Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a primary brain tumor of glial origin, we found overexpression of the alpha-platelet-derived growth factor (alpha-PDGF) receptor mRNA. Southern blot analysis of the gene revealed amplification of the rearranged alpha-PDGF receptor gene in the glioma. A cDNA coding for an aberrant transcript from the amplified receptor gene was obtained and characterized. Partial nucleotide sequence analysis of the cDNA revealed a deletion of 243 nucleotides coding for 81 amino acids in a portion of the immunoglobulin-like domains of the extracellular region of the receptor. cDNA polymerase chain reaction (PCR) of the total cellular RNA in the glioma indicated that more than 80% of the transcripts have a deletion of 243 nucleotides. Analysis of a PCR-amplified DNA fragment derived from the amplified alpha-PDGF receptor gene in the glioma revealed that an exon coding for the 81 amino acids was removed by a 2.1 kb gene deletion. We also found amplification of the alpha-PDGF receptor gene in macroscopically normal cortex adjacent to the glioma from the same patient. The amplified gene in the macroscopically normal cortex has no major gene deletion, suggesting that gene amplification is not sufficient for the development of malignant gliomas.
 ...
PMID:Amplification of alpha-platelet-derived growth factor receptor gene lacking an exon coding for a portion of the extracellular region in a primary brain tumor of glial origin. 131 66

The expression of platelet-derived growth factor (PDGF) and its receptors was analyzed in 14 gliomas of various degrees of malignancy and compared with three gliosis cases by in situ hybridization and immunohistochemistry techniques. Expression of both PDGF A- and B-chains was higher in glioblastomas than in astrocytomas. The PDGF A-chain mRNA was predominantly found in cell-rich areas in glioblastomas. The cognate PDGF-alpha receptor (PDGFR-alpha) mRNA was heterogeneously distributed in gliomas of all grades, and PDGFR-alpha expression was higher in gliomas than in gliosis. Within some glioblastomas probed with PDGFR-alpha complementary RNA, cells heavily loaded with grains were intermingled with others containing low or moderate signals. The heavily labeled cells were often found in the vicinity of proliferating capillaries. Immunostaining with an anti-PDGF antibody and an affinity-purified antiserum against the PDGFR-alpha showed strong staining of most tumor cells with both antibodies in glioblastoma. In addition, the PDGFR-alpha antibodies yielded a strong staining of scattered cells, and the anti-PDGF antibody yielded staining of a few cells within the astrocytoma. Furthermore, high levels of the PDGF-beta receptor (PDGFR-beta) and PDGF B-chain mRNA as well as the beta receptor protein were found in hyperplastic capillaries. These results suggest the presence of autocrine and paracrine loops in glioma, activating the PDGFR-alpha in glioma cells and the PDGFR-beta in endothelial cells.
 ...
PMID:Platelet-derived growth factor and its receptors in human glioma tissue: expression of messenger RNA and protein suggests the presence of autocrine and paracrine loops. 131 61

The establishment of a new glioma cell line, DBTRG-05MG, in a modified RPMI 1640 medium is described. The cells were derived from an adult female with glioblastoma multiforme who had been treated with local brain irradiation and multidrug chemotherapy; the tumor showed substantial change in histologic appearance compared to the original biopsy 13 mo. previously. The line has been successfully cryopreserved and passaged up to 20 times. The karyotype of the cells demonstrated it as a hypotetraploid line; the DNA index of 1.9 confirmed the karyotype analyses. By immunocytochemical analysis, the cell line reacted with polyclonal antibodies to vimentin, S100, and neuron specific enolase, reflecting its primitive neuroectodermal character. Positive immunostaining for epidermal growth factor receptor correlated with the excess of chromosome 7 seen in the karyotype. The cell line reacted negatively to antibodies against platelet-derived growth factor and its receptor, neuronal cell adhesion molecule, and glial fibrillary acidic protein. By flow cytometry, the cells were major histocompatibility class I antigen positive and class I antigen negative. Growth kinetic studies demonstrated an approximate population doubling time of 34 to 41 h and a colony forming efficiency of 71.4%. Western blot analysis showed the presence of low levels of normal-sized retinoblastoma protein. When compared to the patient's lymphocyte DNA, no loss of heterozygosity of the p53 tumor suppressor gene was observed in the DBTRG-05MG cell line DNA.
 ...
PMID:Characterization of a continuous human glioma cell line DBTRG-05MG: growth kinetics, karyotype, receptor expression, and tumor suppressor gene analyses. 133 Oct 21

The effects of platelet-derived growth factor (PDGF) on phospholipase D (PLD) activity and deoxyribonucleic acid (DNA) synthesis in rat C6 glioma cells have been investigated. Pretreatment of serum-starved C6 cells with PDGF results in enhanced choline production and the phosphatidylethanol (PEt) formation in the presence of ethanol, indicating the activation of PLD acting on phosphatidylcholine (PC). The dose-response curve for choline generation and DNA synthesis were comparable. In addition, the effects of PDGF on both PEt formation and [3H]thymidine incorporation into acid-precipitable material was blocked by the potent protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulphonyl)-2-methylpiperazine (H-7) but not by N-(2-guanidinoethyl)-5-isoquinolinesulphonamide (HA1004), a relatively weak inhibitor of PKC, suggesting that PDGF plays an important role as a positive regulator of glioma cell growth via a PLD-mediated mitogenic signal transduction cascades, which depends largely on the activation of PKC.
 ...
PMID:Activation of phospholipase D by platelet-derived growth factor (PDGF) in rat C6 glioma cells: possible role in mitogenic signal transduction. 136 54

We report herein the presence of a 56 kd platelet derived growth factor (PDGF)-related protein as a phosphorylated form in human glioma cells. The phosphorylation of the 56 kd form was found to be the longest of all PDGF-related proteins. By Western blotting using a monoclonal anti-PDGF B-chain, the 80 kd, 56 kd, 40 kd, 28 kd and 17 kd PDGF-related proteins were detected, while after treatment among the nitrocellulose membrane transblotted cell extracts with alkaline phosphatase, 40 kd was the most densely observed while the 56 kd and 80 kd PDGF-related proteins were also detected. In a 32P flush labeling study, it was revealed that PDGF-related proteins incorporated with 32P were detected at 28, 32, 35, 40, 56 and 80 kd but the 17 kd monomer was not labeled. Among the labeled PDGF-related proteins, the 56 kd PDGF-related protein alone remained intracellularly for at least 16 hours. These results indicated that the PDGF-related proteins in human glioma cells are synthesized in a phosphorylated form and partly remain in a 56 kd phosphorylated form intracellularly. The 56 kd form may thus be the most stable form and likely has a substantial biological effect.
 ...
PMID:The 56 kd platelet-derived growth factor (PDGF)-related protein is phosphorylated and the most stable form in human glioma cells. 143 29

Malignant gliomas are characteristically surrounded by marked gliosis. To assess whether glioma-derived products contribute to the proliferation of astrocytes, a feature of the gliosis response, we evaluated the influence of culture supernatants from malignant human glioma lines and tumor cyst fluids collected from two patients with glioblastoma multiforme on the proliferation of non-transformed adult human astrocytes. Both the culture supernatants and cyst fluids significantly increased DNA synthesis in astrocytes as assessed by a double immunofluorescence glial fibrillary acidic protein-bromodeoxyuridine technique. The net proliferative effect mediated by glioma cell line supernatants was tumor growth phase-dependent, being preferentially expressed during the logarithmic phase of glioma cell growth. Specific growth factor molecules and cytokines known to be secreted by gliomas (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, interleukin-6, and tumor necrosis factor-alpha) could not reproduce the mitogenic effects of the glioma-derived soluble factors. Cytokines which can induce DNA synthesis by adult human astrocytes in vitro, gamma-interferon and interleukin-1, were not detected in the culture supernatant of glioma lines used in this study. In conjunction with the documented effects of glioma products on endothelial and lymphoid cells, the current study suggests that soluble glioma products can contribute to the production of surrounding gliosis observed in vivo.
 ...
PMID:Malignant glioma-derived soluble factors regulate proliferation of normal adult human astrocytes. 151 71

Cultures of fetal rat brain cell aggregates and tumor spheroids from the human glioma cell line GaMG were treated with epidermal growth factor (EGF), fibroblast growth factor (FGF) or isoforms of platelet-derived growth factor (PDGF AA or BB). Radioreceptor binding studies displayed a high binding capacity for EGF and FGF, but not binding of PDGF isoforms in the glioma cells. In serum-free culture, 10 ng/ml of both EGF and FGF caused increased growth and cell shedding in the tumor spheroids, whereas PDGF produced no such effect. Similarly, EGF and FGF stimulated tumor cell migration. EGF increased the proliferation and outgrowth of glial fibrillary acidic protein (GFAP)-positive cells in brain cell aggregates, while PDGF AA and BB both stimulated the outgrowth of oligodendrocyte-like cells which were negative for GFAP and neuron-specific enolase. FGF stimulated GFAP+ as well as GFAP- cell types. In co-culture experiments using brain aggregates and tumor spheroids, both EGF and FGF treatment caused increased tumor cell invasion. PDGF had no effect on the tumor cells, but instead stimulated the proliferation of oligodendrocyte-like cells in the brain aggregates. The present results indicate that growth factors may facilitate glioma growth as well as invasiveness, and cause reactive changes in the surrounding normal tissue.
 ...
PMID:Effects of growth factors on a human glioma cell line during invasion into rat brain aggregates in culture. 152 73

The proliferation of many nonglial tumors in vitro depends on the presence of nanomolar concentrations of one or more growth factors. To define the growth factor requirements of malignant glial tumors, the authors examined the response properties of four low-passage human malignant glioma lines to the following mitogens: epidermal growth factor (EGF), acidic and basic fibroblast growth factors (FGF's), insulin-like growth factor I (IGF-I), nerve growth factor (NGF), platelet-derived growth factor (PDGF), 12-O-tetradecanoyl-13-phorbol acetate (TPA), and serum. Each of the tumors showed increased deoxyribonucleic acid (DNA) synthesis (assessed by acid-precipitable [3H]-thymidine incorporation) in response to PDGF with a maximum effect at 50 ng/ml. Three tumors responded to EGF, three to IGF-I, two to acidic FGF, two to basic FGF, and two to TPA with maximum effects at 10, 50, 1, 1, and 10 ng/ml, respectively. None of the tumors responded to NGF. In the responsive tumors, optimum concentrations of EGF, IGF, TPA, acidic FGF, and basic FGF induced, at most, a two- to fourfold increase in [3H]-thymidine incorporation, which was only 30% to 50% of the response seen in 10% serum. In contrast, PDGF increased DNA synthesis eight- to 10-fold, equaling the effect of 10% serum. Measurements of cell proliferation also demonstrated a significant response to PDGF in each of the tumors. Appropriate concentrations of an anti-PDGF neutralizing antibody inhibited baseline DNA synthesis and proliferation in the absence of added growth factors, suggesting the possible role of PDGF in autocrine stimulation of these cells. However, this antibody produced only slight inhibition of serum-induced mitogenesis. Trapidil, an agent reported to inhibit the effects of PDGF, and polymyxin B, an inhibitor of protein kinase C, strongly inhibited baseline as well as PDGF- and serum-induced mitogenesis. It is concluded that, in the malignant gliomas studied, PDGF may be acting as a dominant mitogen to enhance DNA synthesis, and may function in autocrine stimulation. However, other factors contained in serum can also contribute to cell division.
 ...
PMID:Response of low-passage human malignant gliomas in vitro to stimulation and selective inhibition of growth factor-mediated pathways. 164 72

This study was undertaken to evaluate the role of two sets of growth factors, platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), in the induction and maintenance of glial tumors and their phenotypic expression. Explants from eight malignant tumors, five benign tumors, and two nontumor glial cells were analyzed for levels of messenger ribonucleic acid (mRNA) expression of PDGFA, PDGFB, TGF-beta 1, and TGF-beta 2. Results were normalized to the mRNA expression of tubulin, a "housekeeping" gene present in glial cells. Of the 15 explants tested, PDGFB was seen in six, all of which were malignant tumors; PDGFA was seen in all 15 with much higher levels expressed in malignant tumors; and TGF-beta 1 and TGF-beta 2 were seen in all 15 without a clear difference between cell types, although expression tended to be higher in malignant tumors. This project supports the theory that the induction and maintenance of glial tumors is likely to be a multifactorial phenomenon.
 ...
PMID:Expression of platelet-derived growth factor and transforming growth factor and their correlation with cellular morphology in glial tumors. 165 80

Glioma cells in culture express platelet-derived growth factor (PDGF) A- and B-chains and secrete PDGF-like activity that is mainly PDGF-AA. In this work, we show that the PDGF alpha- and beta-receptors are independently expressed in human malignant glioma cells. We also define three different receptor phenotypes that are related to the morphology of glioma cells: cells with only alpha-receptors, only beta-receptors, or with both types of receptors. By the help of Northern blot analyses, 125I-PDGF-binding experiments, and immunoprecipitations the receptors are shown to be structurally normal PDGF receptors, except for minor variations in size that probably are due to differences in glycosylation. PDGF-BB induces DNA synthesis in cells of all three receptor phenotypes, whereas PDGF-AA or PDGF-AB has this effect only on cells with alpha- or with alpha- and beta-receptors. 125I-PDGF-AB binds with high affinity and down-regulates beta-receptors only in cells where alpha-receptors are present in addition to beta-receptors. Thus, the different functional capacities of PDGF isoforms on glioma cells fit with their known receptor-binding specificities and are compatible with the hypothesis that the isoforms act by inducing dimeric receptor complexes. When data on PDGF A- and B-chains, as well as alpha- and beta-receptor expression are compiled and the pattern of receptor binding specificity is taken into account, the majority of glioma cell lines are found to have a phenotype that makes autocrine stimulation possible.
 ...
PMID:Differential expression of platelet-derived growth factor receptors in human malignant glioma cell lines. 165 46


1 2 3 4 5 6 7 8 9 10 Next >>