Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pentapeptide leucine enkephalin induced down-regulation of enkephalin receptors in neuroblastoma-glioma NG108-15 hybrid cells in a reversible fashion, whereas the stable enkephalin analogue D-Ala2-Met-enkephalinamide (AMEA), and the potent opiate alkaloid, etorphine, had a prolonged effect. The opiate alkaloid, morphine, which has low affinity to delta-type enkephalin receptors of these cells did not induce down-regulation, whereas AMEA decreased the binding of both opiate agonists and antagonists but had no effect on the binding of the alpha 2-adrenergic ligand, [3H]yohimbine. From several experiments that were designed to remove the tightly bound AMEA, and from experiments with solubilized receptor we ruled out the possibility that the decreased binding capacity of enkephalin-treated cells reflects only receptor masking. The study suggests that down-regulation of enkephalin receptors that may also occur in vivo can account for some of the abnormal physiological responses of subjects treated chromically with opiates. However, since opiates from the morphine type can induce opiate tolerance in vivo, but not down-regulation of enkephalin receptors in the cultured cells, we suggest that down-regulation of delta-type opiate receptors may not be prerequisite for the development of the physiological tolerance/dependence on these alkaloids.
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PMID:Down regulation of enkephalin (delta) receptors. Demonstration in membrane-bound and solubilized receptors. 629 66

The benozomorphan derivative (-)-2-[2-(p-bromoacetamidophenyl)ethyl]-5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphan (BAB), capable of reacting with nucleophilic groups, acts on neuroblastoma X glioma hybrid cells as a potent, irreversible opiate agonist. Its potency in inhibiting the increase in cellular cyclic AMP, evoked by prostaglandin E1, is comparable to that of Leu-enkephalin. This also applies to its capacity to compete with [3H]D-Ala2-Met-enkephalinamide ([3H]DAEA) in binding on cell membrane preparations. The comparatively lower potency of (-)-2-[2-(p-acetamidophenyl)-ethyl]-5,9 alpha-dimethly-2'-hydroxy-5,7-benzomorphan (AB), which differs from BAB in the substitution of the bromoacetamido group by an acetamido group, is of the same order of magnitude as that of morphine. The covalent interaction of BAB with the opiate receptors is deduced from the observations that (1) it is not possible to wash away this compound from the receptors, (2) the potency of BAB in inhibiting the specific binding of [3H]DAEA increases with prolonged preincubation time, and (3) AB behaves as a reversible agonist.
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PMID:Irreversible activation of the opiate receptor of neuroblastoma X glioma hybrid cells by an alkylating benzomorphan derivative. 631 81

The peptides obtained by proteolysis of both extracted proteins and in vitro translation products from Neuroblastoma x Glioma hybrids were purified by means of HPLC and then submitted to radioimmunoassay. Met-Enkephalin and Met-Enkephalin sulphoxide immunoreactivity was found.
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PMID:Methionine-enkephalin precursor in neuroblastoma x glioma hybrid cells: in vivo and in vitro evidence. 650 13

Partially purified extracts from neuroblastoma x glioma hybrid cells inhibit via opioid receptors the PGE1-elicited formation of cyclic AMP in the same hybrid cell system. The purification of extracts reveals two active fractions very similar to Met- and Leu-enkephalin by several criteria including treatment with cyanogen bromide. On an average, the intracellular concentration of opioids in hybrid cells is 0.1 pmol per mg protein. The concentration is strongly dependent on the cell density. Furthermore, the content in the hybrids of enkephalin-like peptides is specifically elevated by glucocorticoids.
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PMID:Production and regulation of enkephalin-like peptides in neuroblastoma x glioma cells. 712

We investigated the biochemical changes which accompanied the development and reversion of methionine dependence in a human glioma cell line GaMg. This cell line attained a higher proliferation rate and more malignant morphology with increasing passages in vitro. Early passages (P10, P25, and P45) were able to grow in a methionine-deficient medium supplemented with homocysteine (Met-Hcy+), while a later passage (P60) had lost this ability, i.e., it had become methionine-dependent. From P60 cells, a methionine-independent revertant (P60R) was established by exposing the cells to 5-aza-2-deoxycytidine, followed by culture in a Met-Hcy+ medium. In these genetically related cell lines, we investigated homocysteine remethylation and the functional state of cobalamin-dependent methionine synthase, the enzyme responsible for remethylation of homocysteine to methionine. The methionine synthase activity in cell extracts was similar in all cell sublines. Intact cell methionine biosynthesis and nitrous oxide-dependent homocysteine export reflect homocysteine remethylation in cells cultured in a Met-Hcy+ and methionine-containing (Met+Hcy-) medium, respectively. Both of these parameters, as well as the cellular content of the substrate 5-methyltetrahydrofolate, and the cofactor methylcobalamin, in addition to adenosylcobalamin, were high in P10, declined progressively in P45 and P60, and were restored in P60R. P25 cells had some unique features among the methionine-independent phenotypes because both homocysteine remethylation and the level of 5-methyltetrahydrofolate were low in Met+Hcy- medium. The maximal homocysteine export rate in the presence of nitrous oxide, which reflects the overall transmethylation rate, was high in P60 and even higher in P60R compared to the lower passages. The basis for development of methionine dependence during culture of this glioma cell line seems related to the combined effects of reduced methionine biosynthesis and an increased overall transmethylation rate. The single parameter which most closely correlated to the ability to use homocysteine for growth was methylcobalamin. These data support a model for methionine dependence, which implies impaired provision of cobalamin to methionine synthase.
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PMID:Development and reversion of methionine dependence in a human glioma cell line: relation to homocysteine remethylation and cobalamin status. 806 55

In the present study we investigated the frequency of p16 gene exon 2 mutations in 35 malignant gliomas, using either direct sequencing of the PCR products or cloning into the pCRII vector and sequencing of the cloned PCR products. No mutations were detected during direct sequencing of the PCR products. However, after sequencing of individual clones, we found multiple mutations in 5 tumors involving codons 73(GCC to ACC, Ala to Thr), 76 (GCC to GTC, Ala to Val), 85(GCT to ACT, Ala to Thr), 98(CAC to TAC, His to Tyr), 102 (GCG to GTG, Ala to Val), 106 (GTG to ATG, Val to Met), 107 (CGC to TGC, Arg to Cys), 127 (GCA to GTA, Ala to Val), 128 (CGG to TGG, Arg to Trp) and 136 (GGC to GAC, Gly to Asp). Mutations were found only in glioblastomas and were either C to T or G to A transitions. Each mutation was detected in a small percentage of tumor cells (1.3-22%) using individual colony sequencing and southern hybridization with mutant oligonucleotides, consistent with the heterogenous cell population of glioblastomas. The presence of p16 gene mutations only in glioblastomas suggests that they are late events in glioma development.
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PMID:Mutations of the p16 gene in gliomas. 855

A 37-year-old male with mixed glioma was treated with combined radio- and chemotherapy. The amino acid metabolism of the tumor site and normal brain was followed by positron emission tomography using [11C]methionine ([11C]Met). The accumulation of [11C]Met in the tumor decreased during therapy and slightly increased 7 months after completion of the therapy, but then decreased markedly. However, computed tomography revealed no notable changes. The contralateral gray matter also showed a gradual decrease of [11C]Met accumulation. These findings indicate that reduction of amino acid metabolism in the tumor continues after radiochemotherapy although neuroimaging reveals no further morphological changes. Such therapy also has long-term effects on normal brain tissue.
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PMID:Serial positron emission tomography imaging of changes in amino acid metabolism in low grade astrocytoma after radio- and chemotherapy-- Case report. 865 32

11C-methyl-L-methionine (C-11 Met)PET, CT and MR imaging were performed in eleven patients with malignant brain tumors before and after RT to evaluate the usefulness of positron emission tomography (PET) in monitoring tumor response to radiotherapy (RT). The subjects included five cases of intracranial malignant lymphoma (ICML) and six cases of glioma. C-11 Met uptake by the tumor (T) and the contralateral gray matter (NT) was calculated on the PET images. The mean T/NT ratio of the ICMLs and gliomas changed from 2.33 and 1.87, respectively, before RT to 1.31 and 1.58, respectively, after RT.No significant difference was found between the T/NT ratios before and after RT in either the ICMLs or the gliomas (t-test). We tentatively defined the minimum T/NT ratio, 1.2, as the threshold between tumor and nontumor regions. Tumors with a ratio of 1.2 or more were imaged as "hot" (MET) and coincided with CT or MR image lesions which were visualized as contrast-enhancing (CE) and low-density (LD) or high-intensity (HI). The relationships between PET, CT and MRI lesions were classified as follows: Type I (MET < or = CE), Type II [CE < MET < LD (HI)], Type III [LD(HI) < or = MET]. MET lesions extending regionally ( > 1 cm) beyond the respective CT or MR image lesions were designated "MET-extension" and LD (HI) lesions protruding ( > 1 cm) beyond the MET lesions were recorded as "LD (HI)-extension" on the integrated images. The type II pattern of the MET areas in all five cases of ICML before RT had changed to Type I in one case, Type III in one case and Type II in three cases, after RT, while the two Type II patterns and four Type III patterns of the gliomas had converted to four Type II and two Type III patterns. These findings indicate that gliomas tend to invade into areas of peritumoral edema more than ICMLs. There were two ICML MET-extension sites in the cortex before RT, as opposed to two in the cortex, one in the basal ganglia, one in the thalamus, and one in the corpus callosum among the gliomas. On follow-up CT or MR images MET-extension (75%) had converted to a CE or LD (HI) region. Four ICML LD (HI)-extension sites before RT were found in periventricular white matter, versus one in the cortex and three in the white matter among the gliomas. LD (HI)-extension appeared to represent vascular edema because it decreased or diminished after completion of therapy. Sequential analysis of integrated C-11 Met PET, CT and MR images is useful in detecting the extent of tumor infiltration by ICMLs and gliomas, particularly at an early stage, and for evaluating the effect of RT in the treatment of both.
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PMID:[Sequential analysis of the integrated images of PET, CT and MR in malignant brain tumors before and after radiotherapy]. 867 4

Invasive proliferation is a critical biological characteristic of gliomas. We evaluated the activities of hepatocyte growth factor (HGF) on proliferation and motility of glioma cells, comparing them with the effects of other growth factors (EGF, bFGF, PDGF-BB, TGF-beta 1). Seven primary culture lines all expressed c-met and HGF mRNA, and secreted HGF. HGF stimulated 3H-thymidine uptake of every glioma cell line (30 to 70% upregulation). Boyden chamber assay and scattering assay revealed that HGF promoted cell motility with chemokinetic and strong chemotactic activities. Concentric circle assay showed that HGF promoted two-dimensional expansion (proliferation and motility) most strongly among the growth factors studied. Further, we analyzed 23 paraffin-embedded sections of surgically resected gliomas (7 grade II, 8 grade III, and 8 grade IV) by immunohistochemistry. Expression of HGF and Met increased with malignant progression of gliomas, suggesting that gliomas stimulated their invasive proliferation by autocrine HGF production. Neurons and vasculature were HGF-positive, and Met-positive glioma cells gathered around them. The data indicate that neurons and vasculature, which are the main tracks of glioma invasion, augment chemotactic invasion and proliferation of gliomas by paracrine HGF secretion. Clearly HGF plays a critical role in invasive proliferation of glioma cells and it is therefore a candidate target of therapeutic intervention.
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PMID:Modulation of motility and proliferation of glioma cells by hepatocyte growth factor. 926 34

Using double immunofluorescence staining and quantitative confocal laser scan microscopy, we show that the intensity of hepatocyte growth factor/scatter factor (HGF/SF) and Met staining in human primary brain tumors increases with the grade of malignancy and is prevalent in both the infiltrating tumor cells and endothelial hyperplastic areas. HGF/SF and Met also are expressed in vitro in glioblastoma multiforme cell lines as well as in normal human astrocyte (NHA) cells. Moreover, HGF/SF stimulates tyrosine phosphorylation of Met in both glioma cell lines and NHA cells, but only the glioma cell lines proliferate and become motile and invasive in response to HGF/SF, whereas the NHA cells are nonresponsive. These results implicate autocrine/paracrine Met-HGF/SF signaling in glioma tumorigenesis and suggest that HGF/SF signaling through Met is negatively regulated in NHA cells.
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PMID:Met and hepatocyte growth factor/scatter factor expression in human gliomas. 939 65


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