Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown that MRS can substantially improve the non-invasive categorization of human brain tumours. However, in order for MRS to be used routinely by clinicians, it will be necessary to develop reliable automated classification methods that can be fully validated. This paper is in two parts: the first part reviews the progress that has been made towards this goal, together with the problems that are involved in the design of automated methods to process and classify the spectra. The second part describes the development of a simple prototype system for classifying 1H single voxel spectra, obtained at an echo time (TE) of 135 ms, of the four most common types of brain tumour (meningioma (MM), astrocytic (AST), oligodendroglioma (OD) and metastasis (ME)) and cysts. This system was developed in two stages: firstly, an initial database of spectra was used to develop a prototype classifier, based on a linear discriminant analysis (LDA) of selected data points. Secondly, this classifier was tested on an independent test set of 15 newly acquired spectra, and the system was refined on the basis of these results. The system correctly classified all the non-astrocytic tumours. However, the results for the the astrocytic group were poorer (between 55 and 100%, depending on the binary comparison). Approximately 50% of high grade astrocytoma (glioblastoma) spectra in our data base showed very little lipid signal, which may account for the poorer results for this class. Consequently, for the refined system, the astrocytomas were subdivided into two subgroups for comparison against other tumour classes: those with high lipid content and those without.
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PMID:Towards a method for automated classification of 1H MRS spectra from brain tumours. 971 72

Cells from major types of gliomas, i.e. oligodendrogliomas and glioblastomas, are able to generate action potentials upon a current injection similar to neurons (Patt et al. (1996) Neuroscience, 71, 601-611; Labrakakis et al. (1997b) J. Neuropath. Exp. Neurol., 56, 243-254. Here, we report that activation of ionotropic glutamate receptors by the selective agonist, kainate, or by glutamate itself, depolarized the tumour cells in culture and living slices from tumour tissue, and can elicit volleys of action potentials, as recorded with the patch-clamp technique. Sixty-six percent of the glioblastoma cells, 44% of the astocytoma and 86% of the oligodendroglioma cells responded to glutamate and the specific agonist of AMPA/kainate receptors, kainate. The involvement of non-NMDA (N-methyl-D-aspartate) receptors is further supported by the observation that both kainate and glutamate currents were blocked by CNQX (6-cyano-7-nitroquinoxaline-2,3-dione). The receptor activation was accompanied by an increase in cytosolic Ca2+, as recorded with a fura-2 microfluorometric system. The Ca2+ elevation was mediated by the activation of Ca2+ channels due to membrane depolarization. The presence of voltage-gated Ca2+ channels was confirmed by patch-clamp experiments. Taken together, these findings imply that the electrophysiological properties of glioma cells are more reminiscent of those of neurons than of glial cells.
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PMID:Glutamate receptor activation can trigger electrical activity in human glioma cells. 975 1

Neurotrophins regulate the proliferation and differentiation of neurons in the central nervous system via a family of specialized receptors, including TrkA, TrkB, and TrkC. As little is known about their expression or potential role in human glial tissues and glial tumors, we undertook an immunohistochemical analysis of human glia, glioma tissues and cell cultures of glial tumors to characterize the expression of Trk family members (full-length TrkA, TrkB, the truncated form of TrkB, and TrkC). In normal human brain Trk A, B, and C immunoreactivity was found in neurons and some weak staining was also seen astrocytes. No Trk expression was seen on oligodendrocytes. Strong reactivity was seen in reactive astrocytes in a glial scar. In a total of 34 glioma tissue specimens, which included 16 astrocytic tumors (4 low-grade astrocytomas and 12 glioblastomas multiforme) and 15 oligodendrogliomas (8 low-grade and 7 anaplastic) as well as 3 oligoastrocytomas (WHO grade II), TrkA, B, and C immunoreactivity was observed exclusively in specimens from astrocytic gliomas (16/16), but not in any of the oligodendrocytic gliomas (0/15). In the oligoastrocytomas, staining was restricted to the astrocytic component. In the astrocytoma and oligodendroglioma specimens, Trk A, B, and C immunoreactivity was also seen in the surrounding reactive astrocytes. Trk expression was independent of age, sex or histological grade of the investigated tumors. In six primary cell cultures, one derived from human astrocytes and five established from malignant astrocytomas, only TrkA immunoreactivity could be detected, while TrkB (both full-length and truncated isoforms) and TrkC were absent. The TrkA expression in primary cell cultures decreased with continuous cell passaging, and no Trk could be detected in established cell lines derived from glioblastoma. In conclusion, our data suggest that in human glial tissues Trk A, B, and C may be expressed in a lineage-restricted manner, thereby distinguishing between astrocytes and oligodendrocytes in a marker-like fashion. Trk expression, like GFAP expression appears to be increased in activated (reactive)/neoplastic astrocytes.
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PMID:Trk A, B, and C are commonly expressed in human astrocytes and astrocytic gliomas but not by human oligodendrocytes and oligodendroglioma. 979

GLIOMAS: As we demonstrated for supratentorial, diffuse gliomas in adults, a stratification into just two grades of malignancy, 'low' and 'high grade,' proved reliable and prognostically relevant. The discriminating histomorphological criterion for high-grade astrocytoma (WHO glioblastoma) as well as anaplastic oligodendroglioma and anaplastic oligoastrocytoma is endothelial hyperplasia/proliferation, which is usually associated with uptake of contrast medium in computed tomography and magnetic resonance imaging. As neoangiogenesis indicates glioma progression, it is worthwhile considering these radiographic features to judge the representativeness of the tumor samples critically. MENINGIOMAS: The revised edition of the WHO classification of brain tumors now includes the 'atypical' meningioma (WHO 'grade' II): Based on both its histomorphological features and prognosis, it should be placed between the common type and anaplastic meningioma. Nuclear area related Ki-67 proliferation indices, as determined by morphometry, were the prerequisite for outlining its histomorphological spectrum better. Cytogenetically, the most consistent progression-associated feature was loss of the distal part of the short arm of one chromosome 1 (1p-). Thus, a screening method using the tissue non-specific form of alkaline phosphatase (ALPL) as the respective marker enzyme was established. Diagnosing a meningioma of the intermediate type implies careful clinical and radiological patient follow-ups to detect tumor recurrences early.
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PMID:[Classification and grading of gliomas and meningiomas]. 986 48

Locoregional radioimmunotherapy (LR-RIT) was administered to 111 patients (20 were recruited in a phase I and 91 in a phase II study) with malignant gliomas: 1 patient with oligodendroglioma, 7 patients with anaplastic oligodendroglioma, 2 with grade II astrocytoma, 10 with anaplastic astrocytoma and 91 with glioblastoma, amounting to 58 newly diagnosed and 53 recurrent tumours. The 131I-labelled monoclonal antibodies BC-2 and BC-4 were used in order to recognize stromal and intracellular glycoprotein tenascin, an antigen present particularly in glioblastoma. The patients were enrolled between February 1990 and December 1997 after conventional therapy. The radiopharmaceutical was injected directly into the tumour site. Sequential scintigraphies demonstrated a high and enduring uptake in the tumour. The mean irradiation dose in the tumour was 300 Gy per cycle. In the group of 74 phase II glioblastoma patients the clinical responses were as follows: 10 patients with stable disease (SD), 9 with partial responses (PR), 23 with no evidence of disease (NED) and 1 patient with complete response (CR). The median survival was 19 months. The response rate (CR + PR + NED) was 17.8% for those patients with bulky lesions, with a median survival of 17 months, but 66.6% for patients with small lesions, with a median survival of 25 months. Better outcomes were recorded in cases with less aggressive diseases: oligodendroglioma, anaplastic oligodendroglioma and anaplastic astrocytoma. We conclude that fractionated LR-RIT can be safely performed, with promising results especially in patients with minimal disease.
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PMID:131I radioconjugated antibodies for the locoregional radioimmunotherapy of high-grade malignant glioma--phase I and II study. 1038 Aug 27

Culturing human central nervous system tumors has been difficult compared to other neoplasms. We report improved success rates for establishing short term human brain tumor cultures using a modified tissue processing technique. Eighty-seven brain tumor specimens (56 glioblastomas, 8 mid grade astrocytomas, 8 oligodendrogliomas, 15 other) were obtained from June 1988 to March 1997. The first twenty-three samples were processed by dissection, partial enzyme dissociation, and filtration through a tissue culture sieve. Subsequent samples were processed identically except tumor cells were centrifuged on a density gradient prior to plating. Successful cultures were defined as those surviving greater than three passages in tissue culture and growing to sufficient numbers (>10(6) cells) to allow freezing. Success rate was 42% (10/23) using standard processing methods and 86% (55/64) with the addition of density gradient centrifugation. Glial fibrillary acidic protein (GFAP) and vimentin staining, karyotypes, and growth curves were obtained for representative glioma cultures. All cultures tested were positive for vimentin (29/29) while 62% (18/29) were positive for GFAP. Of four cultures karyotyped (two glioblastomas, two oligodendrogliomas), all but one oligodendroglioma culture exhibited clonal cytogenetic abnormalities. These immunohistochemical and karyotypic results are consistent with the malignant glial origin of these cells. Of note, low passage human glioma cultures grew slower and exhibited more contact inhibition than immortalized human glioblastoma cell lines. Nevertheless, this simple method for establishing short term human brain tumor cultures should aid in further developing human brain tumor pre-clinical models as well as enhancing clinical applications dependent on in vitro human brain tumor cell growth adjust.
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PMID:Improved technique for establishing short term human brain tumor cultures. 1044 65

The human erythrocyte GLUT-1 is a transmembrane protein which facilitates transport of glucose in the cell in an energy-independent fashion. Neuroectodermal stem cells show strong membrane immunoreactivitry with this marker at early developmental stages in rodents. Membranous expression by undifferentiated neuroectodermal cells gradually decreases while GLUT-1 becomes confined to the endothelial cells, when these acquire blood-brain barrier function. We thus sought to determine whether GLUT-1 expression was limited to embryonal neoplasms of the central nervous system (CNS) which are presumably derived from developmentally arrested neuroectodermal stem cells. Archival material of 40 primary CNS neoplasms were examined for immunoreactivity with anti-GLUT-1. This included both non-embryonal neoplasms (18 astrocytic tumours, one ependymoma and three oligodendroglioma) and embryonal neoplasms (12 cerebellar medulloblastomas, four supratentorial PNETs and two atypical teratoid/rhabdoid tumours (AT/RhT)). In addition, cell lines and nude mice xenografts derived from both undifferentiated and differentiated tumours were assessed for GLUT-1 immunoreactivity by both immunohistochemistry and Western blotting. All embryonal tumours, MBs and PNET xenografts consistently showed GLUT-1 membrane staining. Non-embryonal neoplasms were negative except for vascular staining. Membrane protein fraction of embryonal tumours cell lines immunoreacted by immunoblot with GLUT-1, whereas the glioblastoma cell line was negative. Expression of GLUT-1 supports the stem cell nature of the cells of origin of MBs, supratentorial PNET and AT/RhTs. As a result, GLUT-1 is a useful marker to define the embryonal nature of CNS neoplasms.
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PMID:Membranous expression of glucose transporter-1 protein (GLUT-1) in embryonal neoplasms of the central nervous system. 1073 70

The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with "glioblastoma multiforme." We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as "short-term" for TTP of less than 6 months (n = 54), and "long-term" for TTP of more than 12 months (n = 52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastoma multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n = 7) or anaplastic oligoastrocytoma (WHO grade III, n = 2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only prognostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy.
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PMID:Long-term survival of glioblastoma multiforme: importance of histopathological reevaluation. 1092 75

To study the role of telomerase in the pathogenesis of different grades and subtype of gliomas, telomerase activity in 31 gliomas was assessed with the use of non-radioisotopic and semi-quantitative procedures for the terminal repeat amplification protocol in this study. Among the samples were 17 glioblastoma multiformes (GBMs); 4 anaplastic astrocytomas (AAs); 5 astrocytomas (ASs); 1 ependymoblastoma (EPB); 2 ependymomas (EPs); 1 oligodendroglioma (OG) and 1 medulloblastoma (MB). Postive telomerase activity was detected in 9 of 17 GBMs (53%), 1 of 4 AAs (25%), 1 of 5 ASs (20%), 1 of 1 EPB (100%), and in positive controls, T 98G and KE-1. Weakly positive activity was detected in 2 of 3 AAs (66%) and 2 of 5 ASs (40%). No telomerase activity was detected in 8 of 17 GBMs (47%), 1 of 4 AAs (25%), 2 of 5 AS (40%), 2 of 2 (100%) EPs, 1 of 1 OG (100%), 1 of 1 MB (100%) and normal brain tissue. We defined telomerase expression as positive and weakly positive cases. The percentage of telomerase activity expression in gliomas tended to correlate with tumour grade in spite of histopathology of tumours. These results indicated that the telomerase activity of gliomas may be used as a tumour marker and that the activation of telomerase should correlate with initiation and malignant progression of gliomas. In addition, non-radioisotopic and semi-quantitative procedure for the terminal repeat amplification protocol appears to be the most suitable to detect telomerase activity expression in small neurosurgical specimens.
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PMID:Telomerase activity in gliomas with the use of non-radioisotopic and semi-quantitative procedure for terminal repeat amplification protocol. 1094 44

The accumulation levels of 201TlCl and Na(+)-K+ ATPase activity in tumor tissue were compared among glioblastoma, benign glioma and meningioma to study the difference in the mechanism of 201TlCl accumulation. The subjects were 19 cases comprised of 6 glioblastoma, 2 oligodendroglioma, 1 fibrillary astrocytoma, 1 pilocytic astrocytoma and 9 meningioma. Preoperative 201TlCl SPECT was performed in all the cases, and Thallium Index (TL index) was calculated by a ratio of 201TlCl in the tumor area and the contralateral area. In addition, cell membrane was extracted from the tumor tissue collected intraoperatively to determine Na(+)-K+ ATPase activity. No statistically significant difference in TL index was noted between the glioblastoma group (6.97 +/- 2.67) and the meningioma group (5.87 +/- 1.99). This fact showed that there was no difference in the accumulation level of 201TlCl between the two groups. On the other hand, the glioblastoma group indicated a higher value of Na(+)-K+ ATPase activity (49.13 +/- 43.76 mumole/hour/mg protein) than the meningioma group (7.73 +/- 13.84 mumole/hour/mg protein) (p < 0.05, t test). These results suggested the involvement of Na(+)-K+ ATPase activity in 201TlCl accumulation in glioblastoma and the influences of other accumulation mechanism than Na(+)-K+ ATPase activity such as the volume of intratumoral vascular bed in meningioma.
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PMID:[Difference in 201TlCl accumulation mechanism in brain tumors: a comparison of their Na(+)-K+ ATPase activities]. 1096 51


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