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)

A comparative immunocytochemical study was carried out on intracerebral and extracranial gliomas of the rat produced by intracerebral injection of low (10th) and high (40th) in vitro passages of neoplastic glial cells. The cells injected were a neoplastic astrocytic clone-A15 A5-derived from a mixed glioma induced transplacentally by N-ethyl-N-nitrosourea (ENU) in a BD-IX rat. An inverse relationship was seen between the expression of the astrocytic markers glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) at low and high passage: GFAP decreased with increasing passage while GS increased. The distribution of vimentin, the major cytoskeletal component of immature glia, was constant, irrespective of passage--a feature consistent with previous in vitro findings. The expression of laminin by both reactive and neoplastic astrocytes increased with increasing passage, while high magnification examination revealed the presence of the glycoprotein fibronectin on the cell-surfaces of A15 A5-derived tumour cells. Both neoplastic and reactive astrocytes expressed S-100 protein with a higher proportion of positive cells in extracranial tumours. Occasional cells, probably actively phagocytizing populations of reactive astrocytes and macrophages, were positive for alpha-1-antitrypsin. None of the neoplastic cells expressed the oligodendrocyte marker carbonic anhydrase II. This immunocytochemical study supports previous morphological findings in differences in differentiation between the cells of tumours produced by high and low passage cells.
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PMID:Immunocytochemical characterization of the A15 A5 transplantable brain tumour model in vivo. 287 14

The first enantiomeric pair of irreversible opioid ligands [(+)- and (-)-4] were synthesized in greater than 99.6% optical purity as determined by HPLC analysis of diastereoisomeric derivatives of the intermediate 3-methyl-N-phenyl-4-piperidinamine enantiomers. Single-crystal X-ray analysis of the (R,R)-L-(+)-tartaric acid salt of (-)-9 revealed the absolute configuration to be 3S,4R. The absolute configuration of (-)-3 [cis-(-)-3-methylfentanyl] and (-)-4 derived from (-)-9 is thus 3S,4R and that of (+)-3 and (+)-4 is 3R,4S. The (+) enantiomer of 4 (SUPERFIT) was shown to be highly potent and specific for acylation of delta opioid receptors (to the exclusion of mu) in rat brain membranes like its achiral prototype FIT and was about 10 times as potent as the latter in this assay. The (+)-4 was about 5 times as potent as FIT in acylation of delta receptors in NG108-15 neuroblastoma X glioma hybrid cells and about 50 times as potent as its enantiomer. Both FIT and (+)-4 behaved as partial agonists in inhibition of delta receptor coupled adenylate cyclase in NG108-15 membranes and (+)-4 was 5-10 times more potent than FIT and about 100 times more potent than its enantiomer in this assay. Dibromination of amine 12, catalytic exchange of bromine with tritium gas, and reaction of the labeled amine with thiophosgene afforded [3H]-(+)-4 with a specific activity of 13 Ci/mmol. Previous experiments indicated (+)-4 acylates the same 58 000-dalton glycoprotein previously shown to be acylated by FIT but with less nonspecific labeling. In view of the high potency and specificity of (+)-4 and the availability of its enantiomer, it seems likely that these compounds will prove to be valuable tools for study of the opioid receptor complex.
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PMID:Probes for narcotic receptor mediated phenomena. 12. cis-(+)-3-Methylfentanyl isothiocyanate, a potent site-directed acylating agent for delta opioid receptors. Synthesis, absolute configuration, and receptor enantioselectivity. 301 85

The bombesin receptor present on the surface of murine and human cells was identified using 125I-labeled gastrin-releasing peptide as a probe, the cross-linking agent disuccinimidyl suberate, and sodium dodecyl sulfate gels. A clone of NIH-3T3 cells which possesses approximately 80,000 bombesin receptors/cell with a single binding constant of approximately 1.9 X 10(-9) M was used in these studies. In addition, we used Swiss 3T3 cells and a human glioma cell line which possesses approximately 100,000 and approximately 55,000 bombesin receptors/cell, respectively. Under conditions found optimal for binding, it is demonstrated that 125I-labeled gastrin-releasing peptide can be cross-linked specifically to a glycoprotein of apparent molecular mass of 65,000 daltons on the surface of the NIH-3T3 cells. Similar results were obtained when the cross-linked product was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing or non-reducing conditions. Moreover, the cross-linking reaction is specific and saturable and the 65,000-dalton polypeptide is not observed when the cross-linking experiments were performed with a NIH-3T3 cell line which is devoid of bombesin receptors. Interestingly, glycoproteins with apparent molecular weights of 75,000 were labeled specifically by 125I-labeled gastrin-releasing peptide when similar experiments were performed with Swiss 3T3 cells and with human glioma cell line GM-340. These different molecular weights may indicate differential glycosylation as treatment with the enzyme N-glycanase reduced the apparent molecular weight of the cross-linked polypeptide to 45,000. On the basis of these results it is concluded that the cross-linked polypeptides represent the bombesin receptor or the ligand-binding subunit of a putative larger bombesin receptor expressed on the surface of these cells.
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PMID:Identification of the bombesin receptor on murine and human cells by cross-linking experiments. 303 12

Cathepsin D was assessed in C6 glioma cells grown in medium with an intermediate- or low-percent composition of serum. The amount, form, and subcellular location of cathepsin D differed after treatment with cyanate or monensin in cells grown in a low-serum, growth-factor-supplemented medium. Immunoblotting showed that cathepsin D in the lysosomal fraction of the C6 cell line had a molecular weight (Mr) of 42 kD, whereas that in the microsomal fraction had Mr's of 42, 47, and 78 kD. After treatment for 1 to 16 hr with 4 mmol/L cyanate and subcellular fractionation, the molecular weight of lysosomal cathepsin D was the same in treated and untreated cells, but more enzyme was found in lysosomes of treated cells at 8 and 16 hr. In the microsomal fraction, the amounts of both the 42 and 47 kD forms were increased after 1 to 16 hr of treatment. When exposed to 20 mmol/L cyanate, C6 cells remained viable, but compared with untreated cells, they showed 25% less lysosomal cathepsin D, with increased amounts found in the microsomal fraction. The 78 kD protein detected by immunoblotting was present in both the lysosomal and microsomal fractions but was predominant in the latter. The apparent molecular weight of this protein was the same after cyanate but differed with monensin, where Mr's of 39, 42, and 73 kD were found. Monensin-treated cells had less lysosomal cathepsin D and relatively more microsomal enzyme. The differing molecular weights of cathepsin D from cyanate- and monensin-treated cells suggest that their inhibitions occur at different processing loci in distal elements of the Golgi stacks. The differences in the pI of cathepsin D and the number of its forms from cyanate- and monensin-treated cells are also consistent with interference in the late stages of glycoprotein maturation. In this paper we show that the amount, molecular form, and consequent intracellular location of cathepsin D in cells of the C6 line can be affected by agents that selectively disrupt stages in Golgi-related protein modification and transport.
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PMID:Alterations of the posttranslational processing of a lysosomal enzyme in C6 glioma cells. 304 14

This article reviews the recent studies reporting the applications of immunocytochemistry to diagnostic problems in clinical cytology. A series of studies with monoclonal antibody (MAb) B72.3 is discussed in detail. MAb B72.3, reactive with a high molecular weight, glycoprotein, tumor-associated antigen, designated TAG-72, has been shown previously to be reactive with formalin-fixed, paraffin-embedded tissue sections of adenocarcinomas of the ovary, colon, and breast, but not a variety of normal adult tissues. It has demonstrated utility as an immunocytochemical adjunct to diagnose carcinoma in cell block and cytocentrifuge preparations of human serous effusions, with selective reactivity for tumor cells (particularly adenocarcinoma) over reactive mesothelium. Using the avidin-biotin complex (ABC) method of immunoperoxidase staining and formalin-fixed, paraffin-embedded cell suspensions, MAb B72.3 detected tumor cells in effusions from the majority of patients with adenocarcinoma of the breast. No reactivity was demonstrated in any cell type in benign effusions. In contrast, MAb B72.3 showed no reactivity to leukemic or lymphomatous effusions, or to mesothelial cells from malignant effusions. MAb B72.3 also detected tumor cells in effusion specimens from most of the patients with "non-small cell" carcinoma of the lung and with carcinoma of the ovary. MAb B72.3 was also used with fine-needle aspiration biopsies (FNABs) and corresponding surgically excised tumors to determine cellular reactivity. Positive staining with MAb B72.3 was observed in needle aspirates of the great majority of "non-small cell" carcinomas of the lung, adenocarcinomas of the breast, adenocarcinomas of the colon, and carcinomas from other body sites. In contrast, small cell carcinomas of the lung, malignant melanomas, lymphomas, sarcomas, and glial tumors stained negatively with the antibody. Most benign lesions from the breast, lung, pancreas, parotid, and thyroid also showed no staining. In many patients, tumor-bearing tissue had also been resected and was available for comparative examination with MAb B723. In more than 90% of these patients, the staining patterns of tumor cells in the aspirates were found to be predictive of the patterns of antibody reactivity in the comparable surgically resected tumors. From these studies it is concluded that MAb B72.3 defines a tumor-associated antigen that is expressed in neoplastic cells versus benign cells, is most selectively expressed in carcinomas, and may be used as a novel adjunct for the diagnosis of neoplasms in effusions and in FNABs.
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PMID:Applications of immunocytochemistry to clinical cytology. 332 72

Studies on the presence of the brain-specific alpha 2-glycoprotein in cultures of newborn rat brain cells revealed that a population of glial precursor cells expressed this antigen at an early stage of development. This cell population consisted of small, phase-dark cells that proliferated in culture and occupied the surface of a layer of flat epithelial-like astrocytes. The latter cell type did not react with the antibodies. The number of alpha 2-glycoprotein positive cells gradually decreased from a high concentration of 88% of the total overlying cells at 6 days of culture to 44% at 23 days. The morphological heterogeneity of the overlying cells was noticeable after 10 days in culture as clusters of cells with elaborate processes started to develop. alpha 2-Glycoprotein was found to be concentrated in these structures. A glioma cell line (C-6 glia) which represents a unique in vitro model for the glial progenitor cells, was also found to express this glycoprotein antigen.
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PMID:Expression of alpha 2-glycoprotein by glial precursor cells: an immunocytochemical study with glial cultures. 353 Mar 81

The distribution of type VI collagen was examined immunohistochemically in normal tissues and in 24 human gliomas and six medulloblastomas. Its localization in the neoplasms was compared with that of fibronectin and glioma-mesenchymal extracellular matrix (GMEM) glycoprotein. In normal non-neural tissues type VI collagen was demonstrated in the interstitial connective tissue and in some basement membranes. In normal brain it was localized to the vasculature, leptomeninges, and pial-glial membrane. In neoplasms type VI collagen and fibronectin codistributed in the vasculature and stromal connective tissue. The GMEM glycoprotein, as identified by monoclonal antibody (MAb) 81C6, and a related glioma-mesenchymal matrix antigen identified by MAb 2A6, were expressed not only in the tumor vasculature and connective tissue, but also within the tumor parenchyma in association with glioma cells. The staining intensity was variable in 20 malignant gliomas and weak to absent in two pilocytic astrocytomas and six medulloblastomas. An oligodendroglioma and ependymoma both expressed the 2A6 epitope, but staining with MAb 81C6 was weak to absent. The antigens identified by MAb 81C6 and MAb 2A6 represent the only recognized extracellular matrix components, other than proteoglycans, that are associated with glioma cells in vivo. As prominent constituents of the pericellular matrix, they may be involved in recognized matrix functions such as the modulation of cell adhesion and migration.
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PMID:Distribution of type VI collagen in human gliomas: comparison with fibronectin and glioma-mesenchymal matrix glycoprotein. 365 35

Current diagnostic and therapeutic modalities for malignant human gliomas are largely nonspecific. The development of monoclonal antibodies (MA's) with their high degree of specificity may allow precise tumor imaging and selective administration of therapeutic agents. However, the ability of these antibodies to specifically localize tumor tissue in vivo remains speculative. This study compares the localization and imaging properties of two MA's: a specific human glioma-associated extracellular matrix glycoprotein MA, 81C6, and a nonspecific control MA, 45.6, against a human glioma cell line, D-54 MG, intracranially inoculated into athymic rats. Forty-one animals received MA's labeled with iodine-131 (131I) or 125I and underwent imaging with a gamma camera. The images were independently evaluated and compared to tissue radioactivity levels. Radiolabeled antiglioma MA 81C6 specifically localized in intracranial xenografts. The percent of injected dose per gram of tissue for tumor was 1.707 +/- 0.405/gm for 81C6 and 0.118 +/- 0.056/gm for 45.6. All other organs had equivalent levels of specific and nonspecific MA's. For brain, these were 0.004 +/- 0.002/gm and 0.005 +/- 0.005/gm, respectively, and for the other organs, the range was from 0.053 to 0.284/gm. Statistically, 45.6 achieved levels in tumor that were significantly higher than normal brain (p less than 0.05) but significantly less than that achieved with 81C6 (p less than 0.005). With 81C6, the degree of localization was high enough to allow imaging of intracranial tumors at sizes as small as 20 mg. Intracranial tumors were imaged with 45.6 only when they achieved sizes greater than 300 mg. In this imaging study, radiolabeled 81C6, a specific antiglioma MA, proved to be significantly better for imaging small and intermediate-sized tumors than the control MA's. Large tumors were visualized by both MA's, although higher quality scans were obtained earlier and more frequently with specific MA's than with nonspecific immunoglobulin G. These data suggest that specific MA's have a role to play in both the diagnosis and treatment of primary intracranial human tumors.
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PMID:In vivo imaging of intracranial human glioma xenografts comparing specific with nonspecific radiolabeled monoclonal antibodies. 394 36

In view of the hypothesis that a biochemical abnormality in the childhood forms of neuronal ceroid-lipofuscinosis may lie in the utilization of dolichols in glycoprotein synthesis, we analyzed the oligosaccharide structures of brain glycoproteins in infantile neuronal ceroid-lipofuscinosis (INCL). Lectin affinity chromatography of purified glycopeptides and of oligosaccharides prepared by hydrazinolysis showed an increase in high mannose-type glycopeptides and a decrease in tri- and tetra-antennary glycopeptides in INCL brain when compared with control brain. These changes were more pronounced in the storage cytosomes than in whole brain. Methylation analysis of the isolated glycopeptide fractions did not reveal differences in substitution patterns of the individual sugar residues between INCL and control brain. In INCL the core disaccharide of the O-glycosidically-linked oligosaccharides was sialylated to a higher degree than in control brain indicating that the structural changes were not confined only to N-glycosidically-linked carbohydrate chains. The observed structural changes in the carbohydrate chains of brain glycopeptides in INCL could be explained by a defect in the biosynthesis of glycoproteins. Alternatively, the changes may reflect the increased glial cell population in the degenerating brain. In fact, the elution profiles in lectin chromatography of oligosaccharides prepared from cultured rat glioma cells resembled those from INCL brain.
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PMID:Enrichment of high mannose-type glycans in nervous tissue glycoproteins in neuronal ceroid-lipofuscinosis. 395 Jun 50

The extracellular matrix is involved in many aspects of tumor cell biology, including tumor invasion and metastasis. 2A6 and 81C6 are murine monoclonal antibodies that identify glioma-mesenchymal extracellular matrix antigens. The 81C6 antigen is a high molecular weight glycoprotein composed of Mr 230,000 subunits. The expression of 2A6 antigen, 81C6 glycoprotein, fibronectin (FN), and laminin (LN) was examined immunohistochemically in ten malignant gliomas (MG) and four medulloblastomas (MBT). 2A6 and 81C6 were expressed in similar patterns by the neoplastic neuroepithelial cells in 9/10 MG and 1/4 MBT. The staining was typically diffuse and amorphous, without visualization of distinct cell bodies or processes. Less frequently, antigen was detected within tumor cell cytoplasm. In most tumors the staining was greatest in the perivascular regions. In two MG, 2A6 and 81C6 were expressed only by a subpopulation of neoplastic cells. Although intense staining was also associated with hyperplastic vascular and mesenchymal cells, many small and medium size blood vessels stained weakly or not at all. In contrast, FN and LN were expressed uniformly and intensely in the tumor vasculature, but were not expressed by neoplastic neuroepithelial cells. The 2A6 antigen and 81C6 glycoprotein are immunohistochemically distinct from FN and LN. These monoclonal antibody-defined antigens are heterogeneously expressed by neoplastic neuroepithelial cells and hyperplastic vascular-mesenchymal elements in MG and MBT. The 2A6 and 81C6 monoclonal antibodies will be useful reagents in the investigation of the extracellular matrix of malignant neuroepithelial neoplasms.
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PMID:Immunolocalization of monoclonal antibody-defined extracellular matrix antigens in human brain tumors. 403 75


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