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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basic fibroblast growth factor (FGF) is a mitogen, a differentiation factor for neuroectoderm-derived cells, and a potent angiogenic factor. The authors have previously demonstrated that the messenger ribonucleic acid of basic FGF is expressed in more than 90% of human gliomas. In the present study, they examined the expression of basic FGF in human glioma tissues using immunohistochemical techniques with a mouse monoclonal antibody against human basic FGF. They also correlated the basic FGF level with the histological grades of malignancy assessed by the number of nucleolar organizer regions (NOR's). Basic FGF was detected in 18 of 19 gliomas, whereas it was undetectable in two normal brains. The expression level of basic FGF peptide increased proportionally with the degree of malignancy. There was also a tendency for the number of NOR's in glioma cells to increase in glioma samples with a high level of basic FGF expression. Furthermore, most of the cases with increased vascularity demonstrated on cerebral angiograms showed a relatively high level of basic FGF expression of tumor cells and a large number of NOR's in endothelial cells in tumor tissues. These results suggest that basic FGF is actually produced in most gliomas and is involved in tumorigenesis and malignant progression as an autocrine growth factor. Moreover, basic FGF may play an important role in tumor neovascularization as a paracrine angiogenic factor.
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PMID:Correlation of basic fibroblast growth factor expression levels with the degree of malignancy and vascularity in human gliomas. 156 42

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.
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PMID:Response of low-passage human malignant gliomas in vitro to stimulation and selective inhibition of growth factor-mediated pathways. 164 72

Basic fibroblast growth factor (bFGF) is a heparin-binding protein expressing potent mitogenic and angiogenic properties. Elevated levels of bFGF have recently been described in human glioma cell lines. The high degree of vascularity and invasiveness which characterize human gliomas suggest that activated expression of bFGF or similar proteins may be related to the aberrant growth patterns of these tumors. The influence of endogenous bFGF on glioma cell growth in vitro was evaluated in the present study by down-regulating bFGF expression using antisense oligonucleotide primers. The addition of 50 microM bFGF-specific antisense primer to the human glioma cell line SNB-19 resulted in an 80% inhibition in glioma growth. This effect was saturable and specific. Antisense primers directed to two different sites of bFGF mRNA were effective in suppressing SNB-19 growth, whereas sense strand primer was ineffective. Furthermore, only the antisense primer significantly reduced the specific activity of bFGF protein in SNB-19 cell extracts. Neither antisense or sense primers inhibited the growth of non-transformed human glia. bFGF mRNA was detected in both transformed and non-transformed human glia by polymerase chain reaction analysis suggesting that alterations in bFGF isoform content or activity may be specifically related to abnormal growth control in human gliomas.
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PMID:Suppression of basic fibroblast growth factor expression by antisense oligodeoxynucleotides inhibits the growth of transformed human astrocytes. 184 92

Basic fibroblast growth factor (bFGF) is a potent mitogen and angiogenic factor. bFGF is expressed by a variety of solid human tumors and has been implicated as an autocrine regulator of tumor growth. Different solid tumor lines including glioma, colon carcinoma and melanoma were examined for intracellular immunoreactive bFGF, high- and low-affinity bFGF receptors and mitogenic response to bFGF when grown in chemically defined medium. All tumor lines contained significant levels of bFGF. In addition, all tumor lines contained subsets of five forms of immunoreactive bFGF, as well as 0.68-20 x 10(6) low affinity bFGF binding sites (Kd = 15-300 nM). Most, but not all lines exhibited high affinity bFGF receptors (Kd = 25-40 pM). Glioma cell lines were distinguished by expressing the highest levels of bFGF protein as well as the most high-affinity receptors for bFGF. Furthermore, glioma cell lines were the only tumor type mitogenically responsive to bFGF. These results indicate that glioma cells express high levels of this potent mitogen and angiogenic factor relative to human colon carcinoma and melanoma cells. The expression of bFGF and bFGF receptors by glioma cells may be related to abnormal growth and neoplastic progression in these tumors.
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PMID:Basic fibroblast growth factor: a potential autocrine regulator of human glioma cell growth. 196 81

Basic fibroblast growth factor (bFGF) is a potent mitogen for several types of cells, including glial cells, which also seem to express bFGF. We have used rat C6 glioma cells as a model system to study the expression and release of bFGF by glioma cells, as well as the effects of exogenous bFGF on these cells. We have shown that C6 cells express 18 kD bFGF and several higher molecular weight immunoreactive forms. The expression of bFGF could be induced by a factor present in fetal calf serum. Subsequent to its initial appearance, bFGF is regulated in a cell density-dependent manner. Neither bFGF-like immunoreactive material, nor bFGF-like neurotrophic activity were found to be released by C6 cells. Exogenously applied bFGF changed C6 cell morphology similar to cyclic AMP induced alterations but had no significant influence on C6 cell proliferation and biochemical differentiation. From these results we conclude that bFGF in C6 cells might act as an endogenous (not autocrine) mitogen. Possible roles for bFGF in glial cells are discussed.
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PMID:Basic fibroblast growth factor (bFGF) and rat C6 glioma cells: regulation of expression, absence of release, and response to exogenous bFGF. 214 53

Basic fibroblast growth factor (bFGF), a potent mitogen and angiogenic peptide, has been examined as an autocrine regulator of glioma cell growth. The addition of purified bovine pituitary bFGF to an established human glioma cell line, SNB-19, doubled the density of these cells in chemically defined medium. Half-maximal stimulation occurred at 8.2 ng/ml (480 pM). Also, human recombinant bFGF (hr-bFGF) significantly enhanced the growth of SNB-19 cells in soft agar. SNB-19 cells expressed both high and low affinity binding sites for hr-bFGF. These cells expressed approximately 13,000 high affinity sites/cell (Kd = 16.6 +/- 1.7 pM) and 9.5 x 10(6) low affinity sites/cell (Kd = 61.2 +/- 4.1 nM). The results of cross-linking experiments with iodinated hr-bFGF demonstrated the presence of two bands with molecular masses of 145 and 130 kDa. High affinity receptors were also demonstrated in SNB-19 tumors grown in nude mice. SNB-19 cell extracts contained mitogenic activity that eluted from heparin-agarose with high salt (1.2-2 M NaCl) and exhibited many properties normally associated with authentic bFGF. This material cross-reacted with a monoclonal antibody to hr-bFGF, comigrated with hr-bFGF by Western blot analysis, competed with 125I-hr-bFGF in a radioreceptor assay, and stimulated SNB-19 cell growth. These results indicate that a human glioma cell line both expresses and utilizes a bFGF-like growth factor. Such a factor may be an important autocrine regulator of glioma cell growth and may also facilitate its neoplastic progression.
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PMID:Basic fibroblast growth factor-like activity and receptors are expressed in a human glioma cell line. 215 22

Basic fibroblast growth factor (bFGF), a growth factor for many cell types including newborn rat astroglial cells, stimulates in a dose-dependent fashion the release of plasminogen activators (PAs) by these cells as measured by the fibrin-overlay method or the Coleman and Green's colorimetric assay. This effect of bFGF on PAs secretion (about 4.5-fold increase at 40 ng/ml bFGF) does not result from an aspecific stimulation of protein secretion by astrocytes and is only partly correlated with the mitogenic activity of bFGF. bFGF was also tested on two clonal glioma cell lines (C6 and LN18). Only one of those cell types (LN18) showed a stimulated PA release in the presence of bFGF. These data are discussed with respect to the putative roles of plasminogen activators in the developing nervous system.
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PMID:Brain basic fibroblast growth factor stimulates the release of plasminogen activators by newborn rat cultured astroglial cells. 318 69

We have previously reported the tissue specific distribution of four different FGF-1 transcripts containing alternative 5' untranslated exons spliced to the first protein coding exon. The predominant transcript in brain is FGF-1.B and in kidney FGF-1.A. Others have shown, by in situ hybridization and immunohistochemical analysis, that expression of FGF-1 in the brain is exclusively in neural cells but not in glial cells. Here we have examined the distribution of FGF-1.B and FGF-1.A transcripts in glioblastoma and retinal tissues and in kidney carcinoma cell lines. Our results show that FGF-1.B is the predominant transcript in neural derived tissues including both the diabetic retina and normal retina tissues. Surprisingly, FGF-1.B transcript is highly expressed in glioblastoma tissues. In contrast, a normal brain glial cell line, CHII, expresses very low levels of FGF-1 mRNA. These results strongly implicate the role of FGF-1 in the etiology of glioblastoma. We also examined several kidney carcinoma derived cell lines for the expression of FGF-1 mRNA. Most of these kidney cell lines do not express any FGF-1 transcripts. An interpretation by deduction is that kidney adenocarcinomas are derived from cortex but medulla has been reported as the site of FGF-1 synthesis. Of the kidney derived cell lines which are positive for FGF-1 message, only one expressed FGF-1.A transcript. The data may suggest that the establishment of kidney cell lines results in a switch of promoter usage from the 1.A seen in kidney tissue. Similarly, culturing of glioma cell lines may result in a switch from FGF-1.B seen in glioma tissues to FGF-1.D seen in most glioma cell lines. Continued studies of the FGF-1 transcripts, their functional promoters and their tissues distribution will provide insight into the potential role of FGF-1 in cell growth, tissue differentiation and malignant transformation.
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PMID:Different fibroblast growth factor 1 (FGF-1) transcripts in neural tissues, glioblastomas and kidney carcinoma cell lines. 754 53

Basic fibroblast growth factor (bFGF) is an autocrine growth factor that is overexpressed in glial tumor cells and promotes their unregulated proliferation. We have previously reported that increased messenger RNA (mRNA) stability contributes to the elevated steady state levels of bFGF mRNA in human U87-MG glioma cells. Stability of bFGF mRNA is regulated by a natural antisense transcript in Xenopus oocytes, but the mammalian equivalent of this transcript has not previously been described. We were interested in identifying the human equivalent of this antisense transcript in order to study its role in bFGF mRNA stability. Analysis of the 3'-untranslated region of the 6.7-kilobase human bFGF mRNA revealed two areas of greater than 75% homology to exons 3 and 4 of the Xenopus antisense transcript, separated by 4300 basepairs of nonhomologous sequence. We used reverse transcription-polymerase chain reaction to amplify, clone, and sequence a 301-basepair fragment of the antisense splice variant from U87-MG cells. The clone (gfg-1) is 73% identical to the Xenopus sequence, with a conserved splice junction and an open reading frame. Strand-specific gfg-1 complementary RNA probes detect a 1.5-kilobase mRNA transcript in normal rat tissues and human T47D breast cancer cells, which contain very low levels of bFGF mRNA. In contrast, antisense transcript expression was undetectable by Northern hybridization in U87-MG cells, which overexpress the bFGF sense mRNA. The reciprocal relationship between bFGF sense and antisense expression suggests that antisense transcripts may regulate bFGF expression in mammalian cells, and that disruption of normal sense/antisense mRNA ratios may lead to overexpression of bFGF in some tumors.
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PMID:Identification and characterization of an antisense RNA transcript (gfg) from the human basic fibroblast growth factor gene. 798 47

The blood-brain barrier GLUT1 glucose transporter is localized in brain to the capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo. However, its expression is markedly downregulated in cultured bovine brain capillary endothelium (ECL cells), possibly due to the absence of brain-derived or astrocyte trophic factors in the tissue culture medium. To examine this hypothesis, we studied the effect of a bovine brain homogenate (BBH), and conditioned media and plasma membranes obtained from the rat C6 glioma cell line, on the abundance of the GLUT1 transcript in ECL cells. BBH induced a significant increase in the abundance of both GLUT1 and actin mRNAs, and this effect was dose and time dependent. The increase in the GLUT1 mRNA levels correlated with an increase in the transcriptional rate of this gene measured by nuclear run-on experiments. C6 conditioned media and C6 plasma membranes had no effect on the abundance of either GLUT1 or actin mRNA. To determine whether known growth factors cause BBH-like induction of GLUT1 and actin mRNAs, a series of growth factors was also tested. EGF and PDGF had no effect on the levels of these mRNAs. Basic FGF had a moderate effect and TNF alpha partially mimicked the effect of BBH on both GLUT1 and actin transcripts. The present data suggests that brain-derived trophic factors present in BBH stimulate BBB-GLUT1 glucose transporter gene expression in ECL cells through a transcriptional mechanism. Although this effect was partially mimicked by TNF alpha, C6 cell membranes or C6 conditioned media were unable to induce changes in the abundance of GLUT1 mRNA. Therefore, BBH may be a useful model to study the characterization of soluble brain-derived trophic factors involved in the induction of BBB-GLUT1 gene expression.
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PMID:Enhanced expression of the blood-brain barrier GLUT1 glucose transporter gene by brain-derived factors. 801 84


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