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)

We cloned a previously characterized glioblastoma-derived parent cell line (12-18) in order to obtain a relatively homogenous population of human neural cells of neoplastic origin. These cells reach high densities in culture (over 100,000 cells/cm2) and have a high mean DNA content per cell of 18.1 +/- 0.9 pg. A histogram of the cloned cells' chromosome numbers revealed one peak and a modal near diploid number of 52, whereas the parent cell line had expressed polyploidy, with several peaks (including 52) at population doubling level 16. Several consistent results were obtained by Giemsa staining. A persistent structural alteration was the duplication of the long arm of chromosome #9 on to another arm of #9, and the translocation of the short arm of #9 to chromosome #21. We further observed that these cloned cells secrete a specific protease, a plasminogen activator (PA), into serum-free medium (SFM). This enzyme was assayed by the conversion of purified plasminogen to plasmin and the subsequent degradation by plasmin of 125I-labelled fibrin. Glioblastoma-derived cells had higher levels of cell-associated PA activity (2.9-fold) and released more PA activity into SFM (22-fold) than human fetal neural cells. The presence of this protease suggests a mechanism for the invasive character of these neoplasms (glioblastoma multiforme) in vivo.
J Neurol Sci 1982 Dec
PMID:Properties of cloned human glioblastoma cells. Release of a specific protease. 676 10

Incorporation of the serine protease active site reagent diisopropyl fluorophosphate (DFP) into a plasminogen activator with an Mr of approximately 52000 released from cultured human glioblastoma cells was strongly enhanced by incubation with plasmin. This observation led to the isolation of an inactive form of the enzyme from serum-free conditioned culture fluid by affinity chromatography on a column of a Sepharose-bound monoclonal antibody raised against urokinase. An 831-fold purification was obtained with a yield of 41%. The purified molecule was homogeneous as evaluated by polyacrylamide gel electrophoresis with sodium dodecyl sulfate (NaDodSO4), having one stainable band under nonreducing as well as reducing conditions with an Mr of approximately 52000. It was unable to activate plasminogen, but catalytic amounts of plasmin converted it into active enzyme. After NaDodSO4-polyacrylamide gel electrophoresis, the active enzyme showed one band under nonreducing conditions, but after reduction, two bands with Mr values of approximately 20000 and 32000 were observed. The active enzyme incorporated [3H]DFP into the approximately Mr 32000 band, while no incorporation was observed into the inactive form. These findings show that the Mr 52000 human plasminogen activator exists in a proenzyme form consisting of a single polypeptide chain that by proteolysis between half-cystine residues is converted into the active enzyme consisting of two chains with molecular weights of approximately 20000 and 32000, the active site being on the latter chain. The results are consistent with the active form of the enzyme being identical with the higher molecular weight form of urokinase, and together with recent observations that a murine plasminogen activator is released from sarcoma virus transformed cells as an inactive proenzyme, they suggest that zymogens to plasminogen activators are of more general occurrence.
Biochemistry 1982 Dec 07
PMID:Purification of zymogen to plasminogen activator from human glioblastoma cells by affinity chromatography with monoclonal antibody. 689 Dec 64

Previous studies have shown that glucocorticoids can induce the sulfatide-forming enzyme galactosylceramide sulfotransferase (GalCer-ST) in cultured glioblastoma cells. To investigate whether a similar process occurs in vivo, we administered corticosterone to infant and adult adrenalectomized rats and then assayed brain GalCer-ST activity and sulfatide content. Both measures were unexpectedly decreased rather than increased by hormone treatment, indicating that glucocorticoids may not regulate brain sulfatide biosynthesis in the same manner as observed in clonal cell lines.
Brain Res 1982 Dec 02
PMID:Effect of glucocorticoids on galactosylceramide sulfotransferase activity in rat brain. 695 86

Two different mechanisms of aggregation of heparinized human platelet-rich plasma have been identified with two tumor cell lines: In neither case are these mechanisms dependent on platelet-derived ADP. U87MG cells from a glioblastoma line of human origin caused a single irreversible wave of aggregation simultaneously with the onset of platelet secretion, and this was inhibited by heparin and hirudin but not by apyrase or phospholipase D. In contrast, Hut 20 cells from an undifferentiated tumor cell line of murine origin gave an initial reversible wave followed by a second irreversible wave, which then led to secretion. The first wave of platelet aggregation was unaffected by heparin or hirudin but was inhibited by apyrase, and the second wave was inhibited by phospholipase D. Citrate caused irreversible inhibition with either cell line, and aggregation did not occur with gel filtered platelets. These results suggest that platelet aggregation by the Hut 20 line is initially dependent on ADP released from the tumor cells, whereas aggregation induced by the U87MG line is dependent on a procoagulant activity of the tumor cell surface.
Am J Hematol 1981 Dec
PMID:Differing platelet aggregating effects by two tumor cell lines: absence of role for platelet-derived ADP. 733 92

The primary transcript of the calcitonin (CT)/calcitonin gene-related peptide (CGRP) is alternatively spliced in a cell-specific fashion to produce CT in thyroid C cells and CGRP in neuronal cells. The key step in this regulatory process is the recognition and inclusion of exon 4 to produce CT mRNA or nonrecognition and exclusion of exon 4 to produce CGRP mRNA. To determine whether inclusion/exclusion of CT exon is regulated independently of its position, we created a series of minigene constructs containing decreasing amounts of CT gene sequence. A human glioblastoma cell line, T98G, was tested and used as a CT exon exclusion cell line, while HeLa cells were used as a CT exon inclusion cell line. CT exon inclusion/exclusion was regulated when either the relative position of exon 4 within the CT gene was changed or when the exon with flanking sequence was inserted into a completely heterologous gene. Our results demonstrate that CT exon functions as a unit in a position-independent fashion in regulating its own inclusion/exclusion. We believe that the heterologous fusion gene containing only exon 4 and part of its flanking intron sequences will be useful for further defining the sequence elements involved in the regulation of CT/CGRP splicing.
Mol Endocrinol 1994 Dec
PMID:The calcitonin exon and its flanking intronic sequences are sufficient for the regulation of human calcitonin/calcitonin gene-related peptide alternative RNA splicing. 753 92

We investigated the frequency of p53 mutations in 47 pediatric brain tumors of various histologic subtypes that were collected over a period of 5 years. The specimens included 15 primitive neuroectodermal tumors (PNETs), 17 low grade astrocytomas, one anaplastic astrocytoma, three glioblastomas (GBMs), one mixed glial tumor, eight ependymomas, one choroid plexus carcinoma, and one gangliocytoma/ganglioneuroma. Mutations were identified by single strand conformation polymorphism analysis of exons 4-8 and verified by sequencing. Mutations were present in 2 of 3 cases of GBM, but not in 17 low grade astrocytomas (P = 0.02, Fisher's exact test). One GBM demonstrated a germline GGC to AGC transition (gly to ser) at codon 245 with loss of the wild-type allele. A second GBM contained a CGG to TGG transition (arg to trp) at codon 248, also with loss of the wild-type allele, but normal tissue was not available for comparison. In addition, one of 15 PNETs retained heterozygosity but demonstrated a somatic CGT to TGT transition (arg to cys) at codon 273. p53 mutations were absent in other histologic subtypes and in two cases with multiple primary cancers. These data are consistent with earlier findings that p53 mutations are rare in PNETs, which are primarily pediatric tumors. In contrast to adult gliomas, p53 mutations in pediatric gliomas appear restricted to the GBMs. The lack of p53 mutations in pediatric low grade astrocytomas suggests not only histological differences, but also a different molecular pathogenesis in adult and pediatric patients.
Med Pediatr Oncol 1995 Dec
PMID:p53 gene mutations in pediatric brain tumors. 756 4

Tumor necrosis factor-alpha is a pluripotent cytokine that is reportedly mitogenic to astrocytes. We examined expression of the astrocyte intermediate filament component glial fibrillary acidic protein in astrocyte cultures and the U373 glioblastoma cell line after treatment with tumor necrosis factor-alpha. Treatment with tumor necrosis factor-alpha for 72 h resulted in a decrease in content of glial fibrillary acidic protein and its encoding mRNA. At the same time, tumor necrosis factor-alpha treatment increased the expression of the cytokine interleukin-6 by astrocytes. The decrease in glial fibrillary acidic protein expression was greater when cells were subconfluent than when they were confluent. Thymidine uptake studies demonstrated that U373 cells proliferated in response to tumor necrosis factor-alpha, but primary neonatal astrocytes did not. However, in both U373 cells and primary astrocytes tumor necrosis factor-alpha induced an increase in total cellular protein content. Treatment of astrocytes and U373 cells for 72 h with the mitogenic cytokine basic fibroblast growth factor also induced a decrease in glial fibrillary acidic protein content and an increase in total protein level, demonstrating that this effect is not specific for tumor necrosis factor-alpha. The decrease in content of glial fibrillary acidic protein detected after tumor necrosis factor-alpha treatment is most likely due to dilution by other proteins that are synthesized rapidly in response to cytokine stimulation.
J Neurochem 1995 Dec
PMID:Tumor necrosis factor-alpha and basic fibroblast growth factor decrease glial fibrillary acidic protein and its encoding mRNA in astrocyte cultures and glioblastoma cells. 759 70

We have recently shown that vascular endothelial growth factor (VEGF) is produced by human malignant glioma cells and acts on tumor endothelial cells, which express VEGF receptors, suggesting that VEGF is a regulator of tumor angiogenesis. To investigate the feasibility of antiangiogenic brain tumor therapy, we developed an intracerebral (i.c.) rat glioma model. We used two transplantable rat glioma cells lines, C6 and GS-9L, to analyze VEGF regulation in vitro and expression of VEGF and its high affinity tyrosine kinase receptors, flt-1 and flk-1, in vivo. Glioma cells were transplanted i.c. or s.c. into syngeneic rats. C6 gliomas exhibit morphological characteristics of human glioblastoma multiforme such as necroses with palisading cells. Immunocytochemistry with von Willebrand factor showed that C6 gliomas are highly vascularized and therefore show another prominent feature of human glioblastoma. GS-9L gliosarcomas were less vascularized. In situ hybridization showed that VEGF is expressed in vivo in rat glioma cells which reside along necrotic areas and therefore closely mimicks the expression pattern of VEGF observed in human glioblastoma. flt-1 and flk-1 are specifically expressed in endothelial cells in the tumor and at the border between tumor and normal brain but are absent from endothelial cells in the normal brain proper. The action of VEGF may therefore be restricted to tumor endothelium. Upregulation of VEGF, but not acid fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor B messenger RNA was observed in hypoxic C6 and GS-9L cells in vitro. These observations are consistent with a role for VEGF in tumor- and hypoxia-induced angiogenesis. Since the expression pattern of VEGF and its receptors in rat glioma appears to be indistinguishable from human glioblastoma multiforme, this model provides an excellent tool to study anti-angiogenic therapy.
Cancer Res 1993 Dec 01
PMID:Up-regulation of vascular endothelial growth factor and its cognate receptors in a rat glioma model of tumor angiogenesis. 769 95

A human pilocytic astrocytoma-derived cell line, a grade III astrocytoma-derived cell line, and a glioblastoma-derived cell line were transfected with the human wild-type p53 gene, in order to demonstrate the possible suppressor role of this gene in low grade as well as in high grade human astrocytomas. p53 exhibited a strong growth suppressor effect on the three cell lines studied, irrespective of the grade of malignancy of the tumours from which they originate. Furthermore, the p53 gene elicited important morphological changes in these cell lines. p53-Transfected cells displayed a flat morphology, a large cell body, and a stellate shape with long processes, characteristic of differentiated astrocytes. In addition, the growth inhibitory effect of p53 was found not to be due to induction of apoptosis. These results indicate that p53 plays a tumour suppressor role in low grade and high grade human astrocytomas and raise the possibility of the involvement of p53 in glioma cell differentiation in vitro.
J Neurol Sci 1994 Dec 20
PMID:Human wild type p53 inhibits cell proliferation and elicits dramatic morphological changes in human glioma cell lines in vitro. 770 71

Sixteen patients with spontaneous intracerebral haematoma due to intracranial tumours are discussed. The total number of patients with intracranial tumour treated in the period concerned was 594, so the incidence of tumour haemorrhage was 2.7%. In most of the patients we found metastatic neoplasm (n = 6) and glioblastoma (n = 3). All patients were acute admissions. Seven were comatose, seven were somnolent, and two patients were alert. In ten patients the haemorrhage represented the first reliable clinical sign. In six patients a tumour disease was known. Fourteen patients were operated on. Six patients died. Extensive neuro-radiological examination is very important, particularly since 30% of these acute intracerebral haemorrhages occur in patients with benign intracranial tumours.
Nervenarzt 1994 Dec
PMID:[Intracerebral hematoma as an acute manifestation of intracranial tumors]. 785 7


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