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Sample records for iii glioma patients

  1. [Cognitive disorders and adult grade II and III gliomas: analysis of a series of 15 patients].

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    Le Rhun, E; Delbeuck, X; Devos, P; Pasquier, F; Dubois, F

    2009-06-01

    Correlated with better follow-up of gliomas, cognitive disorders are increasingly studied. The aim of this study was to describe the cognitive disorders presented by these patients at baseline, before any treatment, and to evaluate the relations between cognitive disorders and return to work. A detailed neuropsychological evaluation was administrated to 15 newly diagnosed patients with a grade II or III glial tumor before any treatment. Patients also completed the quality of life and depression scales. All patients in our study presented with at least one failed cognitive domain during the detailed examination, while the scores on the MMSE scale were within the norm. The most deteriorated functions were divided attention and episodic verbal and nonverbal memory. Moreover, a significant link was found between the number of failed cognitive functions and quality of life. Cognitive disorders are frequent with glial tumors and impact patients' quality of life. Simple tests of global cognitive status are not sufficient to detect cognitive difficulties in these patients. Consequently, detailed and adapted neuropsychological assessment is necessary, especially to detect deteriorated problems with memory, divided attention, or processing speed in this population.

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

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    Takano, Shingo; Ishikawa, Eiichi; Sakamoto, Noriaki; Matsuda, Masahide; Akutsu, Hiroyoshi; Noguchi, Masayuki; Kato, Yukinari; Yamamoto, Tetsuya; Matsumura, Akira

    2016-04-01

    The molecular subgrouping of diffuse gliomas was recently found to stratify patients into prognostically distinct groups better than histological classification. Among several molecular parameters, the key molecules for the subtype diagnosis of diffuse gliomas are IDH mutation, 1p/19q co-deletion, and ATRX mutation; 1p/19q co-deletion is undetectable by immunohistochemistry, but is mutually exclusive with ATRX and p53 mutation in IDH mutant gliomas. Therefore, we applied ATRX and p53 immunohistochemistry instead of 1p/19q co-deletion analysis. The prognostic value of immunohistochemical diagnosis for Grade III gliomas was subsequently investigated. Then, the same immunohistochmical diagnostic approach was expanded for the evaluation of Grade II and IV diffuse glioma prognosis. The results indicate immunohistochemical analysis including IDH1/2, ATRX, p53, and Ki-67 index is valuable for the classification of diffuse gliomas, which is useful for the evaluation of prognosis, especially Grade III gliomas and lower-grade gliomas (i.e., Grade II and III).

  3. Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study

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    Delgado, Anna F.; Nilsson, Markus; Latini, Francesco; Mårtensson, Johanna; Zetterling, Maria; Berntsson, Shala G.; Alafuzoff, Irina; Lätt, Jimmy; Larsson, Elna-Marie

    2016-01-01

    Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T). The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas) on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA) and mean diffusivity (rMD) in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.). Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement. PMID:27190647

  4. Preoperative Quantitative MR Tractography Compared with Visual Tract Evaluation in Patients with Neuropathologically Confirmed Gliomas Grades II and III: A Prospective Cohort Study

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    Anna F. Delgado

    2016-01-01

    Full Text Available Background and Purpose. Low-grade gliomas show infiltrative growth in white matter tracts. Diffusion tensor tractography can noninvasively assess white matter tracts. The aim was to preoperatively assess tumor growth in white matter tracts using quantitative MR tractography (3T. The hypothesis was that suspected infiltrated tracts would have altered diffusional properties in infiltrated tract segments compared to noninfiltrated tracts. Materials and Methods. Forty-eight patients with suspected low-grade glioma were included after written informed consent and underwent preoperative diffusion tensor imaging in this prospective review-board approved study. Major white matter tracts in both hemispheres were tracked, segmented, and visually assessed for tumor involvement in thirty-four patients with gliomas grade II or III (astrocytomas or oligodendrogliomas on postoperative neuropathological evaluation. Relative fractional anisotropy (rFA and mean diffusivity (rMD in tract segments were calculated and compared with visual evaluation and neuropathological diagnosis. Results. Tract segment infiltration on visual evaluation was associated with a lower rFA and high rMD in a majority of evaluated tract segments (89% and 78%, resp.. Grade II and grade III gliomas had similar infiltrating behavior. Conclusion. Quantitative MR tractography corresponds to visual evaluation of suspected tract infiltration. It may be useful for an objective preoperative evaluation of tract segment involvement.

  5. RH-02A PILOT RCT ON THE EFFICACY OF HOME-BASED EXERCISE TO IMPROVE COGNITIVE FUNCTIONING IN GRADE II AND III GLIOMA PATIENTS

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    Gehring, Karin; Stuiver, Martijn; Rutten, Geert-Jan; Taphoorn, Martin; Aaronson, Neil; Sitskoorn, Margriet

    2014-01-01

    Many patients with gliomas suffer from cognitive deficits. Recent findings indicate that physical exercise is effective in ameliorating cognitive decline, in particular in older adults and select neurological patient populations. Studies of exercise interventions in patients with cancer demonstrated to have beneficial effects on various measures of physical and mental well-being. This pilot randomized controlled trial investigates the efficacy of home-based exercise in improving cognitive functioning and self-reported mental well-being in glioma patients. Clinically stable patients with grade II and III glioma will undergo baseline neuropsychological testing, including questionnaires on cognitive symptoms, fatigue, sleep, mood and quality of life; and cardiorespiratory exercise testing (CPET) to determine room for improvement of physical fitness. Sixty patients will be randomized in a 2:1 ratio to the intervention group or active control group. Patients in the intervention group exercise 3 times per week for 6 months, during 20 to 45 minutes at an increasing intensity of 55 to 85% of their maximum heart rate. CPET-outcome (VO2peak) is used to tailor an individual, home-based exercise program. Participants wear heart rate monitors and are supervised by a physical therapist via internet and telephone. Patients in the active control group are advised to walk regularly. Neuropsychological test performance, physical fitness, and mental well-being are assessed again after 6 months. In November 2014, 30 patients are expected to be accrued. Six-month follow-up data on neuropsychological performance, physical fitness and self-reported mental well-being of the currently included 15 patients (12 intervention; 3 control group) will be available. Mean age of this group is 48.1 (±9.8) years; median time since surgery is 4.1 (0.7-14.7) years. Most of these participants are female (n = 11), and have a grade II glioma (n = 10). To our knowledge, this is the first study that

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

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    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.

  7. Rehabilitation of patients with glioma.

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    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.

  8. Armodafinil in Reducing Cancer-Related Fatigue in Patients With High Grade Glioma | Division of Cancer Prevention

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    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. |

  9. 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 ...

  10. A Molecular Predictor Reassesses Classification of Human Grade II/III Gliomas.

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    Thierry Rème

    Full Text Available Diffuse gliomas are incurable brain tumors divided in 3 WHO grades (II; III; IV based on histological criteria. Grade II/III gliomas are clinically very heterogeneous and their prognosis somewhat unpredictable, preventing definition of appropriate treatment. On a cohort of 65 grade II/III glioma patients, a QPCR-based approach allowed selection of a biologically relevant gene list from which a gene signature significantly correlated to overall survival was extracted. This signature clustered the training cohort into two classes of low and high risk of progression and death, and similarly clustered two external independent test cohorts of 104 and 73 grade II/III patients. A 22-gene class predictor of the training clusters optimally distinguished poor from good prognosis patients (median survival of 13-20 months versus over 6 years in the validation cohorts. This classification was stronger at predicting outcome than the WHO grade II/III classification (P≤2.8E-10 versus 0.018. When compared to other prognosis factors (histological subtype and genetic abnormalities in a multivariate analysis, the 22-gene predictor remained significantly associated with overall survival. Early prediction of high risk patients (3% of WHO grade II, and low risk patients (29% of WHO grade III in clinical routine will allow the development of more appropriate follow-up and treatments.

  11. Discrimination between glioma grades II and III in suspected low-grade gliomas using dynamic contrast-enhanced and dynamic susceptibility contrast perfusion MR imaging

    DEFF Research Database (Denmark)

    Falk, Anna; Fahlström, Markus; Rostrup, Egill;

    2014-01-01

    INTRODUCTION: Perfusion magnetic resonance imaging (MRI) can be used in the pre-operative assessment of brain tumours. The aim of this prospective study was to identify the perfusion parameters from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) perfusion imaging...... that could best discriminate between grade II and III gliomas. METHODS: MRI (3 T) including morphological ((T2 fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W)+Gd)) and perfusion (DCE and DSC) sequences was performed in 39 patients with newly diagnosed suspected low-grade glioma after...

  12. 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...

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

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    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.

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

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    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.

  15. Cortical and Subcortical Structural Plasticity Associated with the Glioma Volumes in Patients with Cerebral Gliomas Revealed by Surface-Based Morphometry

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    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. LuIII parvovirus selectively and efficiently targets, replicates in, and kills human glioma cells.

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    Paglino, Justin C; Ozduman, Koray; van den Pol, Anthony N

    2012-07-01

    Because productive infection by parvoviruses requires cell division and is enhanced by oncogenic transformation, some parvoviruses may have potential utility in killing cancer cells. To identify the parvovirus(es) with the optimal oncolytic effect against human glioblastomas, we screened 12 parvoviruses at a high multiplicity of infection (MOI). MVMi, MVMc, MVM-G17, tumor virus X (TVX), canine parvovirus (CPV), porcine parvovirus (PPV), rat parvovirus 1A (RPV1A), and H-3 were relatively ineffective. The four viruses with the greatest oncolytic activity, LuIII, H-1, MVMp, and MVM-G52, were tested for the ability, at a low MOI, to progressively infect the culture over time, causing cell death at a rate higher than that of cell proliferation. LuIII alone was effective in all five human glioblastomas tested. H-1 progressively infected only two of five; MVMp and MVM-G52 were ineffective in all five. To investigate the underlying mechanism of LuIII's phenotype, we used recombinant parvoviruses with the LuIII capsid replacing the MVMp capsid or with molecular alteration of the P4 promoter. The LuIII capsid enhanced efficient replication and oncolysis in MO59J gliomas cells; other gliomas tested required the entire LuIII genome to exhibit enhanced infection. LuIII selectively infected glioma cells over normal glial cells in vitro. In mouse models, human glioblastoma xenografts were selectively infected by LuIII when administered intratumorally; LuIII reduced tumor growth by 75%. LuIII also had the capacity to selectively infect subcutaneous or intracranial gliomas after intravenous inoculation. Intravenous or intracranial LuIII caused no adverse effects. Intracranial LuIII caused no infection of mature mouse neurons or glia in vivo but showed a modest infection of developing neurons.

  17. High bone sialoprotein (BSP expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients.

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    Tao Xu

    Full Text Available OBJECTIVES: To investigate the expression and prognostic value of bone sialoprotein (BSP in glioma patients. METHODS: We determined the expression of BSP using real-time RT-PCR and immunohistochemistry in tissue microarrays containing 15 normal brain and 270 glioma samples. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test. Univariate and multivariate analyses were performed by the stepwise forward Cox regression model. RESULTS: Both BSP mRNA and protein levels were significantly elevated in high-grade glioma tissues compared with those of normal brain and low-grade glioma tissues, and BSP expression positively correlated with tumor grade (P<0.001. Univariate and multivariate analysis showed high BSP expression was an independent prognostic factor for a shorter progression-free survival (PFS and overall survival (OS in both grade III and grade IV glioma patients [hazard ratio (HR = 2.549 and 3.154 for grade III glioma, and HR = 1.637 and 1.574 for grade IV glioma, respectively]. Patients with low BSP expression had a significantly longer median OS and PFS than those with high BSP expression. Small extent of resection and lineage of astrocyte served as independent risk factors of both shorter PFS and OS in grade III glioma patients; GBM patients without O(6-methylguanine (O(6-meG DNA methyltransferase (MGMT methylation and Karnofsky performance score (KPS less than 70 points were related to poor prognosis. Lack of radiotherapy related to shorter OS but not affect PFS in both grade III and grade IV glioma patients. CONCLUSION: High BSP expression occurs in a significant subset of high-grade glioma patients and predicts a poorer outcome. The study identifies a potentially useful molecular marker for the categorization and targeted therapy of gliomas.

  18. 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 ...

  19. RETRACTED: Downregulation of miR-204 expression correlates with poor clinical outcome of glioma patients.

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    Ye, Zhen-Nan; Liu, Jing-Peng; Wu, Ling-Yun; Zhang, Xiang-Sheng; Zhuang, Zong; Chen, Qiang; Lu, Yue; Liu, Ce-Gang; Zhang, Zi-Huan; Zhang, Hua-Sheng; Hou, Wen-Zhong; Hang, Chun-Hua

    2017-05-01

    Glioma is the most common type of malignant neoplasm in the central nervous system, with high incidence and mortality rate. MicroRNAs, as a class of small noncoding RNAs, play an important role in carcinogenesis and correlate with glioma diagnosis and prognosis. In this study, we investigated the microRNA-204 (miR-204) concentration in glioma tissues and its relation to the expression of ezrin and bcl-2 mRNA, as well as its potential predictive and prognostic values in glioma. The concentrations of miR-204 were significantly lower in glioma tissues than in nontumor brain tissues and also were lower in high-grade than in low-grade gliomas (World Health Organization grades III and IV versus grades I and II). The miR-204 concentration was inversely correlated with the ezrin and bcl-2 concentrations. The miR-204 concentration was classified as high or low according to the median value, and low miR-204 correlated with higher World Health Organization grade, larger tumor, and worse Karnofsky performance score. Kaplan-Meier survival analysis demonstrated that patients with low miR-204 expression had shorter progression-free survival and overall survival than patients with high miR-204 expression. In addition, univariate and multivariate analyses showed that miR-204 expression was an independent prognostic feature of overall survival and progression-free survival. In conclusion, our study indicates that miR-204 is downregulated in glioma and may be a biomarker of poor prognosis in patients with this cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Seizure control following radiotherapy in patients with diffuse gliomas: a retrospective study

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    Rudà, Roberta; Magliola, Umberto; Bertero, Luca; Trevisan, Elisa; Bosa, Chiara; Mantovani, Cristina; Ricardi, Umberto; Castiglione, Anna; Monagheddu, Chiara; Soffietti, Riccardo

    2013-01-01

    Background Little information is available regarding the effect of conventional radiotherapy on glioma-related seizures. Methods In this retrospective study, we analyzed the seizure response and outcome following conventional radiotherapy in a cohort of 43 patients with glioma (33 grade II, 10 grade III) and medically intractable epilepsy. Results At 3 months after radiotherapy, seizure reduction was significant (≥50% reduction of frequency compared with baseline) in 31/43 patients (72%) of the whole series and in 25/33 patients (76%) with grade II gliomas, whereas at 12 months seizure reduction was significant in 26/34 (76%) and in 19/25 (76%) patients, respectively. Seizure reduction was observed more often among patients displaying an objective tumor response on MRI, but patients with no change on MRI also had a significant seizure reduction. Seizure freedom (Engel class I) was achieved at 12 months in 32% of all patients and in 38% of patients with grade II tumors. Timing of radiotherapy and duration of seizures prior to radiotherapy were significantly associated with seizure reduction. Conclusions This study showed that a high proportion of patients with medically intractable epilepsy from diffuse gliomas derive a significant and durable benefit from radiotherapy in terms of epilepsy control and that this positive effect is not strictly associated with tumor shrinkage as shown on MRI. Radiotherapy at tumor progression seems as effective as early radiotherapy after surgery. Prospective studies must confirm and better characterize the response to radiotherapy. PMID:23897633

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

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    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.

  2. Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma

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    Il'yasova Dora

    2010-05-01

    Full Text Available Abstract Background Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis. Methods Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV and conducted for all (including proxy subjects and for a subset of self-reported subjects. Results Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n = 748 to self-reported cases only (n = 450. For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg, for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases

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

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    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

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

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    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.

  5. Metabolomic Screening of Tumor Tissue and Serum in Glioma Patients Reveals Diagnostic and Prognostic Information

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    Lina Mörén

    2015-09-01

    Full Text Available Glioma grading and classification, today based on histological features, is not always easy to interpret and diagnosis partly relies on the personal experience of the neuropathologists. The most important feature of the classification is the aimed correlation between tumor grade and prognosis. However, in the clinical reality, large variations exist in the survival of patients concerning both glioblastomas and low-grade gliomas. Thus, there is a need for biomarkers for a more reliable classification of glioma tumors as well as for prognosis. We analyzed relative metabolite concentrations in serum samples from 96 fasting glioma patients and 81 corresponding tumor samples with different diagnosis (glioblastoma, oligodendroglioma and grade (World Health Organization (WHO grade II, III and IV using gas chromatography-time of flight mass spectrometry (GC-TOFMS. The acquired data was analyzed and evaluated by pattern recognition based on chemometric bioinformatics tools. We detected feature patterns in the metabolomics data in both tumor and serum that distinguished glioblastomas from oligodendrogliomas (ptumor = 2.46 × 10−8, pserum = 1.3 × 10−5 and oligodendroglioma grade II from oligodendroglioma grade III (ptumor = 0.01, pserum = 0.0008. Interestingly, we also found patterns in both tumor and serum with individual metabolite features that were both elevated and decreased in patients that lived long after being diagnosed with glioblastoma compared to those who died shortly after diagnosis (ptumor = 0.006, pserum = 0.004; AUROCCtumor = 0.846 (0.647–1.000, AUROCCserum = 0.958 (0.870–1.000. Metabolic patterns could also distinguish long and short survival in patients diagnosed with oligodendroglioma (ptumor = 0.01, pserum = 0.001; AUROCCtumor = 1 (1.000–1.000, AUROCCserum = 1 (1.000–1.000. In summary, we found different metabolic feature patterns in tumor tissue and serum for glioma diagnosis, grade and survival, which indicates that

  6. 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.

  7. 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

  8. 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

  9. CS-27IDH1/2 MUTATIONS INFLUENCE ZEB1 EXPRESSION IN GRADES II AND III GLIOMAS

    OpenAIRE

    Nesvick, Cody; Zhang, Chao; Montgomery, Blake; Lee, Michaela; Yang, Chunzhang; Wang, Herui; Merrill, Marsha; Heiss, John; Ray-Chaudhury, Abhik; Zhuang, Zhengping

    2014-01-01

    Epithelial-mesenchymal transition (EMT) is a cell program that crucially regulates polarity and enhances invasion in normal epithelia and carcinomas. It has been recently demonstrated that EMT-promoting transcription factors (EMT-TFs) also govern cell invasion in glioblastoma, but the role of these proteins in lower-grade gliomas has not yet been investigated. We investigated the impact of EMT-TF expression on overall survival in World Health Organization (WHO) grades II and III gliomas using...

  10. CS-27IDH1/2 MUTATIONS INFLUENCE ZEB1 EXPRESSION IN GRADES II AND III GLIOMAS

    Science.gov (United States)

    Nesvick, Cody; Zhang, Chao; Montgomery, Blake; Lee, Michaela; Yang, Chunzhang; Wang, Herui; Merrill, Marsha; Heiss, John; Ray-Chaudhury, Abhik; Zhuang, Zhengping

    2014-01-01

    Epithelial-mesenchymal transition (EMT) is a cell program that crucially regulates polarity and enhances invasion in normal epithelia and carcinomas. It has been recently demonstrated that EMT-promoting transcription factors (EMT-TFs) also govern cell invasion in glioblastoma, but the role of these proteins in lower-grade gliomas has not yet been investigated. We investigated the impact of EMT-TF expression on overall survival in World Health Organization (WHO) grades II and III gliomas using the National Cancer Institute Repository for Molecular Brain Neoplasis Data (REMBRANDT) and Cancer Genome Atlas Network Lower-Grade Glioma (CGAN LGG) datasets. Surprisingly, while expression of EMT-promoting transcription factors were generally associated with a decrease in overall survival, high ZEB1 expression was associated with an increase in overall survival in both datasets (log-rank test on all grade II and III gliomas: for REMBRANDT, median overall survival (OS) 54.2 months ZEB1-high vs. 19.6 months ZEB1-low, p = 0.0016; for CGAN, median OS 134.3 months ZEB1-high vs. 63.6 months ZEB1-low, p = 0.0038). Mutations in the genes coding for Isocitrate Dehydrogenases 1 and 2 (IDH1/2) are found in 85-90% of grades II and III gliomas and confer a favorable prognosis in these tumors. Using the CGAN LGG dataset, we found that ZEB1 is upregulated in IDH1/2-mutant versus IDH1/2-wild type tumors (unpaired t-test on all grade II and III gliomas: t = 10.292, p < 0.0001). Moreover, IDH1/2-mutant gliomas express lower levels of genes that are suppressed by ZEB1 including MIR200B and MIR200C (unpaired t-test on all grade II and III gliomas: p < 0.0001 for both targets). We further validated these findings in an independent set of 37 grade II and III gliomas using quantitative real-time PCR, Western blot and immunohistochemistry. These findings reveal that ZEB1 not only has an unexpected prognostic significance in grades II and III gliomas but also may play an important role in IDH1

  11. 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.

  12. 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,.

  13. Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

    Science.gov (United States)

    Elaimy, Ameer L; Mackay, Alexander R; Lamoreaux, Wayne T; Demakas, John J; Fairbanks, Robert K; Cooke, Barton S; Lamm, Andrew F; Lee, Christopher M

    2013-12-01

    Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Survival analysis of patients with high-grade gliomas based on data mining of imaging variables.

    Science.gov (United States)

    Zacharaki, E I; Morita, N; Bhatt, P; O'Rourke, D M; Melhem, E R; Davatzikos, C

    2012-06-01

    The prediction of prognosis in HGGs is poor in the majority of patients. Our aim was to test whether multivariate prediction models constructed by machine-learning methods provide a more accurate predictor of prognosis in HGGs than histopathologic classification. The prediction of survival was based on DTI and rCBV measurements as an adjunct to conventional imaging. The relationship of survival to 55 variables, including clinical parameters (age, sex), categoric or continuous tumor descriptors (eg, tumor location, extent of resection, multifocality, edema), and imaging characteristics in ROIs, was analyzed in a multivariate fashion by using data-mining techniques. A variable selection method was applied to identify the overall most important variables. The analysis was performed on 74 HGGs (18 anaplastic gliomas WHO grades III/IV and 56 GBMs or gliosarcomas WHO grades IV/IV). Five variables were identified as the most significant, including the extent of resection, mass effect, volume of enhancing tumor, maximum B0 intensity, and mean trace intensity in the nonenhancing/edematous region. These variables were used to construct a prediction model based on a J48 classification tree. The average classification accuracy, assessed by cross-validation, was 85.1%. Kaplan-Meier survival curves showed that the constructed prediction model classified malignant gliomas in a manner that better correlates with clinical outcome than standard histopathology. Prediction models based on data-mining algorithms can provide a more accurate predictor of prognosis in malignant gliomas than histopathologic classification alone.

  19. 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

  20. EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines

    DEFF Research Database (Denmark)

    Bax, Dorine A; Gaspar, Nathalie; Little, Suzanne E;

    2009-01-01

    , including two anaplastic oligodendrogliomas and a gliosarcoma overexpressing EGFRvIII in the absence of gene amplification and coexpressing platelet-derived growth factor receptor alpha. Pediatric glioblastoma cells transduced with wild-type or deletion mutant EGFRvIII were not rendered more sensitive...... data are lacking. We have sought to clarify the role of EGFR in pediatric high-grade glioma (HGG). EXPERIMENTAL DESIGN: We retrospectively studied a total of 90 archival pediatric HGG specimens for EGFR protein overexpression, gene amplification, and mutation and assessed the in vitro sensitivity...... to erlotinib despite expressing wild-type PTEN. Phosphorylated receptor tyrosine kinase profiling showed a specific activation of platelet-derived growth factor receptor alpha/beta in EGFRvIII-transduced pediatric glioblastoma cells, and targeted coinhibition with erlotinib and imatinib leads to enhanced...

  1. 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.

  2. Prognostic value of preoperative dynamic contrast-enhanced MRI perfusion parameters for high-grade glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Ulyte, Agne [Vilnius University, Faculty of Medicine, Vilnius (Lithuania); Katsaros, Vasileios K. [General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Advanced Imaging Modalities - CT and MRI, Athens (Greece); University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Liouta, Evangelia; Stranjalis, Georgios [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); Boskos, Christos [University of Athens, Department of Neurosurgery, Evangelismos Hospital, Athens (Greece); General Anticancer and Oncological Hospital ' ' St. Savvas' ' , Department of Radiation Oncology, Athens (Greece); Papanikolaou, Nickolas [Champalimaud Foundation, Department of Radiology, Centre for the Unknown, Lisbon (Portugal); Usinskiene, Jurgita [National Cancer Institute, Vilnius (Lithuania); Affidea Lietuva, Vilnius (Lithuania); Bisdas, Sotirios [University College London Hospitals, Department of Neuroradiology, The National Hospital for Neurology and Neurosurgery, London (United Kingdom)

    2016-12-15

    The prognostic value of the dynamic contrast-enhanced (DCE) MRI perfusion and its histogram analysis-derived metrics is not well established for high-grade glioma (HGG) patients. The aim of this prospective study was to investigate DCE perfusion transfer coefficient (K{sup trans}), vascular plasma volume fraction (v{sub p}), extracellular volume fraction (v{sub e}), reverse transfer constant (k{sub ep}), and initial area under gadolinium concentration time curve (IAUGC) as predictors of progression-free (PFS) and overall survival (OS) in HGG patients. Sixty-nine patients with suspected anaplastic astrocytoma or glioblastoma underwent preoperative DCE-MRI scans. DCE perfusion whole tumor region histogram parameters, clinical details, and PFS and OS data were obtained. Univariate, multivariate, and Kaplan-Meier survival analyses were conducted. Receiver operating characteristic (ROC) curve analysis was employed to identify perfusion parameters with the best differentiation performance. On univariate analysis, v{sub e} and skewness of v{sub p} had significant negative impacts, while k{sub ep} had significant positive impact on OS (P < 0.05). v{sub e} was also a negative predictor of PFS (P < 0.05). Patients with lower v{sub e} and IAUGC had longer median PFS and OS on Kaplan-Meier analysis (P < 0.05). K{sup trans} and v{sub e} could also differentiate grade III from IV gliomas (area under the curve 0.819 and 0.791, respectively). High v{sub e} is a consistent predictor of worse PFS and OS in HGG glioma patients. v{sub p} skewness and k{sub ep} are also predictive for OS. K{sup trans} and v{sub e} demonstrated the best diagnostic performance for differentiating grade III from IV gliomas. (orig.)

  3. Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET.

    Science.gov (United States)

    Horiguchi, Keishi; Tosaka, Masahiko; Higuchi, Tetsuya; Arisaka, Yukiko; Sugawara, Kenichi; Hirato, Junko; Yokoo, Hideaki; Tsushima, Yoshito; Yoshimoto, Yuhei

    2017-12-01

    We investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine ((18)F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET in 38 consecutive glioma patients. The tumor to normal brain ratios (T/N ratios) were calculated, and the relationships between T/N ratio and World Health Organization tumor grade or MIB-1 labeling index were evaluated. The diagnostic values of T/N ratios were assessed using receiver operating characteristic (ROC) curve analyses to differentiate between high-grade gliomas (HGGs) and low-grade gliomas (LGGs). Median T/N ratio of (18)F-FAMT PET was 2.85, 4.65, and 4.09 for grade II, III, and IV gliomas, respectively, with significant differences between HGGs and LGGs (p = 0.006). Both T/N ratio (p = 0.016) and maximum standardized uptake value (p = 0.033) of (18)F-FDG PET showed significant differences between HGGs and LGGs. ROC analysis yielded an optimal cut-off of 3.37 for the T/N ratio of (18)F-FAMT PET to differentiate between HGGs and LGGs (sensitivity 81%, specificity 67%, accuracy 76%, area under the ROC curve 0.776). Positive predictive value was 84%, and negative predictive value was 62%. T/N ratio of (18)F-FAMT PET was not correlated with MIB-1 labeling index in all gliomas, whereas T/N ratio of (18)F-FDG PET was positively correlated (r s  = 0.400, p = 0.013). Significant positive correlation was observed between T/N ratios of (18)F-FDG and (18)F-FAMT (r s  = 0.454, p = 0.004), but median T/N ratio of (18)F-FAMT PET was significantly higher than that of (18)F-FDG PET in all grades of glioma. The T/N ratio of (18)F-FAMT uptake has high positive predictive value for detection of HGGs. (18)F-FAMT PET had higher T/N ratio, with better tumor-normal brain contrast, compared to (18)F-FDG PET in both LGGs and HGGs. Therefore, (18)F-FAMT is a useful radiotracer for the preoperative visualization of

  4. SHOX2 is a Potent Independent Biomarker to Predict Survival of WHO Grade II–III Diffuse Gliomas

    Directory of Open Access Journals (Sweden)

    Yu-An Zhang

    2016-11-01

    Interpretation: We have identified that SHOX2 expression or methylation are potent independent prognostic indicators for predicting LGG patient survival, and have potential to identify an important subset of LGG patients with IDHwt status with significantly better overall survival. The combination of IDH or other relevant markers with SHOX2 identified LGG subsets with significantly different survival outcomes, and further understanding of these subsets may benefit therapeutic target identification and therapy selections for glioma patients.

  5. Synchronized brain activity and neurocognitive function in patients with low-grade glioma : a magnetoencephalography study

    NARCIS (Netherlands)

    Bosma, Ingeborg; Douw, Linda; Bartolomei, Fabrice; Heimans, Jan J.; van Dijk, Bob W.; Postma, Tjeerd J.; Stam, Cornelis J.; Reijneveld, Jaap C.; Klein, Martin

    2008-01-01

    We investigated the mechanisms underlying neurocognitive dysfunction in patients with low-grade glioma (LGG) by relating functional connectivity revealed by magnetoencephalography to neurocognitive function. We administered a battery of standardized neurocognitive tests measuring six neurocognitive

  6. 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 ...

  7. EMMPRIN is an independent negative prognostic factor for patients with astrocytic glioma.

    Directory of Open Access Journals (Sweden)

    Li Tian

    Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN, also known as CD147, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs. It has been proved to be associated with tumor invasion and metastasis in various human malignancies. In our study, the protein expression level of EMMPRIN in 306 cases of astrocytic glioma is investigated by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of EMMPRIN with clinicopathological characteristics and prognosis of patients. It was proved that EMMPRIN protein expression was increased in glioma compared with that in normal brain tissue. Moreover, EMMPRIN immunohistochemical staining was correlated with WHO grade and Karnofsky performance score for strong positive EMMPRIN staining is more frequently detected in glioma of advanced grade or low KPS score. It is also demonstrated that EMMPRIN could be an independent negative prognostic factor in glioma for patients with glioma of strong EMMPRIN staining tend to have high risk of death. These results proved that EMMPRIN is associated with prognosis of glioma, which may also suggest the potential role of EMMPRIN in glioma management.

  8. Quality of life after radiation therapy of cerebral low-grade gliomas of the adult: results of a randomised Phase III trial on dose response (EORTC trial 22844)

    Energy Technology Data Exchange (ETDEWEB)

    Kiebert, G.M. [MEDTAP International, 27 Gilbert Street, London (United Kingdom); Curran, D. [EORTC Data Centre Brussels (Belgium); Aaronson, N.K. [The Netherlands Cancer Institute, Amsterdam (Netherlands); Bolla, M. [Centre Hospitalier Regional Universitaire, Grenoble (France); Menten, J. [University Hospital Gasthuisberg Leuven (Belgium); Rutten, E.H.J.M. [University Hospital St. Radboud, Nijmegen (Netherlands); Nordman, E. [Turku University Central Hospital, Turku (Finland); Silvestre, M.E. [Hospital Santa Maria, Lisbon (Portugal); Pierart, M. [EORTC Data Centre, Brussels (Belgium); Karim, A.B.M.F. [Free University Hospital, Amsterdam (Netherlands)

    1998-11-01

    In 1985, the EORTC Radiotherapy Co-operative Group launched a randomised phase III study comparing high-dose (59.4 Gy in 6.5 weeks) versus low-dose (45 Gy in 5 weeks) radiotherapy with conventional techniques in patients diagnosed with low-grade cerebral glioma. The primary endpoint of the study was survival. No difference in survival was observed between the two treatment strategies. A quality of life (QoL) questionnaire consisting of 47 items assessing a range of physical, psychological, social, and symptom domains was included in the trial to measure the impact of treatment over time. Patients who received high-dose radiotherapy tended to report lower levels of functioning and more symptom burden following completion of radiotherapy. These group differences were statistically significant for fatigue/malaise and insomnia immediately after radiotherapy and in leisure time and emotional functioning at 7-15 months after randomisation. These findings suggest that for conventional radiotherapy for low-grade cerebral glioma, a schedule of 45 Gy in 5 weeks not only saves valuable resources, but also spares patients a prolonged treatment at no loss of clinical efficacy. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  9. Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

    Directory of Open Access Journals (Sweden)

    Haidar A. Shamran

    2015-01-01

    Full Text Available Human Cytomegalovirus (HCMV is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n=50 and from benign meningioma patients (n=30 were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG compared to 72.5% among control samples (P=0.04. These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis.

  10. Successful outcome in a patient with glioma of brain with twin pregnancy

    Directory of Open Access Journals (Sweden)

    Anjali Rani

    2014-06-01

    Full Text Available We present a case of glioma in pregnant female with twin pregnancy. Gliomas during pregnancy are rare. Gliomas during pregnancy pose a risk to maternal and fetal life. The benefit-to-risk ratio should be carefully evaluated and discussed prior to get marriage and pregnancy. In present case, patient had non-specific symptom like seizure and no any focal neurological deficit, Caesarean Section (CS was done at term with multidisciplinary group, including a neurosurgeon, obstetrician, anesthesiologist and neonatologist. She has been followed up to the present date and remains in good health. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 827-830

  11. Impact of head immobilization position on dose distribution in patients of brainstem glioma

    Directory of Open Access Journals (Sweden)

    Seema Sharma

    2015-03-01

    Full Text Available Purpose: The purpose of this study is to investigate the impact of patient position (supine and prone on conventional bilateral field, three dimensional conformal radiotherapy (3DCRT and intensity modulated radiotherapy (IMRT treatment plans in patients of brainstem glioma with a view to exploring the possibility of avoiding beam entry through immobilization accessories. Methods: Five patients of brainstem glioma were immobilized and scanned in supine and prone positions with a combination of head rest and thermoplastic cast. Each patient was planned with three techniques: (i 2-fields bilateral (ii 3-fields 3DCRT, and (iii 5-fields IMRT. Plan quality was analyzed in terms of planning target volume (PTV coverage and dose to various critical organs at risk (OAR for both the supine and prone treatment positions. Results: In case of bilateral fields (parallel opposed planning, the PTV coverage and dose to the OAR were almost similar for both the supine and prone positions. In 3DCRT plan, although the PTV coverage and dose to critical structures were comparable for both the supine and prone position, dose to cochlea was lower for the prone position plan. A modest decrease in maximum dose to optic nerves and mean dose to temporal lobes were also observed for the prone position plan. In IMRT plans, the PTV coverage and homogeneity were comparable in both the supine and prone positions. Reduction in average maximum and mean doses to all OARs with functional subunit (FSU in series and parallel respectively was observed in the IMRT plan for prone position when compared to the supine position.Conclusion: Supine and prone positions resulted in almost similar dose distribution in all the three techniques applied. At some instances, the prone position showed better normal tissues sparing when compared to supine. Moreover, prone position is more likely to avoid attenuation due to immobilization devices and uncertainty in dose calculation under large

  12. Putamen involvement and survival outcomes in patients with insular low-grade gliomas.

    Science.gov (United States)

    Wang, Yongheng; Wang, Yinyan; Fan, Xing; Li, Shaowu; Liu, Xing; Wang, Jiangfei; Jiang, Tao

    2016-08-26

    OBJECTIVE Insular glioma has a unique origin and biological behavior; however, the associations between its anatomical features and prognosis have not been well established. The object of this study was to propose a classification system of insular low-grade gliomas based on preoperative MRI findings and to assess the system's association with survival outcome. METHODS A total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved the putamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil's classification, was examined using multivariate analyses. RESULTS Ninety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil's classification. CONCLUSIONS The current study's findings suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas.

  13. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas

    Directory of Open Access Journals (Sweden)

    Torres-Trejo Alejandro

    2007-12-01

    received scheduled vaccinations with no incidence of major adverse events. Monocyte-derived DCs produced high levels of IL-12 p70. Treatment was well tolerated; however, we were unable to observe detectable IFN-γ post-vaccine responses or prolonged progression-free survival in these participants. Conclusion Feasibility challenges inherent in the generation of a patient-specific gene transfection-based vaccine strongly suggests the need for more practical formulations that would allow for the timely administration of vaccines. Nevertheless, successful generation of type-1 DCs and preliminary safety in the current study provide a strong rationale for further efforts to develop novel glioma vaccines.

  14. Increased expression of the 58-kD microspherule protein (MSP58) is correlated with poor prognosis in glioma patients.

    Science.gov (United States)

    Lin, Wei; Li, Xiao-Ming; Zhang, Jing; Huang, Yi; Wang, Jiang; Zhang, Jian; Jiang, Xiao-Fan; Fei, Zhou

    2013-12-01

    The pathological grading system for human gliomas is usually used to evaluate the prognosis of glioma patients. However, some glioma patients with similar grades have obvious discrepancies in survival. It is therefore necessary to identify some new certain tumor biomarkers that are more suitable for the prognostic assessment of gliomas than the grading system. The 58-kD microspherule protein (MSP58) is an evolutionarily conserved nuclear protein and plays an important role in the regulation of cell proliferation and malignant transformation. However, whether MSP58 can be used as a biomarker to evaluate the malignancy and the prognosis of glioma patients is unknown. In the present study, we performed immunohistochemical analysis to evaluate MSP58 protein expression in 158 specimens of human gliomas and 34 normal control brain tissues. Compared with the control tissues, MSP58 expression was not only significantly higher in the glioma tissues (P < 0.05), but also increased with the increasing pathological grade (P < 0.001). Furthermore, the Kaplan-Meier analysis showed that high expression of MSP58 could predict poor survival in glioma patients (P < 0.001). In the multivariate analysis, high expression of MSP58 was also an independent unfavorable prognostic factor for the overall survival in glioma patients (P < 0.001, hazard ratio, 8.177, 95% CI 2.571-26.008). In conclusion, the increased expression of MSP58 is correlated with a higher malignant grade and poor prognosis in glioma patients. MSP58 is valuable both as an indicator of the malignancy of gliomas and as a prognostic factor for the clinical outcome of glioma patients.

  15. Daily Life Experiences of Patients With a High-Grade Glioma and Their Caregivers

    DEFF Research Database (Denmark)

    Piil, Karin; Juhler, Marianne; Jakobsen, Johannes;

    2015-01-01

    BACKGROUND: There is a lack of knowledge regarding the breadth of needs for rehabilitation and supportive care across the disease and treatment trajectory for patients with a high-grade glioma (HGG) and their caregivers. OBJECTIVE: The aim of this study was to elucidate the experiences and needs ...... for rehabilitation programs that target the cognitive ability of the patients to participate actively.......BACKGROUND: There is a lack of knowledge regarding the breadth of needs for rehabilitation and supportive care across the disease and treatment trajectory for patients with a high-grade glioma (HGG) and their caregivers. OBJECTIVE: The aim of this study was to elucidate the experiences and needs...... for rehabilitation and supportive care in patients with HGG and their caregivers. METHODS: Patients with malignant glioma (N = 30) and their caregivers (N = 33) were interviewed five times during the first year of the HGG trajectory. A thematic analysis of interviews at five time points revealed five main themes...

  16. A 12-week interdisciplinary rehabilitation trial in patients with gliomas – a feasibility study

    DEFF Research Database (Denmark)

    Hansen, Anders; Søgaard, Karen; Minet, Lisbeth Rosenbek

    2017-01-01

    %) was achieved at part one. However, the failure to meet predefined feasibility objectives of drop-out, adherence and patient satisfaction of the unsupervised intervention at part two have led to a protocol revision for a future randomized controlled trial. CONCLUSION: This study demonstrates that an intensive...... limitations in physical functioning, cognition, and emotional wellbeing. In a relatively small sample this study shows that supervised physical- and occupational therapy in patients with gliomas is safe and feasible in the initial treatment phase. Patients with gliomas can potentially improve functioning......PURPOSE: This report aims to assess the safety and feasibility of using an interdisciplinary rehabilitation intervention for a future randomized controlled trial in patients with gliomas in the initial treatment phase. METHOD: We conducted an outpatient two-part rehabilitation intervention...

  17. Radiotherapy-induced cerebral abnormalities in patients with low-grade glioma

    NARCIS (Netherlands)

    Postma, TJ; Klein, M; Verstappen, CCP; Bromberg, JEC; Swennen, M; Langendijk, JA; Taphoorn, MJB; Scheltens, P; Slotman, BJ; van der Ploeg, HM; Aaronson, NK; Heimans, JJ

    2002-01-01

    Abnormalities on CT or MRI and neuropsychological performance in patients with low-grade glioma, with (n = 23) or without (n = 16) prior cerebral radiotherapy, were evaluated. Cerebral atrophy was observed in 14 of 23 patients (61%) treated with prior radiotherapy, and in 1 of 16 patients (6%) witho

  18. Association of Telomerase Reverse Transcriptase Promoter Mutations with the Prognosis of Glioma Patients: a Meta-Analysis.

    Science.gov (United States)

    Wang, Xiaogang; Li, Xiaoming; Xu, Feng; Zhang, Youqian; Liu, Hongwei; Tao, Yingqun

    2016-05-01

    Previous studies have found that telomerase reverse transcriptase (TERT) has vital roles in the development of malignant diseases including glioma. The occurrence of TERT promoter mutations in gliomas is frequent. So far, several studies on the association between TERT promoter mutations and prognosis of gliomas had been published, but the conclusion was still not uncertain. The aim of the present meta-analysis was to assess the association between TERT promoter mutations and survival of glioma patients by pooling data from published studies. PubMed, Embase, and Web of Science were searched for articles on the association between TERT promoter mutations and survival of glioma patients until June 30, 2015. Hazard ratios (HR) and the 95% confidence intervals (CIs) were utilized to analyze the prognosis of glioma patients with TERT promoter mutations. Heterogeneity of included studies was assessed using Cochrane's Q test and I (2) method. Eleven studies with a total of 3,444 glioma patients were finally included into the meta-analysis. Nine studies reported the HRs adjusting for other confounding factors. Meta-analysis of total 11 studies suggested that TERT promoter mutations were significantly associated with worse prognosis of patients with gliomas (HR = 2.07, 95% CI = 1.58-2.71, P promoter mutations were independently associated with worse prognosis of patients with gliomas (HR = 2.28, 95% CI = 1.72-3.01, P promoter mutation is a promising biomarker for predicting worse prognosis for patients with gliomas. More prospective well-designed cohort studies are needed to further validate its prognostic role in gliomas.

  19. PTEN gene mutations correlate to poor prognosis in glioma patients: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Han F

    2016-06-01

    Full Text Available Feng Han,1,* Rong Hu,2,* Hua Yang,1 Jian Liu,1 Jianmei Sui,1 Xin Xiang,1 Fan Wang,1 Liangzhao Chu,1 Shibin Song1 1Department of Neurosurgery, Affiliated Hospital of Guizhou Medical University, 2Department of Histology and Embryology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China *These authors contributed equally to this work Background: We conducted this meta-analysis based on eligible trials to investigate the relationship between phosphatase and tensin homolog (PTEN genetic mutation and glioma patients’ survival. Methods: PubMed, Web of Science, and EMBASE were searched for eligible studies regarding the relationship between PTEN genetic mutation and glioma patients’ survival. The primary outcome was the overall survival of glioma patient with or without PTEN genetic mutation, and second outcome was prognostic factors for the survival of glioma patient. A fixed-effects or random-effects model was used to pool the estimates according to the heterogeneity among the included studies. Results: Nine cohort studies, involving 1,173 patients, were included in this meta-analysis. Pooled results suggested that glioma patients with PTEN genetic mutation had a significant shorter overall survival than those without PTEN genetic mutation (hazard ratio [HR] =2.23, 95% confidence interval [CI]: 1.35, 3.67; P=0.002. Furthermore, subgroup analysis indicated that this association was only observed in American patients (HR =2.19, 95% CI: 1.23, 3.89; P=0.008, but not in Chinese patients (HR =1.44, 95% CI: 0.29, 7.26; P=0.657. Histopathological grade (HR =1.42, 95% CI: 0.07, 28.41; P=0.818, age (HR =0.94, 95% CI: 0.43, 2.04; P=0.877, and sex (HR =1.28, 95% CI: 0.55, 2.98; P=0.564 were not significant prognostic factors for the survival of patients with glioma. Conclusion: Current evidence indicates that PTEN genetic mutation is associated with poor prognosis in glioma patients. However, this

  20. Alteration of long-distance functional connectivity and network topology in patients with supratentorial gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Eun; Kim, Ho Sung; Kim, Sang Joon; Shim, Woo Hyun [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-Gu, Seoul (Korea, Republic of); Kim, Jeong Hoon [University of Ulsan College of Medicine, Department of Neurosurgery, Asan Medical Center, Seoul (Korea, Republic of)

    2016-03-15

    The need for information regarding functional alterations in patients with brain gliomas is increasing, but little is known about the functional consequences of focal brain tumors throughout the entire brain. Using resting-state functional MR imaging (rs-fMRI), this study assessed functional connectivity in patients with supratentorial brain gliomas with possible alterations in long-distance connectivity and network topology. Data from 36 patients with supratentorial brain gliomas and 12 healthy subjects were acquired using rs-fMRI. The functional connectivity matrix (FCM) was created using 32 pairs of cortical seeds on Talairach coordinates in each individual subject. Local and distant connectivity were calculated using z-scores in the individual patient's FCM, and the averaged FCM of patients was compared with that of healthy subjects. Weighted network analysis was performed by calculating local efficiency, global efficiency, clustering coefficient, and small-world topology, and compared between patients and healthy controls. When comparing the averaged FCM of patients with that of healthy controls, the patients showed decreased long-distance, inter-hemispheric connectivity (0.32 ± 0.16 in patients vs. 0. 42 ± 0.15 in healthy controls, p = 0.04). In network analysis, patients showed increased local efficiency (p < 0.05), but global efficiency, clustering coefficient, and small-world topology were relatively preserved compared to healthy subjects. Patients with supratentorial brain gliomas showed decreased long-distance connectivity while increased local efficiency and preserved small-world topology. The results of this small case series may provide a better understanding of the alterations of functional connectivity in patients with brain gliomas across the whole brain scale. (orig.)

  1. Alterations in tumour suppressor gene p53 in human gliomas from Indian patients

    Indian Academy of Sciences (India)

    Pornima Phatak; S Kalai Selvi; T Divya; A S Hegde; Sridevi Hegde; Kumaravel Somasundaram

    2002-12-01

    Alterations in the tumour suppressor p53 gene are among the most common defects seen in a variety of human cancers. In order to study the significance of the p53 gene in the genesis and development of human glioma from Indian patients, we checked 44 untreated primary gliomas for mutations in exons 5–9 of the p53 gene by PCR-SSCP and DNA sequencing. Sequencing analysis revealed six missense mutations. The incidence of p53 mutations was 13.6% (6 of 44). All the six mutations were found to be located in the central core domain of p53, which carries the sequence-specific DNA-binding domain. These results suggest a rather low incidence but a definite involvement of p53 mutations in the gliomas of Indian patients.

  2. Chimeric antigen receptor containing ICOS signaling domain mediates specific and efficient antitumor effect of T cells against EGFRvIII expressing glioma.

    Science.gov (United States)

    Shen, Chan-Juan; Yang, Yu-Xiu; Han, Ethan Q; Cao, Na; Wang, Yun-Fei; Wang, Yi; Zhao, Ying-Ying; Zhao, Li-Ming; Cui, Jian; Gupta, Puja; Wong, Albert J; Han, Shuang-Yin

    2013-05-09

    Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells appears to be a promising immunotherapeutic strategy. CAR combines the specificity of antibody and cytotoxicity of cytotoxic T lymphocytes, enhancing T cells' ability to specifically target antigens and to effectively kill cancer cells. Recent efforts have been made to integrate the costimulatory signals in the CAR to improve the antitumor efficacy. Epidermal growth factor receptor variant III (EGFRvIII) is an attractive therapeutic target as it frequently expresses in glioma and many other types of cancers. Our current study aimed to investigate the specific and efficient antitumor effect of T cells modified with CAR containing inducible costimulator (ICOS) signaling domain. A second generation of EGFRvIII/CAR was generated and it contained the EGFRvIII single chain variable fragment, ICOS signaling domain and CD3ζ chain. Lentiviral EGFRvIII/CAR was prepared and human CD3+ T cells were infected by lentivirus encoding EGFRvIII/CAR. The expression of EGFRvIII/CAR on CD3+ T cells was confirmed by flow cytometry and Western blot. The functions of EGFRvIII/CAR+ T cells were evaluated using in vitro and in vivo methods including cytotoxicity assay, cytokine release assay and xenograft tumor mouse model. Chimeric EGFRvIIIscFv-ICOS-CD3ζ (EGFRvIII/CAR) was constructed and lentiviral EGFRvIII/CAR were made to titer of 106 TU/ml. The transduction efficiency of lentiviral EGFRvIII/CAR on T cells reached around 70% and expression of EGFRvIII/CAR protein was verified by immunoblotting as a band of about 57 kDa. Four hour 51Cr release assays demonstrated specific and efficient cytotoxicity of EGFRvIII/CAR+ T cells against EGFRvIII expressing U87 cells. A robust increase in the IFN-γ secretion was detected in the co-culture supernatant of the EGFRvIII/CAR+ T cells and the EGFRvIII expressing U87 cells. Intravenous and intratumor injection of EGFRvIII/CAR+ T cells inhibited the in vivo growth of the EGFRvIII

  3. Initial experience with locoregional radioimmunotherapy using {sup 131}I-labelled monoclonal antibodies against tenascin (BC-4) for treatment of glioma (WHO III and IV)

    Energy Technology Data Exchange (ETDEWEB)

    Poepperl, G.; Gildehaus, F.J.; Hahn, K.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum Grosshadern, Muenchen (Germany); Goetz, C.; Reulen, H.J. [Klinik und Poliklinik fuer Neurochirurgie, Klinikum Grosshadern, Muenchen (Germany); Yousry, T.A. [Inst. fuer Neuroradiologie der LMU Muenchen, Klinikum Grosshadern, Muenchen (Germany)

    2002-06-01

    Aim: None of the established treatments (surgery, radiotherapy, chemotherapy) for malignant glioma has improved its very poor prognosis. Adjuvant locoregional radioimmunotherapy (RIT) represents a new therapeutic approach. We present our initial experience with this therapeutic tool with respect to adverse effects, biokinetics and clinical follow-up. Methods: Following surgery and radiotherapy, 12 patients with glioma (4, WHO stage III; 8, WHO stage IV) underwent 1-5 RIT-cycles (average dose 1100 MBq {sup 131}labelled monoclonal BC-4 antibodies) at six week intervals. Follow-up included serial FDG-PET and MRI investigations. Evaluation of biokinetics included whole body scans, together with analysis of blood, urine and fluid from the tumor cavity. Results: Following RIT, four patients experienced temporary seizures, which, in one case, were associated with temporary aphasia. Eight patients developed HAMA (human anti-mouse anti-bodies) during follow-up. Mean biologic half-life of the radiopharmaceutical in the resection cavity was 3.9 d (range: 1.0-10.2 d) and remained stable intraindividually during further RIT-cycles. The antibody/radionuclide conjugate remain stable in the tumor cavity for at least 5 d. Median survival presently stands at 18.5 months compared to 9.7 months in a historical patient group (n=89) undergoing conventional therapeutic strategies. Five patients show no signs of recurrence. In three patients with post-surgical evidence of residual tumor, one patient showed partial remission, one stable disease, and one progressive disease during RIT. Four patients without evidence of residual tumor mass at the beginning of RIT developed recurrence during therapy. Conclusions: Initial experience demonstrates that locoregional RIT is a well tolerated treatment modality that may represent a promising new approach in the management of patients with malignant glioma. Advantages of local application include passage of the blood-brain barrier, high concentration

  4. SM-03A RANDOMIZED, PLACEBO-CONTROLLED PILOT TRIAL OF ARMODAFINIL FOR FATIGUE IN PATIENTS WITH GLIOMAS UNDERGOING RADIOTHERAPY

    Science.gov (United States)

    Lee, Eudocia; Muzikansky, Alona; Kesari, Santosh; Wong, Eric; Fadul, Camilo; Reardon, David; Norden, Andrew; Nayak, Lakshmi; Rinne, Mikael; Alexander, Brian; Arvold, Nils; Doherty, Lisa; LaFrankie, Debra; Pulverenti, Julee; Smith, Katrina; Gaffey, Sarah; Kenney, Alexandra; Hammond, Samantha; Drappatz, Jan; Wen, Patrick

    2014-01-01

    BACKGROUND: Fatigue is a common symptom among glioma patients and affects quality of life. Armodafinil, a wakefulness-promoting medication, benefits patients with fatigue of various causes. This study evaluates the effects of armodafinil on fatigue in glioma patients undergoing radiation therapy (RT). METHODS: Eligibility criteria included age ≥ 18; KPS ≥ 60; grade 2-4 glioma undergoing RT to a total dose of 50-60 Gy with or without chemotherapy. Patients were randomized 1:1 to armodafinil or placebo. Fatigue assessments were made at baseline, Day 22, Day 43, and Day 56 with the FACIT-F Fatigue Scale, FACT-G, Brief Fatigue Inventory (BFI), and Cancer Fatigue Scale (CFS). The primary aim was to detect a difference in the 42-day change in FACIT-F fatigue subscale scores between the two groups using a 2-sample Wilcoxon statistic. Secondary outcomes include a 42-day change in FACT-G, CFS, and BFI. RESULTS: In the armodafinil arm, median age was 56 (25-79), median KPS was 90 (70-100), 58.5% with grade 4 glioma, 34.2% with grade 3 glioma, 2.4% with grade 2 glioma. In the placebo arm, median age was 54 (19-78), median KPS was 90 (70-100), 47.8% with grade 4 glioma, 30.8% with grade 3 glioma, 10.3% with grade 2 glioma. The median 42-day change in the FACIT-F fatigue subscale scores in the armodafinil arm was 1 (range -40 to 26) and in the placebo arm was -5.50 (range -65 to 28) with Wilcoxon p-value of 0.14. Toxicity was rare and similar between arms. CONCLUSIONS: Treatment with armodafinil is well tolerated in glioma patients undergoing RT. Preliminary results do not demonstrate statistically significant reduction in fatigue between groups. Updated results will be presented.

  5. Inter-hemispheric language functional reorganization in low-grade glioma patients after tumour surgery

    NARCIS (Netherlands)

    Kristo, Gert; Raemaekers, Mathijs; Rutten, Geert Jan; de Gelder, Beatrice; Ramsey, Nick F.

    2015-01-01

    Despite many claims of functional reorganization following tumour surgery, empirical studies that investigate changes in functional activation patterns are rare. This study investigates whether functional recovery following surgical treatment in patients with a low-grade glioma in the left hemispher

  6. Prognostic value of volume-based measurements on {sup 11}C-methionine PET in glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Kentaro; Manabe, Osamu; Shiga, Tohru; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); Hirata, Kenji [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States); Yamaguchi, Shigeru; Terasaka, Shunsuke; Kobayashi, Hiroyuki [Hokkaido University, Department of Neurosurgery, Graduate School of Medicine, Sapporo (Japan); Hattori, Naoya [Hokkaido University, Department of Molecular Imaging, Graduate School of Medicine, Sapporo (Japan); Tanaka, Shinya [Hokkaido University, Department of Cancer Pathology, Graduate School of Medicine, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan)

    2015-04-08

    {sup 11}C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not

  7. Safety and Efficacy of Stereotactic Radiosurgery and Adjuvant Bevacizumab in Patients With Recurrent Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Cuneo, Kyle C. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Vredenburgh, James J.; Sampson, John H.; Reardon, David A.; Desjardins, Annick; Peters, Katherine B.; Friedman, Henry S. [Department of Surgery, Duke University Medical Center, Durham, NC (United States); Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kirkpatrick, John P., E-mail: john.kirkpatrick@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC (United States)

    2012-04-01

    Purpose: Patients with recurrent malignant gliomas treated with stereotactic radiosurgery (SRS) and multiagent systemic therapies were reviewed to determine the effects of patient- and treatment-related factors on survival and toxicity. Methods and Materials: A retrospective analysis was performed on patients with recurrent malignant gliomas treated with salvage SRS from September 2002 to March 2010. All patients had experienced progression after treatment with temozolomide and radiotherapy. Salvage SRS was typically administered only after multiple postchemoradiation salvage systemic therapies had failed. Results: 63 patients were treated with SRS for recurrent high-grade glioma; 49 patients had World Health Organization (WHO) Grade 4 disease. Median follow-up was 31 months from primary diagnosis and 7 months from SRS. Median overall survival from primary diagnosis was 41 months for all patients. Median progression-free survival (PFS) and overall survival from SRS (OS-SRS) were 6 and 10 months for all patients, respectively. The 1-year OS-SRS for patients with Grade 4 glioma who received adjuvant (concurrent with or after SRS) bevacizumab was 50% vs. 22% for patients not receiving adjuvant bevacizumab (p = 0.005). Median PFS for patients with a WHO Grade 4 glioma who received adjuvant bevacizumab was 5.2 months vs. 2.1 months for patients who did not receive adjuvant bevacizumab (p = 0.014). Karnofsky performance status (KPS) and age were not significantly different between treatment groups. Treatment-related Grade 3/4 toxicity for patients receiving and not receiving adjuvant BVZ was 10% and 14%, respectively (p = 0.58).On multivariate analysis, the relative risk of death and progression with adjuvant bevacizumab was 0.37 (confidence interval [CI] 0.17-0.82) and 0.45 (CI 0.21-0.97). KPS >70 and age <50 years were significantly associated with improved survival. Conclusions: The combination of salvage radiosurgery and bevacizumab to treat recurrent malignant

  8. Cognitive strategies and quality of life of patients with high-grade glioma.

    Science.gov (United States)

    Lucchiari, C; Botturi, A; Silvani, A; Lamperti, E; Gaviani, P; Innocenti, A; Finocchiaro, C Y; Masiero, M; Pravettoni, G

    2015-12-01

    The purpose of this study was to analyze the psychological well-being, quality of life, and cognitive strategies activated by patients with high-grade glioma. We hypothesized that the self-perceived quality of life is modulated by physical and psychological factors and that in order to understand this modulation more psychometric approaches are necessary. Data were collected from a sample of 73 consecutive patients with a histological diagnosis of primary malignant brain cancer (grade IV glioblastoma and grade III anaplastic astrocytoma) hospitalized in a specialized Italian center. The Functional Assessment of Cancer Therapy (FACT) scale and the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) scale were used to assess quality of life. The mean FACT-Brain (Br) score was 122.37. Similarly, the median SEIQoL-DW score was 72.9 out of a maximum value of 100. No gender effect was found in relation to overall quality of life. Patients with high depression and/or anxiety scores reported lower quality of life (QoL) scores in all the instruments considered. We did not find any gender effect concerning depression and anxiety levels. However, we found that men and women, though having similar physical and functional well-being, reported different QoL determinants, since men seem to rely more on physical adjustment, while women activate more introspective strategies. Positive actions, family issues, negative thoughts, health, and positive thoughts were found to be the most reported themes. In conclusion, the present study strongly suggests that a positive psychological adjustment is possible also in the event of a severe diagnosis and during aggressive treatments, but QoL determinants might be considered too in order to help health professionals to understand patients' experience and to meet their needs.

  9. The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival.

    Science.gov (United States)

    Fogli, Anne; Chautard, Emmanuel; Vaurs-Barrière, Catherine; Pereira, Bruno; Müller-Barthélémy, Mélanie; Court, Franck; Biau, Julian; Pinto, Afonso Almeida; Kémény, Jean-Louis; Khalil, Toufic; Karayan-Tapon, Lucie; Verrelle, Pierre; Costa, Bruno Marques; Arnaud, Philippe

    2016-02-01

    Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ.

  10. Clinical value of CD133 and nestin in patients with glioma

    DEFF Research Database (Denmark)

    Dahlrot, Rikke H; Hansen, Steinbjørn; Jensen, Stine S

    2014-01-01

    133 and nestin separately and in combination using a novel quantitative approach in a well-characterized population-based cohort of glioma patients. The expression of CD133 and nestin was measured by systematic random sampling in stained paraffin sections from 239 glioma patients diagnosed between......-free survival (PFS) in multivariate analysis. High levels of co-localization were associated with poor PFS in patients with WHO grade II tumors, but not with OS. We conclude that CD133 was not an independent prognostic factor, but a high level of nestin was associated with poor PFS in patients with WHO grade II...... 2005 and 2009. We found that the expression of CD133 did not correlate with WHO grade, and there was no association with overall survival (OS). The level of nestin correlated positively with WHO grade. In patients with WHO grade II tumors, a high level of nestin was associated with short progression...

  11. Relationship between radiation dose and microbleed formation in patients with malignant glioma.

    Science.gov (United States)

    Wahl, Michael; Anwar, Mekhail; Hess, Christopher P; Chang, Susan M; Lupo, Janine M

    2017-08-10

    Cranial irradiation is associated with long-term cognitive changes. Cerebral microbleeds (CMBs) have been identified on susceptibility-weighted MRI (SWI) in patients who have received prior cranial radiation, and serve as radiographic markers for microvascular injury thought to contribute to late cognitive decline. The relationship between CMB formation and radiation dose has not previously been quantified. SWI was performed on 13 patients with stable WHO grade III-IV gliomas between 2 and 4 years after chemoradiotherapy to 60 Gy. The median age at the time of treatment was 41 years (range 25 - 74 years). CMBs were identified as discrete foci of susceptibility on SWI that did not correspond to vessels. CMB density for low (45 Gy) dose regions was computed. Twelve of 13 patients exhibited CMBs. The number of CMBs was significantly higher for late (>3 years from treatment) compared to early (CMBs; late median 27 CMBs; p = 0.001), and there were proportionally more CMBs at lower doses for late scans (p = 0.006). 88% of all CMBs were observed in regions receiving at least 30 Gy, but the CMB density within medium and high dose regions was not significantly different (p = 0.33 and p = 0.9, respectively, for early and late time points). CMBs predominantly form in regions receiving at least 30 Gy, but form in lower dose regions with longer follow-up. We do not observe a clear dose-response relationship at doses above 30 Gy. These findings provide important information to assess the risk of late microvascular sequelae from cranial irradiation.

  12. The positive correlation between DJ-1 and β-catenin expression shows prognostic value for patients with glioma.

    Science.gov (United States)

    Wang, Chao; Fang, Mao; Zhang, Meng; Li, Weiping; Guan, Hong; Sun, Yanhua; Xie, Siming; Zhong, Xueyun

    2013-12-01

    The relationship between DJ-1 and β-catenin, and its impact on the prognosis for glioma patients has not been fully understood. This study determined the effect of DJ-1 on β-catenin and the prognostic significance of this interaction in glioma patients. We collected tumor specimens from 88 glioma patients and determined the expression of DJ-1, β-catenin and PTEN by using immunohistochemical staining. The involvement of DJ-1 and β-catenin in glioma cell lines was evaluated by immunohistochemistry and Western blotting. High DJ-1 expression (37.5%) and high β-catenin expression (34.1%) in glioma specimens were significantly associated with high grade and poor prognosis in glioma patients. However, only high levels of DJ-1 (P = 0.014) was a strong independent prognostic factor, correlated with a reduced overall survival time. In vitro DJ-1 expression was positively correlated with the expression levels of β-catenin and p-Akt, and negatively correlated with PTEN expression in U87, U251 MG, SWO-38 and SHG44 human glioma cell lines. After the knockdown of DJ-1, Akt, p-Akt or β-catenin expression levels were not affected in the PTEN-null cell lines (U87 and U251 MG). However, in the SWO-38 cell line, which has wild-type PTEN protein, the level of PTEN increased while Akt/p-Akt and β-catenin levels were reduced. Furthermore, β-catenin staining weakened in SWO-38 cells after DJ-1 levels decreased according to immunocytochemical analysis. In conclusion, DJ-1 and β-catenin may contribute to the development and recurrence of glioma and are valuable prognostic factors for glioma patients. DJ-1 may regulate β-catenin expression via PTEN and p-Akt.

  13. 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.)

  14. Dendritic cell immunotherapy versus bevacizumab plus irinotecan in recurrent malignant glioma patients: a survival gain analysis

    Science.gov (United States)

    Artene, Stefan-Alexandru; Turcu-Stiolica, Adina; Hartley, Richard; Ciurea, Marius Eugen; Daianu, Oana; Brindusa, Corina; Alexandru, Oana; Tataranu, Ligia Gabriela; Purcaru, Stefana Oana; Dricu, Anica

    2016-01-01

    Background The bevacizumab and irinotecan protocol is considered a standard treatment regimen for recurrent malignant glioma. Recent advances in immunotherapy have hinted that vaccination with dendritic cells could become an alternative salvage therapy for the treatment of recurrent malignant glioma. Methods A search was performed on PubMed, Cochrane Library, Web of Science, ScienceDirect, and Embase in order to identify studies with patients receiving bevacizumab plus irinotecan or dendritic cell therapy for recurrent malignant gliomas. The data obtained from these studies were used to perform a systematic review and survival gain analysis. Results Fourteen clinical studies with patients receiving either bevacizumab plus irinotecan or dendritic cell vaccination were identified. Seven studies followed patients that received bevacizumab plus irinotecan (302 patients) and seven studies included patients that received dendritic cell immunotherapy (80 patients). For the patients who received bevacizumab plus irinotecan, the mean reported median overall survival was 7.5 (95% confidence interval [CI] 4.84–10.16) months. For the patients who received dendritic cell immunotherapy, the mean reported median overall survival was 17.9 (95% CI 11.34–24.46) months. For irinotecan + bevacizumab group, the mean survival gain was −0.02±2.00, while that for the dendritic cell immunotherapy group was −0.01±4.54. Conclusion For patients with recurrent malignant gliomas, dendritic cell immunotherapy treatment does not have a significantly different effect when compared with bevacizumab and irinotecan in terms of survival gain (P=0.535) and does not improve weighted survival gain (P=0.620). PMID:27877052

  15. Assessment of quality of life in patients treated for low-grade glioma: a preliminary report.

    Science.gov (United States)

    Taphoorn, M J; Heimans, J J; Snoek, F J; Lindeboom, J; Oosterink, B; Wolbers, J G; Karim, A B

    1992-01-01

    In this pilot study quality of life was assessed in fourteen adult patients who were treated for a low-grade glioma with surgery and radiotherapy at least one year previously. Apart from widely used parameters, such as the neurological and functional status, the patients' cognitive functioning and actual affective status were determined. In addition the patients were interviewed to evaluate various aspects of quality of life. Generally no serious focal neurological deficits were found, although psychological examination showed serious cognitive and affective disturbances in most cases. Self report measures concerning cognitive functioning were not in all cases in accordance with objective test results. When the results of treatment in glioma patients are evaluated assessment of quality of life, including neuropsychological functioning, should be performed, especially as new therapeutic strategies are being developed. PMID:1602310

  16. Health-related quality of life in patients with high-grade gliomas

    DEFF Research Database (Denmark)

    Piil, K; Jakobsen, J; Christensen, Karl Bang

    2015-01-01

    The diagnosis of a high-grade glioma usual is followed by functional impairment(s), cognitive decline and an impaired psycho-social well-being. This might well have a significant and negative impact on the health related quality of life. The purpose of this study was to explore physical activity...... levels, prevalence and severity of anxiety and depressive symptoms and health-related quality of life among patients with a highgrade glioma. This paper is based on a longitudinal mixed methods study. Patients (n = 30) completed questionnaires at 5 time points from time of diagnosis until the final...... follow-up after 1 year. Scores of Karnofsky Performance Status (KPS), physical activity, anxiety and depression and health-related quality of life (FACT-Br) are obtained. Patients' physical activity level and KPS decrease during the disease- and treatment trajectory. The majority of patients did...

  17. Preliminary Study of Local Immunotherapy with Autologous Cytokine-Induced Killer Cells for Glioma Patients

    Institute of Scientific and Technical Information of China (English)

    Li Lin; Yonggao Mu; Zhongping Chen

    2008-01-01

    OBJECTIVE Cytokine-induced killer (CIK) cells are T-cells that display effective anti-tumor activity. In this study, we investigated the anti-tumor activity of CIK cells in vitro, and conducted a preliminary investigation using autologous CIK cells to treat glioma patients through local administration.METHODS The CIK cells were derived from peripheral blood monocytes (PBMCs) of the glioma patients. The anti-tumor activity of the CIK cells against human T98-G glioma cell was tested In vitro. In addition, the autologous CIK cells were locally administrated into the tumor cavity in the malignant glioma patients through an Ommaya reservoir which was pre-inserted during tumor resection. The 4×108 CIK cells in a 5 ml suspension were injected once a week 2 times per cycle. Five hundreds KU of IL-2 was injected every other day.RESULTS (I) With incubation, the CIK cells showed dual staining of CD3+CD56+ with a positive rate of 3.45% on day 10 and 55.2% on day 30. In vitro anti-tumor activity (againstT98-G cells) of the CIK cells reached the highest level after 18 days of incubation with different effector/target (E:T) ratios. (ii)Six patients received autologous CIK cell treatment (10 cycles).Two patients showed no recurrence and are still alive (24 and 10 months), while 4 cases had a recurrence 3 of which have died. The mean survival time from the first CIK cell treatment to the end of follow-up was 12.5 months. The main side-effects of the local CIK cell treatment was brain edema, which was controlled by mannitol in most of the cases. However for one patient injection of CIK cells and IL-2 had to be discontinued.CONCLUSION In vitro CIK cells are effective anti-glioma T-cells. Local therapy with CIK cells has potential anti-glioma efficacy and tolerable side-effects.

  18. Verbal Learning Processes in Patients with Glioma of the Left and Right Temporal Lobes

    Science.gov (United States)

    Noll, Kyle R.; Weinberg, Jeffrey S.; Ziu, Mateo; Wefel, Jeffrey S.

    2016-01-01

    Recent research supports the utility of process variables in understanding mechanisms underlying memory impairments. The Hopkins Verbal Learning Test-Revised (HVLT-R) was administered to 84 patients with left (LTL, n = 58) or right temporal lobe glioma (RTL, n = 26) prior to surgical resection. Primary HVLT-R measures of learning and memory and numerous learning process indices were computed. Both groups exhibited frequent memory impairment (>30%), with greater severity in the LTL group. Patients with LTL glioma also exhibited lower semantic clustering scores than RTL patients, which were highly associated with Total Recall (ρ = 0.83) and Delayed Recall (ρ = 0.68). Learning slope and a novel measure of learning efficiency were also significantly associated with primary memory measures, though scores were similar across the LTL and RTL groups. While lesions to either temporal lobe impact verbal memory, semantic encoding appears to depend upon the integrity of LTL structures in particular. PMID:26537777

  19. Adaptability of language-related brain network in a low-grade glioma patient

    Institute of Scientific and Technical Information of China (English)

    Olivera Sveljo; Katarina Koprivsek; Milos Lucic

    2011-01-01

    Because functional magnetic resonance imaging can be used for dynamic observation of functional cortical changes after brain injuries, we followed up functional magnetic resonance imaging manifestationsof a language-related brain network in a low -grade glioma patient. Disease progressionand therapy during a 3-year period were followed up at different time points: before and after reoperation,after radiation therapy, and 1 year after irradiation. During the whole 3-year follow -up period,the patient exhibited no neurological deficits while functional magnetic resonance imaging revealeddifferent topologies of the language-related brain network. During disease progression and after irradiation,the language-related brain network was extended or completely transferred to the nondominant(right) hemisphere. In addition, after reoperation and 1 year after irradiation, languageareas were primarily found in the language dominant (left) hemisphere. Our results suggest a highlevel of adaptability of the language-related cortical network of the bilateral hemispheres in thislow -grade glioma patient.

  20. 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

  1. Patient and caregiver perceptions of communication of prognosis in high grade glioma.

    Science.gov (United States)

    Lobb, E A; Halkett, G K B; Nowak, A K

    2011-08-01

    This study sought the views of patients and their caregivers on their experience of being diagnosed with high grade glioma. Purposive sampling was used to recruit 19 patients and 21 caregivers from the medical oncology unit of a tertiary hospital. A semi-structured face-to-face interview was conducted. Interviews were audio-taped and transcribed verbatim. Data was analysed based on Grounded Theory and using the constant comparison method. This paper focuses on patient and carer perceptions of the initial communication about the diagnosis of high grade glioma and its prognosis. Themes identified included: (a) shock at hearing the diagnosis; (b) trying to understand and process prognostic information when still in shock; (c) the perception of hope being taken away; (d) individualizing prognostic information; and (e) clinicians' lack of communication skills. This study shows that the first communication of prognosis to patients with high grade glioma and their caregivers requires careful negotiation. It illustrates the inability of individuals to process detailed prognostic information when in a state of initial shock and distress. The importance of balancing honesty with hope in the communication of a poor prognosis is highlighted. We recommend that clinicians seek patient preferences for the amount and type of information they require and that prognostic information be individualized. Detailed discussions of prognosis should only take place with senior medical staff, or advanced trainees who have demonstrated acceptable communication skills.

  2. Phase I and pharmacokinetic study of COL-3 in patients with recurrent high-grade gliomas.

    Science.gov (United States)

    Rudek, Michelle A; New, Pamela; Mikkelsen, Tom; Phuphanich, Surasak; Alavi, Jane B; Nabors, Louis B; Piantadosi, Steven; Fisher, Joy D; Grossman, Stuart A

    2011-11-01

    COL-3 is a chemically modified tetracycline that targets multiple aspects of matrix metalloproteinase regulation. This phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) of COL-3 in adults with recurrent high-grade glioma, to describe the effects of enzyme-inducing antiseizure drugs (EIADs) on its pharmacokinetics, and to obtain preliminary evidence of activity. Adults with recurrent high-grade glioma were stratified by EIAD use. COL-3 was given orally daily without interruption until disease progression or treatment-related dose-limiting toxicity (DLT). Three patients in each EIAD group were evaluated at each dose level beginning with 25 mg/m(2)/day and escalated by 25 mg/m(2)/day. Toxicity, response, and pharmacokinetics were assessed. Thirty-three patients were evaluated. The MTD was 75 mg/m(2)/day in the -EIAD patients while one was not determined in +EIAD patients. The common toxicities observed were anemia, ataxia, diarrhea, hypokalemia, CNS hemorrhage, and myalgia. One partial response was observed. -EIAD patients tended to have a higher steady-state trough concentration that was apparent only at the 100 mg/m(2)/day dose level (P = 0.01). This study suggests that: (a) EIAD use does affect the pharmacokinetics of COL-3 at higher doses; and (b) there was not enough suggestion of single-agent activity to warrant further study in recurrent high-grade gliomas.

  3. Profound tumor-specific Th2 bias in patients with malignant glioma

    Directory of Open Access Journals (Sweden)

    Shimato Shinji

    2012-11-01

    Full Text Available Abstract Background Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4+ helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4+ helper T cell responses in the peripheral blood of patients with malignant gliomas. Methods Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM (n = 8, recurrent GBM (n = 5, meningioma (n = 7, and healthy controls (n = 6 with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb and an immunodominant peptide epitope derived from myelin basic protein (MBP serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias. Results We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs. Conclusions Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically.

  4. EZH2 overexpression is associated with poor prognosis in patients with glioma

    Science.gov (United States)

    Chen, Ling; Zhang, Zhibin; Feng, Shiyu

    2017-01-01

    Previous studies have investigated the prognostic value of enhancer of zeste homolog 2 (EZH2) expression in patients with glioma but conclude contradictory results. We aimed to comprehensively evaluate the prognostic role of EZH2 in glioma by meta-analysis. The databases of PubMed, Embase and Web of Science were searched. Hazard ratio (HR) and 95% confidence interval (CI) were combined to assess the association between EZH2 and overall survival (OS) as well as progression-free survival (PFS). Odd ratio (OR) and 95% CI were calculated to investigate the relevance of EZH2 on clinical factors. Six studies with 575 patients were included for meta-analysis. The results showed that EZH2 overexpression was correlated with poor OS (n = 6, HR = 2.23, 95% CI: 1.56–3.19, p analysis showed that EZH2 had enhanced prognostic value in Asian patients, for WHO grade I-IV and when using immunohistochemistry (IHC) method. In addition, EZH2 was associated with KPS score analysis. In conclusion, the present study showed that EZH2 was a potential prognostic marker for poor OS, PFS and lower KPS score in glioma patients. PMID:27880940

  5. RH-01THE SIGNIFICANCE OF ACUTE INPATIENT REHABILITATION FOR GLIOMA PATIENTS: IMPROVING THE PHYSICAL FUNCTION, QUALITY OF LIFE AND SURVIVAL

    Science.gov (United States)

    Beverly Fu, D.; Bota, Daniela A.

    2014-01-01

    OBJECTIVE: To assess the effects of inpatient acute rehabilitation on overall function, quality of life and overall survival for glioma patients. DESIGN: A retrospective study of glioma patients treated at UCI Neuro-Oncology Program. PARTICIPANTS: We have identified 12 patients with glioma diagnosis who underwent inpatient acute rehabilitation program using our IRB approved neuro-oncology database. OUTCOME ASSESSMENT TOOLS: Functional status based upon Karnofsky performance scale (KPS), quality of life as assessed by Functional Assessment of Cancer Therapy Brain (FACT-Br) and overall survival. RESULTS: We identified on our study 3 patients with glioblastoma, 7 patients with anaplastic gliomas, and 2 patients with low grade gliomas. All of them had radiation and chemotherapy, except 2 patients with low grade gliomas who had radiation treatment only. The age range is from 26 to 77 and the mean age is 49-year-old. All the patients who underwent the acute inpatient rehabilitation program at our institution, not only improved their KPS scale significantly, but also enhanced their social and emotional well-being. The median KPS improvement is 30 points from a 3-6 weeks stay. Functional Assessment of Cancer Therapy Brain (FACT-Br) is obtained from 4 patients at this time (further information will be presented at SNO conference). The mean FACT-Br TOI is 60.8, and the total FACT0Br Score is 119.6. Survival data are still collected. CONCLUSIONS: The patients who underwent acute inpatient rehabilitation program, showed significant improvements in their functional status and quality of life. The observation from this pilot study warrants further research and demonstrates the acute inpatient rehabilitation may be beneficial to glioma patients with good physical functions and tolerance for 3 hours a day of physical, occupation and speech therapies.

  6. 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.

  7. Treatment of Malignant Gliomas in Elderly Patients: A Concise Overview of the Literature

    Directory of Open Access Journals (Sweden)

    Patrizia Farina

    2014-01-01

    Full Text Available Gliomas are the most frequent primary brain tumors and the incidence data has increased in the elderly population. Unfortunately, prospective studies on this population are few and so the right treatment is unknown. In the elderly patients no standard treatment has been established and therefore the optimal treatment should be individualized. We performed a review analyzing the prognostic and predictive factors, the clinical studies, and the correct management of this population.

  8. Leptomeningeal metastases in high-grade adult glioma: development, diagnosis, management and outcomes in a series of 34 patients.

    Directory of Open Access Journals (Sweden)

    Christopher eDardis

    2014-11-01

    Full Text Available Leptomeningeal metastases (LM in the setting of glioma have often been thought to carry a particularly poor prognosis. We sought to better characterize this phenomenon through a review of patients with glioma seen in our institution over the preceding 10 years. We focus here on 34 cases with LM due to grade III or IV glioma. Over the period in question we estimate a prevalence of almost 4% in those affected by grade IV tumors. Leptomeningeal spread was present at the time of initial diagnosis in 4 patients. In the others, LM occurred at the time of first progression of disease in 17. The median time to development of LM (excluding those where it was present at initial diagnosis was 16.4 months (95% confidence interval (CI 8.2-43.9. The median time to further progression of disease following LM was 4.9 months (95% CI 3.1-6.9. 25 patients were known to have died at the time of writing. Thus median overall survival (OS was 10.2 months (95% CI 8.8-14.7 following LM. At the time of diagnosis of LM, some form of treatment (chemotherapy and/or radiation vs. no treatment increased OS (median 11.7 vs. 3.3 months, p<0.001 by log-rank test. Use of radiation therapy (vs. no radiation also increased OS, although the effect was more modest (7.8 vs. 16.8 months, p=0.07. Higher Karnofsky Performance Status (KPS at the time of diagnosis of LM was associated with OS (p=0.007, median OS for KPS □90 19 months vs. 7.8 for KPS <90.In a two-variable model incorporating the use any treatment (vs. none and KPS, KPS tended to be a more significant predictor of survival (p=0.22 vs. p=0.06 by likelihood-ratio test. This was also true for radiation (vs. none and KPS (p=0.27 vs. p=0.02.No significant benefit could be demonstrated for the use of chemotherapy considered alone, either systemic or intrathecal. It should be noted that 4 of 9 patients receiving intrathecal chemotherapy had a ventriculoperitoneal shunt in place during these injections, which may have affected

  9. Boron neutron capture therapy of EGFR or EGFRvIII positive gliomas using either boronated monoclonal antibodies or epidermal growth factor as molecular targeting agents

    Energy Technology Data Exchange (ETDEWEB)

    Yang, W. [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Barth, R.F. [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States)], E-mail: rolf.barth@osumc.edu; Wu, G. [Department of Pathology, Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States); Tjarks, W. [College of Pharmacy, Ohio State University, Columbus, OH 43210 (United States); Binns, P.; Riley, K. [Nuclear Reactor Laboratory and Department of Nuclear Engineering, Massachusetts Institute of Technology, Cambridge, MA 02215 (United States)

    2009-07-15

    In the present report we have summarized studies carried out over the past five years on molecular targeting of the epidermal growth factor receptor (EGFR) and its mutant isoform, EFGRvIII, for BNCT of genetically engineered F98 rat gliomas, expressing either wildtype (F98{sub EGFR}) or mutant receptors (F98{sub npEGFRvIII}). EGF or the monoclonal antibodies (mAbs), cetuximab (IMC-C225) and L8A4, which recognize wildtype EGFR and EGFRvIII, respectively, were heavily boronated using polyamidoamine (PAMAM) dendrimers (BD) linked to the targeting vehicles by means of heterobifunctional reagents. Boronated EGF or mAbs, alone or in combination with i.v. boronophenylalanine (BPA), were administered intracerebrally (i.c.) by either intratumoral (i.t.) injection or convection enhanced delivery (CED) to rats bearing F98 gliomas following which BNCT was initiated. The best survival data were obtained in rats bearing F98{sub npEGFRvIII} gliomas that had received CED of BD-L8A4 either alone or in combination with i.v. boronophenylalanine (BPA). Studies carried out in rats bearing composite tumors (F98{sub EGFR}/F98{sub npEGFRvIII}) demonstrated that it was essential to target both tumor cell populations in order to obtain an optimal therapeutic effect. Based on these observations, we have concluded that EGFR targeting vehicles are useful, but not stand-alone boron delivery agents due to the heterogeneity of receptor expression in brain tumors. They could, however, be quite useful in combination with the two drugs that currently are being used clinically, BPA and sodium borocaptate (BSH) for BNCT of either brain tumors or head and neck cancers.

  10. 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

  11. [Guidelines for adult diffuse gliomas WHO grade II, III and IV: pathology and biology. Société franc¸aise de neuropathologie . Réseau de neuro-oncologie pathologique].

    Science.gov (United States)

    Figarella-Branger, Dominique; Labrousse, François; Mohktari, Karima

    2012-10-01

    Pathological diagnosis plays a major role in the therapeutic management of adult diffuse gliomas. It is based on the histopathological analysis of a representative specimen. Therefore pathologists might be aware of the neuroradiological features of the lesions. Pathologists play a major role in the management of biological resources. Pathologists should classify adult gliomas according to WHO 2007 classification (histological subtype and grade). In addition, in order to provide the histomolecular classification of adult gliomas, search for molecular markers of diagnostic, prognostic or predictive of therapeutic responses must be performed by appropriate and validated immunohistochemical and molecular techniques. In all diffuse gliomas, whatever their grade, search for IDH1 R132H and P53 expression is required. Search for IDH1 minor mutations and IDH2 mutations is required in grade II and III IDH1 R132H negative gliomas whereas 1p19q codeletion should be searched for in grade II and III gliomas with an oligodendroglial component. Search for EGFR amplification and MGMT promoter methylation is recommended. It is strongly recommended to fill the standardized form for pathology and molecular features (validated by the French Society of Neuropathology) in all adult diffuse gliomas.

  12. FGFR3, as a receptor tyrosine kinase, is associated with differentiated biological functions and improved survival of glioma patients.

    Science.gov (United States)

    Wang, Zheng; Zhang, Chuanbao; Sun, Lihua; Liang, Jingshan; Liu, Xing; Li, Guanzhang; Yao, Kun; Zhang, Wei; Jiang, Tao

    2016-12-20

    Activation of receptor tyrosine kinases is common in Malignancies. FGFR3 fusion with TACC3 has been reported to have transforming effects in primary glioblastoma and display oncogenic activity in vitro and in vivo. We set out to investigate the role of FGFR3 in glioma through transcriptomic analysis. FGFR3 increased in Classical subtype and Neural subtype consistently in CGGA and TCGA cohort. Similar patterns of FGFR3 distribution through subtypes were observed in CGGA and TCGA samples. Gene ontology analysis was performed with genes that were significantly correlated with FGFR3 expression. We found that positively associated biological processes of FGFR3 were focused on differentiated cellular functions and neuronal activities, while negatively correlated biological processes focused on mitosis and cell cycle phase. Clinical investigation showed that higher FGFR3 expression predicted improved survival for glioma patients, especially in Proneural subtype. Moreover, FGFR3 showed very limited relevance with other receptor tyrosine kinases in glioma at transcriptome level. FGFR3 expression data of glioma was obtained from Chinese Glioma Genome Atlas (CGGA) and TCGA (The Cancer Genome Atlas). In total, RNA sequencing data of 325 glioma samples and mRNA microarray data of 301 samples from CGGA dataset were enrolled into this study. To consolidate the findings that we have revealed in CGGA dataset, RNA-seq data of 672 glioma samples from TCGA dataset were used as a validation cohort. R language was used as the main tool to perform statistical analysis and graphical work. FGFR3 expression increased in classical and neural subtypes and was associated with differentiated cellular functions. FGFR3 showed very limited correlation with other common receptor tyrosine kinases, and predicted improved survival for glioma patients.

  13. Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta [Humanitas Clinical and Research Hospital, Nuclear Medicine, Humanitas Cancer Center, Rozzano, MI (Italy); Riva, Marco; Raneri, Fabio; Pessina, Federico [Humanitas Clinical and Research Hospital, Neurosurgery, Rozzano, Milan (Italy); Olivari, Laura; Rossi, Marco; Alfieri, Tommaso [Universita degli Studi di Milano, Milan (Italy); Soffietti, Riccardo; Ruda, Roberta [University and City of Health and Science Hospital, Neuro-Oncology, Turin (Italy); Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine, Genova (Italy); Bizzi, Alberto [Fondazione IRCCS Istituto Neurologico Carlo Besta, Neuroradiology, Milan (Italy); Navarria, Pierina; Ascolese, Anna Maria [Humanitas Clinical and Research Hospital, Radiosurgery and Radiotherapy, Rozzano, Milan (Italy); Fernandes, Bethania [Humanitas Clinical and Research Hospital, Pathology, Rozzano, Milan (Italy); Grimaldi, Marco [Humanitas Clinical and Research Hospital, Medical Oncology, Rozzano, Milan (Italy); Simonelli, Matteo; Zucali, Paolo Andrea [Humanitas Clinical and Research Hospital, Radiology Department, Rozzano, Milan (Italy); Scorsetti, Marta [Humanitas Clinical and Research Hospital, Pathology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Bello, Lorenzo [Humanitas Clinical and Research Hospital, Neurosurgery, Rozzano, Milan (Italy); Universita degli Studi di Milano, Milan (Italy); Chiti, Arturo [Humanitas Clinical and Research Hospital, Nuclear Medicine, Humanitas Cancer Center, Rozzano, MI (Italy); Humanitas University, Rozzano, Milan (Italy)

    2017-07-15

    We evaluated the relationship between {sup 11}C-methionine PET ({sup 11}C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative {sup 11}C-METH PET were analysed. Semiquantitative evaluation of the {sup 11}C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). In all patients, the tumour was identified on {sup 11}C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. {sup 11}C-METH PET parameters are significantly correlated with histological grade and IDH1

  14. LIN28 is involved in glioma carcinogenesis and predicts outcomes of glioblastoma multiforme patients.

    Science.gov (United States)

    Qin, Rong; Zhou, Jingxu; Chen, Chao; Xu, Tao; Yan, Yong; Ma, Yushui; Zheng, Zongli; Shen, Yiping; Lu, Yicheng; Fu, Da; Chen, Juxiang

    2014-01-01

    LIN28, an evolutionarily conversed RNA binding protein which can bind to the terminal loops of let-7 family microRNA precursors and block their processing to maturation, is highly expressed in several subsets of tumors that carry poor prognoses, such as ovarian carcinoma, hepatocellular carcinoma, colon carcinoma and germ cell carcinoma. However, there has been no study on the expression of LIN28 in glioma tissues or their importance as a prognostic predictor of glioma patients. This study aimed to examine the expression of LIN28 in glioma and correlate the results to patient outcome. We found that LIN28 expression was significantly higher in the group of patients with a poor prognosis compared to patients with a good prognosis by gene microarray. Log-rank analysis showed patients with higher LIN28 expression level in tumor had a shorter progression-free survival and overall survival times compared to those with lower LIN28 expression level. Similar results were also obtained from the tissue microarray analysis. Univariate and multivariate analyses showed high LIN28 expression was an independent prognostic factor for a shorter progression-free survival and overall survival in GBM patients. Furthermore in vitro experiments showed that down-regulation of LIN28 in U251 and U373 cells caused cell cycle arrest in the G1 phase, delayed cell proliferation, increased apoptosis, and resulted in fewer colonies compared to controls. Summarily, our data provides a potential target for cancer therapy as an approach to overcome the poor options currently available for GBM patients.

  15. LIN28 is involved in glioma carcinogenesis and predicts outcomes of glioblastoma multiforme patients.

    Directory of Open Access Journals (Sweden)

    Rong Qin

    Full Text Available LIN28, an evolutionarily conversed RNA binding protein which can bind to the terminal loops of let-7 family microRNA precursors and block their processing to maturation, is highly expressed in several subsets of tumors that carry poor prognoses, such as ovarian carcinoma, hepatocellular carcinoma, colon carcinoma and germ cell carcinoma. However, there has been no study on the expression of LIN28 in glioma tissues or their importance as a prognostic predictor of glioma patients. This study aimed to examine the expression of LIN28 in glioma and correlate the results to patient outcome. We found that LIN28 expression was significantly higher in the group of patients with a poor prognosis compared to patients with a good prognosis by gene microarray. Log-rank analysis showed patients with higher LIN28 expression level in tumor had a shorter progression-free survival and overall survival times compared to those with lower LIN28 expression level. Similar results were also obtained from the tissue microarray analysis. Univariate and multivariate analyses showed high LIN28 expression was an independent prognostic factor for a shorter progression-free survival and overall survival in GBM patients. Furthermore in vitro experiments showed that down-regulation of LIN28 in U251 and U373 cells caused cell cycle arrest in the G1 phase, delayed cell proliferation, increased apoptosis, and resulted in fewer colonies compared to controls. Summarily, our data provides a potential target for cancer therapy as an approach to overcome the poor options currently available for GBM patients.

  16. Personalized care in neuro-oncology coming of age: why we need MGMT and 1p/19q testing for malignant glioma patients in clinical practice

    Science.gov (United States)

    Weller, Michael; Stupp, Roger; Hegi, Monika E.; van den Bent, Martin; Tonn, Joerg C.; Sanson, Marc; Wick, Wolfgang; Reifenberger, Guido

    2012-01-01

    Histological subtyping and grading by malignancy are the cornerstones of the World Health Organization (WHO) classification of tumors of the central nervous system. They shall provide clinicians with guidance as to the course of disease to be expected and the choices of treatment to be made. Nonetheless, patients with histologically identical tumors may have very different outcomes, notably in patients with astrocytic and oligodendroglial gliomas of WHO grades II and III. In gliomas of adulthood, 3 molecular markers have undergone extensive studies in recent years: 1p/19q chromosomal codeletion, O6-methylguanine methyltransferase (MGMT) promoter methylation, and mutations of isocitrate dehydrogenase (IDH) 1 and 2. However, the assessment of these molecular markers has so far not been implemented in clinical routine because of the lack of therapeutic implications. In fact, these markers were considered to be prognostic irrespective of whether patients were receiving radiotherapy (RT), chemotherapy, or both (1p/19q, IDH1/2), or of limited value because testing is too complex and no chemotherapy alternative to temozolomide was available (MGMT). In 2012, this situation has changed: long-term follow-up of the Radiation Therapy Oncology Group 9402 and European Organisation for Research and Treatment of Cancer 26951 trials demonstrated an overall survival benefit from the addition to RT of chemotherapy with procarbazine/CCNU/vincristine confined to patients with anaplastic oligodendroglial tumors with (vs without) 1p/19q codeletion. Furthermore, in elderly glioblastoma patients, the NOA-08 and the Nordic trial of RT alone versus temozolomide alone demonstrated a profound impact of MGMT promoter methylation on outcome by therapy and thus established MGMT as a predictive biomarker in this patient population. These recent results call for the routine implementation of 1p/19q and MGMT testing at least in subpopulations of malignant glioma patients and represent an encouraging

  17. 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.

  18. Ischemic stroke in patients with gliomas at The University of Texas-M.D. Anderson Cancer Center.

    Science.gov (United States)

    Kamiya-Matsuoka, Carlos; Cachia, David; Yust-Katz, Shlomit; Rodriguez, Yvo A; Garciarena, Pedro; Rodarte, Elsa M; Tremont-Lukats, Ivo W

    2015-10-01

    Patients with gliomas are at risk of cerebrovascular accidents (CVA) with potential consequences on survival, function, and local tumor control. Our objective was to provide information about CVA in patients with gliomas and to estimate survival in this group. We reviewed all adult glioma patients with ischemic CVA at the University of Texas-M.D. Anderson Cancer Center from 2003 through 2014. We extracted demographic, clinical, imaging, treatment and outcome data. We used descriptive summary data and estimated or compared survival rates where appropriate. 60 of 6500 patients (0.1%) with high-grade (HGG, n = 47) or low-grade glioma (LGG, n = 13) had ischemic CVA Thirty-two (53%) patients had postoperative strokes, and 20 (33%) had CVA after 2 weeks of surgery. Forty-one patients (68%) had gross total resection. For HGG and CVA, the poststroke median overall survival was 17 months versus 61 months in LGG and CVA (P = 0.03; hazard ratio (HR): 2.8; 95% CI 1.07-4.60). Survival stratified by modified Rankin Scale grade was significant (X(2) = 9.8, P = 0.007). Five patients received bevacizumab before stroke onset; none responded to antiangiogenic therapy. There was no stroke-related death. At our institution for 10 years, ischemic CVA in glioma patients was a rare complication, clearly associated in half of cases to surgery, and with a variable negative impact on performance status and neurologic function. In this group, patients with more neurological deficits lived less. The survival difference between and within subgroups was most likely due to tumor grade. More research is necessary to improve prevention of postoperative stroke in glioma patients.

  19. 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.

  20. Spontaneous speech of patients with gliomas in eloquent areas before and early after surgery.

    Science.gov (United States)

    Satoer, Djaina; Vincent, Arnaud; Smits, Marion; Dirven, Clemens; Visch-Brink, Evy

    2013-04-01

    Glioma patients often complain about problems in daily conversation. A detailed spontaneous speech analysis could provide more insight in these communicative problems; no previous studies are reported. To select sensitive parameters in spontaneous speech pre- and post-operatively in patients with gliomas in eloquent areas. We included 27 patients and 21 healthy controls. In addition to a naming and category fluency test, spontaneous speech was collected 1 month pre-operatively and 3 months post-operatively, and analysed with the variables: Self-corrections, Repetitions, Lexical Diversity, Incomplete Sentences and Mean Length of Utterance (MLUw). A correlation analysis was performed between the linguistic variables and tumour characteristics (grade, localisation and volume), treatment related factors, and between the linguistic variables and the language tasks. Pre-operatively, patients produced more Incomplete Sentences than the controls (p speech was influenced by tumour grade and localisation. There was no influence of tumour volume or treatment-related factors. Pre- and post-operatively, patients' performance on the naming and the fluency task deviated from normal (p speech, partly influenced by tumour characteristics. A spontaneous speech analysis appeared to be a valuable addition to standardised language tasks. Both measurements are important tools to obtain a complete linguistic profile.

  1. EPID-28. PROGNOSTIC AND PREDICTIVE BIOMARKERS IN RECURRENT WHO GRADE 3 GLIOMA PATIENTS TREATED WITH BEVACIZUMAB AND IRINOTECAN

    DEFF Research Database (Denmark)

    Toft, Anders; Urup, Thomas; Grunnet, Kirsten

    2016-01-01

    BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients. The prim......BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients....... The primary endpoint of this study was to identify predictive biomarkers associated with response to bevacizumab therapy. The secondary endpoint was to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS). METHODS: A total of 62 consecutive, recurrent grade 3...... glioma patients were administered bevacizumab and irinotecan between December 2005 andNovember 2014 according to a previously published clinical protocol.Awide range of clinical, histopathological and molecular factors were screened for significant correlation (p , 0.05) with response and survival...

  2. EPID-28. PROGNOSTIC AND PREDICTIVE BIOMARKERS IN RECURRENT WHO GRADE 3 GLIOMA PATIENTS TREATED WITH BEVACIZUMAB AND IRINOTECAN

    DEFF Research Database (Denmark)

    Toft, Anders; Urup, Thomas; Grunnet, Kirsten

    2015-01-01

    BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients. The prim......BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients....... The primary endpoint of this study was to identify predictive biomarkers associated with response to bevacizumab therapy. The secondary endpoint was to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS). METHODS: A total of 62 consecutive, recurrent grade 3...... glioma patients were administered bevacizumab and irinotecan between December 2005 andNovember 2014 according to a previously published clinical protocol.Awide range of clinical, histopathological and molecular factors were screened for significant correlation (p , 0.05) with response and survival...

  3. 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.

  4. {sup 18}F-fluoro-ethyl-tyrosine positron emission tomography for grading and estimation of prognosis in patients with intracranial gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Gempt, Jens, E-mail: jens.gempt@tum.de [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Bette, Stefanie; Ryang, Yu-Mi; Buchmann, Niels; Peschke, Patrick [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Pyka, Thomas; Wester, Hans-Jürgen; Förster, Stefan [Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany); Meyer, Bernhard; Ringel, Florian [Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675 München (Germany)

    2015-05-15

    Highlights: • The aim of the present study was to evaluate the use of {sup 18}F-FET-PET (FET-PET) for the grading and estimation of prognosis in newly diagnosed patients with intracranial gliomas in a clinical setting. • One hundred fifty-two patients (39 WHO II, 26 WHO III, 87 WHO IV) were included. The median T/N ratio of low-grade glioma patients was 1.65 (1.1–3.7), and 3.14 (1.61–8.1, p < 0.001) in high-grade glioma patients. • The test of the maximally selected log-rank statistic resulted in a T/N ratio of 1.88 as the cut-off value, with the greatest difference in overall survival between patients with longer and shorter survival. • Regarding the prognostic validity for overall survival ROC-curves display an AUC of 0.847 for the 48-month survival for T/N ratio and MRI contrast-enhancement. • Our study suggests that FET-PET can predict prognosis and survival in patients harboring intracranial gliomas. - Abstract: Introduction: Histopathological examination is the standard for grading and determination of diagnosis in intrinsic brain tumors though the possibility of malignization and tumor heterogeneity always bears the possibility of tumor under-grading or misjudgement regarding the estimation of prognosis. The aim of the present study was to evaluate the use of {sup 18}F-FET-PET (FET-PET) for the grading and estimation of prognosis in newly diagnosed patients with intracranial gliomas in a clinical setting. Methods: Patients who were treated for a newly diagnosed intracranial glioma between January 2007 and May 2012, and had a preoperative FET-PET and MRI scan between were included. The ratio of counts in a tumor VOI (volume of interest) with maximum uptake to the respective counts in a background VOI was calculated to provide the tumor-to-normal (T/N) ratio. The clinical and histopathological data (tumor grading, pre- and postoperative neurological status, Karnofsky Performance Status Scale scores, and overall survival rates) were recorded

  5. Identifying the association between contrast enhancement pattern, surgical resection, and prognosis in anaplastic glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yinyan; Jiang, Tao [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Capital Medical University, Beijing Neurosurgical Institute, Beijing (China); Wang, Kai; Li, Shaowu; Ma, Jun [Capital Medical University, Department of Neuroradiology, Beijing Tiantan Hospital, Beijing (China); Wang, Jiangfei [Capital Medical University, Department of Neurosurgery, Beijing Tiantan Hospital, Beijing (China); Dai, Jianping [Capital Medical University, Beijing Neurosurgical Institute, Beijing (China); Capital Medical University, Department of Neuroradiology, Beijing Tiantan Hospital, Beijing (China)

    2016-04-15

    Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs). Clinical data from 268 patients with histologically confirmed AGs were retrospectively analyzed. Contrast enhancement patterns were classified based on preoperative T1-contrast MR images. Univariate and multivariate analyses were performed to evaluate the prognostic value of MR enhancement patterns on progression-free survival (PFS) and overall survival (OS). The pattern of tumor contrast enhancement was associated with the extent of surgical resection in AGs. A gross total resection was more likely to be achieved for AGs with focal enhancement than those with diffuse (p = 0.001) or ring-like (p = 0.024) enhancement. Additionally, patients with focal-enhanced AGs had a significantly longer PFS and OS than those with diffuse (log-rank, p = 0.025 and p = 0.031, respectively) or ring-like (log-rank, p = 0.008 and p = 0.011, respectively) enhanced AGs. Furthermore, multivariate analysis identified the pattern of tumor enhancement as a significant predictor of PFS (p = 0.016, hazard ratio [HR] = 1.485) and OS (p = 0.030, HR = 1.446). Our results suggested that the contrast enhancement pattern on preoperative MR images was associated with the extent of resection and predictive of survival outcomes in AG patients. (orig.)

  6. 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...

  7. Central neurotoxicity of standard treatment in patients with newly-diagnosed high-grade glioma : a prospective longitudinal study

    NARCIS (Netherlands)

    Froklage, F E; Oosterbaan, L J; Sizoo, E M; de Groot, M; Bosma, I; Sanchez, E; Douw, L; Heimans, J J; Reijneveld, J C; Lagerwaard, F J; Buter, J; Uitdehaag, B M J; Klein, M; Postma, T J

    2014-01-01

    Following tumor resection, the majority of high-grade glioma (HGG) patients are treated with a combined modality regimen of radiotherapy and temozolomide. As a result of the tumor itself or as treatment-related neurotoxic side-effects, these patients may experience cognitive deficits. Additionally,

  8. 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.

  9. Retrospective Comparison of Chemoradiotherapy Followed by Adjuvant Chemotherapy, With or Without Prior Gliadel Implantation (Carmustine) After Initial Surgery in Patients With Newly Diagnosed High-Grade Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Noeel, Georges, E-mail: gnoel@strasbourg.fnclcc.fr [Radiation Oncology Department, Centre de lutte contre le cancer Paul Strauss, Strasbourg (France); Schott, Roland [Medical Oncology Department, Centre de lutte contre le cancer Paul Strauss, Strasbourg (France); Froelich, Sebastien [Neurosurgery Department, Hopital de Hautepierre, F-67098 Strasbourg (France); Gaub, Marie-Pierre [Pathology Department, Hopital de Hautepierre, F-67098 Strasbourg (France); Boyer, Patrick; Fischer-Lokou, David [Neurosurgery Department, Hopital de Hautepierre, F-67098 Strasbourg (France); Dufour, Patrick [Medical Oncology Department, Centre de lutte contre le cancer Paul Strauss, Strasbourg (France); Kehrli, Pierre; Maitrot, Daniel [Neurosurgery Department, Hopital de Hautepierre, F-67098 Strasbourg (France)

    2012-02-01

    Purpose: Retrospective study of patients treated for high-grade glioma, with or without biodegradable carmustine wafers and according to the Stupp protocol. Methods and Materials: Between May 2007 and June 2008, 65 patients underwent surgery for high-grade glioma, 28 had implantation of Gliadel and 37 patients did not. Patients received radiotherapy with concomitant temozolomide followed by 5 consecutive days of temozolomide every month for 6 months. Results: Overall median follow-up was 17.1 months; the median relapse-free survival (RFS) was 14 months with a RFS of 54% at 12 months, and 38% at 24 months. For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89). According to pathology, Gliadel did not influence RFS of patients with Grade III or glioblastoma. However, for all patients, in multivariate analysis, non-methylated methylguanine methyltransferase (MGMT) was the only unfavorable prognostic factor of RFS (p = 0.017; HR 2.8; CI [1.2-7]). Median overall survival (OS) was 20.8 months; the OS rate at 12 months was 78.5%, and at 24 months 35.4%. For patients treated with and without Gliadel, median and 1-year OS were 20.6 months and 78.6% vs. 20.8 months and 78.4%, respectively. According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma. For all patients, in multivariate analysis, unfavorable prognosticators for OS were non-methylated MGMT (p = 0.001; HR: 6.5; CI [2-20]) and irradiation dose <60 Gy (p = 0.02; HR: 6.3; CI [2-20]). With carmustine wafers, before irradiation, median gross tumor volume plus edema was 84 mL (27-229), whereas it was 68 mL (10-362) without carmustine (p = nonsignificant). Four cases of Grade 3 thrombopenia occurred, all in the carmustine wafer group. Conclusion: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival.

  10. 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

  11. Seizure characteristics and outcomes in 508 Chinese adult patients undergoing primary resection of low-grade gliomas: a clinicopathological study

    Science.gov (United States)

    You, Gan; Sha, Zhi-Yi; Yan, Wei; Zhang, Wei; Wang, Yong-Zhi; Li, Shao-Wu; Sang, Lin; Wang, Zi; Li, Gui-Lin; Li, Shou-Wei; Song, Yi-Jun; Kang, Chun-Sheng; Jiang, Tao

    2012-01-01

    Seizure is a common presenting manifestation and plays an important role in the clinical presentation and quality of life for patients with low-grade gliomas (LGGs). The authors set out to identify factors that influence preoperative seizure characteristics and postoperative seizure control. Cases involving adult patients who had undergone initial surgery for LGGs in a single institution between 2005 and 2009 were retrospectively reviewed. Univariate and multivariate logistic regression analyses were used to identify factors associated with preoperative seizures and postoperative seizure control. Of the 508 patients in the series, 350 (68.9%) presented with seizures. Age less than 38 years and cortical involvement of tumor were more likely to be associated with seizures (P = .003 and .001, respectively, multivariate logistic analysis). For the cohort of 350 patients with seizures, Engel classification was used to evaluate 6- and 12-month outcome after surgery: completely seizure free (Engel class I), 65.3% and 62.5%; not seizure free (Engel classes II, III, IV), 34.7% and 37.5%. After multivariate logistic analysis, favorable seizure prognosis was more common in patients with secondary generalized seizure (P = .006) and with calcification on MRI (.031). With respect to treatment-related variables, patients achieved much better seizure control after gross total resection than after subtotal resection (P seizure control in the patients with a history of seizure if overexpressed but was not a predictor for those without preoperative seizures. These factors may provide insight into developing effective treatment strategies aimed at prolonging patients' survival. PMID:22187341

  12. Toxicity profile of temozolomide in the treatment of 300 malignant glioma patients in Korea.

    Science.gov (United States)

    Bae, So Hyun; Park, Min-Jung; Lee, Min Mi; Kim, Tae Min; Lee, Se-Hoon; Cho, Sung Yun; Kim, Young-Hoon; Kim, Yu Jung; Park, Chul-Kee; Kim, Chae-Yong

    2014-07-01

    This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.

  13. A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma: North American Brain Tumor Consortium Study 03-03.

    Science.gov (United States)

    Iwamoto, Fabio M; Lamborn, Kathleen R; Kuhn, John G; Wen, Patrick Y; Yung, W K Alfred; Gilbert, Mark R; Chang, Susan M; Lieberman, Frank S; Prados, Michael D; Fine, Howard A

    2011-05-01

    Romidepsin, a potent histone deacetylase inhibitor, has shown activity in preclinical glioma models. The primary objectives of this trial were to determine the pharmacokinetics of romidepsin in patients with recurrent glioma on enzyme-inducing antiepileptic drugs (EIAEDs) and to evaluate the antitumor efficacy of romidepsin in patients with recurrent glioblastoma who were not receiving EIAEDs. Two dose cohorts were studied in the phase I component of the trial (13.3 and 17.7 mg/m(2)/d). Patients in the phase II component were treated with intravenous romidepsin at a dosage of 13.3 mg/m(2)/day on days 1, 8, and 15 of each 28-day cycle. Eight patients were treated on the phase I component. A similar romidepsin pharmacokinetic profile was demonstrated between patients receiving EIAEDs to those not receving EIAEDs. Thirty-five patients with glioblastoma were accrued to the phase II component. There was no objective radiographic response. The median progression-free survival (PFS) was 8 weeks and only 1 patient had a PFS time ≥6 months (PFS6 = 3%). To date, 34 patients (97%) have died, with a median survival duration of 34 weeks. Despite in vitro studies showing that romidepsin is primarily metabolized by CYP3A4, no decrease in exposure to romidepsin was seen in patients receiving potent CYP3A4 inducers. Romidepsin, at its standard dose and schedule, was ineffective for patients with recurrent glioblastomas. ClinicalTrials.gov identifier: NCT00085540.

  14. Preoperative Evaluation with fMRI of Patients with Intracranial Gliomas

    Directory of Open Access Journals (Sweden)

    Ioannis Z. Kapsalakis

    2012-01-01

    Full Text Available Introduction. Aggressive surgical resection constitutes the optimal treatment for intracranial gliomas. However, the proximity of a tumor to eloquent areas requires exact knowledge of its anatomic relationships to functional cortex. The purpose of our study was to evaluate fMRI’s accuracy by comparing it to intraoperative cortical stimulation (DCS mapping. Material and Methods. Eighty-seven patients, with presumed glioma diagnosis, underwent preoperative fMRI and intraoperative DCS for cortical mapping during tumor resection. Findings of fMRI and DCS were considered concordant if the identified cortical centers were less than 5 mm apart. Pre and postoperative Karnofsky Performance Scale and Spitzer scores were recorded. A postoperative MRI was obtained for assessing the extent of resection. Results. The areas of interest were identified by fMRI and DCS in all participants. The concordance between fMRI and DCS was 91.9% regarding sensory-motor cortex, 100% for visual cortex, and 85.4% for language. Data analysis showed that patients with better functional condition demonstrated higher concordance rates, while there also was a weak association between tumor grade and concordance rate. The mean extent of tumor resection was 96.7%. Conclusions. Functional MRI is a highly accurate preoperative methodology for sensory-motor mapping. However, in language mapping, DCS remains necessary for accurate localization.

  15. 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

  16. Withdrawal of antiepileptic drugs in glioma patients after long-term seizure freedom: design of a prospective observational study.

    Science.gov (United States)

    Koekkoek, Johan A F; Kerkhof, Melissa; Dirven, Linda; Heimans, Jan J; Postma, Tjeerd J; Vos, Maaike J; Bromberg, Jacoline E C; van den Bent, Martin J; Reijneveld, Jaap C; Taphoorn, Martin J B

    2014-08-15

    Epilepsy is common in patients with a glioma. Antiepileptic drugs (AEDs) are the mainstay of epilepsy treatment, but may cause side effects and may negatively impact neurocognitive functioning and quality of life. Besides antiepileptic drugs, anti-tumour treatment, which currently consists of surgery, radiotherapy and/or chemotherapy, may contribute to seizure control as well. In glioma patients with seizure freedom after anti-tumour therapy the question emerges whether AEDs should be continued, particularly in the case where anti-tumour treatment has been successful. We propose to explore the possibility of AED withdrawal in glioma patients with long-term seizure freedom after anti-tumour therapy and without signs of tumour progression. We initiate a prospective, observational study exploring the decision-making process on the withdrawal or continuation of AEDs in low-grade and anaplastic glioma patients with stable disease and prolonged seizure freedom after anti-tumour treatment, and the effects of AED withdrawal or continuation on seizure freedom. We recruit participants through the outpatient clinics of three tertiary referral centers for brain tumour patients in The Netherlands. The patient and the treating physician make a shared decision to either withdraw or continue AED treatment. Over a one-year period, we aim to include 100 glioma patients. We expect approximately half of the participants to be willing to withdraw AEDs. The primary outcome measures are: 1) the outcome of the shared-decision making on AED withdrawal or continuation, and decision related arguments, and 2) seizure freedom at 12 months and 24 months of follow-up. We will also evaluate seizure type and frequency in case of seizure recurrence, as well as neurological symptoms, adverse effects related to AED treatment or withdrawal, other anti-tumour treatments and tumour progression. This study addresses two issues that are currently unexplored. First, it will explore the willingness to

  17. MEK2 is a prognostic marker and potential chemo-sensitizing target for glioma patients undergoing temozolomide treatment.

    Science.gov (United States)

    He, Hua; Yao, Maojin; Zhang, Wenhao; Tao, Bangbao; Liu, Feili; Li, Shu; Dong, Yan; Zhang, Chenran; Meng, Yicheng; Li, Yuxin; Hu, Guohan; Luo, Chun; Zong, Hui; Lu, Yicheng

    2016-09-01

    Although temozolomide (TMZ) is the first-line chemotherapeutic agent for glioblastoma, it is often non-curative due to drug resistance. To overcome the resistance of glioblastoma cells to TMZ, it is imperative to identify prognostic markers for outcome prediction and to develop chemo-sensitizing agents. Here, the gene expression profiles of TMZ-resistant and TMZ-sensitive samples were compared by microarray analysis, and mitogen-activated protein kinase kinase 2 (MEK2) was upregulated specifically in resistant glioma cells but not in sensitive tumor cells or non-tumor tissues. Moreover, a comprehensive analysis of patient data revealed that the increased level of MEK2 expression correlated well with the advancement of glioma grade and worse prognosis in response to TMZ treatment. Furthermore, reducing the level of MEK2 in U251 glioma cell lines or xenografted glioma models through shRNA-mediated gene knockdown inhibited cell proliferation and enhanced the sensitivity of cells toward TMZ treatment. Further analysis of tumor samples from glioma patients by real-time PCR indicated that an increased MEK2 expression level was closely associated with the activation of many drug resistance genes. Finally, these resistance genes were downregulated after MEK2 was silenced in vitro, suggesting that the mechanism of MEK2-induced chemo-resistance could be mediated by the transcriptional activation of these resistance genes. Collectively, our data indicated that the expression level of MEK2 could serve as a prognostic marker for glioma chemotherapy and that MEK2 antagonists can be used as chemo-sensitizers to enhance the treatment efficacy of TMZ.

  18. 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.

  19. Cognitive and radiological effects of radiotherapy in patients with low-grade glioma : long-term follow-up

    NARCIS (Netherlands)

    Douw, Linda; Klein, Martin; Fagel, Selene S. A. A.; van den Heuvel, Josje; Taphoorn, Martin J. B.; Aaronson, Neil K.; Postma, Tjeerd J.; Vandertop, W. Peter; Mooij, Jacob J.; Boerman, Rudolf H.; Beute, Guus N.; Sluimer, Jasper D.; Slotman, Ben J.; Reijneveld, Jaap C.; Heimans, Jan J.

    2009-01-01

    Background Our previous study on cognitive functioning among 195 patients with low-grade glioma (LGG) a mean of 6 years after diagnosis suggested that the tumour itself, rather than the radiotherapy used to treat it, has the most deleterious effect on cognitive functioning; only high fraction dose r

  20. The end-of-life phase of high-grade glioma patients: dying with dignity?

    Science.gov (United States)

    Sizoo, Eefje M; Taphoorn, Martin J B; Uitdehaag, Bernard; Heimans, Jan J; Deliens, Luc; Reijneveld, Jaap C; Pasman, H Roeline W

    2013-01-01

    In the end-of-life (EOL) phase, high-grade glioma (HGG) patients have a high symptom burden and often lose independence because of physical and cognitive dysfunction. This might affect the patient's personal dignity. We aimed to (a) assess the proportion of HGG patients dying with dignity as perceived by their relatives and (b) identify disease and care factors correlated with dying with dignity in HGG patients. We approached relatives of a cohort of 155 deceased HGG patients for the study. Participants completed a questionnaire concerning the EOL phase of the patient, covering several subthemes: (a) symptoms and signs, (b) health-related quality of life, (c) decision making, (d) place and quality of EOL care, and (e) dying with dignity. Relatives of 81 patients participated and 75% indicated that the patient died with dignity. These patients had fewer communication deficits, experienced fewer transitions between health care settings in the EOL phase, and more frequently died at their preferred place of death. Relatives were more satisfied with the physician providing EOL care and reported that the physician adequately explained treatment options. Multivariate analysis identified satisfaction with the physician, the ability to communicate, and the absence of transitions between settings as most predictive of a dignified death. Physicians caring for HGG patients in the EOL phase should timely focus on explaining possible treatment options, because patients experience communication deficits toward death. Physicians should strive to allow patients to die at their preferred place and avoid transitions during the last month of life.

  1. 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

  2. Phase I/II Study of Temozolomide Plus Nimustine Chemotherapy for Recurrent Malignant Gliomas: Kyoto Neuro-oncology Group

    Science.gov (United States)

    AOKI, Tomokazu; ARAKAWA, Yoshiki; UEBA, Tetsuya; ODA, Masashi; NISHIDA, Namiko; AKIYAMA, Yukinori; TSUKAHARA, Tetsuya; IWASAKI, Koichi; MIKUNI, Nobuhiro; MIYAMOTO, Susumu

    2017-01-01

    The objective of this phase I/II study was to examine the efficacy and toxicity profile of temozolomide (TMZ) plus nimustine (ACNU). Patients who had received a standard radiotherapy with one or two previous chemo-regimens were enrolled. In phase I, the maximum-tolerated dose (MTD) by TMZ (150 mg/m2/day) (Day 1–5) plus various doses of ACNU (30, 35, 40, 45 mg/m2/day) (Day 15) per 4 weeks was defined on a standard 3 + 3 design. In phase II, these therapeutic activity and safety of this regimen were evaluated. Forty-nine eligible patients were enrolled. The median age was 50 years-old. Eighty percent had a KPS of 70–100. Histologies were glioblastoma (73%), anaplastic astrocytoma (22%), anaplastic oligodendroglioma (4%). In phase I, 15 patients were treated at four cohorts by TMZ plus ACNU. MTD was TMZ (150 mg/m2) plus ACNU (40 mg/m2). In phase II, 40 patients were treated at the dose of cohort 3 (MTD). Thirty-five percent of patients experienced grade 3 or 4 toxicities, mainly hematologic. The overall response rate was 11% (4/37). Sixty-eight percent (25/37) had stable disease. Twenty-two percent (8/37) showed progression. Progression-free survival (PFS) rates at 6 and 12 months were 24% (95% CI, 12–35%) and 8% (95% CI, 4–15%). Median PFS was 13 months (95% CI, 9.2–17.2 months). Overall survival (OS) at 6 and 12 were 78% (95% CI, 67–89%) and 49% (95% CI, 33–57%). Median OS was 11.8 months (95% CI, 8.2–14.5 months). This phase I/II study showed a moderate toxicity in hematology and may has a promising efficacy in OS, without inferiority in PFS. PMID:27725524

  3. Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas.

    Directory of Open Access Journals (Sweden)

    Anne L Baldock

    Full Text Available Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas.In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness.We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532 from gross total resection over subtotal/biopsy, while those with nodular (less diffuse tumors showed a significant benefit (P = 0.00142 with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors.These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection.

  4. ADVANCED MR IMAGING METHODS FOR PLANNING AND MONITORING RADIATION THERAPY IN PATIENTS WITH HIGH GRADE GLIOMA

    Science.gov (United States)

    Lupo, Janine M.; Nelson, Sarah J.

    2016-01-01

    This review explores how the integration of advanced imaging methods with high quality anatomic images significantly improves the characterization, target definition, assessment of response to therapy, and overall management of patients with high-grade glioma. Metrics derived from diffusion, perfusion, and susceptibility weighted MR imaging in conjunction with MR spectroscopic imaging, allows us to characterize regions of edema, hypoxia, increased cellularity, and necrosis within heterogeneous tumor and surrounding brain tissue. Quantification of such measures may provide a more reliable initial representation of tumor delineation and response to therapy than changes in the contrast enhancing or T2 lesion alone and have a significant impact on targeting resection, planning radiation, and assessing treatment effectiveness. In the long-term, implementation of these imaging methodologies can also aid in the identification of recurrent tumor and its differentiation from treatment-related confounds and facilitate the detection of radiation-induced vascular injury in otherwise normal appearing brain tissue. PMID:25219809

  5. 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 ...

  6. Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome

    National Research Council Canada - National Science Library

    Roessler, K; Donat, M; Lanzenberger, R; Novak, K; Geissler, A; Gartus, A; Tahamtan, A R; Milakara, D; Czech, T; Barth, M; Knosp, E; Beisteiner, R

    2005-01-01

    The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS...

  7. Brain volume perfusion CT performed with 128-detector row CT system in patients with cerebral gliomas: A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Xyda, Argyro [University Hospital of Goettingen, Department of Neuroradiology, Georg-August University, Goettingen (Germany); University Hospital of Heraklion, Department of Radiology, Crete (Greece); Haberland, Ulrike; Klotz, Ernst [Computed Tomography, Siemens AG Healthcare Sector, Forchheim (Germany); Bock, Hans Christoph [University Hospital of Goettingen, Department of Neurosurgery, Georg-August University, Goettingen (Germany); Jung, Klaus [University Hospital of Goettingen, Department of Medical Statistics, Georg-August University, Goettingen (Germany); Knauth, Michael; Schramm, Ramona; Psychogios, Marios Nikos; Schramm, Peter [University Hospital of Goettingen, Department of Neuroradiology, Georg-August University, Goettingen (Germany); Erb, Gunter [Bracco Imaging Deutschland GmbH, Konstanz (Germany)

    2011-09-15

    Validation of the feasibility and efficacy of volume perfusion computed tomography (VPCT) in the preoperative assessment of cerebral gliomas by applying a 128-slice CT covering the entire tumour. Forty-six patients (25 men, 21 women; mean age 52.8 years) with cerebral gliomas were evaluated with VPCT. Two readers independently evaluated VPCT data, drawing volumes of interest (VOIs) around the tumour according to maximum intensity projection volumes, which were mapped automatically onto the cerebral blood volume (CBV), flow (CBF) and permeability (Ktrans) perfusion datasets. As control, a second VOI was placed in the contralateral healthy cortex. Correlation among perfusion parameters, tumour grade, hemisphere and VOIs was assessed. The diagnostic power of perfusion parameters was analysed by receiver operating characteristics curve analyses. VPCT was feasible in the assessment of the entire tumour extent. Mean values of Ktrans, CBV, CBF in high-grade gliomas were significantly higher compared with low-grade (p < 0.01). Ktrans demonstrated the highest diagnostic (97% sensitivity), positive (100%) and negative (94%) prognostic values. VPCT was feasible in all subjects. All areas of different perfusion characteristics are depicted and quantified in colour-coded 3D maps. The derived parameters correlate well with tumour histopathology, differentiating low- from high-grade gliomas. (orig.)

  8. 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

  9. High-grade glioma in elderly patients: can the oncogeriatrician help?

    Directory of Open Access Journals (Sweden)

    Tabouret E

    2013-12-01

    Full Text Available Emeline Tabouret,1 Louis Tassy,2 Olivier Chinot,1 ElodieCrétel,3 Frederique Retornaz,4 Frederique Rousseau5 1Department of Neuro-oncology, Timone Hospital, Marseille, France; 2Department of Medical Oncology, Centre Léon Bérard, Lyon, France; 3Transveral Oncogeriatric Unit, University Hospital Timone, Marseille, France; 4Departmental Gerontologic Center, Marseille, France; 5Department of Medical Oncology, Institut Paoli Calmettes, Marseille, France Abstract: Gliomas are the most frequent primary brain tumors in adults. As the population ages in Western countries, the number of people being diagnosed with glioblastoma is expected to increase. Clinical management of elderly patients with primary brain tumors is difficult, owing to multiple comorbidities, polypharmacy, decreased tolerance to chemotherapy, and an increased risk of radiation-induced neurotoxicity. A few specific randomized studies have shown a benefit for radiotherapy in elderly patients with good performance status. For patients with poor performance status, chemotherapy (temozolomide has been shown to be associated with prolonged duration of response. Patients with methylated O6-alkylguanine deoxyribonucleic acid alkyltransferase promoter seem to have better outcomes. Oncogeriatrics proposes the geriatric evaluation of elderly patients to improve therapeutic choices and optimize the management of treatment toxicities and comorbidities. Keywords: brain tumor, older cancer patient, chemotherapy toxicity, oncogeriatric charter

  10. Immunohistochemical profiles of IDH1, MGMT and P53: practical significance for prognostication of patients with diffuse gliomas.

    Science.gov (United States)

    Ogura, Ryosuke; Tsukamoto, Yoshihiro; Natsumeda, Manabu; Isogawa, Mizuho; Aoki, Hiroshi; Kobayashi, Tsutomu; Yoshida, Seiichi; Okamoto, Kouichiro; Takahashi, Hitoshi; Fujii, Yukihiko; Kakita, Akiyoshi

    2015-08-01

    Genetic and epigenetic status, including mutations of isocitrate dehydrogenase (IDH) and TP53 and methylation of O(6) -methylguanine-DNA methyltransferase (MGMT), are associated with the development of various types of glioma and are useful for prognostication. Here, using routinely available histology sections from 312 patients with diffuse gliomas, we performed immunohistochemistry using antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53 expression to evaluate the possible prognostic significance of these features. With regard to overall survival (OS), univariate analysis indicated that an IDH1-positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative profile in patients with GBM and AA were significantly associated with a favorable outcome. Multivariate analysis revealed that both profiles were independent factors influencing prognosis. The OS of patients with IDH1-positive/MGMT-negative profiles was significantly longer than that of patients with negative/negative and negative/positive profiles. A p53 profile was not an independent prognostic factor. However, for GBM/AA patients with IDH1-negative/MGMT-negative profiles, p53 overexpression was significantly associated with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT and p53 profiles may be useful for prognostication of GBM/AA.

  11. Cannabinoid receptor CB1 regulates STAT3 activity and its expression dictates the responsiveness to SR141716 treatment in human glioma patients' cells.

    Science.gov (United States)

    Ciaglia, Elena; Torelli, Giovanni; Pisanti, Simona; Picardi, Paola; D'Alessandro, Alba; Laezza, Chiara; Malfitano, Anna Maria; Fiore, Donatella; Pagano Zottola, Antonio Christian; Proto, Maria Chiara; Catapano, Giuseppe; Gazzerro, Patrizia; Bifulco, Maurizio

    2015-06-20

    Herein we show that a majority of human brain tumor samples and cell lines over-expressed cannabinoid receptor CB1 as compared to normal human astrocytes (NHA), while uniformly expressed low levels of CB2. This finding prompted us to investigate the therapeutic exploitation of CB1 inactivation by SR141716 treatment, with regard to its direct and indirect cell-mediated effects against gliomas. Functional studies, using U251MG glioma cells and primary tumor cell lines derived from glioma patients expressing different levels of CB1, highlighted SR141716 efficacy in inducing apoptosis via G1 phase stasis and block of TGF-β1 secretion through a mechanism that involves STAT3 inhibition. According to the multivariate role of STAT3 in the immune escape too, interestingly SR141716 lead also to the functional and selective expression of MICA/B on the surface of responsive malignant glioma cells, but not on NHA. This makes SR141716 treated-glioma cells potent targets for allogeneic NK cell-mediated recognition through a NKG2D restricted mechanism, thus priming them for NK cell antitumor reactivity. These results indicate that CB1 and STAT3 participate in a new oncogenic network in the complex biology of glioma and their expression levels in patients dictate the efficacy of the CB1 antagonist SR141716 in multimodal glioma destruction.

  12. 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.

  13. The histone deacetylase SIRT6 suppresses the expression of the RNA-binding protein PCBP2 in glioma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xin; Hao, Bin; Liu, Ying; Dai, Dongwei; Han, Guosheng; Li, Yanan; Wu, Xi; Zhou, Xiaoping; Yue, Zhijian; Wang, Laixing; Cao, Yiqun, E-mail: yiquancao@sohu.com; Liu, Jianmin, E-mail: jianminliuchh@163.com

    2014-03-28

    Highlights: • PCBP2 expression is over-expressed in human glioma tissues and cell lines. • SIRT6 is decreased in glioma and correlated with PCBP2. • SIRT6 inhibits PCBP2 expression by deacetylating H3K9. • SIRT6 inhibits glioma growth in vitro and in vivo. - Abstract: More than 80% of tumors that occur in the brain are malignant gliomas. The prognosis of glioma patients is still poor, which makes glioma an urgent subject of cancer research. Previous evidence and our present data show that PCBP2 is over-expressed in human glioma tissues and predicts poor outcome. However, the mechanism by which PCBP2 is regulated in glioma remains elusive. We find that SIRT6, one of the NAD{sup +}-dependent class III deacetylase SIRTUINs, is down-regulated in human glioma tissues and that the level of SIRT6 is negatively correlated with PCBP2 level while H3K9ac enrichment on the promoter of PCBP2 is positively correlated with PCBP2 expression. Furthermore, we identify PCBP2 as a target of SIRT6. We demonstrate that PCBP2 expression is inhibited by SIRT6, which depends upon deacetylating H3K9ac. Finally, our results reveal that SIRT6 inhibits glioma cell proliferation and colony formation in vitro and glioma cell growth in vivo in a PCBP2 dependent manner. In summary, our findings implicate that SIRT6 inhibits PCBP2 expression through deacetylating H3K9ac and SIRT6 acts as a tumor suppressor in human glioma.

  14. Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor grade and patient survival in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Pyka, Thomas; Hiob, Daniela; Wester, Hans-Juergen [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [Klinikum Rechts der Isar der TU Muenchen, Neurosurgic Department, Munich (Germany); Schlegel, Juergen [Klinikum Rechts der Isar der TU Muenchen, Institute of Pathology and Neuropathology, Munich (Germany); Bette, Stefanie [Klinikum Rechts der Isar der TU Muenchen, Neuroradiologic department, Munich (Germany); Foerster, Stefan [Klinikum Rechts der Isar der TU Muenchen, Department of Nuclear Medicine, Munich (Germany); Klinikum Rechts der Isar der TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Munich (Germany)

    2016-01-15

    Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L-tyrosine (FET) is well established in the diagnostic work-up of malignant brain tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been shown to be highly valuable for the detection of viable hypermetabolic brain tumor tissue; however, it has not proven equally useful for tumor grading. Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a method to quantify the heterogeneity of glucose metabolism in a variety of tumor entities. Herein we evaluate whether textural FET-PET features are of utility for grading and prognostication in patients with high-grade gliomas. One hundred thirteen patients (70 men, 43 women) with histologically proven high-grade gliomas were included in this retrospective study. All patients received static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric parameters and textural parameters based on gray-level neighborhood difference matrices were derived from static FET-PET images. Receiver operating characteristic (ROC) and discriminant function analyses were used to assess the value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox regression were employed for analysis of progression-free and overall survival. All FET-PET textural parameters showed the ability to differentiate between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC 0.775). Further improvement in discriminatory power was possible through a combination of texture and metabolic tumor volume, classifying 85 % of tumors correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with tumor grade, but showed lower AUC values (0.644 and 0.710, respectively). Furthermore, a correlation of FET-PET texture but not TBR was shown with patient PFS and OS, proving significant in multivariate analysis as well. Volumetric parameters were predictive for OS, but this correlation did not

  15. Atypical nuclear localization of VIP receptors in glioma cell lines and patients

    Energy Technology Data Exchange (ETDEWEB)

    Barbarin, Alice; Séité, Paule [Equipe Récepteurs, Régulations et Cellules Tumorales, Université de Poitiers, PBS bât 36, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9 (France); Godet, Julie [Laboratoire d’anatomie et de cytologie pathologiques, CHU de Poitiers, 2 rue de la Milétrie, 86000 Poitiers (France); Bensalma, Souheyla; Muller, Jean-Marc [Equipe Récepteurs, Régulations et Cellules Tumorales, Université de Poitiers, PBS bât 36, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9 (France); Chadéneau, Corinne, E-mail: corinne.chadeneau@univ-poitiers.fr [Equipe Récepteurs, Régulations et Cellules Tumorales, Université de Poitiers, PBS bât 36, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9 (France)

    2014-11-28

    Highlights: • The VIP receptor VPAC1 contains a putative NLS signal. • VPAC1 is predominantly nuclear in GBM cell lines but not VPAC2. • Non-nuclear VPAC1/2 protein expression is correlated with glioma grade. • Nuclear VPAC1 is observed in 50% of stage IV glioma (GBM). - Abstract: An increasing number of G protein-coupled receptors, like receptors for vasoactive intestinal peptide (VIP), are found in cell nucleus. As VIP receptors are involved in the regulation of glioma cell proliferation and migration, we investigated the expression and the nuclear localization of the VIP receptors VPAC1 and VPAC2 in this cancer. First, by applying Western blot and immunofluorescence detection in three human glioblastoma (GBM) cell lines, we observed a strong nuclear staining for the VPAC1 receptor and a weak nuclear VPAC2 receptor staining. Second, immunohistochemical staining of VPAC1 and VPAC2 on tissue microarrays (TMA) showed that the two receptors were expressed in normal brain and glioma tissues. Expression in the non-nuclear compartment of the two receptors significantly increased with the grade of the tumors. Analysis of nuclear staining revealed a significant increase of VPAC1 staining with glioma grade, with up to 50% of GBM displaying strong VPAC1 nuclear staining, whereas nuclear VPAC2 staining remained marginal. The increase in VPAC receptor expression with glioma grades and the enhanced nuclear localization of the VPAC1 receptors in GBM might be of importance for glioma progression.

  16. The Clinical Significance of Ependymal Enhancement at Presentation in Patients with Malignant Glioma

    Science.gov (United States)

    Kaidar-Person, Orit; Darawshe, Firas; Tzuk-Shina, Tzahala; Eran, Ayelet

    2015-01-01

    Introduction The current study evaluated the rate of ependymal enhancement and whether its presence influences survival of patients with malignant glioma (GBM). Methods A retrospective review of all patients who were treated in our institution from 2005 to 2011 was conducted. Data extracted from the medical records included age, date of diagnosis, co-morbidities, treatment regimen, and time of death. Magnetic resonance images (MRI) were evaluated for the presence of ependymal enhancement and its extent, and the correlation to survival was investigated. Results Between 2005 and 2011, 230 patients were treated for GBM. Eighty-nine patients were excluded from the study due to insufficient data, leaving 141 patients for analysis. Median age at diagnosis was 60 years. Sixty-seven (40.6%) patients had evidence of ependymal enhancement on MRI (group A), and 70 (42.4%) patients did not have evidence of enhancement. The assessment of ependymal enhancement was inconclusive due to mass effect and ventricular compression that precluded accurate assessment for 28 (17%) patients (group C). Median survival was 14 months for group A (range, 12–16 months), 15.9 months for group B (range, 14.28–17.65 months), and 11.7 months for group C (range, 6.47–16.92 months) (P>0.05). A multivariate analysis to predict survival indicated that male gender (P=0.039), hypertension (P=0.012), and biopsy only compared to complete gross tumor resection (P=0.001) were significant for poor survival. Conclusions Pretreatment ependymal enhancement on MRI was not found to be associated with poorer survival. These results might be due to better treatments options compared to prior reports. PMID:26886770

  17. The Clinical Significance of Ependymal Enhancement at Presentation in Patients with Malignant Glioma

    Directory of Open Access Journals (Sweden)

    Orit Kaidar-Person

    2015-10-01

    Full Text Available Introduction. The current study evaluated the rate of ependymal enhancement and whether its presence influences survival of patients with malignant glioma (GBM. Methods. A retrospective review of all patients who were treated in our institution from 2005 to 2011 was conducted. Data extracted from the medical records included age, date of diagnosis, co-morbidities, treatment regimen, and time of death. Magnetic resonance images (MRI were evaluated for the presence of ependymal enhancement and its extent, and the correlation to survival was investigated. Results. Between 2005 and 2011, 230 patients were treated for GBM. Eighty-nine patients were excluded from the study due to insufficient data, leaving 141 patients for analysis. Median age at diagnosis was 60 years. Sixty-seven (40.6% patients had evidence of ependymal enhancement on MRI (group A, and 70 (42.4% patients did not have evidence of enhancement. The assessment of ependymal enhancement was inconclusive due to mass effect and ventricular compression that precluded accurate assessment for 28 (17% patients (group C. Median survival was 14 months for group A (range, 12–16 months, 15.9 months for group B (range, 14.28–17.65 months, and 11.7 months for group C (range, 6.47–16.92 months (P>0.05. A multivariate analysis to predict survival indicated that male gender (P=0.039, hypertension (P=0.012, and biopsy only compared to complete gross tumor resection (P=0.001 were significant for poor survival. Conclusions. Pretreatment ependymal enhancement on MRI was not found to be associated with poorer survival. These results might be due to better treatments options compared to prior reports.

  18. Quality of life in low-grade glioma patients receiving temozolomide

    Science.gov (United States)

    Liu, Raymond; Solheim, Karla; Polley, Mei-Yin; Lamborn, Kathleen R.; Page, Margaretta; Fedoroff, Anne; Rabbitt, Jane; Butowski, Nicholas; Prados, Michael; Chang, Susan M.

    2009-01-01

    The purpose of this study was to describe the quality of life (QOL) of low-grade glioma (LGG) patients at baseline prior to chemotherapy and through 12 cycles of temozolomide (TMZ) chemotherapy. Patients with histologically confirmed LGG with only prior surgery were given TMZ for 12 cycles. QOL assessments by the Functional Assessment of Cancer Therapy–Brain (FACT-Br) were obtained at baseline prior to chemotherapy and at 2-month intervals while receiving TMZ. Patients with LGG at baseline prior to chemotherapy had higher reported social well-being scores (mean difference = 5.0; p < 0.01) but had lower reported emotional well-being scores (mean difference = 2.2; p < 0.01) compared to a normal population. Compared to patients with left hemisphere tumors, patients with right hemisphere tumors reported higher physical well-being scores (p = 0.01): 44% could not drive, 26% did not feel independent, and 26% were afraid of having a seizure. Difficulty with work was noted in 24%. Mean change scores at each chemotherapy cycle compared to baseline for all QOL subscales showed either no significant change or were significantly positive (p < 0.01). Patients with LGG on TMZ at baseline prior to chemotherapy reported QOL comparable to a normal population with the exception of social and emotional well-being, and those with right hemisphere tumors reported higher physical well-being scores compared to those with left hemisphere tumors. While remaining on therapy, LGG patients were able to maintain their QOL in all realms. LGG patients’ QOL may be further improved by addressing their emotional well-being and their loss of independence in terms of driving or working. PMID:18713953

  19. Upregulation of miR-183 expression and its clinical significance in human brain glioma.

    Science.gov (United States)

    Ye, Zhennan; Zhang, Zihuan; Wu, Lingyun; Liu, Cegang; Chen, Qiang; Liu, Jingpeng; Wang, Xiaoliang; Zhuang, Zong; Li, Wei; Xu, Shanshui; Hang, Chunhua

    2016-08-01

    Glioma is the most common type of primary malignant tumor in the central nervous system (CNS) with a high incidence and a high mortality rate, as well as an extremely low 5-year survival rate. As a class of small non-coding RNAs, microRNAs (miRNAs) may be closely involved in carcinogenesis and might also be connected with glioma diagnosis and prognosis. In this study, we aimed at investigating the expression level of microRNA-183 (miR-183) in 105 cases of glioma tissues of four World Health Organization (WHO) grades and 10 cases of normal brain tissues and its potential predictive and prognostic values in glioma. We found that the expression levels of miR-183 were significantly higher in glioma tissues than that in normal brain tissues, and also higher in high-grade gliomas (WHO grade III and IV) compared with low-grade gliomas (WHO grade I and II). The miR-183 expression level was classified as low or high according to the median value. High expression of miR-183 was found to significantly correlate with larger tumor size, higher WHO grade, and worse Karnofsky performance score (KPS). Kaplan-Meier survival analysis showed that patients with high miR-183 expression had worse overall survival (OS) and progression-free survival (PFS) than patients with low miR-183 expression. Moreover, univariate and multivariate analyses indicated that miR-183 expression level was an independent prognostic parameter of a patient's OS and PFS. In conclusion, our study indicated that miR-183 was upregulated in glioma, and that it may be used as a potential biomarker of poor prognosis in patients with glioma.

  20. NI-79RAPID ASSESSMENT OF LESION VOLUMES FOR PATIENTS WITH GLIOMA USING THE SMARTBRUSH SOFTWARE PACKAGE

    Science.gov (United States)

    Vaziri, Sana; Lafontaine, Marisa; Olson, Beck; Crane, Jason C.; Chang, Susan; Lupo, Janine; Nelson, Sarah J.

    2014-01-01

    The increasing interest in enhancing the RANO criteria by using quantitative assessments of changes in lesion size and image intensities has highlighted the need for rapid, easy-to-use tools that provide DICOM compatible outputs for evaluation of patients with glioma. To evaluate the performance of the SmartBrush software (Brainlab AG), which provides computer-assisted definitions of regions of interest (ROIs), a cohort of 20 patients with glioma (equal number having high and low grade and treated and un-treated) were scanned using a 3T whole-body MR system prior to surgical resection. The T2-weighted FLAIR, pre- and post-contrast T1-weighted gradient echo DICOM images were pushed from the scanner to an offline workstation where analysis of lesion volumes was performed using SmartBrush. Volumes of the T2Ls ranged from 7.9 to 110.2cm3 and the volumes of the CELs was 0.1 to 28.5 cm3 with 19/20 of the subjects having CELs and all 20 having T2Ls. the computer-assisted analysis was performed rapidly and efficiently, with the mean time for defining both lesions per subject was 5.77 (range 3.5 to 7.5) minutes. Prior analysis of ROIS with the SLICER package (www.slicer.org) took approximately 30 minutes/subject. SmartBrush provides lesion volumes and cross-sectional diameter as a PDF report, which can be stored in DICOM. The ROIs were also saved as DICOM objects and transferred to other packages for performing histogram analysis from ADC or other functional parameter maps. Ongoing studies that will be reported in this presentation are performing a similar analysis with multiple users in order to compare the relative intra- and inter-operator variations in terms of both the speed of analysis and the ROIs that are identified. Acknowledgements: The authors would like to acknowledge Rowena Thomson and Natalie Wright from Brainlab for helping to set up this study.

  1. Association between small heat shock protein B11 and the prognostic value of MGMT promoter methylation in patients with high-grade glioma.

    Science.gov (United States)

    Cheng, Wen; Li, Mingyang; Jiang, Yang; Zhang, Chuanbao; Cai, Jinquan; Wang, Kuanyu; Wu, Anhua

    2016-07-01

    OBJECT This study investigated the role and prognostic value of heat shock proteins (HSPs) in glioma. METHODS Data from 3 large databases of glioma samples (Chinese Glioma Genome Atlas, Repository for Molecular Brain Neoplasia Data, and GSE16011), which contained whole-genome messenger RNA microarray expression data and patients' clinical data, were analyzed. Immunohistochemical analysis was performed to validate protein expression in another set of 50 glioma specimens. RESULTS Of 28 HSPs, 11 were overexpressed in high-grade glioma (HGG) compared with low-grade glioma. A univariate Cox analysis revealed that HSPB11 has significant prognostic value for each glioma grade, which was validated by a Kaplan-Meier survival analysis. HSPB11 expression was associated with poor prognosis and was independently correlated with overall survival (OS) in HGG. This study further explored the combined role of HSPB11 and other molecular markers in HGG, such as isocitrate dehydrogenase 1 (IDH1) mutation and O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. HSPB11 expression was able to refine the prognostic value of IDH1 mutation in patients with HGG. However, when combined with MGMT promoter methylation status, among patients with a methylated MGMT promoter, those with lower levels of HSPB11 expression had longer OS and progression-free survival than patients with higher levels of HSPB11 expression or with an unmethylated MGMT promoter. Moreover, within the MGMT promoter methylation group, patients with low levels of HSPB11 expression were more sensitive to combined radiochemotherapy than those with high levels of HSPB11 expression, which may explain why some patients with HGG with a methylated MGMT promoter show tolerance to radiochemotherapy. CONCLUSIONS HSPB11 was identified as a novel prognostic marker in patients with HGG. Together with MGMT promoter methylation status, HSPB11 expression can predict outcome for patients with HGG and identify those who

  2. WAIS-III and WMS-III profiles of mildly to severely brain-injured patients.

    Science.gov (United States)

    Fisher, D C; Ledbetter, M F; Cohen, N J; Marmor, D; Tulsky, D S

    2000-01-01

    Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-III (WMS-III; The Psychological Corporation, 1997) scores of patients with mild traumatic brain injury (MTBI, n = 23) to moderate-severe traumatic brain injury (M-S TBI, n = 22) were compared to those of 45 matched normal control patients. WAIS-III results revealed that IQ and index scores of MTBI patients did not significantly differ from those of controls, whereas M-S TBI patients received significantly lower mean scores on all measures. All M-S TBI patients' WMS-III index scores also revealed significantly lower scores in comparison to those of control participants, with the exception of Delayed Auditory Recognition. MTBI patients showed significantly lower mean index scores compared to normal controls on measures of immediate and delayed auditory memory, immediate memory, visual delayed memory, and general memory. Eta-squared analyses revealed that WMS-III visual indexes and WAIS-III processing speed showed particularly large effect sizes. These results suggest that symptomatic MTBI patients obtain some low WMS-III test scores comparable to those of more severely injured patients.

  3. Rare synchronous association of vestibular schwannoma and indolent insular oligodendroglioma in a patient without neurofibromatosis: controversial issue of timing for surgical treatment of asymptomatic low-grade gliomas.

    Science.gov (United States)

    Iacoangeli, Maurizio; Di Rienzo, Alessandro; Colasanti, Roberto; Alvaro, Lorenzo; Nocchi, Niccolò; Polonara, Gabriele; Di Somma, Lucia Giovanna Maria; Zizzi, Antonio; Scarpelli, Marina; Scerrati, Massimo

    2012-01-01

    The co-occurrence of a vestibular schwannoma and a low-grade glioma is rare, and even rarer is the association with an oligodendroglioma. Although various authors have addressed the problem of treating patients with incidentally discovered indolent low-grade gliomas, an established protocol does not exist to date. The common approach is to reserve surgery until there is radiological evidence of tumor growth or high-grade transformation. However, because incidental low-grade glioma may represent the first stage of unavoidable pathological progression towards high-grade glioma, early and radical surgical resection should be advocated in order to increase the chance of a "cure" and prolonged survival. This case report supports this view, and suggests reflection on a possible change from a conservative philosophy to preventative surgical treatment.

  4. Rare synchronous association of vestibular schwannoma and indolent insular oligodendroglioma in a patient without neurofibromatosis: controversial issue of timing for surgical treatment of asymptomatic low-grade gliomas

    Science.gov (United States)

    Iacoangeli, Maurizio; Di Rienzo, Alessandro; Colasanti, Roberto; Alvaro, Lorenzo; Nocchi, Niccolò; Polonara, Gabriele; Di Somma, Lucia Giovanna Maria; Zizzi, Antonio; Scarpelli, Marina; Scerrati, Massimo

    2012-01-01

    The co-occurrence of a vestibular schwannoma and a low-grade glioma is rare, and even rarer is the association with an oligodendroglioma. Although various authors have addressed the problem of treating patients with incidentally discovered indolent low-grade gliomas, an established protocol does not exist to date. The common approach is to reserve surgery until there is radiological evidence of tumor growth or high-grade transformation. However, because incidental low-grade glioma may represent the first stage of unavoidable pathological progression towards high-grade glioma, early and radical surgical resection should be advocated in order to increase the chance of a “cure” and prolonged survival. This case report supports this view, and suggests reflection on a possible change from a conservative philosophy to preventative surgical treatment. PMID:23180968

  5. Notch signaling contributes to the maintenance of both normal neural stem cells and patient-derived glioma stem cells

    Directory of Open Access Journals (Sweden)

    Fu Luo-An

    2011-02-01

    Full Text Available Abstract Background Cancer stem cells (CSCs play an important role in the development and recurrence of malignant tumors including glioma. Notch signaling, an evolutionarily conserved pathway mediating direct cell-cell interaction, has been shown to regulate neural stem cells (NSCs and glioma stem cells (GSCs in normal neurogenesis and pathological carcinogenesis, respectively. However, how Notch signaling regulates the proliferation and differentiation of GSCs has not been well elucidated. Methods We isolated and cultivate human GSCs from glioma patient specimens. Then on parallel comparison with NSCs, we inhibited Notch signaling using γ-secretase inhibitors (GSI and assessed the potential functions of Notch signaling in human GSCs. Results Similar to the GSI-treated NSCs, the number of the primary and secondary tumor spheres from GSI-treated GSCs decreased significantly, suggesting that the proliferation and self-renewal ability of GSI-treated GSCs were attenuated. GSI-treated GSCs showed increased differentiation into mature neural cell types in differentiation medium, similar to GSI-treated NSCs. Next, we found that GSI-treated tumor spheres were composed of more intermediate progenitors instead of CSCs, compared with the controls. Interestingly, although inhibition of Notch signaling decreased the ratio of proliferating NSCs in long term culture, we found that the ratio of G2+M phase-GSCs were almost undisturbed on GSI treatment within 72 h. Conclusions These data indicate that like NSCs, Notch signaling maintains the patient-derived GSCs by promoting their self-renewal and inhibiting their differentiation, and support that Notch signal inhibitor GSI might be a prosperous candidate of the treatment targeting CSCs for gliomas, however, with GSI-resistance at the early stage of GSCs cell cycle.

  6. Clustering of mutations in the 5' tertile of the NF1 gene in Slovakia patients with optic pathway glioma.

    Science.gov (United States)

    Bolcekova, A; Nemethova, M; Zatkova, A; Hlinkova, K; Pozgayova, S; Hlavata, A; Kadasi, L; Durovcikova, D; Gerinec, A; Husakova, K; Pavlovicova, Z; Holobrada, M; Kovacs, L; Ilencikova, D

    2013-01-01

    Optic pathway gliomas (OPG) occur in 15% of patients with neurofibromatosis type 1 (NF1; OMIM 162200). Genotype-phenotype correlations in patients with NF1 may help to determine the risk group for developing complications such as OPG in coincidence with other NF1.features. We evaluated 52 patients with NF1 (25 with OPG and 27 without OPG). All subjects underwent a clinical examination focused on neurofibromatosis type 1 and molecular diagnostics of NF1 gene using protocol based on RNA analysis confirming the diagnosis of NF1. In the group with OPG patients, there was a significantly higher incidence of freckling (P=0.017), neurofibromatosis bright objects (NBO) (P=0.0038), compared to the group without OPG. The differences between the groups with respect to Lisch nodules were on the borderline of statistical significance (P=0.088). The frequency of neurofibromas in the group with OPG was not significant (P=0.9). From all patients with the mutation localized in the first tertile of the NF1 gene majority (71%) had optic glioma compared to individuals who didn't have the OPG 29% (P=0.0049). Our results present the clustering of mutations in the 5'tertile of NF1 gene in patients with optic nerve glioma and suggest higher incidence of freckling and neurofibromatosis brain objects in these patients. Molecular analysis of NF1 gene is important part in complex management of NF1 patients and contributes to a better understanding of clinical picture of NF1 patients. .

  7. 68Ga-NOTA-Aca-BBN(7–14) PET/CT in Healthy Volunteers and Glioma Patients

    Science.gov (United States)

    Zhang, Jingjing; Li, Deling; Lang, Lixin; Zhu, Zhaohui; Wang, Ling; Wu, Peilin; Niu, Gang; Li, Fang; Chen, Xiaoyuan

    2017-01-01

    This work was designed to study the safety, biodistribution, and radiation dosimetry of a gastrin-releasing peptide receptor (GRPR)– targeting, 68Ga-labeled bombesin (BBN) peptide derivative PET tracer, NOTA-Aca-BBN(7–14) (denoted as 68Ga-BBN) in healthy volunteers and to assess the level of receptor expression in glioma patients. Methods Four healthy volunteers (2 male and 2 female) underwent whole-body PET/CT at multiple time points after a bolus injection of 68Ga-BBN (111 ± 148 MBq). Regions of interest were drawn manually over major organs, and time–activity curves were obtained. Dosimetry was calculated using the OLINDA/EXM software. Twelve patients with glioma diagnosed by contrast-enhanced MRI underwent PET/CT at 30–45 min after 68Ga-BBN injection. Within 1 wk afterward, the tumor was surgically removed and immunohistochemical staining of tumor samples against GRPR was performed and correlated with the PET/CT results. Results 68Ga-BBN was well tolerated in all healthy volunteers, with no adverse symptoms being noticed or reported. 68Ga-BBN cleared rapidly from the circulation and was excreted mainly through the kidneys and urinary tract. The total effective dose equivalent and effective dose were 0.0335 ± 0.0079 and 0.0276 ± 0.0066 mSv/MBq, respectively. In glioma patients, all MRI-identified lesions showed high signal intensity on 68Ga-BBN PET/CT. SUVmax and SUVmean were 2.08 ± 0.58 and 1.32 ± 0.37, respectively. With normal brain tissue as background, tumor-to-background ratios were 24.0 ± 8.85 and 13.4 ± 4.54 based on SUVmax and SUVmean, respectively. The immunohistochemical staining confirmed a positive correlation between SUV and GRPR expression level (r2 = 0.71, P < 0.001). Conclusion 68Ga-BBN is a PET tracer with favorable pharmacokinetics and a favorable dosimetry profile. It has the potential to evaluate GRPR expression in glioma patients and guide GRPR-targeted therapy of glioma. PMID:26449838

  8. A disconnection account of subjective empathy impairments in diffuse low-grade glioma patients.

    Science.gov (United States)

    Herbet, Guillaume; Lafargue, Gilles; Moritz-Gasser, Sylvie; Menjot de Champfleur, Nicolas; Costi, Emanuele; Bonnetblanc, François; Duffau, Hugues

    2015-04-01

    Human empathic experience is a multifaceted psychological construct which arises from functional integration of multiple neural networks. Despite accumulating knowledge about the cortical circuitry of empathy, almost nothing is known about the connectivity that may be concerned in conveying empathy-related neural information. To bridge this gap in knowledge, we studied dispositional empathy in a large-sized cohort of 107 patients who had undergone surgery for a diffuse low-grade glioma. The self-report questionnaire used enabled us to obtain a global measure of subjective empathy but also, importantly, to assess the two main components of empathy (cognitive and emotional). Data were processed by combining voxelwise and tractwise lesion-symptom analyses. Several major findings emerged from our analyses. First of all, topological voxelwise analyses were inconclusive. Conversely, tractwise multiple regression analyses, including all major associative white matter pathways as potential predictors, yielded to significant models explaining substantial part of the behavioural variance. Among the main results, we found that disconnection of the left cingulum bundle was a strong predictor of a low cognitive empathy (pempathy. Finally, although we failed to relate emotional empathy to disruption of a specific tract, correlation analyses indicated a positive association between this component of empathy and the volumes of residual lesion infiltration in the right hemisphere (pempathy. They may help to better understand the pathophysiology of empathy impairments in pathological conditions characterized by abnormalities of long-range anatomical connectivity, such as autism spectrum disorders, schizophrenia and fronto-temporal dementia.

  9. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas.

    Science.gov (United States)

    Lasky, Joseph L; Panosyan, Eduard H; Plant, Ashley; Davidson, Tom; Yong, William H; Prins, Robert M; Liau, Linda M; Moore, Theodore B

    2013-05-01

    Immunotherapy has the potential to improve clinical outcomes with little toxicity for pediatric patients with brain tumors. We conducted a pilot feasibility study of tumor lysate-pulsed dendritic cell (DC) vaccination in pediatric patients (1 to 18 years old) with newly diagnosed or recurrent high-grade glioma (HGG). A total of nine DC vaccine doses, each containing 1 × 10(6) cells per dose were administered to three out of the seven originally enrolled patients. Toxicities were limited to mild side-effects, except in one case of elevated alkaline phosphatase, which resolved without clinical consequences. Two patients with primary lesions amongst the three vaccinated were alive at the time of writing, both without evidence of disease. Pre- and post-vaccination tumor samples from a patient with an anaplastic oligoastrocytoma that recurred failed to demonstrate immune cell infiltration by immunohistochemistry. Peripheral cytokine levels were evaluated in one patient following DC vaccination and demonstrated some changes in relation to vaccination. DC vaccine is tolerable and feasible with some limitations for pediatric patients with HGG. Dendritic cell based immunotherapy may provide some clinical benefit in pediatric patients with glioma, especially for patients with minimal residual disease, but further investigation of this modality is required.

  10. Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects

    Energy Technology Data Exchange (ETDEWEB)

    McLendon, Roger E. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States)]. E-mail: mclen001@mc.duke.edu; Akabani, Gamal [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Friedman, Henry S. [Department of Pediatrics, Duke University Medical Center, Durham, NC 27710 (United States); Reardon, David A. [Department of Medicine, Duke University Medical Center, Durham, NC 27710 (United States); Cleveland, Linda [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Cokgor, Ilkcan [Department of Pediatrics, Duke University Medical Center, Durham, NC 27710 (United States); Herndon, James E. [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710 (United States); Wikstrand, Carol [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Boulton, Susan T. [Department of Surgery, Duke University Medical Center, Durham, NC 27710 (United States); Friedman, Allan H. [Department of Surgery, Duke University Medical Center, Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R. [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)

    2007-05-15

    Introduction: The neurohistological findings in patients treated with targeted {beta} emitters such as {sup 131}I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting of a {sup 131}I-labeled monoclonal antibody (mAb) injected into surgically created resection cavities during brain tumor resections. Methods: Directed tissue samples of the cavity walls were obtained because of suspected tumor recurrence from 28 patients. Samples and clinical follow-up were evaluated on all patients (Group A) based on total radiation dose received and a subset of these (n=18; Group B, proximal therapy subset) who had received external beam therapy within {<=}3 months of mAb therapy and undergoing 26 biopsies over 37 months. Histologic outcomes were 'proliferative glioma,' 'quiescent glioma' and negative for neoplasm. Statistical analysis was used to assess the casual relation between total absorbed dose ({sup 131}I-mAb+external beam) and histologic diagnosis. Results: The lesions observed after {sup 131}I-mAb therapy were qualitatively similar to those reported for other types of radiation therapy; however, the high localized dose rate and absorbed doses produced by the short range of {sup 131}I {beta} particles seem to have resulted in an earlier necrotic reaction in the tumor bed. Among all 28 (Group A) patients, median survival from tissue analysis after mAb therapy depended on histopathology and total radiation absorbed dose. Median survival for patients with tissue classified as proliferative glioma, quiescent glioma and negative for neoplasm were 3.5, 15 and 27.5 months, respectively. Without categorization, total dose was a significant predictor of survival (P<.002) where patients with higher doses had better prognoses. For example, median survival in patients receiving a total radiation dose greater than 86 Gy was 19 months compared with 7 months for those

  11. 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.

  12. Health-related quality of life in high-grade glioma patients

    Institute of Scientific and Technical Information of China (English)

    Linda Dirven; Neil K. Aaronson; Jan J. Heimans; Martin J.B. Taphoorn

    2014-01-01

    Gliomas are malignant primary brain tumors and yet incurable. Palliation and the maintenance or improvement of the patient's quality of life is therefore of main importance. For that reason, health-related quality of life (HRQoL) has become an important outcome measure in clinical trials, next to traditional outcome measures such as overal and progression-free survivals, and radiological response to treatment. HRQoL is a multidimensional concept covering physical, psychological, and social domains, as well as symptoms induced by the disease and its treatment. HRQoL is assessed by using self-reported, validated questionnaires. Various generic HRQoL questionnaires, which can be supplemented with a brain tumor-specific module, are available. Both the tumor and its treatment can have a negative effect on HRQoL. However, treatment with surgery, radiotherapy, chemotherapy, and supportive treatment may also improve patients’ HRQoL, in addition to extending survival. It is expected that the impact of HRQoL measurements in both clinical trials and clinical practice wil increase. Hence, it is important that HRQoL data are col ected, analyzed, and interpreted correctly. Methodological issues such as selection bias and missing data may hamper the interpretation of HRQoL data and should therefore be accounted. In clinical trials, HRQoL can be used to assess the benefits of a new treatment strategy, which should be weighed careful y against the adverse effects of that treatment. In daily clinical practice, HRQoL assessments of an individual patient can be used to inform physicians about the impact of a specific treatment strategy, and it may facilitate the communication between the physicians and the patients.

  13. {sup 18}F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Ledezma, Carlos J. [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail: ledezmacjl@gmail.com; Chen, Wei [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail: weichen@mednet.ucla.edu; Sai, Victor [School of Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail: vsai@ucla.edu; Freitas, Bonnie [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail: bfreitas@mednet.ucla.edu; Cloughesy, Tim [Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail: tcloughe@ucla.edu; Czernin, Johannes [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail: jczernin@mednet.ucla.edu; Pope, Whitney [Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)], E-mail: wpope@mednet.ucla.edu

    2009-08-15

    Background and purpose: {sup 18}F-FDOPA PET demonstrates higher sensitivity and specificity for gliomas than traditional [{sup 18}F] FDG PET imaging. However, PET provides limited anatomic localization. The purpose of this study was to determine whether {sup 18}F-FDOPA PET/MRI fusion can provide precise anatomic localization of abnormal tracer uptake and how this activity corresponds to MR signal abnormality. Methods: Two groups of patients were analyzed. Group I consisted of 21 patients who underwent {sup 18}F-FDOPA PET and MRI followed by craniotomy for tumor resection. Group II consisted of 70 patients with a pathological diagnosis of glioma that had {sup 18}F-FDOPA PET and MRI but lacked additional pathologic follow-up. Fused {sup 18}F-FDOPA PET and MRI images were analyzed for concordance and correlated with histopathologic data. Results: Fusion technology facilitated precise anatomical localization of {sup 18}F-FDOPA activity. In group I, all 21 cases showed pathology-confirmed tumor. Of these, {sup 18}F-FDOPA scans were positive in 9/10 (90%) previously unresected tumors, and 11/11 (100%) of recurrent tumors. Of the 70 patients in group II, concordance between MRI and {sup 18}F-FDOPA was found in 49/54 (90.1%) of patients with sufficient follow-up; in the remaining 16 patients concordance could not be determined due to lack of follow-up. {sup 18}F-FDOPA labeling was comparable in both high- and low-grade gliomas and identified both enhancing and non-enhancing tumor equally well. In some cases, {sup 18}F-FDOPA activity preceded tumor detection on MRI. Conclusion: {sup 18}F-FDOPA PET/MRI fusion provides precise anatomic localization of tracer uptake and labels enhancing and non-enhancing tumor well. In a small minority of cases, {sup 18}F-FDOPA activity may identify tumor not visible on MRI.

  14. Atypical nuclear localization of VIP receptors in glioma cell lines and patients.

    Science.gov (United States)

    Barbarin, Alice; Séité, Paule; Godet, Julie; Bensalma, Souheyla; Muller, Jean-Marc; Chadéneau, Corinne

    2014-11-28

    An increasing number of G protein-coupled receptors, like receptors for vasoactive intestinal peptide (VIP), are found in cell nucleus. As VIP receptors are involved in the regulation of glioma cell proliferation and migration, we investigated the expression and the nuclear localization of the VIP receptors VPAC1 and VPAC2 in this cancer. First, by applying Western blot and immunofluorescence detection in three human glioblastoma (GBM) cell lines, we observed a strong nuclear staining for the VPAC1 receptor and a weak nuclear VPAC2 receptor staining. Second, immunohistochemical staining of VPAC1 and VPAC2 on tissue microarrays (TMA) showed that the two receptors were expressed in normal brain and glioma tissues. Expression in the non-nuclear compartment of the two receptors significantly increased with the grade of the tumors. Analysis of nuclear staining revealed a significant increase of VPAC1 staining with glioma grade, with up to 50% of GBM displaying strong VPAC1 nuclear staining, whereas nuclear VPAC2 staining remained marginal. The increase in VPAC receptor expression with glioma grades and the enhanced nuclear localization of the VPAC1 receptors in GBM might be of importance for glioma progression.

  15. Antithrombin III for critically ill patients

    DEFF Research Database (Denmark)

    Allingstrup, Mikkel; Wetterslev, Jørn; Ravn, Frederikke B

    2016-01-01

    PURPOSE: Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients. METHODS: We searched from inception to 27 August 2015 in CENTRAL, MEDLINE, EMBASE, CAB, BIOSIS and CINAHL. We included randomized cont...

  16. A North American brain tumor consortium phase II study of Poly-ICLC for adult patients with recurrent anaplastic gliomas

    Science.gov (United States)

    Butowski, Nicholas; Lamborn, Kathleen R.; Lee, Bee L; Prados, Michael D.; Cloughesy, Timothy; DeAngelis, Lisa M.; Abrey, Lauren; Fink, Karen; Lieberman, Frank; Mehta, Minesh; Robins, H. Ian; Junck, Larry; Salazar, Andres M.; Chang, Susan M.

    2011-01-01

    Purpose This phase II study was designed to determine the objective response rate and 6-month progression free survival of adult patients with recurrent supratentorial anaplastic glioma when treated with the immune modulator, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC). Methods and Materials This was an open-labeled, single arm phase II study. Patients were treated with poly-ICLC alone. Patients may have had treatment for no more than two prior relapses. Treatment with poly-ICLC continued until tumor progression. Results 55 patients were enrolled in the study. 10 were ineligible after central review of pathology. 11% of patients (5 of 45) had a radiographic response. Time to progression was known for 39 patients and 6 remain on treatment. The estimated 6-month progression free survival was 24%. The median survival time was 43 weeks. Conclusions Poly-ICLC was well tolerated, but there was no improvement in 6-month progression free survival compared to historical database nor was there an encouraging objective radiographic response rate. Based on this study, poly-ICLC does not improve 6moPFS in patients with recurrent anaplastic gliomas but may be worth further study in combination with agents such as temozolomide. PMID:18850068

  17. Controlled rehabilitative and supportive care intervention trials in patients with high-grade gliomas and their caregivers

    DEFF Research Database (Denmark)

    Piil, K; Juhler, M; Jakobsen, J

    2016-01-01

    training improves functional outcome and massage therapy reduces stress. Patients and caregivers found that telephone follow-up and a specialist nurse function was an effective and useful way to achieve information and support. Finally, psycho-education increased feelings of mastery among caregivers......, quantitative and mixed methods primary studies in mixed study reviews. RESULTS: The search yielded 914 unique publications, of which 9 were classified eligible for this review. There is preliminary evidence that cognitive group therapy improves memory skills in patients with high-grade gliomas, early physical...

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

    Science.gov (United States)

    Hutter, Sonja; Piro, Rosario M; Waszak, Sebastian M; Kehrer-Sawatzki, Hildegard; Friedrich, Reinhard E; Lassaletta, Alvaro; Witt, Olaf; Korbel, Jan O; Lichter, Peter; Schuhmann, Martin U; Pfister, Stefan M; Tabori, Uri; Mautner, Victor F; Jones, David T W

    2016-05-01

    Neurofibromatosis type 1 (NF1) is a common monogenic disorder whereby affected individuals are predisposed to developing CNS tumors, including optic pathway gliomas (OPGs, occurring in ~15 to 20 % of cases). So far, no definite genotype-phenotype correlation determining NF1 patients at risk for tumor formation has been described, although enrichment for mutations in the 5' region of the NF1 gene in OPG patients has been suggested. We used whole exome sequencing, targeted sequencing, and copy number analysis to screen 77 unrelated NF1 patients with (n = 41) or without (n = 36; age ≥10 years) optic pathway glioma for germline NF1 alterations. We identified germline NF1 mutations in 69 of 77 patients (90 %), but no genotype-phenotype correlation was observed. Our data using a larger patient cohort did not confirm the previously reported clustering of mutations in the 5' region of the NF1 gene in patients with OPG. Thus, NF1 mutation location should not currently be used as a clinical criterion to assess the risk of developing OPGs.

  19. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas.

    Science.gov (United States)

    Jiao, Yuchen; Killela, Patrick J; Reitman, Zachary J; Rasheed, Ahmed B; Heaphy, Christopher M; de Wilde, Roeland F; Rodriguez, Fausto J; Rosemberg, Sergio; Oba-Shinjo, Sueli Mieko; Nagahashi Marie, Suely Kazue; Bettegowda, Chetan; Agrawal, Nishant; Lipp, Eric; Pirozzi, Christopher; Lopez, Giselle; He, Yiping; Friedman, Henry; Friedman, Allan H; Riggins, Gregory J; Holdhoff, Matthias; Burger, Peter; McLendon, Roger; Bigner, Darell D; Vogelstein, Bert; Meeker, Alan K; Kinzler, Kenneth W; Papadopoulos, Nickolas; Diaz, Luis A; Yan, Hai

    2012-07-01

    Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequency of these mutations in many subtypes of gliomas, and their association with clinical features of the patients, is poorly understood. Here we analyzed these loci in 363 brain tumors. ATRX is frequently mutated in grade II-III astrocytomas (71%), oligoastrocytomas (68%), and secondary glioblastomas (57%), and ATRX mutations are associated with IDH1 mutations and with an alternative lengthening of telomeres phenotype. CIC and FUBP1 mutations occurred frequently in oligodendrogliomas (46% and 24%, respectively) but rarely in astrocytomas or oligoastrocytomas ( more than 10%). This analysis allowed us to define two highly recurrent genetic signatures in gliomas: IDH1/ATRX (I-A) and IDH1/CIC/FUBP1 (I-CF). Patients with I-CF gliomas had a significantly longer median overall survival (96 months) than patients with I-A gliomas (51 months) and patients with gliomas that did not harbor either signature (13 months). The genetic signatures distinguished clinically distinct groups of oligoastrocytoma patients, which usually present a diagnostic challenge, and were associated with differences in clinical outcome even among individual tumor types. In addition to providing new clues about the genetic alterations underlying gliomas, the results have immediate clinical implications, providing a tripartite genetic signature that can serve as a useful adjunct to conventional glioma classification that may aid in prognosis, treatment selection, and therapeutic trial design.

  20. Disturbed small-world networks and neurocognitive function in frontal lobe low-grade glioma patients.

    Directory of Open Access Journals (Sweden)

    Qingling Huang

    Full Text Available BACKGROUND: Brain tumor patients often associated with losses of the small-world configuration and neurocognitive functions before operations. However, few studies were performed on the impairments of frontal lobe low-grade gliomas (LGG after tumor resection using small-world network features. METHODOLOGY/PRINCIPAL FINDINGS: To detect differences in the whole brain topology among LGG patients before and after operation, a combined study of neurocognitive assessment and graph theoretical network analysis of fMRI data was performed. We collected resting-state fMRI data of 12 carefully selected frontal lobe LGG patients before and after operation. We calculated the topological properties of brain functional networks in the 12 LGG, and compared with 12 healthy controls (HCs. We also applied Montreal Cognitive Assessment (MoCA in a subset of patients (n = 12, including before and after operation groups and HCs (n = 12. The resulting functional connectivity matrices were constructed for all 12 patients, and binary network analysis was performed. In the range of 0.05 ≤ Kcos t ≤ 0.35, the functional networks in preoperative LGG and postoperative one both fitted the definition of small-worldness. We proposed Knet = 0.20 as small-world network interval, and the results showed that the topological properties were found to be disrupted in the two LGG groups, meanwhile the global efficiency increased and the local efficiency decreased. Lnet in the two LGG groups both were longer than HCs. Cnet in the LGG groups were smaller than HCs. Compared with the Hcs, MoCA in the two LGG groups were lower than HCs with significant difference, and the disturbed networks in the LGG were negatively related to worse MoCA scores. CONCLUSIONS: Disturbed small-worldness preperty in the two LGG groups was found and widely spread in the strength and spatial organization of brain networks, and the alterated small-world network may be responsible for cognitive

  1. Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas

    DEFF Research Database (Denmark)

    Berntsson, Shala Ghaderi; Wibom, Carl; Sjöström, Sara;

    2011-01-01

    The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade ...

  2. Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma

    DEFF Research Database (Denmark)

    Tietze, Anna; Mouridsen, Kim; Lassen-Ramshad, Yasmin

    2015-01-01

    of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival......Objectives: Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI) based indices of microvascular flow control provide more information on tumor grade and patient outcome...... than does the established PWI angiogenesis marker, cerebral blood volume (CBV). Material and Methods: Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas) were included. Capillary transit time heterogeneity (CTH) and COV, its ratio to blood mean transit time, provide indices...

  3. Occlusal rehabilitation of pseudo-class III patient.

    Science.gov (United States)

    Cardoso, Antônio Carlos; Ferreira, Cimara Fortes; Oderich, Elisa; Pedroso, Moira Leão; Wicks, Russell

    2015-01-01

    To treat a patient with anterior crossbite, the clinician should first assess if it is a genuine class III or a pseudo-class III malocclusion. Cephalometric analysis is important; however, registering a patient's centric relation (CR) is simple, quick, and costless and can play a decisive role in a differential diagnosis for this type of patient profile. This clinical report depicts a patient clinically diagnosed as class III. After mandible manipulation in CR, it was noted that the patient in question was a pseudo-class III. The treatment was based on the pseudo-class III diagnosis. Therefore, the patient was rehabilitated by occlusal adjustments and conventional and implant-supported prostheses and without the need for invasive orthognathic surgery.

  4. 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

  5. P60WHY ANIMAL MODELS OF GENE THERAPY HAVE LET GLIOMA PATIENTS DOWN

    Science.gov (United States)

    Hirst, Theodore C.; Vesterinen, Hanna M.; Conlin, Samantha; Egan, Kieren J.; Antonic, Ana; McLean, Aaron Lawson; Macleod, Malcolm R.; Whittle, Ian R.; Grant, Robin; Brennan, Paul M.; Sena, Emily S.

    2014-01-01

    INTRODUCTION: The development of new therapeutics is often characterised by promising animal research that fails to translate into clinical efficacy; this holds for the development of gene therapy in glioma. We set out to test the hypothesis that this is because of limitations in the internal and external validity of studies reporting the use of gene therapy in rodent models of glioma. METHOD: We systematically identified studies testing gene therapy in rodent glioma models by searching three online databases. The number of animals treated and median survival were extracted and studies graded using a 9-point quality checklist. We calculated median survival ratios and used random effects meta-analysis to provide estimates of efficacy. We explored the effects of study design and quality and searched for evidence of publication bias. RESULTS: We found 194 publications using gene therapy in experimental glioma, describing 427 experiments involving 6366 animals. Overall, genetherapy improved median survival by 1.60 fold (95%CI 1.53-1.67). Study quality was low and the type of gene therapy did not account for observed differences in outcome. Study design characteristics accounted for a significant proportion of between-study heterogeneity and we observedsimilar findings in a subset of data limited to the most common genetherapy. CONCLUSION: As the dysregulation of key molecular pathways is characteristic of gliomas, gene therapy remains a promising treatment forglioma. Nevertheless, we have identified areas for improvement in conduct and reporting of such studies. Further work should focus on genes of interest in paradigms that recapitulate human disease. This may improve the translation of such therapies into the clinic.

  6. Perfusion MRI derived indices of microvascular shunting and flow control correlate with tumor grade and outcome in patients with cerebral glioma.

    Directory of Open Access Journals (Sweden)

    Anna Tietze

    Full Text Available Deficient microvascular blood flow control is thought to cause tumor hypoxia and increase resistance to therapy. In glioma patients, we tested whether perfusion-weighted MRI (PWI based indices of microvascular flow control provide more information on tumor grade and patient outcome than does the established PWI angiogenesis marker, cerebral blood volume (CBV.Seventy-two glioma patients (sixty high-grade, twelve low-grade gliomas were included. Capillary transit time heterogeneity (CTH and the coefficient of variation (COV, its ratio to blood mean transit time, provide indices of microvascular flow control and the extent to which oxygen can be extracted by tumor tissue. The ability of these parameters and CBV to differentiate tumor grade were assessed by receiver operating characteristic curves and logistic regression. Their ability to predict time to progression and overall survival was examined by the Cox proportional-hazards regression model, and by survival curves using log-rank tests.The best prediction of grade (AUC = 0.876; p < 0.05 was achieved by combining knowledge of CBV and CTH in the enhancing tumor and peri-focal edema, and patients with glioblastoma multiforme were identified best by CTH (AUC = 0.763; p<0.001. CTH outperformed CBV and COV in predicting time to progression and survival in all gliomas and in a subgroup consisting of only high-grade gliomas.Our study confirms the importance of microvascular flow control in tumor growth by demonstrating that determining CTH improves tumor grading and outcome prediction in glioma patients compared to CBV alone.

  7. Optimizing a machine learning based glioma grading system using multi-parametric MRI histogram and texture features.

    Science.gov (United States)

    Zhang, Xin; Yan, Lin-Feng; Hu, Yu-Chuan; Li, Gang; Yang, Yang; Han, Yu; Sun, Ying-Zhi; Liu, Zhi-Cheng; Tian, Qiang; Han, Zi-Yang; Liu, Le-De; Hu, Bin-Quan; Qiu, Zi-Yu; Wang, Wen; Cui, Guang-Bin

    2017-07-18

    Current machine learning techniques provide the opportunity to develop noninvasive and automated glioma grading tools, by utilizing quantitative parameters derived from multi-modal magnetic resonance imaging (MRI) data. However, the efficacies of different machine learning methods in glioma grading have not been investigated.A comprehensive comparison of varied machine learning methods in differentiating low-grade gliomas (LGGs) and high-grade gliomas (HGGs) as well as WHO grade II, III and IV gliomas based on multi-parametric MRI images was proposed in the current study. The parametric histogram and image texture attributes of 120 glioma patients were extracted from the perfusion, diffusion and permeability parametric maps of preoperative MRI. Then, 25 commonly used machine learning classifiers combined with 8 independent attribute selection methods were applied and evaluated using leave-one-out cross validation (LOOCV) strategy. Besides, the influences of parameter selection on the classifying performances were investigated. We found that support vector machine (SVM) exhibited superior performance to other classifiers. By combining all tumor attributes with synthetic minority over-sampling technique (SMOTE), the highest classifying accuracy of 0.945 or 0.961 for LGG and HGG or grade II, III and IV gliomas was achieved. Application of Recursive Feature Elimination (RFE) attribute selection strategy further improved the classifying accuracies. Besides, the performances of LibSVM, SMO, IBk classifiers were influenced by some key parameters such as kernel type, c, gama, K, etc. SVM is a promising tool in developing automated preoperative glioma grading system, especially when being combined with RFE strategy. Model parameters should be considered in glioma grading model optimization.

  8. TSPO PET for glioma imaging using the novel ligand (18)F-GE-180: first results in patients with glioblastoma.

    Science.gov (United States)

    Albert, Nathalie L; Unterrainer, M; Fleischmann, D F; Lindner, S; Vettermann, F; Brunegraf, A; Vomacka, L; Brendel, M; Wenter, V; Wetzel, C; Rupprecht, R; Tonn, J-C; Belka, C; Bartenstein, P; Niyazi, M

    2017-08-19

    The 18-kDa mitochondrial translocator protein (TSPO) was reported to be upregulated in gliomas. (18)F-GE-180 is a novel 3rd generation TSPO receptor ligand with improved target-to-background contrast compared to previous tracers. In this pilot study, we compared PET imaging with (18)F-GE-180 and MRI of patients with untreated and recurrent pretreated glioblastoma. Eleven patients with histologically confirmed IDH wildtype gliomas (10 glioblastomas, 1 anaplastic astrocytoma) underwent (18)F-GE-180 PET at initial diagnosis or recurrence. The PET parameters mean background uptake (SUVBG), maximal tumour-to-background ratio (TBRmax) and PET volume using different thresholds (SUVBG × 1.6, 1.8 and 2.0) were evaluated in the 60-80 min p.i. summation images. The different PET volumes were compared to the contrast-enhancing tumour volume on MRI. All gliomas were positive on (18)F-GE-180 PET and were depicted with extraordinarily high tumour-to-background contrast (median SUVBG 0.47 (0.37-0.93), TBRmax 6.61 (3.88-9.07)). (18)F-GE-180 uptake could be found even in areas without contrast enhancement on MRI, leading to significantly larger PET volumes than MRI-based volumes (median 90.5, 74.5, and 63.8 mL vs. 31.0 mL; p = 0.003, 0.004, 0.013). In percentage difference, the PET volumes were on average 179%, 135%, and 90% larger than the respective MRI volumes. The median spatial volumetric correlation (Sørensen-Dice coefficient) of PET volumes and MRI volumes prior to radiotherapy was 0.48, 0.54, and 0.58. (18)F-GE-180 PET provides a remarkably high tumour-to-background contrast in untreated and pretreated glioblastoma and shows tracer uptake even beyond contrast enhancement on MRI. To what extent (18)F-GE-180 uptake reflects the tumour extent of human gliomas and inflammatory cells remains to be evaluated in future prospective studies with guided stereotactic biopsies and correlation of histopathological results.

  9. A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy†

    Science.gov (United States)

    Raizer, Jeffrey J.; Abrey, Lauren E.; Lassman, Andrew B.; Chang, Susan M.; Lamborn, Kathleen R.; Kuhn, John G.; Yung, W.K. Alfred; Gilbert, Mark R.; Aldape, Kenneth A.; Wen, Patrick Y.; Fine, Howard A.; Mehta, Minesh; DeAngelis, Lisa M.; Lieberman, Frank; Cloughesy, Timothy F.; Robins, H. Ian; Dancey, Janet; Prados, Michael D.

    2010-01-01

    Patients with (a) recurrent malignant glioma (MG): glioblastoma (GBM) or recurrent anaplastic glioma (AG), and (b) nonprogressive (NP) GBM following radiation therapy (RT) were eligible. Primary objective for recurrent MG was progression-free survival at 6 months (PFS-6) and overall survival at 12 months for NP GBM post-RT. Secondary objectives for recurrent MGs were response, survival, assessment of toxicity, and pharmacokinetics (PKs). Treatment with enzyme-inducing antiepileptic drugs was not allowed. Patients received 150 mg/day erlotinib. Patients requiring surgery were treated 7 days prior to tumor removal for PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) and intracellular signaling pathways. Ninety-six patients were evaluable (53 recurrent MG and 43 NP GBM); 5 patients were not evaluable for response. PFS-6 in recurrent GBM was 3% with a median PFS of 2 months; PFS-6 in recurrent AG was 27% with a median PFS of 2 months. Twelve-month survival was 57% in NP GBMs post-RT. Primary toxicity was dermatologic. The tissue-to-plasma ratio normalized to nanograms per gram dry weight for erlotinib and OSI-420 ranged from 25% to 44% and 30% to 59%, respectively, for pretreated surgical patients. No effect on EGFR or intratumoral signaling was seen. Patients with NP GBM post-RT who developed rash in cycle 1 had improved survival (P < .001). Single-agent activity of erlotinib is minimal for recurrent MGs and marginally beneficial following RT for NP GBM patients. Development of rash in cycle 1 correlates with survival in patients with NP GBM after RT. PMID:20150372

  10. 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...

  11. Rare synchronous association of vestibular schwannoma and indolent insular oligodendroglioma in a patient without neurofibromatosis: controversial issue of timing for surgical treatment of asymptomatic low-grade gliomas

    Directory of Open Access Journals (Sweden)

    Zizzi A

    2012-11-01

    Full Text Available Maurizio Iacoangeli,1 Alessandro Di Rienzo,1 Roberto Colasanti,1 Lorenzo Alvaro,1 Niccolò Nocchi,1 Gabriele Polonara,2 Lucia Giovanna Maria Di Somma,1 Antonio Zizzi,3 Marina Scarpelli,3 Massimo Scerrati11Department of Neurosurgery, 2Department of Radiology, Section of Neuroradiology, 3Department of Pathology, Università Politecnica delle Marche, Umberto I General Hospital, Ancona, ItalyAbstract: The co-occurrence of a vestibular schwannoma and a low-grade glioma is rare, and even rarer is the association with an oligodendroglioma. Although various authors have addressed the problem of treating patients with incidentally discovered indolent low-grade gliomas, an established protocol does not exist to date. The common approach is to reserve surgery until there is radiological evidence of tumor growth or high-grade transformation. However, because incidental low-grade glioma may represent the first stage of unavoidable pathological progression towards high-grade glioma, early and radical surgical resection should be advocated in order to increase the chance of a "cure" and prolonged survival. This case report supports this view, and suggests reflection on a possible change from a conservative philosophy to preventative surgical treatment.Keywords: multiple primary intracranial tumors, vestibular schwannoma, oligodendroglioma, indolent low grade gliomas, incidentaloma, surgery

  12. Can {sup 18}F-FDOPA PET/CT predict survival in patients with suspected recurrent glioma? A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Karunanithi, Sellam, E-mail: drsellam84@yahoo.co.in [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Sharma, Punit; Kumar, Abhishek [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Gupta, Deepak Kumar [Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi (India); Khangembam, Bangkim Chandra; Ballal, Sanjana; Kumar, Rakesh; Kumar, Rajeev [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India); Bal, Chandrasekhar, E-mail: csbal@hotmail.com [Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi (India)

    2014-01-15

    Purpose of the present study was to evaluate the role of {sup 18}F-FDOPA PET/CT for predicting survival in patients with suspected recurrent glioma. Methods: A total of 33 previously treated, histopathologically proven glioma patients with clinical and contrast enhanced MRI findings suspicious for recurrence were enrolled in this prospective study. All patients underwent {sup 18}F-FDOPA PET/CT. Ratios of tumor uptake to normal tissue uptake were generated by dividing the tumor SUVmax with SUVmax of the contralateral normal brain tissue (T/N), normal striatum (T/S), normal white matter (T/W) and normal cerebellum (T/C). Patients were followed up clinically and by repeated imaging. Data was censored, if the patient died of disease or at the end of the study. Survival analysis was performed for the distributions of each variable and by multivariate analysis. Results: {sup 18}F-FDOPA PET/CT was positive for recurrence in 25 patients and negative in 8. Death occurred in nineteen patients. Median follow up period was 20.2 months. Median survival in this study was 39.2 months. In univariate analysis significant association of survival was noted with results of {sup 18}F-FDOPA PET/CT (P = 0.007) and {sup 18}F-FDOPA PET/CT quantitative parameters namely SUVmax (P = 0.001), T/S (P = 0.005), T/W (P = 0.0004), T/N (P = 0.001) and T/C (P = 0.003) were found to be significant. On multivariate analysis, only MRI size of the recurrent tumor (P = 0.002) and T/N ratio of {sup 18}F-FDOPA PET/CT (P = 0.005) were found to be independent predictors of survival. Conclusion: T/N ratio on {sup 18}F-FDOPA PET/CT is an independent predictor of survival in patients with suspected recurrent glioma, along with size of recurrent tumor on MRI.

  13. Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era

    Science.gov (United States)

    Perry, Christina; Agarwal, Devika; Abdel-Fatah, Tarek M.A.; Lourdusamy, Anbarasu; Grundy, Richard; Auer, Dorothee T.; Walker, David; Lakhani, Ravi; Scott, Ian S.; Chan, Stephen; Ball, Graham; Madhusudan, Srinivasan

    2014-01-01

    Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Cancer Genome Atlas’ (TCGA) cohort (n=508). A DNA repair prognostic index model was generated. Artificial neural network analysis (ANN) was conducted to investigate global gene interactions. Protein expression by immunohistochemistry was conducted in 61 tumours. A fourteen DNA repair gene expression panel was associated with poor survival in Test and TCGA cohorts. A Cox multivariate model revealed APE1, NBN, PMS2, MGMT and PTEN as independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients in to three prognostic sub-groups with worsening survival. APE1, NBN, PMS2, MGMT and PTEN also have predictive significance in patients who received chemotherapy and/or radiotherapy. ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in transcription, hypoxia and metabolic regulation. At the protein level, low APE1 and low PTEN remain associated with poor prognosis. In conclusion, multiple DNA repair pathways operate to influence biology and clinical outcomes in adult high grade gliomas. PMID:25026297

  14. Expression and prognostic value of the WEE1 kinase in gliomas.

    Science.gov (United States)

    Music, Darija; Dahlrot, Rikke Hedegaard; Hermansen, Simon Kjær; Hjelmborg, Jacob; de Stricker, Karin; Hansen, Steinbjørn; Kristensen, Bjarne Winther

    2016-04-01

    High-grade gliomas have an aggressive clinical course and new clinical biomarkers and therapeutic targets are highly needed. WEE1 is a regulator of the G2 checkpoint in glioblastoma (GBM) cells. Inhibition of this kinase has, in experimental glioma studies, been suggested to enhance sensitivity 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 positive nuclei. We found that WEE1 protein was localized in tumor cell nuclei and expressed in all glioma types and grades. Although WEE1 protein levels are higher in GBMs (mean 24.5%) relative to grade III (mean 14,0%, p < 0.05) and grade II (mean 6.8%, p < 0.001) gliomas, high WEE1 protein was associated with better survival in GBMs (p = 0.002). This was confirmed in multivariate analysis (HR 0.60, p = 0.003) even when adjusted for MGMT status (HR 0.60, p = 0.005). In conclusion, we report a nuclear expression of WEE1 protein in all glioma grades and types. The WEE1 positive nuclear area was correlated with malignancy grade but it was inversely associated with prognosis in GBM. Although WEE1 is a frequently occurring protein and has been proposed as a novel target in GBM, the role of WEE1 in glioma patient survival appears to be connected to the MGMT status and is more complex than previously anticipated.

  15. The prevalence of human cytomegalovirus DNA in gliomas of Brazilian patients

    Directory of Open Access Journals (Sweden)

    Renata Fragelli Fonseca

    2012-11-01

    Full Text Available Members of the Herpesviridae family have been implicated in a number of tumours in humans. At least 75% of the human population has had contact with cytomegalovirus (HCMV. In this work, we screened 75 Brazilian glioma biopsies for the presence of HCMV DNA sequences. HCMV DNA was detected in 36% (27/75 of the biopsies. It is possible that HCMV could be a co-factor in the evolution of brain tumours.

  16. [Prosthetic rehabilitation in patient with forced class III malocclusion].

    Science.gov (United States)

    Krunić, N; Kostić, M; Janośević, P; Petrović, D; Kostić, I; Petrović, M; Igić, M

    2014-01-01

    The paper presents clinical case of 63 years old edentulous patient with slight class III malocclusion. For 15 years he was using inadequately fabricated dentures causing forced severe class III malocclusion. Forced progeny was corrected by newly fabricated dentures which restored normal orofacial function and facial harmony.

  17. Impact on prognosis of the regional distribution of MGMT methylation with respect to the CpG island methylator phenotype and age in glioma patients.

    Science.gov (United States)

    Mur, Pilar; Rodríguez de Lope, Ángel; Díaz-Crespo, Francisco Javier; Hernández-Iglesias, Teresa; Ribalta, Teresa; Fiaño, Concepción; García, Juan Fernando; Rey, Juan Antonio; Mollejo, Manuela; Meléndez, Bárbara

    2015-05-01

    Clinical and molecular prognostic factors in gliomas include age, IDH mutation, the glioma CpG island methylator phenotype (G-CIMP+) and promoter methylation of the O(6)-methylguanine DNA-methyltransferase (MGMT) gene. Among these markers, a predictive value was reported in glioblastomas (GBM) for MGMT promoter methylation, in particular in elderly GBM patients. In this study, methylation data from 46 glioma samples with the Illumina 450K platform were obtained and extended using external data to include a total of 247 glioma samples. Methylation analysis of the whole MGMT gene with this platform revealed two strongly survival-associated CpG regions within the promoter and the gene body, which were confirmed in a reported dataset of high grade-gliomas. Methylation at the promoter (CpG 25, cg12981137 and the prognostic model MGMT-STP27) and at the gene body CpG 165 (cg07933035), were significantly associated with better overall survival, and strongly correlated with G-CIMP+ status. In this series, the prognostic value of MGMT methylation at the promoter was not observed in G-CIMP- cases, although around 50 % of them were MGMT-methylated. These results were also obtained in an homogeneously-treated series of chemoradiated G-CIMP- GBMs analyzed by MSP and qMSP, and confirmed in a reported pyrosequencing-analyzed series of gliomas. Interestingly, in contrast to the MGMT promoter, gene body methylation was of prognostic value in G-CIMP-patients older than 65 years. Our study highlights the relevance of the prognostic value of the different regions of methylation throughout the MGMT gene that could be affected by specific G-CIMP profiles and age groups.

  18. Prospective study of p-[{sup 123}I]iodo-L-phenylalanine and SPECT for the evaluation of newly diagnosed cerebral lesions: specific confirmation of glioma

    Energy Technology Data Exchange (ETDEWEB)

    Hellwig, Dirk; Schaefer, Andrea; Farmakis, Georgios; Grgic, Aleksandar; Kirsch, Carl-Martin [Saarland University Medical Center, Department of Nuclear Medicine, Homburg/Saar (Germany); Ketter, Ralf; Moringlane, Jean R.; Steudel, Wolf-Ingo [Saarland University Medical Center, Department of Neurosurgery, Homburg (Germany); Romeike, Bernd F.M. [Saarland University Medical Center, Institute of Neuropathology, Homburg (Germany); Friedrich-Schiller-University, Department of Neuropathology, Jena (Germany); Samnick, Samuel [Saarland University Medical Center, Department of Nuclear Medicine, Homburg/Saar (Germany); University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany)

    2010-12-15

    The differentiation between gliomas, metastases and gliotic or inflammatory lesions by imaging techniques remains a challenge. Gliomas frequently exhibit increased uptake of radiolabelled amino acids and are thus amenable to PET or SPECT imaging. Recently, p-[{sup 123}I]iodo-L-phenylalanine (IPA) was validated for the visualization of glioma by SPECT and received orphan drug status. Here we investigated its diagnostic performance for differentiating indeterminate brain lesions. This prospective open study included 67 patients with newly diagnosed brain lesions suspicious for glioma (34 without and 33 with contrast enhancement in the MRI scan). Patients received 250 MBq IPA intravenously after overnight fasting. SPECT images at 30 min and 3 h post-injection were iteratively reconstructed and visually interpreted after image fusion with an MRI brain scan (fluid-attenuated inversion recovery sequence or T1-weighted contrast-enhanced image). Findings were correlated with results of stereotactic or open biopsies or serial imaging. Twenty-seven low-grade (2 WHO I, 25 WHO II) and 24 high-grade gliomas (1 WHO III, 23 WHO IV), 3 metastases originating from lung cancer as well as 13 non-neoplastic lesions were proven. All non-neoplastic lesions and all metastases were negative with IPA SPECT. Forty gliomas were true-positive (TP) and 11 false-negative (FN) findings (8 WHO II, 1 WHO III, 2 WHO IV) occurred. There were no false-positive (FP) findings. For the differentiation of primary brain tumours and non-neoplastic lesions, sensitivity and specificity were 78 and 100%. In 34 lesions without contrast enhancement in MRI, IPA SPECT resulted in 17 TP, 8 true-negative, 9 FN and no FP findings (sensitivity 65%, specificity 100%). In patients with suspected glioma, IPA SPECT shows a high specificity, but especially in low-grade gliomas FN findings may occur. Due to the high positive predictive value a positive finding allows a suspected glioma to be confirmed. (orig.)

  19. Aberrations in the Iron Regulatory Gene Signature Are Associated with Decreased Survival in Diffuse Infiltrating Gliomas.

    Science.gov (United States)

    Weston, Cody; Klobusicky, Joe; Weston, Jennifer; Connor, James; Toms, Steven A; Marko, Nicholas F

    2016-01-01

    Iron is a tightly regulated micronutrient with no physiologic means of elimination and is necessary for cell division in normal tissue. Recent evidence suggests that dysregulation of iron regulatory proteins may play a role in cancer pathophysiology. We use public data from The Cancer Genome Atlas (TCGA) to study the association between survival and expression levels of 61 genes coding for iron regulatory proteins in patients with World Health Organization Grade II-III gliomas. Using a feature selection algorithm we identified a novel, optimized subset of eight iron regulatory genes (STEAP3, HFE, TMPRSS6, SFXN1, TFRC, UROS, SLC11A2, and STEAP4) whose differential expression defines two phenotypic groups with median survival differences of 52.3 months for patients with grade II gliomas (25.9 vs. 78.2 months, p< 10-3), 43.5 months for patients with grade III gliomas (43.9 vs. 87.4 months, p = 0.025), and 54.0 months when considering both grade II and III gliomas (79.9 vs. 25.9 months, p < 10-5).

  20. [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.

  1. Advanced PET and MR imaging in re-irradiation of high grade glioma

    DEFF Research Database (Denmark)

    Møller, Søren

    2014-01-01

    . The goal of this Ph.D. project was to evaluate the side-effects and efficacy of re-irradiation of highgrade glioma and to determine the value of positron emission tomography (PET) using an amino acid tracer for re-irradiation. Moreover, to identify imaging biomarkers capable of predicting the clinical...... course following radiotherapy. Two prospective studies were carried out; a Phase I/II study of re-irradiation to patients with progressive high-grade glioma and an observational study where tumor blood perfusion was measured using magnetic resonance imaging (MRI) in the course of radiotherapy...

  2. Isocitrate dehydrogenase 1 Gene Mutation Is Associated with Prognosis in Clinical Low-Grade Gliomas.

    Directory of Open Access Journals (Sweden)

    Ming-Yang Li

    Full Text Available Isocitrate dehydrogenase 1 gene mutations are found in most World Health Organization grade II and III gliomas and secondary glioblastomas. Isocitrate dehydrogenase 1 mutations are known to have prognostic value in high-grade gliomas. However, their prognostic significance in low-grade gliomas remains controversial. We determined the predictive and prognostic value of isocitrate dehydrogenase 1 status in low-grade gliomas. The association of isocitrate dehydrogenase 1 status with clinicopathological and genetic factors was also evaluated. Clinical information and genetic data including isocitrate dehydrogenase 1 mutation, O 6-methylguanine DNA methyltransferase promoter methylation, 1p/19q chromosome loss, and TP53 mutation of 417 low-grade gliomas were collected from the Chinese Glioma Genome Atlas database. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the prognostic effect of clinical characteristics and molecular biomarkers. Isocitrate dehydrogenase 1 mutation was identified as an independent prognostic factor for overall, but not progression-free, survival. Notably, isocitrate dehydrogenase 1 mutation was found to be a significant prognostic factor in patients with oligodendrogliomas, but not in patients with astrocytomas. Furthermore, O 6-methylguanine DNA methyltransferase promoter methylation (p = 0.017 and TP53 mutation (p < 0.001, but not 1p/19q loss (p = 0.834, occurred at a higher frequency in isocitrate dehydrogenase 1-mutated tumors than in isocitrate dehydrogenase 1 wild-type tumors. Younger patient age (p = 0.041 and frontal lobe location (p = 0.010 were significantly correlated with isocitrate dehydrogenase 1 mutation. Chemotherapy did not provide a survival benefit in patients with isocitrate dehydrogenase 1-mutated tumors. Isocitrate dehydrogenase 1 mutation was an independent prognostic factor in low-grade gliomas, whereas it showed no predictive value for chemotherapy response

  3. Isocitrate dehydrogenase 1 Gene Mutation Is Associated with Prognosis in Clinical Low-Grade Gliomas.

    Science.gov (United States)

    Li, Ming-Yang; Wang, Yin-Yan; Cai, Jin-Quan; Zhang, Chuan-Bao; Wang, Kuan-Yu; Cheng, Wen; Liu, Yan-Wei; Zhang, Wei; Jiang, Tao

    2015-01-01

    Isocitrate dehydrogenase 1 gene mutations are found in most World Health Organization grade II and III gliomas and secondary glioblastomas. Isocitrate dehydrogenase 1 mutations are known to have prognostic value in high-grade gliomas. However, their prognostic significance in low-grade gliomas remains controversial. We determined the predictive and prognostic value of isocitrate dehydrogenase 1 status in low-grade gliomas. The association of isocitrate dehydrogenase 1 status with clinicopathological and genetic factors was also evaluated. Clinical information and genetic data including isocitrate dehydrogenase 1 mutation, O 6-methylguanine DNA methyltransferase promoter methylation, 1p/19q chromosome loss, and TP53 mutation of 417 low-grade gliomas were collected from the Chinese Glioma Genome Atlas database. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the prognostic effect of clinical characteristics and molecular biomarkers. Isocitrate dehydrogenase 1 mutation was identified as an independent prognostic factor for overall, but not progression-free, survival. Notably, isocitrate dehydrogenase 1 mutation was found to be a significant prognostic factor in patients with oligodendrogliomas, but not in patients with astrocytomas. Furthermore, O 6-methylguanine DNA methyltransferase promoter methylation (p = 0.017) and TP53 mutation (p isocitrate dehydrogenase 1-mutated tumors than in isocitrate dehydrogenase 1 wild-type tumors. Younger patient age (p = 0.041) and frontal lobe location (p = 0.010) were significantly correlated with isocitrate dehydrogenase 1 mutation. Chemotherapy did not provide a survival benefit in patients with isocitrate dehydrogenase 1-mutated tumors. Isocitrate dehydrogenase 1 mutation was an independent prognostic factor in low-grade gliomas, whereas it showed no predictive value for chemotherapy response. Isocitrate dehydrogenase 1 mutation was highly associated with O 6-methylguanine DNA

  4. Discriminant value of Rome III questionnaire in dyspeptic patients

    Directory of Open Access Journals (Sweden)

    Shahab Abid

    2011-01-01

    Full Text Available Background/Aim: Rome III criteria has modified the description of functional dyspepsia (FD and divided this into subgroups. However, the discriminative value of Rome III questionnaire-based diagnosis of FD is yet to be determined. Objectives: To evaluate the Rome III questionnaire for the diagnosis of FD and whether it can discriminate between postprandial distress syndrome (PDS and epigastric pain syndrome (EPS in patients with dyspeptic symptoms. Patients and Methods: Consecutive patients, who were not on proton pump inhibitors (PPI, were asked to participate. Patients who have previously established acid peptic disease or predominantly reflux symptoms or having alarm symptoms such as weight loss and hematemesis were excluded. Rome III questionnaire for FD was used to identify the patients as having FD and divide into its subgroups; PDS or EPS. Gastro-duodenal biopsies, liver function tests and ultrasound were done to establish the diagnosis of FD. Results: Out of 272 patients with upper gastrointestinal (GI symptoms without alarm features, who were enrolled in the study, a total of 191 (70% fulfilled the criteria of FD based upon Rome III questionnaire. EPS subgroup was found in 109 (57%, PDS in 17 (9% patients, overlap between EPS and PDS was present in 56 (29% patients. Nine (5% patients remained indeterminate. Diagnosis of FD was established in 136/191 (71% patients only. Gastritis was present in 116 patients (85%, Duodenitis in 44 (32% and Helicobacter pylori infection in 70 (51% patients. Among 55 patients (29% who had organic diseases, EPS was seen in 35 (64%, PDS in 5 (9% and overlap in 15 (27% patients. Underlying organic causes were gastric or duodenal ulcers in 14 patients, Barrett esophagus in five, chronic liver disease in seven, gall stones in five, Giardiasis and celiac disease in three each. Gastric carcinoma, Crohns disease and gastric polyps were seen in one patient each. Conclusion: This study indicates that 30% of patients

  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. Discriminant value of Rome III questionnaire in dyspeptic patients.

    Science.gov (United States)

    Abid, Shahab; Siddiqui, Shaheryar; Jafri, Wasim

    2011-01-01

    Rome III criteria has modified the description of functional dyspepsia (FD) and divided this into subgroups. However, the discriminative value of Rome III questionnaire-based diagnosis of FD is yet to be determined. To evaluate the Rome III questionnaire for the diagnosis of FD and whether it can discriminate between postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) in patients with dyspeptic symptoms. Consecutive patients, who were not on proton pump inhibitors (PPI), were asked to participate. Patients who have previously established acid peptic disease or predominantly reflux symptoms or having alarm symptoms such as weight loss and hematemesis were excluded. Rome III questionnaire for FD was used to identify the patients as having FD and divide into its subgroups; PDS or EPS. Gastro-duodenal biopsies, liver function tests and ultrasound were done to establish the diagnosis of FD. Out of 272 patients with upper gastrointestinal (GI) symptoms without alarm features, who were enrolled in the study, a total of 191 (70%) fulfilled the criteria of FD based upon Rome III questionnaire. EPS subgroup was found in 109 (57%), PDS in 17 (9%) patients, overlap between EPS and PDS was present in 56 (29%) patients. Nine (5%) patients remained indeterminate. Diagnosis of FD was established in 136/191 (71%) patients only. Gastritis was present in 116 patients (85%), Duodenitis in 44 (32%) and Helicobacter pylori infection in 70 (51%) patients. Among 55 patients (29%) who had organic diseases, EPS was seen in 35 (64%), PDS in 5 (9%) and overlap in 15 (27%) patients. Underlying organic causes were gastric or duodenal ulcers in 14 patients, Barrett esophagus in five, chronic liver disease in seven, gall stones in five, Giardiasis and celiac disease in three each. Gastric carcinoma, Crohns disease and gastric polyps were seen in one patient each. This study indicates that 30% of patients who fulfilled the Rome III criteria for FD actually had organic disease

  7. WMS-III performance in epilepsy patients following temporal lobectomy.

    Science.gov (United States)

    Doss, Robert C; Chelune, Gordon J; Naugle, Richard I

    2004-03-01

    We examined performances on the Wechsler Memory Scale-3rd Edition (WMS-III) among patients who underwent temporal lobectomy for the control of medically intractable epilepsy. There were 51 right (RTL) and 56 left (LTL) temporal lobectomy patients. All patients were left hemisphere speech-dominant. The LTL and RTL patients were comparable in terms of general demographic, epilepsy, and intellectual/attention factors. Multivariate analyses revealed a significant crossover interaction (p WMS-III is sensitive to modality-specific memory performance associated with unilateral temporal lobectomy.

  8. DDX3X Biomarker Correlates with Poor Survival in Human Gliomas

    Directory of Open Access Journals (Sweden)

    Dueng-Yuan Hueng

    2015-07-01

    Full Text Available Primary high-grade gliomas possess invasive growth and lead to unfavorable survival outcome. The investigation of biomarkers for prediction of survival outcome in patients with gliomas is important for clinical assessment. The DEAD (Asp-Glu-Ala-Asp box helicase 3, X-linked (DDX3X controls tumor migration, proliferation, and progression. However, the role of DDX3X in defining the pathological grading and survival outcome in patients with human gliomas is not yet clarified. We analyzed the DDX3X gene expression, WHO pathological grading, and overall survival from de-linked data. Further validation was done using quantitative RT-PCR of cDNA from normal brain and glioma, and immunohistochemical (IHC staining of tissue microarray. Statistical analysis of GEO datasets showed that DDX3X mRNA expression demonstrated statistically higher in WHO grade IV (n = 81 than in non-tumor controls (n = 23, p = 1.13 × 10−10. Moreover, DDX3X level was also higher in WHO grade III (n = 19 than in non-tumor controls (p = 2.43 × 10−5. Kaplan–Meier survival analysis showed poor survival in patients with high DDX3X mRNA levels (n = 24 than in those with low DDX3X expression (n = 53 (median survival, 115 vs. 58 weeks, p = 0.0009, by log-rank test, hazard ratio: 0.3507, 95% CI: 0.1893–0.6496. Furthermore, DDX3X mRNA expression and protein production significantly increased in glioma cells compared with normal brain tissue examined by quantitative RT-PCR, and Western blot. IHC staining showed highly staining of high-grade glioma in comparison with normal brain tissue. Taken together, DDX3X expression level positively correlates with WHO pathologic grading and poor survival outcome, indicating that DDX3X is a valuable biomarker in human gliomas.

  9. Antithrombin III for critically ill patients

    DEFF Research Database (Denmark)

    Allingstrup, Mikkel; Wetterslev, Jørn; Ravn, Frederikke B

    2016-01-01

    , bleeding events, the effect on sepsis and disseminated intravascular coagulation (DIC) and the length of stay in the intensive care unit (ICU) and in hospital in general.  Search methods: We searched the following databases from inception to 27 August 2015: Cochrane Central Register of Controlled Trials...... data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI). We performed subgroup analyses to assess risk of bias, the effect of AT III in different populations (sepsis......). For participants with severe sepsis and DIC the RR for mortality was non-significant, 0.95 (95% Cl 0.88 to 1.03, I2 statistic = 0%, fixed-effect model, 12 trials, 2858 participants, moderate quality of evidence). We conducted 14 subgroup and sensitivity analyses with respect to the different domains of risk...

  10. Diagnostic Performance and Safety of Positron Emission Tomography Using 18F-Fluciclovine in Patients with Clinically Suspected High- or Low-grade Gliomas: A Multicenter Phase IIb Trial

    OpenAIRE

    Toshihiko Wakabayashi; Toshihiko Iuchi; Naohiro Tsuyuguchi; Ryo Nishikawa; Yoshiki Arakawa; Takashi Sasayama; Keisuke Miyake; Tadashi Nariai; Yoshitaka Narita; Naoya Hashimoto; Osamu Okuda; Hiroshi Matsuda; Kazuo Kubota; Kimiteru Ito; Yoichi Nakazato

    2017-01-01

    Objective(s): The study objective was to assess the diagnostic performance of positron emission tomography (PET) for gliomas using the novel tracer 18F-fluciclovine (anti-[18F]FACBC) and to evaluate the safety of this tracer in patients with clinically suspected gliomas.Methods: Anti-[18F]FACBC was administered to 40 patients with clinically suspected high- or low-grade gliomas, followed by PET imaging. T1-weighted, contrast-enhanced T1-weighted, and fluid-attenuated inversion recovery (or T2...

  11. [{sup 11}C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches

    Energy Technology Data Exchange (ETDEWEB)

    Su, Zhangjie; Herholz, Karl; Gerhard, Alexander; Jackson, Alan; Hinz, Rainer [University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom); Roncaroli, Federico [Imperial College London, ' ' John Fulcher' ' Neuro-Oncology Lab, London (United Kingdom); Du Plessis, Daniel [Salford Royal NHS Foundation Trust, Neuropathology Unit, Salford (United Kingdom); Turkheimer, Federico [King' s College London, Centre for Neuroimaging, Institute of Psychiatry, London (United Kingdom)

    2013-09-15

    Translocator protein (TSPO) is a biomarker of neuroinflammation that can be imaged by PET using [{sup 11}C]-(R)PK11195. We sought to characterize the [{sup 11}C]-(R)PK11195 kinetics in gliomas of different histotypes and grades, and to compare two reference tissue input functions (supervised cluster analysis versus cerebellar grey matter) for the estimation of [{sup 11}C]-(R)PK11195 binding in gliomas and surrounding brain structures. Twenty-three glioma patients and ten age-matched controls underwent structural MRI and dynamic [{sup 11}C]-(R)PK11195 PET scans. Tissue time-activity curves (TACs) were extracted from tumour regions as well as grey matter (GM) and white matter (WM) of the brains. Parametric maps of binding potential (BP{sub ND}) were generated with the simplified reference tissue model using the two input functions, and were compared with each other. TSPO expression was assessed in tumour tissue sections by immunohistochemistry. Three types of regional kinetics were observed in individual tumour TACs: GM-like kinetics (n = 6, clearance of the tracer similar to that in cerebellar GM), WM-like kinetics (n = 8, clearance of the tracer similar to that in cerebral WM) and a form of mixed kinetics (n = 9, intermediate rate of clearance). Such kinetic patterns differed between low-grade astrocytomas (WM-like kinetics) and oligodendrogliomas (GM-like and mixed kinetics), but were independent of tumour grade. There was good agreement between parametric maps of BP{sub ND} derived from the two input functions in all controls and 10 of 23 glioma patients. In 13 of the 23 patients, BP{sub ND} values derived from the supervised cluster input were systematically smaller than those using the cerebellar input. Immunohistochemistry confirmed that TSPO expression increased with tumour grade. The three types of [{sup 11}C]-(R)PK11195 kinetics in gliomas are determined in part by tracer delivery, and indicated that kinetic analysis is a valuable tool in the study of

  12. Comparison of cerebral blood volume and permeability in preoperative grading of intracranial glioma using CT perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Bei; Ling, Hua Wei; Chen, Ke Min [Shanghai Jiaotong University, Department of Radiology, Ruijin Hospital, School of Medicine, Shanghai (China); Jiang, Hong [Shanghai Jiaotong University, Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai (China); Zhu, Yan Bo [Shanghai Jiaotong University, Department of Neurosurgery, Ruijin Hospital, School of Medicine, Shanghai (China)

    2006-10-15

    Regional cerebral blood volume (rCBV) and permeability surfaces (rPS) permit in vivo assessment of glioma microvasculature, which provides quite important pathophysiological information in grading gliomas. The aim of our study was to simultaneously examine rCBV and rPS in glioma patients to determine their correlation with histological grade using CT perfusion imaging. A total of 22 patients with gliomas underwent multislice CT perfusion imaging preoperatively. Low-grade and high-grade groups were categorized corresponding to WHO grade II gliomas and WHO grade III or IV gliomas, respectively, as determined by histopathological examination. rCBVs and rPSs were obtained from regions of maximal abnormality in tumor parenchyma on CBV and PS color perfusion maps. Perfusion parameters were compared using the Kruskal-Wallis test in order to evaluate the differences in relation to tumor grade. The Pearson coefficients of rCBV and rPS for each tumor grade were assessed using SPSS 13.0 software. (orig.)

  13. DNA sequences within glioma-derived extracellular vesicles can cross the intact blood-brain barrier and be detected in peripheral blood of patients

    Science.gov (United States)

    Lázaro-Ibáñez, Elisa; Peris-Celda, María; Alonso, Marta M.; Guzmán-De-Villoria, Juan; Fernández-Carballal, Carlos; de Mendivil, Ana Ortiz; García-Duque, Sara; Escobedo-Lucea, Carmen; Prat-Acín, Ricardo; Belda-Iniesta, Cristóbal; Ayuso-Sacido, Angel

    2017-01-01

    Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs−apoptotic bodies, shedding microvesicles and exosomes−cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF). Furthermore, these EVs can be readily distinguished from total murine EVs, since they carry human-specific DNA sequences relevant for GBM biology. In a small cohort of glioma patients, we finally demonstrated that peripheral blood EVs cargo can be successfully used to detect the presence of IDH1G395A, an essential biomarker in the current management of human glioma PMID:27902458

  14. FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients

    Directory of Open Access Journals (Sweden)

    Hagedorn Martin

    2007-02-01

    Full Text Available Abstract Background In the quest for novel molecular mediators of glioma progression, we studied the regulation of FBXW7 (hCDC4/hAGO/SEL10, its association with survival of patients with glioblastoma and its potential role as a tumor suppressor gene in glioma cells. The F-box protein Fbxw7 is a component of SCFFbxw7, a Skp1-Cul1-F-box E3 ubiquitin ligase complex that tags specific proteins for proteasome degradation. FBXW7 is mutated in several human cancers and functions as a haploinsufficient tumor suppressor in mice. Any of the identified targets, Cyclin E, c-Myc, c-Jun, Notch1/4 and Aurora-A may have oncogenic properties when accumulated in tumors with FBXW7 loss. Results We tested the expression of FBXW7 in human glioma biopsies by quantitative PCR and compared the transcript levels of grade IV glioma (glioblastoma, G-IV with those of grade II tumors (G-II. In more than 80% G-IV, expression of FBXW7 was significantly reduced. In addition, levels of FBXW7 were correlated with survival indicating a possible implication in tumor aggressiveness. Locus 4q31.3 which carries FBXW7 was investigated by in situ hybridization on biopsy touchprints. This excluded allelic loss as the principal cause for low expression of FBXW7 in G-IV tumors. Two targets of Fbxw7, Aurora-A and Notch4 were preferentially immunodetected in G-IV biopsies. Next, we investigated the effects of FBXW7 misregulation in glioma cells. U87 cells overexpressing nuclear isoforms of Fbxw7 lose the expression of the proliferation markers PCNA and Ki-67, and get counterselected in vitro. This observation fits well with the hypothesis that Fbxw7 functions as a tumor suppressor in astroglial cells. Finally, FBXW7 knockdown in U87 cells leads to defects in mitosis that may promote aneuploidy in progressing glioma. Conclusion Our results show that FBXW7 expression is a prognostic marker for patients with glioblastoma. We suggest that loss of FBXW7 plays an important role in glioma

  15. Radiation injury of boron neutron capture therapy using mixed epithermal- and thermal neutron beams in patients with malignant glioma

    Energy Technology Data Exchange (ETDEWEB)

    Kageji, T. E-mail: kageji@clin.med.tokushima-u.ac.jp; Nagahiro, S.; Mizobuchi, Y.; Toi, H.; Nakagawa, Y.; Kumada, H

    2004-11-01

    The purpose of this study was to clarify the radiation injury in acute or delayed stage after boron neutron capture therapy (BNCT) using mixed epithermal- and thermal neutron beams in patients with malignant glioma. Eighteen patients with malignant glioma underwent mixed epithermal- and thermal neutron beam and sodium borocaptate between 1998 and 2004. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the protocol used between 1998 and 2000 (Protocol A, n=8) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B, n=4); it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to 6 glioblastoma patients (Protocol C, n=6). The average values of the maximum vascular dose of brain surface in Protocol A, B and C were 11.4{+-}4.2 Gy, 15.7{+-}1.2 and 13.9{+-}3.6 Gy, respectively. Acute radiation injury such as a generalized convulsion within 1 week after BNCT was recognized in three patients of Protocol B. Delayed radiation injury such as a neurological deterioration appeared 3-6 months after BNCT, and it was recognized in 1 patient in Protocol A, 5 patients in Protocol B. According to acute radiation injury, the maximum vascular dose was 15.8{+-}1.3 Gy in positive and was 12.6{+-}4.3 Gy in negative. There was no significant difference between them. According to the delayed radiation injury, the maximum vascular dose was 13.8{+-}3.8 Gy in positive and was 13.6{+-}4.9 Gy in negative. There was no significant difference between them. The dose escalation is limited because most patients in Protocol B suffered from acute radiation injury. We conclude that the maximum vascular dose does not exceed over 12 Gy to avoid the delayed radiation injury, especially, it should be limited under 10 Gy in the case that tumor

  16. Shift of microRNA profile upon glioma cell migration using patient-derived spheroids and serum-free conditions.

    Science.gov (United States)

    Munthe, Sune; Halle, Bo; Boldt, Henning B; Christiansen, Helle; Schmidt, Steffen; Kaimal, Vivek; Xu, Jessica; Zabludoff, Sonya; Mollenhauer, Jan; Poulsen, Frantz R; Kristensen, Bjarne W

    2017-03-01

    Glioblastoma multiforme (GBM) is the most frequent malignant primary brain tumor. A major reason for the overall median survival being only 14.6 months is migrating tumor cells left behind after surgery. Another major reason is tumor cells having a so-called cancer stem cell phenotype being therefore resistant towards traditional chemo- and radiotherapy. A group of novel molecular targets are microRNAs (miRNAs). MiRNAs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. The aim of this study was to identify differentially expressed miRNAs in migrating GBM cells using serum-free stem cell conditions. We used patient-derived GBM spheroid cultures for a novel serum-free migration assay. MiRNA expression of migrating tumor cells isolated at maximum migration speed was compared with corresponding spheroids using an OpenArray Real-Time PCR System. The miRNA profiling revealed 30 miRNAs to be differentially expressed. In total 13 miRNAs were upregulated and 17 downregulated in migrating cells compared to corresponding spheroids. The three most deregulated miRNAs, miR-1227 (up-regulated), miR-32 (down-regulated) and miR-222 (down-regulated), were experimentally overexpressed. A non-significantly increased migration rate was observed after miR-1227 overexpression. A significantly reduced migration rate was observed after miR-32 and miR-222 overexpression. In conclusion a shift in microRNA profile upon glioma cell migration was identified using an assay avoiding serum-induced migration. Both the miRNA profiling and the functional validation suggested that miR-1227 may be associated with increased migration and miR-32 and miR-222 with decreased migration. These miRNAs may represent potential novel targets in migrating glioma cells.

  17. The value of (11)C-methionine PET in the early differentiation between tumour recurrence and radionecrosis in patients treated for a high-grade glioma and indeterminate MRI.

    Science.gov (United States)

    Garcia, J R; Cozar, M; Baquero, M; Fernández Barrionuevo, J M; Jaramillo, A; Rubio, J; Maida, G; Soler, M; Riera, E

    To evaluate the contribution of (11)C-Methionine PET in the early differentiation between tumour recurrence and radionecrosis in patients treated for a high grade glioma. The study included 30 patients with glioma (III/IV grade) treated with surgery/radiotherapy/chemotherapy (5-8 months) and with an indeterminate MRI. All patients underwent a (11)C-Methione PET (within 15 days of MRI) and studies were visually analysed (intensity and morphology of uptake), quantified (SUV max/SUV mean background), and coregistered to MRI (3D-Flair). Patient management was decided by the neuro-oncology committee to clinical and imaging follow-up, second-line treatment, or surgery. There were 23 (11)C-Methionine PET studies visually positive. Morphology of uptake was focal in 15, diffuse in 4, and ring-shaped in 4. Three out of the focal uptake cases underwent resection (Histopathology +). Sixteen underwent second-line therapy (11 responded; 5 progressed). The 4 cases with ring-shaped uptake were followed-up, and progression was found in 2 (true-positive), and disease-free in 2 (follow-up of 6 and 7 months, respectively) (false-positive). Seven out of (11)C-Methionine studies PET were visually negative, and all of them were disease-free (follow-up of 3-12 months). SUV lesion/background was 2.79±1.35 in tumour recurrence, and 1.53±0.39 in radionecrosis (PVisual analysis, quantitative and PET/MRI coregistration of (11)C-Methionine PET showed their complementary role in patients with indeterminate MRI results, thus allowing early differentiation between tumour recurrence and radionecrosis, and helping in the individual therapy approach. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  18. A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas†

    Science.gov (United States)

    Raizer, Jeffrey J.; Abrey, Lauren E.; Lassman, Andrew B.; Chang, Susan M.; Lamborn, Kathleen R.; Kuhn, John G.; Yung, W.K. Alfred; Gilbert, Mark R.; Aldape, Kenneth D.; Wen, Patrick Y.; Fine, Howard A.; Mehta, Minesh; DeAngelis, Lisa M.; Lieberman, Frank; Cloughesy, Timothy F.; Robins, H. Ian; Dancey, Janet; Prados, Michael D.

    2010-01-01

    The objective of this phase I study was to determine the maximal tolerated dose (MTD) of erlotinib in patients with recurrent malignant gliomas (MGs) or recurrent meningiomas on enzyme-inducing antiepileptic drugs (EIAEDs). Dose escalation was by a standard 3 × 3 design. The initial starting dose of erlotinib was 150 mg daily. If no dose-limiting toxicity (DLT) was observed, then dose escalation occurs as follows: 200 mg/day, 275 mg/day, and then increased in 125 mg increments until the MTD was reached. The MTD was defined as the dose where ≤1 of 6 patients experienced a DLT and the dose above had 2 or more DLTs. The MTD was 650 mg/day; the observed DLTs were grade 3 rash in 2 patients at 775 mg/day. Pharmacokinetic analysis showed a significant influence of EIAEDs on the metabolism of erlotinib when compared with our phase II data published separately. Primary toxicities were rash and diarrhea. The MTD of erlotinib in patients receiving EIAEDs is substantially higher than the standard dose of 150 mg. This has important implications for further development of this drug in the treatment of MG as well as the optimal management of patients with other malignancies such as NSCLC who are on enzyme-inducing drugs. PMID:20150371

  19. 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.)

  20. Identifying preoperative language tracts and predicting postoperative functional recovery using HARDI q-ball fiber tractography in patients with gliomas.

    Science.gov (United States)

    Caverzasi, Eduardo; Hervey-Jumper, Shawn L; Jordan, Kesshi M; Lobach, Iryna V; Li, Jing; Panara, Valentina; Racine, Caroline A; Sankaranarayanan, Vanitha; Amirbekian, Bagrat; Papinutto, Nico; Berger, Mitchel S; Henry, Roland G

    2016-07-01

    OBJECT Diffusion MRI has uniquely enabled in vivo delineation of white matter tracts, which has been applied to the segmentation of eloquent pathways for intraoperative mapping. The last decade has also seen the development from earlier diffusion tensor models to higher-order models, which take advantage of high angular resolution diffusion-weighted imaging (HARDI) techniques. However, these advanced methods have not been widely implemented for routine preoperative and intraoperative mapping. The authors report on the application of residual bootstrap q-ball fiber tracking for routine mapping of potentially functional language pathways, the development of a system for rating tract injury to evaluate the impact on clinically assessed language function, and initial results predicting long-term language deficits following glioma resection. METHODS The authors have developed methods for the segmentation of 8 putative language pathways including dorsal phonological pathways and ventral semantic streams using residual bootstrap q-ball fiber tracking. Furthermore, they have implemented clinically feasible preoperative acquisition and processing of HARDI data to delineate these pathways for neurosurgical application. They have also developed a rating scale based on the altered fiber tract density to estimate the degree of pathway injury, applying these ratings to a subset of 35 patients with pre- and postoperative fiber tracking. The relationships between specific pathways and clinical language deficits were assessed to determine which pathways are predictive of long-term language deficits following surgery. RESULTS This tracking methodology has been routinely implemented for preoperative mapping in patients with brain gliomas who have undergone awake brain tumor resection at the University of California, San Francisco (more than 300 patients to date). In this particular study the authors investigated the white matter structure status and language correlation in a

  1. [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.

  2. 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...

  3. Evaluation of serial changes on computed tomography and magnetic resonance imaging after implantation of carmustine wafers in patients with malignant gliomas for differential diagnosis of tumor recurrence.

    Science.gov (United States)

    Ohue, Shiro; Kohno, Shohei; Inoue, Akihiro; Yamashita, Daisuke; Suehiro, Satoshi; Seno, Toshimoto; Kumon, Yoshiaki; Kikuchi, Keiichi; Ohnishi, Takanori

    2016-01-01

    Carmustine wafers are approved for localized treatment of malignant glioma. In this study, overall changes in computed tomography (CT) and magnetic resonance (MR) images of malignant glioma patients treated with carmustine wafer implantation were evaluated. The subjects were 25 patients undergoing craniotomy for malignant glioma resection and carmustine wafer implantation. Changes in the appearance of wafers, the resection cavity, and the adjacent parenchyma on CT and MR imaging were evaluated retrospectively. On CT, the wafers changed from an initially high-dense to an iso-dense appearance. All MR studies showed a low-intense wafer within 2 days. The wafers changed to a high- or iso-intense appearance on fluid attenuated inversion recovery and T1-weighted imaging, whereas they changed to an iso- to low-intense appearance on T2-weighted imaging. Gas in the cavity increased gradually after surgery, achieved a peak at 1 week postoperatively, and then disappeared in 1-3 months. Increased volume of the resection cavity was observed in 48% of patients. Regarding changes in the adjacent parenchyma, obvious contrast enhancement at the wall of the resection cavity was seen in 91% of cases at 1 month, but this disappeared gradually. Edema around the resection cavity was increased in 7 patients (28%), of whom only two experienced symptoms due to edema. We conclude that these radiological changes after carmustine wafer implantation should be carefully followed up, because these changes can easily be mistaken for infectious disease or recurrent tumors.

  4. 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...

  5. Diagnostic, treatment, and demographic factors influencing survival in a population-based study of adult glioma patients in the San Francisco Bay Area1

    OpenAIRE

    Wrensch, Margaret; Rice, Terri; Miike, Rei; McMillan, Alex; Lamborn, Kathleen R.; Aldape, Kenneth; Prados, Michael D.

    2006-01-01

    We compare survival estimates for population-based glioma cases by using two diagnostic coding schemes, (1) the International Classification of Diseases, Oncology, second edition (ICD-O-2) as reported by the Surveillance, Epidemiology, and End Results (SEER) program and (2) central neuropathology review diagnosis based on the World Health Organization II classification. In addition, among review categories, we estimate survival in relation to several patient demographic and treatment factors....

  6. Long-Term Cognitive Functioning and Psychological Well-Being in Surgically Treated Patients with Low-Grade Glioma.

    Science.gov (United States)

    Campanella, Fabio; Palese, Alvisa; Del Missier, Fabio; Moreale, Renzo; Ius, Tamara; Shallice, Tim; Fabbro, Franco; Skrap, Miran

    2017-07-01

    The aim of this work is to provide an in-depth investigation of the impact of low-grade gliomas (LGG) and their surgery on patients' cognitive and emotional functioning and well-being, carried out via a comprehensive and multiple-measure psychological and neuropsychological assessment. Fifty surgically treated patients with LGG were evaluated 40 months after surgery on their functioning over 6 different cognitive domains, 3 core affective/emotional aspects, and 3 different psychological well-being measures to obtain a clearer picture of the long-term impact of illness and surgery on their psychological and relational world. Close relatives were also involved to obtain an independent measure of the psychological dimensions investigated. Cognitive status was satisfactory, with only mild short-term memory difficulties. The affective and well-being profile was characterized by mild signs of depression, good satisfaction with life and psychological well-being, and good personality development, with patients perceiving themselves as stronger and better persons after illness. However, patients showed higher emotional reactivity, and psychological well-being measures were negatively affected by epileptic burden. Well-being was related to positive affective/emotional functioning and unrelated to cognitive functioning. Good agreement between patients and relatives was found. In the long-term, patients operated on for LGG showed good cognitive functioning, with no significant long-term cognitive sequelae for the extensive surgical approach. Psychologically, patients appear to experience a deep psychological change and maturation, closely resembling that of so-called posttraumatic growth, which, to our knowledge, is for the first time described and quantified in patients with LGG. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. ADC histograms predict response to anti-angiogenic therapy in patients with recurrent high-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Nowosielski, Martha; Tinkhauser, Gerd; Stockhammer, Guenther [Innsbruck Medical University, Department of Neurology, Innsbruck (Austria); Recheis, Wolfgang; Schocke, Michael; Gotwald, Thaddaeus [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Goebel, Georg [Innsbruck Medical University, Department of Medical Statistics, Informatics and Health Economics, Innsbruck (Austria); Gueler, Oezguer [Innsbruck Medical University, 4D Visualization Laboratory, University Clinic of Oto-, Rhino- and Laryngology, Innsbruck (Austria); Kostron, Herwig [Innsbruck Medical University, Department of Neurosurgery, Innsbruck (Austria); Hutterer, Markus [Innsbruck Medical University, Department of Neurology, Innsbruck (Austria); Paracelsus Medical University Salzburg-Christian Doppler Hospital, Department of Neurology, Salzburg (Austria)

    2011-04-15

    The purpose of this study is to evaluate apparent diffusion coefficient (ADC) maps to distinguish anti-vascular and anti-tumor effects in the course of anti-angiogenic treatment of recurrent high-grade gliomas (rHGG) as compared to standard magnetic resonance imaging (MRI). This retrospective study analyzed ADC maps from diffusion-weighted MRI in 14 rHGG patients during bevacizumab/irinotecan (B/I) therapy. Applying image segmentation, volumes of contrast-enhanced lesions in T1 sequences and of hyperintense T2 lesions (hT2) were calculated. hT2 were defined as regions of interest (ROI) and registered to corresponding ADC maps (hT2-ADC). Histograms were calculated from hT2-ADC ROIs. Thereafter, histogram asymmetry termed ''skewness'' was calculated and compared to progression-free survival (PFS) as defined by the Response Assessment Neuro-Oncology (RANO) Working Group criteria. At 8-12 weeks follow-up, seven (50%) patients showed a partial response, three (21.4%) patients were stable, and four (28.6%) patients progressed according to RANO criteria. hT2-ADC histograms demonstrated statistically significant changes in skewness in relation to PFS at 6 months. Patients with increasing skewness (n = 11) following B/I therapy had significantly shorter PFS than did patients with decreasing or stable skewness values (n = 3, median percentage change in skewness 54% versus -3%, p = 0.04). In rHGG patients, the change in ADC histogram skewness may be predictive for treatment response early in the course of anti-angiogenic therapy and more sensitive than treatment assessment based solely on RANO criteria. (orig.)

  8. O 6 -methylguanine DNA methyltransferase gene promoter methylation in high-grade gliomas: A review of current status

    Directory of Open Access Journals (Sweden)

    Vaishali Suri

    2011-01-01

    Full Text Available Assessment of promoter methylation of the O 6 -methylguanine DNA methyltransferase (MGMT gene has recently gained importance in molecular profiling of high-grade gliomas. It has emerged not only as an important prognostic marker but also as a predictive marker for response to temozolomide in patients with newly diagnosed glioblastoma. Further, recent studies indicate that MGMT promoter methylation has strong prognostic relevance even in anaplastic (grade III gliomas, irrespective of therapy (chemotherapy or radiotherapy. This article provides an overview of its use as a predictive and prognostic biomarker, as well as the methods employed for its assessment and use in therapeutic decision making.

  9. Evaluation of preoperative high magnetic field motor functional MRI (3 Tesla) in glioma patients by navigated electrocortical stimulation and postoperative outcome.

    Science.gov (United States)

    Roessler, K; Donat, M; Lanzenberger, R; Novak, K; Geissler, A; Gartus, A; Tahamtan, A R; Milakara, D; Czech, T; Barth, M; Knosp, E; Beisteiner, R

    2005-08-01

    The validity of 3 Tesla motor functional magnetic resonance imaging (fMRI) in patients with gliomas involving the primary motor cortex was investigated by intraoperative navigated motor cortex stimulation (MCS). Twenty two patients (10 males, 12 females, mean age 39 years, range 10-65 years) underwent preoperative fMRI studies, performing motor tasks including hand, foot, and mouth movements. A recently developed high field clinical fMRI technique was used to generate pre-surgical maps of functional high risk areas defining a motor focus. Motor foci were tested for validity by intraoperative motor cortex stimulation (MCS) employing image fusion and neuronavigation. Clinical outcome was assessed using the Modified Rankin Scale. FMRI motor foci were successfully detected in all patients preoperatively. In 17 of 22 patients (77.3%), a successful stimulation of the primary motor cortex was possible. All 17 correlated patients showed 100% agreement on MCS and fMRI motor focus within 10 mm. Technical problems during stimulation occurred in three patients (13.6%), no motor response was elicited in two (9.1%), and MCS induced seizures occurred in three (13.6%). Combined fMRI and MCS mapping results allowed large resections in 20 patients (91%) (gross total in nine (41%), subtotal in 11 (50%)) and biopsy in two patients (9%). Pathology revealed seven low grade and 15 high grade gliomas. Mild to moderate transient neurological deterioration occurred in six patients, and a severe hemiparesis in one. All patients recovered within 3 months (31.8% transient, 0% permanent morbidity). The validation of clinically optimised high magnetic field motor fMRI confirms high reliability as a preoperative and intraoperative adjunct in glioma patients selected for surgery within or adjacent to the motor cortex.

  10. 12 years' experience with intraoperative radiotherapy (IORT) of malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Schueller, P.; Micke, O.; Moustakis, C.; Bruns, F.; Schuck, A.; Willich, N. [University Hospital Muenster (Germany). Dept. of Radiotherapy and Radiation Oncology; Palkovic, S.; Schroeder, J.; Wassmann, H. [University Hospital Muenster (Germany). Dept. of Neurosurgery

    2005-08-01

    Background: Even after surgery and radiotherapy, malignant gliomas still have a poor prognosis. The authors report on their experience with IORT in 71 patients. Patients and methods: From May 1992 to February 2004, 71 patients with malignant gliomas were treated with IORT. 26 patients suffered from grade III gliomas, 45 patients from glioblastomas (GBM). IORT was carried out using a standard electron tube and 9- to 18-MeV electrons. 52/71 patients who were primarily treated received 20 Gy IORT + 60 Gy postoperative radiotherapy, 19/71 patients with recurrences only received IORT (20-25 Gy). Results: The complication rates were 1.4% for wound infections and 5.6% for hemorrhage. Median disease-specific survival amounted to 14.9 months (gliomass III) and 14.2 months (GBM). The 2-year survival rates amounted to 26.9% (gliomas III) and 6.8% (GBM; p=0.0296). Total versus subtotal resection had no significant influence on survival (p=0.0741), nor had age, sex, tumor site, performance status, size, primary versus recurrence, and radiation dose. A comparison to a conventionally treated patient group did not show a significant survival improvement. 3 months after treatment, initial symptoms had improved in 59% (hemiparesis), 50% (aphasia), 50% (hemianopsia), and 60% (convulsions). Conclusion: IORT has been shown to be feasible; perioperative complication rates were not increased. Survival was generally not improved compared to a historical control group. Recurrences achieved the same survival as primary tumors, and GBM also had a slightly increased survival, thus being possible indications for IORT. (orig.)

  11. {sup 123}I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients

    Energy Technology Data Exchange (ETDEWEB)

    Keyaerts, Marleen; Lahoutte, Tony; Caveliers, Vicky; Vanhove, Chris; Franken, Philippe R.; Bossuyt, Axel [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Nuclear Medicine, Brussels (Belgium); ICMIC Brussels, Vrije Universiteit Brussel VUB, In Vivo Cellular and Molecular Imaging Center, Brussels (Belgium); Neyns, Bart [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Medical Oncology, Oncologisch Centrum, Brussels (Belgium); Everaert, Hendrik; Kersemans, Ken; Mertens, John [Academic Hospital, Vrije Universiteit Brussel AZ-VUB, Department of Nuclear Medicine, Brussels (Belgium)

    2007-07-15

    {sup 123}I-2-iodo-tyrosine ({sup 123}I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. For the biodistribution study, six male volunteers received 60-95 MBq {sup 123}I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of {sup 123}I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. {sup 123}I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, {sup 123}I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39-3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). {sup 123}I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients. (orig.)

  12. Type 2 diabetes mellitus and obesity are independent risk factors for poor outcome in patients with high-grade glioma.

    Science.gov (United States)

    Chambless, Lola B; Parker, Scott L; Hassam-Malani, Laila; McGirt, Matthew J; Thompson, Reid C

    2012-01-01

    Type 2 diabetes mellitus (DM) and obesity are known risk factors for poor outcomes in patients with systemic malignancies but are not well-studied in the brain tumor population. In this study we asked if type 2 DM and elevated body mass index (BMI) are independent risk factors for poor prognosis in patients with high-grade glioma (HGG.). We conducted a retrospective cohort study of 171 patients surgically treated for HGG at a single institution. BMI and records of pre-existing type 2 DM were obtained from medical histories. Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P 0.05 were then removed from the multivariate model in a step-wise fashion. Mean age at diagnosis was 55.0 ± 17.3 years. Fifteen (8.8%) patients had a history of type 2 DM. Fifty-eight (35.8%) patients had a BMI 30. Radiation therapy, temozolomide, and higher KPS score were independently associated with prolonged survival while increasing age was associated with decreased survival. DM (P = 0.001) and increasing BMI (P = 0.003) were found to be independently associated with decreased survival. Diabetics had a decreased median overall survival (312 vs. 470 days, P = 0.003) and PFS (106 vs. 166 days, P = 0.04) compared to non-diabetics. Increasing BMI (30) was also associated with decreased median PFS: 195 vs. 165 vs. 143 days, respectively. Pre-existing DM and elevated BMI are independent risk factors for poor outcome in patients with HGG.

  13. Immunochemotherapy with levamisole for stage III gastric cancer patients.

    Directory of Open Access Journals (Sweden)

    Miwa,Hiroaki

    1983-12-01

    Full Text Available Levamisole (LMS was given to stage III gastric cancer patients starting three days before gastrectomy, at a does of 150 mg/day for three consecutive days every other week. Survival rates of these patients were compared with those of stage III gastric cancer patients previously operated in our Department who had not received levamisole. The background factors of both groups were matched as closely as possible. Both groups were concomitantly treated with mitomycin C and FT-207. The survival rate of the LMS group was significantly higher than that of the control group when the tumor had a diameter of 4.0-8.0 cm, cancer cells infiltrated to the gastric serosa, there were metastases within the regional lymph nodes, cancer cells slightly invaded the venous capillaren and there was moderate infiltration of the stroma.

  14. Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

    Directory of Open Access Journals (Sweden)

    Eliane C Miotto

    Full Text Available Patients with low-grade glioma (LGG have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR, related-non-structured (RNS, and related-structured words (RS, allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG and middle frontal gyrus (MFG during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

  15. Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

    Science.gov (United States)

    Miotto, Eliane C; Balardin, Joana B; Vieira, Gilson; Sato, Joao R; Martin, Maria da Graça M; Scaff, Milberto; Teixeira, Manoel J; Junior, Edson Amaro

    2014-01-01

    Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

  16. Signal intensity in T2' magnetic resonance imaging is related to brain glioma grade

    Energy Technology Data Exchange (ETDEWEB)

    Saitta, Laura; Castellan, Lucio [San Martino Hospital, Department of Diagnostic and Interventional Neuroradiology, Genoa (Italy); Heese, Oliver; Westphal, Manfred [UKE, Department of Neurosurgery, Hamburg (Germany); Foerster, Ann-Freya; Siemonsen, Susanne; Fiehler, Jens; Goebell, Einar [University Medical Center Hamburg-Eppendorf (UKE), Department of Diagnostic and Interventional Neuroradiology, Hamburg (Germany); Matschke, Jakob [UKE, Department of Neuropathology, Hamburg (Germany)

    2011-05-15

    T2' values reflect the presence of deoxyhaemoglobin related to high local oxygen extraction. We assessed the feasibility of T2' imaging to display regions with high metabolic activity in brain gliomas. MRI was performed in 25 patients (12 female; median age 46 years; range 2-69) with brain gliomas with additional T2 and T2* sequences. T2' maps were derived from T2 and T2*. Dynamic susceptibility weighted contrast (DSC) perfusion was performed in 12/25 patients. Images were visually assessed by two readers and five ROIs were evaluated for each patient. Pearson correlation, Mann-Whitney and Kruskal-Wallis tests were applied for statistical analysis. Three patients were not further evaluated because of artefacts. Mean values of high-grade (III-IV) gliomas showed significantly lower T2' values than low-grade (II) gliomas (p < 0.001). An inverse relationship was observed between rCBV and sqr (T2') (r = -0.463, p < 0.001). No correlation was observed between T2' and rCBV for grade II tumours (r = 0.038; p = 0.875). High-grade tumours revealed lower T2' values, presumably because of higher oxygen consumption in proliferating tissue. Our results indicate that T2' imaging can be used as an alternative to DSC perfusion in the detection of subtle deviations in tumour metabolism. (orig.)

  17. Cervical vertebrae anomalies in patients with class III skeletal malocclusion

    Directory of Open Access Journals (Sweden)

    Shahin Emami Meibodi

    2011-01-01

    Full Text Available Background and Objective : Studies have documented that deviations in skeletal components such as the cranial base, the mid-facial complex and the mandible may be associated with morphological factors in patients with class III skeletal malocclusion. Furthermore, deviations in head and neck posture may be associated with the class III skeletal malocclusion. The purpose of this study was to compare cervical vertebrae morphology in patients with class III skeletal malocclusion and adults with normal occlusion. Materials and Methods: This case-control study assessed 30 patients with class III skeletal malocclusion (aged 17-30 yrs, with normal vertical growth pattern and ANB<0 were compared with 46 controls (aged 17-30 years, with normal vertical growth pattern, ANB=3+1. Cervical vertebrae anomalies (fusion anomalies and posterior arch deficiency were assessed via evaluation of their lateral cephalograms. The t- test and Fisher′s exact test were used for statistical analysis. Results: In the study group, 73.3% had fusion of the body of the cervical vertebrae, while in the control group only 32.6% showed fusion. The fusion in the control group was between C2 and C3 in all cases; whereas, in the study group, fusion was seen between C2-C3, C3-C¬4 or C4-C¬5. Additionally, cervical column deviations occurred significantly more often in the study group compared to the control group (P<0.001. Conclusion : Class III skeletal malocclusion may be associated with fusion of cervical vertebrae and deviation of the cervical column.

  18. 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.

  19. Optic radiation fiber tractography in glioma patients based on high angular resolution diffusion imaging with compressed sensing compared with diffusion tensor imaging - initial experience.

    Directory of Open Access Journals (Sweden)

    Daniela Kuhnt

    Full Text Available OBJECTIVE: Up to now, fiber tractography in the clinical routine is mostly based on diffusion tensor imaging (DTI. However, there are known drawbacks in the resolution of crossing or kissing fibers and in the vicinity of a tumor or edema. These restrictions can be overcome by tractography based on High Angular Resolution Diffusion Imaging (HARDI which in turn requires larger numbers of gradients resulting in longer acquisition times. Using compressed sensing (CS techniques, HARDI signals can be obtained by using less non-collinear diffusion gradients, thus enabling the use of HARDI-based fiber tractography in the clinical routine. METHODS: Eight patients with gliomas in the temporal lobe, in proximity to the optic radiation (OR, underwent 3T MRI including a diffusion-weighted dataset with 30 gradient directions. Fiber tractography of the OR using a deterministic streamline algorithm based on DTI was compared to tractography based on reconstructed diffusion signals using HARDI+CS. RESULTS: HARDI+CS based tractography displayed the OR more conclusively compared to the DTI-based results in all eight cases. In particular, the potential of HARDI+CS-based tractography was observed for cases of high grade gliomas with significant peritumoral edema, larger tumor size or closer proximity of tumor and reconstructed fiber tract. CONCLUSIONS: Overcoming the problem of long acquisition times, HARDI+CS seems to be a promising basis for fiber tractography of the OR in regions of disturbed diffusion, areas of high interest in glioma surgery.

  20. Post Traumatic Glioma – An association questioned

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    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.

  1. IDH1/2 Mutation and MGMT Promoter Methylation - the Relevant Survival Predictors in Czech Patients with Brain Gliomas.

    Science.gov (United States)

    Kramář, F; Minárik, M; Benešová, L; Halková, T; Netuka, D; Bradáč, O; Beneš, V

    2016-01-01

    Gliomas are a heterogeneous group of tumours varying in prognosis, treatment approach, and overall survival. Recently, novel markers have been identified which are linked to patient prognosis and therapeutic response. Especially the mutation of the enzyme isocitrate dehydrogenase 1 or 2 (IDH1/2) gene and the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status seem to be the most important predictors of survival. From 2012 to 2015, 94 Czech patients with primary brain tumours were enrolled into the study. The IDH1/2 mutation was detected by denaturing capillary electrophores.The methylation status of the MGMT gene and other 46 genes was revealed by MS-MLPA. In all 94 patients, the clinical data were correlated with molecular markers by Kaplan-Meier analyses and Cox regression model. The MGMT promoter methylation status was established and compared to clinical data. In our study eight different probes were used to elucidate the MGMT methylation status; hypermethylation was proclaimed if four and more probes were positive. This 3 : 5 ratio was tested and confirmed by Kaplan-Meier and Cox analyses. The study confirmed the importance of the IDH1/2 mutation and hypermethylation of the MGMT gene promoter being present in tumour tissue. Both markers are independent positive survival predictors; in the Cox model the IDH hazard ratio was 0.10 and in the case of MGMT methylation it reached 0.32. The methylation analysis of the panel of additional 46 genes did not reveal any other significant epigenetic markers; none of the candidate genes have been confirmed in the Cox regression analyses as an independent prognostic factor.

  2. 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.

  3. 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.

  4. 7-Tesla Susceptibility-Weighted Imaging to Assess the Effects of Radiotherapy on Normal-Appearing Brain in Patients With Glioma

    Energy Technology Data Exchange (ETDEWEB)

    Lupo, Janine M., E-mail: janine.lupo@ucsf.edu [Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA (United States); Chuang, Cynthia F. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Chang, Susan M. [Department of Neurosurgery, University of California, San Francisco, San Francisco, CA (United States); Barani, Igor J. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Jimenez, Bert; Hess, Christopher P. [Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA (United States); Nelson, Sarah J. [Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA (United States); Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA (United States)

    2012-03-01

    Purpose: To evaluate the intermediate- and long-term imaging manifestations of radiotherapy on normal-appearing brain tissue in patients with treated gliomas using 7T susceptibility-weighted imaging (SWI). Methods and Materials: SWI was performed on 25 patients with stable gliomas on a 7 Tesla magnet. Microbleeds were identified as discrete foci of susceptibility that did not correspond to vessels. The number of microbleeds was counted within and outside of the T2-hyperintense lesion. For 3 patients, radiation dosimetry maps were reconstructed and fused with the 7T SWI data. Results: Multiple foci of susceptibility consistent with microhemorrhages were observed in patients 2 years after chemoradiation. These lesions were not present in patients who were not irradiated. The prevalence of microhemorrhages increased with the time since completion of radiotherapy, and these lesions often extended outside the boundaries of the initial high-dose volume and into the contralateral hemisphere. Conclusions: High-field SWI has potential for visualizing the appearance of microbleeds associated with long-term effects of radiotherapy on brain tissue. The ability to visualize these lesions in normal-appearing brain tissue may be important in further understanding the utility of this treatment in patients with longer survival.

  5. 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).

  6. Roles of the Wada Test and Functional Magnetic Resonance Imaging in Identifying the Language-dominant Hemisphere among Patients with Gliomas Located near Speech Areas

    Science.gov (United States)

    ISHIKAWA, Tatsuya; MURAGAKI, Yoshihiro; MARUYAMA, Takashi; ABE, Kayoko; KAWAMATA, Takakazu

    2017-01-01

    This study examined the accuracy of functional magnetic resonance imaging (fMRI) in identifying the language-dominant hemisphere and the situations in which the Wada test can be skipped among patients with gliomas located near speech areas. We examined 74 patients [48 men (64.9%); mean ± standard deviation age of 42.7 ± 13.6 years (range: 13 to 70 years); 71 right-handed, 2 left-handed, and 1 ambidextrous] with gliomas located near speech areas. All patients underwent the Wada test and fMRI, and 34 patients underwent awake surgery. The “last-and-first” task was administered during fMRI. The Wada test was successful in determining the language-dominant hemisphere in 73 patients (98.6%): left hemisphere in 68 patients (91.9%), right hemisphere in 4 patients (5.4%), and bilateral in 1 patient (1.4%). The dominant hemisphere for right-handed patients (n = 71) was the left hemisphere in 67 patients (94.3%), right hemisphere in 3 patients (4.2%), and undetectable in 1 patient (1.4%). The fMRI was successful in determining the language-dominant hemisphere in 53 patients (71.6%). The results of the Wada test and fMRI were inconsistent in 5 patients (8.6%), of which 3 (5.2%) exhibited dominance in opposite hemispheres. Furthermore, 2 of these 3 cases (2.7%) were contralateral false positive cases, whereby fMRI identified the right-hemisphere as language dominant for right-handed individuals with tumors in the left hemisphere. Based on these findings, we concluded that the Wada test can be skipped if language dominancy can be detected by fMRI. PMID:27980284

  7. Tumor Extension in High-Grade Gliomas Assessed with Diffusion Magnetic Resonance Imaging: Values and Lesion-to-Brain Ratios of Apparent Diffusion Coefficient and Fractional Anisotropy

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    Westen, D. van; Laett, J.; Englund, E.; Brockstedt, S.; Larsson, E.M. [Lund Univ. Hospital (Sweden). Depts. of Radiology, of Medical Radiation Physics and of Pathology and Cytology

    2006-04-15

    Purpose: To determine whether the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) can distinguish tumor-infiltrated edema in gliomas from pure edema in meningiomas and metastases. Material and Methods: Thirty patients were studied: 18 WHO grade III or IV gliomas, 7 meningiomas, and 5 metastatic lesions. ADC and FA were determined from ROIs placed in peritumoral areas with T2-signal changes, adjacent normal appearing white matter (NAWM), and corresponding areas in the contralateral healthy brain. Values and lesion-to-brain ratios from gliomas were compared to those from meningiomas and metastases. Results: Values and lesion-to-brain ratios of ADC and FA in peritumoral areas with T2-signal changes did not differ between gliomas, meningiomas, and metastases (P = 0.40, P = 0.40, P = 0.61, P 0.34). Values of ADC and FA and the lesion-to-brain ratio of FA in the adjacent NAWM did not differ between tumor types (P = 0.74, P = 0.25, and P = 0.31). The lesion-to-brain ratio of ADC in the adjacent NAWM was higher in gliomas than in meningiomas and metastases (P = 0.004), but overlapped between tumor types. Conclusion: Values and lesion-to-brain ratios of ADC and FA in areas with T2-signal changes surrounding intracranial tumors and adjacent NAWM were not helpful for distinguishing pure edema from tumor-infiltrated edema when data from gliomas, meningiomas, and metastases were compared.

  8. Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [[sup 99m]Tc ]PnAO-biotin

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, G. (INB-CNR, Milan Univ. (Italy). Dept. of Nuclear Medicine Scientific Inst. H San Raffaele, Milan (Italy)); Magnani, P. (INB-CNR, Milan Univ. (Italy). Dept. of Nuclear Medicine Scientific Inst. H San Raffaele, Milan (Italy)); Zito, F. (INB-CNR, Milan Univ. (Italy). Dept. of Nuclear Medicine Scientific Inst. H San Raffaele, Milan (Italy)); Lucignani, G. (INB-CNR, Milan Univ. (Italy). Dept. of Nuclear Medicine Scientific Inst. H San Raffaele, Milan (Italy)); Sudati, F. (INB-CNR, Milan Univ. (Italy). Dept. of Nuclear Medicine Scientific Inst. H San Raffaele, Milan (Italy)); Truci, G. (Div. of Neurology, Milan Univ. (Italy) Scientific Inst. H San Raffaele, Milan (Italy)); Motti, E. (Div. of Neurosurgery, Milan Univ. (Italy) Scientific Inst. H San Raffaele, Milan (Italy)); Terreni, M. (Dept. of Pathology, Scientific Inst. H San Raffaele, Milan (Italy)); Pollo, B. (Dept. of Pathology, Scientific Inst. G. Besta, Milan (Italy)); Giovanelli, M. (Div. of Neurosurgery, Milan

    1994-04-01

    We have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24-36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15-20 mCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [[sup 99m]Tc]PnAO-biotin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1-2 h after the administration of [[sup 99m]Tc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential adminsitration of anti-tenascin MoAb BC2, avidin and [[sup 99m]Tc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. (orig./MG)

  9. Advantages of high b-value diffusion-weighted imaging to diagnose pseudo-responses in patients with recurrent glioma after bevacizumab treatment

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Fumiyuki; Kurisu, Kaoru [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Aoki, Tomokazu [Department of Neurosurgery, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555 (Japan); Yamanaka, Masami [Department of Neurosurgery, Otagawa Hospital, Hiroshima 732-0009 (Japan); Kajiwara, Yoshinori; Watanabe, Yosuke; Takayasu, Takeshi [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Akiyama, Yuji [Department of Clinical Radiology, Hiroshima University Hospital, Hiroshima 734-8551 (Japan); Sugiyama, Kazuhiko, E-mail: sugiyama-hma@umin.ac.jp [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan)

    2012-10-15

    Background: The diagnosis of pseudo-responses after bevacizumab treatment is difficult. Because diffusion-weighted imaging (DWI) is associated with cell density, it may facilitate the differentiation between true- and pseudo-responses. Furthermore, as high b-value DWI is even more sensitive to diffusion, it has been reported to be diagnostically useful in various clinical settings. Materials and methods: Between September 2008 and May 2011, 10 patients (5 males, 5 females; age range 6–65 years) with recurrent glioma were treated with bevacizumab. All underwent pre- and post-treatment MRI including T2- or FLAIR imaging, post-gadolinium contrast T1-weighted imaging, and DWI with b-1000 and b-4000. Response rates were evaluated by MacDonald- and by response assessment in neuro-oncology working group (RANO) criteria. We also assessed the response rate by calculating the size of high intensity areas using high b-value diffusion-weighted criteria. Prognostic factors were evaluated using Kaplan–Meier survival curves (log-rank test). Results: It was easier to identify pseudo-responses with RANO- than MacDonald criteria, however the reduction of edema by bevacizumab rendered the early diagnosis of tumor progression difficult by RANO criteria. In some patients with recurrent glioma treated with bevacizumab, high b-value diffusion-weighted criteria did, while MacDonald- and RANO criteria did not identify pseudo-responses at an early point after the start of therapy. Discussion and conclusion: High b-value DWI reflects cell density more accurately than regular b-value DWI. Our findings suggest that in patients with recurrent glioma, high b-value diffusion-weighted criteria are useful for the differentiation between pseudo- and true responses to treatment with bevacizumab.

  10. Comparison of Different Post-Processing Algorithms for Dynamic Susceptibility Contrast Perfusion Imaging of Cerebral Gliomas.

    Science.gov (United States)

    Kudo, Kohsuke; Uwano, Ikuko; Hirai, Toshinori; Murakami, Ryuji; Nakamura, Hideo; Fujima, Noriyuki; Yamashita, Fumio; Goodwin, Jonathan; Higuchi, Satomi; Sasaki, Makoto

    2017-04-10

    The purpose of the present study was to compare different software algorithms for processing DSC perfusion images of cerebral tumors with respect to i) the relative CBV (rCBV) calculated, ii) the cutoff value for discriminating low- and high-grade gliomas, and iii) the diagnostic performance for differentiating these tumors. Following approval of institutional review board, informed consent was obtained from all patients. Thirty-five patients with primary glioma (grade II, 9; grade III, 8; and grade IV, 18 patients) were included. DSC perfusion imaging was performed with 3-Tesla MRI scanner. CBV maps were generated by using 11 different algorithms of four commercially available software and one academic program. rCBV of each tumor compared to normal white matter was calculated by ROI measurements. Differences in rCBV value were compared between algorithms for each tumor grade. Receiver operator characteristics analysis was conducted for the evaluation of diagnostic performance of different algorithms for differentiating between different grades. Several algorithms showed significant differences in rCBV, especially for grade IV tumors. When differentiating between low- (II) and high-grade (III/IV) tumors, the area under the ROC curve (Az) was similar (range 0.85-0.87), and there were no significant differences in Az between any pair of algorithms. In contrast, the optimal cutoff values varied between algorithms (range 4.18-6.53). rCBV values of tumor and cutoff values for discriminating low- and high-grade gliomas differed between software packages, suggesting that optimal software-specific cutoff values should be used for diagnosis of high-grade gliomas.

  11. A patient with optic pathway glioma, scoliosis, Chiari type I malformation and syringomyelia : is it Neurofibromatosis type 1?

    Directory of Open Access Journals (Sweden)

    Chakravarty A

    2002-10-01

    Full Text Available A 22 years old girl had features of optic pathway glioma, scoliosis, Chiari type 1 malformation and cervical syringomyelia. She had no cutaneous lesions. We considered this combination to be more than coincidental and argue in favour of considering the case as a variant form of Neurofibromatosis type 1. The relevent literature in favour of our contention has been reviewed.

  12. Tissue microarray analysis for epithelial membrane protein-2 as a novel biomarker for gliomas.

    Science.gov (United States)

    Chung, Lawrance K; Pelargos, Panayiotis E; Chan, Ann M; Demos, Joanna V; Lagman, Carlito; Sheppard, John P; Nguyen, Thien; Chang, Yu-Ling; Hojat, Seyed A; Prins, Robert M; Liau, Linda M; Nghiemphu, Leia; Lai, Albert; Cloughesy, Timothy F; Yong, William H; Gordon, Lynn K; Wadehra, Madhuri; Yang, Isaac

    2017-09-08

    Epithelial membrane protein-2 (EMP2) expression is noted in many human cancers. We evaluated EMP2 as a biomarker in gliomas. A large tissue microarray of lower grade glioma (WHO grades II-III, n = 19 patients) and glioblastoma (GBM) (WHO grade IV, n = 50 patients) was stained for EMP2. EMP2 expression was dichotomized to low or high expression scores and correlated with clinical data. The mean EMP2 expression was 1.68 in lower grade gliomas versus 2.20 in GBMs (P = 0.01). The percentage of samples with high EMP2 expression was greater in GBMs than lower grade gliomas (90.0 vs. 52.6%, P = 0.001). No significant difference was found between median survival among patients with GBM tumors exhibiting high EMP2 expression and survival of those with low EMP2 expression (8.38 vs. 10.98 months, P = 0.39). However, EMP2 expression ≥2 correlated with decreased survival (r = -0.39, P = 0.001). The EMP2 expression level also correlated with Ki-67 positivity (r = 0.34, P = 0.008). The mortality hazard ratio for GBM patients with EMP2 score of 3 or higher was 1.92 (CI 0.69-5.30). Our findings suggest that elevated EMP2 expression is associated with GBM. With other biomarkers, EMP2 may have use as a molecular target for the diagnosis and treatment of gliomas.

  13. The prognostic value of a seven-microRNA classifier as a novel biomarker for the prediction and detection of recurrence in glioma patients.

    Science.gov (United States)

    Chen, Wanghao; Yu, Qiang; Chen, Bo; Lu, Xingyu; Li, Qiaoyu

    2016-08-16

    Glioma is often diagnosed at a later stage, and the high risk of recurrence remains a major challenge. We hypothesized that the microRNA expression profile may serve as a biomarker for the prognosis and prediction of glioblastoma recurrence. We defined microRNAs that were associated with good and poor prognosis in 300 specimens of glioblastoma from the Cancer Genome Atlas. By analyzing microarray gene expression data and clinical information from three random groups, we identified 7 microRNAs that have prognostic and prognostic accuracy: microRNA-124a, microRNA-129, microRNA-139, microRNA-15b, microRNA-21, microRNA-218 and microRNA-7. The differential expression of these miRNAs was verified using an independent set of glioma samples from the Affiliated People's Hospital of Jiangsu University. We used the log-rank test and the Kaplan-Meier method to estimate correlations between the miRNA signature and disease-free survival/overall survival. Using the LASSO model, we observed a uniform significant difference in disease-free survival and overall survival between patients with high-risk and low-risk miRNA signature scores. Furthermore, the prognostic capability of the seven-miRNA signature was demonstrated by receiver operator characteristic curve analysis. A Circos plot was generated to examine the network of genes and pathways predicted to be targeted by the seven-miRNA signature. The seven-miRNA-based classifier should be useful in the stratification and individualized management of patients with glioma.

  14. Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma

    Energy Technology Data Exchange (ETDEWEB)

    Goettler, Jens; Preibisch, Christine [TU Muenchen, Department of Neuroradiology, Klinikum rechts der Isar, Munich (Germany); TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Munich (Germany); Lukas, Mathias; Mustafa, Mona; Schwaiger, Markus; Pyka, Thomas [TU Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kluge, Anne; Kaczmarz, Stephan; Zimmer, Claus [TU Muenchen, Department of Neuroradiology, Klinikum rechts der Isar, Munich (Germany); Gempt, Jens; Ringel, Florian; Meyer, Bernhard [TU Muenchen, Department of Neurosurgery, Klinikum rechts der Isar, Munich (Germany); Foerster, Stefan [TU Muenchen, TUM Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Munich (Germany); TU Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Klinikum Bayreuth, Department of Nuclear Medicine, Bayreuth (Germany)

    2017-03-15

    {sup 18}F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV. Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined. While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average. Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology. (orig.)

  15. MGMT promoter methylation in serum and cerebrospinal fluid as a tumor-specific biomarker of glioma.

    Science.gov (United States)

    Wang, Zheng; Jiang, Wei; Wang, Yahong; Guo, Yang; Cong, Zheng; DU, Fangfang; Song, Bin

    2015-07-01

    O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a conventional technique to predict the prognosis or individualized treatment of glioma in tumor tissue following surgery or biopsy. However, the technique cannot be applied in those glioma patients with concomitant neurological dysfunctions or advanced age. The present study aimed to find a new minimally invasive and efficient alternative method for the detection of MGMT promoter methylation. The expression of MGMT promoter methylation was assessed in peripheral blood and cerebrospinal fluid (CSF), and compared to the corresponding tumor tissue from glioma patients. The 89 patients in the study [32 World Health Organization (WHO) grade II, 19 WHO grade III and 38 WHO grade IV) were pathologically-diagnosed glioma and received radiation therapy following sample collection. The resected glioma tumor tissue (89), corresponding serum (89) and CSF (78) samples were collected for the detection of MGMT promoter methylation using methylation-specific polymerase chain reaction. The sensitivity and specificity of detecting MGMT promoter methylation in CSF and serum were compared. Among the tumor tissue samples, 51/89 (57.3%) showed MGMT promoter methylation. The specificity of the detection in the CSF and serum samples reached 100%. The sensitivity of MGMT promoter methylation detection in CSF and serum were 26/40 (65.0%) and 19/51 (37.3%), respectively (PMGMT promoter methylation detection using CSF were 8/12 (66.7%), 11/18 (61.1%) and 7/10 (70.0%), respectively, which were significantly higher than the sensitivities using serum (7/21, 33.3%; 7/19, 36.8%; and 5/11, 45.5%, respectively PMGMT promoter methylation using CSF and serum were 18/25 (72.0%) and 10/24 (41.7%), respectively, both of which were significantly higher than the corresponding values for patients without residual tumors (8/15, 53.3% and 6/19, 31.6%, respectively; PMGMT promoter methylation in CSF specimens shows higher sensitivity

  16. Cognitive Rehabilitation in Patients with Gliomas and Other Brain Tumors: State of the Art

    Directory of Open Access Journals (Sweden)

    E. Bergo

    2016-01-01

    Full Text Available Disease prognosis is very poor in patients with brain tumors. Cognitive deficits due to disease or due to its treatment have an important weight on the quality of life of patients and caregivers. Studies often take into account quality of life as a fundamental element in the management of disease and interventions have been developed for cognitive rehabilitation of neuropsychological deficits with the aim of improving the quality of life and daily-life autonomy of patients. In this literature review, we will consider the published studies of cognitive rehabilitation over the past 20 years.

  17. 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.

  18. Interstitial Chemotherpy with doxorubicin-loaded PLA polymer for S.C. C6 glioma model in rats and examining PLA-doxorubicin controlled-release capacity with HPLC

    Institute of Scientific and Technical Information of China (English)

    WANG Qin; LI Bao-lu; ZHANG Ming-chen; LI Xin-gang; HAO Xiao-guang

    2001-01-01

    @@ Glioma has the highest incidence in the brain tumors. Though treated with surgical resection, external beam radiation therapy, and systemic chemotherapy, patients with glioma have poor prognosis because of glioma recurrence.

  19. 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.

  20. Compensatory canine angulation in angle Class II and III patients

    Directory of Open Access Journals (Sweden)

    Mauro Carlos Agner Busato

    2009-09-01

    Full Text Available The aim of this study was to evaluate the occurence of compensation in mesiodistal axial inclinations of canines in skeletal malocclusions patients. The sample consisted of 25 Angle Class II, division 1 malocclusion (group 1 and 19 Angle Class III malocclusion patients (group 2. After measurement of dental angulations through a method that associates plaster model photography and AutoCad software, comparisons between the groups were performed by T-test for independent samples. Results showed that there was no statistically significant difference (p < 0.05 between groups, when maxillary canine angulations were compared. Regarding the mandibular canines, there was a statistically significant difference in dental angulation, expressed by 3.2° for group 1 and 0.15° for group 2. An upright position tendency for mandibular canines was observed in the Angle Class III sample. This configures a pattern of compensatory coronary positioning, since the angulation of these teeth makes them occupy less space in the dental arch and consequently mandibular incisors can be in a more retracted position in the sagittal plane.

  1. Diagnostic Performance and Safety of Positron Emission Tomography Using 18F-Fluciclovine in Patients with Clinically Suspected High- or Low-grade Gliomas: A Multicenter Phase IIb Trial

    Directory of Open Access Journals (Sweden)

    Toshihiko Wakabayashi

    2017-01-01

    Full Text Available Objective(s: The study objective was to assess the diagnostic performance of positron emission tomography (PET for gliomas using the novel tracer 18F-fluciclovine (anti-[18F]FACBC and to evaluate the safety of this tracer in patients with clinically suspected gliomas.Methods: Anti-[18F]FACBC was administered to 40 patients with clinically suspected high- or low-grade gliomas, followed by PET imaging. T1-weighted, contrast-enhanced T1-weighted, and fluid-attenuated inversion recovery (or T2-weighted magnetic resonance imaging (MRI scans were obtained to plan for the tissue collection. Tissues were collected from either “areas visualized using anti-[18F]FACBC PET imaging but not using contrast-enhanced T1-weighted imaging” or “areas visualized using both anti-[18F]FACBC-PET imaging and contrast-enhanced T1-weighted imaging” and were histopathologically examined to assess the diagnostic accuracy of anti-[18F]FACBC-PET for gliomas.Results: The positive predictive value of anti-[18F]FACBC-PET imaging for glioma in areas visualized using anti-[18F]FACBC-PET imaging, but not visualized using contrast-enhanced T1- weighted images, was 100.0% (26/26, and the value in areas visualized using both contrastenhanced T1-weighted imaging and anti- [18F]FACBC-PET imaging was 87.5% (7/8. Twelve adverse events occurred in 7 (17.5% of the 40 patients who received anti-[18F]FACBC. Five events in five patients were considered to be adverse drug reactions; however, none of the events were serious, and all except one resolved spontaneously without treatment.Conclusion: This Phase IIb trial showed that anti-[18F]FACBC-PET imaging was effective for the detection of gliomas in areas not visualized using contrast-enhanced T1-weighted MRI and the tracer was well tolerated.

  2. 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.

  3. Genetics and immunotherapy: using the genetic landscape of gliomas to inform management strategies.

    Science.gov (United States)

    Wang, Joanna Y; Bettegowda, Chetan

    2015-07-01

    Recent work in genetics has identified essential driver mutations in gliomas and has profoundly changed our understanding of tumorigenesis. New insights into the molecular basis of glioma has informed the development of therapies demonstrating considerable potential, including immunotherapeutic approaches such as peptide and dendritic cell vaccines against EGFRvIII. However, the selective targeting of one component of a dysregulated pathway may be inadequate for a durable clinical response, given the intratumoral heterogeneity of glioblastoma (GBM) and hypermutated profiles displayed by tumor recurrences. Immune checkpoint blockade with anti-cytotoxic T lymphocyte antigen-4 (CTLA) and anti-programmed cell death 1 (PD-1) have demonstrated encouraging results in clinical trials with other solid tumors, and recent data suggest that this type of therapy may be particularly useful for tumors with high mutational burdens. Although the survival for patients with GBM has remains grim, the use of immunotherapy may finally change patient outcomes.

  4. Dosimetric advantages of proton therapy over conventional radiotherapy with photons in young patients and adults with low-grade glioma

    Energy Technology Data Exchange (ETDEWEB)

    Harrabi, S.B.; Herfarth, K. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Bougatf, N. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); University Hospital Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Department of Medical Physics in Radiation Oncology, Heidelberg (Germany); Mohr, A. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); University Hospital Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Haberer, T. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Combs, S.E. [Helmholtz Zentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovative Radiotherapy (iRT), Oberschleissheim (Germany); Deutsches Konsortium fuer Translationale Krebsforschung (dktk), Partner Site Munich, Munich (Germany); Debus, J.; Adeberg, S. [Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); University Hospital Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany)

    2016-11-15

    Low-grade glioma (LGG) is a very common brain tumor in pediatric patients typically associated with a very good prognosis. This prognosis makes it imperative that the risk of long-term treatment-related side effects be kept at an absolute minimum. Proton therapy (PRT) provides a radiation technique that has the potential to further reduce the genesis of radiogenic impairment. We retrospectively assessed 74 patients with LGG who underwent PRT. Conventional three-dimensional photon and PRT plans were generated after contouring structures of neurogenesis, crucial neuronal structures, and areas susceptible to secondary malignancies. Target volume coverage was evaluated using the homogeneity index (HI) and inhomogeneity coefficient (IC). Results were compared using the Wilcoxon-signed rank test, with p < 0.05 being statistically significant. Target volume coverage was comparable for the photon and proton plans. Overall, we could show an essential reduction in maximal, mean, and integral doses in critical neurologic structures, areas of neurogenesis, and structures of neurocognitive function. The study indicated specifically how contralaterally located structures could be spared with PRT. PRT is a highly conformal radiation technique offering superior dosimetric advantages over conventional radiotherapy by allowing significant dose reduction for organs at risk (OAR) that are essential for neurologic function, neurocognition, and quality of life, thus demonstrating the potential of this technique for minimizing long-term sequelae. (orig.) [German] Niedriggradige Gliome (LGG) zaehlen zu den haeufigsten Hirntumoren im Kindesalter und sind ueblicherweise mit einer sehr guten Prognose vergesellschaftet. Es gilt daher, das Risiko fuer therapieassoziierte Spaetfolgen so gering wie moeglich zu halten. Mit der Protonenbestrahlung steht eine Bestrahlungsmodalitaet zur Verfuegung, mit der das Auftreten radiogener Spaetfolgen im Vergleich zu konventionellen Bestrahlungstechniken

  5. N(4)-tolyl-2-acetylpyridine thiosemicarbazones and their platinum(II,IV) and gold(III) complexes: cytotoxicity against human glioma cells and studies on the mode of action.

    Science.gov (United States)

    Ferraz, Karina S O; Da Silva, Jeferson G; Costa, Flávia M; Mendes, Bruno M; Rodrigues, Bernardo L; dos Santos, Raquel G; Beraldo, Heloisa

    2013-10-01

    Complexes [Au(2Ac4oT)Cl][AuCl2] (1), [Au(Hpy2Ac4mT)Cl2]Cl·H2O (2), [Au(Hpy2Ac4pT)Cl2]Cl (3), [Pt(H2Ac4oT)Cl]Cl (4), [Pt(2Ac4mT)Cl]·H2O (5), [Pt(2Ac4pT)Cl] (6) and [Pt(L)Cl2OH], L = 2Ac4mT (7), 2Ac4oT (8), 2Ac4pT (9) were prepared with N(4)-ortho- (H2Ac4oT), N(4)-meta- (H2Ac4mT) and N(4)-para- (H2Ac4pT) tolyl-2-acetylpyridine thiosemicarbazone. The cytotoxic activities of all compounds were assayed against U-87 and T-98 human malignant glioma cell lines. Upon coordination cytotoxicity improved in 2, 5 and 8. In general, the gold(III) complexes were more cytotoxic than those with platinum(II,IV). Several of these compounds proved to be more active than cisplatin and auranofin used as controls. The gold(III) complexes probably act by inhibiting the activity of thioredoxin reductase enzyme whereas the mode of action of the platinum(II,IV) complexes involves binding to DNA. Cells treated with the studied compounds presented morphological changes such as cell shrinkage and blebs formation, which indicate cell death by apoptosis induction.

  6. Correlation between {sup 18}F-fluoromisonidazole PET and expression of HIF-1α and VEGF in newly diagnosed and recurrent malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Nobuyuki; Ogawa, Daisuke; Miyake, Keisuke; Tamiya, Takashi [Kagawa University, Department of Neurological Surgery, Faculty of Medicine, Kagawa (Japan); Lin, Wei [Kagawa University, Department of Neurological Surgery, Faculty of Medicine, Kagawa (Japan); Fourth Military Medical University, Department of Neurosurgery, Xijing Hospital, Xi' an (China); Cao, Wei-Dong [Fourth Military Medical University, Department of Neurosurgery, Xijing Hospital, Xi' an (China); Haba, Reiji [Kagawa University, Department of Diagnostic Pathology, Faculty of Medicine, Kagawa (Japan); Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro [Kagawa University, Department of Radiology, Faculty of Medicine, Kagawa (Japan)

    2014-10-15

    Hypoxia and its consequences at the molecular level promote tumour progression and affect patient prognosis. One of the main early cellular events evoked by hypoxia is induction of hypoxia-inducible factor 1 (HIF-1) and subsequent upregulation of vascular endothelial growth factor (VEGF). In this study we sought to determine whether hypoxia detected by {sup 18}F-fluoromisonidazole (FMISO) PET accurately reflects the expression of HIF-1α and VEGF in the tumour and can be used as a biomarker of antiangiogenic treatment and as a prognostic factor in newly diagnosed and recurrent malignant gliomas. Enrolled in this study were 32 patients with newly diagnosed glioma and 16 with recurrent glioma of grade III or grade IV. All the patients had undergone FMISO PET preoperatively. The maximum tumour-to-blood FMISO activity ratio (T/B{sub max}) was used to evaluate the degree of tumour hypoxia and the hypoxic volume (HV) was calculated using a tumour-to-blood FMISO uptake ratio of ≥1.2. Immunohistochemical expressions of HIF-1α and VEGF were evaluated semiquantitatively using the immunoreactivity score (IRS, scores 0 to 12) and the correlation was examined between IRS of HIF-1α or VEGF and FMISO uptake of the tumour (SUV{sub tumour}) using navigation-based sampling. Survival was estimated using the Kaplan-Meier method in relation to the T/B{sub max} and the HV. The T/B{sub max} and the HV in grade IV gliomas were significantly higher than in grade III gliomas (P < 0.01 and P < 0.01, respectively). Moderate to strong HIF-1α and VEGF expression was observed in the majority of malignant gliomas. The IRS of HIF-1α and VEGF in the tumour were not significantly different between grade III and grade IV gliomas. The IRS of HIF-1α in the tumour did not correlate with the SUV{sub tumour} of FMISO in either newly diagnosed or recurrent glioma. There was a significant but weak correlation between the IRS of VEGF and the SUV{sub tumour} of FMISO in newly diagnosed glioma, but not

  7. 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

  8. 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

  9. Usefulness of {sup 18}F-FDG-PET/CT in Evaluating a Brainstem Glioma in an Adult Patient with Neurofibromatosis Type 1

    Energy Technology Data Exchange (ETDEWEB)

    Treglia, Giorgio [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Muoio, Barbara; Del Ciello, Annemilia [Univ. of the Sacred, Rome (Italy); Bertagna, Francesco [Univ. of Brescia, Brescia (Italy)

    2013-09-15

    We describe a case of a brainstem glioma (BSG) occurred in an adult patient with neurofibromatosis type 1 (NF1) and evaluated by Flourine-18-Fluorodeoxyglucose-positron emission tomography/computed tomography ({sup 18}F-FDG-PET/CT). A 32-year-old male patient with NF1 underwent brain magnetic resonance imaging (MRI) for the onset of diplopia, facial paresis and cerebellar signs and symptoms. MRI showed a brainstem lesion compatible with BSG. Biopsy was not performed. {sup 18}F-FDG-PET/CT demonstrated intense {sup 18}F-FDG uptake in the brainstem lesion, suggesting an aggressive neoplasm. The patient was referred to radiotherapy but he developed rapid disease progression. In this case, {sup 18}F-FDG-PET/CT provided useful information about this rare NF1-associated tumor. Subsequently, the patient was referred to radiotherapy, but he developed rapid disease progression and died 3 months later. NF-1 is an autosomal dominant disorder characterized by multiple cafe-au-lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, and iris Lisch nodules. NF-1 is also characterized by low-grade tumors of the central and peripheral nervous system. There is also an increased risk of developing malignant tumors such as malignant peripheral nerve sheath tumors or central nervous system high-grade gliomas. NF1-associated BSGs are less common than NF1-associated optic gliomas (OGs) and seem to represent a particular entity which tend, as a whole, to have a more favorable prognosis and a more indolent course than BSGs in patients without NF1; nevertheless, some NF1-associted BSG may rapidly progress. {sup 18}F-FDG-PET/CT has demonstrated to provide useful information to the surveillance of OGs in children with NF1, particularly to identify progressive, symptomatic tumors. To the best of our knowledge, there are no data about the usefulness of {sup 18}F-FDG-PET/CT in adult patients with NF1-associated BSG. In our case, {sup 18}F-FDG-PET/CT has been useful in

  10. 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.

  11. Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033) : a randomised, open-label, phase 3 intergroup study

    NARCIS (Netherlands)

    Reijneveld, Jaap C; Taphoorn, Martin J B; Coens, Corneel; Bromberg, Jacoline E C; Mason, Warren P; Hoang-Xuan, Khê; Ryan, Gail; Hassel, Mohamed Ben; Enting, Roelien H; Brandes, Alba A; Wick, Antje; Chinot, Olivier; Reni, Michele; Kantor, Guy; Thiessen, Brian; Klein, Martin; Verger, Eugenie; Borchers, Christian; Hau, Peter; Back, Michael; Smits, Anja; Golfinopoulos, Vassilis; Gorlia, Thierry; Bottomley, Andrew; Stupp, Roger; Baumert, Brigitta G

    2016-01-01

    BACKGROUND: Temozolomide chemotherapy versus radiotherapy in patients with a high-risk low-grade glioma has been shown to have no significant effect on progression-free survival. If these treatments have a different effect on health-related quality of life (HRQOL), it might affect the choice of ther

  12. Expression of 58-kD Microspherule Protein (MSP58 is Highly Correlated with PET Imaging of Tumor Malignancy and Cell Proliferation in Glioma Patients

    Directory of Open Access Journals (Sweden)

    Wei Lin

    2016-02-01

    Full Text Available Background/Aims: The nucleolar 58-kDa microspherule protein (MSP58 has important transcriptional regulation functions and plays a crucial role in the tumorigenesis and progression of cancers. 3'-deoxy-3'-[18F]fluorothymidine (FLT has emerged as a promising positron emission tomography (PET tracer for evaluating tumor malignancy and cell proliferation. Methods: In the present study, the expression of MSP58 was evaluated by immunohistochemistry and the corresponding PET image was examined using FLT-PET in 55 patients with various grades of gliomas. Results: The immunoreactivity score (IRS of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P r = 0.61, P r = 0.59, P Conclusion: These results indicate that MSP58 plays an important role in cell proliferation and will be one of the potential candidates of molecular therapy targeting proliferation. FLT-PET might be used as an early measure of treatment response in the proliferation-targeted therapy.

  13. TH-E-BRF-05: Comparison of Survival-Time Prediction Models After Radiotherapy for High-Grade Glioma Patients Based On Clinical and DVH Features

    Energy Technology Data Exchange (ETDEWEB)

    Magome, T; Haga, A; Igaki, H; Sekiya, N; Masutani, Y; Sakumi, A; Mukasa, A; Nakagawa, K [The University of Tokyo Hospital, Tokyo, JP (Japan)

    2014-06-15

    Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyo Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R{sup 2}) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R{sup 2} between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R{sup 2} was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by

  14. 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)

  15. Tissue motion and strain in the human brain assessed by intraoperative ultrasound in glioma patients.

    Science.gov (United States)

    Selbekk, Tormod; Brekken, Reidar; Solheim, Ole; Lydersen, Stian; Hernes, Toril A N; Unsgaard, Geirmund

    2010-01-01

    The objective of the study was to investigate tissue motion and strain imposed by cardiovascular pulsation in pathologic and normal brain parenchyma, as quantified from in vivo ultrasound data. Ultrasound acquired during surgery of 16 patients with glial tumors was retrospectively processed and analyzed. The tissue velocity was quantified at depths of 1cm, 2cm and 3cm from brain cortex to investigate spatial dependency with depth. Comparison of strain and velocity in tumor and adjacent normal parenchyma was performed by selecting two regions-of-interest in the hyperechoic tumor and two regions in the low-echogenic areas interpreted as mainly normal tissue with some degree of tumor cell infiltration. The absolute maximum tissue velocity is seen to increase with increasing depths in 14 of 16 cases (87.5%). The maximum tissue velocities in the four regions close to the ultrasound visible tumor border are not statistically different (p=0.163 to p=0.975). The strain magnitudes are significantly higher in the regions with expected normal brain parenchyma than in regions with expected glial tumor tissue, both for the two regions being closest to the tumor border (p=0.0004) and for the two regions further away from the tumor border (p=0.0009). We conclude that the velocity of the brain parenchyma imposed by arterial pulsation during a cardiac cycle is generally increasing with increasing depth from cortex. The maximum velocity appears to be similar in regions with expected normal brain and tumor tissue, thus, does not seem to be affected by pathology. Strain magnitude is, however, a suitable parameter for discrimination of glial tumor and normal brain parenchyma. (E-mail: Tormod.Selbekk@sintef.no).

  16. Susceptibility-weighted MR imaging of radiation therapy-induced cerebral microbleeds in patients with glioma: a comparison between 3T and 7T

    Energy Technology Data Exchange (ETDEWEB)

    Bian, Wei [University of California San Francisco, The UC Berkeley and UCSF Graduate Program in Bioengineering, San Francisco, CA (United States); University of California San Francisco, Department of Radiology and Biomedical Imaging, 1700 4th Street, Byers Hall Room 303, UCSF Campus Box 2532, San Francisco, CA (United States); Hess, Christopher P.; Lupo, Janine M. [University of California San Francisco, Department of Radiology and Biomedical Imaging, 1700 4th Street, Byers Hall Room 303, UCSF Campus Box 2532, San Francisco, CA (United States); Chang, Susan M. [University of California San Francisco, Department of Neurological Surgery, San Francisco, CA (United States); Nelson, Sarah J. [University of California San Francisco, The UC Berkeley and UCSF Graduate Program in Bioengineering, San Francisco, CA (United States); University of California San Francisco, Department of Radiology and Biomedical Imaging, 1700 4th Street, Byers Hall Room 303, UCSF Campus Box 2532, San Francisco, CA (United States); University of California San Francisco, Department of Bioengineeing and Therapeutic Sciences, San Francisco, CA (United States)

    2014-02-15

    Cerebral microbleeds have been observed in normal-appearing brain tissue of patients with glioma years after receiving radiation therapy. The contrast of these paramagnetic lesions varies with field strength due to differences in the effects of susceptibility. The purpose of this study was to compare 3T and 7T MRI as platforms for detecting cerebral microbleeds in patients treated with radiotherapy using susceptibility-weighted imaging (SWI). SWI was performed with both 3T and 7T MR scanners on ten patients with glioma who had received prior radiotherapy. Imaging sequences were optimized to obtain data within a clinically acceptable scan time. Both T2*-weighted magnitude images and SWI data were reconstructed, minimum intensity projection was implemented, and microbleeds were manually identified. The number of microbleeds was counted and compared among datasets. Significantly more microbleeds were identified on SWI than magnitude images at both 7T (p = 0.002) and 3T (p = 0.023). Seven-tesla SWI detected significantly more microbleeds than 3T SWI for seven out of ten patients who had tumors located remote from deep brain regions (p = 0.016), but when the additional three patients with more inferior tumors were included, the difference was not significant. SWI is more sensitive for detecting microbleeds than magnitude images at both 3T and 7T. For areas without heightened susceptibility artifacts, 7T SWI is more sensitive to detecting radiation therapy-induced microbleeds than 3T SWI. Tumor location should be considered in conjunction with field strength when selecting the most appropriate strategy for imaging microbleeds. (orig.)

  17. 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.

  18. Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

    Science.gov (United States)

    Franceschi, E; Cavallo, G; Lonardi, S; Magrini, E; Tosoni, A; Grosso, D; Scopece, L; Blatt, V; Urbini, B; Pession, A; Tallini, G; Crinò, L; Brandes, A A

    2007-04-10

    To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mg day(-1)) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1-36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2-104+) weeks and PFS-6 was 14.3% (95% CI 4.0-32.7%). The median overall survival was 24.6 weeks (range 4-104+). No grade 3-4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug.

  19. 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.

  20. SVM-based glioma grading. Optimization by feature reduction analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zoellner, Frank G.; Schad, Lothar R. [University Medical Center Mannheim, Heidelberg Univ., Mannheim (Germany). Computer Assisted Clinical Medicine; Emblem, Kyrre E. [Massachusetts General Hospital, Charlestown, A.A. Martinos Center for Biomedical Imaging, Boston MA (United States). Dept. of Radiology; Harvard Medical School, Boston, MA (United States); Oslo Univ. Hospital (Norway). The Intervention Center

    2012-11-01

    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 ({proportional_to}87%) while reducing the number of features by up to 98%. (orig.)

  1. 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.

  2. 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.

  3. The impact on empathetic perception of pain in insular gliomas patients%岛叶胶质瘤对疼痛共情功能的影响

    Institute of Scientific and Technical Information of China (English)

    王兴朝; 赵赋; 王博; 杨智君; 高之宪; 刘丕楠

    2014-01-01

    目的 利用认知神经科学试验手段,采用疼痛共情功能测试范例,结合一般情感及人格特征评估,研究局限性岛叶胶质瘤对高级认知功能的影响.方法 对5例单纯岛叶胶质瘤术前患者及18例健康成人对照进行疼痛共情功能及一般人格测试,采用非参数自助法检验,比较两组人群高级认知功能的差异.结果 岛叶胶质瘤患者的疼痛共情功能明显低于健康对照组(P<0.05),同时一般人格特质及情感没有出现明显变化(P>0.05).结论 岛叶涉及多种高级神经认知功能,尤其在疼痛共情的产生中发挥重要作用,岛叶胶质瘤会引起该功能的显著减退,但对于基本情感及人格没有影响.%Objective To investigate the influence of focal insular glioma to high-level cognitive function by adopting the Empathy of other's Pain (EOP) task followed the experimental methods in cognitive neuroscience and combined with the assessments of general emotional and personalitie feature.Methods Examing the empathy of pain and general personalities among five patients with focal insular glioma before operation and 18 healthy people as control group,compare the variation on advanced cognitivefunction between the two groups by the nonparametric bootstrapping method.Results By contrast with normal control group,deficits in both explicit and implicit empathetic pain processing were found in patients (P < 0.05),although there is no significant difference of general personality feature and emotion between the two groups (P > 0.05).Conclusions The insular lobe is related to a variety of advanced neurocognitive functions,especially plays an essential role of empathic pain processing.The insular glioma would lead to a significantly decline in this function but with little influence on general emotion and personalities.

  4. Blood-brain barrier impairment in MPS III patients.

    Science.gov (United States)

    Garbuzova-Davis, Svitlana; Mirtyl, Santhia; Sallot, Sebastian A; Hernandez-Ontiveros, Diana G; Haller, Edward; Sanberg, Paul R

    2013-11-13

    Mucopolysaccharidosis type III (MPS III) is an autosomal recessive disorder caused by deficiency of a specific enzyme leading to heparan sulfate (HS) accumulation within cells and to eventual progressive cerebral and systemic organ abnormalities. Different enzyme deficiencies comprise the MPS III subcategories (A, B, C, D). Since neuropathological manifestations are common to all MPS III types, determining blood-brain barrier (BBB) condition may be critical to understand potential additional disease mechanisms. We investigated BBB integrity in various brain structures of post-mortem tissues from an eleven year old Caucasian female with MPS III A and from a twenty four year old Caucasian female with MPS III D. Control tissues were obtained post-mortem from three Caucasians without neurological deficits: a twelve year old male, a twenty four year old female, and a twenty seven year old female. BBB capillary ultrastructure (electron microscopy) and capillary functional integrity (IgG leakage, tight junction proteins, and lysosomal accumulation within endothelium) were examined. Compromised BBB integrity was found in both MPS III cases. Major study findings were: (1) capillary endothelial and pericyte cell damage; (2) mucopolysaccharide bodies in a majority of endothelial cells and pericytes rupturing cell membranes; (3) severe extracellular edema; (4) IgG microvascular leakage and reductions of occludin and claudin-5 with variations between MPS III types; (5) extensive lysosomal accumulation in capillary endothelium. These new findings of BBB structural and functional impairment, although from only two cases, MPS III A and III D, may have implications for disease pathogenesis and should be considered in treatment development for MPS III.

  5. 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.

  6. 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.

  7. Influence of surgical orthodontic treatment on masticatory function in skeletal Class III patients.

    Science.gov (United States)

    Kubota, T; Yagi, T; Tomonari, H; Ikemori, T; Miyawaki, S

    2015-10-01

    Skeletal Class III patients exhibit malocclusion characterised by Angle Class III and anterior crossbite, and their occlusion shows total or partially lateral crossbite of the posterior teeth. Most patients exhibit lower bite force and muscle activity than non-affected subjects. While orthognathic surgery may help improve masticatory function in these patients, its effects have not been fully elucidated. The aims of the study were to evaluate jaw movement and the electromyographic (EMG) activity of masticatory muscles before and after orthognathic treatment in skeletal Class III patients in comparison with control subjects with normal occlusion. Jaw movement variables and EMG data were recorded in 14 female patients with skeletal Class III malocclusion and 15 female controls with good occlusion. Significant changes in jaw movement, from a chopping to a grinding pattern, were observed after orthognathic treatment (closing angle P Class III patients improves the masticatory chewing pattern and muscle activity. However, the chewing pattern remains incomplete compared with controls.

  8. Automated Grading of Gliomas using Deep Learning in Digital Pathology Images: A modular approach with ensemble of convolutional neural networks.

    Science.gov (United States)

    Ertosun, Mehmet Günhan; Rubin, Daniel L

    2015-01-01

    Brain glioma is the most common primary malignant brain tumors in adults with different pathologic subtypes: Lower Grade Glioma (LGG) Grade II, Lower Grade Glioma (LGG) Grade III, and Glioblastoma Multiforme (GBM) Grade IV. The survival and treatment options are highly dependent of this glioma grade. We propose a deep learning-based, modular classification pipeline for automated grading of gliomas using digital pathology images. Whole tissue digitized images of pathology slides obtained from The Cancer Genome Atlas (TCGA) were used to train our deep learning modules. Our modular pipeline provides diagnostic quality statistics, such as precision, sensitivity and specificity, of the individual deep learning modules, and (1) facilitates training given the limited data in this domain, (2) enables exploration of different deep learning structures for each module, (3) leads to developing less complex modules that are simpler to analyze, and (4) provides flexibility, permitting use of single modules within the framework or use of other modeling or machine learning applications, such as probabilistic graphical models or support vector machines. Our modular approach helps us meet the requirements of minimum accuracy levels that are demanded by the context of different decision points within a multi-class classification scheme. Convolutional Neural Networks are trained for each module for each sub-task with more than 90% classification accuracies on validation data set, and achieved classification accuracy of 96% for the task of GBM vs LGG classification, 71% for further identifying the grade of LGG into Grade II or Grade III on independent data set coming from new patients from the multi-institutional repository.

  9. FLAIR signal increase of the fluid within the resection cavity after glioma surgery: generally valid as early recurrence marker?

    Science.gov (United States)

    Bette, Stefanie; Gempt, Jens; Huber, Thomas; Delbridge, Claire; Meyer, Bernhard; Zimmer, Claus; Kirschke, Jan S; Boeckh-Behrens, Tobias

    2017-08-01

    OBJECTIVE Recent studies have indicated that a signal intensity increase of the fluid within the resection cavity on FLAIR images may predict tumor recurrence after glioma surgery. The aim of this study was to assess the increase in FLAIR signal intensity in a large patient cohort and in subgroups to assess its prognostic value for early tumor recurrence in glioma patients. METHODS A total of 212 patients (213 cases) who had undergone surgery for an intracranial glioma (WHO Grade IV [n = 103], WHO Grade III [n = 57], and WHO Grade II [n = 53]) were included in this retrospective study. FLAIR signal within the resection cavity at the time of tumor recurrence/last contact and on the previous MRI study was assessed qualitatively and quantitatively. Appearance of FLAIR signal increase was studied over time using Kaplan-Meier estimates in subgroups. RESULTS Patients with WHO Grade II glioma and connection of the resection cavity to CSF who did not undergo radiotherapy did not regularly develop this sign and were excluded from further analysis. For the remaining 87 cases, FLAIR signal intensity increase was observed in 27 cases. Recurrent disease was found in 26 of these 27 cases, resulting in a specificity of 80.0%, a sensitivity of 31.7%, and positive and negative predictive values of 96.3% and 6.7%, respectively. In 4 cases this sign had been observed prior (range 2.8-8.5 months) to tumor recurrence defined by standard criteria. Quantitative analysis underlined the results of qualitative analysis, but it did not add a diagnostic value. CONCLUSIONS Signal intensity increase of the fluid within the resection cavity on FLAIR images is a rare but highly specific and early sign for tumor recurrence/tumor progression in completely and incompletely resected high-grade glioma without connection of the resection cavity to CSF and with radiotherapy.

  10. Early experience with formalin-fixed paraffin-embedded (FFPE) based commercial clinical genomic profiling of gliomas-robust and informative with caveats.

    Science.gov (United States)

    Movassaghi, Masoud; Shabihkhani, Maryam; Hojat, Seyed A; Williams, Ryan R; Chung, Lawrance K; Im, Kyuseok; Lucey, Gregory M; Wei, Bowen; Mareninov, Sergey; Wang, Michael W; Ng, Denise W; Tashjian, Randy S; Magaki, Shino; Perez-Rosendahl, Mari; Yang, Isaac; Khanlou, Negar; Vinters, Harry V; Liau, Linda M; Nghiemphu, Phioanh L; Lai, Albert; Cloughesy, Timothy F; Yong, William H

    2017-08-01

    Commercial targeted genomic profiling with next generation sequencing using formalin-fixed paraffin embedded (FFPE) tissue has recently entered into clinical use for diagnosis and for the guiding of therapy. However, there is limited independent data regarding the accuracy or robustness of commercial genomic profiling in gliomas. As part of patient care, FFPE samples of gliomas from 71 patients were submitted for targeted genomic profiling to one commonly used commercial vendor, Foundation Medicine. Genomic alterations were determined for the following grades or groups of gliomas; Grade I/II, Grade III, primary glioblastomas (GBMs), recurrent primary GBMs, and secondary GBMs. In addition, FFPE samples from the same patients were independently assessed with conventional methods such as immunohistochemistry (IHC), Quantitative real-time PCR (qRT-PCR), or Fluorescence in situ hybridization (FISH) for three genetic alterations: IDH1 mutations, EGFR amplification, and EGFRvIII expression. A total of 100 altered genes were detected by the aforementioned targeted genomic profiling assay. The number of different genomic alterations was significantly different between the five groups of gliomas and consistent with the literature. CDKN2A/B, TP53, and TERT were the most common genomic alterations seen in primary GBMs, whereas IDH1, TP53, and PIK3CA were the most common in secondary GBMs. Targeted genomic profiling demonstrated 92.3%-100% concordance with conventional methods. The targeted genomic profiling report provided an average of 5.5 drugs, and listed an average of 8.4 clinical trials for the 71 glioma patients studied but only a third of the trials were appropriate for glioma patients. In this limited comparison study, this commercial next generation sequencing based-targeted genomic profiling showed a high concordance rate with conventional methods for the 3 genetic alterations and identified mutations expected for the type of glioma. While it may not be feasible to

  11. Improving the extent of malignant glioma resection by dual intraoperative visualization approach.

    Directory of Open Access Journals (Sweden)

    Ilker Y Eyüpoglu

    Full Text Available Despite continuing debates around cytoreductive surgery in malignant gliomas, there is broad consensus that increased extent of tumor reduction improves overall survival. However, maximization of the extent of tumor resection is hampered by difficulty in intraoperative discrimination between normal and pathological tissue. In this context, two established methods for tumor visualization, fluorescence guided surgery with 5-ALA and intraoperative MRI (iMRI with integrated functional neuronavigation were investigated as a dual intraoperative visualization (DIV approach. Thirty seven patients presumably suffering from malignant gliomas (WHO grade III or IV according to radiological appearance were included. Twenty-one experimental sequences showing complete resection according to the 5-ALA technique were confirmed by iMRI. Fourteen sequences showing complete resection according to the 5-ALA technique could not be confirmed by iMRI, which detected residual tumor. Further analysis revealed that these sequences could be classified as functional grade II tumors (adjacent to eloquent brain areas. The combination of fluorescence guided resection and intraoperative evaluation by high field MRI significantly increased the extent of tumor resection in this subgroup of malignant gliomas located adjacent to eloquent areas from 61.7% to 100%; 5-ALA alone proved to be insufficient in attaining gross total resection without the danger of incurring postoperative neurological deterioration. Furthermore, in the case of functional grade III gliomas, iMRI in combination with functional neuronavigation was significantly superior to the 5-ALA resection technique. The extent of resection could be increased from 57.1% to 71.2% without incurring postoperative neurological deficits.

  12. Comparison of {sup 18}F-FET PET and 5-ALA fluorescence in cerebral gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Floeth, Frank Willi; Sabel, Michael; Steiger, Hans Jakob [Heinrich Heine University, Department of Neurosurgery, Duesseldorf (Germany); Ewelt, Christian; Stummer, Walter [Westfaelische Wilhelms University, Department of Neurosurgery, Muenster (Germany); Felsberg, Joerg; Reifenberger, Guido [Heinrich Heine University, Department of Neuropathology, Duesseldorf (Germany); Stoffels, Gabriele; Langen, Karl-Josef [Medical Imaging Physics, Forschungszentrum Juelich, Institute of Neuroscience and Medicine 4, Juelich (Germany); Coenen, Heinz Hubert [Nuclear Chemistry, Forschungszentrum Juelich, Institute of Neuroscience and Medicine 5, Juelich (Germany)

    2011-04-15

    The aim of the study was to compare presurgical {sup 18}F-fluoroethyl-L-tyrosine ({sup 18}F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas. {sup 18}F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for {sup 18}F-FET or Gd and checked for 5-ALA fluorescence. {sup 18}F-FET uptake with a mean tumour to brain ratio {>=}1.6 was rated as positive. Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III (n = 19) or IV (n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, {sup 18}F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, {sup 18}F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on {sup 18}F-FET PET. There are differences between {sup 18}F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. {sup 18}F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning. (orig.)

  13. Simultaneous occurrence of a supra- and an infratentorial glioma in a patient with Ollier's disease : more evidence for non-mesodermal tumor predisposition in multiple enchondromatosis

    NARCIS (Netherlands)

    Heeg, M; Klein, JP; Krikke, AP

    1998-01-01

    A case is presented in which two neuro-ectodermal tumors, an infra- and a supratentorial glioma, developed in a young man with multiple enchondromatosis of Ollier's disease. This is the third such case of multifocal low-grade glioma in Ollier's disease, suggesting a predisposition for non-mesodermal

  14. 18F-FDOPA PET/CT or PET/MRI in Measuring Tumors in Patients With Newly-Diagnosed or Recurrent Gliomas

    Science.gov (United States)

    2017-01-30

    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; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Oligoastrocytoma; Recurrent Childhood Oligodendroglioma; Recurrent Childhood Pilomyxoid Astrocytoma; Recurrent Childhood Protoplasmic Astrocytoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Untreated Childhood Anaplastic Astrocytoma; Untreated Childhood Anaplastic Oligoastrocytoma; Untreated Childhood Anaplastic Oligodendroglioma; Untreated Childhood Brain Stem Glioma; Untreated Childhood Cerebellar Astrocytoma; Untreated Childhood Cerebral Astrocytoma; Untreated Childhood Diffuse Astrocytoma; Untreated Childhood Fibrillary Astrocytoma; Untreated Childhood Gemistocytic Astrocytoma; Untreated Childhood Giant Cell Glioblastoma; Untreated Childhood Glioblastoma; Untreated Childhood Gliomatosis Cerebri; Untreated Childhood Gliosarcoma; Untreated Childhood

  15. Fluorine F 18 Fluorodopa-Labeled PET Scan in Planning Surgery and Radiation Therapy in Treating Patients With Newly Diagnosed High- or Low-Grade Malignant Glioma

    Science.gov (United States)

    2016-10-10

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Diffuse Astrocytoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma

  16. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas.

    Science.gov (United States)

    Lamborn, Kathleen R; Yung, W K Alfred; Chang, Susan M; Wen, Patrick Y; Cloughesy, Timothy F; DeAngelis, Lisa M; Robins, H Ian; Lieberman, Frank S; Fine, Howard A; Fink, Karen L; Junck, Larry; Abrey, Lauren; Gilbert, Mark R; Mehta, Minesh; Kuhn, John G; Aldape, Kenneth D; Hibberts, Janelle; Peterson, Pamela M; Prados, Michael D

    2008-04-01

    The North American Brain Tumor Consortium (NABTC) uses 6-month progression-free survival (6moPFS) as the efficacy end point of therapy trials for adult patients with recurrent high-grade gliomas. In this study, we investigated whether progression status at 6 months predicts survival from that time, implying the potential for prolonged survival if progression could be delayed. We also evaluated earlier time points to determine whether the time of progression assessment alters the strength of the prediction. Data were from 596 patient enrollments (159 with grade III gliomas and 437 with grade IV tumors) in NABTC phase II protocols between February 1998 and December 2002. Outcome was assessed statistically using Kaplan-Meier curves and Cox proportional hazards models. Median survivals were 39 and 30 weeks for patients with grade III and grade IV tumors, respectively. Twenty-eight percent of patients with grade III and 16% of patients with grade IV tumors had progression-free survival of >26 weeks. Progression status at 9, 18, and 26 weeks predicted survival from those times for patients with grade III or grade IV tumors (p < 0.001 and hazard ratios < 0.5 in all cases). Including KPS, age, number of prior chemotherapies, and response in a multivariate model did not substantively change the results. Progression status at 6 months is a strong predictor of survival, and 6moPFS is a valid end point for trials of therapy for recurrent malignant glioma. Earlier assessments of progression status also predicted survival and may be incorporated in the design of future clinical trials.

  17. 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

  18. 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.

  19. 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.

  20. Brainstem gliomas - A clinicopathological study of 45 cases with p53 immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Badhe Prerna

    2004-01-01

    Full Text Available BACKGROUND: Brainstem tumors represent 10% of central nervous system tumors, accounting for 30% of pediatric posterior fossa tumors. AIMS: The aim of this study was to clinicopathologically correlate 45 cases of brain stem gliomas and determine the occurrence and prognostic significance of p53 expression. MATERIALS AND METHOD: 45 cases of brain stem gliomas encountered during a 19-year period. 30 were diagnosed by surgical biopsy and 15 at autopsy. In 25 cases p53 immunohistochemistry (Avidin Biotinylated technique was performed. The WHO brain tumor classification and Stroink's CT classification were applied. STATISTICAL ANALYSIS USED: Chi square test. RESULTS AND CONCLUSIONS: 51 % of gliomas were observed in the first decade of life. The female to male ratio was 1.04: 1. The commonest presenting features were cranial nerve palsies (33% and cerebellar signs (29.8%. 55.55% of cases were located in the pons, 31.01% in the medulla and 13.33% in the midbrain. Diffuse astrocytomas were seen in 40 cases (5% were Grade I, 47.5%Grade II, 32.5% Grade III and 15% Grade IV and pilocytic astrocytomas in 5 cases. Grade IV patients had 2- 3 mitoses /10 high power fields and had a poorer survival rate. Grade II astrocytomas were treated with excision and radiotherapy, while grade III and IV tumors were treated with radiotherapy and chemotherapy (CCNU. Improvement was noted in 20% of patients postoperatively. The outcome was better in patients who were treated surgically. p53 is a frequently mutated gene in brain stem astrocytomas. It was found in 50 % of glioblastoma multiforme, 28.57% of grade III astrocytoma and 12.5% of grade II astrocytoma, while grade 1 astrocytomas failed to express p53 protein. p53 positivity was more in high grade lesions, decreasing significantly in lower grade lesions.

  1. {sup 18}F-Fluoromisonidazole positron emission tomography may differentiate glioblastoma multiforme from less malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Kenji; Shiga, Tohru; Tamaki, Nagara [Hokkaido University, Department of Nuclear Medicine, Graduate School of Medicine, Sapporo, Hokkaido (Japan); Terasaka, Shunsuke; Kobayashi, Hiroyuki; Yamaguchi, Shigeru; Houkin, Kiyohiro [Graduate School of Medicine, Hokkaido University, Department of Neurosurgery, Sapporo (Japan); Hattori, Naoya [Graduate School of Medicine, Hokkaido University, Department of Molecular Imaging, Sapporo (Japan); Magota, Keiichi [Hokkaido University Hospital, Department of Radiology, Sapporo (Japan); Tanaka, Shinya [Graduate School of Medicine, Hokkaido University, Department of Cancer Pathology, Sapporo (Japan); Kuge, Yuji [Hokkaido University, Central Institute of Isotope Science, Sapporo (Japan)

    2012-05-15

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor and its prognosis is significantly poorer than those of less malignant gliomas. Pathologically, necrosis is one of the most important characteristics that differentiate GBM from lower grade gliomas; therefore, we hypothesized that {sup 18}F fluoromisonidazole (FMISO), a radiotracer for hypoxia imaging, accumulates in GBM but not in lower grade gliomas. We aimed to evaluate the diagnostic value of FMISO positron emission tomography (PET) for the differential diagnosis of GBM from lower grade gliomas. This prospective study included 23 patients with pathologically confirmed gliomas. All of the patients underwent FMISO PET and {sup 18}F-fluorodeoxyglucose (FDG) PET within a week. FMISO images were acquired 4 h after intravenous administration of 400 MBq of FMISO. Tracer uptake in the tumor was visually assessed. Lesion to normal tissue ratios and FMISO uptake volume were calculated. Of the 23 glioma patients, 14 were diagnosed as having GBM (grade IV glioma in the 2007 WHO classification), and the others were diagnosed as having non-GBM (5 grade III and 4 grade II). In visual assessment, all GBM patients showed FMISO uptake in the tumor greater than that in the surrounding brain tissues, whereas all the non-GBM patients showed FMISO uptake in the tumor equal to that in the surrounding brain tissues (p {<=} 0.001). One GBM patient was excluded from FDG PET study because of hyperglycemia. All GBM patients and three of the nine (33%) non-GBM patients showed FDG uptake greater than or equal to that in the gray matter. The sensitivity and specificity for diagnosing GBM were 100 and 100% for FMISO, and 100 and 66% for FDG, respectively. The lesion to cerebellum ratio of FMISO uptake was higher in GBM patients (2.74 {+-} 0.60, range 1.71-3.81) than in non-GBM patients (1.22 {+-} 0.06, range 1.09-1.29, p {<=} 0.001) with no overlap between the groups. The lesion to gray matter ratio of FDG was also

  2. Immunotherapy for malignant glioma

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    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.

  3. Near-infrared spectroscopic study and the Wada test for presurgical evaluation of expressive and receptive language functions in glioma patients: with a case report of dissociated language functions.

    Science.gov (United States)

    Sato, Yosuke; Uzuka, Takeo; Aoki, Hiroshi; Natsumeda, Manabu; Oishi, Makoto; Fukuda, Masafumi; Fujii, Yukihiko

    2012-02-29

    Near-infrared spectroscopy (NIRS) has proven to be useful for the evaluation of language lateralization in healthy subjects, infants, and epileptic patients. This study for the first time investigated the expressive and receptive language functions separately, using NIRS in presurgical glioma patients. We also describe a special case with dissociated pattern of language functions. Ten glioma patients were examined. Using NIRS, the hemodynamic changes during a verb generation task or story listening task were measured in the cerebral hemisphere on either side covering the language areas. Following the NIRS study, the Wada test was performed in all the patients. The NIRS study revealed increases of oxyhemoglobin and decreases of deoxyhemoglobin in the language areas elicited by both tasks. In 9 patients, who were all right-handed, the expressive and receptive language functions were lateralized to the left hemisphere. The results of the NIRS study were completely consistent with those of the Wada test. In the remaining 1 patient with a right sided insular glioma, who was right-handed, the NIRS study revealed stronger activation of the right inferior frontal region during the verb generation task, and stronger activation of the left superior temporal region during the story listening task. This dissociated language function was validated by the Wada test and the postoperative neurological course. These results demonstrate that a NIRS study using our technique is extremely valuable for preoperative assessment of the language functions and exemplifies how a preoperative NIRS study can allow detection of unforeseen language lateralization.

  4. [Application of positron-emission tomography-magnetic resonance imaging fusion in biopsy and resection of gliomas].

    Science.gov (United States)

    Guo, Xu; Guo, Yi; Cheng, Xin; Zhong, Ding-rong; Wang, Yu; Wang, Ren-zhi; Ma, Wen-bin

    2013-01-01

    To assess the value and feasibility of positron-emission tomography-magnetic resonance imaging (PET-MRI) fusion technology in delineating tumor boundaries and positioning biopsy targets of gliomas so as to facilitate the diagnosis and treatment of gliomas. A total of 18 patients with a preoperative diagnosis of gliomas discharged from our hospital from January 2010 to April 2011 were recruited. All of them underwent the preoperative examinations of MRI, fluorodeoxyglucose (FDG) PET and fluoroethyl-choline (FECH) PET. The digital image data were transferred into Brain LAB planning software and three types of images automatically fused. The tumor contours were drawn on the basis of each image modality separately. The extent of tumor resection or biopsy target was determined on the integrated information including tumor contours on PET and MRI images and intraoperative observation of tumor texture. On PET scans, the average standard uptake value (SUV) of glioblastomas was higher than that of grade II-III gliomas. With regard to the patients with both biopsy and tumor resection, the pathological diagnosis of the specimen obtained from the PET-guided biopsy was consistent with that of subsequently resected tissue. All 11 patients undergoing tumor resection were classified according to relationship between the image-based tumor contour and actual extent of resection. Six of them benefited from contour delineated by FDG PET images and 3 of them benefited from FECH PET. The combined contribution ratio of both PET methods was 9/11. PET-MRI fusion technology may accurately delineate tumor boundary and sensitively target the region of high proliferation or metabolism. A more radical resection and more accurate histological diagnosis can be thus achieved and yield a probably better prognosis of gliomas.

  5. Perillyl alcohol: Dynamic interactions with the lipid bilayer and implications for long-term inhalational chemotherapy for gliomas

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    Clovis Orlando da Fonseca

    2016-01-01

    Full Text Available Background: Gliomas display a high degree of intratumor heterogeneity, including changes in physiological parameters and lipid composition of the plasma membrane, which may contribute to the development of drug resistance. Biophysical interactions between therapeutic agents and the lipid components at the outer plasma membrane interface are critical for effective drug uptake. Amphipathic molecules such as perillyl alcohol (POH have a high partition coefficient and generally lead to altered lipid acyl tail dynamics near the lipid-water interface, impacting the lipid bilayer structure and transport dynamics. We therefore hypothesized that glioma cells may display enhanced sensitivity to POH-induced apoptosis due to plasma membrane alterations, while in non-transformed cells, POH may be expelled through thermal agitation. Methods: Interactions between POH and the plasma membrane was studied using molecular dynamics simulations. In this phase I/II trial, we set up to evaluate the clinical effectiveness of long-term (up to 5 years daily intranasal administration of POH in a cohort of 19 patients with low-grade glioma (LGG. Importantly, in a series of clinical studies previously published by our group, we have successfully established that intranasal delivery of POH to patients with malignant gliomas is a viable and effective therapeutic strategy. Results: POH altered the plasma membrane potential of the lipid bilayer of gliomas and prolonged intranasal administration of POH in a cohort of patients with LGG halted disease progression with virtually no toxicity. Conclusion: Altogether, the results suggest that POH-induced alterations of the plasma membrane might be contributing to its therapeutic efficacy in preventing LGG progression.

  6. 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.

  7. Glioma: application of whole-tumor texture analysis of diffusion-weighted imaging for the evaluation of tumor heterogeneity.

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    Young Jin Ryu

    Full Text Available BACKGROUND AND PURPOSE: To apply a texture analysis of apparent diffusion coefficient (ADC maps to evaluate glioma heterogeneity, which was correlated with tumor grade. MATERIALS AND METHODS: Forty patients with glioma (WHO grade II (n = 8, grade III (n = 10 and grade IV (n = 22 underwent diffusion-weighted imaging (DWI, and the corresponding ADC maps were obtained. Regions of interest containing the lesions were drawn on every section of the ADC map containing the tumor, and volume-based data of the entire tumor were constructed. Texture and first order features including entropy, skewness and kurtosis were derived from the ADC map using in-house software. A histogram analysis of the ADC map was also performed. The texture and histogram parameters were compared between low-grade and high-grade gliomas using an unpaired student's t-test. Additionally, a one-way analysis of variance analysis with a post-hoc test was performed to compare the parameters of each grade. RESULTS: Entropy was observed to be significantly higher in high-grade gliomas than low-grade tumors (6.861±0.539 vs. 6.261±0.412, P  = 0.006. The fifth percentiles of the ADC cumulative histogram also showed a significant difference between high and low grade gliomas (836±235 vs. 1030±185, P = 0.037. Only entropy proved to be significantly different between grades III and IV (6.295±0.4963 vs. 7.119±0.3165, P<0.001. The diagnostic accuracy of ADC entropy was significantly higher than that of the fifth percentile of the ADC histogram (P = 0.0034 in distinguishing high- from low-grade glioma. CONCLUSION: A texture analysis of the ADC map based on the entire tumor volume can be useful for evaluating glioma grade, which provides tumor heterogeneity.

  8. Stathmin expression in glioma-derived microvascular endothelial cells: a novel therapeutic target.

    Science.gov (United States)

    Dong, Baijing; Mu, Luyan; Qin, Xiangying; Qiao, Wanchen; Liu, Xiaodong; Yang, Liming; Xue, Li; Rainov, Nikolai G; Liu, Xiaoqian

    2012-03-01

    The purpose of this study was to investigate stathmin expression and its mechanisms of action in GDMEC. Microvascular endothelial cells were isolated from human gliomas (n=68) and normal brain specimans (n=20), and purified by magnetic beads coated with anti-CD105 antibody. The expression of stathmin mRNA and protein were detected by RT-PCR and western blotting, respectively. Stathmin expression was silenced by application of specific siRNA in high grade GDMEC. The proliferation, apoptosis and invasion behavior of GDMEC were investigated. The stathmin positive rate of endothelial cells in normal brain, grade I-II glioma and grade III-IV glioma was 20, 66 and 95.5%, respectively (Pstathmin, cell viability was reduced, the apoptosis rate increased and the migration of vascular endothelial cells was suppressed significantly (Pstathmin suppressed neoangiogenesis of glioma and provides a potential target for glioma treatment.

  9. Comparison of long-term survival between temozolomide-based chemoradiotherapy and radiotherapy alone for patients with low-grade gliomas after surgical resection

    Directory of Open Access Journals (Sweden)

    Gai XJ

    2016-08-01

    Full Text Available Xiu-juan Gai,1,2 Yu-mei Wei,2 Heng-min Tao,1,2 Dian-zheng An,2 Jia-teng Sun,1,2 Bao-sheng Li2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology VI, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China Purpose: This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT vs radiotherapy alone (RT-alone for low-grade gliomas (LGGs after surgical resection. Patients and methods: In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31 and RT-alone (n=38 at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50–100 mg oral TMZ every day until the radiotherapy regimen was completed. Results: The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06. There were statistically significant intergroup differences in the progression-free survival rate (P=0.037, with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS rate was 89.86%. Age distribution (≥45 years and <45 years and resection margin (complete resection or not were significantly associated with OS (P=0.03 and P=0.004, respectively. Conclusion: Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between

  10. 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

  11. Non-Gaussian diffusion MR imaging of glioma: comparisons of multiple diffusion parameters and correlation with histologic grade and MIB-1 (Ki-67 labeling) index

    Energy Technology Data Exchange (ETDEWEB)

    Yan, Ren; Haopeng, Pang; Xiaoyuan, Feng; Jiawen, Zhang; Zhenwei, Yao [Fudan University, Department of Radiology, Huashan Hospital, Shanghai (China); Jinsong, Wu; Chengjun, Yao; Tianming, Qiu [Fudan University, Department of Neurosurgery, Huashan Hospital, Shanghai (China); Ji, Xiong [Fudan University, Department of Neuropathology, Huashan Hospital, Shanghai (China); Mao, Sheng; Yueyue, Ding [Department of Imaging, Suzhou Children' s Hospital, Suzhou, Jiangsu (China); Yong, Zhang [MR Research, GE Healthcare, Shanghai (China); Jianfeng, Luo [Fudan University, Department of Biostatistics, Public Health School, Shanghai (China)

    2016-02-15

    This study was conducted to compare the association of Gaussian and non-Gaussian magnetic resonance imaging (MRI)-derived parameters with histologic grade and MIB-1 (Ki-67 labeling) index (MI) in brain glioma. Sixty-five patients with pathologically confirmed glioma, who underwent diffusion-weighted MRI with 2 b values (0, 1000 s/mm{sup 2}) and 22 b values (≤5000 s/mm{sup 2}), respectively, were divided into three groups of grade II (n = 35), grade III (n = 8), and grade IV (n = 22). Comparisons by two groups were made for apparent diffusion coefficient (ADC), slow diffusion coefficient (Dslow), distributed diffusion coefficient (DDC), and heterogeneity index α. Analyses of receiver operating characteristic (ROC) curve were performed to maximize the area under the curve (AUC) for differentiating grade III + IV (high-grade glioma, HGG) from grade II (low-grade glioma, LGG) and grade IV (glioblastoma multiforme, GBM) from grade II + III (other grade glioma, OGG). Correlations with MI were analyzed for the MRI parameters. On tumor regions, the values of ADC, Dslow, DDC, and α were significantly higher in grade II [(1.37 ± 0.29, 0.70 ± 0.11, 1.39 ± 0.34) (x 10{sup -3} mm{sup 2}/s) and 0.88 ± 0.05, respectively] than in grade III [(0.99 ± 0.13, 0.55 ± 0.07, 1.04 ± 0.20) (x 10{sup -3} mm{sup 2}/s) and 0.80 ± 0.03, respectively] and grade IV [(1.03 ± 0.14, 0.50 ± 0.05, 1.02 ± 0.16) (x 10{sup -3} mm{sup 2}/s) and 0.76 ± 0.04, respectively] (all P < 0.001). The parameter α showed the highest AUCs of 0.950 and 0.922 in discriminating HGG from LGG and GBM from OGG, respectively. Significant correlations with histologic grade and MI were observed for the MRI parameters. The non-Gaussian MRI-derived parameters α and Dslow are superior to ADC in glioma grading, which are comparable with ADC as reliable biomarkers in noninvasively predicting the proliferation level of glioma malignancy. (orig.)

  12. Generation and validation of a prognostic score to predict outcome after re-irradiation of recurrent glioma

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E.; Welzel, Thomas; Debus, Juergen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], E-mail: Stephanie.combs@med.uni-heidelberg.de; Edler, Lutz; Rausch, Renate [German Cancer Research Center (dkfz), Dept. of Biostatistics, Heidelberg (Germany); Wick, Wolfgang [Univ. Hospital of Heidelberg, Dept. of Neurooncology, Heidelberg (Germany)

    2013-01-15

    Re-irradiation using high-precision radiation techniques has been established within the clinical routine for patients with recurrent gliomas. In the present work, we developed a practical prognostic score to predict survival outcome after re-irradiation. Patients and methods. Fractionated stereotactic radiotherapy (FSRT) was applied in 233 patients. Primary histology included glioblastoma (n = 89; 38%), WHO Grade III gliomas (n = 52; 22%) and low-grade glioma (n = 92; 40%). FSRT was applied with a median dose of 36 Gy in 2 Gy single fractions. We evaluated survival after re-irradiation as well as progression-free survival after re-irradiation; prognostic factors analyzed included age, tumor volume at re-irradiation, histology, time between initial radiotherapy and re-irradiation, age and Karnofsky Performance Score. Results. Median survival after FSRT was 8 months for glioblastoma, 20 months for anaplastic gliomas, and 24 months for recurrent low-grade patients. The strongest prognostic factors significantly impacting survival after re-irradiation were histology (p <0.0001) and age (<50 vs. ={>=}50, p < 0.0001) at diagnosis and the time between initial radiotherapy and re-irradiation {<=}12 vs. >12 months (p < 0.0001). We generated a four-class prognostic score to distinguish patients with excellent (0 points), good (1 point), moderate (2 points) and poor (3-4 points) survival after re-irradiation. The difference in outcome was highly significant (p < 0.0001). Conclusion. We generated a practical prognostic score index based on three clinically relevant factors to predict the benefit of patients from re-irradiation. This score index can be helpful in patient counseling, and for the design of further clinical trials. However, individual treatment decisions may include other patient-related factors not directly influencing outcome.

  13. 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.

  14. International Differences in Treatment and Clinical Outcomes for High Grade Glioma.

    Directory of Open Access Journals (Sweden)

    Li-Nien Chien

    Full Text Available High grade gliomas are the most common type of malignant brain tumor, and despite their rarity, cause significant morbidity and mortality. This study aimed to compare the treatment patterns of high grade glioma to examine survival patterns in patients who receive specific treatments between cohorts in Ohio and Taiwan.Patients aged 18 years and older at age of diagnosis with World Health Organization (WHO grade III or IV astrocytoma from 2007-2012 were selected from the Ohio Brain Tumor Study and the Taiwan Cancer Registry. The treatment information was derived from medical chart reviews in Ohio and National Health Insurance Research Data in Taiwan. Treatment examined included surgical procedure (brain biopsy and/or resection, radiotherapy (radiation and/or radiosurgery, and alkylating chemotherapy. Kaplan-Meier and parametric survival models were used to examine the effect of treatment on survival, adjusted for age, sex, and comorbidities.294 patients in Ohio and 1,097 patients in Taiwan met the inclusion criteria. 70.3% patients in Ohio and 51.4% in Taiwan received surgical resection, followed by concurrent chemoradiation. Patients who received this treatment had the highest survival rate, with a 1-year survival rate of 72.8% in Ohio and 73.4% in Taiwan. Patients who did not receive surgical resection, followed by concurrent chemoradiation had an increased risk of death (hazard ratio of 5.03 [95% confidence interval (CI: 3.61-7.02] in Ohio and 1.49 [95% CI: 1.31-1.71] in Taiwan after adjustment for age, sex, and comorbidities.Surgical resection followed by concurrent chemoradiation was associated with higher survival rate of patients with high grade glioma in both Ohio and Taiwan; however, one-third of patients in Ohio and half in Taiwan did not receive this treatment.

  15. The value of level III clearance in patients with axillary and sentinel node positive breast cancer.

    LENUS (Irish Health Repository)

    Dillon, Mary F

    2012-02-01

    BACKGROUND: The value of level III axillary clearance is contentious, with great variance worldwide in the extent and levels of clearance performed. OBJECTIVE: To determine rates of level III positivity in patients undergoing level I-III axillary clearance, and identify which patients are at highest risk of involved level III nodes. METHODS: From a database of 2850 patients derived from symptomatic and population-based screening service, 1179 patients who underwent level I-III clearance between the years 1999-2007 were identified. The pathology, surgical details, and prior sentinel nodes biopsies of patients were recorded. RESULTS: Eleven hundred seventy nine patients had level I-III axillary clearance. Of the patients, 63% (n = 747) were node positive. Of patients with node positive disease, 23% (n = 168) were level II positive and 19% (n = 141) were level III positive. Two hundred fifty patients had positive sentinel node biopsies prior to axillary clearance. Of these, 12% (n = 30) and 9% (n = 22) were level II and level III positive, respectively. On multivariate analysis, factors predictive of level III involvement in patients with node positive disease were tumor size (P < 0.001, OR = 1.36; 95% CI: 1.2-1.5), invasive lobular disease (P < 0.001, OR = 3.6; 95% CI: 1.9-6.95), extranodal extension (P < 0.001, OR = 0.27; 95% CI: 0.18-0.4), and lymphovascular invasion (P = 0.04, OR = 0.58; 95% CI: 0.35-1). Lobular invasive disease (P = 0.049, OR = 4.1; 95% CI: 1-16.8), extranodal spread (P = 0.003, OR = 0.18; 95% CI: 0.06-0.57), and having more than one positive sentinel node (P = 0.009, OR = 4.9; 95% CI: 1.5-16.1) were predictive of level III involvement in patients with sentinel node positive disease. CONCLUSION: Level III clearance has a selective but definite role to play in patients who have node positive breast carcinoma. Pathological characteristics of the primary tumor are of particular use in identifying those who are at various risk of level III nodal

  16. Differences in the architecture of low-grade and high-grade gliomas evaluated using fiber density index and fractional anisotropy.

    Science.gov (United States)

    Chen, Yiyong; Shi, Yonghong; Song, Zhijian

    2010-07-01

    Accurate pre-operative assessment of tumor grade is important for the selection of appropriate treatment strategies. The aim of this study was to retrospectively evaluate whether the fiber density index (FDi) and fractional anisotropy (FA) via diffusion tensor MRI (DTI) could assist with pre-operative diagnosis of glioma grade. A total of 31 patients who had histologically confirmed gliomas underwent DTI performed using a 1.5-Tesla magnetic resonance scanner. To reconstruct the white matter adjacent to the tumor, DTI fiber tracking (DTI-FT) using an FA threshold of 0.15 was implemented. Regions of interest (ROIs) were defined (i-iv) as: the tumor center (ROI i); white matter adjacent to the tumor (ROI ii); contralateral centrum semiovale (ROI iii); and the homologous fiber tracts to ROI ii in the contralateral hemisphere (ROI iv). We calculated six parameters from different ROIs and compared high-grade and low-grade gliomas: FA values and ratios; FDi values and ratios with an FA threshold of 0.15; and FDi values and ratios with an FA threshold of 0.25. The results showed that FA ratios and FDi ratios with FA thresholds of 0.25 were significantly different between patients with high-grade and low-grade gliomas. This may be useful for developing surgical strategies and appraising patient prognosis.

  17. [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.)

  18. 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...

  19. 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.

  20. Phase I trial of aflibercept (VEGF trap) with radiation therapy and concomitant and adjuvant temozolomide in patients with high-grade gliomas.

    Science.gov (United States)

    Nayak, Lakshmi; de Groot, John; Wefel, Jeffrey S; Cloughesy, Timothy F; Lieberman, Frank; Chang, Susan M; Omuro, Antonio; Drappatz, Jan; Batchelor, Tracy T; DeAngelis, Lisa M; Gilbert, Mark R; Aldape, Kenneth D; Yung, Alfred W K; Fisher, Joy; Ye, Xiaobu; Chen, Alice; Grossman, Stuart; Prados, Michael; Wen, Patrick Y

    2017-03-01

    Anti-vascular endothelial growth factor (VEGF) therapy has shown promise in the treatment of high-grade gliomas (HGG). Aflibercept is a recombinant human fusion protein that acts as a soluble decoy receptor for VEGF-A, VEGF-B and placental growth factor, depleting circulating levels of these growth factors. The Adult Brain Tumor Consortium conducted a phase I trial of aflibercept and temozolomide (TMZ) in patients with newly diagnosed HGG with 2 dose levels and a 3+3 design. Three arms using aflibercept were examined; with radiation and concomitant temozolomide; with adjuvant temozolomide using the 5/28 regimen; and with adjuvant temozolomide using the 21/28 day regimen. Fifty-nine patients were enrolled, 21 in arm 1, 20 in arm 2 and 18 in arm 3. Median age was 56 years (24-69); median KPS 90 (60-100). The maximum tolerated dose (MTD) of aflibercept for all 3 arms was 4 mg/kg every 2 weeks. Dose limiting toxicities at the MTD were: Arm 1: 0/21 patients; Arm 2: 2/20 patients (G3 deep vein thrombosis, G4 neutropenia; Arm 3: 3/18 patients) (G4 biopsy-confirmed thrombotic microangiopathy, G3 rash, G4 thrombocytopenia). The median number of cycles of aflibercept was 5 (range, 1-16). All patients stopped treatment; 28 (47%) for disease progression, 21 (36%) for toxicities, 8 (14%) for other reasons, and 2 (3%) patients completed the full treatment course. This study met its primary endpoint and the MTD of aflibercept with radiation and concomitant and adjuvant temozolomide is 4 mg/kg every 2 weeks.

  1. 脑胶质瘤患者血清及脑脊液中游离DNA的检测%Diagnostic value of the content and integrity of free DNA in patients with glioma

    Institute of Scientific and Technical Information of China (English)

    陈建; 施炜; 吕成林; 夏亮; 戚青; 景蓉蓉; 鞠少卿

    2012-01-01

    目的 检测不同级别脑胶质瘤患者血清及脑脊液中游离DNA的含量及完整性,探讨其对脑胶质瘤的诊断及预后判断的意义.方法 术前采集70例脑胶质瘤患者和22例健康对照的外周血;其中30例胶质瘤患者同时采集脑脊液.通过实时荧光定量聚合酶链反应( RT-qPCR)方法检测血清及脑脊液中游离DNA短串联重复序列(ALU)的长片段(247 bp)与短片段(115 bp)的含量以及DNA完整性.结果 血清中ALU-247 bp与115 bp含量以及游离DNA完整性在胶质瘤组与对照组间差异无统计学意义(P>0.05).脑脊液中游离DNA ALU-247 bp与115 bp含量均较非肿瘤对照组高,DNA完整性(ALU-247/ALU-115 bp)较对照组也显著增高.ROC曲线分析ALU-247 bp,ALU-115 bp含量与DNA完整性的AUC分别为0.775、0.875和0.912.结论 胶质瘤患者术前脑脊液中游离DNA ALU-247 bp、ALU-115 bp的含量以及DNA完整性对胶质瘤的术前诊断具有一定价值.%Objective To detect the content of free DNA and the DNA integrity in serum and cerebrospinal fluid (CSF) from glioma patients in order to assess their diagnostic value for the glioma.Methods Serum samples were obtained from 70 patients with glioma and 22 healthy volunteers as controls,and CSF samples from 20 patients with glioma and 8 nonneoplastic controls with hydrocephalus or arachnoid cyst.Free DNA concentration and integrity were detected by using real-time quantitative polymerase chain reaction (RT-qPCR) before operation.With 2 primers sets amplifying short and long free DNA fragments ( ALU115 and ALU247 ),free DNA integrity was determined by ratio of the concentration of ALU247 over ALU115 (ALU 247/115).Results The concentration of serum ALU had no significant differences between glioma patients and healthy controls.ALU115 and ALU247 contents,and free DNA integrity in CSF were significantly higher in glioma patients than in the controls ( all P<0.05 ).Area under curve of ROC curve analysis for the CSF

  2. 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.

  3. 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.

  4. Gadobutrol Versus Gadopentetate Dimeglumine or Gadobenate Dimeglumine Before DCE-MRI in Diagnosing Patients With Multiple Sclerosis, Grade II-IV Glioma, or Brain Metastases

    Science.gov (United States)

    2016-11-15

    Adult Anaplastic (Malignant) Meningioma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Neoplasm; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Primary Melanocytic Lesion of Meninges; Adult Supratentorial Primitive Neuroectodermal Tumor; Malignant Adult Intracranial Hemangiopericytoma; Metastatic Malignant Neoplasm in the Brain; Multiple Sclerosis; Recurrent Adult Brain Neoplasm

  5. Outcomes of Multidisciplinary Management in Pediatric Low-Grade Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Kevin S., E-mail: koh2@partners.org [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI (United States); Hung, Jonathan [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI (United States); Robertson, Patricia L. [Department of Pediatrics and Communicable Diseases, University of Michigan Health System, Ann Arbor, MI (United States); Department of Neurology, University of Michigan Health System, Ann Arbor, MI (United States); Garton, Hugh J.; Muraszko, Karin M. [Department of Neurosurgery, University of Michigan Health System, Ann Arbor, MI (United States); Sandler, Howard M. [Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, MI (United States); Hamstra, Daniel A. [Department of Pediatrics and Communicable Diseases, University of Michigan Health System, Ann Arbor, MI (United States)

    2011-11-15

    Purpose: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. Methods and Materials: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). Results: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 {+-} 4% (standard error) and 94 {+-} 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age {<=}5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 {+-} 9% and 100%, respectively. Conclusions: Low-grade gliomas in children {<=}5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.

  6. 测定脑胶质瘤患者神经肽、神经降压素的含量变化及意义%Clinical Significance and Detection of Neuro- Peptide and Neurotensin in Patients with Brain Glioma

    Institute of Scientific and Technical Information of China (English)

    尹秋霞; 司永兵; 齐法莲

    2001-01-01

    Objective To investigate the change of neuropeptide Y(NPY)and neurotensin(NT)in pqtients with brain glioma.Method The concentration of NPY and NT in and around brain glioma tissue and plasma were detected with inequilibrant radio- imunology method.Result NPY concentrqtion in brain glioma tissue was obviously higher than that in tissue around the tumor(P<0.01).The Concentration of NT in brain glioma tissue was obviously higher that in tissue around the glioma(P<0.01).Conclusion Detection of NPY and NTin brain glion aprovides basis for further study on brain glioma and explainning dlinical and imaginal symiptom of brain glioma.

  7. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    Science.gov (United States)

    2010-01-01

    Background Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. Methods 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Results Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Conclusions Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs. PMID:20663133

  8. Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide. A 10-year experience at a single institution

    Energy Technology Data Exchange (ETDEWEB)

    Ausili Cefaro, Giampiero; Genovesi, Domenico; Vinciguerra, Annamaria; Trignani, Marianna; Taraborrelli, Maria; Augurio, Antonietta [G. d' Annunzio Univ. of Chieti, SS. Annunziata Hospital, Chieti (Italy). Dept. of Radiation Oncology; Buonaguidi, Roberto [G. d' Annunzio Univ. of Chieti, Spirito Santo Hospital, Pescara (Italy). Dept. of Neurosurgery; Galzio, Renato J. [Univ. of L' Aquila, San Salvatore Hospital, L' Aquila (Italy). Dept. of Operative Unit of Neurosurgery and Health Sciences; Di Nicola, Marta [G. d' Annunzio Univ. of Chieti (Italy). Lab. of Biostatistics

    2011-12-15

    To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level {<=} 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level {<=} 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

  9. 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.

  10. Oral Impacts on Quality of Life in Adult Patients with Class I, II and III Malocclusion

    OpenAIRE

    Javed, Omair; Bernabé, Eduardo

    2016-01-01

    PURPOSE: To compare the social impact of malocclusion on quality of life between adult patients with Angle Class I, II and III malocclusion.MATERIALS AND METHODS: A total of 222 adult patients (139, 42 and 41 with Angle Class I, II and III malocclusion, respectively) were recruited voluntarily from those attending the Orthodontic Clinic of Khyber College of Dentistry in Pesh awar, Pakistan. Participants were asked to complete the Urdu version of the short form of the Oral Health Impact Profil...

  11. Rome III criteria cannot distinguish patients with chronic gastritis from those functional dyspepsia patients.

    Science.gov (United States)

    Wei, Zhu; Ying, Liu; Wen, Guo; Mengnan, Zhang; Yali, Zhang

    2014-04-01

    Functional dyspepsia is thought to be a diagnosis made after excluding endoscopically detectable lesions by the current Rome III criteria. However, whether these "functional dyspepsia" patients were diagnosed appropriately is still controversial. A total of 223 patients diagnosed with functional dyspepsia by Rome III criteria were enrolled. All patients were submitted to endoscopic examination, rapid urease test, and histologic evaluation. We also appraised the effect of a 7-day treatment based on the Glasgow Dyspepsia Severity Score. Helicobacter pylori infection and neutrophil infiltration were found in 37.7% and 36.3% cases, respectively, and were both more frequent in the subgroup with epigastric pain symptom (EPS) than in the other two subgroups. In addition, neutrophil infiltration was more common and severe in the H. pylori-positive individuals than in the patients without infection (Mann-Whitney U-test = 431.500, p < .001). The treatment was useful in symptom improvement of all three subgroups, and the EPS subgroup had the greatest change of symptom scores before and after treatment as compared with the subgroup with postprandial distress symptom (PDS) and PDS/EPS subgroup (χ(2) = 42.745, p < .001), and the eradication of H. pylori revealed a statistical significant difference in different subgroups (χ(2) = 11.300, p = .001). Our findings showed that many H. pylori-positive subjects diagnosed as "functional dyspepsia" were actually chronic gastritis patients, especially the EPS cases who are more likely to be patients with "active gastritis under microscope," and also benefit most from the treatment of proton-pump inhibitors or eradication of H. pylori. © 2014 John Wiley & Sons Ltd.

  12. The impact of reliable prebolus T{sub 1} measurements or a fixed T{sub 1} value in the assessment of glioma patients with dynamic contrast enhancing MRI

    Energy Technology Data Exchange (ETDEWEB)

    Tietze, Anna [Aarhus University Hospital, Dept. of Neuroradiology, Aarhus (Denmark); Aarhus University, Center of Functionally Integrative Neuroscience, Aarhus (Denmark); Mouridsen, Kim; Mikkelsen, Irene Klaerke [Aarhus University, Center of Functionally Integrative Neuroscience, Aarhus (Denmark)

    2015-03-06

    Accurate quantification of hemodynamic parameters using dynamic contrast enhanced (DCE) MRI requires a measurement of tissue T{sub 1} prior to contrast injection (T{sub 1}). We evaluate (i) T{sub 1} estimation using the variable flip angle (VFA) and the saturation recovery (SR) techniques and (ii) investigate if accurate estimation of DCE parameters outperform a time-saving approach with a predefined T{sub 1} value when differentiating high- from low-grade gliomas. The accuracy and precision of T{sub 1} measurements, acquired by VFA and SR, were investigated by computer simulations and in glioma patients using an equivalence test (p > 0.05 showing significant difference). The permeability measure, K{sub trans}, cerebral blood flow (CBF), and - volume, V{sub p}, were calculated in 42 glioma patients, using fixed T{sub 1} of 1500 ms or an individual T{sub 1} measurement, using SR. The areas under the receiver operating characteristic curves (AUCs) were used as measures for accuracy to differentiate tumor grade. The T{sub 1} values obtained by VFA showed larger variation compared to those obtained using SR both in the digital phantom and the human data (p > 0.05). Although a fixed T{sub 1} introduced a bias into the DCE calculation, this had only minor impact on the accuracy differentiating high-grade from low-grade gliomas, (AUC{sub fix} = 0.906 and AUC{sub ind} = 0.884 for K{sub trans}; AUC{sub fix} = 0.863 and AUC{sub ind} = 0.856 for V{sub p;} p for AUC comparison > 0.05). T{sub 1} measurements by VFA were less precise, and the SR method is preferable, when accurate parameter estimation is required. Semiquantitative DCE values, based on predefined T{sub 1} values, were sufficient to perform tumor grading in our study. (orig.)

  13. A cancer research UK pharmacokinetic study of BPA-mannitol in patients with high grade glioma to optimise uptake parameters for clinical trials of BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Cruickshank, G.S. [University of Birmingham and University Hospital Birmingham, Birmingham (United Kingdom)], E-mail: garth.cruickshank@uhb.nhs.uk; Ngoga, D.; Detta, A.; Green, S.; James, N.D.; Wojnecki, C.; Doran, J.; Hardie, J.; Chester, M.; Graham, N.; Ghani, Z. [University of Birmingham and University Hospital Birmingham, Birmingham (United Kingdom); Halbert, G.; Elliot, M.; Ford, S. [CR-UK Formulation Unit, University of Strathclyde, Glasgow (United Kingdom); Braithwaite, R.; Sheehan, T.M.T. [Regional Laboratory for Toxicology, Sandwell and West Birmingham Hospitals Trust, Birmingham (United Kingdom); Vickerman, J.; Lockyer, N. [Surface Analysis Research Centre, University of Manchester, Manchester (United Kingdom); Steinfeldt, H.; Croswell, G. [CR-UK Drug Development Office, London (United Kingdom)] (and others)

    2009-07-15

    This paper describes results to-date from a human pharmacokinetic study which began recruitment in December 2007. Results are presented for a single patient recruited in December 2007. A second patient was recruited in July 2008 but detailed data are not available at the time of writing. The trial is an open-label, non-comparative, non-therapeutic study of BPA-mannitol in patients with high-grade glioma, who will be undergoing stereotactic brain biopsy as part of the diagnostic process before definitive treatment. The study investigates the route of infusion (intra-venous (IV) or intra-carotid artery) and in each case will assess the effect of administration of mannitol as a blood-brain barrier disrupter. All cohorts will receive a 2 h infusion of BPA-mannitol, and for some cohorts an additional mannitol bolus will be administered at the beginning of this infusion. Measurements are made by inductively coupled plasma mass spectrometry (ICP-MS) of {sup 10}B concentration in samples of blood, urine, extra-cellular fluid in normal brain (via a dialysis probe), brain tissue around tumour and tumour tissue. Additional analysis of the tumour tissue is performed using secondary ion mass spectrometry (SIMS). The first patient was part of the cohort having intra-venous infusion without mannitol bolus. No serious clinical problems were experienced and the assay results can be compared with available patient data from other BNCT centres. In particular we note that the peak {sup 10}B concentration in blood was 28.1 mg/ml for a total BPA administration of 350 mg/kg which is very consistent with the previous experience with BPA-fructose reported by the Helsinki group.

  14. Clinical effect of oldenlandia diffusa on postoperative glioma patients%胶质瘤术后白花蛇舌草的应用体会

    Institute of Scientific and Technical Information of China (English)

    张焱; 陈坚; 袁志诚; 李巧玉; 湛利平

    2012-01-01

    目的 评价术后采用白花蛇舌草注射液治疗脑胶质瘤的临床疗效.方法 我们对2010年2月至9月10例胶质瘤患者,在手术后给予白花蛇舌草注射液20ml加入5%葡萄糖250ml中静脉滴注,15d为1个周期,1周后重复上述治疗,3个周期为1个疗程,1个疗程后间歇1个月,常规治疗2个疗程.观察肿瘤的复发情况及治疗的毒副作用.结果 肿瘤全切9例,次全切1例.使用白花蛇舌草最常见毒副反应为消化道症状,本组5例出现恶性呕吐,静脉滴注减慢及对症治疗后症状消失.未见骨髓抑制及肾脏毒性.血常规及肝肾功能检查术前与术后无明显变化.全部病例随访至今均存活,1例复发.结论 手术后使用白花蛇舌草注射液是一种治疗脑胶质瘤的有效方法,但远期疗效有待进一步观察研究.%Objective To assess the clinical effect of oldenlandia diffusa on postoperative glioma patients. Methods The clinical data of 10 cases of glioma were treated with intravenous infusion of 20 ml oldenlandia diffusa injection mixed into 250ml 5% glucose resolution after surgery from February 2010 to September 2010. The 15 - day treatment cycle was repeated after a week, and 3 treatment cycles constituted a course. There were 2 courses with an 1 - month interval. Tumor recurrence and treatment side effects were observed. Results Total tumor removal was achieved in 11 cases ( 91. 6% ) and subtotal in 1 (8.3% ). The main toxicities of oldenlandia diffusa were gastrointestinal symptoms, as 5 cases in this group reported nausea and vomit,and symptoms disappeared after treatment with slowing the infusion rate and symptomatic treatment. There was no marrow depression or renal toxicity. Changes of blood routine examination or liver function were not observed before or after operation. One case recurred. Conclusion Combined application of operation with oldenlandia diffusa injection is an effective way to treat glioma. However the long - term effect

  15. 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)

  16. 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.

  17. 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.

  18. [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].

    Science.gov (United States)

    Iturri Clavero, F; González Uriarte, A; Tamayo Medel, G; Gamboa Setién, P M

    2014-01-01

    Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted.

  19. Detection of HTLV-III RNA in lungs of patients with AIDS and pulmonary involvement

    Energy Technology Data Exchange (ETDEWEB)

    Chayt, K.J.; Harper, M.E.; Marselle, L.M.; Lewin, E.B.; Rose, R.M.; Oleske, J.M.; Epstein, L.G.; Wong-Staal, F.; Gallo, R.C.

    1986-11-07

    A majority of pediatric patients and rare adult patients with the acquired immunodeficiency syndrome (AIDS) develop a chronic respiratory disorder referred to as lymphocytic interstitial pneumonitis (LIP). Efforts to identify an infectious agent responsible for this process so far have failed. In this study, frozen sections of lungs from patients with AIDS and pulmonary disease were tested by in situ molecular hybridization for the presence of cells infected with human T-cell lymphotropic virus type III (HTLV-III) and expressing viral RNA. In the case of an infant with LIP, a relatively high frequency (0.1%) of cells in the lung were found to be positive for HTLV-III RNA. This number is the lower limit of total cells infected since the in situ hybridization technique as applied in this study depends on expression of HTLV-III genes, and previous evidence indicates that a proportion of cells infected with HTLV-III may not express viral RNA. Moreover, this degree of infection of the lung is likely limited to LIP, since in ten patients with AIDS and pulmonary diseases other than LIP, only 0% to 0.002% of cells in lung were positive for viral RNA expression. Thus, HTLV-III may play a direct causal role in the development of LIP in infected patients, implicating its involvement in yet another of the diverse clinical diseases associated with this virus.

  20. Micro-environment causes reversible changes in DNA methylation and mRNA expression profiles in patient-derived glioma stem cells.

    Directory of Open Access Journals (Sweden)

    Mehmet Baysan

    Full Text Available In vitro and in vivo models are widely used in cancer research. Characterizing the similarities and differences between a patient's tumor and corresponding in vitro and in vivo models is important for understanding the potential clinical relevance of experimental data generated with these models. Towards this aim, we analyzed the genomic aberrations, DNA methylation and transcriptome profiles of five parental tumors and their matched in vitro isolated glioma stem cell (GSC lines and xenografts generated from these same GSCs using high-resolution platforms. We observed that the methylation and transcriptome profiles of in vitro GSCs were significantly different from their corresponding xenografts, which were actually more similar to their original parental tumors. This points to the potentially critical role of the brain microenvironment in influencing methylation and transcriptional patterns of GSCs. Consistent with this possibility, ex vivo cultured GSCs isolated from xenografts showed a tendency to return to their initial in vitro states even after a short time in culture, supporting a rapid dynamic adaptation to the in vitro microenvironment. These results show that methylation and transcriptome profiles are highly dependent on the microenvironment and growth in orthotopic sites partially reverse the changes caused by in vitro culturing.

  1. Amplified voltammetric detection of miRNA from serum samples of glioma patients via combination of conducting magnetic microbeads and ferrocene-capped gold nanoparticle/streptavidin conjugates.

    Science.gov (United States)

    Lu, Zhixuan; Tang, Hailin; Wu, Daohong; Xia, Yonghong; Wu, Minghua; Yi, Xinyao; Li, Hengfeng; Wang, Jianxiu

    2016-12-15

    MicroRNA (miRNA) plays a key regulatory role in many biological processes, emerging as an important biomarker for a large variety of cancer diseases. Employing gold nanoparticle (AuNP)-coated magnetic microbeads (AuNP-MMBs) as an immobilization matrix for higher loading density of hairpin-structured DNA probes and then ferrocene (Fc)-capped gold nanoparticle/streptavidin conjugates, amplified electrochemical assay of miRNA has been performed. In the presence of target miRNA, a novel assembly was formed via linking biotinylated hairpin DNA probe-covered AuNP-MMBs with Fc-capped gold nanoparticle/streptavidin conjugates and then collected by magnetic electrodes for voltammetric detection. The enlarged surface area, good conductivity of AuNP-MMBs and the multiple Fc tags on the electrode surface ensure high sensitivity of the method. The oxidation peak current of Fc tags is proportional to the concentrations of miRNA ranging from 5 fM to 100 fM, and a detection limit of 0.14 fM was achieved. The proposed assay is highly selective and reproducible, serving as a viable alternative for the detection of miRNA-182 from serum samples of glioma patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Comparison of long-term survival between temozolomide-based chemoradiotherapy and radiotherapy alone for patients with low-grade gliomas after surgical resection

    Science.gov (United States)

    Gai, Xiu-juan; Wei, Yu-mei; Tao, Heng-min; An, Dian-zheng; Sun, Jia-teng; Li, Bao-sheng

    2016-01-01

    Purpose This study was designed to compare the survival outcomes of temozolomide-based chemoradiotherapy (TMZ + RT) vs radiotherapy alone (RT-alone) for low-grade gliomas (LGGs) after surgical resection. Patients and methods In this retrospective analysis, we reviewed postoperative records of 69 patients with LGGs treated with TMZ + RT (n=31) and RT-alone (n=38) at the Shandong Cancer Hospital Affiliated to Shandong University between June 2011 and December 2013. Patients in the TMZ + RT group were administered 50–100 mg oral TMZ every day until the radiotherapy regimen was completed. Results The median follow-up since surgery was 33 months and showed no significant intergroup differences (P=0.06). There were statistically significant intergroup differences in the progression-free survival rate (P=0.037), with 83.9% for TMZ-RT group and 60.5% for RT-alone group. The overall 2-year overall survival (OS) rate was 89.86%. Age distribution (≥45 years and <45 years) and resection margin (complete resection or not) were significantly associated with OS (P=0.03 and P=0.004, respectively). Conclusion Although no differences were found in the 2-year OS between the TMZ + RT and RT-alone groups, there was a trend toward increased 2-year progression-free survival in the TMZ + RT group. With better tolerability, concurrent TMZ chemoradiotherapy may be beneficial for postoperative patients with LGGs. Age distribution and surgical margin are likely potential indicators of disease prognosis. The possible differences in long-term survival between the two groups and the links between prognostic factors and long-term survival may be worthy of further investigation. PMID:27574452

  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. 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 ...

  6. 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.

  7. 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.

  8. Contributions of aryl hydrocarbon receptor genetic variants to the risk of glioma and PAH-DNA adducts.

    Science.gov (United States)

    Gu, Aihua; Ji, Guixiang; Jiang, Tao; Lu, Ailin; You, Yongping; Liu, Ning; Luo, Chengzhang; Yan, Wei; Zhao, Peng

    2012-08-01

    The aryl hydrocarbon receptor (AHR) gene is involved in the response to polycyclic aromatic hydrocarbon (PAH) exposure. To investigate the hypothesis that the genetic variants in the AHR gene might be a causal genetic susceptibility to PAH-DNA adduct formation and glioma risk, we conducted a case-control study of 384 glioma cases and 384 cancer-free controls to explore the association between six common single-nucleotide polymorphisms of the AHR gene and glioma risk. Using PAH-DNA adducts as biomarkers, we then evaluated the association between PAH-DNA adduct levels and glioma risk based on a tissue microarray including 11 controls and 77 glioma patients. We further explored the contributions of the glioma risk-associated AHR polymorphisms to the levels of PAH-DNA adducts in glioma tissues based on 77 glioma patients. We found that PAH-DNA adduct staining existed in normal brain tissues and grades I-IV gliomas, and the staining intensity was significantly associated with the glioma grade. Two AHR polymorphisms (rs2066853 and rs2158041) demonstrated significant association with glioma risk. Intriguingly, we also found statistically significant associations between these two variants and PAH-DNA adduct levels in glioma tissue. These data suggest the contributions of AHR rs2066853 and rs2158041 to glioma risk and the PAH-DNA adduct levels, which shed new light on gene-environment interactions in the etiology of glioma. Further studies with a larger sample size and ethnically diverse populations are required to elucidate the potential biological mechanism for, as well as the impact of, the susceptibility to glioma due to genetic variants of AHR.

  9. 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.

  10. Treatment Options for Class III Malocclusion in Growing Patients with Emphasis on Maxillary Protraction.

    Science.gov (United States)

    Azamian, Zeinab; Shirban, Farinaz

    2016-01-01

    It is very difficult to diagnose and treat Class III malocclusion. This type of malocclusion involves a number of cranial base and maxillary and mandibular skeletal and dental compensation components. In Class III malocclusion originating from mandibular prognathism, orthodontic treatment in growing patients is not a good choice and in most cases orthognathic surgery is recommended after the end of growth. Approximately 30-40% of Class III patients exhibit some degree of maxillary deficiency; therefore, devices can be used for maxillary protraction for orthodontic treatment in early mixed dentition. In cases in which dental components are primarily responsible for Class III malocclusion, early therapeutic intervention is recommended. An electronic search was conducted using the Medline database (Entrez PubMed), the Cochrane Collaboration Oral Health Group Database of Clinical Trials, Science Direct, and Scopus. In this review article, we described the treatment options for Class III malocclusion in growing patient with an emphasis on maxillary protraction. It seems that the most important factor for treatment of Class III malocclusion in growing patient is case selection.

  11. 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

  12. Correction of skeletal Class III in a growing male patient by reverse pull facemask

    Directory of Open Access Journals (Sweden)

    P Kapoor

    2011-01-01

    Full Text Available The following case report describes the management of a 6-year-old male patient in early mixed dentition with a mesial step molar relation, an anterior reverse overjet, and skeletal Class III due to a slightly deficient maxilla. The treatment plan included protraction of the maxilla by a reverse pull Petit type facemask for 10 months followed by 15 months of active retention by a Frankel III appliance.

  13. Evaluation of long-term soft tissue changes after bimaxillary orthognathic surgery in Class III patients.

    Science.gov (United States)

    Aydemir, Halise; Efendiyeva, Ruchengiz; Karasu, Hakan; Toygar-Memikoğlu, Ufuk

    2015-07-01

    To assess soft tissues in the short and long term after bimaxillary surgery in Class III patients by comparing the hard tissue changes and results between time periods. Twenty-six Class III adult patients treated with bimaxillary surgery were included in the study. Cephalometric records were taken before surgery (T1) and 5 months (T2), 1.4 years (T3), 3 years (T4), and 5 years (T5) after surgery. There was no significant relapse in skeletal parameters. Overjet was significantly reduced between T4-T3 time intervals (P bimaxillary surgery patients in the first 3 years after surgery.

  14. Two-phase treatment of patients with crossbite and tendency toward skeletal Class III malocclusion

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Machado Bayerl

    2014-08-01

    Full Text Available Angle Class III malocclusion is characterized by an inadequate anteroposterior dental relationship which may or may not be accompanied by skeletal changes. In general, patients are distressed by a significantly compromised facial aspect which, when associated with a deficient middle third, encourages patients to seek treatment. This article reports a two-phase treatment carried out in a female patient aged six years and six months with a tendency towards a Class III skeletal pattern. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO. It is representative of the Discrepancy Index (DI category, and fulfills part of the requirements for obtaining BBO Diploma.

  15. Serial audiometry and speech recognition findings in Finnish Usher syndrome type III patients.

    NARCIS (Netherlands)

    Plantinga, R.F.; Kleemola, L.; Huygen, P.L.M.; Joensuu, T.; Sankila, E.M.; Pennings, R.J.E.; Cremers, C.W.R.J.

    2005-01-01

    Audiometric features, evaluated by serial pure tone audiometry and speech recognition tests (n = 31), were analysed in 59 Finnish Usher syndrome type III patients (USH3) with Finmajor/Finmajor (n = 55) and Finmajor/Finminor (n = 4) USH3A mutations. These patients showed a highly variable type and de

  16. Characteristics of acute pain attacks in patients with irritable bowel syndrome meeting Rome III criteria

    DEFF Research Database (Denmark)

    Hellström, P.M.; Saito, Y.A.; Bytzer, P.

    2011-01-01

    Objectives: An international multicenter, prospective, non-interventional, 2-month study characterized acute pain attacks in patients with irritable bowel syndrome (IBS). Methods: Adult patients meeting the Rome III IBS diagnostic criteria with a history of 3 pain attacks per month participated...

  17. Craniofacial stability in patients with crouzon or apert syndrome after le fort III distraction osteogenesis

    NARCIS (Netherlands)

    J.H. Reitsma (Jacobus Harmen); E.M. Ongkosuwito (Edwin); P.H. Buschang (Peter); L.N.A. V Adrichem (Léon); B. Prahl-Andersen (Birte)

    2013-01-01

    textabstractObjective: Le Fort III osteotomy with distraction osteogenesis (DO) is used to improve the retruded midface in patients with Crouzon or Apert syndrome. This study aimed to evaluate sagittal and vertical preoperative and postoperative cephalometric changes of DO of the midface in patients

  18. Risk of recurrence in patients with colon cancer stage II and III

    DEFF Research Database (Denmark)

    Bockelman, C.; Engelmann, Bodil E.; Kaprio, T.;

    2015-01-01

    Background. Adjuvant chemotherapy is established routine therapy for colon cancer (CC) patients with radically resected stage III and 'high-risk' stage II disease. The decision on recommending adjuvant chemotherapy, however, is based on data from older patient cohorts not reflecting improvements...

  19. Evaluation of morphologic changes of mandibular symphysis after chin cup therapy in skeletally Cl III patients

    Directory of Open Access Journals (Sweden)

    Hosseinzadeh Nik T.

    2008-04-01

    Full Text Available Background and Aim: Chin cup is an orthopedic appliance for treating growing skeletally Cl III patients. The amount of chin forward movement in addition to morphologic changes in bony structure, determines the final profile of treated patients. The aim of this study was to evaluate the amount of morphologic changes of symphysis after chin cup therapy in skeletally Cl III patients.Materials and Methods: In this clinical trial, twenty eight cephalometries before and after chin cup therapy of 14 skeletally Cl III patients were analyzed. Landmarks introduced by Ricketts were determined to evaluate the symphysis and describe its relation to mandible. َAlso four additional measurements regarding the symphysis individually were evaluated and analyzed. Data were analyzed by paired t and pearson tests with P<0.05 as the level of significance.Results: The results showed that the height of symphysis increased after treatment (P=0.02, but its depth decreased (P=0.04. The sysmphysis turned down and back.Conclusion: These findings suggest that in Cl III malocclusions with a prognathic mandible, chin cup therapy creates changes in the horizontal dimension of symphysis morphology, which improves the Cl III profile. If the patient isn't a vertical grower, vertical changes of symphysis would be desirable. In addition, changes in the vertical dimension of the mandible (body and ramus could be observed as a backward and downward rotation.

  20. TERT promoter mutations lead to high transcriptional activity under hypoxia and temozolomide treatment and predict poor prognosis in gliomas.

    Science.gov (United States)

    Chen, Chen; Han, Sheng; Meng, Lingxuan; Li, Zhonghua; Zhang, Xue; Wu, Anhua

    2014-01-01

    This study explored the effects of telomerase reverse transcriptase (TERT) promoter mutations on transcriptional activity of the TERT gene under hypoxic and temozolomide (TMZ) treatment conditions, and investigated the status and prognostic value of these mutations in gliomas. The effect of TERT promoter mutations on the transcriptional activity of the TERT gene under hypoxic and TMZ treatment conditions was investigated in glioma cells using the luciferase assay. TERT promoter mutations were detected in 101 glioma samples (grades I-IV) and 49 other brain tumors by sequencing. TERT mRNA expression in gliomas was examined by real-time PCR. Hazard ratios from survival analysis of glioma patients were determined relative to the presence of TERT promoter mutations. Mutations in the TERT promoter enhanced gene transcription even under hypoxic and TMZ treatment conditions, inducing upregulation of TERT mRNA expression. Mutations were detected in gliomas, but not in meningiomas, pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, or peripheral blood of glioma patients. Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age. TERT promoter mutations were specific to gliomas. TERT promoter mutations maintained its ability of inducing high transcriptional activity even under hypoxic and TMZ treatment conditions, and the presence of mutations was associated with poor prognosis in glioma patients. These findings demonstrate that TERT promoter mutations are novel prognostic markers for gliomas that can inform prospective therapeutic strategies.

  1. 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.

  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. 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.

  4. 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

  5. Type I and III procollagen propeptides in growth hormone-deficient patients

    DEFF Research Database (Denmark)

    Jensen, L T; Jørgensen, J O; Risteli, J;

    1991-01-01

    The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal...... propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days...... procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective...

  6. Chemotherapy of malignant gliomas: studies of the BTCG.

    Science.gov (United States)

    Shapiro, W R

    1992-01-01

    Phase III Trial 8,301 tested the efficacy and safety of intraarterial (IA) BCNU for the treatment of newly resected malignant glioma, comparing IA BCNU vs intravenous (IV) BCNU (200 mg/m2 q 8 wks), each regimen without or with IV 5-FU (1 g/m2/d x 3 two wks after BCNU). All patients also received radiation therapy. 505 patients entered the study; 448 were in the Valid Study Group (VSG). Excluding 190 patients who for medical reasons were not eligible for IA BCNU, 315 patients were randomized between IA (167) and IV (148) BCNU. Actuarial analysis (log-rank) demonstrated worse survival for the IA group (p = 0.002). Serious toxicity was observed in the IA group; 16 patients (9.5%) developed irreversible encephalopathy with CT evidence of cerebral edema, and 26 patients developed visual loss ipsilateral to the infused carotid artery. 5-FU did not influence survival. Survival between the IV and the IA BCNU patients with glioblastoma multiforme did not differ, but was worse for IA BCNU patients with anaplastic astrocytoma than for IV BCNU (p = 0.002). Neuropathologically, IA BCNU produced white matter necrosis. IA BCNU is neither safe nor effective. Phase II Trial 8420, compared IA cisplatin, 60 mg/m2 every 4 wks, vs IV PCNU, 100 mg/m2 q 8 wks; 311 patients were randomized. Preliminary results have been presented. Severe encephalopathy occurred in only 1.5% of patients receiving IA cisplatin. The median survival of the IV PCNU patients was 11.8 months; that of the IA cisplatin patients was 9.4 months, not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Performance characteristics of postacute traumatic brain injury patients on the WAIS-III and WMS-III.

    Science.gov (United States)

    Axelrod, B N; Fichtenberg, N L; Liethen, P C; Czarnota, M A; Stucky, K

    2001-12-01

    Publication of the third editions of the Wechsler intelligence and memory batteries in 1997 created a need for research identifying Wechsler Adult Intelligence Scale-Third Edition/Wechsler Memory Scale-Third Edition (WAIS-III/WMS-III) profile patterns associated with neuropathology. The WAIS-III/WMS-III Technical Manual offers data on various diagnostic groups, including traumatic brain injury (TBI). Hawkins (1998) employed Technical Manual data to propose certain diagnostic guidelines. In order to validate the conclusions put forth by Hawkins as they apply to brain injury, we examined WAIS-III and WMS-III profiles in an independent sample of 46 TBI cases. As expected, the WAIS-III Processing Speed Index (PSI) was more sensitive to brain injury than other WAIS-III composites; and specific WAIS-III scores were stronger than certain WMS-III scores. On the other hand, the predicted relationship for WMS-III auditory and visual indexes was not found. The lack of specificity for TBI of the proposed index comparisons confirms the need to validate such hypotheses in independent samples.

  8. Psychological distress in Rome III functional dyspepsia patients presenting for testing of gastric emptying.

    Science.gov (United States)

    Dibaise, J K; Islam, R S; Dueck, A C; Roarke, M C; Crowell, M D

    2016-02-01

    There have been conflicting results from studies that have evaluated psychological disturbances in functional dyspepsia (FD). We conducted a comprehensive survey of psychological measures in patients undergoing gastric emptying testing (GET) in order to determine the relationship among psychological distress, gastric emptying, and dyspeptic symptoms. Consecutive patients referred for GET were prospectively enrolled. Details regarding patient characteristics, health care utilization, dyspeptic symptoms, quality of life, and psychological dysfunction were obtained. Depression, anxiety, somatization, stress, positive and negative affect, and alexithymia were queried using validated questionnaires. We compared those dyspeptic patients who met Rome III criteria for FD to those who did not meet these criteria. Two hundred and nine patients (160 female; mean age 46.6 years ± 17.3 years) participated. Around 151 patients (72%) met Rome III criteria for FD. In the entire group, a high level of depression, anxiety, somatization, and perceived stress was present compared to population norms. Health care seeking behavior and symptom severity were greater in those with FD and quality of life was lower compared to non-FD. Gastric emptying did not differentiate the two groups and similar degrees of psychological distress were present whether emptying was delayed or normal. In patients referred for GET, substantial psychological distress is present. The degree of distress was similar regardless of whether the patient met Rome III FD criteria or not. Further evaluation of psychological dysfunction in FD patients may lead to improved diagnosis and determination of the most appropriate treatment. © 2015 John Wiley & Sons Ltd.

  9. Evaluation of the risk of liver damage from the use of 5-aminolevulinic acid for intra-operative identification and resection in patients with malignant gliomas

    DEFF Research Database (Denmark)

    Offersen, Cecilie Mørck; Skjoeth-Rasmussen, Jane

    2017-01-01

    BACKGROUND: The clinical efficacy of 5-aminolevulinic acid (5-ALA) for fluorescence-guided surgery of malignant gliomas is evident from several studies; however, as post-operative elevations of liver enzymes have been seen, there is a potential risk of liver damage upon administration. The aim of...

  10. A longitudinal, qualitative and quantitative exploration of daily life and need for rehabilitation among patients with high-grade gliomas and their caregivers

    DEFF Research Database (Denmark)

    Piil, K; Jarden, Mary Ellen; Jakobsen, J

    2013-01-01

    High-grade gliomas (HGGs) are the most malignant type of brain tumours. The 5-year survival is 10% and a significant part of the ongoing research aims to increase survival through surgical and oncological treatments. Accordingly, there is an increasing need for investigating the HGG trajectory in...

  11. Patients with High-Grade Gliomas Harboring Deletions of Chromosomes 9p and 10q Benefit from Temozolomide Treatment

    Directory of Open Access Journals (Sweden)

    Silke Wemmert

    2005-10-01

    Full Text Available Surgical cure of glioblastomas is virtually impossible and their clinical course is mainly determined by the biologic behavior of the tumor cells and their response to radiation and chemotherapy. We investigated whether response to temozolomide (TMZ chemotherapy differs in subsets of malignant glioblastomas defined by genetic lesions. Eighty patients with newly diagnosed glioblastoma were analyzed with comparative genomic hybridization and loss of heterozygosity. All patients underwent radical resection. Fifty patients received TMZ after radiotherapy (TMZ group and 30 patients received radiotherapy alone (RT group. The most common aberrations detected were gains of parts of chromosome 7 and losses of 10% 9p, or 13q. The spectrum of genetic aberrations did not differ between the TMZ and RT groups. Patients treated with TMZ showed significantly better survival than patients treated with radiotherapy alone (19.5 vs 9.3 months. Genomic deletions on chromosomes 9 and 10 are typical for glioblastoma and associated with poor prognosis. However, patients with these aberrations benefited significantly from TMZ in univariate analysis. In multivariate analysis, this effect was pronounced for 9p deletion and for elderly patients with 10q deletions, respectively. This study demonstrates that molecular genetic and cytogenetic analyses potentially predict responses to chemotherapy in patients with newly diagnosed glioblastomas.

  12. 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

  13. 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...

  14. 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.

  15. The prevalence of celiac disease in patients fulfilling Rome III criteria for irritable bowel syndrome.

    Science.gov (United States)

    Korkut, Esin; Bektas, Mehmet; Oztas, Erkin; Kurt, Mevlut; Cetinkaya, Hulya; Ozden, Ali

    2010-10-01

    Celiac disease shares several symptoms which constitute some of the ROME criteria used for the diagnosis of irritable bowel syndrome (IBS), and as such many patients with underlying Celiac disease may be mistakenly diagnosed as having IBS. The aim of the present study was to determine the prevalence of Celiac disease in patients with IBS fulfilling ROME III criteria. Patients who fulfilled ROME III criteria for irritable bowel syndrome were screened for Celiac disease using the Biocard(TM) Celiac Disease Stick test, and patients who tested positive had their serum samples analyzed for antigliadin IgA and IgG, and anti-tissue transglutaminase IgA antibodies. Patients with detectable antibody levels underwent endoscopic duodenal biopsy to confirm a diagnosis of Celiac disease. Two of 100 patients who were diagnosed as having irritable bowel syndrome as per the Roma III criteria were found to have elevated levels of serum antigliadin IgA and IgG, and anti-tissue transglutaminase IgA antibodies, with histological evidence of Celiac disease on examination of duodenal biopsy. Both patients were started on a gluten-free diet, showing significant improvement in their symptoms on follow-up. Celiac disease is a common finding among patients labeled as IBS. Celiac disease must be considered in differential diagnosis of IBS especially in the therapy refractory group. Copyright (c) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  16. Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients.

    Science.gov (United States)

    Mactier, Swetlana; Kaufman, Kimberley L; Wang, Penghao; Crossett, Ben; Pupo, Gulietta M; Kohnke, Philippa L; Thompson, John F; Scolyer, Richard A; Yang, Jean Y; Mann, Graham J; Christopherson, Richard I

    2014-11-01

    Outcomes for melanoma patients with stage III disease differ widely even within the same subcategory. Molecular signatures that more accurately predict prognosis are needed to stratify patients according to risk. Proteomic analyses were used to identify differentially abundant proteins in extracts of surgically excised samples from patients with stage IIIc melanoma lymph node metastases. Analysis of samples from patients with poor (n = 14, 4 yr) survival outcomes identified 84 proteins that were differentially abundant between prognostic groups. Subsequent selected reaction monitoring analysis verified 21 proteins as potential biomarkers for survival. Poor prognosis patients are characterized by increased levels of proteins involved in protein metabolism, nucleic acid metabolism, angiogenesis, deregulation of cellular energetics and methylation processes, and decreased levels of proteins involved in apoptosis and immune response. These proteins are able to classify stage IIIc patients into prognostic subgroups (P < 0.02). This is the first report of potential prognostic markers from stage III melanoma using proteomic analyses. Validation of these protein markers in larger patient cohorts should define protein signatures that enable better stratification of stage III melanoma patients.

  17. An Investigation of Craniocervical Posture in Class II & Class III Skeletal Patients

    Directory of Open Access Journals (Sweden)

    T. HoseinZadeh-Nik

    2005-02-01

    Full Text Available Statement of Problem: Craniocervical Posture is a factor in the development and function of Craniofacial Structure. Previous studies of different samples have demonstrated associations between craniocervical posture and craniofacial morphology.Purpose: This study aimed lo examine whether any significant association is evident or not between craniocervical posture and the occurrence of Class il & Class III skeletal malocclusions.Materials and Methods: A sample of 76 subjects with Class II & Class III skeletal malocclusion aged 9-i 1 and>18 years were selected. None of them had received orthodontic treatment. Lateral cephalometric radiographs were taken in natural head position (NHP, and craniocervical and craniohorizental angels were traced and determined for analysis of craniocervical posture. Results: According to the craniocervical posture, most class II skeletal patients have flexed heads and class MI skeletal patients have extended heads, as a result malocclusion in these patients seems to become more severe. With increase in age. class II skeletal patients have more flexed their heads and malocclusion become more severe, while with increase in age in class ill skeletal patients, their heads become extended and once again malocclusion thought lo be more severe. In class II skeletal patients, craniocervical posture has a significant correlation with the vertical growth pattern, but shows little correlation with the horizontal growth pattern. In class 111 skeletal patients, craniocervical posture shows no correlation to any of the vertical & horizontal growth patterns, of course the mean of vertical angles is less in these patients and probably in order to make these relation significant in Class III skeletal patients there is need for more samples, in class II & class III skeletal patients, the amount of Na.prep-point A and pog-Na.prep with craniocervical posture shows a significant correlation. Conclusion: Consideration of craniocervical

  18. [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.

  19. Ulceration of Striae distensae in high-grade glioma patients on concurrent systemic corticosteroid and bevacizumab therapy.

    Science.gov (United States)

    Peters, Katherine B; Coyle, Thomas E; Vredenburgh, James J; Desjardins, Annick; Friedman, Henry S; Reardon, David A

    2011-01-01

    Striae distensae (stretch marks) are a common complication seen in patients on chronic corticosteroid therapy. Under certain circumstances, primary brain tumor patients require chronic corticosteroid therapy and can suffer from striae distensae. Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor-A (VEGF-A) is now more widely used for the treatment of primary brain tumors. In this paper, we present four cases of ulcerated striae distensae in primary brain tumor patients on concurrent corticosteroid and bevacizumab therapy. Because of bevacizumab's effects on wound healing and its recent accelerated approval for recurrent glioblastoma multiforme (GBM), the most common malignant primary brain tumor in adults, this novel skin complication should be considered in patients on concurrent corticosteroid and bevacizumab therapy.

  20. A simple tool for mortality prediction in burns patients: APACHE III score and FTSA.

    Science.gov (United States)

    Moore, E C; Pilcher, D V; Bailey, M J; Cleland, H; McNamee, J

    2010-11-01

    Prediction of outcome for patients with major thermal injury is important to inform clinical decision making, alleviate individual suffering and improve hospital resource allocation. Age and burn size are widely accepted as the two largest contributors of mortality amongst burns patients. The APACHE (Acute Physiology and Chronic Health Evaluation) III-j score, which incorporates patient age, is also useful for mortality prediction, of intensive care populations. Validation for the burns specific cohort is unclear. A retrospective cohort study was performed on patients admitted to the Intensive Care Unit (ICU) via the Victorian Adult Burns Service (VABS), to compare observed mortality with burns specific markers of illness severity and APACHE III-j score. Our primary aim was to develop a mortality prediction tool for the burns population. Between January 1, 2002 and December 31, 2008, 228 patients were admitted to the ICU at The Alfred with acute burns. The mean age was 45.6 years and 81% (n=184) were male. Patients had severe injuries: the average percent TBSA (total body surface area) was 28% (IQR 10-40) and percent FTSA (full thickness surface area) was 18% (IQR 10-25). 86% (n=197) had airway involvement. Overall mortality in the 7-year period was 12% (n=27). Non-survivors were older, had larger and deeper burns, a higher incidence of deliberate self-harm, higher APACHE III-j scores and spent less time in hospital (but similar time in ICU), compared with survivors. Independent risk factors for death were percent FTSA (OR 1.03, 95% CI 1.01-1.05, p=0.01) and APACHE III-j score (OR 1.04, 95% CI 1.02-1.07, pAPACHE III-j score and percent FTSA. Prospective validation of our model on different burn populations is necessary.

  1. The ability of panoramic radiographs to correlate transverse with sagittal dimensions in class III patients

    Directory of Open Access Journals (Sweden)

    Mohsen Shirazi

    2017-02-01

    Full Text Available Background and Aims: In the field of orthodontics, gaining comprehensive information around dento-skeletal complex is necessary to choose the best treatment plan for each patient. The aim of this study was to investigate the linear and angular parameters in panoramic radiographs to find a path to correlate transvers to sagittal dimensions. Materials and Methods: Total number of sixty two, 8-14 years old children who sought for orthodontic therapy were selected (32 skeletal Class III and 30 skeletal Class I. They were exposed to x-ray to obtain the panoramic and lateral views in a controlled condition. Various linear and angular parameters were measured after tracing the landmarks on the panoramic radiograph. Data were obtained and analyzed using T-test. The level of significance was set at 0.05 (P<0.05. Results: Linear parameters of Co-Co, Go-Go and PTM-PTM were significantly lower in class III patients than class I ones (P=0.04, 0.04, 0.02, respectively. The ramus width value was also lower in class III patients. Angular parameters of  Me˄ and N˄ also showed the same results (P<0.001. Go˄ angle was significantly lower in the class I than class III patients (P=0.002, 0.007. Conclusion: Some traceable linear and angular parameters were found in the panoramic radiographs which had the potential to correlate the transverse with sagittal dimension.

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

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    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.

  3. The majority of patients with metastatic melanoma are not represented in pivotal phase III immunotherapy trials

    DEFF Research Database (Denmark)

    Donia, Marco; Kimper-Karl, Marie Louise; Høyer, Katrine Lundby

    2017-01-01

    in 2014, were included in the analysis. Seven pre-defined eligibility criteria, all used to select patients for enrolment in five recent randomised phase III immunotherapy trials, were analysed. Results Fifty-five percent of the total population with MM did not meet one or more eligibility criteria (‘not...... worse baseline prognostic features. However, patients treated with immunotherapy had similar survival outcomes regardless of eligibility. Conclusion Over half of the patients evaluated for systemic treatment of MM are not represented in phase III registration immunotherapy trials. The data reveal a huge...... knowledge gap regarding the usefulness of new immunotherapies in the ‘real-world’ patient population, and urge additional testing of known regimens in selected poor prognosis cohorts....

  4. Early treatment of patient with Class III skeletal and dental patterns

    Directory of Open Access Journals (Sweden)

    Marcos Alan Vieira Bittencourt

    2015-12-01

    Full Text Available Abstract Class III skeletal pattern is characterized by disharmony between maxillary and mandibular basal bones anteroposteriorly, and might or might not be associated with dental changes. In general, facial esthetics is hindered significantly, which most of times is the reason why patients or patient's guardians seek treatment. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO in partial fulfillment of the requirements for Diplomate recertification and revalidation.

  5. Response assessment of bevacizumab in patients with recurrent malignant glioma using [{sup 18}F]Fluoroethyl-l-tyrosine PET in comparison to MRI

    Energy Technology Data Exchange (ETDEWEB)

    Galldiks, Norbert; Fink, Gereon R. [Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Juelich, Juelich (Germany); University of Cologne, Department of Neurology, Cologne (Germany); Rapp, Marion; Sabel, Michael [University of Duesseldorf, Department of Neurosurgery, Duesseldorf (Germany); Stoffels, Gabriele; Shah, Nadim J.; Coenen, Heinz H.; Langen, Karl-Josef [Institute of Neuroscience and Medicine (INM-3,-4,-5), Forschungszentrum Juelich, Juelich (Germany); Juelich-Aachen Research Alliance (JARA) - Section JARA-Brain, Aachen (Germany)

    2013-01-15

    To investigate prospectively the potential of O-(2-[{sup 18}F]fluoroethyl)-l-tyrosine ({sup 18}F-FET) PET in comparison to MRI for the assessment of the response of patients with recurrent high-grade glioma (rHGG) to antiangiogenic treatment. Ten patients with rHGG were treated biweekly with bevacizumab/irinotecan (BEV/IR). MR images and dynamic {sup 18}F-FET PET scans were obtained at baseline and at follow-up after the start of treatment (median 4.9 weeks). Using MRI treatment response was evaluated according to RANO (Response Assessment in Neuro-Oncology) criteria. For {sup 18}F-FET PET evaluation, a reduction >45 % of the metabolically active tumour volume was considered as a treatment response, with the metabolically active tumour being defined as a tumour-to-brain ratio (TBR) of {>=}1.6. The results of the treatment assessments were related to progression-free survival (PFS) and overall survival (OS). For further evaluation of PET data, maximum and mean TBR were calculated using region-of-interest analysis at baseline and at follow-up. Additionally, {sup 18}F-FET uptake kinetic studies were performed at baseline and at follow-up in all patients. Time-activity curves were generated and the times to peak (TTP) uptake (in minutes from the beginning of the dynamic acquisition to the maximum uptake) were calculated. At follow-up, MRI showed a complete response according to RANO criteria in one of the ten patients (10 %), a partial response in five patients (50 %), and stable disease in four patients (40 %). Thus, MRI did not detect tumour progression. In contrast, {sup 18}F-FET PET revealed six metabolic responders (60 %) and four nonresponders (40 %). In the univariate survival analyses, a response detected by {sup 18}F-FET PET predicted a significantly longer PFS (median PFS, 9 vs. 3 months; P = 0.001) and OS (median OS 23.0 months vs. 3.5 months; P = 0.001). Furthermore, in four patients (40 %), diagnosis according to RANO criteria and by {sup 18}F-FET PET was

  6. Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide

    NARCIS (Netherlands)

    W. Taal (Walter); D. Brandsma (Dieta); H.G. de Bruin (Hein); J.E.C. Bromberg (Jacolien); A.T. Swaak-Kragten (Annemarie); P.A. Smitt (Peter); C.A. van Es (Corine); M.J. van den Bent (Martin)

    2008-01-01

    textabstractBACKGROUND. Radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ) is now the standard of care for patients with newly diagnosed glioblastoma. The occurrence of pseudo-progression directly after RT is a recognized phenomenon, but to the authors' knowledge its incidence after

  7. 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.

  8. Morphometric analysis of treatment effects of bone-anchored maxillary protraction in growing Class III patients

    Science.gov (United States)

    De Clerck, H. J.; Cevidanes, L. H.; Franchi, L.

    2011-01-01

    The aim of the present morphometric investigation was to evaluate the effects of bone-anchored maxillary protraction (BAMP) in the treatment of growing patients with Class III malocclusion. The shape and size changes in the craniofacial configuration of a sample of 26 children with Class III malocclusions consecutively treated with the BAMP protocol were compared with a matched sample of 15 children with untreated Class III malocclusions. All subjects in the two groups were at a prepubertal stage of skeletal development at time of first observation. Average duration of treatment was 14 months. Significant treatment-induced modifications involved both the maxilla and the mandible. The most evident deformation consisted of marked forward displacement of the maxillary complex with more moderate favourable effects in the mandible. Deformations in the vertical dimension were not detected. The significant deformations were associated with significant differences in size in the group treated with the BAMP protocol. PMID:21187527

  9. Two-phase treatment of patients with crossbite and tendency toward skeletal Class III malocclusion.

    Science.gov (United States)

    Bayerl, Maria de Lourdes Machado

    2014-01-01

    Angle Class III malocclusion is characterized by an inadequate anteroposterior dental relationship which may or may not be accompanied by skeletal changes. In general, patients are distressed by a significantly compromised facial aspect which, when associated with a deficient middle third, encourages patients to seek treatment. This article reports a two-phase treatment carried out in a female patient aged six years and six months with a tendency towards a Class III skeletal pattern. This case was presented to the Brazilian Board of Orthodontics and Facial Orthopedics (BBO). It is representative of the category with Discrepancy Index (DI) equal or greater than 10, and fulfills part of the requirements for obtaining BBO Diploma.

  10. Gross-total resection of temporal low grade gliomas is a critically important factor in achieving seizure-freedom

    Directory of Open Access Journals (Sweden)

    Lucas Crociati Meguins

    2015-11-01

    Full Text Available Objective To present a surgical series of patients with low grade temporal gliomas causing intractable epilepsy, focusing on long-term seizure outcome.Method A retrospective study was conducted with patients with temporal low-grade gliomas (LGG.Results Sixty five patients with were operated in our institution. Males were more affected than females and the mean age at surgery was 32.3 ± 8.4 (9-68 years. The mean age at seizure onset was 25.7 ± 9.2 (11-66 years. Seizure outcome was classified according with Engel classification. After one year of follow up, forty two patients (64.6% were Engel I; seventeen (26.2% Engel II; four (6.2% Engel III and two (3.1% Engel IV. Statistically significant difference in seizure outcome was obtained when comparing the extension of resection. Engel I was observed in 39 patients (69.6% with total resection and in only 3 (33.3% patients with partial resection.Conclusion Gross-total resection of temporal LGGs is a critically important factor in achieving seizure-freedom.

  11. Gross-total resection of temporal low grade gliomas is a critically important factor in achieving seizure-freedom.

    Science.gov (United States)

    Meguins, Lucas Crociati; Adry, Rodrigo Antônio Rocha da Cruz; Silva Júnior, Sebastião Carlos da; Pereira, Carlos Umberto; Oliveira, Jean Gonçalves de; Morais, Dionei Freitas de; Araújo Filho, Gerardo Maria de; Marques, Lúcia Helena Neves

    2015-11-01

    To present a surgical series of patients with low grade temporal gliomas causing intractable epilepsy, focusing on long-term seizure outcome. A retrospective study was conducted with patients with temporal low-grade gliomas (LGG). Sixty five patients with were operated in our institution. Males were more affected than females and the mean age at surgery was 32.3 ± 8.4 (9-68 years). The mean age at seizure onset was 25.7 ± 9.2 (11-66 years). Seizure outcome was classified according with Engel classification. After one year of follow up, forty two patients (64.6%) were Engel I; seventeen (26.2%) Engel II; four (6.2%) Engel III and two (3.1%) Engel IV. Statistically significant difference in seizure outcome was obtained when comparing the extension of resection. Engel I was observed in 39 patients (69.6%) with total resection and in only 3 (33.3%) patients with partial resection. Gross-total resection of temporal LGGs is a critically important factor in achieving seizure-freedom.

  12. Abnormal collagen I to III distribution in the skin of patients with incisional hernia.

    Science.gov (United States)

    Klinge, U; Si, Z Y; Zheng, H; Schumpelick, V; Bhardwaj, R S; Klosterhalfen, B

    2000-01-01

    The surgical mesh-free repair of incisional hernias has to face recurrence rates of up to 50%. Apart from technical faults this is probably due to collagen metabolic disorders, known to play an important role in the development of inguinal hernia. In particular an altered ratio of collagen types I and III with an increase in collagen type III has been claimed to reduce the mechanical strength of connective tissues. Therefore, we investigated the content of collagen types I and III in the skin of patients with incisional hernia (n = 7) and recurrent incisional hernia (n = 5) in comparison to controls with healthy skin (n = 7) and normal skin scar (n = 7) both by immunohistochemistry and Western blot analysis. Both immunohistochemistry and Western blot analysis revealed a decrease in the ratio of collagen I/III due to a concomitant increase in collagen III. The patients with incisional hernias and with recurrent incisional hernias showed a ratio of 1.0 +/- 0.1 and 0.8 +/- 0.1, respectively, whereas the controls exhibit a ratio of 2.1 +/- 0.2 in healthy skin and of 1.2 +/- 0.2 in normal skin scar, respectively. The decrease was highly significant (p scar, as well as between controls and normal scar, whereas there was not any significant difference between primary and recurrent hernia (p > 0.05). Our data for the first time confirmed that the presence of incisional hernia is accompanied by impaired collagen synthesis in the skin. The decreased tensile strength of collagen type III may play a key role in the development of incisional hernias. Furthermore, it might explain the high recurrence rates of hernia repair by simple closure, as a repetition of the primarily failing technique, and the improvement by the additional use of alloplastic material.

  13. 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

  14. An intra-individual comparison of MRI, [18F]-FET and [18F]-FLT PET in patients with high-grade gliomas.

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    Martha Nowosielski

    Full Text Available OBJECTIVES: Intra-individual spatial overlap analysis of tumor volumes assessed by MRI, the amino acid PET tracer [18F]-FET and the nucleoside PET tracer [18F]-FLT in high-grade gliomas (HGG. METHODS: MRI, [18F]-FET and [18F]-FLT PET data sets were retrospectively analyzed in 23 HGG patients. Morphologic tumor volumes on MRI (post-contrast T1 (cT1 and T2 images were calculated using a semi-automatic image segmentation method. Metabolic tumor volumes for [18F]-FET and [18F]-FLT PETs were determined by image segmentation using a threshold-based volume of interest analysis. After co-registration with MRI the morphologic and metabolic tumor volumes were compared on an intra-individual basis in order to estimate spatial overlaps using the Spearman's rank correlation coefficient and the Mann-Whitney U test. RESULTS: [18F]-FLT uptake was negative in tumors with no or only moderate contrast enhancement on MRI, detecting only 21 of 23 (91% HGG. In addition, [18F]-FLT uptake was mainly restricted to cT1 tumor areas on MRI and [18F]-FLT volumes strongly correlated with cT1 volumes (r = 0.841, p<0.001. In contrast, [18F]-FET PET detected 22 of 23 (96% HGG. [18F]-FET uptake beyond areas of cT1 was found in 61% of cases and [18F]-FET volumes showed only a moderate correlation with cT1 volumes (r = 0.573, p<0.001. Metabolic tumor volumes beyond cT1 tumor areas were significantly larger for [18F]-FET compared to [18F]-FLT tracer uptake (8.3 vs. 2.7 cm3, p<0.001. CONCLUSION: In HGG [18F]-FET but not [18F]-FLT PET was able to detect metabolic active tumor tissue beyond contrast enhancing tumor on MRI. In contrast to [18F]-FET, blood-brain barrier breakdown seems to be a prerequisite for [18F]-FLT tracer uptake.

  15. 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.

  16. Tumor-associated methylation of the putative tumor suppressor AJAP1 gene and association between decreased AJAP1 expression and shorter survival in patients with glioma

    Institute of Scientific and Technical Information of China (English)

    David Cogdell; Woonbok Chung; Yuexin Liu; Matthew McDonald; Kenneth Aldape; Jean-Pierre J. Issa; Gregory N. Fuller; Wei Zhang

    2011-01-01

    Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion.AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1.Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n = 27), and the degree of methylation correlated with Iow levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that Iow AJAP1 gene expression was associated with decreased survival. Thus,both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.

  17. Tumor-associated methylation of the putative tumor suppressor AJAP1 gene and association between decreased AJAP1 expression and shorter survival in patients with glioma.

    Science.gov (United States)

    Cogdell, David; Chung, Woonbok; Liu, Yuexin; McDonald, J Matthew; Aldape, Kenneth; Issa, Jean-Pierre J; Fuller, Gregory N; Zhang, Wei

    2011-04-01

    Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion. AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1. Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that low AJAP1 gene expression was associated with decreased survival. Thus, both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.

  18. 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.

  19. Glioma grade assessment by using histogram analysis of diffusion tensor imaging-derived maps.

    Science.gov (United States)

    Jakab, András; Molnár, Péter; Emri, Miklós; Berényi, Ervin

    2011-07-01

    Current endeavors in neuro-oncology include morphological validation of imaging methods by histology, including molecular and immunohistochemical techniques. Diffusion tensor imaging (DTI) is an up-to-date methodology of intracranial diagnostics that has gained importance in studies of neoplasia. Our aim was to assess the feasibility of discriminant analysis applied to histograms of preoperative diffusion tensor imaging-derived images for the prediction of glioma grade validated by histomorphology. Tumors of 40 consecutive patients included 13 grade II astrocytomas, seven oligoastrocytomas, six grade II oligodendrogliomas, three grade III oligoastrocytomas, and 11 glioblastoma multiformes. Preoperative DTI data comprised: unweighted (B (0)) images, fractional anisotropy, longitudinal and radial diffusivity maps, directionally averaged diffusion-weighted imaging, and trace images. Sampling consisted of generating histograms for gross tumor volumes; 25 histogram bins per scalar map were calculated. The histogram bins that allowed the most precise determination of low-grade (LG) or high-grade (HG) classification were selected by multivariate discriminant analysis. Accuracy of the model was defined by the success rate of the leave-one-out cross-validation. Statistical descriptors of voxel value distribution did not differ between LG and HG tumors and did not allow classification. The histogram model had 88.5% specificity and 85.7% sensitivity in the separation of LG and HG gliomas; specificity was improved when cases with oligodendroglial components were omitted. Constructing histograms of preoperative radiological images over the tumor volume allows representation of the grade and enables discrimination of LG and HG gliomas which has been confirmed by histopathology.

  20. Machine learning methods for the classification of gliomas: Initial results using features extracted from MR spectroscopy.

    Science.gov (United States)

    Ranjith, G; Parvathy, R; Vikas, V; Chandrasekharan, Kesavadas; Nair, Suresh

    2015-04-01

    With the advent of new imaging modalities, radiologists are faced with handling increasing volumes of data for diagnosis and treatment planning. The use of automated and intelligent systems is becoming essential in such a scenario. Machine learning, a branch of artificial intelligence, is increasingly being used in medical image analysis applications such as image segmentation, registration and computer-aided diagnosis and detection. Histopathological analysis is currently the gold standard for classification of brain tumors. The use of machine learning algorithms along with extraction of relevant features from magnetic resonance imaging (MRI) holds promise of replacing conventional invasive methods of tumor classification. The aim of the study is to classify gliomas into benign and malignant types using MRI data. Retrospective data from 28 patients who were diagnosed with glioma were used for the analysis. WHO Grade II (low-grade astrocytoma) was classified as benign while Grade III (anaplastic astrocytoma) and Grade IV (glioblastoma multiforme) were classified as malignant. Features were extracted from MR spectroscopy. The classification was done using four machine learning algorithms: multilayer perceptrons, support vector machine, random forest and locally weighted learning. Three of the four machine learning algorithms gave an area under ROC curve in excess of 0.80. Random forest gave the best performance in terms of AUC (0.911) while sensitivity was best for locally weighted learning (86.1%). The performance of different machine learning algorithms in the classification of gliomas is promising. An even better performance may be expected by integrating features extracted from other MR sequences. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Glioma grade assessment by using histogram analysis of diffusion tensor imaging-derived maps

    Energy Technology Data Exchange (ETDEWEB)

    Jakab, Andras; Berenyi, Ervin [University of Debrecen Medical and Health Science Center, Department of Biomedical Laboratory and Imaging Science, Faculty of Medicine, Debrecen (Hungary); Molnar, Peter [University of Debrecen Medical and Health Science Center, Institute of Pathology, Faculty of Medicine, Debrecen (Hungary); Emri, Miklos [University of Debrecen Medical and Health Science Center, Institute of Nuclear Medicine, Faculty of Medicine, Debrecen (Hungary)

    2011-07-15

    Current endeavors in neuro-oncology include morphological validation of imaging methods by histology, including molecular and immunohistochemical techniques. Diffusion tensor imaging (DTI) is an up-to-date methodology of intracranial diagnostics that has gained importance in studies of neoplasia. Our aim was to assess the feasibility of discriminant analysis applied to histograms of preoperative diffusion tensor imaging-derived images for the prediction of glioma grade validated by histomorphology. Tumors of 40 consecutive patients included 13 grade II astrocytomas, seven oligoastrocytomas, six grade II oligodendrogliomas, three grade III oligoastrocytomas, and 11 glioblastoma multiformes. Preoperative DTI data comprised: unweighted (B{sub 0}) images, fractional anisotropy, longitudinal and radial diffusivity maps, directionally averaged diffusion-weighted imaging, and trace images. Sampling consisted of generating histograms for gross tumor volumes; 25 histogram bins per scalar map were calculated. The histogram bins that allowed the most precise determination of low-grade (LG) or high-grade (HG) classification were selected by multivariate discriminant analysis. Accuracy of the model was defined by the success rate of the leave-one-out cross-validation. Statistical descriptors of voxel value distribution did not differ between LG and HG tumors and did not allow classification. The histogram model had 88.5% specificity and 85.7% sensitivity in the separation of LG and HG gliomas; specificity was improved when cases with oligodendroglial components were omitted. Constructing histograms of preoperative radiological images over the tumor volume allows representation of the grade and enables discrimination of LG and HG gliomas which has been confirmed by histopathology. (orig.)

  2. WMS-III performance in patients with temporal lobe epilepsy: group differences and individual classification.

    Science.gov (United States)

    Wilde, N; Strauss, E; Chelune, G J; Loring, D W; Martin, R C; Hermann, B P; Sherman, E; Hunter, M

    2001-11-01

    The utility of the WMS-III in detecting lateralized impairment was examined in a large sample of patients with temporal lobe epilepsy. Methods of analysis included evaluation of group means on the various indexes and subtest scores, the use of ROC curves, and an examination of Auditory-Visual Index discrepancy scores. In addition, performance on immediate and delayed indexes in the auditory and the visual modality was compared within each group. Of the WMS-III scores, the Auditory-Visual Delayed Index difference score appeared most sensitive to side of temporal dysfunction, although patient classification rates were not within an acceptable range to have clinical utility. The ability to predict laterality based on statistically significant index score differences was particularly weak for those with left temporal dysfunction. The use of unusually large discrepancies led to improved prediction, however, the rarity of such scores in this population limits their usefulness. Although the utility of the WMS-III in detecting laterality may be limited in preoperative cases, the WMS-III may still hold considerable promise as a measure of memory in documenting baseline performance and in detecting those that may be at risk following surgery.

  3. Direct Cranial Nerve Involvement by Gliomas: Case series and review of the literature

    Science.gov (United States)

    Mabray, Marc C.; Glastonbury, Christine M.; Mamlouk, Mark D.; Punch, Gregory E.; Solomon, David A.; Cha, Soonmee

    2017-01-01

    Malignant gliomas are characterized by infiltrative growth of tumor cells, including along white matter tracts. This may result in clinical cranial neuropathy due to direct involvement of a cranial nerve rather than by leptomeningeal spread along cranial nerves. Gliomas directly involving cranial nerves III-XII are rare with only eleven cases reported in the literature prior to 2014, including eight with imaging. We present eight additional cases demonstrating direct infiltration of a cranial nerve by glioma. Asymmetric cisternal nerve expansion as compared to the contralateral nerve was noted with a mean length of involvement of 9.4 mm. Based on our case series, the key imaging feature to recognize direct cranial nerve involvement by a glioma is the detection of an intra-axial mass in the pons or midbrain that is directly associated with expansion, signal abnormality, and/or enhancement of the adjacent cranial nerve(s). PMID:25857757

  4. Natural killer cells eradicate galectin-1-deficient glioma in the absence of adaptive immunity.

    Science.gov (United States)

    Baker, Gregory J; Chockley, Peter; Yadav, Viveka Nand; Doherty, Robert; Ritt, Michael; Sivaramakrishnan, Sivaraj; Castro, Maria G; Lowenstein, Pedro R

    2014-09-15

    Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside-binding lectin galectin-1. Conversely, galectin-1-deficient glioma cells could be eradicated by host NK cells before the initiation of an antitumor T-cell response. In vitro experiments demonstrated that galectin-1-deficient GL26-Cit glioma cells are ∼3-fold more sensitive to NK-mediated tumor lysis than galectin-1-expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells. Cancer Res; 74(18); 5079-90. ©2014 AACR. ©2014 American Association for Cancer Research.

  5. Application of iron oxide nanoparticles in glioma imaging and therapy: from bench to bedside

    Science.gov (United States)

    Liu, Heng; Zhang, Jun; Chen, Xiao; Du, Xue-Song; Zhang, Jin-Long; Liu, Gang; Zhang, Wei-Guo

    2016-04-01

    Gliomas are the most common primary brain tumors and have a very dismal prognosis. However, recent advancements in nanomedicine and nanotechnology provide opportunities for personalized treatment regimens to improve the poor prognosis of patients suffering from glioma. This comprehensive review starts with an outline of the current status facing glioma. It then provides an overview of the state-of-the-art applications of iron oxide nanoparticles (IONPs) to glioma diagnostics and therapeutics, including MR contrast enhancement, drug delivery, cell labeling and tracking, magnetic hyperthermia treatment and magnetic particle imaging. It also addresses current challenges associated with the biological barriers and IONP design with an emphasis on recent advances and innovative approaches for glioma targeting strategies. Opportunities for future development are highlighted.

  6. 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.

  7. 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.

  8. 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.

  9. Expression of EGFRvIII in Glioblastoma: Prognostic Significance Revisited

    Directory of Open Access Journals (Sweden)

    Nicola Montano

    2011-12-01

    Full Text Available The epidermal growth factor receptor variant III (EGFRvIII is associated with increased proliferation of glioma cells. However, the impact of EGFRvIII on survival of patients with glioblastoma (GBM has not been definitively established. In the present study, we prospectively evaluated 73 patients with primary GBM treated with surgical resection and standard radio/chemotherapy. The EGFRvIII was assessed by reverse transcription–polymerase chain reaction (PCR, O6-methylguanine methyltransferase (MGMT promoter methylation was assessed by methylation-specific PCR, and phosphatase and tension homolog (PTEN expression was assessed by immunohistochemistry. In 14 patients of this series, who presented with tumor recurrence, EGFRvIII was determined by real-time PCR. Sensitivity to temozolomide (TMZ was assessed in vitro on GBM neurosphere cell cultures with different patterns of EGFRvIII expression. Age 60 years or younger, preoperative Karnofsky Performance Status score of 70 or higher, recursive partitioning analysis score III and IV, methylated MGMT, and Ki67 index of 20% or less were significantly associated with longer overall survival (OS; P = .0069, P =.0035, P = .0007, P = .0437, and P = .0286, respectively. EGFRvIII identified patients with significantly longer OS (P = .0023 and the association of EGFRvIII/Ki67 of 20% or less, EGFRvIII/normal PTEN, EGFRvIII/methylated MGMT, and EGFRvIII/normal PTEN/methylated MGMT identified subgroups of GBM patients with better prognosis. In recurred GBMs, EGFRvIII expression was approximately two-fold lower than in primary tumors. In vitro, the EGFRvIII-negative GBM neurosphere cells were more resistant to TMZ than the positive ones. In conclusion, in contrast with previous studies, we found that EGFRvIII is associated with prolonged survival of GBM patients treated with surgery and radio/chemotherapy. Depletion of EGFRvIII in recurrent GBMs as well as differential sensitivity to TMZ in vitro indicates that

  10. 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.

  11. 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.

  12. [Phase III clinical trial using autologous mesenchymal stem cells for stroke patients].

    Science.gov (United States)

    Honmou, Osamu

    2016-04-01

    We conduct a double-blind randomized placebo-controlled clinical trial (Phase III: confirmatory trial) of intravenous infusion of autologous mesenchymal stem cells for cerebral infarction patients. The objectives of this study were to examine feasibility, safety, and efficacy of cell therapy using auto serum-expanded autologous mesenchymal stem cells derived from bone marrow in the stroke patients. Inclusion criteria is (1) Cerebral infarction onset within 40 days, (2) Supra-tentorial cerebral infarction(NINDS-III 1990) diagnosed by MRI(or CT), MRA (3D-CTA or DSA), ECG, chest X-ray etc., (3) Classified under grade 4 or 5 of mRS (modified Rankin scale), (4) Age between 20 to 80, (5) The written informed consent from subjects and legal representative is provided.

  13. Increased nitric oxide release by neutrophils of a patient with tyrosinemia type III.

    Science.gov (United States)

    D'Eufemia, Patrizia; Finocchiaro, Roberto; Celli, Mauro; Raccio, Ivana; Properzi, Enrico; Zicari, Alessandra

    2009-06-01

    Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (4-HPD). Few cases have been described with mental retardation or neurological symptoms. Recently it has been demonstrated that 4-HPD participates to nitric oxide (NO) intracellular sequestration in Pseudomonas aeruginosa. 4-HPD is an ubiquitous enzyme with a prominent expression in neutrophils and neurons. In the nervous system NO has been perceived to be a potential neuromodulator although prolonged excessive generation is detrimental. We analyzed NO release by neutrophils of a patient with tyrosinemia type III in order to evaluate a possible influence of 4-HPD deficiency on this process. Our patient, previously described, is a 30-year-old women with persistent tyrosinemia (450-680 micromol/l) and deficient activity of 4-HPD. At 17 months of age she experienced an acute ataxia and drowsiness lasting for 10 days, but further clinical course showed persistent tyrosinemia with normal growth and psychomotor development. Neutrophils isolated from our patient exhibited a NO release greatly higher in respect to the controls (mean+/-SEM 23.2+/-1.8 micromol/10(6) cells vs 3.5+/-0.5 micromol/10(6) cells). Clinical findings of tyrosinemia type III include neurological symptoms and mental retardation but no consistent phenotype has emerged. Therefore the pathogenesis of neurological involvement is yet not well understood. Our results suggest that an excessive neutrophils of NO release could reflect the lack of scavenging action of 4-HPD. Considering the prominent expression of this enzyme in neurons, we hypothesize that excessive NO release could participate in neuronal damage explaining the neurological involvement described in patients with tyrosinemia type III.

  14. 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

  15. Identification of histological correlates of overall survival in lower grade gliomas using a bag-of-words paradigm: A preliminary analysis based on hematoxylin & eosin stained slides from the lower grade glioma cohort of the cancer genome Atlas

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    Reid Trenton Powell

    2017-01-01

    Full Text Available Background: Glioma, the most common primary brain neoplasm, describes a heterogeneous tumor of multiple histologic subtypes and cellular origins. At clinical presentation, gliomas are graded according to the World Health Organization guidelines (WHO, which reflect the malignant characteristics of the tumor based on histopathological and molecular features. Lower grade diffuse gliomas (LGGs (WHO Grade II–III have fewer malignant characteristics than high-grade gliomas (WHO Grade IV, and a better clinical prognosis, however, accurate discrimination of overall survival (OS remains a challenge. In this study, we aimed to identify tissue-derived image features using a machine learning approach to predict OS in a mixed histology and grade cohort of lower grade glioma patients. To achieve this aim, we used H and E stained slides from the public LGG cohort of The Cancer Genome Atlas (TCGA to create a machine learned dictionary of “image-derived visual words” associated with OS. We then evaluated the combined efficacy of using these visual words in predicting short versus long OS by training a generalized machine learning model. Finally, we mapped these predictive visual words back to molecular signaling cascades to infer potential drivers of the machine learned survival-associated phenotypes. Methods: We analyzed digitized histological sections downloaded from the LGG cohort of TCGA using a bag-of-words approach. This method identified a diverse set of histological patterns that were further correlated with OS, histology, and molecular signaling activity using Cox regression, analysis of variance, and Spearman correlation, respectively. A support vector machine (SVM model was constructed to discriminate patients into short and long OS groups dichotomized at 24-month. Results: This method identified disease-relevant phenotypes associated with OS, some of which are correlated with disease-associated molecular pathways. From these image

  16. Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions

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    Krzysztof Roszkowski

    2016-11-01

    Full Text Available The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma. Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months had a better prognosis than those with MGMT methylation alone (OS = 18 months. In patients with astrocytoma anaplasticum (n = 7 with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months. In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments.

  17. Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions

    Science.gov (United States)

    Roszkowski, Krzysztof; Furtak, Jacek; Zurawski, Bogdan; Szylberg, Tadeusz; Lewandowska, Marzena A.

    2016-01-01

    The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy) with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months) had a better prognosis than those with MGMT methylation alone (OS = 18 months). In patients with astrocytoma anaplasticum (n = 7) with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months). In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments. PMID:27834917

  18. Comparability of the expanded WMS-III standardization protocol to the published WMS-III among right and left temporal lobectomy patients.

    Science.gov (United States)

    Doss, R C; Chelune, G J; Naugle, R I

    2000-11-01

    We examined whether differences between the expanded standardization protocol (SP) used to derive norms for the final published version (PB) of the Wechsler Memory Scale - Third Edition (WMS-III; Wechsler, 1997a) would result in differences on the Primary Indexes in a neurologic sample. Specifically, we examined the comparability of the performances of 63 patients with temporal lobectomy (TL) who were administered either the expanded SP protocol (n = 33: 22 left TL and 11 right TL) or the PB battery (n = 30: 11 left TL and 19 right TL). Patients who were administered the SP or PB were comparable in terms of age, sex, education, seizure duration, postsurgical seizure status, and Full Scale IQ. Postoperative intervals were significantly longer for the SP group, although correlational analyses demonstrated no significant relationship between postoperative follow-up interval and WMS-III performance. A series of t tests revealed no significant differences on any of the eight Primary Index scores between patients taking the two versions of the WMS-III for either left or right TL groups. Furthermore, repeated measures analyses of variance failed to show significant differences on modality-specific memory scores between the SP and PB for the left and right TL groups. The current study indicates that temporal lobectomy patients obtained comparable scores on the two versions of the WMS-III.

  19. The prevalence of coeliac disease in patients fulfilling Rome III criteria for irritable bowel syndrome.

    Science.gov (United States)

    Shalaby, Sayed A; Sayed, Moataz M; Ibrahim, Wesam A; Abdelhakam, Sara M; Rushdy, Marwa

    2016-06-01

    The clinical presentation of coeliac disease can vary from a classical malabsorption syndrome to more subtle atypical gastrointestinal manifestations similar to irritable bowel syndrome (IBS). The aim of this study was to investigate the prevalence of coeliac disease in Egyptian patients with clinically diagnosed diarrhoea-predominant IBS (according to Rome III criteria). This study was conducted on 100 patients with clinically diagnosed diarrhoea-predominant IBS (fulfilling Rome III criteria). They were subjected to complete clinical evaluation, routine laboratory investigations, abdominal ultrasonography and serum anti-tissue transglutaminase antibody (anti-tTG) test as a predictor marker for coeliac disease. All patients who tested positive for serum anti-tTG underwent upper gastrointestinal endoscopy with four to eight biopsy samples collected from the second part of the duodenum. All of the studied 100 patients presented with abdominal pain or discomfort, flatulence and diarrhoea. Eight patients (8%) exhibited high levels of serum anti-tTG, and their duodenal biopsy samples satisfied the histopathological criteria of coeliac disease. The studied patients were divided into two groups: Group I comprising 92 patients with IBS and negative anti-tTG results and Group II comprising eight patients with IBS and positive anti-tTG results. A non-significant difference was noted between the two groups in age, gender and duration of abdominal pain (p>0.05). The haemoglobin level was found to be significantly reduced in anti-tTG-positive patients (p<0.01), as was the Na level in anti-tTG-negative patients (p<0.05). A highly statistically significant inverse correlation was noted between anti-tTG and both serum total protein and serum albumin. Some symptoms overlap between coeliac disease and IBS. A lack of awareness may lead to a diagnostic delay in these patients. Copyright © 2016 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

  20. Analysis of the characteristics of patients with open tibial fractures of Gustilo and Anderson type III

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    Frederico Carlos Jaña Neto

    2016-04-01

    Full Text Available OBJECTIVE: To analyze the characteristics of patients with Gustilo-Anderson Type III open tibial fractures treated at a tertiary care hospital in São Paulo between January 2013 and August 2014. METHODS: This was a cross-sectional retrospective study. The following data were gathered from the electronic medical records: age; gender; diagnosis; trauma mechanism; comorbidities; associated fractures; Gustilo and Anderson, Tscherne and AO classifications; treatment (initial and definitive; presence of compartment syndrome; primary and secondary amputations; MESS (Mangled Extremity Severity Score index; mortality rate; and infection rate. RESULTS: 116 patients were included: 81% with fracture type IIIA, 12% IIIB and 7% IIIC; 85% males; mean age 32.3 years; and 57% victims of motorcycle accidents. Tibial shaft fractures were significantly more prevalent (67%. Eight patients were subjected to amputation: one primary case and seven secondary cases. Types IIIC (75% and IIIB (25% predominated among the patients subjected to secondary amputation. The MESS index was greater than 7 in 88% of the amputees and in 5% of the limb salvage group. CONCLUSION: The profile of patients with open tibial fracture of Gustilo and Anderson Type III mainly involved young male individuals who were victims of motorcycle accidents. The tibial shaft was the segment most affected. Only 7% of the patients underwent amputation. Given the current controversy in the literature about amputation or salvage of severely injured lower limbs, it becomes necessary to carry out prospective studies to support clinical decisions.

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

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    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.

  2. 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.

  3. Clinical Significance of Serum miR-128 and miR-720 Relative Expressionsin Patients with Glioma%脑胶质瘤患者血清miR-128和miR-720相对表达量及临床意义

    Institute of Scientific and Technical Information of China (English)

    李春生

    2013-01-01

    目的 探讨血清miR-128和miR-720相对表达量对脑胶质瘤的诊断价值.方法 采用TaqMan MicroRNA Assays Real-time PCR技术检测62名健康对照者、54例低级别脑胶质瘤患者和57例高级别脑胶质瘤患者血清miR-128和miR-720相对表达量.结果 低级别脑胶质瘤组与健康对照组比较血清miR-720相对表达量差异有统计学意义(P<0.05),高级别脑胶质瘤组miR-128和miR-720相对表达量差异均有统计学意义(P<0.05);与低级别脑胶质瘤组比较,高级别脑胶质瘤组的miR-128和miR-720相对表达量差异均有统计学意义(P<0.05).miR-128和miR-720联合检测区分健康对照组和脑胶质瘤组的诊断灵敏性和特异性分别为92.3%和87.2%,区分低级别脑胶质瘤组和高级别脑胶质瘤组的诊断灵敏性和特异性分别为84.3%和88.9%.结论 血清miR-128和miR-720相对表达量联合诊断为临床脑胶质瘤的诊断和预后提供一种辅助方法.%Objective To explore the diagnostic values of serum miR-128 and miR-720 relative expressions in patients with glioma.Methods The serum miR-128 and miR-720 relative expressions were detected by TaqMan MicroRNA Assays Real-time PCR in 54 low-grade glioma patients group,57 high grade glioma patients group and 62 healthy controls group.Results Compared to the healthy control group,miR-720 relative expression in patients with low-grade glioma were showed significant difference,miR-128 and miR-720 relative expressions in the high-grade glioma group showed significant difference.Compared to the low-grade glioma group,miR-128 and miR-720 relative expressions in the high-grade glioma were showed significant difference.The diagnostic sensitivity and specificity of miR-128 and miR-720 relative expressions for discriminating the healthy control group and the glioma group were 92.3% and 87.2%,respectively.The diagnostic sensitivity and specificity for discriminating the low-grade glioma group and the high

  4. Association of BCL2-938C>A genetic polymorphism with glioma risk in Chinese Han population.

    Science.gov (United States)

    Li, Wei; Qian, Chunfa; Wang, Linxiong; Teng, Hong; Zhang, Li

    2014-03-01

    Glioma is the most common type of primary brain malignancy in adults. The anti-apoptotic protein B-cell lymphoma 2 (BCL2) has been implicated in the pathogenesis of glioma. This study aimed to evaluate the potential association between BCL2-938C>A genetic polymorphism and glioma susceptibility. This case-control study was conducted in Chinese Han populations consisting of 248 glioma cases and 252 cancer-free controls. The BCL2-938C>A genetic polymorphism was detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified using DNA sequencing methods. Our data suggested that the genotype/allele of BCL2-938C>A polymorphism were statistically associated with the increased risk of glioma where the risk of glioma for genotype AA or allele A is significantly higher than wild genotype CC (odds ratio (OR) = 2.23, 95% confidence interval (CI) 1.21-4.10, p = 0.009) or allele C (OR = 1.39, 95% CI 1.06-1.82, p = 0.016), respectively. In addition, the BCL2-938AA genotype was significantly more common in patients with glioblastoma and in patients with grade IV glioma. Our findings indicate that the BCL2-938C>A polymorphism is associated with the susceptibility to glioma in Chinese Han populations and might be used as molecular markers for evaluating glioma risk.

  5. Long-term Outcomes Following Radiotherapy for Adolescent Patients With Nonmetastatic WHO Type III Nasopharyngeal Carcinoma.

    Science.gov (United States)

    Greenwalt, Julie C; Indelicato, Daniel J; Amdur, Robert J; Morris, Christopher G; Kirwan, Jessica M; Mendenhall, William M

    2016-12-01

    To report long-term results of primary radiotherapy for nasopharyngeal cancer (NPC) presenting in the adolescent group. Ten adolescent patients with World Health Organization (WHO) type III NPC were treated with primary radiotherapy at our institution between 1969 and 2007. Median age was 16.5 years (range, 11 to 21). Median radiotherapy dose to the primary target volume was 67.5 Gy (range, 60 to 74.8). The bilateral neck received 51.1 Gy (range, 50 to 60 Gy). Five patients were treated with once-daily radiotherapy and 5 received twice-daily radiotherapy. Three patients received neoadjuvant cisplatin and 5FU, and 1 patient received adjuvant maintenance cisplatin and 5FU. Median follow-up time was 9.5 years (range, 1.94 to 34.74). Fifteen-year overall survival, cause-specific survival, and progression-free survival rates were all 70%. Fifteen-year local and regional control rates were 100% and 90%. One patient recurred regionally and distantly simultaneously, and 2 patients developed distant metastases alone. All 3 died of their disease within 3 years. One patient died from multiple radiation-induced secondary meningiomas 34 years after radiotherapy. Five patients developed hypothyroidism, 3 developed sensorineural hearing loss, and 4 developed dental complications. The overall rates of CTCAE grade 3, 4, and 5 toxicity were 40%, 10%, and 10%, respectively. Despite high-radiation doses to the skull base, none of the patients in this study developed grade 3+ cognitive or vision toxicity. Radiotherapy achieves excellent local control in adolescent patients with unresectable WHO type III NPC. Our data support current protocols to systematically tailor treatment volumes and deescalate radiation doses to reduce treatment toxicity.

  6. Advanced-stage III/IV follicular lymphoma. Treatment strategies for individual patients

    Energy Technology Data Exchange (ETDEWEB)

    Heinzelmann, Frank; Bamberg, Michael; Weinmann, Martin [Dept. of Radiation Oncology, Univ. of Tuebingen (Germany); Ottinger, Hellmut [Dept. of Bone Marrow Transplantation, Univ. of Essen (Germany); Engelhard, Marianne [Dept. of Radiation Oncology, Univ. of Essen (Germany); Soekler, Martin [Dept. of Internal Medicine II, Univ. of Tuebingen (Germany)

    2010-05-15

    Background: in patients with advanced-stage III/IV follicular lymphoma (FL), there are many treatment options available. The current challenge is to choose the optimal strategy for the individual patient. Methods: the literature was reviewed with respect to treatment strategies in patients with advanced FL by screening the PubMed databank. Results: in advanced-stage III/IV FL, median survival may approach 8-10 years. Treatment strategies include a watch-and-wait strategy, chemoimmunotherapy, monotherapy with rituximab, and - as an experimental approach so far - radioimmunotherapy. The use of autologous hematopoietic stem cell transplantation (HSCT) for patients in first remission or chemosensitive relapse prolongs progression-free survival while the effect on overall survival remains unclear compared to standard chemotherapy. However, long-term results are flawed by high relapse rates and risk of secondary malignancies. In patients with relapsed/chemoresistant disease, allogeneic HSCT constitutes the only curative approach but is associated with high treatment-related mortality. In the palliative setting, low-dose involved-field irradiation constitutes an effective treatment option in order to control local symptoms with potential long-lasting response. Conclusion: in case of advanced-disease FL, asymptomatic patients can be managed expectantly. In symptomatic patients, chemoimmunotherapy is regarded as standard therapy. In symptomatic elderly patients with relevant comorbidities, rituximab {+-} single-agent chemotherapy, or low-dose involved-field radiotherapy might be appropriate. For younger patients with chemoresistant/relapsed disease, allogeneic HSCT might be considered, since advances in supportive care and better patient selection have resulted in improved outcomes. (orig.)

  7. 全程无缝隙护理模式在胶质瘤术后患者中的应用%Aapplication of seamless nursing model to postoperative patients with gliomaRen

    Institute of Scientific and Technical Information of China (English)

    任琳; 任学芳; 郎黎薇; 殷志雯

    2013-01-01

    目的 探讨全程无缝隙护理模式在胶质瘤患者中的应用效果.方法 选择手术联合放化疗的Ⅲ、Ⅳ级胶质瘤患者200例,随机分为观察组与对照组各100例.对照组采用胶质瘤手术及放化疗护理常规护理.观察组实施全程无缝隙的模式护理,即在常规护理的基础上,于患者放化疗期间发放专病健康教育手册、建立电话短信平台、上门访视、举办病友沙龙等.分别于放疗、化疗疗程结束时测定两组患者的癌因性疲乏与生活质量.结果 观察组癌因性疲乏得分显著低于对照组,生活质量评分显著优于对照组(均P<0.01).结论 全程无缝隙护理模式有助于缓解胶质瘤患者在放化疗期间的身心疲劳,提高其生活质量.%Objective To explore the effect of seamless nursing model on glioma patients. Methods We chose 200 patients with grade Ⅲ /Ⅳ gliomas who received a combination of surgery, radiation therapy, and chemotherapy were randomly divided into an observation group and a control group, with 100 cases in each group. The control group were given routine nursing care. Beside routine nursing care, the observation group additionally received seamless nursing care: we provided disease-oriented health education manual, set up telephone and text message platform, paid visits, and held ward mate salons, etc. At the end of radiation and chemotherapy, we measured the level of cancer-related fatigue and quality of life for the 2 groups. Results The level of cancer-related fatigue were significantly lower, and the quality of life were significantly higher in the observation group than in the control group(P<0. 01 for both). Conclusion Seamless nursing care helps to ease physical and mental fatigue of glioma patients, and therefore improves their quality of life.

  8. Acute physiology, age, and chronic health evaluation (APACHE) III score is an alternative efficient predictor of mortality in burn patients.

    Science.gov (United States)

    Tanaka, Yohei; Shimizu, Mikio; Hirabayashi, Hidemitsu

    2007-05-01

    The present study was performed to evaluate the prognostic value of the acute physiology, age, chronic health evaluation (APACHE) III score in burn patients. We hypothesised that APACHE III score efficiently predicts mortality of burn patients as it reflects the physiological changes in the acute phase and the severity of the underlying illness. Data such as age, gender, inhalation injury, total burn surface area (TBSA), burn index (BI), prognostic burn index (PBI), APACHE III score and outcome of 105 hospitalised patients were analysed retrospectively. TBSA, BI, PBI, and APACHE III score in the mortality group were significantly higher than those of surviving group. The mean scores of surviving versus mortality groups were as follows: TBSA, 19.2+/-17.8% versus 69.1+/-28.4%, pAPACHE III score, 28.4+/-22.2% versus 71.3+/-32.1%, pAPACHE III score showed marked associations between higher scores and higher mortality. APACHE III score showed a significant correlation with PBI (pAPACHE III score could be used as an alternative efficient predictor of mortality in burn patients.

  9. 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.)

  10. [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.

  11. 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...

  12. 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....

  13. Fatty acid oxidation is required for the respiration and proliferation of malignant glioma cells.

    Science.gov (United States)

    Lin, Hua; Patel, Shaan; Affleck, Valerie S; Wilson, Ian; Turnbull, Douglass M; Joshi, Abhijit R; Maxwell, Ross; Stoll, Elizabeth A

    2017-01-01

    Glioma is the most common form of primary malignant brain tumor in adults, with approximately 4 cases per 100 000 people each year. Gliomas, like many tumors, are thought to primarily metabolize glucose for energy production; however, the reliance upon glycolysis has recently been called into question. In this study, we aimed to identify the metabolic fuel requirements of human glioma cells. We used database searches and tissue culture resources to evaluate genotype and protein expression, tracked oxygen consumption rates to study metabolic responses to various substrates, performed histochemical techniques and fluorescence-activated cell sorting-based mitotic profiling to study cellular proliferation rates, and employed an animal model of malignant glioma to evaluate a new therapeutic intervention. We observed the presence of enzymes required for fatty acid oxidation within human glioma tissues. In addition, we demonstrated that this metabolic pathway is a major contributor to aerobic respiration in primary-cultured cells isolated from human glioma and grown under serum-free conditions. Moreover, inhibiting fatty acid oxidation reduces proliferative activity in these primary-cultured cells and prolongs survival in a syngeneic mouse model of malignant glioma. Fatty acid oxidation enzymes are present and active within glioma tissues. Targeting this metabolic pathway reduces energy production and cellular proliferation in glioma cells. The drug etomoxir may provide therapeutic benefit to patients with malignant glioma. In addition, the expression of fatty acid oxidation enzymes may provide prognostic indicators for clinical practice. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

  14. Alterations of thoraco-abdominal volumes and asynchronies in patients with spinal muscle atrophy type III.

    Science.gov (United States)

    LoMauro, Antonella; Romei, Marianna; Priori, Rita; Laviola, Marianna; D'Angelo, Maria Grazia; Aliverti, Andrea

    2014-06-15

    Spinal muscular atrophy (SMA) is characterized by degeneration of motor neurons resulting in muscle weakness. For the mild type III form, a sub-classification into type IIIA and IIIB, based on age of motor impairment, was recently proposed. To investigate if SMA IIIA (more severe) and IIIB differ also in terms of respiratory function, thoracoabdominal kinematics was measured during quiet breathing, inspiration preceding cough and inspiratory capacity on 5 type IIIA and 9 type IIIB patients. Four patients with SMA II (more severe than types III) and 19 healthy controls were also studied. Rib cage motion was similar in SMA IIIB and controls. Conversely, in SMA IIIA and SMA II it was significantly reduced and sometime paradoxical during quiet breathing in supine position. Our results suggest that in SMA IIIA intercostal muscles are weakened and the diaphragm is preserved similarly to SMA II, while in SMA IIIB the action of all inspiratory muscles is maintained. Sub-classification of type III seems feasible also for respiratory function.

  15. Two-Step Extraction of the Lower First Molar for Class III Treatment in Adult Patient

    Science.gov (United States)

    Paulin, Ricardo Fabris; Raveli, Taísa Barnabé; Raveli, Dirceu Barnabé

    2016-01-01

    The aim of this article is to describe a case report of Class III malocclusion treatment with lower first molar extraction. The 27-year-old Caucasian male patient presented a symmetric face with a straight profile, hyperdivergent growth pattern, molar and cuspid Class III relation, and an anterior crossbite as well as a mild crowding on cuspids area, in both upper and lower arches and a tendency to posterior crossbite. The treatment was performed by the use of Haas expansion appliance followed by an initial alignment and leveling of the upper and lower arches with a fixed edgewise appliance, extraction of lower teeth aiming the correction of the incisors proclination and end the treatment with a Class I molar relationship. It resulted in a significant change in the patient's profile, dentoalveolar Class III correction, upper arch expansion, leveling and alignment of the upper and lower arches, and improvement of tipping of the upper and lowers incisors. In cases of a dentoalveolar compensation in well positioned bone bases the treatment with fixed appliances is an alternative and extraction of lower teeth is considered. PMID:27699072

  16. Perampanel in Drug-Resistant Epilepsy with Gliomas Seizure Response to Perampanel in Drug-resistant Epilepsy with Gliomas: Early Observations

    OpenAIRE

    Vecht, Charles; Duran-Peña, Alberto; Houillier, Caroline; Durand, Thomas; Capelle, Laurent; Huberfeld, Gilles

    2017-01-01

    International audience; Drug-resistant epilepsy (DRE) occurs commonly in gliomas, possibly due to a shared mechanism of AMPA-activation involving both seizure activity and tumor growth. We tested the AMPA-receptor blocker perampanel (PER) in patients with DRE in low- and high-grade gliomas. Seizure response was defined as 50% drop in seizure frequency or as seizure-freedom. Cognitive function was examined by computerized test on cognitive speed (CTCS), which is sensitive to the type of cognit...

  17. Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma

    Science.gov (United States)

    Wu, Wenting; Lamborn, Kathleen R.; Buckner, Jan C.; Novotny, Paul J.; Chang, Susan M.; O'Fallon, Judith R.; Jaeckle, Kurt A.; Prados, Michael D.

    2010-01-01

    The purpose of this study is to determine prognostic factors in patients with high-grade recurrent glioma for 3 outcome variables (overall survival, progression-free survival [PFS], and PFS rate 6 months after study registration [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n = 469, 1980–2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n = 596, 1998–2002) were included. Eighteen prognostic variables were considered including type of treatment center (community/academic) and initial low-grade histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional hazards, and logistic regression models with bootstrap resampling were used to identify prognostic variables. Longer survival was associated with last known grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time from initial diagnosis (DxTime), and no baseline steroid use. Factors associated with longer PFS were Grade III and shorter DxTime. For patients without temozolomide as part of the treatment regimen, the only factor associated with better PFS6 was Grade III, although DxTime was important in RPA and PS was important in logistic regression. Grade was the most important prognostic factor for all three endpoints regardless of the statistical method used. Other important variables for one or more endpoints included age, PS, and DxTime. Neither type of treatment center nor initial low-grade histology was identified as a major predictor for any endpoint. PMID:20150383

  18. 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.

  19. Mutations in the 4-hydroxyphenylpyruvate dioxygenase gene (HPD) in patients with tyrosinemia type III.

    Science.gov (United States)

    Rüetschi, U; Cerone, R; Pérez-Cerda, C; Schiaffino, M C; Standing, S; Ugarte, M; Holme, E

    2000-06-01

    Tyrosinemia type III (OMIM 276710) is an autosomal recessive disorder caused by the deficiency of 4-hydroxyphenylpyruvate dioxygenase (HPD), the second enzyme in the tyrosine catabolic pathway. The enzyme deficiency results in an accumulation and increased excretion of tyrosine and phenolic metabolites. Only a few cases with the disorder have been described, and the clinical spectrum of the disorder is unknown. Reported patients have presented with mental retardation or neurological symptoms or have been picked up by neonatal screening. We have identified four presumed pathogenic mutations (two missense and two nonsense mutations) in the HPD gene in three unrelated families encompassing four homozygous individuals and one compound heterozygous individual with tyrosinemia type III. Furthermore, a number of polymorphic mutations have been identified in the HPD gene. No correlation of the severity of the mutation and enzyme deficiency and mental function has been found; neither do the recorded tyrosine levels correlate with the clinical phenotype.

  20. Leptomeningeal metastasis from adult high-grade glioma: clinical analysis of 16 patients%成人高级别胶质瘤脑膜转移16例临床分析

    Institute of Scientific and Technical Information of China (English)

    潘振宇; 于洪泉; 许海洋; 徐松柏; 赵刚; 李蕴潜; 董丽华

    2016-01-01

    Objective To further understand the clinical manifestations and improve clinical diagnosis of patients with leptomeningeal metastasizing high-grade glioma.Methods Sixteen patients with leptomeningeal metastasizing high-grade glioma (WHO classification:grade Ⅲ-Ⅳ) in Department of Radiotherapy,the First Hospital of Jilin University from July 2010 to September 2015 were respectively analyzed.The pathological types included anaplastic gliomas (1),anaplastic oligodenastrocytoma (1),glioblastoma (12),small-cell glioblastoma (1),gliosarcoma (1).We reviewed the relative clinical manifestations of the patients,and further compared them with 163 patients with systemic malignant solid tumors at corresponding period.Results The median time from initial diagnosis to the diagnosis of leptomeningeal metastasis was 13.0 months (range 2-19 months).Plain and enhanced magnetic resonance imaging was obtained in all patients.The main radiographic characteristics included ependymal enhancement (11),leptomeningeal enhancement (3),nodules of implantation metastasis in spinal canal (1),cranial nerve enhancement (2),and ventricular dilatation (1).Eight patients received cerebrospinal fluid examination.The diagnosis of leptomeningeal metastasis in 15/16 patients was determined by radiographic findings.Comparing with leptomeningeal metastasis from systemic malignant tumors at the corresponding period,the incidence of headache in patients with high-grade glioma was significantly lower (6/16 vs 81.6% (133/163);x2 =16.3,P < 0.01);and the incidence of cranial nerve paralysis was also significantly lower (4/16 vs 56.4% (92/163);x2 =5.79,P =0.016 1).The incidence of nerve root symptoms was lower than that of systemic malignant tumors,though without statistically significant difference (2/16 vs 26.4% (43/163);x2 =1.49,P=0.222).Nine patients respectively received chemotherapy,intrathecal chemotherapy or intrathecal chemotherapy combined with whole brain radiotherapy.The median survival

  1. Multivariate Analysis of Prognostic Factors Among 2,313 Patients With Stage III Melanoma: Comparison of Nodal Micrometastases Versus Macrometastases

    Science.gov (United States)

    Balch, Charles M.; Gershenwald, Jeffrey E.; Soong, Seng-jaw; Thompson, John F.; Ding, Shouluan; Byrd, David R.; Cascinelli, Natale; Cochran, Alistair J.; Coit, Daniel G.; Eggermont, Alexander M.; Johnson, Timothy; Kirkwood, John M.; Leong, Stanley P.; McMasters, Kelly M.; Mihm, Martin C.; Morton, Donald L.; Ross, Merrick I.; Sondak, Vernon K.

    2010-01-01

    Purpose To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma. Patients and Methods Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American