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)

Direct measurement of protein kinase C (PKC) activity in vitro revealed a significant increase in the activity of the enzyme in all human malignant glioma lines examined and the rat C6 tumor in comparison with control nonneoplastic astrocyte and mixed glial cultures. The total and particulate PKC activity in these cell types correlated strongly [r = 0.98 (P less than 0.001) and 0.94 (P = 0.002), respectively] with the maximal growth rates as measured by 3H-thymidine incorporation in each of the samples. An alteration in the growth rate of an individual glioma line (A172) by varying the serum concentration in the growth medium produced comparative changes in the measured PKC activity. The addition of the phorbol ester phorbol-12-myristate-13-acetate to this tumor line under high serum conditions produced down-regulation of the enzyme, which was accompanied by a corresponding reduction in thymidine incorporation. The administration of the PKC inhibitor staurosporine produced a dose-related decrease in the basal proliferation rate of glioma lines A172 and C6, as measured by 3H-thymidine uptake and confirmed by flow cytometry, indicating that the high intrinsic PKC activity is amenable to pharmacological manipulation. Cytofluorometric deoxyribonucleic acid cell cycle analysis of the tumors treated with PKC modulators demonstrated that reduced proliferation rates were caused by an inhibition of entrance into the deoxyribonucleic acid synthesis (S) phase (decrease in proliferative index), supporting the evidence that these modulators are not slowing the tumor growth in a nonspecific cytotoxic manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurosurgery 1991 Dec
PMID:Enhanced protein kinase C activity correlates with the growth rate of malignant gliomas in vitro. 175 1

Carboxypeptidase E (CPE) catalyses the removal of C-terminal basic amino acids and is implicated in the processing of peptides and hormones in secretory vesicles. The enzyme has been isolated in multiple forms from both soluble and membrane-bound compartments, and has been demonstrated to be co-secreted with peptides from pancreatic and adrenal cells. To address the question regarding the origin of the multiple forms of the enzyme, we have transfected a construct containing the cDNA for human CPE under the control of the murine-sarcoma-virus enhancer and metallothionein promoter into the C6 rat glioma cell line, which itself has extremely low levels of CPE expression. Within transfectants, multiple forms of the enzyme have been detected by Western blotting, and their sizes are comparable with that in pituitary. Fractionation of the intracellular forms of CPE with Triton X-114 at various pH values indicates that the membrane-bound, but not the soluble, form is amphipathic; this difference probably arises from post-translational modification of the enzyme. Interestingly, the secreted enzyme is found to have the amphipathic characteristics of the membrane-bound form. By modification of the cDNA sequence, enzyme lacking N-terminal and C-terminal domains have been expressed: deletion of the 'pro' region of CPE, leading to loss of the signal cleavage site, gives a more hydrophobic but active enzyme which is not efficiently secreted from the cell; deletion of a C-terminal region gives a secreted form of the enzyme which no longer exhibits amphipathic behaviour. Our data indicate that a single mRNA species can give rise to the multiple forms of CPE enzyme that have been identified and that the C6 cells are able to carry out the intracellular processing events to generate these forms.
Biochem J 1991 Dec 15
PMID:Processing and secretion of human carboxypeptidase E by C6 glioma cells. 176 34

In a neuronal cell line (108CC15, NG108-15) the levels of inositol 1,4,5-trisphosphate (InsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4), as measured by receptor binding assays, rise transiently after stimulation with bradykinin (EC50 approx. 150 nM). Maximal InsP3 level of 354 pmol/mg protein (15-fold basal level) is obtained at 10-15 s after addition of bradykinin, the InsP4 level rises maximally to 78 pmol/mg protein (14-fold basal level) at 20-30 s. In a rat glioma cell line, bradykinin (2 microM) causes a fast 6-fold increase in InsP3 and InsP4 levels. In the neuronal cells the bradykinin-dependent rise of the inositolphosphate levels is diminished with reduced extracellular Ca2+ concentration. However, depletion of internal Ca2+ stores does not affect the bradykinin-induced rise in InsP3 and InsP4 levels. Homologous desensitization to bradykinin occurs in the signal transduction pathway already at the production of inositolphosphates, since after a 2 min stimulation with bradykinin the rise in cellular masses of InsP3 and InsP4, inducible by a following second bradykinin stimulus, is substantially reduced.
Biochem Biophys Res Commun 1991 Dec 31
PMID:Mass measurements of inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in a neuronal cell line stimulated with bradykinin: inositolphosphate response shows desensitization. 176 9

An optic chiasm glioma may cause loss of vision, endocrine disturbances, hydrocephalus and cerebral ischemia due to its proximity to the pituitary, hypothalamus, III ventricle and internal carotids. A 3-month-old infant with optic chiasm glioma developed hypopituitarism and inappropriate secretion of antidiuretic hormone with plasma hypo-osmolality. The cerebrospinal fluid (CSF) protein concentration was markedly elevated. The impairment of fluid absorption via arachnoid villi and peritoneum by the high protein content, and reversed osmotic gradient between protein-rich CSF and hypo-osmolar plasma may have contributed to both nonobstructive hydrocephalus and recurrent ascites following ventriculoperitoneal shunting. Cerebral ischemia from carotid compression may have led to cerebral atrophy.
Childs Nerv Syst 1991 Dec
PMID:Optic chiasm glioma associated with inappropriate secretion of antidiuretic hormone, cerebral ischemia, nonobstructive hydrocephalus and chronic ascites following ventriculoperitoneal shunting. 179 May 31

Expression of the Cytokine genes in human astroglial cell lineage was studied. Primers for 5 different human cytokine, TNF-alpha, -beta, IFN-gamma, G-CSF and GM-CSF, were used to analyze messenger RNA transcripts in 5 cultured human astrocytoma, one neuroblastoma cell lines and fresh brain specimens by polymerase chain reaction (PCR). Three out of 5 unstimulated astrocytomas, U138, U251, U373 MG and IMR32 neuroblastoma cells expressed TNF-alpha genes. After stimulation with IL-1 beta (1000 U/ml) all these cell lines expressed TNF-alpha genes. TNF-beta genes could not be detected in these cell lines even in the presence of any cytokine stimuli. We were able to detect expression of IFN-gamma genes within 2 astrocytoma cell lines (U87MG and A172), which interestingly did not show TNF-alpha activity. Constitutive expression of mRNA transcripts of GM -CSF could be detected in all astrocytoma and two out of 5 unstimulated astrocytomas, U87MG and U138MG, expressed G-CSF genes. After stimulation with IL-1 beta, all cell lines expressed G-CSF. In addition, we also examined gene expression of these cytokines within 4 human malignant astrocytoma specimens, 2 peritumoral brain and 2 autopsied normal brains. The results show that tumor and surrounding lesions express TNF-alpha (4 of 6), TNF-beta (1/6), IFN-gamma (4/6), G-CSF (3/6) and GM-CSF (5/6) but not normal brains. One tumor specimen also expresses TNF-beta as well as TNF-alpha genes (case 2). From these results, it is suspected that astroglial cell-derived cytokines may participate in local immune reactions accompanying glioma in the brain.
No To Shinkei 1991 Dec
PMID:[Expression of cytokine genes within astrocytoma cell lines and brain specimens]. 179 21

During neurulation, neural crest cells migrate to many regions of the body to give rise to a wide variety of cell types. Many premigratory neural crest cells are pluripotent, their potency for differentiation being gradually restricted as they migrate along definite pathways and interact with factors present in the microenvironment. Effects of growth factors on these cells have been discussed in the present review. Mediation of growth factors in differentiation varies with the cell type. Growth factors exert a direct influence on the differentiation of neural and other related neural crest-derived tissues such as endocrinal tissues but evidence for such influences on neural crest-derived mesenchymal tissues is limited. For example, NGF, BDNF, and other factors present in neural tube extracts and glioma cell conditioned medium are essential for the differentiation of sensory neurons. Similarly, NGF, insulin, IGFs and possibly other undescribed factors are necessary for the differentiation of sympathetic neurons. IGFs also enhance the proliferation of mesenchymal derivatives of both neural crest and mesodermal origin. Glucocorticoid-mediated differentiation of neural crest-derived chromaffin endocrine cells that are ontogenetically closely related to sympathetic neurons can be inhibited by NGF, and chromaffin cells can be induced to express the neuronal phenotype by NGF. Some growth factors, such as NGF, act on neural crest- and not on placodally-derived neurons, whether the former are sensory or sympathetic. Placodal sensory neurons possess NGF receptors, but only display a limited response to NGF, perhaps because of low affinity of the receptors. Other growth factors, such as BDNF, selectively act upon sensory neurons, whether neural crest- or placodally-derived. Although extracellular matrix products play a role in initiating the differentiative process, signals from growth factors are necessary for the establishment of the functionally competent phenotype of neural crest-derived neurons, a situation that does not apply for neural crest-derived mesenchymal cells. It is interactions with ECM components deposited by epithelia that govern the differentiation of mesenchymal derivatives. Growth factors do effect proliferation of mesenchymal derivatives and inhibit mesenchymal differentiation. Although direct involvement of single growth factors in transformation o f one mesenchymal phenotype to another has not been reported so far, their localization at sites of epithelial-mesenchymal interactions in palate teeth and mandible, and the ability of excess growth factors to interrupt normal development is suggestive of their possible involvement. One group of growth factors, BMPs, can influence differentiation of cartilage, including those of neural crest origin.(ABSTRACT TRUNCATED AT 400 WORDS)
Int J Dev Biol 1991 Dec
PMID:Effects of growth factors on the differentiation of neural crest cells and neural crest cell-derivatives. 180 64

We have investigated the regulation of phospholipase D (PLD) activity by guanine nucleotides and Ca2+ in cells of the NG108-15 neuroblastoma X glioma line that were permeabilized with digitonin. The nonhydrolyzable GTP analogue guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) caused a nearly sixfold increase (EC50 = 3 microM) in production of [3H]phosphatidylethanol (specific product of the PLD transphosphatidylation reaction). Other GTP analogues were less effective than GTP gamma S, and guanosine-5'-O-(2-thiodiphosphate) inhibited PLD activation by GTP gamma S. Both basal and GTP gamma S-stimulated PLD activities were potentiated by MgATP and Mg2+. Adenosine-5'-O-(3-thiotriphosphate) and ADP also potentiated the effect of GTP gamma S, but non-phosphorylating analogues of ATP had no such effect. The activation of PLD by GTP gamma S did not require Ca2+ and was independent of free Ca2+ ions up to a concentration of 100 nM (resting intracellular concentration). Higher Ca2+ concentrations (greater than or equal to 1 microM) completely inhibited PLD activation by GTP gamma S. It is concluded that elevated intracellular Ca2+ concentrations may negatively modulate PLD activation by a guanine nucleotide-binding protein, thus affecting receptor-PLD coupling in neural-derived cells.
Cell Regul 1991 Dec
PMID:Ca2+ inhibits guanine nucleotide-activated phospholipase D in neural-derived NG108-15 cells. 180 22

The subcellular distribution of the alpha subunit(s) of Gi has an obvious bearing on the ability of this protein to interact with receptors and targets and on its potential to serve in still unexplored capacities. In this study, we have examined the distribution of Gi alpha by means of light and electron microscopy. The cells employed were mouse 3T3 fibroblasts, normal rat kidney fibroblasts, rat C6 glioma cells, human umbilical vein endothelial cells, and human 293 kidney fibroblasts. By indirect immunofluorescence, two patterns of Gi alpha were evident. The more prominent was that associated with phase-dense, cytoplasmic structures exhibiting a tubule-like morphology. A similar distribution was noted for mitochondria, indicating attachment to a subset of microtubules. The second pattern appeared as a diffuse, particulate fluorescence associated with the plasma membrane. By immunogold labeling and electron microscopy, two populations of Gi alpha were again evident. In this instance, labeling of the plasma membrane was the more prominent. Gold particles were most often evenly distributed along the plasma membrane and were concentrated along microspikes. The second, less abundant population of Gi alpha represented the subunit (or fragments) within lysosomes. Specificity in immunolabeling was confirmed in all instances by immunotransfer blotting, the use of antibodies differing in specificities for epitopes within Gi alpha, the absence of labeling with preimmune sera, and the decrease in labeling after preincubation of antisera with appropriate peptides. These results support the proposal that several populations of Gi alpha exist: those evident within the cytoplasm by immunofluorescence, those present at the plasma membrane, and those evident within lysosomes by immunogold labeling.
Cell Regul 1991 Dec
PMID:Subcellular distribution of the alpha subunit(s) of Gi: visualization by immunofluorescent and immunogold labeling. 180 26

A transient alkalosis of similar magnitude to that observed in vivo has been observed using 31P NMR and 2-deoxy-D-glucose-6-phosphate as a pH marker in a human glioma cell line, SKI-1, with demonstrated sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea. At an effective dose of 5 +/- 1 x 10 micrograms/ml, an increase of 0.13 +/- 0.05 pH units was observed within 4 +/- 1 x 10 min of introducing the drug into the perfusion chamber. Although the in vitro response is of a time course much faster than that in vivo, these results suggest that this immediate pH change could be an indicator of the cytotoxic action of the drug.
Magn Reson Med 1991 Dec
PMID:Alkalosis monitored by 31P NMR in a human glioma cell line exposed to the anti-tumor drug 1,3-bis(2-chloroethyl)-1-nitrosourea. 181 75

Boron analogues of piperidine, piperazine, morpholine, and imidazole proved to be cytotoxic against the growth of murine and human tissue culture cells. Significant activity was demonstrated for single-cell suspensions of L1210 lymphoid leukemia, Tmolt3 lymphoblastic leukemia, and HeLa-S3 cervical carcinoma. Trimethylamine-imidazole carbonyldihydroborane 17 demonstrated activity against solid tumor growth of human colorectal adenocarcinoma, KB nasopharynx, and osteosarcoma. In addition, 4-methylpiperidine-carbomethoxyborane 12, 2-methylimidazole-3-cyanoborane 16, and 1-methylimidazole-3-(N-ethylcarbamoyl)borane 19 were active against the KB nasopharynx growth. Piperidine-cyanoborane 2, piperidine-carboxyborane 4, and 1-methylimidazole-3-(N-ethylcarbamoyl)borane 19 were effective in reducing the growth of osteosarcoma cells. The imidazole derivatives 13-19, as well as 4-methylpiperidine-carboxyborane 11 and carbomethoxyborane 12, demonstrated good activity against lung bronchogenic and glioma growth. In the in vivo studies, N-methylmorpholine-carboxyborane 7,4-phenylpiperidine-carboxyborane 9, 4-phenylpiperidine-carbomethoxyborane 10, 4-methylpiperidine-carboxyborane 11, imidazole cyanoborane 14, and 1-methylimidazole-3-carbomethoxyborane 18 demonstrated the best activity against Lewis Lung growth and P388 lymphocytic leukemia growth in mice. Mode of action studies in L1210 leukemia cells demonstrated that piperidine-carboxyborane 4 and N-methylmorpholine-carboxyborane 7 inhibited DNA synthesis, purine synthesis at PRPP amido transferase and IMP dehydrogenase sites, and thymidine kinase and thymidine diphosphate kinase activities, while lowering d(NTP) pool levels. Also, DNA strand scission was evident after incubation with these drugs.
J Pharm Sci 1991 Dec
PMID:Synthesis and antineoplastic activity of some cyano-, carboxy-, carbomethoxy-, and carbamoylborane adducts of heterocyclic amines. 181 71


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