) received a 5 μl intramedullary implantation of 9L gliosarcomal (105) cells. Group 2 (n=8) received a 5 μl intramedullary injection of Dulbecco's modified Eagle medium. The rats were anesthetized, the spinous process of the T10 vertebra and the ligamentum flavum were removed to expose the T10-11 intervertebral space and an intramedullary injection was conducted into the spinal cord. The rats were evaluated preoperatively and daily postoperatively for neurological deficits using the Basso, Beattie and Bresnahan scale. High resolution magnetic resonance images were acquired preoperatively and weekly postoperatively.When score equal to 0, rats were sacrificed for histopathological examination.Results Rats implanted with 9L gliosarcoma cells had a statistically significant median onset of hind limb paraplegia at (16.0±0.4) days, compared with rats in the control group in which neurological deficits were absent. Imaging and pathological cross sections confirmed intramedullary 9L gliosarcoma invading the spinal cord. Rats in the control group showed no significant functional, radiological or histopathological findings of tumour.Conclusions Rats implanted with 9L cells regularly develop paraplegia in a reliable and reproducible manner. The progression of neurological deficits, neuroimaging and histopathological characteristics of intramedullary spinal cord gliomas in rats is comparable with the behaviour of infiltrative intramedullary spinal cord gliomas in patients.

  12. Innate immune functions of microglia isolated from human glioma patients

    Directory of Open Access Journals (Sweden)

    Grimm Elizabeth

    2006-03-01

    Full Text Available Abstract Background Innate immunity is considered the first line of host defense and microglia presumably play a critical role in mediating potent innate immune responses to traumatic and infectious challenges in the human brain. Fundamental impairments of the adaptive immune system in glioma patients have been investigated; however, it is unknown whether microglia are capable of innate immunity and subsequent adaptive anti-tumor immune responses within the immunosuppressive tumor micro-environment of human glioma patients. We therefore undertook a novel characterization of the innate immune phenotype and function of freshly isolated human glioma-infiltrating microglia (GIM. Methods GIM were isolated by sequential Percoll purification from patient tumors immediately after surgical resection. Flow cytometry, phagocytosis and tumor cytotoxicity assays were used to analyze the phenotype and function of these cells. Results GIM expressed significant levels of Toll-like receptors (TLRs, however they do not secrete any of the cytokines (IL-1β, IL-6, TNF-α critical in developing effective innate immune responses. Similar to innate macrophage functions, GIM can mediate phagocytosis and non-MHC restricted cytotoxicity. However, they were statistically less able to mediate tumor cytotoxicity compared to microglia isolated from normal brain. In addition, the expression of Fas ligand (FasL was low to absent, indicating that apoptosis of the incoming lymphocyte population may not be a predominant mode of immunosuppression by microglia. Conclusion We show for the first time that despite the immunosuppressive environment of human gliomas, GIM are capable of innate immune responses such as phagocytosis, cytotoxicity and TLR expression but yet are not competent in secreting key cytokines. Further understanding of these innate immune functions could play a critical role in understanding and developing effective immunotherapies to malignant human gliomas.

  13. Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal.

    Science.gov (United States)

    Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Bucris, Efrat; Ziv-Av, Amotz; Xiang, Cunli; Bobbitt, Kevin; Rempel, Sandra A; Hasselbach, Laura; Mikkelsen, Tom; Slavin, Shimon; Brodie, Chaya

    2013-02-01

    MicroRNAs (miRNAs) have emerged as potential cancer therapeutics; however, their clinical use is hindered by lack of effective delivery mechanisms to tumor sites. Mesenchymal stem cells (MSCs) have been shown to migrate to experimental glioma and to exert anti-tumor effects by delivering cytotoxic compounds. Here, we examined the ability of MSCs derived from bone marrow, adipose tissue, placenta and umbilical cord to deliver synthetic miRNA mimics to glioma cells and glioma stem cells (GSCs). We examined the delivery of miR-124 and miR-145 mimics as glioma cells and GSCs express very low levels of these miRNAs. Using fluorescently labeled miRNA mimics and in situ hybridization, we demonstrated that all the MSCs examined delivered miR-124 and miR-145 mimics to co-cultured glioma cells and GSCs via gap junction- dependent and independent processes. The delivered miR-124 and miR-145 mimics significantly decreased the luciferase activity of their respected reporter target genes, SCP-1 and Sox2, and decreased the migration of glioma cells and the self-renewal of GSCs. Moreover, MSCs delivered Cy3-miR-124 mimic to glioma xenografts when administered intracranially. These results suggest that MSCs can deliver synthetic exogenous miRNA mimics to glioma cells and GSCs and may provide an efficient route of therapeutic miRNA delivery in vivo.

  14. Presymplectic structures and intrinsic Lagrangians

    CERN Document Server

    Grigoriev, Maxim

    2016-01-01

    It is well-known that a Lagrangian induces a compatible presymplectic form on the equation manifold (stationary surface, understood as a submanifold of the respective jet-space). Given an equation manifold and a compatible presymplectic form therein, we define the first-order Lagrangian system which is formulated in terms of the intrinsic geometry of the equation manifold. It has a structure of a presymplectic AKSZ sigma model for which the equation manifold, equipped with the presymplectic form and the horizontal differential, serves as the target space. For a wide class of systems (but not all) we show that if the presymplectic structure originates from a given Lagrangian, the proposed first-order Lagrangian is equivalent to the initial one and hence the Lagrangian per se can be entirely encoded in terms of the intrinsic geometry of its stationary surface. If the compatible presymplectic structure is generic, the proposed Lagrangian is only a partial one in the sense that its stationary surface contains the...

  15. Intrinsic Alignments in the Illustris Simulation

    CERN Document Server

    Hilbert, Stefan; Schneider, Peter; Springel, Volker; Vogelsberger, Mark; Hernquist, Lars

    2016-01-01

    We study intrinsic alignments (IA) of galaxy image shapes within the Illustris cosmic structure formation simulations. We investigate how IA correlations depend on observable galaxy properties such as stellar mass, apparent magnitude, redshift, and photometric type, and on the employed shape measurement method. The correlations considered include the matter density-intrinsic ellipticity (mI), galaxy density-intrinsic ellipticity (dI), gravitational shear-intrinsic ellipticity (GI), and intrinsic ellipticity-intrinsic ellipticity (II) correlations. We find stronger correlations for more massive and more luminous galaxies, as well as for earlier photometric types, in agreement with observations. Moreover, shape measurement methods that down-weight the outer parts of galaxy images produce much weaker IA signals on intermediate and large scales than methods employing flat radial weights. Thus, the expected contribution of intrinsic alignments to the observed ellipticity correlation in tomographic cosmic shear sur...

  16. The relation of consciousness level and cerebral blood flow in glioma and meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Hirofumi; Niwa, Masahiro; Kida, Yoshihisa; Tanaka, Takayuki; Maezawa, Satoshi; Kobayashi, Tatsuya [Komaki City Hospital, Nagoya (Japan)

    1997-03-01

    The relation between the consciousness level and cerebral blood flow (CBF) was analyzed in 17 cases of glioma and 6 cases of meningioma. CBF was in normal range in the alert groups of patients with glioma and meningioma. By contrast, CBF decreased generally not only in the affected side, but also in the non-affected side in the drowsy patient group with glioma. Widespread infiltration of glioma was seen in 4 cases of 6 drowsy cases. CBF increased after the partial resection of the tumor in 2 cases of glioma. Thus the disturbance of consciousness level was attributable to diffuse hypofunction accompanying the diffuse infiltration of glioma and the decrease of cerebral perfusion pressure caused by the increased intracranial pressure. (author)

  17. Neural progenitor and hemopoietic stem cells inhibit the growth of low-differentiated glioma.

    Science.gov (United States)

    Baklaushev, V P; Grinenko, N F; Savchenko, E A; Bykovskaya, S N; Yusubalieva, G M; Viktorov, I V; Bryukhovetskii, A S; Bryukhovetskii, I S; Chekhonin, V P

    2012-02-01

    The effects of neural progenitor and hemopoietic stem cells on C6 glioma cells were studied in in vivo and in vitro experiments. Considerable inhibition of proliferation during co-culturing of glioma cells with neural progenitor cells was revealed by quantitative MTT test and bromodeoxyuridine incorporation test. Labeled neural progenitor and hemopoietic stem cells implanted into the focus of experimental cerebral glioma C6 survive in the brain of experimental animals for at least 7 days, migrate with glioma cells, and accumulate in the peritumoral space. Under these conditions, neural progenitor cells differentiate with the formation of long processes. Morphometric analysis of glioma cells showed that implantation of neural progenitor and hemopoietic stem cells is accompanied by considerable inhibition of the growth of experimental glioma C6 in comparison with the control. The mechanisms of tumor-suppressive effects of neural and hemopoietic stem cells require further investigation.

  18. Expression of metastasis-associated protein 3 in human brain glioma related to tumor prognosis.

    Science.gov (United States)

    Shan, Shouqin; Hui, Guangyan; Hou, Fanggao; Shi, Hua; Zhou, Guoqing; Yan, Han; Wang, Lu; Liu, Jinfeng

    2015-10-01

    Glioma represents a disparate group of tumors characterized by high invasion ability, and therefore it is of clinical significance to identify molecular markers and therapeutic targets for better clinical management. Previously, metastasis-associated protein family (MTA) is considered to promote tumor cell invasion and metastasis of human malignancies. Recently, the newly identified MTA3 has been shown to play conflicting roles in human malignancies, while the expression pattern and potential clinical significance of MTA3 in human glioma have not been addressed yet. In the present study, we investigated the protein expression of MTA3 by immunohistochemistry assay and analyzed its association with glioma prognosis in 186 cases of patients. Results showed that MTA3 expression was decreased in glioma compared with that in normal brain (P human glioma and negatively associated with prognosis of patients, suggesting that MTA3 may play a tumor suppressor role in glioma.

  19. Light-controlled inhibition of malignant glioma by opsin gene transfer

    Science.gov (United States)

    Yang, F; Tu, J; Pan, J-Q; Luo, H-L; Liu, Y-H; Wan, J; Zhang, J; Wei, P-F; Jiang, T; Chen, Y-H; Wang, L-P

    2013-01-01

    Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach. PMID:24176851

  20. Methionine and cystine double deprivation stress suppresses glioma proliferation via inducing ROS/autophagy.

    Science.gov (United States)

    Liu, Huailei; Zhang, Weiguang; Wang, Kaikai; Wang, Xiaoxiong; Yin, Fei; Li, Chenguang; Wang, Chunlei; Zhao, Boxian; Zhong, Chen; Zhang, Jiakang; Peng, Fei; Bi, Yunke; Shen, Chen; Hou, Xu; Zhang, Daming; Liu, Yaohua; Ai, Jing; Zhao, Shiguang

    2015-01-22

    Cancer cells are highly dependent on methionine and cystine (Met-Cys) for survival and proliferation. However, the molecular mechanism is not fully clear. The present study is to investigate the effects of Met-Cys deprivation on glioma cells proliferation. The results showed that Met-Cys double deprivation had synergistic action on elevating ROS level, decreased GSH level and inhibition of glioma cell proliferation. Moreover, both of them deprivation triggered autophagy of glioma cells both in vitro and in vivo. Importantly, Met-Cys double restriction diet inhibited growth of glioma. These results provided a new regulation mechanism of Met-Cys metabolism on affecting glioma cell proliferation, suggesting that targeting Met-Cys metabolism may be a potential strategy for glioma therapy.

  1. A three-dimensional collagen scaffold cell culture system for screening anti-glioma therapeutics

    Science.gov (United States)

    Lv, Donglai; Yu, Shi-cang; Ping, Yi-fang; Wu, Haibo; Zhao, Xilong; Zhang, Huarong; Cui, Youhong; Chen, Bing; Zhang, Xia; Dai, Jianwu

    2016-01-01

    Three-dimensional (3D) culture, which can simulate in vivo microenvironments, has been increasingly used to study tumor cell biology. Since most preclinical anti-glioma drug tests still rely on conventional 2D cell culture, we established a collagen scaffold for 3D glioma cell culture. Glioma cells cultured on these 3D scaffolds showed greater degree of dedifferentiation and quiescence than cells in 2D culture. 3D-cultured cells also exhibited enhanced resistance to chemotherapeutic alkylating agents, with a much higher proportion of glioma stem cells and upregulation of O6-methylguanine DNA methyltransferase (MGMT). Importantly, tumor cells in 3D culture showed chemotherapy resistance patterns similar to those observed in glioma patients. Our results suggest that 3D collagen scaffolds are promising in vitro research platforms for screening new anti-glioma therapeutics. PMID:27486877

  2. Spinal projections from the lower brain stem in the cat as demonstrated by the horseradish peroxidase technique. II. Projections from the dorsolateral pontine tegmentum and raphe nuclei.

    Science.gov (United States)

    Tohyama, M; Sakai, K; Touret, M; Salvert, D; Jouvet, M

    1979-11-02

    The descending projections to the spinal cord arising from the dorsolateral pontine tegmentum and brain stem raphe nuclei have been investigated by means of the horseradish peroxidase (HRP) technique. Particular attention was taken to clarify the cells of origin and the funicular trajectory of these spinal projections. After injections of HRP into the spinal cord, a significant of HRP labeled neurons were observed in the following dorsolateral pontine tegmental structures: (1) an area ventral to the nucleus cuneiformis; (2) principal locus coeruleus; (3) locus coeruleus a; (4) locuse subcoeruleus; (5) Kölliker-Fuse nucleus; and (6) nucleus parabrachialis lateralis. As a rule, the projections are ipsilateral and descendaphe-spinal projections, we have demonstrated that the nucleus raphe dorsalis also sends axons to the cervical segment of the spinal cord. Furthermore, in accord with previous reports, HRP labeled cells were also identified in the nucleus raphe magnus, pallidus and obscurus, but not in the nucleus raphe centralis superior and pontis. On the whole the present study further clarified the organization of spinal projections from the dorsolateral pons and raphe nuclei and provided some additional anatomical data for the physiology of the tegmentospinal and raphe-spinal projections.

  3. Chordoid glioma with intraventricular dissemination: A case report with perfusion MR imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Ki, So Yeon; Kim, Seul Kee; Heo, Tae Wook; Baek, Byung Hyun; Kim, Hyung Seok; Yoon, Woong [Chonnam National University Medical School, Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2016-02-15

    Chordoid glioma is a rare low grade tumor typically located in the third ventricle. Although a chordoid glioma can arise from ventricle with tumor cells having features of ependymal differentiation, intraventricular dissemination has not been reported. Here we report a case of a patient with third ventricular chordoid glioma and intraventricular dissemination in the lateral and fourth ventricles. We described the perfusion MR imaging features of our case different from a previous report.

  4. Diffusion kurtosis imaging can efficiently assess the glioma grade and cellular proliferation

    OpenAIRE

    Jiang, Rifeng; Jiang, Jingjing; Zhao, Lingyun; Zhang, Jiaxuan; Zhang, Shun; Yao, Yihao; Yang, Shiqi; Shi, Jingjing; Shen, Nanxi; Su, Changliang; Zhang, Ju; Zhu, Wenzhen

    2015-01-01

    Conventional diffusion imaging techniques are not sufficiently accurate for evaluating glioma grade and cellular proliferation, which are critical for guiding glioma treatment. Diffusion kurtosis imaging (DKI), an advanced non-Gaussian diffusion imaging technique, has shown potential in grading glioma; however, its applications in this tumor have not been fully elucidated. In this study, DKI and diffusion weighted imaging (DWI) were performed on 74 consecutive patients with histopathologicall...

  5. MGMT testing-the challenges for biomarker-based glioma treatment

    OpenAIRE

    Wick, W; Weller, M; Van Den Bent, M.; Sanson, M; Weiler, M.; von Deimling, A.; Plass, C; Hegi, M.; Platten, M.; Reifenberger, G.

    2014-01-01

    Many patients with malignant gliomas do not respond to alkylating agent chemotherapy. Alkylator resistance of glioma cells is mainly mediated by the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT). Epigenetic silencing of the MGMT gene by promoter methylation in glioma cells compromises this DNA repair mechanism and increases chemosensitivity. MGMT promoter methylation is, therefore, a strong prognostic biomarker in paediatric and adult patients with glioblastoma treated wit...

  6. Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas

    OpenAIRE

    Costa, Angela Margarida; Pinto, Filipe; Martinho, Olga; Oliveira, Maria José; Jordan, Peter; Reis,R.M.

    2014-01-01

    Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade extracellular matrix (ECM), thus assisting invasion. Upregulation of MMPs, frequently reported in gliomas, is associated with aggressive behavior. WNK2 is a tumor suppressor gene expressed in normal brain, and silenced by promoter methylation in gliomas. Patients without WNK2 exhibited poor prognosis, and its downregulation was associated with increased glioma cell invasion. Here we showed that MMP2 expression and activity ...

  7. Retinoids in the treatment of glioma: a new perspective

    Directory of Open Access Journals (Sweden)

    Mawson AR

    2012-08-01

    Full Text Available Anthony R MawsonDepartment of Health Policy and Management, School of Health Sciences, College of Public Service, Jackson State University, Jackson, MS, USAAbstract: Primary brain tumors are among the top ten causes of cancer-related deaths in the US. Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors diagnosed in adults each year and are associated with high morbidity and mortality. Despite optimal treatment, the prognosis for patients with gliomas remains poor. The use of retinoids (vitamin A and its congeners in the treatment of certain tumors was originally based on the assumption that these conditions were associated with an underlying deficiency of vitamin A and that supplementation with pharmacological doses would correct the deficiency. Yet the results of retinoid treatment have been only modestly beneficial and usually short-lived. Studies also indicate that vitamin A excess and supplementation have pro-oxidant effects and are associated with increased risks of mortality from cancer and other diseases. The therapeutic role of vitamin A in cancer thus remains uncertain and a new perspective on the facts is needed. The modest and temporary benefits of retinoid treatment could result from a process of feedback inhibition, whereby exogenous retinoid temporarily inhibits the endogenous synthesis of these compounds. In fact, repeated and/or excessive exposure of the tissues to endogenous retinoic acid may contribute to carcinogenesis. Gliomas, in particular, may result from an imbalance in retinoid receptor expression initiated by environmental factors that increase the endogenous production of retinoic acid in glia. At the receptor level, it is proposed that this imbalance is characterized by excessive expression of retinoic acid receptor-α(RARα and reduced expression of retinoic acid receptor-β (RARβ. This suggests a potential new treatment strategy for gliomas, possibly even at a

  8. In vitro enhancement of dendritic cell-mediated anti-glioma immune response by graphene oxide

    Science.gov (United States)

    Wang, Wei; Li, Zhongjun; Duan, Jinhong; Wang, Chen; Fang, Ying; Yang, Xian-Da

    2014-06-01

    Malignant glioma has extremely poor prognosis despite combination treatments with surgery, radiation, and chemotherapy. Dendritic cell (DC)-based immunotherapy may potentially serve as an adjuvant treatment of glioma, but its efficacy generally needs further improvement. Here we explored whether graphene oxide (GO) nanosheets could modulate the DC-mediated anti-glioma immune response in vitro, using the T98G human glioma cell line as the study model. Pulsing DCs with a glioma peptide antigen (Ag) generated a limited anti-glioma response compared to un-pulsed DCs. Pulsing DCs with GO alone failed to produce obvious immune modulation effects. However, stimulating DCs with a mixture of GO and Ag (GO-Ag) significantly enhanced the anti-glioma immune reaction ( p < 0.05). The secretion of interferon gamma (IFN-γ) by the lymphocytes was also markedly boosted by GO-Ag. Additionally, the anti-glioma immune response induced by GO-Ag appeared to be target-specific. Furthermore, at the concentration used in this study, GO exhibited a negligible effect on the viability of the DCs. These results suggested that GO might have potential utility for boosting a DC-mediated anti-glioma immune response.

  9. MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism.

    Science.gov (United States)

    Bandopadhayay, Pratiti; Ramkissoon, Lori A; Jain, Payal; Bergthold, Guillaume; Wala, Jeremiah; Zeid, Rhamy; Schumacher, Steven E; Urbanski, Laura; O'Rourke, Ryan; Gibson, William J; Pelton, Kristine; Ramkissoon, Shakti H; Han, Harry J; Zhu, Yuankun; Choudhari, Namrata; Silva, Amanda; Boucher, Katie; Henn, Rosemary E; Kang, Yun Jee; Knoff, David; Paolella, Brenton R; Gladden-Young, Adrianne; Varlet, Pascale; Pages, Melanie; Horowitz, Peleg M; Federation, Alexander; Malkin, Hayley; Tracy, Adam A; Seepo, Sara; Ducar, Matthew; Van Hummelen, Paul; Santi, Mariarita; Buccoliero, Anna Maria; Scagnet, Mirko; Bowers, Daniel C; Giannini, Caterina; Puget, Stephanie; Hawkins, Cynthia; Tabori, Uri; Klekner, Almos; Bognar, Laszlo; Burger, Peter C; Eberhart, Charles; Rodriguez, Fausto J; Hill, D Ashley; Mueller, Sabine; Haas-Kogan, Daphne A; Phillips, Joanna J; Santagata, Sandro; Stiles, Charles D; Bradner, James E; Jabado, Nada; Goren, Alon; Grill, Jacques; Ligon, Azra H; Goumnerova, Liliana; Waanders, Angela J; Storm, Phillip B; Kieran, Mark W; Ligon, Keith L; Beroukhim, Rameen; Resnick, Adam C

    2016-03-01

    Angiocentric gliomas are pediatric low-grade gliomas (PLGGs) without known recurrent genetic drivers. We performed genomic analysis of new and published data from 249 PLGGs, including 19 angiocentric gliomas. We identified MYB-QKI fusions as a specific and single candidate driver event in angiocentric gliomas. In vitro and in vivo functional studies show that MYB-QKI rearrangements promote tumorigenesis through three mechanisms: MYB activation by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of the tumor suppressor QKI. To our knowledge, this represents the first example of a single driver rearrangement simultaneously transforming cells via three genetic and epigenetic mechanisms in a tumor.

  10. Mechanism of SEMA3B gene silencing and clinical significance in glioma.

    Science.gov (United States)

    Pang, C H; Du, W; Long, J; Song, L J

    2016-03-18

    The aim of the current study was to explore mechanisms of SEMA3B gene expression and its clinical significance in glioma, and provide a theoretical foundation for investigating individualized treatment in glioma. Paraffin-embedded tissues from 43 patients with a confirmed clinical diagnosis of glioma following neurosurgery at the First Affiliated Hospital of Zhengzhou University from December 2013 to April 2014 were selected randomly. An additional three normal brain tissues were obtained following encephalic decompression excision due to acute craniocerebral injury in the same period, which were used as the control group. Immunohistochemical staining for vascular endothelial growth factor was performed on the glioma tissues from the 43 patients. Genomic DNA was extracted for bisulfate conversion and sequencing. SEMA3B was fully expressed in the three normal brain tissues, and incompletely expressed in the 43 glioma tissues, with a lack of expression in 48.8% (21/43) of samples. Moreover, 58% of high-grade gliomas (grade III and IV) lacked SEMA3B expression, which was significantly more than those that lacked expression (20%) in low-grade gliomas (grade I and II), indicating that, as the clinical pathological grade increased, SEMA3B expression decreased. The occurrence and development of malignant tumors is a product of multiple genes and other factors. Here, we provide theoretical basis for glioma development and prognosis involving DNA-methylation driven silencing of SEMA3B, and thus, SEMA3B is a potential target for directed treatments against glioma.

  11. Adhesion molecules and the extracellular matrix as drug targets for glioma.

    Science.gov (United States)

    Shimizu, Toshihiko; Kurozumi, Kazuhiko; Ishida, Joji; Ichikawa, Tomotsugu; Date, Isao

    2016-04-01

    The formation of tumor vasculature and cell invasion along white matter tracts have pivotal roles in the development and progression of glioma. A better understanding of the mechanisms of angiogenesis and invasion in glioma will aid the development of novel therapeutic strategies. The processes of angiogenesis and invasion cause the production of an array of adhesion molecules and extracellular matrix (ECM) components. This review focuses on the role of adhesion molecules and the ECM in malignant glioma. The results of clinical trials using drugs targeted against adhesion molecules and the ECM for glioma are also discussed.

  12. EXPERIMENTAL STUDY ON THE GENE THERAPY OF MALIGNANT GLIOMA WITH ANTISENSE VEGF RNA

    Institute of Scientific and Technical Information of China (English)

    浦佩玉; 王建桢; 黄强; 张敬; 张云亭

    2003-01-01

    Objective: To study the effect of antisense VEGF RNA on rat C6 gliomas in vivo and find out the feasibility of antiangiogenesis therapy with antisense VEGF RNA for malignant gliomas. Methods: Parental rat C6 glioma cells and C6 cells transfected with antisense VEGF cDNA were implanted intracerebrally and subcutaneously into SD rats as control and transfected group. Rats bearing cerebral and subcutaneous C6 gliomas were treated with antisense VEGF cDNA as treated group and sense VEGF cDNA and empty vector as control of treated group. The general manifestation, survival time, MRI and histopathological changes of all rats were observed. The volume of subcutaneously implanted tumors was determined regularly. In situ hybridization and immunohistochemical staining were used for detection of VEGF gene expression of gliomas while PCNA immunostaining and TUNEL method for examination of proliferation activity and apoptosis of gliomas, respectively. Results: The survival of the rats in transfected and treated group was prolonged. There were two rats surviving over 90 d in the treated group and their tumors disappeared. The VEGF gene expression, the number of microvessels and the proliferation activity were decreased and a large amount of apoptotic cells could be found in cerebral and subcutaneous gliomas in treated and transfected groups. Conclusion: VEGF is one of the candidate genes for gene therapy of malignant gliomas. Antisense VEGF RNA combined with other therapies should be studied further for enhancing the therapeutic effect of malignant gliomas.

  13. Increased Expression of microRNA-17 Predicts Poor Prognosis in Human Glioma

    Directory of Open Access Journals (Sweden)

    Shengkui Lu

    2012-01-01

    Full Text Available Aim. To investigate the clinical significance of microRNA-17 (miR-17 expression in human gliomas. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR analysis was used to characterize the expression patterns of miR-17 in 108 glioma and 20 normal brain tissues. The associations of miR-17 expression with clinicopathological factors and prognosis of glioma patients were also statistically analyzed. Results. Compared with normal brain tissues, miR-17 expression was significantly higher in glioma tissues (P<0.001. In addition, the increased expression of miR-17 in glioma was significantly associated with advanced pathological grade (P=0.006 and low Karnofsky performance score (KPS, P=0.01. Moreover, Kaplan-Meier survival and Cox regression analyses showed that miR-17 overexpression (P=0.008 and advanced pathological grade (P=0.02 were independent factors predicting poor prognosis for gliomas. Furthermore, subgroup analyses showed that miR-17 expression was significantly associated with poor overall survival in glioma patients with high pathological grades (for grade III~IV: P<0.001. Conclusions. Our data offer the convinced evidence that the increased expression of miR-17 may have potential value for predicting poor prognosis in glioma patients with high pathological grades, indicating that miR-17 may contribute to glioma progression and be a candidate therapeutic target for this disease.

  14. The effects of CD147 on the cell proliferation, apoptosis, invasion, and angiogenesis in glioma.

    Science.gov (United States)

    Yin, Haoyuan; Shao, Ying; Chen, Xuan

    2017-01-01

    To analyze the effects of extracellular matrix metalloproteinase inducer (CD147) on glioma proliferation, apoptosis, invasion, and angiogenesis. Tissue samples were obtained from 101 glioma cases while normal brain tissues were obtained from 30 brain injury cases. Immunohistochemical assay was performed to detect the expressions of CD147, CD34, and VEGF in tissue samples. QRT-PCR was performed to detect the relative expression of CD147 mRNA in human glioma cell lines. CD147 siRNA was transfected into glioma cell line U251. Cell proliferation, apoptosis, invasion, and angiogenesis were tested by MTT, flow cytometry, Transwell assay, and vasculogenic mimicry assay, respectively. Expressions of relative proteins were analyzed with western blot. CD147 was positively expressed with the percentage of 0, 37.5, 44.8, 67.9, and 85.7 % in normal tissues and glioma tissues with WHO grades I-IV, respectively, and the scores of MVDand VEGF were associated with the expression of CD147. CD147 was significantly upregulated in the human glioma cell lines (P CD147 suppressed cell proliferation, blocked cell cycle, induced apoptosis, inhibited cell invasion and angiogenesis in glioma cells in vitro. The expression of CD147 was significantly associated with WHO tumor grade and angiogenesis; silencing of CD147 contributed to inhibition of glioma proliferation, invasion, and angiogenesis. Our study provided firm evidence that CD 147 is a potential glioma target for anti-angiogenic therapies.

  15. Intrinsic optimization using stochastic nanomagnets

    Science.gov (United States)

    Sutton, Brian; Camsari, Kerem Yunus; Behin-Aein, Behtash; Datta, Supriyo

    2017-01-01

    This paper draws attention to a hardware system which can be engineered so that its intrinsic physics is described by the generalized Ising model and can encode the solution to many important NP-hard problems as its ground state. The basic constituents are stochastic nanomagnets which switch randomly between the ±1 Ising states and can be monitored continuously with standard electronics. Their mutual interactions can be short or long range, and their strengths can be reconfigured as needed to solve specific problems and to anneal the system at room temperature. The natural laws of statistical mechanics guide the network of stochastic nanomagnets at GHz speeds through the collective states with an emphasis on the low energy states that represent optimal solutions. As proof-of-concept, we present simulation results for standard NP-complete examples including a 16-city traveling salesman problem using experimentally benchmarked models for spin-transfer torque driven stochastic nanomagnets. PMID:28295053

  16. Intrinsic plasmarons in warm graphene

    Science.gov (United States)

    Liu, Daqing; Chen, Shuyue; Zhang, Shengli; Ma, Ning

    2017-10-01

    Based on a self-consistent method, we predict theoretically that there exist intrinsic plasmarons in graphene at nonzero temperature, with a well defined mode, as shown by the result of Landau damping. We find that there are sharp differences between the discussed system and the QCD/QED system. Firstly, the thermal mass is proportional to α_g3/4T but not αg T . Secondly, at 0c , the fermion channel and plasmaron channel are nearly degenerate, and furthermore the energy difference between fermion and plasmaron becomes larger and larger with increasing q in the region q>qc . Thirdly, the fermion behaves as a ‘relativistic particle’ with nonzero mass, and the plasmaron exhibits an abnormal dispersion at moderate momentum.

  17. Intrinsic Instability of Coronal Streamers

    CERN Document Server

    Chen, Y; Song, H Q; Shi, Q Q; Feng, S W; Xia, L D; 10.1088/0004-637X/691/2/1936

    2009-01-01

    Plasma blobs are observed to be weak density enhancements as radially stretched structures emerging from the cusps of quiescent coronal streamers. In this paper, it is suggested that the formation of blobs is a consequence of an intrinsic instability of coronal streamers occurring at a very localized region around the cusp. The evolutionary process of the instability, as revealed in our calculations, can be described as follows: (1) through the localized cusp region where the field is too weak to sustain the confinement, plasmas expand and stretch the closed field lines radially outward as a result of the freezing-in effect of plasma-magnetic field coupling; the expansion brings a strong velocity gradient into the slow wind regime providing the free energy necessary for the onset of a subsequent magnetohydrodynamic instability; (2) the instability manifests itself mainly as mixed streaming sausage-kink modes, the former results in pinches of elongated magnetic loops to provoke reconnections at one or many loc...

  18. CDK4 amplification is an alternative mechanism to p16 gene homozygous deletion in glioma cell lines

    National Research Council Canada - National Science Library

    He, J; Allen, J R; Collins, V P; Allalunis-Turner, M J; Godbout, R; Day, 3rd, R S; James, C D

    1994-01-01

    ... those established from malignant gliomas. Here we have examined 32 glioma cell lines for amplification-associated overexpression of the CDK4 gene as an alternative mechanism for abrogating the growth-regulatory effects of p16...

  19. Armodafinil in Reducing Cancer-Related Fatigue in Patients With High Grade Glioma | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase III trial studies armodafinil to see how well it works in reducing cancer-related fatigue in patients with high grade glioma. Armodafinil may help relieve fatigue in patients with high grade glioma. |

  20. Fenofibrate dose not protect glioma cells from irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ro, Jae Lim; Kim, Won Dong; Park, Woo Yoon [Radiation Oncology, Chungbuk National University College of Medicine, Jeonju (Korea, Republic of)

    2012-04-15

    Fenofibrate(FF) is a ligand for peroxisome proliferator-activated receptor (PPAR) α and used clinically as a hypolipidemic drug. FF has been reported to have a radioprotective effect of newborn cells in the dentate gyrus 1) and inhibit radiation-induced microglial pro-inflammatory response 2). However, if FF also protect tumor cells, it can not be used clinically during radiotherapy. Thus, we're interested in whether FF has an radioprotective effect of brain tumor cells or not Although the radiosensitive G0/G1 phase cells were increased, radiosensitization by FF was not observed in three human glioma cells. This may be due to counterbalance of radiosensitizing and radioprotecting proteins increased by FF. Taken together, FF neither radiosensitize nor radioprotect glioma cells, so it can be used to protect normal neural cells from radiation damage.

  1. Dianhydrogalactitol and radiation therapy. Treatment of supratentorial glioma.

    Science.gov (United States)

    Eagan, R T; Childs, D S; Layton, D D; Laws, E R; Bisel, H F; Holbrook, M A; Fleming, T R

    1979-05-11

    Dianhydrogalactitol was the most active of 177 agents tested against a mouse ependymoblastoma tumor. We conducted a prospectively randomized trial comparing whole-brain irradiation alone vs identical irradiation plus dianhydrogalactitol in 42 patients with grade 3 and 4 supratentorial astrocytomas. Patients receiving dianhydrogalactitol in addition to irradiation had a significantly longer median survival time (67 vs 35 weeks) than did patients receiving only irradiation. The major toxic effect of dianhydrogalactitol is hematologic suppression of a cumulative nature. Dianhydrogalactitol may play an important role (in conjunction with radiation therapy) in the initial treatment of patients with supratentorial glioma. Our data may indicate that the mouse ependymoblastoma system is a useful screen for agents to be used in the treatment of human glioma.

  2. Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers.

    LENUS (Irish Health Repository)

    Jansen, Michael

    2010-07-01

    Over the past 10 years, there has been an increasing use of molecular markers in the assessment and management of adult malignant gliomas. Some molecular signatures are used diagnostically to help pathologists classify tumours, whereas others are used to estimate prognosis for patients. Most crucial, however, are those markers that are used to predict response to certain therapies, thereby directing clinicians to a particular treatment while avoiding other potentially deleterious therapies. Recently, large-scale genome-wide surveys have been used to identify new biomarkers that have been rapidly developed as diagnostic and prognostic tools. Given these developments, the pace of discovery of new molecular assays will quicken to facilitate personalised medicine in the setting of malignant glioma.

  3. The engineered Salmonella typhimurium inhibits tumorigenesis in advanced glioma

    Directory of Open Access Journals (Sweden)

    Chen JQ

    2015-09-01

    Full Text Available Jian-qiang Chen,1 Yue-fu Zhan,2 Wei Wang,1 Sheng-nan Jiang,2,3 Xiang-ying Li21Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Radiology, Affiliated to Haikou Hospital Xiangya School of Medicine, Central South University, Haikou, People’s Republic of China; 3Department of Nuclear Medicine, Central South University Xiangya School of Medicine Affiliated HaiKou Hospital, Haikou, Hainan, People’s Republic of ChinaObjective: To explore the antitumor role of the attenuated Salmonella typhimurium ΔppGpp with inducible cytolysin A (ClyA in advanced stage of glioma.Materials and methods: The C6 rat glioma cells were orthotopically implanted by surgery into the caudate nucleus of rat brains. The rats were then randomly divided into the treatment group (SL + ClyA (n=12, negative control group (SL (n=12, and control group (phosphate-buffered saline [PBS] (n=12. In the treatment group, the attenuated S. typhimurium were transformed with the plasmid-encoded antitumor gene ClyA. The expression of ClyA was controlled by the TetR-regulated promoter in response to extracellular doxycycline. The plasmid also contained an imaging gene lux to allow illumination of the tumor infected by the bacteria. The rat glioma C6 cells were implanted into the caudate nucleus of all rats. The engineered S. typhimurium and respective controls were injected intravenously into the rats 21 days after initial tumor implantation. The pathological analysis of the glioma tumor was performed at 21 days and 28 days (7 days after doxycycline treatment postimplantation. All rats underwent MRI (magnetic resonance imaging and bioluminescence study at 21 days and 28 days postimplantation to detect tumor volume. The differences between the three groups in tumor volume and survival time were analyzed.Results: Advanced stage glioma  was detected at 21 days postimplantation. Bioluminescence showed that the

  4. Role of Dicer on tumorigenesis in glioma cells

    Institute of Scientific and Technical Information of China (English)

    Anling Zhang; Lei Han; Guangxiu Wang; Zhifan Jia; Peiyu Pu; Chunsheng Kang

    2010-01-01

    Micro RNAs(miRNAs)are non-coding,single-stranded RNAs that regulate target gene expression by repressing translation or promoting RNA cleavage.Recent studies show that miRNA expression is globally decreased in some human tumors.Dicer is an essential component of the miRNA processing machinery.To determine whether global reduction of miRNA effects tumorigenesis,small interfering RNA were designed to target Dicer to restrain whole miRNA expression in the glioblastoma cell line-TJ905.With effective knock-down of Dicer,tumor cells were invasive and proliferative,and globally impaired miRNA processing enhanced proliferation and invasiveness of glioma cells in vitro.Suppression of Dicer expression resulted in a more aggressive glioma phenotype,which suggests that global reduction of miRNA expression could have an oncogenic role in glioblastoma cells.

  5. SVM-based glioma grading: Optimization by feature reduction analysis.

    Science.gov (United States)

    Zöllner, Frank G; Emblem, Kyrre E; Schad, Lothar R

    2012-09-01

    We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CBV) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity=89%, specificity=84%) when reducing the feature vector from 101 (100-bins rCBV histogram+age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values (∼87%) while reducing the number of features by up to 98%.

  6. Mechanisms of Glioma Formation: Iterative Perivascular Glioma Growth and Invasion Leads to Tumor Progression, VEGF-Independent Vascularization, and Resistance to Antiangiogenic Therapy

    Directory of Open Access Journals (Sweden)

    Gregory J. Baker

    2014-07-01

    Full Text Available As glioma cells infiltrate the brain they become associated with various microanatomic brain structures such as blood vessels, white matter tracts, and brain parenchyma. How these distinct invasion patterns coordinate tumor growth and influence clinical outcomes remain poorly understood. We have investigated how perivascular growth affects glioma growth patterning and response to antiangiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion is also shown to characterize de novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma (GBM, and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual glioma cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. Our results provide compelling experimental evidence in support of the recently described failure of clinically used antiangiogenics to extend the overall survival of human GBM patients.

  7. Design of intrinsically safe power supply

    Institute of Scientific and Technical Information of China (English)

    LI Rui-jin; JIN Lin

    2012-01-01

    Aiming to make a high power direct current supply safely used in coal mine production,this paper made a deep research on characteristics of intrinsically safe power supply,using the mathematical model established according to coal mine intrinsic safety standards.It provides theory support for the application of high power intrinsically safe power supply.The released energy of output short circuit of switch power supply,and the close related factors that influence the biggest output short-circuit spark discharge energy are the theoretical basis of the power supply.It is shown how to make a high power intrinsically safe power supply using the calculated values in the mathematical model,and take values from intrinsically safe requirements parameters scope,then this theoretical calculation value can be developed as the ultimate basis for research of the power supply.It gets the identification method of intrinsically safe from mathematics model of intrinsically safe power supply characteristics study,which solves the problem of theory and application of designing different power intrinsically safe power supply,and designs a kind of high power intrinsically safe power supply through this method.

  8. Algebraic description of intrinsic modes in nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Leviatan, A. (Los Alamos National Lab., NM (USA))

    1990-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intrinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. (author).

  9. Incentives and intrinsic motivation in healthcare

    Directory of Open Access Journals (Sweden)

    Mikel Berdud

    2016-11-01

    Conclusions: The conclusions could act as a guide to support the optimal design of incentive policies and schemes within health organisations when healthcare professionals are intrinsically motivated.

  10. Multimodal imaging in cerebral gliomas and its neuropathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Gempt, Jens, E-mail: jens.gempt@lrz.tum.de [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Soehngen, Eric [Abteilung für Neuroradiologie, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Abteilung für Neuropathologie des Instituts für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Förster, Stefan [Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Ryang, Yu-Mi [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Schlegel, Jürgen [Abteilung für Neuropathologie des Instituts für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); and others

    2014-05-15

    Introduction: Concerning the preoperative clinical diagnostic work-up of glioma patients, tumor heterogeneity challenges the oncological therapy. The current study assesses the performance of a multimodal imaging approach to differentiate between areas in malignant gliomas and to investigate the extent to which such a combinatorial imaging approach might predict the underlying histology. Methods: Prior to surgical resection, patients harboring intracranial gliomas underwent MRIs (MR-S, PWI) and {sup 18}F-FET-PETs. Intratumoral and peritumoral biopsy targets were defined, by MRI only, by FET-PET only, and by MRI and FET-PET combined, and biopsied prior to surgical resection and which then received separate histopathological examinations. Results: In total, 38 tissue samples were acquired (seven glioblastomas, one anaplastic astrocytoma, one anaplastic oligoastrocytoma, one diffuse astrocytoma, and one oligoastrocytoma) and underwent histopathological analysis. The highest mean values of Mib1 and CD31 were found in the target point “T’ defined by MRI and FET-PET combined. A significant correlation between NAA/Cr and PET tracer uptake (−0.845, p < 0.05) as well as Cho/Cr ratio and cell density (0.742, p < 0.05) and NAA/Cr ratio and MIB-1 (−0761, p < 0.05) was disclosed for this target point, though not for target points defined by MRI and FET-PET alone. Conclusion: Multimodal-imaging-guided stereotactic biopsy correlated more with histological malignancy indices, such as cell density and MIB-1 labeling, than targets that were based solely on the highest amino acid uptake or contrast enhancement on MRI. The results of our study indicate that a combined PET-MR multimodal imaging approach bears potential benefits in detecting glioma heterogeneity.

  11. Efficacy and toxicity of postoperative temozolomide radiochemotherapy in malignant glioma

    Energy Technology Data Exchange (ETDEWEB)

    Kocher, M.; Kunze, S.; Eich, H.T.; Semrau, R.; Mueller, R.P. [Dept. of Radiation Oncology, Univ. of Cologne (Germany)

    2005-03-01

    Purpose: to evaluate the feasibility, safety and efficacy of daily temozolomide concurrent with postoperative radiotherapy in malignant glioma. Patients and methods: from 11/1999 to 03/2003, n = 81 patients aged 15-72 years (median 52 years, karnofsky score 80-100% in 83%) suffering from primary glioblastoma (n = 47), anaplastic astrocytoma (n = 6), anaplastic oligodendroglioma (n = 16), and recurrent glioma (n = 12) were treated. Patients with primary gliomas received a combination of postoperative radiotherapy (60 Gy/1.8- to 2.0-Gy fractions) and daily oral temozolomide (75 mg/m{sup 2}) at all irradiation days (30-33 doses), while recurrent tumors were treated with 45-60 Gy and temozolomide. Initially, 6/81 patients had daily temozolomide doses of 50 mg/m{sup 2}. Results: in total, 70/81 patients (86%) completed both radio- and chemotherapy. Grade 1 nausea/vomiting was seen in 28%, grade 2 in 11%, grade 3 in 1%. Antiemetics were applied in 41%. Hematologic toxicities were observed as follows: leukopenia grade 3/4 1%, lymphopenia grade 3/4 46%, thrombopenia grade 3/4 1%. Two patients under dexamethasone suffered herpes encephalitis after one and 16 doses of temozolomide (75 mg/m{sup 2}). Median survival was 15 months for glioblastoma. In oligodendroglioma patients, a 4-year survival rate of 78% was observed. Conclusion: postoperative radiochemotherapy with 30-33 daily doses of temozolomide (75 mg/m{sup 2}) is safe in patients with malignant glioma. The combined schedule is effective in oligodendroglioma patients and may prolong survival in glioblastoma. Effort should be taken to minimize corticosteroid doses, since both steroids and temozolomide lead to immunosuppression. (orig.)

  12. A human brainstem glioma xenograft model enabled for bioluminescence imaging

    OpenAIRE

    Hashizume, Rintaro; Ozawa, Tomoko; Dinca, Eduard B.; Banerjee, Anuradha; Prados, Michael D.; James, Charles D.; Gupta, Nalin

    2009-01-01

    Despite the use of radiation and chemotherapy, the prognosis for children with diffuse brainstem gliomas is extremely poor. There is a need for relevant brainstem tumor models that can be used to test new therapeutic agents and delivery systems in pre-clinical studies. We report the development of a brainstem-tumor model in rats and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to therapy as part of this model. Luciferase-modified human glioblastoma...

  13. Involvement of the kynurenine pathway in human glioma pathophysiology.

    Directory of Open Access Journals (Sweden)

    Seray Adams

    Full Text Available The kynurenine pathway (KP is the principal route of L-tryptophan (TRP catabolism leading to the production of kynurenine (KYN, the neuroprotectants, kynurenic acid (KYNA and picolinic acid (PIC, the excitotoxin, quinolinic acid (QUIN and the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD(+. The enzymes indoleamine 2,3-dioxygenase-1 (IDO-1, indoleamine 2,3-dioxygenase-2 (IDO-2 and tryptophan 2,3-dioxygenase (TDO-2 initiate the first step of the KP. IDO-1 and TDO-2 induction in tumors are crucial mechanisms implicated to play pivotal roles in suppressing anti-tumor immunity. Here, we report the first comprehensive characterisation of the KP in 1 cultured human glioma cells and 2 plasma from patients with glioblastoma (GBM. Our data revealed that interferon-gamma (IFN-γ stimulation significantly potentiated the expression of the KP enzymes, IDO-1 IDO-2, kynureninase (KYNU, kynurenine hydroxylase (KMO and significantly down-regulated 2-amino-3-carboxymuconate semialdehyde decarboxylase (ACMSD and kynurenine aminotransferase-I (KAT-I expression in cultured human glioma cells. This significantly increased KP activity but significantly lowered the KYNA/KYN neuroprotective ratio in human cultured glioma cells. KP activation (KYN/TRP was significantly higher, whereas the concentrations of the neuroreactive KP metabolites TRP, KYNA, QUIN and PIC and the KYNA/KYN ratio were significantly lower in GBM patient plasma (n = 18 compared to controls. These results provide further evidence for the involvement of the KP in glioma pathophysiology and highlight a potential role of KP products as novel and highly attractive therapeutic targets to evaluate for the treatment of brain tumors, aimed at restoring anti-tumor immunity and reducing the capacity for malignant cells to produce NAD(+, which is necessary for energy production and DNA repair.

  14. Tumor infiltrating immune cells in gliomas and meningiomas.

    Science.gov (United States)

    Domingues, Patrícia; González-Tablas, María; Otero, Álvaro; Pascual, Daniel; Miranda, David; Ruiz, Laura; Sousa, Pablo; Ciudad, Juana; Gonçalves, Jesús María; Lopes, María Celeste; Orfao, Alberto; Tabernero, María Dolores

    2016-03-01

    Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood. Overall, these studies have shown significant but variable levels of infiltration of CNS tumors by macrophage/microglial cells (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells, and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate numbers where they frequently show an immune suppressive phenotype and functional behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas, particularly in cases that carry isolated monosomy 22, where the immune infiltrates also contain greater numbers of cytotoxic T and NK-cells associated with an enhanced anti-tumoral immune response. In line with this, the presence of regulatory T cells, is usually limited to a small fraction of all meningiomas, while frequently found in gliomas. Despite these differences between gliomas and meningiomas, both tumors show heterogeneous levels of infiltration by immune cells with variable functionality. In this review we summarize current knowledge about tumor-infiltrating immune cells in the two most common types of CNS tumors-gliomas and meningiomas-, as well as the role that such immune cells may play in the tumor microenvironment in controlling and/or promoting tumor development, growth and control.

  15. Cortical and Subcortical Structural Plasticity Associated with the Glioma Volumes in Patients with Cerebral Gliomas Revealed by Surface-Based Morphometry

    Directory of Open Access Journals (Sweden)

    Jinping Xu

    2017-06-01

    Full Text Available Postlesional plasticity has been identified in patients with cerebral gliomas by inducing a large functional reshaping of brain networks. Although numerous non-invasive functional neuroimaging methods have extensively investigated the mechanisms of this functional redistribution in patients with cerebral gliomas, little effort has been made to investigate the structural plasticity of cortical and subcortical structures associated with the glioma volume. In this study, we aimed to investigate whether the contralateral cortical and subcortical structures are able to actively reorganize by themselves in these patients. The compensation mechanism following contralateral cortical and subcortical structural plasticity is considered. We adopted the surface-based morphometry to investigate the difference of cortical and subcortical gray matter (GM volumes in a cohort of 14 healthy controls and 13 patients with left-hemisphere cerebral gliomas [including 1 patients with World Health Organization (WHO I, 8 WHO II, and 4 WHO III]. The glioma volume ranges from 5.1633 to 208.165 cm2. Compared to healthy controls, we found significantly increased GM volume of the right cuneus and the left thalamus, as well as a trend toward enlargement in the right globus pallidus in patients with cerebral gliomas. Moreover, the GM volumes of these regions were positively correlated with the glioma volumes of the patients. These results provide evidence of cortical and subcortical enlargement, suggesting the usefulness of surface-based morphometry to investigate the structural plasticity. Moreover, the structural plasticity might be acted as the compensation mechanism to better fulfill its functions in patients with cerebral gliomas as the gliomas get larger.

  16. Neuroarchitecture of the central complex of the desert locust: Intrinsic and columnar neurons.

    Science.gov (United States)

    Heinze, Stanley; Homberg, Uwe

    2008-12-01

    The central complex is a group of neuropils in the center of the insect brain. It consists of four major subunits: the upper and lower divisions of the central body (CBU, CBL), the protocerebral bridge (PB), and the paired noduli. A distinctive feature of the central complex is a modular architecture characterized by rows of 16 columns, intersected in the central body by stacks of layers. Evidence from locusts suggests that the central complex plays a major role in sky compass orientation. To understand signal processing in this brain area further, we have analyzed the morphologies of columnar neurons of the central complex of the locust Schistocerca gregaria. Intracellular dye fills revealed 21 types of columnar neurons that connect columns of different subunits, three types of pontine neurons linking pairs of columns within the CBU, and one amacrine cell. Most neurons appeared to be part of isomorphic sets with cell type-specific heterolateral projection patterns. Evaluation of arborization areas and neuron polarity suggests that these neurons are either intrinsic to the central complex or provide output to the lateral accessory lobes (LALs) or anterior lip region. No direct connections were found between the CBU and CBL. Instead, neurons of either subdivision were connected with the PB, but projected to non-overlapping regions in the LALs and to different layers of the noduli. This study provides novel insights into the functional organization of the central complex, especially with respect to its likely role in right-left signal matching and decision making. (c) 2008 Wiley-Liss, Inc.

  17. Carboxyl terminus of Hsp70-interacting protein (CHIP) contributes to human glioma oncogenesis.

    Science.gov (United States)

    Xu, Tao; Zhou, Quan; Zhou, Jingxu; Huang, Yan; Yan, Yong; Li, Weiqing; Wang, Chunlin; Hu, Guohan; Lu, Yicheng; Chen, Juxiang

    2011-05-01

    Malignant glioma is the most common adult primary brain tumor, and the mechanism of its oncogenesis is poorly understood. Growing evidence has shown that E3 ubiquitin ligases can promote tumorgenesis of glioma. CHIP is an E3 ubiquitin ligase that can induce ubiquitylation and degradation of many tumor-related proteins, and it has been reported to act as an upstream regulator in breast cancer; however, its role in human gliomas has not been evaluated yet. In this study, the expression of CHIP in glioma tissues was studied using immunohistochemistry. CHIP expression in glioma cells was studied by real-time RT-PCR, western blot and double immunofluorescence staining. The role of CHIP in glioma oncogenesis was investigated by lentivirus-mediated RNA interference (RNAi) and overexpression in vitro and in vivo. We showed CHIP expression in glioma samples was related to tumor grades, with stronger staining in high-grade gliomas than in low-grade gliomas. Knocking down of CHIP suppressed proliferation, colony formation of U251 and U87 glioma cells, while overexpression of CHIP resulted in enhanced proliferation and colony formation in vitro. In a nude mouse xenograft model, intratumoral injection of CHIP RNAi lentivirus significantly delayed tumor growth. In contrast, overexpression of CHIP resulted in enhanced tumor growth in vivo. After CHIP RNAi, both survivin mRNA and protein were decreased, while CHIP overexpression induced increased mRNA and protein levels of survivin. This is the first study demonstrating CHIP contributes to oncogenesis of glioma. © 2011 Japanese Cancer Association.

  18. Cluster Analysis and Significance of Novel Genes Related to Molecular Classification of Glioma

    Institute of Scientific and Technical Information of China (English)

    Juxiang Chen; Yicheng Lu; Guohan Hu; Kehua Sun; Chun Luo; Meiqing Lou; Kang Ying; Yao Li

    2005-01-01

    OBJECTIVE To screen differentially expressed genes in the development of human glioma and establish a primary molecular classification of glioma based on gene expression using cDNA microarrays.METHODS Brain specimens were obtained from 18 patients with glioma, 10males and 8 females, ages 14~62 with an average age of 44.4. The total RNAs of these glioma specimens and two specimens of donated brain of normal adults were extracted. BioStarH140S microarrays (including 8,347old genes and 5,592 novel genes) were adopted and hybridized with probes which were prepared from the total RNAs. Differentially expressed genes between normal tissues and glioma tissues were assayed after scanning cDNA microarrays with ScanArray4000. Northern hybridization and in situ hybridization (ISH) were used to identify functions of novel genes. Those differentially expressed genes were studied with a Hierarchical method and molecular classification of glioma was preliminary carried out.RESULTS Among the 13,939 target genes, there were 1,200 (8.61%)differentially expressed genes, of which 395 (2.83%) were novel genes. A total of 348 genes were up-regulated and 852 genes were down-regulated in the gliomas. The results of bioinformatical analysis, Northern hybridization and ISH revealed that those novel genes were highly associated with gliomas. There were multiple genes, such as the MAP gene、cytoskeleton & matrix motility genes, etc, which were of relevance to classification by the Hierarchical method. Molecular classification of glioma using a Hierarchical cluster was in accordance with pathology and suggested a molecular process of tumorigenesis and development.CONCLUSION Multiple genes play important roles in development of glioma. cDNA microarray technology is a powerful technique in screening for differentially expressed genes between two different kinds of tissues. Further analysis of gene expression and novel genes would be helpful to understand the molecular mechanism of glioma

  19. The ketogenic diet for the treatment of malignant glioma.

    Science.gov (United States)

    Woolf, Eric C; Scheck, Adrienne C

    2015-01-01

    Advances in our understanding of glioma biology has led to an increase in targeted therapies in preclinical and clinical trials; however, cellular heterogeneity often precludes the targeted molecules from being found on all glioma cells, thus reducing the efficacy of these treatments. In contrast, one trait shared by virtually all tumor cells is altered (dysregulated) metabolism. Tumor cells have an increased reliance on glucose, suggesting that treatments affecting cellular metabolism may be an effective method to improve current therapies. Indeed, metabolism has been a focus of cancer research in the last few years, as many pathways long associated with tumor growth have been found to intersect metabolic pathways in the cell. The ketogenic diet (high fat, low carbohydrate and protein), caloric restriction, and fasting all cause a metabolic change, specifically, a reduction in blood glucose and an increase in blood ketones. We, and others, have demonstrated that these metabolic changes improve survival in animal models of malignant gliomas and can potentiate the anti-tumor effect of chemotherapies and radiation treatment. In this review we discuss the use of metabolic alteration for the treatment of malignant brain tumors.

  20. External irradiation models for intracranial 9L glioma studies

    Directory of Open Access Journals (Sweden)

    Feuvret Loïc

    2010-11-01

    Full Text Available Abstract Purpose Radiotherapy has been shown to be an effective for the treatment human glioma and consists of 30 fractions of 2 Gy each for 6-7 weeks in the tumor volume with margins. However. in preclinical studies, many different radiation schedules are used. The main purpose of this work was to review the relevant literature and to propose an external whole-brain irradiation (WBI protocol for a rat 9L glioma model. Materials and methods 9L cells were implanted in the striatum of twenty 344-Fisher rats to induce a brain tumor. On day 8, animals were randomized in two groups: an untreated group and an irradiated group with three fractions of 6 Gy at day 8, 11 and 14. Survival and toxicity were assessed. Results Irradiated rats had significantly a longer survival (p = 0.01. No deaths occurred due to the treatment. Toxicities of reduced weight and alopecia were increased during the radiation period but no serious morbidity or mortality was observed. Moreover, abnormalities disappeared the week following the end of the therapeutic schedule. Conclusions Delivering 18 Gy in 3 fractions of 6 Gy every 3 days, with mild anaesthesia, is safe, easy to reproduce and allows for standardisation in preclinical studies of different treatment regimens glioma rat model.

  1. Role of Inflammation and Oxidative Stress Mediators in Gliomas

    Directory of Open Access Journals (Sweden)

    Alfredo Conti

    2010-04-01

    Full Text Available Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

  2. Radiochemotherapy of malignant glioma in adults. Clinical experiences

    Energy Technology Data Exchange (ETDEWEB)

    Kortmann, R.D.; Jeremic, B.; Plasswilm, L.; Bamberg, M. [Dept. for Radiation Oncology, Univ. of Tuebingen (Germany); Weller, M. [Dept. of Neurology, Univ. of Tuebingen (Germany)

    2003-04-01

    Background: Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has led to the investigation of additional chemotherapy. Material and Methods: Recent results of radiochemotherapy published in the literature were reviewed with respect to outcome in phase II and III trials. Based on these experiences, aspects of future strategies were discussed. Results: 3 decades of intensive research had, unfortunately, little impact on the overall results. While early prospective studies established adjuvant nitrosoureas, particularly BCNU, as suitable adjuvant to surgery and postoperative radiotherapy, further studies largely concentrated on combined chemotherapeutic protocols, mostly procarbazine, CCNU and vincristine (PCV), which was shown to prolong survival in anaplastic astrocytoma. The recent MRC study, however, showed no effect for adjuvant PCV in grade III and IV malignant glioma. Only in high-grade glioma with an oligodendroglial component, additional chemotherapy may be of a decisive benefit. The introduction of newer drugs such as paclitaxel, temozolomide, or gemcitabine demonstrated no decisive advantage. Different modes of application and sequencing of radiotherapy and chemotherapy are presently actively investigated, but failed to substantially improve outcome. Conclusions: Therefore, search for newer and more effective drugs continues, as well as for ''optimal'' administration and sequencing, especially from the standpoint of accompanying acute and late toxicity. Finally, recent endeavors focused on basic research such as angiogenesis, migration and invasion, or induction of cell differentiation, but these strategies are still away from broader clinical investigation. (orig.)

  3. RETROVIRAL-MEDIATED SUICIDE GENE THERAPY OF EXPERIMENTAL GLIOMA

    Institute of Scientific and Technical Information of China (English)

    Xu Lingfei; Ge Kai; Zheng Zhongcheng; Sun Lanying; Liu Xinyuan

    1998-01-01

    Objective: To establish a retroviral-mediated suicide gene therapy system for experimental glioma and test its efficacy. Methods: C6 rat glioma cells were infected with recombinant retrovirus containing HSV-tk gene. The C6/tk cell line which stably expressed tk was selected and cloned. The sensitivities of C6/tk cells to several nucleoside analogues, such as GCV, BVdU, ACV were compared by the growth inhibition studies. Antitumor effects were also observed after GCV treatment in nude mice bearing tumors derived from C6/tk cells. Results:The growth inhibition studies showed that GCV was the most efficient prodrug in this system. C6/tk cells were highly sensitive to GCV, with an IC50<0.2 μmol/L, being 500-fold less than that in tk-negative C6 cells. In vivo studies showed significant tumor inhibition in the treatment group. Conclusion: Glioma cells can be eradicated by using retroviral-mediated suicide gene system in vitro as well as in vivo.

  4. ASYMMETRIC CELL DIVISION: IMPLICATIONS FOR GLIOMA DEVELOPMENT AND TREATMENT

    Science.gov (United States)

    Lewis, Kate Marie; Petritsch, Claudia

    2014-01-01

    Glioma is a heterogeneous disease process with differential histology and treatment response. It was previously thought that the histological features of glial tumors indicated their cell of origin. However, the discovery of continuous neuro-gliogenesis in the normal adult brain and the identification of brain tumor stem cells within glioma have led to the hypothesis that these brain tumors originate from multipotent neural stem or progenitor cells, which primarily divide asymmetrically during the postnatal period. Asymmetric cell division allows these cell types to concurrently self-renew whilst also producing cells for the differentiation pathway. It has recently been shown that increased symmetrical cell division, favoring the self-renewal pathway, leads to oligodendroglioma formation from oligodendrocyte progenitor cells. In contrast, there is some evidence that asymmetric cell division maintenance in tumor stem-like cells within astrocytoma may lead to acquisition of treatment resistance. Therefore cell division mode in normal brain stem and progenitor cells may play a role in setting tumorigenic potential and the type of tumor formed. Moreover, heterogeneous tumor cell populations and their respective cell division mode may confer differential sensitivity to therapy. This review aims to shed light on the controllers of cell division mode which may be therapeutically targeted to prevent glioma formation and improve treatment response. PMID:25530875

  5. Dipeptidyl peptidase IV in two human glioma cell lines

    Directory of Open Access Journals (Sweden)

    A Sedo

    2009-12-01

    Full Text Available There is growing evidence that dipeptidyl peptidase IV [DPP-IV, EC 3.4.14.5] takes part in the metabolism of biologically active peptides participating in the regulation of growth and transformation of glial cells. However, the knowledge on the DPP-IV expression in human glial and glioma cells is still very limited. In this study, using histochemical and biochemical techniques, the DPP-IV activity was demonstrated in two commercially available human glioma cell lines of different transformation degree, as represented by U373 astrocytoma (Grade III and U87 glioblastoma multiforme (Grade IV lines. Higher total activity of the enzyme, as well as its preferential localisation in the plasma membrane, was observed in U87 cells. Compared to U373 population, U87 cells were morphologically more pleiomorphic, they were cycling at lower rate and expressing less Glial Fibrillary Acidic Protein. The data revealed positive correlation between the degree of transformation of cells and activity of DPP-IV. Great difference in expression of this enzyme, together with the phenotypic differences of cells, makes these lines a suitable standard model for further 57 studies of function of this enzyme in human glioma cells.

  6. Fluorescence and image guided resection in high grade glioma.

    Science.gov (United States)

    Panciani, Pier Paolo; Fontanella, Marco; Schatlo, Bawarjan; Garbossa, Diego; Agnoletti, Alessandro; Ducati, Alessandro; Lanotte, Michele

    2012-01-01

    The extent of resection in high grade glioma is increasingly been shown to positively effect survival. Nevertheless, heterogeneity and migratory behavior of glioma cells make gross total resection very challenging. Several techniques were used in order to improve the detection of residual tumor. Aim of this study was to analyze advantages and limitations of fluorescence and image guided resection. A multicentric prospective study was designed to evaluate the accuracy of each method. Furthermore, the role of 5-aminolevulinc acid and neuronavigation were reviewed. Twenty-three patients harboring suspected high grade glioma, amenable to complete resection, were enrolled. Fluorescence and image guides were used to perform surgery. Multiple samples were obtained from the resection cavity of each lesion according to 5-ALA staining positivity and boundaries as delineated by neuronavigation. All samples were analyzed by a pathologist blinded to the intra-operative labeling. Decision-making based on fluorescence showed a sensitivity of 91.1% and a specificity of 89.4% (pimage-guided resection accuracy was low (sensitivity: 57.8%; specificity: 57.4%; p=0.346). We observed that the sensitivity of 5-ALA can be improved by the combined use of neuronavigation, but this leads to a significant reduction in specificity. Thus, the use of auxiliary techniques should always be subject to critical skills of the surgeon. We advocate a large-scale study to further improve the assessment of multimodal approaches.

  7. Bromelain reversibly inhibits invasive properties of glioma cells.

    Science.gov (United States)

    Tysnes, B B; Maurer, H R; Porwol, T; Probst, B; Bjerkvig, R; Hoover, F

    2001-01-01

    Bromelain is an aqueous extract from pineapple stem that contains proteinases and exhibits pleiotropic therapeutic effects, i.e., antiedematous, antiinflammatory, antimetastatic, antithrombotic, and fibrinolytic activities. In this study, we tested bromelain's effects on glioma cells to assess whether bromelain could be a potential contributor to new antiinvasive strategies for gliomas. Several complementary assays demonstrated that bromelain significantly and reversibly reduced glioma cell adhesion, migration, and invasion without affecting cell viability, even after treatment periods extending over several months. Immunohistochemistry and immunoblotting experiments demonstrated that alpha3 and beta1 integrin subunits and hyaluronan receptor CD44 protein levels were reduced within 24 hours of bromelain treatment. These effects were not reflected at the RNA level because RNA profiling did not show any significant effects on gene expression. Interestingly, metabolic labelling with 35-S methionine demonstrated that de novo protein synthesis was greatly attenuated by bromelain, in a reversible manner. By using a transactivating signaling assay, we found that CRE-mediated signaling processes were suppressed. These results indicate that bromelain exerts its antiinvasive effects by proteolysis, signaling cascades, and translational attenuation.

  8. Bromelain Reversibly Inhibits Invasive Properties of Glioma Cells

    Directory of Open Access Journals (Sweden)

    Berit B. Tysnes

    2001-01-01

    Full Text Available Bromelain is an aqueous extract from pineapple stem that contains proteinases and exhibits pleiotropic therapeutic effects, i.e., antiedematous, antiinflammatory, antimetastatic, antithrombotic, fibrinolytic activities. In this study, we tested bromelain's effects on glioma cells to assess whether bromelain could be a potential contributor to new antiinvasive strategies for gliomas. Several complementary assays demonstrated that bromelain significantly and reversibly reduced glioma cell adhesion, migration, invasion without affecting cell viability, even after treatment periods extending over several months. Immunohistochemistry and immunoblotting experiments demonstrated that a3 and α1 integrin subunits and hyaluronan receptor CD44 protein levels were reduced within 24 hours of bromelain treatment. These effects were not reflected at the RNA level because RNA profiling did not show any significant effects on gene expression. Interestingly, metabolic labelling with 35-S methionine demonstrated that de novo protein synthesis was greatly attenuated by bromelain, in a reversible manner. By using a transactivating signaling assay, we found that CRE-mediated signaling processes were suppressed. These results indicate that bromelain exerts its antiinvasive effects by proteolysis, signaling cascades, translational attenuation.

  9. Second Surgery in Insular Low-Grade Gliomas

    Directory of Open Access Journals (Sweden)

    Tamara Ius

    2015-01-01

    Full Text Available Background. Given the technical difficulties, a limited number of works have been published on insular gliomas surgery and risk factors for tumor recurrence (TR are poorly documented. Objective. The aim of the study was to determine TR in adult patients with initial diagnosis of insular Low-Grade Gliomas (LGGs that subsequently underwent second surgery. Methods. A consecutive series of 53 patients with insular LGGs was retrospectively reviewed; 23 patients had two operations for TR. Results. At the time of second surgery, almost half of the patients had experienced progression into high-grade gliomas (HGGs. Univariate analysis showed that TR is influenced by the following: extent of resection (EOR (P<0.002, ΔVT2T1 value (P<0.001, histological diagnosis of oligodendroglioma (P=0.017, and mutation of IDH1 (P=0.022. The multivariate analysis showed that EOR at first surgery was the independent predictor for TR (P<0.001. Conclusions. In patients with insular LGG the EOR at first surgery represents the major predictive factor for TR. At time of TR, more than 50% of cases had progressed in HGG, raising the question of the oncological management after the first surgery.

  10. Targeted therapy in the treatment of malignant gliomas

    Directory of Open Access Journals (Sweden)

    Rimas V Lukas

    2009-05-01

    Full Text Available Rimas V Lukas1, Adrienne Boire2, M Kelly Nicholas1,2 1Department of Neurology; 2Department of Medicine, University of Chicago, Chicago, IL, USAAbstract: Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical and clinical settings as potential targets in the treatment of malignant gliomas. We will review many of the therapies that target the cancer cell, including the epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylase, and farnesyl transferase. In addition, we will discuss strategies that target the extracellular matrix in which these cells reside as well as angiogenesis, a process emerging as central to tumor development and growth. Finally, we will briefly touch on the role of neural stem cells as both potential targets as well as delivery vectors for other therapies. Interdependence between these varied pathways, both in maintaining health and in causing disease, is clear. Thus, attempts to easily classify some targeted therapies are problematic.Keywords: glioma, EGFR, mTOR, HDAC, Ras, angiogenesis

  11. Post-treatment imaging of high-grade gliomas

    Directory of Open Access Journals (Sweden)

    Darshana Sanghvi

    2015-01-01

    Full Text Available Current standard of care for treatment of newly diagnosed high grade gliomas is surgery followed by concomitant radiotherapy (RT and chemotherapy (CT with temozolomide (TMZ. Recently, bevacizumab, an anti - angiogenic agent has also been approved for treatment of recurrent gliomas. Baseline imaging after excision is optimally obtained in the first 24 hours. When baseline postoperative imaging is delayed beyond 24 hours, subacute hemorrhage, subacute ischemia and inflammation at the resection margins render differentiation from residual tumor challenging. Radiation necrosis is a well recognized entity and is differentiated from recurrence based on morphology on structural imaging, presence of lipid - lactate complexes with lack of choline on spectroscopy and low normalized cerebral blood volume (CBV ratios at perfusion imaging. Novel chemotherapies have lead to the occurrence of interesting but sometimes confusing post treatment imaging appearances including the phenomena of ′pseudoprogression′ and ′pseudoresponse′. Pseudoprogression refers to transient, self resolving focal enhancement mediated by TMZ-induced increased vascular permeability and local inflammatory response. Pathologically, these lesions do not have viable tumor. The lesions stabilize or regress without further treatment and are usually clinically asymptomatic. Pseudoresponse refers to rapid regression of enhancement, perfusion, mass effect and midline shift caused by the anti - angiogenic effect of bevacizumab. It is termed pseudoresponse since biological tumor persists as non-enhancing altered signal. It is important for radiologists to be aware of these entities seen on post treatment imaging of gliomas, as misinterpretation may lead to inappropriate management decisions and prognostication.

  12. Atypical crossmodal emotional integration in patients with gliomas.

    Science.gov (United States)

    Luherne-du Boullay, Viviane; Plaza, Monique; Perrault, Annabelle; Capelle, Laurent; Chaby, Laurence

    2014-11-01

    The relevance of emotional perception in interpersonal relationships and social cognition has been well documented. Although brain diseases might impair emotional processing, studies concerning emotional recognition in patients with brain tumours are relatively rare. The aim of this study was to explore emotional recognition in patients with gliomas in three conditions (visual, auditory and crossmodal) and to analyse how tumour-related variables (notably, tumour localisation) and patient-related variables influence emotion recognition. Twenty six patients with gliomas and 26 matched healthy controls were instructed to identify 5 basic emotions and a neutral expression, which were displayed through visual, auditory and crossmodal stimuli. Relative to the controls, recognition was weakly impaired in the patient group under both visual and auditory conditions, but the performances were comparable in the crossmodal condition. Additional analyses using the 'race model' suggest differences in multisensory emotional integration abilities across the groups, which were potentially correlated with the executive disorders observed in the patients. These observations support the view of compensatory mechanisms in the case of gliomas that might preserve the quality of life and help maintain the normal social and professional lives often observed in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Therapeutic vaccination against malignant gliomas based on allorecognition and syngeneic tumour antigens: proof of principle in two strains of rat

    NARCIS (Netherlands)

    Stathopoulos, A.; Samuelson, C.; Milbouw, G.; Hermanne, J.P.; Schijns, V.E.J.C.; Chen, T.C.

    2008-01-01

    In the present study we investigated whether allogeneic glioma cells can be utilized to evoke prophylactic or therapeutic immune-mediated elimination of syngeneic glioma in two rat strains. Fisher 344 and Sprague–Dawley (SD) rats were injected with two syngeneic glioma cell lines, 9L and C6, respect

  14. Celiac Family Health Education Video Series

    Medline Plus

    Full Text Available ... Treatments Go to Conditions + Treatments Health Conditions Hernia (Umbilical or Inguinal) Diffuse pontine glioma Tethered spinal cord Plagiocephaly More Treatments Spinal tap and lumbar puncture ...

  15. Intrinsically photosensitive retinal ganglion cells

    Institute of Scientific and Technical Information of China (English)

    Gary; E.PICKARD; Patricia; J.SOLLARS

    2010-01-01

    A new mammalian photoreceptor was recently discovered to reside in the ganglion cell layer of the inner retina.These intrinsically photosensitive retinal ganglion cells(ipRGCs) express a photopigment,melanopsin,that confers upon them the ability to respond to light in the absence of all rod and cone photoreceptor input.Although relatively few in number,ipRGCs extend their dendrites across large expanses of the retina making them ideally suited to function as irradiance detectors to assess changes in ambient light levels.Phototransduction in ipRGCs appears to be mediated by transient receptor potential channels more closely resembling the phototransduction cascade of invertebrate rather than vertebrate photoreceptors.ipRGCs convey irradiance information centrally via the optic nerve to influence several functions.ipRGCs are the primary retinal input to the hypothalamic suprachiasmatic nucleus(SCN),a circadian oscillator and biological clock,and this input entrains the SCN to the day/night cycle.ipRGCs contribute irradiance signals that regulate pupil size and they also provide signals that interface with the autonomic nervous system to regulate rhythmic gene activity in major organs of the body.ipRGCs also provide excitatory drive to dopaminergic amacrine cells in the retina,providing a novel basis for the restructuring of retinal circuits by light.Here we review the ground-breaking discoveries,current progress and directions for future investigation.

  16. Gliomas do nervo óptico: estudo de 11 casos Optic nerve gliomas: a study of 11 cases

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Bleggi Torres

    1996-06-01

    Full Text Available Os gliomas do nervo óptico podem apresentar-se esporadicamente ou como componentes da neurofibromatose. São neoplasias raras, correspondendo a 2 a 5% dos tumores intracranianos e cerca de 6% dos tumores intra-orbitários. No presente estudo, analisamos 11 casos de glioma de nervo óptico diagnosticados em Curitiba num período de 25 anos, sendo 10 pacientes do sexo feminino e 1 do sexo masculino. As idades variaram de 3 a 25 anos; 6 pacientes apresentavam idades inferiores a 15 anos. Dos casos desta série, 27,3% (n=3 apresentavam associação com neurofibromatose. Quanto à localização dos tumores, em 5 pacientes a lesão estava restrita ao nervo óptico e no restante havia extensão para o quiasma óptico, região supra-selar, lobo frontal ou temporal. Todos os pacientes tinham astrocitoma pilocítico.Optic nerve gliomas may occur alone or as components of neurofibromatosis. They are rare tumors accounting for 2 to 5% of all intracranial tumors and 6% of the intra-orbitary neoplasms. The authors present 11 cases of optic nerve glioma diagnosed in Curitiba in the last 25 years. Out of these 11 patients there were 10 women and only 1 man. The ages ranged from 3 to 25 years old, and 6 patients were under 15 years. In this series, 27,3% (n=3 of the cases were associated with neurofibromatosis. Five patients had their tumors restricted to the optic nerve while the others had either extension to the optic chiasm, supra-selar region, frontal or temporal lobe. All the patients had pilocytic astrocytomas.

  17. Conditional astroglial Rictor overexpression induces malignant glioma in mice.

    Directory of Open Access Journals (Sweden)

    Tariq Bashir

    Full Text Available BACKGROUND: Hyperactivation of the mTORC2 signaling pathway has been shown to contribute to the oncogenic properties of gliomas. Moreover, overexpression of the mTORC2 regulatory subunit Rictor has been associated with increased proliferation and invasive character of these tumor cells. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether Rictor overexpression was sufficient to induce glioma formation in mice, we inserted a Cre-lox-regulated human Rictor transgene into the murine ROSA26 locus. This floxed Rictor strain was crossed with mice expressing the Cre recombinase driven from the glial fibrillary acidic protein (GFAP promoter whose expression is limited to the glial cell compartment. Double transgenic GFAP-Cre/Rictor(loxP/loxP mice developed multifocal infiltrating glioma containing elevated mTORC2 activity and typically involved the subventricular zone (SVZ and lateral ventricle. Analysis of Rictor-dependent signaling in these tumors demonstrated that in addition to elevated mTORC2 activity, an mTORC2-independent marker of cortical actin network function, was also elevated. Upon histological examination of the neoplasms, many displayed oligodendroglioma-like phenotypes and expressed markers associated with oligodendroglial lineage tumors. To determine whether upstream oncogenic EGFRvIII signaling would alter tumor phenotypes observed in the GFAP-Cre/Rictor(loxP/loxP mice, transgenic GFAP-EGFRvIII; GFAP-Cre/Rictor(loxP/loxP mice were generated. These mice developed mixed astrocytic-oligodendroglial tumors, however glioma formation was accelerated and correlated with increased mTORC2 activity. Additionally, the subventricular zone within the GFAP-Cre/Rictor(loxP/loxP mouse brain was markedly expanded, and a further proliferation within this compartment of the brain was observed in transgenic GFAP-EGFRvIII; GFAP-Cre/Rictor(loxP/loxP mice. CONCLUSION/SIGNIFICANCE: These data collectively establish Rictor as a novel oncoprotein and support

  18. Conditional Astroglial Rictor Overexpression Induces Malignant Glioma in Mice

    Science.gov (United States)

    Bashir, Tariq; Cloninger, Cheri; Artinian, Nicholas; Anderson, Lauren; Bernath, Andrew; Holmes, Brent; Benavides-Serrato, Angelica; Sabha, Nesrin; Nishimura, Robert N.; Guha, Abhijit; Gera, Joseph

    2012-01-01

    Background Hyperactivation of the mTORC2 signaling pathway has been shown to contribute to the oncogenic properties of gliomas. Moreover, overexpression of the mTORC2 regulatory subunit Rictor has been associated with increased proliferation and invasive character of these tumor cells. Methodology/Principal Findings To determine whether Rictor overexpression was sufficient to induce glioma formation in mice, we inserted a Cre-lox-regulated human Rictor transgene into the murine ROSA26 locus. This floxed Rictor strain was crossed with mice expressing the Cre recombinase driven from the glial fibrillary acidic protein (GFAP) promoter whose expression is limited to the glial cell compartment. Double transgenic GFAP-Cre/RictorloxP/loxP mice developed multifocal infiltrating glioma containing elevated mTORC2 activity and typically involved the subventricular zone (SVZ) and lateral ventricle. Analysis of Rictor-dependent signaling in these tumors demonstrated that in addition to elevated mTORC2 activity, an mTORC2-independent marker of cortical actin network function, was also elevated. Upon histological examination of the neoplasms, many displayed oligodendroglioma-like phenotypes and expressed markers associated with oligodendroglial lineage tumors. To determine whether upstream oncogenic EGFRvIII signaling would alter tumor phenotypes observed in the GFAP-Cre/RictorloxP/loxP mice, transgenic GFAP-EGFRvIII; GFAP-Cre/RictorloxP/loxP mice were generated. These mice developed mixed astrocytic-oligodendroglial tumors, however glioma formation was accelerated and correlated with increased mTORC2 activity. Additionally, the subventricular zone within the GFAP-Cre/RictorloxP/loxP mouse brain was markedly expanded, and a further proliferation within this compartment of the brain was observed in transgenic GFAP-EGFRvIII; GFAP-Cre/RictorloxP/loxP mice. Conclusion/Significance These data collectively establish Rictor as a novel oncoprotein and support the role of dysregulated

  19. Angiogenic Signalling Pathways Altered in Gliomas: Selection Mechanisms for More Aggressive Neoplastic Subpopulations with Invasive Phenotype

    Directory of Open Access Journals (Sweden)

    Susana Bulnes

    2012-01-01

    Full Text Available The angiogenesis process is a key event for glioma survival, malignancy and growth. The start of angiogenesis is mediated by a cascade of intratumoural events: alteration of the microvasculature network; a hypoxic microenvironment; adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a chaotic blood flow, a consequence of an aberrant microvasculature, tissue hypoxia phenomena are induced. Hypoxia inducible factor 1 is a major regulator in glioma invasiveness and angiogenesis. Clones of neoplastic cells with stem cell characteristics are selected by HIF-1. These cells, called “glioma stem cells” induce the synthesis of vascular endothelial growth factor. This factor is a pivotal mediator of angiogenesis. To elucidate the role of these angiogenic mediators during glioma growth, we have used a rat endogenous glioma model. Gliomas induced by prenatal ENU administration allowed us to study angiogenic events from early to advanced tumour stages. Events such as microvascular aberrations, hypoxia, GSC selection and VEGF synthesis may be studied in depth. Our data showed that for the treatment of gliomas, developing anti-angiogenic therapies could be aimed at GSCs, HIF-1 or VEGF. The ENU-glioma model can be considered to be a useful option to check novel designs of these treatment strategies.

  20. Mitochondrial DNA copy number in whole blood and glioma risk: A case control study.

    Science.gov (United States)

    Shen, Jie; Song, Renduo; Lu, Zhimin; Zhao, Hua

    2016-12-01

    Alterations in mitochondrial DNA (mtDNA) copy number are observed in human gliomas. However, whether variations in mtDNA copy number in whole blood play any role in glioma carcinogenesis is still largely unknown. In current study with 395 glioma patients and 425 healthy controls, we intended to investigate the association between mtDNA copy number in whole blood and glioma risk. Overall, we found that levels of mtDNA copy number were significantly higher in glioma cases than healthy controls (mean: 1.48 vs. 1.32, P copy number were inversely correlated with age (P copy number than their counterparts (P = 0.02, P copy number levels were associated with a 1.63-fold increased risk of glioma (adjusted odds ratio (OR) = 1.63, 95% confidence interval (CI) = 1.23-2.14). In further quartile analysis, study subjects who had highest levels of mtNDA copy number had 1.75-fold increased risk of gliomas (adjOR = 1.75, 95%CI = 1.18-2.61). In brief, our findings support the role of mtDNA copy number in the glioma carcinogenesis. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

    NARCIS (Netherlands)

    A.M. Gravendeel (Lonneke); J.J. de Rooi (Johan); P.H.C. Eilers (Paul); M.J. van den Bent (Martin); P.A.E. Sillevis Smitt (Peter); P.J. French (Pim)

    2012-01-01

    textabstractBackground: We have recently demonstrated that expression profiling is a more accurate and objective method to classify gliomas than histology. Similar to most expression profiling studies, our experiments were performed using fresh frozen (FF) glioma samples whereas most archival sample

  2. Suppression of Glioma-Cell Survival by Antisense and Dominant-Negative AKT2 RNA

    Institute of Scientific and Technical Information of China (English)

    Peiyu Pu; Chunsheng Kang; Jie Li; Guangxiu Wang

    2005-01-01

    OBJECTIVE Overexpression of growth factors and their receptors such as PDGF, FGF, VEGF, IGF, EGF, TGFα etc. Play a critical role in the development and progression of malignant gliomas. AKT, one of the most potent downstream signaling effectors of these growth factor receptors is usually overactivated in malignant gliomas. The present study was undertaken to investigate the effects of antisense and dominant negative AKT2 RNA on the survival of glioma cells with overexpression of AKT2.METHODS Antisense and dominant negative AKT2 constructs (AS-AKT2,DN-AKT2) were transfected into human glioblastoma cell line TJ905 with overexpression of AKT2. Using Western blotting, MTT assay, Ki67 labeling index (Ki67 LI), flow cytometry and the TUNEL method, the expression of AKT2 and GFAP, the proliferation rate and apoptosis of glioma cells transfected with AS-AKT2 or DN-AKT2 were compared to those characteristics of parental and glioma cells transfected with an empty vector.RESULTS Cell proliferation was inhibited in glioma cells transfected with ASAKT2 and DN-AKT2 RNA, while GFAP expression and apoptosis were markedly increased in those cells.CONCLUSION AKT is an important mediator in the growth signaling pathway of malignant gliomas and is a potential promising therapeutic target for malignant gliomas.

  3. Hyperbaric oxygen promotes malignant glioma cell growth and inhibits cell apoptosis.

    Science.gov (United States)

    Wang, Yong-Gang; Zhan, Yi-Ping; Pan, Shu-Yi; Wang, Hai-Dong; Zhang, Dun-Xiao; Gao, Kai; Qi, Xue-Ling; Yu, Chun-Jiang

    2015-07-01

    Glioblastoma multiforme (GBM) is the most frequently diagnosed intracranial malignant tumor in adults. Clinical studies have indicated that hyperbaric oxygen may improve the prognosis and reduce complications in glioma patients; however, the specific mechanism by which this occurs remains unknown. The present study investigated the direct effects of hyperbaric oxygen stimulation on glioma by constructing an intracranial transplanted glioma model in congenic C57BL/6J mice. Bioluminescent imaging (BLI) was used to assess the growth of intracranial transplanted GL261-Luc glioma cells in vivo, while flow cytometric and immunohistochemical assays were used to detect and compare the expression of the biomarkers, Ki-67, CD34 and TUNEL, reflecting the cell cycle, apoptosis and angiogenesis. BLI demonstrated that hyperbaric oxygen promoted the growth of intracranially transplanted GL261-Luc glioma cells in vivo. Flow cytometric analysis indicated that hyperbaric oxygen promoted GL261-Luc glioma cell proliferation and also prevented cell cycle arrest. In addition, hyperbaric oxygen inhibited the apoptosis of the transplanted glioma cells. Immunohistochemical analysis also indicated that hyperbaric oxygen increased positive staining for Ki-67 and CD34, while reducing staining for TUNEL (a marker of apoptosis). The microvessel density was significantly increased in the hyperbaric oxygen treatment group compared with the control group. In conclusion, hyperbaric oxygen treatment promoted the growth of transplanted malignant glioma cells in vivo and also inhibited the apoptosis of these cells.

  4. Alisertib and Fractionated Stereotactic Radiosurgery in Treating Patients With Recurrent High Grade Gliomas

    Science.gov (United States)

    2016-10-19

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Recurrent Adult Brain Tumor

  5. A complex mechanism for HDGF-mediated cell growth, migration, invasion, and TMZ chemosensitivity in glioma.

    Science.gov (United States)

    Song, Ye; Hu, Zheng; Long, Hao; Peng, Yuping; Zhang, Xi'an; Que, Tianshi; Zheng, Shihao; Li, Zhiyong; Wang, Gang; Yi, Liu; Liu, Zhen; Fang, Weiyi; Qi, Songtao

    2014-09-01

    HDGF is overexpressed in gliomas as compared to normal brain. We therefore analyzed the molecular mechanisms of HDGF action in gliomas. HDGF was downregulated in normal brain tissue as compared to glioma specimens at both the mRNA and the protein levels. In glioma samples, increased HDGF expression was associated with disease progression. Knocking down HDGF expression not only significantly decreased cellular proliferation, migration, invasion, and tumorigenesis, but also markedly enhanced TMZ-induced cytotoxicity and apoptosis in glioma cells. Mechanistic analyses revealed that CCND1, c-myc, and TGF-β were downregulated after stable HDGF knockdown in the U251 and U87 glioma cells. HDGF knockdown restored E-cadherin expression and suppressed mesenchymal cell markers such as vimentin, β-catenin, and N-cadherin. The expression of cleaved caspase-3 increased, while Bcl-2 decreased in each cell line following treatment with shHDGF and TMZ, as compared to TMZ alone. Furthermore, RNAi-based knockdown study revealed that HDGF is probably involved in the activation of both the PI3K/Akt and the TGF-β signaling pathways. Together, our data suggested that HDGF regulates glioma cell growth, apoptosis and epithelial-mesenchymal transition (EMT) probably through the Akt and the TGF-β signaling pathways. These results provide evidence that targeting HDGF or its downstream targets may lead to novel therapies for gliomas.

  6. Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

    NARCIS (Netherlands)

    Bijnsdorp, Irene; Berg, van den Jaap; Kuipers, Gitta; Wedekind, Laurine; Slotman, Ben; Rijn, van Johannes; Lafleur, M.; Sminia, Peter

    2007-01-01

    The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 in

  7. Interleukin-2 expression and glioma cell proliferation following Vaceinia vector gene transfection in vivo

    Institute of Scientific and Technical Information of China (English)

    Xiaogang Wang; Xuezhong Wei; Jiangqiu Liu

    2008-01-01

    BACKGROUND: The effectiveness of gene therapy is closely related to the efficiency of vector transfection and expression.OBJECTIVE: This study was designed to transfect a human brain glioma cell line with recombinant Vaccinia virus expressing the interleukin-2 (rVV-IL-2) gene, and to observe IL-2 expression and glioma cell proliferation potential after transfection. DESIGN: Experimental observation. SETTING: Department of Neurosurgery, Shenyang Military Area Command of Chinese PLA. MATERIALS: The rVV-IL-2 vectors were obtained through homologous recombination and screening in the Second Military Medical University of Chinese PLA. The human brain glioma cell line and IL-2-dependent cells were produced by the Second Military Medical University of Chinese PLA. Human IL-2 was produced by Genzyme Corporation. MAIN OUTCOME MEASURES: IL-2 expression at different time points after transfection of human brain glioma cells with varying MOI of Vaccinia viral vectors; in vitro proliferation capacity of human brain glioma cells among the 4 groups. RESULTS: IL-2 expression was detectable 4 hours after Vaccinia viral vector transfection and reached 300 kU/L by 8 hours. There was no significant difference in the proliferating rate of human brain glioma cells among the 4 groups (P > 0.05).CONCLUSION: Vaccinia viral vectors can transfect human brain glioma cells in vitro and express high levels of IL-2. Vaccinia virus and high IL-2 expression do not influence the proliferation rate of human brain glioma cells in vitro.

  8. Angiogenic Signalling Pathways Altered in Gliomas: Selection Mechanisms for More Aggressive Neoplastic Subpopulations with Invasive Phenotype

    Science.gov (United States)

    Bulnes, Susana; Bengoetxea, Harkaitz; Ortuzar, Naiara; Argandoña, Enrike G.; Garcia-Blanco, Álvaro; Rico-Barrio, Irantzu; Lafuente, José V.

    2012-01-01

    The angiogenesis process is a key event for glioma survival, malignancy and growth. The start of angiogenesis is mediated by a cascade of intratumoural events: alteration of the microvasculature network; a hypoxic microenvironment; adaptation of neoplastic cells and synthesis of pro-angiogenic factors. Due to a chaotic blood flow, a consequence of an aberrant microvasculature, tissue hypoxia phenomena are induced. Hypoxia inducible factor 1 is a major regulator in glioma invasiveness and angiogenesis. Clones of neoplastic cells with stem cell characteristics are selected by HIF-1. These cells, called “glioma stem cells” induce the synthesis of vascular endothelial growth factor. This factor is a pivotal mediator of angiogenesis. To elucidate the role of these angiogenic mediators during glioma growth, we have used a rat endogenous glioma model. Gliomas induced by prenatal ENU administration allowed us to study angiogenic events from early to advanced tumour stages. Events such as microvascular aberrations, hypoxia, GSC selection and VEGF synthesis may be studied in depth. Our data showed that for the treatment of gliomas, developing anti-angiogenic therapies could be aimed at GSCs, HIF-1 or VEGF. The ENU-glioma model can be considered to be a useful option to check novel designs of these treatment strategies. PMID:22852079

  9. Expression and prognostic value of the WEE1 kinase in gliomas

    DEFF Research Database (Denmark)

    Music, Darija; Dahlrot, Rikke Hedegaard; Hermansen, Simon Kjær

    2016-01-01

    to irradiation and temozolomide. However, expression level and prognostic potential of WEE1 protein in gliomas remain uninvestigated. In this study, glioma samples from 235 patients across all four WHO grades were analyzed by immunohistochemistry. Using image analysis, we calculated the area fraction of WEE1...

  10. Transferrin modified PEG-PLA-resveratrol conjugates: in vitro and in vivo studies for glioma.

    Science.gov (United States)

    Guo, Wanhua; Li, Aimei; Jia, Zhijun; Yuan, Yi; Dai, Haifeng; Li, Hongxiu

    2013-10-15

    Glioblastoma is one of the most malignant brain tumors with a poor prognosis. In this study, we examined the effects of transferrin (Tf)-modified poly ethyleneglycol-poly lactic acid (PEG-PLA) nanoparticles conjugated with resveratrol (Tf-PEG-PLA-RSV) to glioma therapy in vitro and in vivo. The cell viability of Tf-PEG-PLA-RSV on C6 and U87 glioma cells was determined by the MTT assay. In vivo biodistribution and antitumor activity were investigated in Brain glioma bearing rat model of C6 glioma by i.p. administration of RSV-polymer conjugates. We found that the average diameter of each Tf-PEG-PLA-RSV is around 150 nm with 32 molecules of Tf on surface. In vitro cytotoxicity of PEG-PLA-RSV against C6 and U87 cells was higher than that of free RSV, and further the modification of Tf enhanced the cytotoxicity of the RSV-polymer conjugates as a result of the increased cellular uptake of the RSV-modified conjugates by glioma cells. In comparison with free RSV, RSV conjugates could significantly decrease tumor volume and accumulate in brain tumor, which resulted in prolonging the survival of C6 glioma-bearing rats. These results suggest that Tf-NP-RSV had a potential of therapeutic effect to glioma both in vitro and in vivo and might be a potential candidate for targeted therapy of glioma and worthy of further investigation.

  11. Establishment of C6 brain glioma models through stereotactic technique for laser interstitial thermotherapy research

    Directory of Open Access Journals (Sweden)

    Jian Shi

    2015-01-01

    Conclusion: The rat C6 brain glioma model established in the study was a perfect model to study LITT of glioma. Infrared thermograph technique measured temperature conveniently and effectively. The technique is noninvasive, and the obtained data could be further processed using software used in LITT research. To measure deep-tissue temperature, combining thermocouple with infrared thermograph technique would present better results.

  12. Malignant glioma of the optic chiasm eight years after radiotherapy for prolactinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hufnagel, T.J.; Kim, J.H.; Lesser, R.; Miller, J.M.; Abrahams, J.J.; Piepmeier, J.; Manuelidis, E.E.

    1988-12-01

    A 41-year-old man had rapidly progressive visual loss caused by a malignant glioma that developed in the optic chiasm eight years after radiation therapy for a recurrent prolactinoma. Radiation-induced glioma should be considered as a cause of progressive visual loss in patients who have received irradiation in the region of the sella turcica.

  13. Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance.

    Science.gov (United States)

    Shahi, M H; Farheen, S; Mariyath, M P M; Castresana, J S

    2016-11-01

    Chemoresistance is a common hurdle for the proper treatment of gliomas. The role of Shh-Gli1 signaling in glioma progression has been reported. However, its role in glioma chemoresistance has not been well studied yet. In this work, we found that Shh-Gli1 signaling regulates the expression of one stem cell marker, BMI1 (B cell-specific Moloney murine leukemia virus), in glioma. Interestingly, we also demonstrated high expression of MRP1 (multi-drug resistance protein 1) in glioma. MRP1 expression was decreased by BMI1 siRNA and Shh-Gli1 cell signaling specific inhibitor GANT61 in our experiments. GANT61 very efficiently inhibited cell colony growth in glioma cell lines, compared to temozolomide. Moreover, a synergic effect of GANT61 and temozolomide drastically decreased the LD50 of temozolomide in the cell colony experiments. Therefore, our results suggest that there is a potential nexus of Shh-Gli1-BMI1 cell signaling to regulate MRP1 and to promote chemoresistance in glioma. Henceforth, our study opens the possibility of facing new targets, Gli1 and BMI1, for the effective treatment of glioma suppression of chemoresistance with adjuvant therapy of GANT61 and temozolomide.

  14. The epidemiology of glioma in adults: a "state of the science" review.

    Science.gov (United States)

    Ostrom, Quinn T; Bauchet, Luc; Davis, Faith G; Deltour, Isabelle; Fisher, James L; Langer, Chelsea Eastman; Pekmezci, Melike; Schwartzbaum, Judith A; Turner, Michelle C; Walsh, Kyle M; Wrensch, Margaret R; Barnholtz-Sloan, Jill S

    2014-07-01

    Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O⁶-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults.

  15. MiR-661 inhibits glioma cell proliferation, migration and invasion by targeting hTERT

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhen, E-mail: lizhen7111@163.com [Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, 110004 (China); Liu, Yun-hui; Diao, Hong-yu [Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, 110004 (China); Ma, Jun [Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, 110001 (China); Yao, Yi-long [Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, 110004 (China)

    2015-12-25

    In this study, we analyzed the functional role of miR-661 in glioma cell proliferation, migration and invasion. We found that overexpression of miR-661 obviously suppressed the proliferation, migration and invasion of glioma cells. MiRNA target prediction algorithms implied that hTERT is a candidate target gene for miR-661. A fluorescent reporter assay confirmed that miR-661 could lead to hTERT gene silencing by recognizing and specifically binding to the predicted site of the hTERT mRNA 3′ untranslated region (3′UTR) specifically. Furthermore, hTERT knockdown significantly decreased the growth and viability of glioma cells. These results indicate that miR-661 can inhibit glioma cell proliferation, migration and invasion by targeting hTERT. - Highlights: • MiR-661 was downregulated in glioma tissues and functional as a tumor suppressor. • MiR-661 modulates cell proliferation, invasion and migration of glioma cells. • MiR-661 directly target hTERT in glioma cells. • MiR-661 inhibits glioma cell tumorgenesis by targeting hTERT.

  16. Delta-24-RGD oncolytic adenovirus elicits anti-glioma immunity in an immunocompetent mouse model

    NARCIS (Netherlands)

    H. Jiang (Hao); K. Clise-Dwyer (Karen); K.E. Ruisaard (Kathryn); X. Fan (Xuejun); W. Tian (Weihua); J. Gumin (Joy); M.L.M. Lamfers (Martine); A. Kleijn (Anne); F.F. Lang (Frederick); S. Yung (Sun); L.M. Vence (Luis); C. Gomez-Manzano (Candelaria); J. Fueyo (Juan)

    2014-01-01

    textabstractBackground: Emerging evidence suggests anti-cancer immunity is involved in the therapeutic effect induced by oncolytic viruses. Here we investigate the effect of Delta-24-RGD oncolytic adenovirus on innate and adaptive anti-glioma immunity. Design: Mouse GL261-glioma model was set up in

  17. Hedgehog signaling sensitizes glioma stem cells to endogenous nano-irradiation

    NARCIS (Netherlands)

    Morgenroth, Agnieszka; Vogg, Andreas T J; Ermert, Katja; Zlatopolskiy, Boris; Mottaghy, Felix M

    2014-01-01

    The existence of therapy resistant glioma stem cells is responsible for the high recurrence rate and incurability of glioblastomas. The Hedgehog pathway activity plays an essential role for self-renewal capacity and survival of glioma stem cells. We examined the potential of the Sonic hedgehog ligan

  18. Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk

    DEFF Research Database (Denmark)

    Amirian, E Susan; Zhou, Renke; Wrensch, Margaret R

    2016-01-01

    BACKGROUND: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Gliom...

  19. Rotational Crofton formulae for flagged intrinsic volumes

    DEFF Research Database (Denmark)

    Auneau, Jeremy Michel

    , and the integration is over all sections containing the fixed point origo. Our main result is a local stereological analogue to the well-known Crofton formula. More precisely, we derive geometric formulae that relate new flagged intrinsic volumes of a set with the flagged intrinsic volumes of its sections...

  20. Intrinsic bioremediation of landfills interim report

    Energy Technology Data Exchange (ETDEWEB)

    Brigmon, R.L. [Westinghouse Savannah River Company, Aiken, SC (United States); Fliermans, C.B.

    1997-07-14

    Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP).