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)

Overexpression of the alpha-Platelet Derived Growth Factor Receptor (alpha-PDGF) gene was detected in a case of malignant glioma. This overexpression was accompanied with amplification of rearranged alpha-PDGF receptor gene. We have isolated a cDNA for the transcript derived from the amplified receptor gene. Characterization of the cDNA revealed a deletion of 243 nucleotides coding for 81 amino acids in the extracellular region of the receptor. This in-frame deletion removed a part of the immunoglobulin-like domains in the extracellular region of the receptor. Analysis of the amplified alpha-PDGF receptor gene in the glioma indicated that exons coding for the 81 amino acids were lost by a gene deletion. The gene amplification was also detected in macroscopically normal cortex adjacent to the glioma from the same patient. However, the amplified gene in the macroscopically normal cortex had no major gene rearrangement. These data suggest that the overproduction of structurally altered alpha-PDGF receptor may take part in the onset and the development of malignant glioma.
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PMID:Overexpression and amplification of alpha-PDGF receptor gene lacking exons coding for a portion of the extracellular region in a malignant glioma. 130 11

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.
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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.
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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

Glycolipids of U-1242 MG were characterized because results of previous studies showed that exogenous gangliosides, especially GM3, inhibit PDGF-stimulated growth of this human glioma cell line. GM3 and GM2 are the major gangliosides; both separate as doublets with thin-layer chromatography. The major neutral glycolipid is glucocerebroside with nonhydroxy fatty acids, but paragloboside, ceramide dihexoside, globoside, and asialoGM2 (GA2) are also present. The coexistence in U-1242 MG of these gangliosides and the PDGF receptor, whose mitogenic signal is modulated by GM3 in these cells, suggests a possible functional relationship among them with respect to growth regulation.
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PMID:Glycolipids of a human glioma cell line bearing receptors for platelet-derived growth factor (PDGF). 132 93

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.
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PMID:Effects of growth factors on a human glioma cell line during invasion into rat brain aggregates in culture. 152 73

PDGF-like peptides secreted from smooth muscles have been suggested to be responsible for the smooth muscle growth. In order to elucidate the nature of PDGF-like molecules expressed in vascular smooth muscles, we have isolated and characterized cDNA clones for PDGF-A chain from a rabbit embryonic aorta cDNA library. One of the cDNA clones was found to encode a novel PDGF-A chain, named PDGF-A3 in this report. PDGF-A3 arises from a single PDGF-A chain gene by alternative RNA splicing and differs from the sequences of previously reported endothelial- or the glioma-type transcripts by a 110 bp insertion. Expression of PDGF-A3 mRNA was selectively induced by Angiotensin II in the smooth muscle cell in vitro. Total PDGF-A mRNA is most enriched in embryonic aortas, but its expression is down-regulated with vascular development. PDGF-A mRNA is markedly increased in primary-cultured smooth muscle cells during the log-phase growth. Our results suggest that autocrine production of PDGF-A chains from the smooth muscle cell may play a role in early vascular development and in Angiotensin II-induced smooth muscle cell proliferation.
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PMID:Identification of three types of PDGF-A chain gene transcripts in rabbit vascular smooth muscle and their regulated expression during development and by angiotensin II. 157 49

A panel of 11 established human glioma cell lines was used to evaluate PDGF receptor binding using radioiodinated biosynthetic PDGF-AA and PDGF-AB as primary ligands. It was found that PDGF-receptor-binding was qualitatively heterogeneous. The affinities for PDGF-AA as well as PDGF-AB binding were within a close range of 0.13-0.33 nM and 0.16-1.1 nM, respectively. The number of binding sites per cell ranged between 56.000 and 250.000 for PDGF-AA and 72.000 to 300.000 for PDGF-AB. Two lines had only background levels of PDGF-AA binding. PDGF-AB binding was the dominant binding component in all but one cell line. In seven cell lines there were two binding components upon saturation analysis consisting of a high affinity component and a non-saturable low affinity component. PDGF and PDGF-receptors are suspected to be part of an autocrine loop in gliomas. Therefore, the effect of suramin on cell proliferation in serumfree cultures was tested in the same cell lines using doses of 25,200 or 500 micrograms/ml. It was found that the response to suramin was variable and that two cell lines still reached 2.8 fold and 4.5 fold their initial cell density even in the presence of 500 micrograms/ml whereas all other cells were completely arrested. Analyzing the response to 200 micrograms/ml it became evident, that the PDGF binding characteristics are of no reliable predictive value in respect to the efficacy of suramin.
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PMID:Receptors for platelet derived growth factor in human glioma cell lines and influence of suramin on cell proliferation. 166 6

Suramin is an anti-helminthic drug that has been shown to antagonize the effects of a variety of growth factors including EGF, PDGF and TGF beta. When added to the culture medium, suramin inhibited the proliferation of both human colonic adenocarcinoma cells HT29-D4 and rat glioma cells C6. Suramin also induced the differentiation of both cell lines: appearance of cellular extensions for C6 cells, enterocyte-like epithelial differentiation for HT29-D4-cells. In the latter case, suramin probably acts at the level of glucose metabolism, which is likely to be modulated by autocrine growth factors. The permanent secretion of such factors probably stimulates HT29-D4 proliferation and simultaneously inhibits their differentiation. It is hypothesized that interfering with this autocrine loop, suramin allows HT29-D4 cells to differentiate.
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PMID:[Suramin inhibits the proliferation and stimulates the differentiation of tumoral cell lines HT29-D4 and C6]. 175 32

Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a covalently bound form. Although there are some discrepancies in the molecular weights of these proteins, it is significant that many investigators have reported a molecular weight of about 60 kd for the receptor, regardless of whether it is of the mu, delta, or kappa type. This finding, together with immunological evidence, suggests that different opioid receptor types may be highly similar, and could conceivably even share a common ligand-binding subunit. Several groups have prepared monoclonal or polyclonal antibodies to purified opioid-binding proteins, which should be useful in mapping the brain regional distribution of the opioid receptors, determining the regions in the peptide involved in ligand binding and association with second messengers, and in determining the relationships among different opioid receptor types. One group has in fact already established an antigenic similarity between a mu-selective opioid-binding protein in mammalian brain, and the delta opioid receptor in NG108-15 neuroblastoma-glioma hybrid cells. One group has reported cloning of the cDNA for a purified opioid-binding protein. Somewhat surprisingly, its predicted amino acid sequence places it in the immunoglobulin superfamily, with strongest homologies to cell-adhesion molecules such as N-CAM. MAG, amalgam and fasciclin II, as well as receptors for peptides such as PDGF and interleukin-6. However, this is consistent with evidence that opioids can modulate cell-cell interactions of monocytes, and provides further support for links between opioids and the immune system. The second messengers mediating opioid actions are still unknown. Opioid agonists affect the activity of adenylate cyclase and ion channels in some tissues, but neither has been shown to mediate opioid analgesia. The sequence homologies of the purified opioid-binding protein OBCAM with tyrosine kinase growth factor receptors suggest additional possibilities for second messengers.
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PMID:Molecular characterization of opioid receptors. 216 Jul 90

Two cell lines (U-343 MG and U-343 MGa) with different phenotypic characteristics were established from the same human glioblastoma multiforme biopsy. Previous studies have shown that a clonal derivative (Cl 2) of the U-343 MGa line produces a PDGF-like growth factor. In the present investigation glioma PDGF production and 125I-PDGF binding were found to be differently expressed in U-343 MG, U-343 MGa, and U-343 MGa Cl 2 cultures, providing evidence for a clonal variation in these properties. In order to investigate this point further, several clones were derived from low (23 clones) and high (30 clones) passage U-343 MGa cultures, as well as from U-343 MGa Cl 2 cells (30 clones). The clones could be divided into 4 groups according to morphology and growth pattern. A determination of the amount of PDGF receptor competing activity in serum-free conditioned media gave evidence for a clonal variation in the production of glioma PDGF, corresponding to 0-87 ng of authentic PDGF per ml. There was also a considerable range in 125I-PDGF binding (0-44 fmol of tracer bound per 10(6) cells). Scatchard plots performed on two clones confirmed the presence of saturable, high affinity PDGF receptors. High passage cultures were found to give rise to a higher number of high producing clones than did low passage cultures. There appeared to be a negative correlation between production of glioma PDGF and binding of 125I-PDGF, probably due to the receptor blocking activity of the endogenous growth factor. However, the presence of clones, apparently devoid of both glioma PDGF production and 125I-PDGF binding, suggests a true clonal variation in these two parameters. The growth rate in serum-free medium was found to correlate fairly well to the extent of glioma PDGF production. Production of glioma PDGF was found to have a morphological correlate and be most prominent among clones of "immature" looking, tightly growing cells. Clones that had large star-shaped cells with some resemblance to normal glia-like cells in culture were found to have a low production and a high 125I-PDGF binding capacity.
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PMID:Clonal variation in the production of a platelet-derived growth factor-like protein and expression of corresponding receptors in a human malignant glioma. 299 9


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