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 have used a tumorigenic glioblastoma cell line, SNB-19, as a model system to identify fucose-containing glycoprotein candidates for tumor suppressor function. Glycoproteins were analyzed after treatment with a variety of chemical differentiating agents by two-dimensional SDS-PAGE, followed by electroblotting and visualization using the fucose-specific lectin, Ulex europeaus I. Approximately 25 fucose-containing glycoproteins (FUCGLAPs) were routinely visualized in control extracts using 60-70 micrograms of protein per gel and staining with Vectastain ABC kits. Retinoic acid induced the most marked change in FUCGLAP expression, causing a fivefold increase in one FUCGLAP (M(r) = 125 kDa, pI = 6.6). Neither butyric acid, dibutyryl cAMP, nor combinations of these compounds gave a similar result. Using this model system and analytical approach, it should be possible to identify, isolate, and evaluate glycoprotein oligosaccharides for their tumor modulating capability.
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PMID:The identification of glioblastoma-associated, fucose-containing glycoproteins induced by retinoic acid. 808 41

To establish stable culture conditions which support persistence of the human cytomegalovirus (HCMV) genome in a latent state, the expression of the bacterial neomycin phosphotransferase (neo) from HCMV recombinants was used for selection. Different cell lines were infected with HCMV recombinants. The human glioblastoma line U138-MG was rendered resistant to G418 and retained the viral genome. More than 90% of the cells expressed the viral IE1 protein of 72 kDa for a culture period of 18 months. Many fewer cells expressed IE2-encoded proteins. No late gene expression or infectious virus was detectable. IE2 gene expression in latently infected cells appeared to be restricted at the level of RNA accumulation. Treatment with TPA or retinoic acid led to enhanced expression of the IE2 gene and the early genes encoding pp65 (UL83) and p52 (UL44). Superinfection with wild-type HCMV led to replication of neo-recombinant virus, indicating that replication-competent virus had been retained in latently infected U138-MG and that the cells had kept their permissive phenotype. Latent HCMV infection in U138-MG cells provides a useful model system for studying the role of particular viral and cellular genes in latent and permissive infections.
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PMID:Reduced levels of IE2 gene expression and shutdown of early and late viral genes during latent infection of the glioblastoma cell line U138-MG with selectable recombinants of human cytomegalovirus. 809 45

The cell-surface expression of major histocompatibility (MHC) antigens and the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) is essential for target cell recognition by T lymphocytes. The expression of both classes of molecule is induced by various cytokines, notably interferon gamma (IFN gamma). Since transforming growth factor beta (TGF beta) has been recently reported to antagonise HLA-DR induction by IFN gamma we have examined, using a number of murine and human cell lines, the effect of TGF beta on IFN gamma-induced MHC class I and class II and ICAM-1 expression. All of the cell lines tested expressed elevated class I MHC following IFN gamma treatment. Class II MHC induction was seen on most but not all of the cells, the exceptions being among a panel of human colorectal carcinoma cell lines. A striking difference between cells of different origin was noted in the response to TGF beta. TGF beta was found to antagonise IFN gamma-induced class I and class II MHC expression on C3H 10T1/2 murine fibroblasts, early-passage BALB/c mouse embryo fibroblasts, a murine oligodendroglioma cell line, and on MRC5 human fibroblasts and two human glioblastoma cell lines. Class II MHC was much more strongly inhibited (sometimes completely) than class I MHC. TGF beta also inhibited induction of class I MHC expression by IFN alpha. However, TGF beta did not inhibit class I or class II MHC induction by IFN gamma in any of the nine colorectal carcinoma cell lines, although two of five of the lines tested were growth-inhibited by TGF beta. On the other hand, human ICAM-1 induction by IFN gamma was not affected by simultaneous treatment with TGF beta in any of the cell lines. The down-regulation of IFN gamma-induced MHC antigens by TGF beta is not, therefore, the result of a general antagonism of IFN gamma. Retinoic acid has recently been reported to induce ICAM-1 expression on human tumour cells. We have confirmed this observation on MRC5, and the two human glioblastoma cell lines, however six colorectal carcinoma cell lines tested did not respond. In contrast to IFN gamma-induced ICAM-1 expression, retinoic-acid-induced ICAM-1 expression was inhibited by TGF beta on two of the three responsive lines.
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PMID:Interactions between interferon gamma and retinoic acid with transforming growth factor beta in the induction of immune recognition molecules. 810 Apr 85

Platelet-activating factor (PAF), a potent lipid mediator generated in cell injury and in the inflammatory and immune responses, promotes transcriptional activation of several primary response genes. TIS10/PGS-2 is a primary response gene encoding the inducible form of prostaglandin synthase. The inductive effects of PAF and retinoic acid (RA), alone and in combination, were studied with the regulatory region of TIS10/PGS-2 transfected into an exponentially growing glioblastoma-neuroblastoma NG108-15 hybrid in the human SH-SY5Y neuroblastoma or in the NIH 3T3 cell. RA alone exhibited only a small inductive effect. However, in the presence of RA (100 nM), a PAF-dependent (1-50 nM) synergistic activation of luciferase reporter constructs driven by regulatory regions of the TIS10/PGS-2 gene was found. The hetrazepine BN-50730, an antagonist selective for intracellular PAF binding sites, inhibited PAF and RA induction of luciferase from the TIS10/PGS-2 promoter. Thus, the intracellular PAF binding site is involved in TIS10/PGS-2 expression. Induction is rapid, suggesting that the combination of PAF and RA activates a preexisting latent transcription factor(s). Deletion studies restrict the major PAF and RA cis-acting response element of the TIS10/PGS-2 gene to a 70-nucleotide sequence as an intracellular inducer of TIS10/PGS-2 expression. The synergistic effect of RA and PAF represents an unusual convergence of nuclear signaling pathways by which, through the modulation of preexisting transcription factors, specific gene expression can be upregulated. PAF-dependent induction of TIS10/PGS-2 expression may play a role in cell injury, differentiation, inflammation, and immune responses.
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PMID:Platelet-activating factor and retinoic acid synergistically activate the inducible prostaglandin synthase gene. 820 77

Neuroectodermal tumours express hormones which are post-translationally processed and inactivated by the action of specific proteases and peptidases. The data reported here show the presence of a novel thermolysin-like metallo-endopeptidase activity in several human cell lines. The soluble fractions of neuroblastoma, melanoma and a glioblastoma tumour cell lines are able, with different degrees, to cleave the Ser12-Phe13 bond of a DVDERDVRGFAS decreases FLNH2 substrate. The inhibition pattern suggests a metallo-endopeptidase thermolysin-like character, with the involvement of thiol group(s), clearly distinct from neutral endopeptidase (NEP; EC 3.4.24.11). This metallo-endopeptidase activity is down regulated during retinoic acid(RA)-induced neuronal differentiation in the RA-sensitive SK-N-BE(2) cells but not in the RA-resistant BE(2)-M17 cells, suggesting that the down regulation is related to neuronal differentiation and not a direct effect of RA on the enzymatic activity.
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PMID:Modulation of a novel thermolysin-like metallo-endopeptidase activity during retinoic acid-induced differentiation of human neuroectodermal tumor cell lines. 838 87

The biological significance of vitamin D receptors expressed by glioblastoma and other glial tumours is still unclear. In an effort to clarify this issue we studied the effects of increasing concentrations of 25-dihydroxyvitamin D3 and its metabolite 1 alpha,25-dihydroxyvitamin D3 on two human glioblastoma cell lines. Both substances were capable of inducing a significant (> 50%) reduction in growth of the two glioblastoma cell lines at dosages over 5 microM. When the HU 70 cell line was treated by increasing dilutions of 25-dihydroxyvitamin D3 combined with 1 microM all trans-retinoic acid, significant inhibition was apparent even after addition of 25-dihydroxyvitamin D3 in the nanomolar range. Reduction of growth index was mainly due to induced cell death. Our results provide in vitro evidence that vitamin D metabolites alone or in combination with retinoids may be potentially useful agents in the differentiation therapy of human malignant gliomas.
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PMID:Effects of vitamin D and retinoic acid on human glioblastoma cell lines. 874 64

Preliminary data have shown that IL-6 may act as an autocrine growth factor to control proliferation. We further characterised the role of IL-6 in tumour growth as an autocrine/paracrine growth factor in neuroectodermal tumours. We evaluated the production and secretion of IL-6 by seven human melanoma, five neuroblastoma and one glioblastoma cell lines. Moreover, we determined their IL-6-dependent growth in serum free-medium or under minimal growth-supplement conditions: IL-6 dependent growth was observed in two non-IL-6 producing melanoma and in one neuroblastoma cell lines. In addition, expression of IL-6 mRNA and peptide was increased by retinoic acid. The data support the hypothesis that IL-6 contributes to neuroectodermal tumour growth, even though it shows a less potent effect than other reported growth factor such as IGF-II.
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PMID:A possible growth factor role of IL-6 in neuroectodermal tumours. 904 37

Retinoids play fundamental roles in CNS development, but their distribution, metabolism, and function within the mature human CNS are unknown. In these studies, extracts of autopsy tissues recovered from histopathologically confirmed control and Alzheimer diseased brains were tested for their ability to synthesize retinoic acid. Retinaldehyde dehydrogenase (RLDH), the enzyme that forms retinoic acid from retinaldehyde, was present in hippocampus, frontal cortex, and parietal cortex. The RLDH activity of hippocampus and parietal cortex from Alzheimer diseased brains was 1.5- to 2-fold higher (p < 0.05) compared to the controls. In contrast, the RLDH activity of frontal cortex was the same for both Alzheimer diseased and control groups. A cultured human glioblastoma (U251) and neuroblastoma (LA-N-5) cell line synthesized retinoic acid from retinaldehyde or retinol, suggesting that a variety of neural cell types possess this activity. LA-N-5 cells grown in vitamin A-depleted medium had higher (p < 0.05) RLDH activity (0.35 +/- 0.04 nmol/mg/h) than LA-N-5 cells grown in vitamin A-replete media (0.15 +/- 0.02 nmol/mg/h). This difference was lost when retinol was added back to the medium, confirming that a reduction in vitamin A supply can induce RLDH activity in neural cells. However, this feedback mechanism does not appear to explain the higher RLDH activity of Alzheimer diseased hippocampus and parietal cortex, because the overall vitamin A status as indicated by serum retinol and carotenoid levels and by hippocampal retinoid content was similar for the Alzheimer diseased and control groups. These studies establish the presence of retinoids and RLDH activity in human brain tissues, and indicate that retinoic acid synthesis is modulated in some regions of Alzheimer diseased brain.
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PMID:Retinoic acid synthesis in normal and Alzheimer diseased brain and human neural cells. 916 89

The Radiation Therapy Oncology Group enrolled 30 patients with recurrent malignant astrocytomas onto a phase II study (RTOG 91-13). Patients were treated with all-trans-retinoic acid at a starting dose of 120 mg/m2 per day orally continuously until disease progression. Fourteen patients had glioblastoma, 14 had anaplastic astrocytoma, and 2 had other histologies; 53% were under 50 years of age. All patients had failed radiation therapy and/or at least one chemotherapy regimen. All patients had a Karnofsky performance status score of at least 70, but only 37% had a KPS of 90-100. Forty percent had a neurologic function status of grade 1 (able to work). A minimum of 4 weeks of all-trans-retinoic acid defined adequate treatment. Twenty-five patients received adequate therapy. Most common toxicities were dry skin, cheilitis, anemia, and headache; 3 patients had grade 3 headache requiring suspension of all-trans-retinoic acid. No grade 3 hematologic toxicity was observed. Of 25 adequately treated patients, 3 showed objective regression of tumor on magnetic resonance imaging and computed tomography scans, 3 patients remained stable, and 19 patients had disease progression. The median time to tumor progression was 3.8 months and the median survival time was 5.7 months. This study suggests that this dose of single agent all-trans-retinoic acid has modest clinical activity against recurrent malignant gliomas with tolerable side effects. A response rate of 12% and a stabilization rate of 12% are lower than expected. Future studies with higher dosage or in combination with biological response modifiers or chemotherapy may be warranted.
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PMID:All-trans-retinoic acid: a phase II Radiation Therapy Oncology Group study (RTOG 91-13) in patients with recurrent malignant astrocytoma. 921 68

Biased hypermutation events found predominantly in the matrix gene of measles virus isolated from persistent human CNS infections have been attributed to the action of a cellular unwinding/modifying activity (UMA). To define the level and distribution of this activity in brain cells, fractionated extracts were prepared from the nuclei and cytoplasm of human glioblastoma (D-54, U-251) and neuroblastoma (IMR-32, SKN-MC) cells and analyzed for their ability to modify synthetic dsRNAs specific for the measles virus (MV) matrix (M) gene. On a quantitative basis we could show that the activity localized to both the nuclear and cytoplasmic compartments of both cell types analyzed independent of cell proliferation. The presence of significant levels of UMA in the cytoplasm of human brain cells following growth arrestment in vitro with retinoic acid supports the interpretation that UMA may contribute to the attenuation of MV gene functions during the primary infection of brain cells, thereby supporting the establishment of virus persistence.
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PMID:Measles virus-specific dsRNAs are targets for unwinding/modifying activity in neural cells in vitro. 922 45


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