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)

To begin understanding the regulation and biological significance of changes in the expression of intermediate filament proteins in astrocytic tumors, we have recently shown that TGF-alpha alters the protein level of glial fibrillary acidic protein (GFAP), nestin, and vimentin in U-373 MG glioblastoma cells. Here, we have determined the molecular mechanisms regulating these changes. In addition, to evaluate the significance of these changes we have examined whether TGF-alpha affects various cellular properties related to differentiation. Our results show that, in U-373 MG cells treated with TGF-alpha, GFAP gene transcription, mRNA level, and specific protein synthesis decrease by approximately 50%. This suggests that, in U-373 MG cells, TGF-alpha down-regulates the expression of this marker of astrocytic differentiation at the transcriptional level, resulting in decreased GFAP mRNA level and specific protein synthesis. In contrast, TGF-alpha does not change vimentin gene transcription, but increases by about 50% the transcription of the gene for nestin, a marker for undifferentiated astrocytic precursors. This differential regulation of GFAP, nestin, and vimentin gene expression indicates that TGF-alpha induces further dedifferentiation of U-373 MG cells. This notion is also supported by our findings that TGF-alpha increases the motility of U-373 MG cells and induces a less stellate morphology.
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PMID:TGF-alpha differentially regulates GFAP, vimentin, and nestin gene expression in U-373 MG glioblastoma cells: correlation with cell shape and motility. 1064 Apr 25

Glioblastomas are particularly resistant to classical antitumor treatments. Retinoids, which proved effective in the treatment of promyelocytic leukemia, have been used for clinical assays on glioma tumors with only moderate effects; however in some cases they were active in combination with another therapy. These observations prompted us to analyse the efficacy of combining retinoic acid (RA) with a cytokine on a clonal human glioma cell line. On GL-15 cells, RA and tumor necrosis factor alpha (TNFalpha) both reduced the glial fibrillary acidic protein level and DNA synthesis and induced apoptotic pathways, but they were significantly more effective when used together. The up-regulation of the p55 TNF receptors observed during RA exposure might explain this cooperative effect.
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PMID:Effects of retinoic acid and tumor necrosis factor alpha on GL-15 glioblastoma cells. 1067 92

Keratin intermediate filaments (Ifs) are specific for epithelial cell differentiation. This study demonstrates the presence of keratin in two recently established human glioblastoma cell lines 8-MG-BA and 42-MG-BA. Immunofluorescence staining was performed on cells within passage 230 to 235 using monoclonal pan-cytokeratin antibodies. The cells were analyzed during several DIV at different cell density. Keratin-positive stained cells reached 5 to 7% in 8-MG-BA and less than 0.1% in 42-MG-BA cell line. The presence of keratin-positive cells was independent on cell density and days in vitro. Keratin-positive cells appeared unevenly distributed in both cell lines. They were observed as single or areas of keratin-positive cells. The morphological features of keratin-positive and keratin-negative cells were similar. The results are discussed with respect to previous studies on glial fibrillary acidic protein (GFAP) and vimentin to show the heterogeneity of IFs expression in glioma cell lines.
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PMID:Heterogeneity of keratin intermediate filaments expression in human glioma cell lines. 1073 69

A case of a glioblastoma multiforme is presented. Craniotomy was performed with total resection of the right temporal tumor. Postoperatively, the patient received adjuvant radiotherapy, but 6 months after therapy he developed severe nausea and weight loss. Recurrence of an intracranial tumor in the right temporal region with nodules in the liver and spleen were detected by CT scan. Fine-needle biopsies of the liver confirmed the diagnosis of a glioblastoma metastasis with characteristic immunohistochemical staining for glial fibrillary acidic protein. This rare case of an intracerebral glioblastoma metastasizing to liver and spleen was managed by systemic chemotherapy.
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PMID:Uncommon metastasis of a glioblastoma multiforme in liver and spleen. 1077 29

Brain tumors based on their histogenesis, consist of all tumors, derive from the entirely tissue in the intracranial space, both from the neuro-ectodermal/neuro-epithelial tissue and the mesenchymal tissue. By their location they can be divided into infratentorial or supratentorial, and further into deep vs. superficial. The interesting and unique, there are age distribution or location-sex specificity of some brain tumors (BT). WHO Histopathological Typing of Tumors by the CNS, also showing progress on both of their members and new special types of some BT, especially for the meningiomas and neuro-epithelial/neuroglial type. Periodic investigations by the Department of Anatomic Pathology, the Faculty of Medicine, University of Indonesia did not show major changes in their BT types, but there was on their tumors ranging. Astrocytoma (including glioblastoma multiforma) for a while was replaced by meningioma as the most common CNS/Intracranial tumor. There are some techniques for the handling of CNS specimens depending on further purposes through on biomolecular activities or defects. The routine technique using light microscope examination was the most useful one for daily diagnosis for many years. Some immunohistochemistry techniques are needed for difficult cases, e.g., GFAP, NE 14, NSE, S100, and MBP. Diagnostic problems could be caused by tissue- or cell-sampling errors, which are influenced by the tumor location itself. Thus, neurosurgeons encounter problems to pick biopsy intraoperative, or by mishandling by the laboratory of anatomic pathology. Formerly, as final diagnosis, grading of CNS tumors must be put according to the Clinical interest for further management of the patient. CNS grading ranges from grade I (benign looking) to IV (malignant). Morphological grading is based on Kernohan and Adson (1949), or Kernohan and Sayre (1952).
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PMID:Pathological aspects of brain tumors. 1089 65

Oncostatin M (OSM) and other members of the interleukin-6 cytokines, like ciliary neurotrophic factor and leukemia inhibitory factor, can induce differentiation of glial cells. We have recently described that OSM inhibited the growth of human glioma cells in vitro and induced a cell morphology resembling that of mature astrocytes. Using the glioblastoma cell line 86HG39, we demonstrated that treatment of the glioma cells with OSM also leads to a differentiation of the malignant glioma cells as judged by a strong increase in glial fibrillary acidic protein expression. The differentiation and the growth inhibition were not significantly blocked by expression of a dominant-negative (dn) signal transducer and activator of transcription (Stat) 3 protein. OSM exerted a reduction in DNA synthesis even in the presence of a high expression level of dnStat3. Moreover, inhibition of the ras-raf-mitogen-activated protein kinase (MAPK) pathway by the MAPK kinase 1 inhibitor PD98059 resulted in a synergistic enhancement of the OSM effect, indicating that the activation of this pathway counteracts the activity of the cytokine.
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PMID:Oncostatin M-mediated growth inhibition of human glioblastoma cells does not depend on stat3 or on mitogen-activated protein kinase activation. 1093 78

The human glioblastoma-astrocytoma cell line U-373-MG shows morphological features typical of its neuroectodermal origin. Cells showed positive immunostaining for the glial fibrillary acidic protein. We used this cell culture for studying the putative production of TRH and TRH-related peptides. In a cell extract and conditioned medium, cation and anion exchange chromatography and HPLC revealed the presence of TRH and acidic TRH-like peptides which were identified, at least in part, as pGlu-Glu-ProNH(2). These findings demonstrated that U-373-MG cells are able to produce and release these peptides. Further evidence of TRH synthesis was obtained by amplification using RT-PCR of a 396 bp fragment that corresponds to the TRH precursor mRNA. Our results therefore suggest that the U-373-MG cell line may be a useful model for studying the regulation of TRH and TRH-related peptide production and the interaction of these peptides with other classical neurotransmitter systems. In fact, pilocarpine (a muscarinic cholinergic agonist) enhanced and nicotine (a nicotinic cholinergic agonist) decreased TRH and TRH-related compound production by this cell line. These data also point out that glia may produce substances with neuromodulatory action.
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PMID:Expression of TRH and TRH-like peptides in a human glioblastoma-astrocytoma cell line (U-373-MG). 1097 63

Interleukin 1-beta (IL-1beta) induces apoptosis in a glioblastoma-derived human cell line, exhibiting a poorly differentiated astrocytic phenotype. The apoptotic effect was demonstrated by analyzing nuclear morphology, in situ DNA fragmentation, and by ELISA detection of cytoplasmatic nucleosomes. We correlated the degree of differentiation of GL15 cells with the apoptotic response: 1) 4',6-diamidino-2-phenylindole staining, combined with glial fibrillary acidic protein (GFAP) immunofluorescence, showed that the cells with apoptotic nuclei express low levels of GFAP; and 2) at 13 days of subculture, in a more differentiated state, GL15 cells did not respond with apoptosis to IL-1beta. In this cell line, nonrandom chromosome changes and the expression of SV40 early region have been previously shown. The involvement of p42/p44 mitogen-activated protein kinase (MAPK) pathway in the induction of apoptosis by IL-1beta was hypothesized. Previous studies have shown that SV40 small T antigen partially inhibits phosphatase 2A, leading to an enhancement of the steady-state activity of p42/p44 MAPK pathway. PD-098059, specific inhibitor of p42/p44 MAPK pathway, counteracts the apoptotic effect of IL-1beta, whereas SB-203580, specific inhibitor of p38 stress-activated protein kinase (SAPK) pathway, is ineffective. The imbalance between MAPK and SAPK pathways has been proposed as a key factor in determination of cell fate. Our results demonstrate that a further stimulation of p42/p44 MAPK pathway can constitute a death signal in tumor cells in which genomic damage and MAPK pathway control alterations occur.
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PMID:Interleukin-1beta induces apoptosis in GL15 glioblastoma-derived human cell line. 1107 22

In transformed human glial cells, abnormalities of the p53 gene and altered expression of glial-specific properties (GSPs) have been observed. We therefore investigated whether (i) expression of the altered p53 protein is involved in the reduced expression of GSPs; and (ii) expression of the wild-type p53 (wt-p53) gene leads to induction of GSPs. We first determined that the p53 gene is mutated in human glioblastoma U-373MG cells. In these cells, and in human T-98G glioblastoma cells reported to possess a mutated p53 (m-p53) gene, nuclear m-p53 expression was intense while GSP expression was low in the same cell as revealed by double labelling immunocytochemistry. Conversely, glial fibrillary acidic protein (GFAP) and glutamate synthase (GS) were expressed in cells devoid of nuclear m-p53 immnunoreactivity. Therefore, a mutually exclusive relationship exists between the cytoplasmic GSPs and nuclear m-p53. Upon treatment with retinoic acid (RA) and dibutyryl cyclic AMP (dbcAMP), overall GSP staining were increased concomitant with suppression of nuclear m-p53. Their mutually exclusive expression pattern was maintained suggesting a functional relationship. This is supported by the observation of a similar mutually exclusive expression pattern for p53 and GSPs in pathologic specimens of human glioblastoma tissues. We then explored the role of the wt-p53 gene in the induction of GSPs using a wt-p53 tetracycline-regulated conditional expression system in human LN-Z308 glioblastoma cells. These cells normally express no p53 and no appreciable levels of GS or GFAP. Induced expression of wt-p53 lead to induction of GSP. These observations are consistent with the hypotheses that (i) nuclear m-p53 expression and cytoplasmic expression of GFAP and GS are inversely correlated, and (ii) expression of the wt-p53 gene leads to the expression of GSPs.
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PMID:Alteration in p53 modulates glial proteins in human glial tumour cells. 1110 Aug 17

Compounds that could block tumor angiogenesis and induce tumor cell differentiation in malignant gliomas represent a very valuable tool in anticancer treatments. In this paper, we demonstrate that more selective drugs, which interfere with specific cellular targets, could treat glioma more effectively. 8-Cl-cAMP and tiazofurin (TR) are site-specific analogs that selectively inhibit PKAI and IMP dehydrogenase, are directly involved in cell proliferation and apoptosis, and mediate the mitogenic effects of different oncogenes and growth factors. In this study, we have examined influence of 8-Cl-cAMP and TR on the production of an angiogenic factor [vascular endothelial growth factor (VEGF)] by human glioblastoma U251 MG cells, as well as their influence on the expression of a differentiating marker [glial fibrillary acidic protein (GFAP)]. Using a cell proliferation assay, VEGF enzyme-linked immunoassay and GFAP immunocytochemistry we demonstrated the effects of these compounds. Our results demonstrate that 8-Cl-cAMP and TR decrease VEGF production by U251 MG cells, and that under the influence of both agents these cells increase GFAP expression and change their morphology, becoming more differentiated. These findings also suggest that 8-Cl-cAMP and TR may have potential for further investigation of their antiangiogenic and differentiational role in malignant disease such as human gliomas.
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PMID:8-Cl-cAMP and tiazofurin affect vascular endothelial growth factor production and glial fibrillary acidic protein expression in human glioblastoma cells. 1112 40


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