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 cytologic evaluation of poorly differentiated tumors frequently poses a diagnostic dilemma as to the tissue of origin. To assess the diagnostic utility of monoclonal antibodies (MAbs) in these situations, we applied a panel of three highly purified MAbs specific for tumor-associated ganglioside epitopes to a diverse series of cytologic specimens. The panel was composed of DMAb-3, reactive with the epitope GalNAc beta 1-4 (NeuAc alpha 2-3)Gal- of GM2; DMAb-7, reactive with the epitope (NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4(Glc or GlcNAc)- of GD3 and 3'8'-LD1; and DMAb-20, reactive with the epitope GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal- of GD2. The cytologic material consisted of air-dried Cytospin preparations prepared predominantly from fine needle aspirates and stained with the ABC immunohistochemical method. Positive reactivity was recognized when greater than 5% of tumor cells stained with the antibody; lesser reactivity was called negative. DMAb-3 stained 9/14 (64%) glial tumors, 4/13 (31%) nonglial central nervous system tumors, 1/21 (5%) melanomas, 7/38 (18%) non-small cell carcinomas (NSCC), 1/15 (7%) small cell carcinomas (SCC), 0/9 (0%) lymphomas/leukemias, 2/10 (20%) sarcomas, 1/7 (14%) miscellaneous tumors and 2/2 (100%) reactive fluids. DMAb-7 recognized 14/14 (100%) glial tumors, 9/13 (69%) non-glial central nervous system tumors, 19/22 (86%) melanomas, 19/43 (44%) NSCC, 5/15 (33%) SCC, 2/9 (22%) lymphomas/leukemias, 6/10 (60%) sarcomas, 1/7 (14%) miscellaneous tumors and 4/4 (100%) reactive fluids. DMAb-20 stained 6/14 (43%) glial tumors, 2/13 (15%) nonglial central nervous system tumors, 1/21 (5%) melanomas, 4/38 (10%) NSCC, 0/15 (0%) SCC, 0/9 (0%) lymphomas/leukemias, 1/10 (10%) sarcomas, 1/7 (14%) miscellaneous tumors and 1/3 (33%) reactive fluids. The GD3-reactive DMAb-7 recognized a large portion of many tumor types and thus is not diagnostically useful alone. DMAb-3 and DMAb-20 were more selective and showed the strongest reactivity for glial tumors and minimal reactivity for melanomas, small cell carcinomas, and lymphomas or leukemias. DMAb-3 and DMAb-20 may be useful as components of a larger panel of MAbs in distinguishing between poorly differentiated tumors in samples derived from the central nervous system.
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PMID:Application of a panel of antiganglioside monoclonal antibodies to cytologic specimens. 152 27

Monoclonal antibodies (MAb; DMAb, monoclonal antibodies derived at Duke Medical Center) directed against the oncofetally expressed lactotetraosyl gangliosides 3'-isoLM1 (IV3NeuAc-LcOse4Cer) and 3',6'-isoLD1 (IV3NeuAc,III6NeuAc-LcOse4Cer) were produced and their reactivity spectra compared to that of the alpha-3'-isoLM1 MAb SL-50. The IgM MAb SL-50 defines the epitope NeuAc (or NeuGc)alpha 2-3Gal beta 1-3GlcNAc, the terminal sequence of both gangliosides. SL-50 requires an unsubstituted GlcNAc residue; IgM DMAb-14 will accept the alpha 2-6 linked sialic acid to GlcNAc found in 3',6'-isoLD1. Immunohistochemical localization of 3'-isoLM1 was performed on 31 biopsy specimens of human gliomas; 15 (48%) expressed 3'-isoLM1 as defined by binding of MAb SL-50. Staining of small anaplastic cells, giant cells, and the glial component of gliosarcomas was observed. Neoplastic gemistocytes, when present, showed particularly intense staining. The 3'-isoLM1 and 3',6'-isoLD1 distribution in cultured cell lines and derived xenografts of primary tumors of the human central nervous system and of embryonal or neuroectodermal tumor derivation was determined. Six of 29 cell lines expressed 3'-isoLM1: 2/16 gliomas, 3/3 teratomas, 1/1 pancreatic adenocarcinoma. No cell line expressed detectable 3',6'-isoLD1 by immunostain analysis of ganglioside extracts. The 3'-iso-LM1-positive cell lines expressed it in xenograft form; in five xenografts, the corresponding cell lines of which were 3'-isoLM1-negative, it was a proportion of the monosialoganglioside fraction. 3',6'-isoLD1 was detected in two xenografts, D-54 MG (glioma) and PA-1 (teratoma). The demonstration of 3'-isoLM1 in gliomas in in vivo forms and the relatively infrequent expression by derived cultured cells suggest that ganglioside expression is modified by environmental forces. Expression of 3'-isoLM1 and 3',6'-isoLD1 in fetal and neonatal brain, in intense reactive astrocytosis such as polyunsaturated fatty acid lipidosis, and in primary neoplasms of the central nervous system suggests their role in cell-cell attachment during development, migration, and neoplastic transformation.
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PMID:Occurrence of lacto series gangliosides 3'-isoLM1 and 3',6'-isoLD1 in human gliomas in vitro and in vivo. 174 82

Seven monoclonal antibodies (mAbs) reactive with ganglioside II3(NeuAc)2-LacCer (GD3) were generated; four of these mAbs (DMAb-21, DMAb-22, DMAb-23, and DMAb-24) by immunizing mice with GD3 adsorbed to Salmonella minnesota and the remaining three (DMAb-7, DMAb-8, and DMAb-17) with melanoma line SK-MEL 28, which contains 1.4 nmol sialic acid of GD3 per mg protein. The specificities of the mAbs were defined by high-performance thin-layer chromatography (HPTLC) immunostain and solid-phase radioimmunoassay (SP-RIA) with a panel of purified gangliosides. DMAb-7 and DMAb-8 reacted with GD3, IV3(NeuAc)2nLcOse4Cer(3',8'-LD1), and very weakly with IV3(NeuAc)2II3NeuAcGgOse4Cer (GT1a), but not with II3NeuAc-LacCer (GM3), II3NeuAcGgOse3Cer(GM2), II3NeuAcGgOse4Cer (GM1), II3NeuAc, IV3NeuAcGgOse4Cer (GD1a), II3(NeuAc)2GgOse3(GD2), II3(NeuAc)2GgOse4Cer (GD1b), IV3NeuAcII3(NeuAc)2, GgOse4Cer(GT1b), suggesting the binding epitope to be a terminal tetrasaccharide NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4(Glc or GlcNAc). DMAb-7 and DMAb-8 were used to investigate the expression of GD3 on cultured human tumor cells of neuroectodermal origin. Thirteen of 19 gliomas, 3 of 5 medulloblastomas, 5 of 5 neuroblastomas, 2 of 2 melanomas, and 1 of 3 teratomas were shown to react with DMAb-8 and/or DMAb-7 by cell surface-RIA (CS-RIA) and immunofluorescence (IF) assays. HPTLC and densitometric analysis confirmed these results, as positive immunostains in the GD3 region were obtained with oligoganglioside fractions from 9 glioma, 1 medulloblastoma, 2 neuroblastoma, 1 melanoma, and 1 teratoma cell line. Glioma cell line U-105 MG and medulloblastoma cell line Daoy contain GD3 as shown by HPTLC immunostain analysis of extracts, although GD3 was undetectable on the cell surface as determined by CS-RIA and IF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GD3 expression by cultured human tumor cells of neuroectodermal origin. 260 39

The major mono- and disialogangliosides of the extensively characterized established human glioma line D54MG were isolated and purified from subcutaneous solid xenografts grown in athymic (nu/nu) mice. Structural determination showed that they belonged to the lactotetraosylceramide series. The sialyllactotetraosylceramide contained 90% N-glycolyl- and 10% N-acetylneuraminic acid linked in an alpha 2-3 linkage (IV3NeuGc-LcOse4Cer, IV3NeuAc-LcOse4Cer). The disialogangliosides had a previously undescribed type of structure with sialic acids linked to the terminal galactose in an alpha 2-3 linkage and to N-acetylglucosamine in an alpha 2-6 linkage. Not only did species with NeuAc or NeuGc occur, but also species with mixtures of the two sialic acids, e.g. NeuAc and NeuGc. The schematic structures of the new disialogangliosides are (Formula:see text).
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PMID:Characterization of new gangliosides of the lactotetraose series in murine xenografts of a human glioma cell line. 301

The antibiotic tunicamycin blocks the transfer of GlcNAc-1-P from UDP-GlcNAc to dolichol phosphate, thereby blocking the synthesis of N-linked oligosaccharide chains on glycoproteins. Its effect on the biosynthesis of gangliosides has not been reported. We report that tunicamycin caused a 70-80% reduction in incorporation of [(3)H]GlcN into gangliosides and neutral glycosphingolipids of the neuroblastoma-glioma hybrid cell line NG 108-15 at antibiotic concentrations that caused a 90% reduction of the radiolabel incorporation into glycoproteins. The effect of tunicamycin on ganglioside biosynthesis was apparent after only 4 hr of incubation, and maximum inhibition was seen within 6 hr. When control or tunicamycin-treated (5 mug/ml) cells were collected and fractionated to separate glycoproteins, neutral glycosphingolipids, gangliosides, and nucleotide sugar-precursor pools, the following results were obtained: (i) UDP-GlcNAc and UDP-GalNAc pool sizes increased >3-fold, and specific activities decreased 50% upon treatment with tunicamycin; (ii) when corrected for this value, the percentage inhibition of GlcN incorporation into various glycoconjugates by tunicamycin in these cells was 82% for glycoproteins, 54% for neutral glycosphingolipids, and 50% for gangliosides; and (iii) the different gangliosides were affected differentially, with the most striking inhibition apparent in GM(3) biosynthesis, which was decreased 78% in the presence of tunicamycin. These data suggest that the effects of tunicamycin on glycosphingolipids as well as on glycoproteins must be considered when interpreting its effects on intact cells and organisms.
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PMID:Tunicamycin inhibits ganglioside biosynthesis in neuronal cells. 657 17

To determine the N-linked oligosaccharide structure of beta-amyloid precursor protein (beta APP), soluble derivative of beta APP (APPs) was purified from the conditioned medium of beta APP cDNA-transfected C6 glioma cells. Two types of APPs with different molecular weight (larger APPs, L-APPs; smaller APPs, S-APPs) were obtained. The antibody against the N-terminal half of amyloid beta-protein showed no immunoreactivity with S-APPs, suggesting extensive truncation at the carboxyl terminus. From lectin blot analysis, the main structure of the N-linked oligosaccharide shared by L- and S-APPs was deduced to be of bi- or triantennary complex type with a fucosylated trimannosyl core and a bisecting GlcNAc residue. Additionally L-APPs was deduced to have Gal beta 1-->4GlcNAc, Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures on its outer chains. However, lectins which recognize Fuc alpha 1-->2Gal beta and Sia alpha 2-->6Gal beta structures showed no reactivity with S-APPs. The present results suggest that the processing of beta APP may be regulated via the heterogeneity in the fine structure of its sugar chains.
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PMID:N-linked oligosaccharide of beta-amyloid precursor protein (beta APP) of C6 glioma cells: putative regulatory role in beta APP processing. 776 44

CMP-NeuAc: Galbeta1,3(4)GlcNAc alpha2,3-sialyltransferase (alpha2,3-ST) mRNA was expressed in human glioma specimens, human fetal astrocytes, and a panel of brain tumor cell lines. Maackia amurensis agglutinin staining revealed the presence of alpha2,3-linked sialic acids on glioma cell surfaces and extracellular matrices whereas normal human adult astrocytes were negative. Increased expression of alpha2,3-linked glycoprotein sialylation may play a role in glial tumorigenesis.
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PMID:alpha2,3-sialyltransferase mRNA and alpha2,3-linked glycoprotein sialylation are increased in malignant gliomas. 916 57

N-Acetylglucosamine-6-O-sulfotransferase catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 6 of a non-reducing N-acetylglucosamine (GlcNAc) residue. We have cloned human GlcNAc-6-O-sulfotransferase cDNA, based on the sequence homology to cloned cDNA of mouse GlcNAc-6-O-sulfotransferase. The predicted protein sequence of the human enzyme was highly homologous to that of the mouse enzyme; in the 363 amino acid stretch of the catalytic region, the two proteins were nearly identical except for conservative changes in 3 amino acid residues. The expressed enzyme transferred sulfate to GlcNAcbeta1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Gl cNAc. Co-transfection of the enzyme cDNA and fucosyltransferase VII cDNA into COS-7 cells resulted in cell surface expression of 6-sulfo sialyl Lewis X. Fluorescence in situ hybridization analysis revealed that the GlcNAc-6-O-sulfotransferase gene is located on human chromosome 7q31. mRNA of the human enzyme was strongly expressed in the bone marrow, peripheral blood leukocytes, spleen, brain, spinal cord, ovary, and placenta, and moderate levels of expression were observed in many organs including lymph nodes and thymus. In situ hybridization with the mouse system showed that the transcript was localized in specific regions of the brain, i.e. pyramidal cells in the CA3 subregion of the hippocampus, cerebellar nucleus and Purkinje cells. Among human tumor cells, strong expression of the mRNA was found in MOLT-4 and Jarkat lymphoblastic leukemia cells, Raji lymphoma cells, K-562 chronic myelogeneous leukemia cells, U251 glioma cells, and G361 melanoma cells. Carbohydrate structures synthesized by the sulfotransferase may be involved in various aspects of the differentiation and behavior of blood cells, their progenitor cells, and neurons in the central nervous system.
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PMID:Human N-acetylglucosamine-6-O-sulfotransferase involved in the biosynthesis of 6-sulfo sialyl Lewis X: molecular cloning, chromosomal mapping, and expression in various organs and tumor cells. 972 82

Increased expression of the bisecting GlcNAc has been correlated with tumor progression in several experimental tumor models. Its expression and function in brain tumors are, however, not yet known. In this study, we investigated expression of the bisecting GlcNAc structure in a series of pediatric brain tumors and its relationship to tumor response to vinblastine. A plant lectin (E-PHA) that recognizes the bisecting GlcNAc structure was used for detection of this molecule in a total of 90 pediatric brain tumors and normal brain tissue specimens. Our results showed that, whereas E-PHA staining was undetectable in the normal brain tissue, pediatric brain tumor specimens exhibited different levels of reactivity. Lectin staining was particularly prominent in high-grade astrocytomas (73%) and ependymomas (72%). In astrocytomas, there was a positive correlation with the tumor grade, which suggests that the bisecting GlcNAc may be of particular interest as a tumor marker for diagnosis and/or prognosis. By using a human glioma cell culture model, we have found that treatment of these cells with E-PHA lectin enhances their sensitivity to vinblastine. E-PHA interacted directly with the drug transporter P-glycoprotein and inhibited its drug efflux function. In a drug-resistant glioma cell line transfected with the mdr1 gene, drug resistance was reversed by E-PHA. Our findings indicate that: (a) expression of the bisecting GlcNAc in pediatric brain tumors may have a potential relevance as a tumor marker; and (b) glioma response to chemotherapy may be modulated through the bisecting GlcNAc.
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PMID:Expression of bisecting GlcNAc in pediatric brain tumors and its association with tumor cell response to vinblastine. 1058 84

The metastatic potential of tumor cells has been shown to be correlated with the expression of tri- and tetra-antennary beta1,6-N-acetylglucosamine (beta1,6-GlcNAc)-bearing N-glycans, which are recognized by Phaseolus vulgaris leukoagglutinating lectin (L-PHA). The expression of beta1,6-GlcNAc-bearing N-glycans also has been used as a marker of tumor progression in human breast and colon cancers. In this report, the role of N-glycan branching in regulating glioma migration and invasion was examined. The expression of beta1,6-GlcNAc-bearing N-glycans was found in human glioma specimens, whereas astrocytes from normal adult brain were negative. The expression of N-acetylglucosaminyltransferase V (GnT-V) mRNA, which is responsible for the biosynthesis of beta1,6-GlcNAc-bearing N-glycans, was high in glioma cell lines with robust ets-1 expression. To study the molecular mechanism of GnT-V expression in human glioma cells, an inducible ets-1 gene was stably transfected into SNB-19 cells using a tetracycline repressor system. GnT-V mRNA expression was increased by the induction of c-ets-1, suggesting that the Ets-1 transcription factor directly regulates the transcription of GnT-V. Stable transfection of GnT-V into human glioma U-373 MG cells resulted in changes in cell morphology and focal adhesions and a marked increase in glioma invasivity in vitro. L-PHA has little effect on cell migration. On the contrary, Phaseolus vulgaris erythroagglutinating lectin (E-PHA), which recognizes bisecting beta1,4-GlcNAc-bearing N-glycans, strongly inhibits cell migration (haptotaxis) on a fibronectin substrate in U-373 MG transfectants and other glioma cell lines tested. These results suggest that the increased beta1,6-GlcNAc-bearing N-glycan expression found in malignant gliomas is modulated by GnT-V through the Ets-1 transcription factor, and that the branching of complex type N-glycans plays a major role in glioma invasivity.
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PMID:Beta1,6-N-acetylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity. 1064 65


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