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)

We examined the expression of fibroblast growth factor receptor-1 (FGFR-1), namely FLG, in tissues of 18 human gliomas, 10 human meningiomas, 3 human metastatic brain tumors, and 2 normal human brains by means of immunohistochemistry. All tissues were positively stained for FGFR-1. Primary brain tumors were more abundantly immunoreactive than normal brain tissues (Mann-Whitney U test, P < 0.05). There was significant correlation between the expression level of basic fibroblast growth factor (basic FGF) and that of FGFR-1 in tissues of human glioma (Spearman's test, P < 0.05). The expression level of FGFR-1 of tumor cells increased in correlation with that of endothelial cells in glioma tissues (Spearman's test, P < 0.001). We previously reported that basic FGF is produced in more than 90% of human glioma and meningioma tissues. Together with these data, it is suggested that basic FGF is involved in autonomous cell growth and tumorigenesis of gliomas and meningiomas as an autocrine growth factor in vivo.
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PMID:Expression of fibroblast growth factor receptor-1 in human glioma and meningioma tissues. 817 81

Multiple basic fibroblast growth factor (bFGF) mRNAs are transcribed in rat brain at 6.0, 3.7, 2.5, 1.8, 1.6, 1.4, and 1.0 kb. These seven transcripts are also seen in Rat-1 fibroblasts and ras-transformed Rat-1 fibroblasts in culture. However, only a single bFGF transcript at 6.0 kb is detectable in the rat astrocytoma cell line, C6, and this mRNA is identical to that seen in a primary culture of cortical astrocytes. C6 glioma cells also transcribe message for FGF receptor 1 (FR1), suggesting possible autocrine growth by these cells. Growth factor activity in a C6 cell lysate was characterized by heparin affinity chromatography and Western blot analysis using an anti-bFGF antibody. Proteins of 18, 21.5, and 22 kDa were detected in C6 cells, indicating that the 6.0-kb mRNA is translated into the three characteristic bFGF proteins. Rat-1 fibroblasts also synthesize bFGF proteins of identical molecular weight. The small transcripts detected in brain probably represent bFGF or FGF-related mRNAs in cell types other than glia, such as fibroblasts, endothelial cells, or neurons. In cultured C6 cells, bFGF protein levels are highest in confluent, quiescent cells, whereas mRNA levels are low. Addition of serum, phorbol ester, or cycloheximide to both C6 cells and fibroblasts induces the level bFGF mRNA transcripts 10-fold after 1-4 h. This rapid induction after cell activation indicates that bFGF is an early response gene. Therefore, even though there are abundant intracellular stores of the factor, the transcriptional activation seen after mitogenic activation of cells implies that de novo bFGF mRNA synthesis is an important part of the mitogenic response.
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PMID:Regulation of basic fibroblast growth factor mRNA expression in rat C6 glioma cells. 826 39

Rapidly growing human teratocarcinoma cells (Tera-2) can be induced to differentiate into quiescent, nontumorigenic cells expressing neuronal markers. To more closely mimic the in vivo conditions for tumor growth, we grew Tera-2 cells in three-dimensional collagen gel cultures. The undifferentiated cells proliferated in the gel, forming tight colonies. Addition of soluble fibroblast growth factor 1 or 2 (FGF1 or FGF2) into the gel resulted in scattering of single cells throughout the collagen gel. In a FGF gradient the cells moved rapidly toward a higher concentration. On the contrary, cells first differentiated for 8 days in retinoic acid died within a few days after transfer into the collagen gel. Alternatively, if retinoic acid was included in the collagen gel, the proliferating undifferentiated cells died after 4-5 days in the gel. This differentiation-related cell death was completely opposed by including FGF in the collagen gel. When placed in the FGF gradient, the fully differentiated cells survived at the areas of higher FGF concentration, but no more migrated. The survival of retinoic acid-differentiated Tera-2 cells in collagen was also mediated by direct contact with glioma cells or the heparan sulfate-rich portion of glioma or endothelial cell matrix. These effects on differentiated cells were sensitive to inhibition by affinity-purified anti-FGF2 IgG. Thus, FGF has the potential to act as a migration-inducing factor either in solution or, more likely, in vivo, as an immobilized, matrix-bound growth factor directing the movement of responsive cells. The development of differentiation-associated FGF dependency allows survival of the cells only at places where they are in close contact with either FGF-synthesizing cells or FGF-rich extracellular structures such as basement membranes.
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PMID:Development of FGF-dependency in human embryonic carcinoma cells after retinoic acid-induced differentiation. 829 70

Glia-activating factor (GAF) is a novel heparin-binding growth factor purified from the culture supernatant of a human glioma cell line. It shows a spectrum of activity slightly different from those of other known growth factors. We have isolated the cDNA which encodes human GAF. A homology search revealed that GAF would be the ninth member of the FGF family, and we therefore call it FGF-9. The human FGF-9 cDNA cloned by using oligonucleotide probes encoded a polypeptide consisting of 208 amino acids. Sequence similarity to other members of the FGF family was estimated to be around 30%. Two cysteine residues and other consensus sequences in family members were also well conserved in the FGF-9 sequence. FGF-9 was found to have no typical signal sequence in its N terminus like those in acidic FGF and basic FGF. Acidic FGF and basic FGF are known not to be secreted from cells in a conventional manner. However, FGF-9 was found to be secreted from cells after synthesis despite its lack of a typical signal sequence. It could be detected exclusively in the culture medium of cDNA-transfected COS cells. The amino acid sequence of proteins purified from culture supernatant of the CHO cell line, which was cDNA transfected and selected as a high producer of FGF-9, showed that no peptides were cleaved from the N terminus except the initiation methionine. The rat FGF-9 cDNA was also cloned, and the structural analysis indicated that the PGF-9 gene is highly conserved. Expression of the FGF-9 gene could be detected in the brain and kidney of the adult rat. Restricted gene expression in organs and the unique secretion nature of the protein suggest that FGF-9 plays a physiological role which differs from those of well-characterized acidic FGF and basic FGF.
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PMID:Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property. 832 Dec 27

Cloned neoplastic astrocytes from a human glioma-derived cell line (IPSB-18) were grown in fetal calf serum (FCS)-supplemented culture medium in the presence of three growth factors. Basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) but not platelet-derived growth factor (PDGF) induced an increase in the number of cells positive for the ganglioside-recognizing monoclonal antibody, A2B5. No such growth factor-mediated induction could be detected in cells maintained in plasma-derived serum (PDS)-supplemented medium. Small molecules, removed from PDS during dialysis, may, therefore, act synergistically with growth factors in the control of ganglioside synthesis.
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PMID:Growth factor modulation of surface ganglioside expression in cloned neoplastic glia. 846 69

Basic fibroblast growth factor (bFGF) is a heparin-binding protein, expressing potent mitogenic and angiogenic properties. Elevated levels of bFGF have been identified in human gliomas and glioma cell lines, suggesting that bFGF expression is involved in the aberrant growth patterns associated with these tumors. In the present study, the influence of bFGF on additional parameters of glioma cell malignancy was evaluated utilizing three distinct methods to suppress bFGF expression or activity including antisense oligonucleotide primers, a neutralizing monoclonal antibody or an inhibitor of the agonist action of bFGF: (1) The addition of 30 microM bFGF-specific antisense oligonucleotide primer to the human glioma cell line SNB-19 resulted in a 55% inhibition in colony formation in soft agar. This effect was dose-dependent and specific, as sense strand primer was ineffective in suppressing growth. In addition to exhibiting fewer colonies, antisense treatment significantly altered colony morphology. (2) SNB-19 cell growth in culture was suppressed in the presence of a neutralizing bFGF-specific monoclonal antibody. (3) Inositolhexakisphosphate, a newly identified antagonist of FGF binding and activity, suppressed SNB-19 cell growth in soft agar culture. These results demonstrate that bFGF may regulate glioma growth and progression independent of its role in tumor angiogenesis and that bFGF release or secretion may be required for these actions.
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PMID:Basic fibroblast growth factor expression is required for clonogenic growth of human glioma cells. 847 85

Basic fibroblast growth factor (bFGF) is a potent stimulator of angiogenesis, proliferation, and invasion in human gliomas. To test the hypothesis that bFGF is important in the development of the malignant phenotype of human gliomas, bFGF expression was prospectively modulated in primary human fetal astrocytes and in an established human glioma cell line. Fetal astrocytes were transfected with a vector expressing bFGF modified by the addition of a secretory signal peptide sequence. Two of these bFGF astrocyte clones examined in vitro demonstrated anchorage-independent growth, loss of contact inhibition, and decreased glial fibrillary acidic protein immunoreactivity, changes consistent with cellular transformation. To analyze the inhibition of bFGF expression, phosphorothioated bFGF antisense oligodeoxynucleotides were added to cultures of the U-87 human glioma cell line. The U-87 cell proliferation was inhibited to 70.6 +/- 0.4% of control at 10 mumol/L and to 53.2 +/- 5.6% of control at 20 mumol/L (P < 0.05). Both the 7.0- and 4.0-kilobase bFGF messenger ribonucleic acid transcripts were reduced after exposure to the antisense oligodeoxynucleotide, and cell-associated bFGF protein was reduced by 44%. The sense oligodeoxynucleotide, a negative control, failed to inhibit U-87 proliferation. These data support the concept that bFGF expression could be a key event in glial tumorigenesis that may be necessary for the sustained growth of human gliomas.
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PMID:The potential role of basic fibroblast growth factor in the transformation of cultured primary human fetal astrocytes and the proliferation of human glioma (U-87) cells. 855 2

Glia cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, has been implicated in the survival, morphological and functional differentiation of midbrain dopaminergic neurons and motoneurons in vitro and in vivo. The factor may thus have utility in the treatment of various human neurodegenerative disorders. Mechanisms regulating expression of GDNF in normal and diseased brain as a possible means to increase the local availability of GDNF are only beginning to be explored. We have established and employed a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to study and compare levels of expression of GDNF mRNA in several cell types and to investigate its regulation. GDNF expression was clearly evident in primary cultured astrocytes, the glioma B49 and C6 cell, but less pronounced in the Schwannoma RN22 cell lines. Little or no signal could be observed in neuroblastoma cell lines (IMR32, LAN-1) or the pheochromocytoma cell line PC12, emphasizing the glial character of this factor. Using the C6 cell line we found that fibroblast growth factor-2 (FGF-2; bFGF) can increase GDNF mRNA levels, whereas FGF-1, platelet-derived growth factor (PDGF), and vasoactive intestinal polypeptide (VIP) are apparently ineffective. Several other factors (forskolin, kainic acid, triiodothyronine dexamethasone, GDNF, TGF-beta 1, and interleukin-6) appear to have slightly negative effects on GDNF mRNA levels at the concentrations tested. To further explore the relationship between FGF-2 and GDNF, we also addressed the question whether GDNF, like FGF-2, may have an effect on C6 cell proliferation. We conclude that (1) glial and glial tumor cells, rather than neuronal cell lines, express GDNF, (2) that FGF-2 has a prominent inductive effect on GDNF expression and (3) that GDNF stimulates C6 cell proliferation. Finally, these data suggest that neurotrophic actions of FGF-2 in mixed glial-neuronal cell cultures might be mediated in part by GDNF.
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PMID:GDNF mRNA levels are induced by FGF-2 in rat C6 glioblastoma cells. 888 50

Morphological and immunocytological changes of intermediate filaments of cultured human malignant glioma cells were studied by adding various growth factors or cytokines using stereoscopic high voltage electron microscopy operated at 1,000 kV. The gold-colloid immuno-cytochemical method was used to stain GFAP and vimentin. Growth rate of tumor cells increased when EGF, TGF-alpha, and PDGF administered and decreased when FGF, TNF, and CLN-IgG administered. Morphological changes of cells were not remarkable when EGF, PDGF, IL-1, and FGF were administered. The cytoplalsmic organellaes were damaged after administrating TNF and CLN-IgG to cells.
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PMID:Changes of intermediate filaments in cultured human glioma cells with various growth factors and cytokines using high voltage immunoelectron microscopy. 891 26

Basic fibroblast growth factor (bFGF) is mitogenic to neuroectoderm- and mesoderm-derived cells and is a potent angiogenic factor. Abundant amounts of this factor and its receptor are detected in human glioma tissues and cells, and bFGF in glioma is thought to be involved in autonomous cell growth as an autocrine growth factor. A neutralizing mouse monoclonal antibody (MAb) against bFGF, 3H3 MAb, has been shown to inhibit both in vitro and in vivo growth of human glioma cell lines. This study shows that the human glioma cell lines U-87MG and U-251MG, which express high levels of bFGF and its receptor, can be induced to undergo apoptosis when cultured with 3H3 MAb. It is also demonstrated that 3H3 MAb can cause apoptosis in the same glioma cells that were transplanted into nude mice. Furthermore, enforced overexpression of bcl-2 protein by gene transfection prevented 3H3 MAb-induced apoptosis of glioma cells. It is concluded that induction of apoptosis by the neutralizing antibody is a promising therapeutic strategy for glioma.
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PMID:Apoptosis of human glioma cells in vitro and in vivo induced by a neutralizing antibody against human basic fibroblast growth factor. 892 97


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