UMLS:C0017638 - FACTA Search

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Query: UMLS:C0017638 (glioma)
30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A fluorescent derivative of ganglioside GM1 was prepared by oxidation of the sialic acid residue with sodium periodate and reaction of the resulting aldehyde with Lucifer yellow CH. The biological activity of the fluorescent derivative was compared with that of native GM1 using GM1-deficient rat glioma C6 cells. When the cells were exposed to either native or fluorescent GM1, their ability to bind 125I-labeled cholera toxin was increased to a similar extent. This increase in binding was directly proportional to the amount of ganglioside added to the medium. The affinity of the toxin for cells treated with either native or fluorescent GM1 also was similar. More importantly, the fluorescent GM1 was as effective as native GM1 in enhancing the responsiveness of the cells to cholera toxin. Thus, the ganglioside-treated cells exhibited a 9-fold increase in toxin-stimulated cyclic AMP production over cells not exposed to GM1. There was a similar increase in iodotoxin binding and toxin-stimulated cyclic AMP accumulation in cells treated with other GM1 derivatives containing rhodaminyl or dinitrophenyl groups. On the basis of these results, it is clear that these modified gangliosides retain the ability to function as receptors for cholera toxin. Consequently, fluorescent gangliosides are likely to be useful as probes for investigating the dynamics and function of these membrane components.
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PMID:Fluorescent derivatives of ganglioside GM1 function as receptors for cholera toxin. 300 28

This study was designed to establish an in vitro model with biochemical and morphological similarities to the human neurodegenerative disease GM1 gangliosidosis. Utilizing a specific inactivator of the lysosomal enzyme GM1-ganglioside beta-galactosidase (beta-D-galactopyranosylmethyl-p-nitrophenyltriazene [beta-GalMNT]) and neuroblastoma X glioma hybrid cells (NG108-15), we suppressed beta-galactosidase activity for up to 72 hours. Coincidental with suppression of this enzyme to levels less than 1% of control, we found up to a nine-fold accumulation of its substrate, the GM1-ganglioside, and the ultrastructural appearance of membranous cytoplasmic bodies. beta-GalMNT treatment suppressed growth but had little effect on the specific activity of choline acetyltransferase, lactate dehydrogenase, or other lysosomal enzymes including galactosylceramidase. This model should permit studies of the neurophysiological effects of increased ganglioside accumulation and their reversibility.
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PMID:Inactivation of GM1-ganglioside beta-galactosidase by a specific inhibitor: a model for ganglioside storage disease. 303 98

The transplantability of experimental tumors into the brain (i.c.) and s.c. tissues of C3Hf/Sed and athymic NCr/Sed nude mice was examined using quantitative cell transplantation assays. Studies using the immune-competent C3H animals showed that brain is a more favorable site for the transplantation of syngeneic tumor than s.c. tissue and that this is true for nonimmunogenic as well as immunogenic tumors. The capacity of the brain to act as an immunological sanctuary can be overwhelmed by a strong, systemic, secondary immune response such as that evoked by the methylcholanthrene-induced sarcoma FSal. In studies performed using NCr/Sed nude mice, the allogeneic tumor MCaIV was found not to be demonstrably immunogenic. The cell dose required to transplant the tumor into 50% of recipients (TD50) could neither be increased by immunization procedures nor decreased by six Gy whole-body irradiation (WBI) prior to transplantation. Delayed-type hypersensitivity to this tumor was not expressed by nude mice after rechallenge with tumor antigen. The TD50 was again lower for i.c. than s.c. transplantation and the ratio s.c./i.c. was comparable to that found in syngeneic C3Hf/Sed hosts. Three human tumors have been similarly tested. They were: FaDu, a pharyngeal squamous carcinoma; HFSal, a fibrosarcoma; and U87, a malignant glioma. s.c. TD50 values were in all cases significantly higher than those obtained i.c. The ratios TD50 s.c./i.c. ranged from 6.4 to greater than 50 in five studies, substantially higher than those found for transplantation of murine tumors into either the syngeneic or the allogeneic recipients. Six Gy WBI reduced the s.c. TD50 for these tumors, but in each case the value remained significantly higher than that obtained i.c. 19.4 Gy WBI given in 10 equal fractions and followed by i.v. bone marrow rescue reduced further the s.c. TD50 for FaDu. NCr/Sed nude mice demonstrated cross-reacting delayed-type hypersensitivity against FaDu and HFSal. A small proportion of FaDu tumors (less than 2%) displayed a spontaneous halt in growth or even regression. When the host cell infiltrate of these tumors was analyzed, an increase was seen in the proportion of Thy 1.2 and asialo-GM1-positive cells as compared with progressively growing tumors. These data strongly suggest that a residual low level of immune reactivity exists in nude mice against xenotransplanted human tumors. This resistance to s.c. transplantation may be diminished by WBI and is less for intracerebral implantation.
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PMID:Quantitative studies on the transplantability of murine and human tumors into the brain and subcutaneous tissues of NCr/Sed nude mice. 305 3

As an initial approach to experiments directed toward effective adoptive immunotherapy for cancer using lymphokine genes, we transferred retrovirally a complementary DNA encoding mouse gamma-interferon (IFN-gamma) into a specific cytotoxic T-lymphocyte clone, designated E-4, against 203 glioma cells (a 20-methylcholanthrene-induced mouse glioma line) and confirmed the efficacy of IFN-gamma production from the exogenous gene on augmentation of tumor targeting. Of five, two gene-transferred subclones constitutively produced 8 to 10 times the amount of IFN-gamma as compared with the parental E-4. Correspondingly, these two subclones exhibited 2 to 3 times higher killing activity against 203 glioma than the parental cells; the enhancement of the killing activities was abrogated by an adequate addition of anti-IFN-gamma antibody. No alteration was seen after the gene transfer in cell surface phenotypes, Thy-1+, Lyt-1-, Lyt-2+,3+, and asialo-GM1-. The surface expression of a major histocompatibility complex Class I antigen, H-2Kb, was not altered remarkably, but the Class II antigen, I-Ab, was partially and slightly enhanced on the two IFN-gamma-producing sublines mentioned above on fluorescence-activated cell sorter analysis. Since it is considered that in the vicinity of the constitutively IFN-gamma producing cytotoxic T-lymphocyte cells tumor cells are exposed to a high concentration of IFN-gamma, the cells may be stimulated to induce or enhance the expression of surface antigens including major histocompatibility complex antigens as well as tumor-associated antigens relevant to immune recognition. The 203 glioma cells pretreated with IFN-gamma were more efficiently killed by both the parental E-4 and the gene-transferred sublines. Taken together, the results suggested that the augmented specific tumor-killing activity of our gene-transferred cytotoxic T-lymphocytes was ascribed to the constitutive production of IFN-gamma derived from the exogenous gene.
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PMID:Augmentation of tumor targeting in a line of glioma-specific mouse cytotoxic T-lymphocytes by retroviral expression of mouse gamma-interferon complementary DNA. 313 12

The monosialoganglioside GM1 can potentiate the neuritogenic activity of media conditioned by several cell types: neonatal glia, C6 glioma, embryonic chick heart or skeletal muscle and the rat myogenic line L6. To probe further the neuritogenic activity of conditioned media (CM), 5 mouse monoclonal antibodies (mAbs) against GM1, designated B6, C3, C4h2, D1 and D3 were incorporated individually into nutrient medium (NM) supplemented with CM prior to incubation with sensory ganglia. Nine-day embryonic chick dorsal root ganglia were explanted onto collagen-coated coverslips and incubated at 35 degrees C for 5 h in NM supplemented with 150 micrograms/ml GM1. After washing with NM, the explants were re-fed with NM + CM containing 20% mAb and cultured for an additional 43 h. The resultant neuritogenesis was evaluated microscopically by determining mean neurite number and length of randomly mixed cultures. The 5 antibodies differed in their capacities to inhibit CM-mediated neuritogenesis of these primed target cells. D1 and D3 were most effective in reducing neurite length and number produced by all sources of the CM, while C3 and C4h2 were intermediate in their inhibition of neurite initiation (number). The effect of B6 on neurite initiation and elongation was the least. The ability of these mAbs to inhibit neuritogenic activity of CM derived from both glial and myogenic tissue suggests that gangliosides play a basic role in neuronal development. The differing responses elicited by the individual mAbs may reflect a relationship between the structural complexity of the GM1 molecule and the neuritogenic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of conditioned media-mediated neuritogenesis of sensory ganglia by monoclonal antibodies to GM1 ganglioside. 340 9

The ability of gangliosides to potentiate nerve growth factor (NGF)-independent trophic agents was determined by examining the capacity of an exogenous mixture of bovine brain gangliosides (BBG) and the monosialoganglioside GM1 to enhance the neuritogenic action of conditioned media (CM). CM were prepared with cultures of C6 glioma cells, neonatal rat astroglial cells, rat L6 myoblasts and chick embryonic skeletal muscle. Chick embryonic (9 day) dorsal root ganglia (DRG) were cultured on collagen-coated surfaces. The nutrient media with serum added or serum-free N1 medium were supplemented with 50% of one of the CM with or without BBG (150 micrograms/ml) or GM1 (150 micrograms/ml). The neuritogenic responses of DRG 48 h in vitro were evaluated microscopically on the basis of neurite length and number. The neurite promoting action of the factor(s) present in the various CM was potentiated by BBG or GM1 and resulted in increased neurite length and number.
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PMID:Ganglioside potentiation of NGF-independent trophic agents on sensory ganglia. 341 44

In an attempt to facilitate the long-term proliferative growth and subsequent cloning of cytotoxic T lymphocytes (CTL's) against syngeneic murine 203-glioma (20-methylcholanthrene-induced ependymoblastoma of C57BL/6 mouse origin), sensitized T lymphocytes from tumor-bearing mice were cultured in the presence of T cell growth factor (TCGF). Of five clones established by a limiting dilution technique, two clones (G-CTLL 1 and 2) exhibited tumor-specific cytotoxicity. G-CTLL 1 cells, which possessed much higher cytotoxic activity than G-CTLL 2 cells, were further analyzed. G-CTLL 1 cells were maintained in a TCGF-dependent exponential proliferative culture for over 18 months and continued to mediate an extremely high cytotoxic activity with the target specificity (50- to 100-fold increases over the peak cytotoxic activity of sensitized T lymphocytes in tumor-bearing mice). Their phenotypes of surface antigens were Thy-1+ (weak positive), Lyt-1.-2.+3+, and asialo-GM1-, and their cytotoxicity was blocked by adding only anti-Lyt-2 monoclonal antibodies. These results indicated that the cloned cells originated from CTL's. The cloned cells were characterized by the production of immune interferon with the glioma antigen-stimulation, suggesting that the immune interferon could enhance the cytotoxic activity of the CTL clone at the site of a clone-target cell recognition event.
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PMID:Establishment of experimental malignant glioma-specific cytotoxic T lymphocyte clone by T cell growth factor. 620 98

Cellular differentiation of the neuroblastoma X glioma hybrid cell line NG108-15 was measured and correlated with quantitative changes in the cells' ganglioside composition. The degree of differentiation was measured using an enzymatic marker, choline acetyltransferase (CAT), which is responsible for neurotransmitter synthesis in this cell line. Differentiation of these cells is commonly induced by agents such as dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP). However, in our studies, we observed that these cells "self-differentiated," in the absence of chemical inducers, when the cells became dense in culture. The differentiation marker, CAT specific activity, rose from 150 to more than 400 pmol/min/mg of protein as cell density increased, attaining a level higher than that achieved by treatment with Bt2cAMP. Differentiation of sparse cultures could be induced by conditioned medium removed from dense cultures. This effect was not due to depletion of a serum component from the medium by the cells, since it was not mimicked by serum depletion or inhibited by addition of fresh serum to the conditioned medium. These data suggest that cell density-dependent differentiation was caused by release of a factor from the cells which induced differentiation in a concentration-dependent manner. Gangliosides, therefore, were purified from sparse control cultures, dense cultures, and cultures treated with the differentiating agents Bt2cAMP, prostaglandin E1 (plus theophylline), or butyric acid. Quantitative thin layer chromatography revealed that all of the cultures contained the four gangliosides GM3, GM2, GM1, and GD1a. The concentration of one of the gangliosides, GM2, increased markedly (up to 12-fold) during differentiation. The GM2 concentration correlated closely with the level of CAT activity in the different cultures (r = 0.99). These data demonstrate that the ganglioside concentration in these cells is regulated during differentiation, a finding consistent with a possible role for gangliosides in the differentiated phenotype.
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PMID:Ganglioside composition is regulated during differentiation in the neuroblastoma X glioma hybrid cell line NG108-15. 630 Mar 57

When added to the culture medium, 3H-labeled GM1 (tritiated predominantly in the terminal galactose residue) was taken up by murine NCTC 2071 and rat glioma C6 cells, both of which are GM1-deficient. Upon incubating the labeled cells in fresh medium, the cell-associated GM1 was metabolized by the cells with a half-life of 1 to 2 days. Some of the GM1 was converted to GD1a but the bulk of the label appeared in the medium as degradation products. When GM1 labeled in the sialic acid or lipid portion of the molecule was utilized, GM2 also was detected with time in the cells and only a small fraction of the radioactivity was detected in the medium. The rat glioma C6 cells appeared unable to degrade the GM2 that they accumulated; this was demonstrated directly by incubating the cells with labeled GM2. The uptake and subsequent metabolism of GM1 was observed over a wide range of GM1 concentrations (10(-8) to 10(-4) M). The GM1-treated cells initially bound more iodinated choleragen than did untreated cells; but with time, binding capacity decreased. When GM1-treated cells were transferred to fresh medium in the presence of excess choleragen, the amount of cell-associated GM1 remained relatively constant for several days; the conversion of GM1 to GD1a also was blocked. Although labeled GM3 and GD1b also were taken up by the cells, choleragen had no effect on their subsequent metabolism. Choleragenoid, the binding subunit of choleragen, also inhibited GM1 metabolism without activating adenylate cyclase. These results indicate that exogenous gangliosides taken up by cultured cells are metabolized and that choleragen, which binds with high affinity to GM1, specifically prevents the metabolism of this ganglioside.
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PMID:Uptake and metabolism of exogenous gangliosides by cultured cells: effect of choleragen on the turnover of GM1. 663 Dec 29

Human glioma cells (12-18) and fetal neural cells (CH II) in culture were exposed for 20 hr to [14C]glucosamine to determine the level and distribution of radiolabel incorporated into gangliosides. Cells of identical passage levels at two stages of growth, preconfluent and confluent, were preincubated for 0 to 60 hr in serum-free medium (SFM). Both higher cell densities and longer incubations in SFM caused a change in the amounts and patterns of radiolabeled gangliosides. Preincubation for 60 hr in SFM caused an increase (P less than 0.05) in the percent of total recovered ganglioside radiolabel in GM1 of CH II cells, from 10.5 to 16.7% in preconfluent cells and from 14.1 to 31.9% in confluent cells. Conversely, the proportion of radiolabel in GM3 and GM2 decreased with longer preincubations in SFM. A similar preincubation of glioma cells caused an increase in the proportion of label into GD1a of both preconfluent and confluent cells (P less than 0.02) from 4 to 11% of the total ganglioside radioactivity. Higher cell densities also resulted in consistently higher percent (of total ganglioside) incorporation into GD1a of 12-18 cells (P less than 0.05) and GM1 of CH II (P less than 0.01). These results show that there is a shift in the incorporation of precursor label into more complex gangliosides under conditions associated with the arrest of cell division. These phenomena may represent a regulatory response of the ganglioside biosynthetic apparatus to changes in extracellular environment and cell contact.
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PMID:Effects of human brain cell culture conditions on [14C]glucosamine radioactivity incorporation into gangliosides. 687 78

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