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 composition of the free amino acid pools in various brain tumors and in normal brains obtained at surgery or at autopsy is determined with an automatic amino acid analyzer and the results statistically evaluated. The tumors have lower ratios of GABA in the pools than the normal brain; tumors with higher GABA ratios are found in those which are in close contact with and have an invasive nature to brain tissue. In gliomas, the more malignant a tumor becomes, the more different the composition in that tumor is from that in normal brain tissue. But conversely, the ratio of GABA is highest in glioblastoma. The composition of the pool in oligodendroglioma is not significantly different from that in the normal brain. Metastatic brain tumors show the highest ratios of phenylalanine, tyrosine and methionine in the pool among the tumors and the normal brain. From the viewpoint of the composition of the free amino acid pools, like from that of the histological aspects, brain tumors seem to be classified into four groups: glioma, neurinoma, meningioma and metastatic tumors.
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PMID:Composition of free amino acids in brain tumors. 54 90

After exposure to low density lipoprotein (LDL) that had been minimally modified by oxidation (MM-LDL), human endothelial cells (EC) and smooth muscle cells (SMC) cultured separately or together produced 2- to 3-fold more monocyte chemotactic activity than did control cells or cells exposed to freshly isolated LDL. This increase in monocyte chemotactic activity was paralleled by increases in mRNA levels for a monocyte chemotactic protein 1 (MCP-1) that is constitutively produced by the human glioma U-105MG cell line. Antibody that had been prepared against cultured baboon smooth muscle cell chemotactic factor (anti-SMCF) did not inhibit monocyte migration induced by the potent bacterial chemotactic factor f-Met-Leu-Phe. However, anti-SMCF completely inhibited the monocyte chemotactic activity found in the media of U-105MG cells, EC, and SMC before and after exposure to MM-LDL. Moreover, monocyte migration into the subendothelial space of a coculture of EC and SMC that had been exposed to MM-LDL was completely inhibited by anti-SMCF. Anti-SMCF specifically immunoprecipitated 10-kDa and 12.5-kDa proteins from EC. Incorporation of [35S]methionine into the immunoprecipitated proteins paralleled the monocyte chemotactic activity found in the medium of MM-LDL stimulated EC and the levels of MCP-1 mRNA found in the EC. We conclude that (i) SMCF is in fact MCP-1 and (ii) MCP-1 is induced by MM-LDL.
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PMID:Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. 169 10

Melphalan, a nitrogen mustard derivative of the neutral amino acid L-phenylalanine, was transported across the rat blood-brain barrier by the large (L-system) neutral amino acid transporter in tumor-bearing brain, but no evidence for blood-brain barrier transport by the alanine-serine-cysteine system carrier was obtained in the present study. The ability of melphalan to inhibit phenylalanine uptake was compared in rats implanted with two experimental CNS tumors: the C-6 glioma (a model of primary brain tumors) and Walker carcinoma (a model of metastatic brain tumors). The melphalan concentration which caused 50% inhibition of blood-brain barrier (BBB) phenylalanine uptake (Ki) was 0.49 +/- 0.18 mM in the Walker tumor, compared with 0.46 +/- 0.19 mM in the contralateral control brain. In the ipsilateral hemisphere (Ki = 0.59 +/- 0.25 mM) and contralateral hemisphere (Ki = 0.45 +/- 0.19 mM), drug entry was also via the neutral amino acid transporter. In C-6 gliomas (Ki = 0.77 +/- 0.20 mM) and contralateral control brain (Ki = 0.84 +/- 0.29 mM), melphalan also inhibited BBB phenylalanine transport. A major finding was that, at melphalan concentrations greater than 1.0 mM, BBB permeability of radiolabeled indium (chelated to EDTA) increased in proportion to melphalan concentration. In the contralateral hemisphere of rats implanted with C-6 gliomas, brain extractions of indium-EDTA measured 3 to 4% in the absence of drug, 5 to 6% at 2.5 mM melphalan, and 9 to 10% at 5 mM melphalan. A similar phenomenon was observed in the nontumoral brain regions of rats implanted with Walker carcinoma cells. In normal (nonimplanted) rats, melphalan's inhibition (Ki = 0.29 mM) of phenylalanine and tryptophan (Ki = 0.20 mM) uptake was confirmed, and brain extraction of sucrose (a nonspecific marker which does not penetrate the intact BBB) was observed to increase in proportion to melphalan concentration. We conclude that melphalan not only enters the brain via the neutral amino acid transporter, but at higher concentrations (greater than 1 mM) may open the blood-brain barrier in a nonspecific manner.
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PMID:Melphalan penetration of the blood-brain barrier via the neutral amino acid transporter in tumor-bearing brain. 172 74

Tritiated DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr) binds with high affinity, specificity and saturability to neuroblastoma N18TG2 and hybrid neuroblastoma x glioma NG108-15 and NG108-5 intact cells. The delta-opioid receptor density in cells cultured in chemically defined medium was increased about 2 times compared to that in cells cultured in 10% fetal calf serum. A major and a minor protein species covalently and specifically bound to [125I]azido-DTLET (Tyr-D-Thr-Gly-pN3Phe-Leu-Thr), photoactivatable ligand, migrated on SDS-gel electrophoresis with Mr values near 33,000 and 58,000, respectively.
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PMID:Photoaffinity labeling of a 33 kDa protein subunit of the delta-opioid receptor in neuroblastoma and hybrid cell lines. 283 23

Two series of dimeric enkephalin analogues were assayed for opioid activity in two isolated smooth muscle preparations: the guinea pig ileum (GPI) and the mouse vas deferens (MVD). Dimers have the general structure: X-(CH2)n-X, where X is H-Tyr-D-Ala-Gly-Phe-Leu-NH-(n = 0, 2, 4, 6, 8, 10, 12), for the first series of dimeric pentapeptide enkephalins (DPEn), and H-Tyr-D-Ala-Gly-Phe-NH-(n = 2, 4, 6, 8, 12), for the series of dimeric tetrapeptide enkephalins (DTEn). Comparison of biological activities with binding affinities revealed that: (1) the DPE series with n = 2-8 showed increased potency in the MVD assay relative to monomeric [D-Ala2, Leu5]enkephalinamide (DALEA); (2) there was an associated increase affinity for the delta receptor of rat brain or neuroblastoma-glioma hybrid cells. (however, the relative potencies were higher in the MVD assay then predicted on the basis of binding affinities); (3) the DTE series also showed an increase in delta receptor affinities and MVD potencies relative to DALEA, for n = 2-12; (4) for the DTE series, the increase in MVD activities was less than that expected on the basis of delta binding affinity; (5) for both the DPE and DTE series, activities in the GPI assay and mu-receptor affinities were highly correlated: as the length of the methylene bridge increased from 2 to 12, there was a progressive loss of activity in both assays, with a similar pattern for DPE and DTE. Two selected dimers and their corresponding monomers were also assayed for antinociceptive activity in vivo: results were consistent with GPI and mu-binding but not with MVD and delta-binding. Two alkylamide analogs of penta- and tetrapeptide monomers, representing the monomer with the attached spacer of the most active dimers, were also assayed in biological and binding assays. Comparison of these compounds with the corresponding dimers suggest that the changes in activities and selectivities induced by dimerization are not a spurious effect of the presence of an akylamide derivative of the carboxy terminal of enkephalin but rather may represent a specific effect due to the bivalent nature of the ligands.
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PMID:Receptor binding and biological activity of bivalent enkephalins. 298 28

The binding of alkylendiamide dimers of the three N-terminal residues of [D-Ala2,D-Leu5]enkephalin (DADL) to rat brain and Ng108-15 neuroblastoma-glioma cell membranes was compared with that of DADL, Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO) and morphiceptin. Tritiated DADL and DAGO were used as labeled ligands for delta- and mu-receptors, respectively. Dimerization of the tripeptides resulted in dramatic increases in both mu and delta binding. The binding to mu-receptors showed two peaks at an alkyl chain length of n = 2 and approximately n = 16. In contrast, delta binding (NG108-15 cells) increased steadily with increasing chain length. The dimers with n less than 18 were mu-preferential, and the one with n = 2 showed the most dramatic increase in mu selectivity with a 400 fold higher affinity to mu- than to delta-receptors. For long-chain alkyl spacers the compounds became delta selective.
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PMID:Increased affinity and selectivity of enkephalin tripeptide (Tyr-D-Ala-Gly) dimers. 299 Sep 53

Iodinated human beta-endorphin was affinity-cross-linked to opioid receptors present in membrane preparations from bovine frontal cortex, bovine striatum, guinea pig whole brain, and rat thalamus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography revealed covalently labeled peptides of 65, 53, 41, and 38 kilodaltons (kDa). The 65- and 38-kDa peptides were present in all four tissues. The 41-kDa peptide was seen only in bovine caudate and guinea pig whole brain while the 53-kDa peptide was absent in rat thalamus. All four labeled peptides were constituents of opioid receptors since their labeling was fully suppressed by the presence of excess opiates, such as bremazocine, during binding. The distribution and levels of the labeled species in the brain tissues examined and, in earlier work, in the neuroblastoma X glioma NG 108-15 cell line suggested that the 65-kDa peptide is a binding component of mu receptors while the 53-kDa peptide is a binding subunit of delta receptors. This result was strongly supported by the finding that the labeling of the 65-kDa peptide is selectively reduced by the presence of the highly mu-selective ligand Tyr-D-Ala-Gly-(N-Me)Phe-Gly-ol (DAMGE) during binding, while while the labeling of the 53-kDa peptide is selectively reduced or eliminated by the highly mu-selective ligand [D-Pen2, D-Pen5]enkephalin (DPDPE). The labeling of the 41- and 38-kDa bands was reduced by either DAMGE or DPDPE. The relationship of these lower molecular weight opioid-binding peptides to mu and delta receptors is not understood. Several possible explanations are presented.
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PMID:Identification of distinct binding site subunits of mu and delta opioid receptors. 300 57

[3H]Az-DTLET (Tyr-D-Thr-Gly-Phe(pN3)-Leu-Thr), a photoaffinity probe for delta opioid receptors binds to a single class of sites in rat brain membranes with a high affinity (KD = 1.66 nM). The selectivity index of Az-DTLET (KI delta/KI mu = 0.036) is better than that of its precursor DTLET (0.053). Rat brain or neuroblastoma glioma cells membranes were incubated with 10 nM [3H]Az-DTLET, washed and irradiated with U.V. After irradiation a fraction (20-30%) of specific binding was found to remain indissociable after 10 min at 60 degrees C and was considered as irreversible. This fraction increased as a function of the irradiation time. The radioactivity irreversibly bound to rat brain membranes, solubilized by sodium cholate, was associated with high molecular weight species (200,000 daltons). In denaturing conditions (SDS 2%), the [3H]Az-DTLET specific binding was associated with molecular components of 45-50 K and 90-100 K daltons. In contrast, when opioid receptors were prelabelled by [3H]Az-DTLET, solubilized by Na-cholate and irradiated, the radioactivity was only recovered with subunits of 45-50 K daltons. The autoradiographic localization of the irreversibly bound [3H]Az-DTLET in rat brain was identical to that of reversibly bound [3H]DTLET or [3H]Az-DTLET. These results suggest that [3H]Az-DTLET represents an adequate specific probe for studies on the structure, function and anatomical distribution at light and even electron microscopic level of delta-opioid receptors.
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PMID:Irreversible labelling of delta-opioid receptors in rat brain and neuroblastoma cells by [3H]azido-DTLET: characterization of subunits and autoradiographic visualization of the covalent binding. 303 96

A unique tissue kallikrein-binding protein was identified and partially characterized in the brain and serum of Sprague-Dawley rats and in the serum-free conditioned media of mouse anterior pituitary cells (AtT 20) and rodent neuroblastoma x glioma hybrids (NG108-15). Kallikrein and kallikrein-binding protein(s) form SDS- and heat-stable complexes with a molecular weight (Mr) of approximately 92,000. The complex formation of 125I-labelled kallikrein and the binding protein in the serum and brain is inhibited by excess unlabelled rat urinary kallikrein, rat arginine esterase A (a kallikrein-like kininogenase), and human urinary kallikrein. When the active site of kallikrein was blocked by phenylmethylsulfonyl fluoride or D-Phe-D-Phe-L-Arg-CH2Cl, no complex formation was detected. Kallikrein-binding protein only forms complexes with active kallikrein or trypsin-activated prokallikrein but not with prokallikrein. 125I-labelled kallikrein forms a 92-kilodalton protein with binding protein in various brain regions of perfused normotensive rats of the Wistar-Kyoto strain (WKY), including the cerebral cortex, cerebellum and brain stem; but complex formation was not found in corresponding brain regions of the spontaneously hypertensive rat (SHR). Similarly, the kallikrein-binding protein was identified in various tissues including thymus, lung, liver, prostate, Cowper's gland, adrenal gland, kidney, and pancreas of WKY rats but not in tissues of SHR. The results suggest a major difference in the kallikrein-binding protein in hypertensive versus normotensive rats. The role of this specific kallikrein-binding protein in cellular hemodynamic processes and blood pressure regulation remains to be investigated.
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PMID:A major difference of kallikrein-binding protein in spontaneously hypertensive versus normotensive rats. 317 Nov 70

Five opioid peptides (immunoreactivity) derived from their respective opioid precursors were measured in neuroblastoma-glioma hybrid cells (NG 108CC15; pmol/g protein): heptapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Phe), 13.0 +/- 2.6; alpha-neoendorphin, 6.6 +/- 0.8; dynorphin A, 4.4 +/- 1.5; dynorphin A 1-8, 1.3 +/- 0.29; beta-endorphin, 0.3 +/- 0.13. These peptides originate from preproenkephalin A (heptapeptide), prodynorphin (alpha-neonedorphin, dynorphin A, dynorphin A 1-8) and proopiomelanocortin (beta-endorphin). The data suggest the expression of all three known opioid precursors in a single hybrid cell line, permitting a simultaneous investigation of the processing of different opioid peptides under identical experimental conditions.
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PMID:Evidence for the expression of peptides derived from three opioid precursors in NG 108CC15 hybrid cells. 356 21


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