UMLS:C0017636 - FACTA Search

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Query: UMLS:C0017636 (glioblastoma)
18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent cloning studies confirm the presence of two subtypes of bombesin (Bn) receptors. In contrast to the gastrin-releasing peptide (GRP)-preferring subtype, which has been widely studied, nothing is known about the cellular mechanisms of the neuromedin B (NMB)-preferring subtype, which occurs widely in the central nervous system and gastrointestinal tissues, partially because of the lack of a cell line with functional receptors. In the present study we have investigated Bn receptors on the rat glioblastoma cell line C-6, reported to contain mRNA of the NMB receptor subtype. Binding of 125I-[D-Tyr0]NMB to these cells was time- and temperature-dependent, saturable, reversible, and only inhibited by Bn receptor agonists or antagonists. For Bn receptor agonists the relative potencies were: NMB (1.7 nM) approximately equal to litorin (3 nM) greater than ranatensin (8 nM) greater than Bn (19 nM) greater than neuromedin C (NMC) (210 nM) greater than GRP (500 nM). These relative affinities were almost identical to those for the NMB receptor subtype on rat oesophageal tissue and for Balb 3T3 cells stably transfected with the NMB receptor subtype. These potencies differed from those for the GRP receptor subtype on rat pancreatic acini [Bn approximately equal to litorin (4 nM) greater than ranatensin, NMC, GRP (15-20 nM) much greater than NMB (351 nM)]. The relative potencies of four different classes of Bn receptor antagonists were compared. Results from C-6 tumour cells agreed closely with those for binding to the NMB receptor subtype on rat oesophageal tissue and in Balb 3T3 cells stably transfected with this receptor, and differed markedly from those for binding to the GRP receptor subtype on rat pancreatic acini. Four Bn receptor antagonists had a higher affinity for the GRP subtype ([D-Phe6]Bn-(6-13)ethyl ester (500 x), [D-Phe6][psi 13-14,Cpa14]Bn- (6-14) (70 x) (where psi 13-14 refers to the replacement of the -CONH- peptide bond between Leu13 and Met14 by -CH2NH2) [psi 13-14,Leu14]Bn, [D-Phe6]Bn-(6-13) propylamide (30 x)] and two had a higher affinity for the NMB subtype on C-6 cells and transfected cells ([D-Pro4,D-Trp7,9,10] substance P-(4-11) (9 x) and [Tyr4,D-Phe12]Bn (18 x)]. In C-6 tumour cells, Bn receptor agonists caused an increase in cytosolic Ca2+ and the generation of inositol phosphates. For both responses, NMB was more than 50-fold more potent than GRP. Neither NMB nor GRP increased cyclic AMP. These results demonstrate that the rat glioblastoma cell line C-6 possesses functional NMB-preferring Bn receptors, and agonist occupation activates phospholipase C, thus increasing cytosolic Ca2+ and inositol phosphate formation. Because the interaction of Bn-related peptides with C-6 cell receptors is identical with that reported in other tissues containing the mRNA for the NMB subtype, this cell line should prove useful in exploring further the cellular basis of action of the peptides that interact with this receptor in the central nervous system and various other tissues.
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PMID:Activation of neuromedin B-preferring bombesin receptors on rat glioblastoma C-6 cells increases cellular Ca2+ and phosphoinositides. 132 46

The expression of the genes in the human HOX2 locus has been studied during differentiation of two human neuroblastoma (SH-SY5Y and Kelly), a human glioblastoma (251-MG), and the murine F9 embryonal carcinoma cell lines. Cells were differentiated with retinoic acid (RA), or with RA together with dibutyral cyclic AMP (db-cAMP) and nerve growth factor (NGF) in order to assess the changes in the expression patterns of these homeobox genes during neuronal differentiation. We show that the genes of the HOX2 locus are expressed in a complex transcription pattern that varies with cell type. The two uninduced neuroblastoma cell lines show a similar pattern of expression for a number of HOX2 genes although the levels of expression are different for individual cell lines. The embryonal carcinoma cell line F9 expresses low levels of several HOX2 genes which is restricted to the 5' region of the HOX2 cluster. The glioblastoma cell line, 251-MG expresses almost all of the genes of the HOX2 locus. Differentiation of these cells modulates the expression of the HOX2 genes in a manner that is dependent upon the cell type as well as the differentiation factor. Differentiation affects both the level of HOX2 gene expression and the distribution of transcript sizes. In conclusion, our analysis reveals a complex pattern of expression for the genes of the HOX2 locus in neuronal and glial cells and suggests that the cell-specific expression of these genes may be correlated with the phenotypic differences that are observed between different neuronal and glial cell populations within the nervous system.
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PMID:Modulation of HOX2 gene expression following differentiation of neuronal cell lines. 136 Apr 33

5'-Nucleotidase has been purified from rat glioblastoma cells (Rugli cells). The enzyme has been solubilized from plasma membranes by using Triton X-100 and CHAPS. Two affinity chromatographies on concanavalin A and 5'-AMP-Sepharose render the purified enzyme with a high specific activity (76.36 mumol AMP.min-1.mg-1). The purified enzyme gives a single polypeptide band on SDS-PAGE with an apparent molecular mass of 74 kDa. Active forms with an apparent molecular mass of 135 kDa and 268 kDa are observed when the purified enzyme is analyzed by gel filtration in the presence of either 0.6% sodium deoxycholate or 0.1% Triton X-100, respectively. The purified 5'-nucleotidase presents optimum activity at pH 7.8-8.1 either in the presence or in the absence of Mg2+. A linear Arrhenius plot is observed in the 25-46 degrees C temperature range and an activation energy of 33.7 KJ/mol is calculated. The enzyme is inhibited by EDTA; the activity is partially restored by different divalent cations as Zn2+, Mn2+, and Co2+. The hydrolysis of nucleosides 5'-monophosphate shows Michaelis kinetic. The enzyme is inhibited by nucleosides di- and triphosphate. 5'-Nucleotidase is a glycoprotein, being its activity inhibited at different extent by various lectins.
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PMID:Isolation and characterization of the ecto-5'-nucleotidase from a rat glioblastoma cell line. 148 Jan 62

The aim of this study was to identify targets for rational chemotherapy of glioblastoma. In order to elucidate differences in the biochemistry of tumor and normal human brain, in vivo pool sizes of purine nucleotides, nucleosides, and nucleobases and of purine metabolizing enzymes in biopsy material from 14 grade IV astrocytomas and 4 normal temporal lobe samples were analyzed. Specimens were collected during surgery using the freeze-clamp sampling technique and analyzed by high pressure liquid chromatography. Total purine nucleotides, adenylates, and guanylates in the tumors were 2186, 1865, and 310 nmol/g (wet weight), respectively, which corresponds to 61, 60, and 71% of normal brain tissue concentrations. Relative to normal brain the tumors had significantly lower ATP and GTP levels, essentially normal pool sizes of purine nucleosides and bases, unchanged activities of the salvage enzymes hypoxanthine-guanine phosphoribosyltransferase, adenine phosphoribosyltransferase, and adenosine kinase (659, 456, and 98 nmol/h/mg protein, respectively) and 4-fold higher activities of IMP dehydrogenase (11.6 nmol/h/mg protein); the latter is the rate limiting enzyme for guanylate de novo synthesis. IMP pools in the tumors were 64% of values in normal brain. Modulation of the guanylate pathway in glioblastoma by inhibition of IMP dehydrogenase with tumor specific agents such as tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) appears to be a rational therapeutic approach. Preliminary in vitro experiments with normal and malignant tissue specimens from 2 additional patients revealed that significant amounts of the active metabolite thiazole-4-carboxamide adenine dinucleotide are formed from tiazofurin. At a concentration of 200 microM this drug was able to deplete guanylate pools in the tumors to a median of 54% of phosphate buffered saline treated controls. Flux studies with [14C]formate showed that tiazofurin strongly inhibited de novo synthesis of guanylates in glioblastoma to an average of 10% of controls. This effect was more pronounced in the tumors as compared to normal brain. No inhibition of salvage of [14C]guanine by tiazofurin could be observed in normal and malignant tissues. Supportive measures have to be considered to inhibit the highly active salvage enzyme hypoxanthine-guanine phosphoribosyltransferase that can partly antagonize a tiazofurin induced decrease in guanine nucleotides.
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PMID:Purine metabolism of human glioblastoma in vivo. 215 28

The addition of norepinephrine to cultured glioblastoma cells results in an inhibition of uptake of radioactivity from D-[2-(3)H]glucose, D-[1-(14)C]glucose, D-[2-(14)C]glucose, and D-[6-(14)C]glucose. In addition, if the glioblastoma cells are previously labeled with these substrates, norepinephrine causes an increase in the release of radioactivity. These effects were not observed with cultured neuroblastoma cells. It is suggested that the breakdown of glycogen is activated by norepinephrine as a result of an increase in 3':5'-cyclic AMP.
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PMID:Effect of norepinephrine on glucose metabolism in glioblastoma and neuroblastoma cells in cell culture. 434 Jan 54

The replication of measles virus in human neural and nonneural cell lines in terms of growth and cytopathic effect was affected by treatment of the cells with papaverine, which increases endogenous cyclic AMP. Suppression of virus growth was most prominent in neuroblastoma cells, followed by that in epidermoid carcinoma and glioblastoma cells, whereas the suppressive effect was relatively weak in oligodendroglioma cells. The papaverine-induced suppression of virus growth in neuroblastoma cells was studied in detail. The suppression that occurred was dependent on the dose of papaverine and was reversible. By treatment with 10 microM papaverine, virus-cell interactions were modified as follows: (i) early replication steps such as adsorption, penetration, and uncoating of the virus were not affected; (ii) synthesis of viral RNAs, including genomic RNA and mRNA, was inhibited; (iii) translation of viral proteins from mRNA was not blocked; and (iv) glycosylation and transport of viral glycoproteins to the cell membrane were not inhibited, but phosphorylation was blocked. The significance of suppressed virus replication in neural cells is discussed in relation to the persistence mechanisms of measles virus in the central nervous system.
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PMID:Effect of papaverine treatment on replication of measles virus in human neural and nonneural cells. 670 72

Possible differentiation mechanisms were investigated in a glioblastoma multiform cell line (GL15) presenting an undifferentiated phenotype with weak glial fibrillary acidic protein (GFAP) and strong vimentin (VIM) expression. Serum-free conditions induced time-dependent increases of GFAP-mRNA and GFAP protein levels, associated with a process-bearing astrocytic morphology. Activation of protein kinase C (PKC) by tumor promoter phorbol 12-myrystate 13-acetate (PMA) induced a rapid morphological differentiation and a decrease in GFAP mRNA, whereas the GFAP level remained unchanged. Such parameters were shown to characterize a physiological differentiation stage in astroglial cultures. Treatment of process-bearing GL15 cells with dibutyryl cyclic AMP (dbcAMP), a protein kinase A (PKA) activator, induced a time-dependent decrease in the GFAP mRNA and GFAP protein levels and reverted morphological changes induced by serum-free conditions. Neither PMA nor dbcAMP influenced the VIM mRNA expression. In GL15 cells, PKC and PKA activation have opposite effects. Understanding the role of these kinases in malignant transformation and in the in vitro differentiation process is of both basic and clinical interest.
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PMID:PKA and PKC activation induces opposite glial fibrillary acidic protein (GFAP) expression and morphology changes in a glioblastoma multiform cell line of clonal origin. 754 74

The responses of two low-molecular-weight stress proteins, alpha B crystallin and HSP28, to various types of stress were determined quantitatively by specific immunoassays in a human glioblastoma cell line (U118 MG). Levels of alpha B crystallin (2-4 ng/mg protein) and HSP28 (1-1.5 micrograms/mg protein) in the soluble fraction from cells that had been cultured at 37 degrees C increased about 100-fold and 3-fold, respectively, within 24 h after heat treatment for 15 min at 45 degrees C, with a temporary decrease, due to redistribution to the insoluble fraction, during the heat treatment. Exposure of cells to arsenite (NaAsO2, 100 microM for 1 h) also induced the two proteins with a time course similar to that observed after heat stress, but without a decrease during the stress period. L-Azetidine-2-carboxylate (5 mM for 5 h) was also effective in inducing the two proteins, but to a lesser extent. Other chemicals, including CdCl2, ZnCl2, AlCl3, ethanol, caffeine, nicotine, NaN3, dibutyryl 3',5'-cyclic AMP, forskolin, and a phorbol ester, did not induce the two proteins. Expression of alpha B crystallin and HSP28 mRNAs in cells was enhanced after heat stress and after exposure to arsenite. When cells were challenged with heat stress in the presence of arsenite, the effect on the induction of the two proteins was synergistic. Ethanol (1-2%) enhanced the responses to heat stress or arsenite stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coinduction of two low-molecular-weight stress proteins, alpha B crystallin and HSP28, by heat or arsenite stress in human glioma cells. 811 14

We investigated the expression of glutamine synthetase (GS), an enzyme involved in astroglial metabolism and marker of astroglial functional maturity, in a glioblastoma cell-line (GL-15) of clonal origin. In spite of their phenotypic immaturity, evidenced in a mosaic fashion by a poor glial fibrillary acidic protein (GFAP) expression, the level of GS-mRNA is high in GL15 cells and the considerable amount of GS biological activity can be further induced and stabilized by glucocorticoids. A correlation between the induction by dexamethasone of the GS-mRNA level and the GS biological activity suggests a transcriptional regulation of GS expression by the aforesaid hormone. Under this hormonal action, changes in cell morphology occur and they are correlated with an overexpression of the GFAP, a marker of astroglial differentiation. On the contrary, dibutyryl cyclic AMP (dbc AMP) down-regulates the GS-mRNA expression and decreases GS activity. These results suggest that GL-15 cells have a common glucocorticoid dependent mechanism able to induce GS and GFAP as well as morphological changes. However in these cells AMPc responsive elements are involved in the negative modulation of the GS expression, contrary to what occurs in normal astroglial cells.
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PMID:Glutamine synthetase gene expression in a glioblastoma cell-line of clonal origin: regulation by dexamethasone and dibutyryl cyclic AMP. 874 97

In human glioblastoma A172 cells, interleukin-6 (IL-6) production was induced by interleukin-1 beta (IL-1 beta) and dibutyryl cyclic AMP. These cells have been shown to induce IL-6 production via a cAMP-protein kinase A system. Since calcitonin (CT) and calcitonin gene-related peptide (CGRP) are known to increase cAMP accumulation in murine and rat astrocytes, we examined whether these neuropeptides induced IL-6 production in A172 cells. Human CT and human CGRP increased IL-6 production and cAMP accumulation in a dose-dependent manner. A specific protein kinase A inhibitor, H-89, inhibited both CT- and CGRP-induced IL-6 production. CT and CGRP have been shown to cross-react with each other. To exclude the possibility of this cross-reactivity, we studied the additive effects of CT and CGRP and the inhibitory effects of specific inhibitors. When 100 nM CT was added, cAMP accumulation stimulated by 10 nM CGRP (the maximal dose) was increased. CGRP (8-37), a specific CGRP receptor inhibitor, inhibited cAMP accumulation and IL-6 production induced by CGRP, but did not inhibit these effects when they were induced by CT. Salmon CT (8-32), a specific inhibitor of the CT receptor, inhibited cAMP accumulation induced by CT, but did not inhibit the effect induced by CGRP. These results demonstrated that CT can induce IL-6 production via cAMP accumulation and the effects of CT are mediated via its own receptors.
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PMID:Protein kinase A-dependent IL-6 production induced by calcitonin in human glioblastoma A172 cells. 918 43

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