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)

Synthetic peptides meeting certain guidelines have been used as immunogens to generate antibodies with predefined specificity. We have raised and characterized using established methods a monoclonal antibody against a synthetic peptide corresponding to the 18-amino acid carboxyterminal sequence (A194-211) of the platelet-derived growth factor (PDGF) A chain expressed by the U343 human glioma cell line. This antibody was generated in order to carry out structure-function studies on this region of PDGF whose biological significance is not yet clear. Anti-PDGF-A194-211 was found to be a low titre, IgM kappa molecule, with a Kd of 2.8 x 10(-7) M. When antibody reactivity was tested with parent PDGF-AAL (A chain homodimer containing a carboxyterminal extension) significant binding was observed. Surprisingly, 125I-PDGF-AAS, consisting of truncated A chains but lacking the extension was also bound. Moreover, poly-L-lysine, beta-thromboglobulin, PDGF-A194-211, and myoglobin competed dose-dependently with 125I-PDGF-AAL for antibody. 125I-bovine serum albumin was also bound. Examination of the primary sequence of proteins and peptides bound by the antibody revealed only one shared structural motif: a lysyl-lysine moiety. Selected small synthetic peptides containing this and other sequences were used as potential competitors of 125I-PDGF-A194-211 in antibody binding. Lysyl-lysyl-glycyl-glutamic acid [corrected] and lysyl-lysine competed, whereas lysyl-leucine did not. These results suggest that as few as two amino acid residues constitute a functional antigenic determinant and contrast with most previous estimates of the minimum number of residues required. Furthermore, we show that guidelines governing the design of synthetic peptides for their use as antigens to produce monoclonal antibodies of predetermined specificity may be unreliable.
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PMID:A crossreactive antipeptide monoclonal antibody with specificity for lysyl-lysine. 171 72

Human glioma-associated markers can be exploited for the development of new diagnostic strategies and treatment modalities for these malignancies. A goat antiserum was first raised against human anaplastic astrocytoma (AC or AA) and glioblastoma multiforme (GB or GBM) extracts. Extensive sequential absorptions with normal brain tissue, normal serum, and human serum albumin (HSA) gave an antibody fraction specific for glioma. Balb/c mice were subsequently immunized with these glioma extracts. B-cell hybridomas from these mice were then cloned and subcloned by limiting dilution, yielding six monoclonal antibodies (MAbs) that were entirely specific for tumor tissues, and did not react with normal human serum or with normal human brain, liver, kidney, spleen, or muscle. Moreover, the murine MAbs did not cross-react with certain other human tumors, including melanoma. The fully absorbed antiserum and the murine MAbs both identify a polypeptide pattern possibly related to human glial fibrillary acidic protein (GFAP) or other intermediate filament proteins on immunoblots. These immunological reagents could serve as powerful tools for the diagnosis and possibly therapy of these uniformly fatal tumors.
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PMID:Preparation and characterization of antisera and of murine monoclonal antibodies to human glioma-associated antigen(s). 180 72

We have previously reported the isolation of a 66 kDa melanoma-associated antigen, identified by autologous antibody, in serum and unfractionated spent tissue culture media by Western blot analysis. The antigen, detected by autologous serum S150, was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma and head and neck carcinoma cell lines. S150 did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, autologous cultured lymphocytes or fetal calf serum. To further characterize the antigen, spent tissue culture media, obtained from autologous melanoma cell line, Y-Mel 84:420, was separated by an isoelectric focusing column. Unabsorbed control serum S150 was noted to have a maximum titer of 1:2040 against autologous melanoma cells as measured by protein A hemadsorption. Following isoelectric focusing the greatest decrease in autologous antibody titer (30-fold) occurred with fractions having a pI between 2 and 3. Further resolution of the antigen was accomplished with high-pressure ion-exchange chromatography. One of these fractions showed a significantly higher concentration of antigen and was distinctly resolved from bulk serum albumin. Subsequent Western blot analysis, with autologous antibody, of the isolated antigen-containing fraction, confirmed the presence of a single 66 kDa band. Exposure of the antigen, purified by high-pressure ion-exchange chromatography, to neuraminidase ablated recognition by autologous antibody and suggests that sialic acid is present on the protein and may be part of the antigenic epitope. Binding of antigen, obtained following DEAE anion exchange chromatography, was noted to lectins derived from Triticum vulgaris, Dolichos biflorus and Lycopersicon esculentum. Preparative purification of the antigen was accomplished by anion exchange followed by lectin affinity chromatography with a Dolichos biflorus column. Antigen obtained following lectin affinity chromatography subjected to SDS-PAGE and silver stain revealed a single band at 66 kDa. We conclude that a melanoma-associated antigen detected by autologous antibody in spent tissue culture media is an unusually acidic glycoprotein (pI 2-3).
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PMID:Purification and partial characterization of a shed 66 kDa melanoma-associated antigen identified by autologous antibody. 193 77

Cat brain tumors were produced by stereotactical xenotransplantation of rat glioma clone F98 into the internal capsule of the left hemisphere. Two to four weeks after implantation, the tissue content of water, sodium, potassium, calcium, magnesium, serum albumin, serum immunoglobulin, and hemoglobin was measured in samples taken from the tumor, from peritumoral white and gray matter, and from homotopic regions of the opposite hemisphere. Extravasated serum protein content was determined by subtracting intravascular from total tissue protein, using the hemoglobin content as a marker of blood volume. The development of brain tumors was accompanied by severe vasogenic brain edema, which was clearly confined to the ipsilateral white matter. The increase of water was paralleled by an increase of sodium, calcium, and serum proteins. Potassium and magnesium content remained constant. The calculated sodium and calcium content of edema fluid approximated that of blood serum. The content of blood proteins was about 50% lower, but the ratio of albumin/immunoglobulin was the same as in blood. It is concluded that peritumoral edema is a combination of plasma ultrafiltrate and whole plasma extravasation with different modes of formation. Implications for the pathophysiology and therapy of peritumoral edema are discussed.
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PMID:Quantitative analysis of experimental peritumoral edema in cats. 239 38

Chronic treatment of neuroblastoma X glioma NG108-15 hybrid cells with opiate agonist resulted in loss of the acute opiate inhibition of adenylate cyclase activity with a concomitant increase in the enzymatic activity observable on addition of the antagonist naloxone. The role of membrane lipids in the cellular expression of these chronic opiate effects was investigated by the hydrolysis of phospholipids with various lipases. Treatment with phospholipase C from Clostridium welchii produced an enzyme concentration-dependent decrease of prostaglandin E1-stimulated adenylate cyclase activity in control or etorphine-treated (1 microM for 4 h) hybrid cells. In addition, incubation of hybrid cells with phospholipase C concentrations of greater than or equal to 0.5 U/ml completely abolished the compensatory increase in adenylate cyclase activity after chronic opiate treatment. This attenuation of the increase in adenylate cyclase activity by phospholipase C could be prevented by inclusion of phosphatidylcholine but not of phosphatidic acid during the enzymatic incubations. The specificity of the phospholipids involved in expression of the chronic opiate effect could be demonstrated further by the absence of effect exhibited by phospholipase C from Bacillus cereus and phospholipase D. Hydrolysis of the acyl side chains of phospholipids with phospholipase A2 did not alter the chronic opiate effect after removal of lysophosphatides with bovine serum albumin. Because the guanylylimidodiphosphate- and NaF-sensitive adenylate cyclase activities were not affected by these phospholipase treatments, the expression of the compensatory increase in adenylate cyclase activity is mediated via an increase in the coupling between hormonal receptor and adenylate cyclase with the participation of the polar head groups of the phospholipids and not the hydrophobic side chains.
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PMID:Effect of phospholipases on chronic opiate action in neuroblastoma X glioma NG108-15 hybrid cells. 301 58

The functional association of astroglial footplates with blood vessels is important because astrocytes may provide a channel between the blood and neurons deeper in the brain parenchyma for the passage of ions and metabolites. This hypothesized function is very difficult to study in vivo or in monolayer cultures. We have produced a three-dimensional cell culture model of perivascular astroglia by means of an artificial capillary system. Conventional primary cultures of astroglia were first prepared from neonatal rat cerebral hemispheres in 75-cm2 tissue culture flasks. After 25 days, the cells were seeded in Amicon Vitafiber hollow fiber culture vessels. Direct seeding of brain cell suspensions was not successful. A culture unit consists of a bundle of hollow, semi-permeable polysulfone fibers encased in a plastic shell. The fibers were coated with fibronectin and bovine serum albumin, and astroglia were seeded on their outer surfaces. Warmed medium was pumped through the lumina of the fibers. After 13 days the cells were fixed with paraformaldehyde and examined. Scanning electron microscopy revealed the tubes to be uniformly covered with astroglia with short processes that contacted nearby cells. Transmission electron microscopy showed glial filaments and gap junctions. Astrocyte cultures were compared morphologically to C6 rat glioma cells in hollow fiber culture. The astrocytes formed a monolayer, whereas C6 cells formed a stratified culture. Furthermore, C6 cells did not form gap junctions. Astrocytes have been hypothesized to take up K+ discharged to the extracellular space by depolarizing neurons and move it to areas of low concentration, i.e., to act as a K+ spatial buffer. Our culture system should permit direct testing of this hypothesis.
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PMID:Glial culture on artificial capillaries: electron microscopic comparisons of C6 rat glioma cells and rat astroglia. 309 88

It is still controversial whether edema fluid around a malignant brain tumor is derived from capillaries inside the tumor itself or not only from tumor vessels but also from peritumoral tissue. The purpose of this study is to clarify the region where the capillary permeability is increased using double autoradiographic method. A suspension of 1 X 10(4) rat glioma cells (RG-12) was stereotactically implanted into the right basal ganglia of C-D Fisher rats. In this model, all animals are dead 20 +/- 1 days after the implantation. Two kinds of tracers, 14C-alpha-aminoisobutyric acid (AIB) and 131I-human serum albumin (HSA), were administered 14 to 17 days after the tumor implantation. In all rats, 14C-AIB was intravenously injected 10 min before decapitation. 131I-HSA was given 10 min before decapitation in five animals (group 1), one hour before in four animals (group 2), and six hours before in three animals (group 3). Autoradiograms for 131I-HSA were exposed for initial one to two days after the decapitation, while the exposure for 14C-AIB was delayed until 4 months later. Autoradiograms of these two tracers were compared with the corresponding sections with H-E stain for neuropathological examination. In group 1, the distribution of HSA as well as AIB was quite similar to tumor itself. In group 2 and group 3, the distributions of AIB were similar to the tumor. However, the distributions of HSA were 1.4 fold larger (group 2) and 3.6 fold larger (group 3) than the tumor and expanded into the peritumoral region.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Changes in capillary permeability in experimental brain tumor]. 337 Jan 67

Cerebral edema produced by brain tumors is clinically and experimentally reduced by steroid therapy. Nonsteroid anti-inflammatory drugs (NSAID's) which have been used to treat non-neural inflammation and swelling have not been evaluated for their ability to affect edema produced by brain tumors. The authors have used the rat C6 glioma spheroid implantation model to compare the effects of two steroids (dexamethasone and methylprednisolone) and two NSAID's (ibuprofen and indomethacin) on protein extravasation caused by intracranial gliomas. Evans blue dye was used as a marker for serum albumin extravasation. The concentration of Evans blue dye was measured in the tumor and peritumoral and contralateral brain tissue 1 hour after intravenous injection. Extravasation of Evans blue dye within the tumor was decreased in all treatment groups when compared to placebo-injected control animals. The differences between the control specimens and those treated with dexamethasone, methylprednisolone, and indomethacin were highly significant (p less than 0.005). The Evans blue staining was also decreased in the peritumoral and contralateral brain. These results indicate that NSAID's compare favorably with steroids in diminishing tumor-induced protein extravasation. It is suggested that NSAID's may prove to be beneficial in clinical instances used either in conjunction with steroid therapy or alone when steroids are contraindicated.
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PMID:Effects of steroids and nonsteroid anti-inflammatory agents on vascular permeability in a rat glioma model. 372 82

A trypsin-degradable nerve growth factor (NGF) receptor associated with the phospholipid component of the surface membrane has been detected on F98 anaplastic glioma cells. NGF also bound to the nucleus of F98 cells. Bound NGF was not displaceable by insulin, cytochrome C, growth hormone, or bovine serum albumin. Specific binding of NGF occurred with a Kd of 8.79 X 10(-12) M as determined by Scatchard analysis with approximately 34,000 receptors per cell. Specific NGF binding was also evident to C6 rat glioma cells and IMR-32 human neuroblastoma cells, but not to 3T3 mouse fibroblasts. These observations coupled with previous findings suggest that the NGF receptor may be a marker found on cells of neural derivation. As little as 1 ng/ml NGF caused an increase in the adhesiveness of F98 cells to culture flasks. Increased adhesiveness could be observed in as little as 5 min and was apparent for at least 45 min. At 25 min in NGF-containing medium, 24 +/- 3% of the cells adhered to the flasks compared to 13 +/- 1% of control cells. The NGF-induced increase in adhesiveness was not duplicated by epidermal growth factor, insulin, cytochrome c, bovine serum albumin, dibutyryl cyclic AMP, or sodium butyrate. Oxidized NGF blocked the effect of native NGF, but had little or no adhesion-promoting activity itself. Pretreatment of the cells with NGF was also effective in promoting adhesion, even though nerve growth factor was not added to the binding medium. The effect of this pretreatment was reversible; when NGF-pretreated cells were grown in medium without supplemental NGF, the adhesiveness of the cells returned to control levels or lower.
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PMID:Increased adhesion response of anaplastic glioma cells to nerve growth factor and the presence of specific receptors. 631 24

In rats experimental brain tumors were produced by intracerebral implantation of a glioma cell clone. Peritumorous edema was investigated by light and electron microscopy, using exogenous tracers [human serum albumin (HSA), horseradish peroxidase] and immuno-histochemical methods for localization of endogenous serum proteins. An infiltration by serum proteins was observed in peritumoral grey and white matter. Peroxidase was found in pinocytotic vesicles of vascular endothelial cells, in pericytes and diffusely in the extracellular space. High concentrations of endogenous rat serum proteins and exogenous human serum albumin were also found in neurons of the grey matter and in oligodendrocytes of the white matter. A cellular uptake of extravasated proteins, therefore, may contribute to edema resolution.
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PMID:Experimental brain tumors and edema in rats. III. Peritumorous edema. 654 42


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