Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B cells derived from peripheral-blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from a patient with a high serum antibody titer to autologous melanoma were transformed with Epstein-Barr virus (EBV) and evaluated for reactivity against autologous tumor. B cells producing antibody reactive with autologous tumor and unreactive with normal fibroblasts were detected both in TIL and in PBL. One cell line derived from PBL and another derived from TIL sustained production of tumor-reactive antibody for 10 weeks and over 15 months respectively. The cell line derived from PBL, 2D11, produced an antibody reactive with a trypsin-resistant antigen expressed on the cell membrane of autologous and allogeneic melanoma cell lines. The cell line derived from TIL, 1F6, produced an antibody reactive with a cell-surface glycoprotein expressed by 5 autologous melanoma cell lines derived from 5 different metastases and 16/19 allogeneic melanoma cell lines. 1F6 also showed reactivity with cell lines derived from a blue nevus, a congenital nevus, an astrocytoma, and 1/4 renal-cell carcinomas; but it was not reactive with 5 foreskin melanocyte cell lines, 2 normal fibroblast lines, 5 leukemia/lymphoma lines, 8 lung-cancer lines, 8 glioblastoma lines, or lines derived from 1 ovarian carcinoma, 1 colon carcinoma, 1 vulvar carcinoma, 1 fibrosarcoma, 1 murine melanoma, or 4 murine leukemia/lymphomas. We describe here an antibody that detects a new melanoma specificity obtained by EBV transformation of tumor-infiltrating B cells.
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PMID:Analysis of two human monoclonal antibodies against melanoma. 145 38

Protease nexin-II (PN-II) is a protease inhibitor that forms SDS-resistant inhibitory complexes with the epidermal growth factor (EGF)-binding protein, the gamma-subunit of nerve growth factor, and trypsin. The properties of PN-II indicate that it has a role in the regulation of certain proteases in the extracellular environment. Here we describe more of the amino-acid sequence of PN-II and its identity to the deduced sequence of the amyloid beta-protein precursor (APP). Amyloid beta-protein is present in neuritic plaques and cerebrovascular deposits in individuals with Alzheimer's disease and Down's syndrome. A monoclonal antibody against PN-II (designated mAbP2-1) recognized PN-II in immunoblots of serum-free culture medium from human glioblastoma cells and neuroblastoma cells, as well as in homogenates of normal and Alzheimer's disease brains. In addition, mAbP2-1 stained neuritic plaques in Alzheimer's disease brain. PN-II was a potent inhibitor of chymotrypsin with an inhibition constant Ki of 6 x 10(-10)M. Together, these data demonstrate that PN-II and APP are probably the same protein. The regulation of extracellular proteolysis by PN-II and the deposition of at least parts of the molecule in senile plaques is consistent with previous reports that implicate altered proteolysis in the pathogenesis of Alzheimer's disease.
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PMID:Protease nexin-II, a potent antichymotrypsin, shows identity to amyloid beta-protein precursor. 250 28

Binding of type C neurotoxin (C1 toxin) from Clostridium botulinum (strain Stockholm) to neuroblastoma cell lines was studied by using biotinylated anti-toxin antibody and avidin-biotinylated peroxidase complex. The neurotoxin bound with high efficiency to mouse neuroblastoma (NS-20Y and NIE-115) cells and to hybridomas of rat glioblastoma and mouse neuroblastoma (NG108-C15) cells. The toxin bound little to human neuroblastoma, rat astrocytoma, and nonneural cell lines. Binding of the neurotoxin to NG108-C15 cells was inhibited by gangliosides (GT1b and GM1) and by monoclonal antibodies (CA-12 and C-9), although inhibition was not complete. Sequential preincubation of C1 toxin with GT1b and CA-12 caused complete inhibition. A Scatchard plot of binding of 125I-labeled C1 toxin to NG108-C15 cells showed a hyperbolic curve. Monoclonal antibody CA-12 but not C-9 neutralized the lethal activity of the toxin toward mice. Only C-9 clearly inhibited toxin binding to GT1b. These results suggest that NG108-C15 cells have at least two kinds of receptors for C1 toxin. From the results of binding tests with neuraminidase-, pronase-, and trypsin-treated NG108-C15 cells, the chemical nature of the high-affinity site was presumed to be a glycoprotein containing sialic acid. GT1b may have an important role in low-affinity sites.
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PMID:Binding of Clostridium botulinum type C neurotoxin to different neuroblastoma cell lines. 253 34

The cytosol of a human glioblastoma cell line (KNS-42) stimulated the growth of both bovine aortic endothelial cells and smooth muscle cells in a dose-dependent manner. The endothelial cell growth activity eluted at an apparent molecular weight of about 30,000 on a Sephadex G-100 column and bound to a heparin-Sepharose column with high affinity to elute at 1.3-1.7 M NaCl. The growth activity was destroyed by heating at 56 degrees C for 30 min, but not by exposure to trypsin, deoxyribonuclease or ribonuclease at 37 degrees C for 30 min. As this factor stimulated the growth of vascular endothelial cells and smooth muscle cells, and vasoproliferative responses in chick embryo chorioallantoic membranes were apparent, this factor may possibly be related to tumor angiogenesis.
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PMID:Endothelial cell growth factor derived from a human glioblastoma cell line and possible association with tumor angiogenesis. 266 83

In the present study we have evaluated the effect of recombinant human fibroblast, IFN-beta ser, and immune, IFN-gamma, interferon, alone and in combination, on the proliferation of fifteen early passage human glioblastoma cell cultures. Explant cultures were established from glioblastoma tumor tissue obtained at the time of surgery. After sufficient outgrowth, cultures were dispersed with trypsin/versene and maintained as independent cell lines. IFN-beta ser induced a greater than or equal to 50% reduction in the 7 day growth of 6 of the 15 cultures. The majority of cultures, 9 of 15, displayed less than or equal to 50% growth suppression in comparison with control cultures after 7 days exposure to 2000 Units/ml of IFN-beta ser. When treated with 2000 Units/ml of IFN-gamma, only 1 of the 15 glioblastoma cultures exhibited a greater than or equal to 50% reduction in growth. In contrast, when treated with the combination of IFN-beta ser plus IFN-gamma, 1000 Units/ml of each interferon preparation, 12 of 15 cultures were inhibited by greater than or equal to 50% after 7 days growth. The combination of interferons was effective in suppressing glioblastoma growth both in cultures displaying relative sensitivity and those exhibiting innate resistance to either or both types of interferon when employed alone. One glioblastoma culture, G-7, was studied through 45 passages and displayed the same sensitivity at different passages to growth inhibition when exposed to IFN-beta ser, IFN-gamma or both interferons. Based on previous clinical studies indicating that IFN-beta or IFN-gamma when administered alone to patients do not generally alter the clinical progression of malignant gliomas, the present results suggest that the combination of IFN-beta plus IFN-gamma may prove more effective than either agent alone in the clinical treatment of patients with glioblastoma multiforme.
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PMID:Enhanced in vitro growth suppression of human glioblastoma cultures treated with the combination of recombinant fibroblast and immune interferons. 283 97

Alzheimer's disease is characterized by cerebral deposits of amyloid beta-protein (AP) as senile plaque core and vascular amyloid, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain. From a cDNA library of a human glioblastoma cell line, we have isolated a cDNA identical to that previously reported, together with a new cDNA which contains a 225-nucleotide insert. The sequence of the 56 amino acids at the N-terminal of the protein deduced from this insert is highly homologous to the basic trypsin inhibitor family, and the lysate from COS-1 cells transfected with the longer APP cDNA showed an increased inhibition of trypsin activity. Partial sequencing of the genomic DNA encoding APP showed that the 225 nucleotides are located in two exons. At least three messenger RNA species, apparently transcribed from a single APP gene by alternative splicing, were found in human brain. We suggest that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism.
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PMID:Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. 289 91

Methods are described to study cell surface and cytoplasmic antigens of cultured human glioma, fetal brain cells and fibroblasts using flow cytometry. This required harvesting the cultured cells with Versene or mild trypsin treatment and fixation in 4% paraformaldehyde prior to staining for glial fibrillary acidic protein (GFAP) and fibronectin using indirect immunofluorescence. At passage 10, 38% of fetal brain cells [CHII] were GFAP-positive but at passage 14 only 3.5% expressed GFAP. Two glioblastomas and an anaplastic astrocytoma had 38.8%, 6.7% and 81.3% GFAP-positive cells, respectively. Of the 10(4) cells studied, 91.6%, 79.1% and 40.8% were fibronectin-positive for glioblastoma multiforme [12-18], oligodendroglioma [12-10] and fetal brain [CHII] cells, respectively. Two fibroblast lines had 33.5% and 43.1% of the cells expressing fibronectin. The validity of these results was confirmed by staining for GFAP and fibronectin using peroxidase-antiperoxidase and immunofluorescence microscopy. Using low angle forward light scatter to estimate cell size and gating techniques it was found that GFAP-positive CHII and anaplastic astrocytoma cells were generally larger than GFAP-negative cells of the same type. No correlation between cell size and fibronectin expression was found for glioblastoma [12-18] cells. These results demonstrate the validity of the described methods and illustrate some specific applications and the potential value of flow cytometry to neurooncology.
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PMID:Application of flow cytometry to analyses of cultured human glioma and fetal brain cells. 388 48

The nature of the refractoriness of C6 glioblastoma cells to herpes simplex virus type I (HSV-I) infection has been studied. The cells were restricted in susceptibility to HSV-I since only a small proportion of the cells could be infected by HSV-I and the virus yield per cell was low. The susceptibility to infection was increased by treating the cells with trypsin-EDTA prior to infection. The cells so treated recovered resistance to the virus when incubated at 37 degrees C, their resistance being restored to the initial level in 2 days. This restoration was inhibited by addition of cycloheximide or puromycin. Trypsin-EDTA treatment of C6 cells increased the efficiency of adsorption of HSV-I and the formation of stable cell-virus complexes from which the virus could not be dissociated by heparin.
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PMID:Stimulation of herpes simplex type I infection of C6 cells by trypsin-EDTA. 624 84

Accumulating evidence suggests that an inhibitory influence of the environment on growth cones plays a crucial role in development and regeneration of neuronal projections. Oligodendrocyte-associated neurite growth inhibiting substance is one of the most extensively studied molecules. Molecular biological studies, however, remain slow in progress. Although finding clonal cells that express such factors would facilitate the analysis of inhibitory influences on neurite growth, few cell lines have been reported to express neurite growth inhibitor. We therefore investigated the possibility of a clonal glial cell line to differentiate and express inhibitory or non-permissive features for neurite outgrowth in culture. We chose the C6 glioblastoma cell line and examined neurite extension from chick dorsal root ganglion (DRG) explants. Neurites from embryonic day 9 DRG extensively grew on C6 cells that were cultured at low cell density, while they failed to grow on C6 cells cultured at high density, even in the presence of nerve growth factor in high concentrations. Membrane extract from high density C6 cells, when used as culture substratum, was less permissive for neurite outgrowth compared to extract from low density cells. Treatment of the membrane extract derived from high density C6 cells with trypsin made it less non-permissive for neurite growth. These results suggest that C6 cells are induced to express a non-permissive property for neurite outgrowth by culturing them at high density.
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PMID:Low density, but not high density, C6 glioma cells support dorsal root ganglion and sympathetic ganglion neurite growth. 798 77

C6 rat glioblastoma cells are able to attach to and to spread on culture dishes which are coated with purified central nervous system myelin, in contrast to normal astrocytes, fibroblasts or neurons which adhere poorly and are unable to spread on this substrate. The metalloprotease blockers o-phenanthroline and a newly developed oligopeptide could specifically inhibit C6 cell spreading on central nervous system myelin, suggesting a crucial role for a metalloprotease. Here we characterize this metalloproteolytic activity of C6 cells using a peptide degradation assay with the iodinated tetrapeptide carbobenzoxy-Phe-Ala-Phe-125I-Tyr-amide as a substrate. Purified, salt-washed C6 plasma membranes cleaved the peptide between alanine and phenylalanine, an effect which is strongly inhibited by o-phenanthroline, but not by thiol-blocking agents or aspartic and serine protease inhibitors. The metalloendoprotease is highly sensitive to phosphoramidon but insensitive to thiorphan. The enzyme is tightly bound to the plasma membrane but not G protein-phosphatidylinositol linked. It can be solubilized in part by the detergents 3-(3-cholamidopropyldimethylamino)-1-propanesulfonate or Triton X-114. Gel filtration chromatography using the Triton X-114-solubilized proteins or the proteins removed by a short trypsin treatment revealed a molecular weight range for the C6 enzyme of 60,000-100,000. Polymerase chain reaction with primers corresponding to endopeptidase 24.11 or to the highly conserved motif of the "astacin family" showed that both enzymes were not detectable in the C6 glioblastoma cells.
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PMID:Characterization of a membrane-bound metalloendoprotease of rat C6 glioblastoma cells. 803 33


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