UMLS:C0017638 - FACTA Search

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

The human glioblastoma-derived cell lines 86HG-39, 87HG-28 and 87HG-31, used for the production of monoclonal antibodies (mAbs) against glioma-associated antigens (GAA), were characterized in terms of morphology, growth behaviour, chromosomes and antigen expression. In the primary tumours, differential expression of glial fibrillary acidic protein, S100 protein, Leu-7 and GAA as defined by mAbs MUC 2-39, MUC 2-63 and MUC 8-22 was demonstrated. Receptors for epidermal growth factor (EGFr) and nerve growth factor (NGFr) were found in many cells in short-term cultures, but the transferrin receptor (Tr) was found in only a few cells of 87HG-28. In permanent cell lines, differentiation antigens and EGFr decreased and Tr increased markedly. NGFr and GAA remained stable. Transplantation tumours of 86HG-39 were partly positive for Tr and GAA. Chromosomal analysis revealed that the 86HG-39 and 87HG-28 cell lines had a hypodiploid or diploid stem line with lines in the hypotetraploid to tetraploid region for 50 in vitro passages. The 87HG-31 cell line had chromosomal patterns in the hypotriploid to triploid region. A gain of chromosomes was seen in the groups C7, C8, C10, D14, F19, F20, G21, G22. The variability of antigens in these tumours and especially during long-term cultivation probably reveals an ability to influence the growth of malignant glioma cells via the respective effector molecules.
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PMID:Morphological, immunocytochemical and growth characteristics of three human glioblastomas established in vitro. 170 26

Monoclonal antibody (mAb) 425 (IgG2a) binds to the external domain of the epidermal growth factor receptor. This determinant is highly expressed by human glioma tissues but rarely by normal brain tissues, and is absent on peripheral blood lymphocytes and bone marrow cells. The mAb exerts variable cytotoxic effects against cultured human glioma cells in conjunction with human and murine effector cells. Inhibition of growth of s.c. glioma xenografts in nude mice by the mAb may be mediated by murine macrophages or may be related to the capacity of the mAb to antagonize growth stimulation of glioma cells by epidermal growth factor. In approaches to radioimmunotherapy of human glioma with mAb 425, the 125I-labeled mAb 425 exhibited more significant antitumor effects than the 131I-labeled mAb both in vitro and in vivo in xenotransplanted nude mice. These differences may be due to enhanced nuclear damage caused by 125I-labeled versus 131I-labeled fragments following their internalization into the glioma cells. Our studies provide the rationale for immunotherapy of glioma patients with either unlabeled or 125I-labeled anti-epidermal growth factor receptor mAb 425.
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PMID:Immunotherapy of human glioma xenografts with unlabeled, 131I-, or 125I-labeled monoclonal antibody 425 to epidermal growth factor receptor. 172 72

Low-grade astrocytomas, anaplastic astrocytomas and glioblastomas in vitro were found to ubiquitously produce the mRNA of transforming growth factor-beta (TGF beta). TGF beta 1 and TGF beta 2 mRNA were expressed to a lesser degree among the hyperdiploid malignant gliomas. By radioreceptor assay of conditioned medium, TGF beta was secreted predominantly in latent form, in both latent and active form, or only in active form within a panel of low-grade and malignant gliomas. The TGF beta receptor (types I, II, and III) was evident among the glioma lines. Many near-diploid gliomas were growth-inhibited by TGF beta 1 and TGF beta 2 in vitro. Most hyperdiploid glioblastomas showed a positive mitogenic response to exogenous TGF beta 1 and TGF beta 2. A synergistic or additive mitogenic interaction with epidermal growth factor and insulin was observed among some. Under serum-free conditions, anti-TGF beta antibody neutralized the expected growth-regulatory effect of endogenous TGF beta, thus establishing the specificity of the response in vitro. TGF beta 1 also enhanced the clonogenicity of certain gliomas which had been growth-stimulated in monolayer. Thus, basic elements in support of an autocrine hypothesis have been demonstrated: TGF beta mRNA was expressed among low-grade and malignant gliomas, TGF beta was secreted in latent and/or active form into conditioned media and appeared to serve as an endogenous regulator of glioma proliferation in vitro. The mitogenic response, either positive or negative, correlated with the degree of anaplasia and karyotypic divergence.
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PMID:TGF beta 1 and TGF beta 2 are potential growth regulators for low-grade and malignant gliomas in vitro: evidence in support of an autocrine hypothesis. 187 66

Recent efforts have been directed at identifying and characterizing candidate tumor suppressor genes and the activities of oncogenes in primary brain tumors. The p53 gene mapping to region p13 of chromosome 17 has several characteristics as a tumor suppressor gene. The wild-type p53 protein, which is a transcriptional activator, may serve as a barrier to the progression of neoplastic processes, and alterations of p53 are involved in genesis of various cancers including astrocytomas. The NF1 gene, which is responsible for the susceptibility to neurofibromatosis type 1, has recently been isolated. This gene is assumed to play a role in the signal transduction pathway by interacting with the ras gene product. Recent observation revealed that the NF1 gene may regulate the neuronal differentiation, and the alteration in regulation of the NF1 transcript is potentially related to the progression of neuroectodermal tumors. Restriction fragment length polymorphism studies have also shown chromosomal losses associated with chromosome 9, 10 and 17. These losses of genetic material are suspected to involve loci near or at the p53 gene for chromosome 17, and neighboring the interferon genes on chromosome 9. Although no sublocalization of chromosome 10 deletions has been accomplished, all of these loci are thought to harbor tumor suppressor genes. Recent advances in oncogene research have focused on understanding the mechanisms of action of growth factors, growth factor receptors, and their substrates, particularly in glial oncogenesis. Fibroblast growth factor, epidermal growth factor, and their respective receptors are of particular interest. However, the ROS oncogene, which is expressed and rearranged in some glioma cell lines, may not be a critical factor in the development of gliomas.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathways of oncogenesis in primary brain tumors. 190

The biological effects of nerve growth factor (NGF) have been shown to be mediated by the high-affinity form of the nerve growth factor receptor (NGF-R) in sympathetic and sensory neurons, and in PC12 cells. We report here that the central nervous system C6 rat glioma cell line likewise expresses functional high-affinity NGF-Rs. The expression of NGF-R mRNA in C6 cells can be up-regulated by cycloheximide and its own ligand, NGF; and it can be rapidly down-regulated by epidermal growth factor (EGF). Furthermore, C6 cells display NGF responsiveness by expressing c-fos mRNA within 30 minutes of treatment with NGF; and after 4-5 days of NGF exposure, C6 cells cease dividing as measured by [3H]-thymidine uptake, change shape, and reveal neurite-like processes. Scatchard analysis of [125I]-labelled NGF bound to solubilized C6 cells confirms the presence of both high- and low-affinity receptor protein. Crosslinking radiolabeled NGF to its receptor in the presence or absence of excess unlabeled NGF, followed by immunoprecipitation with monoclonal antibody (mAb) 192-IgG (a known anti-NGF-R antibody) and SDS-PAGE reveals a 100 kD band corresponding to the NGF/NGF-R complex. An identical band is observed when the immunoprecipitation is carried out with mAb 217c, suggesting that the 217c epitope is related to NGF-R. The 217c antibody was generated against C6 cells and shown to be a cell surface antibody (Peng et al., Science 215:1102-4, 1982); several investigators have used it subsequently as an immunocytochemical marker for Schwann cells. The significance of NGF-Rs in a CNS glial cell line is unclear, but association of NGF with the control of proliferation and/or differentiation of primitive glial cells is suggested.
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PMID:Characterization of functional nerve growth factor-receptors in a CNS glial cell line: monoclonal antibody 217c recognizes the nerve growth factor-receptor on C6 glioma cells. 196 39

Growths factors, defined as polypeptides that stimulate cell proliferation, are major growth-regulatory molecules for cells in culture and probably also for cells in vivo. Evidence has been derived for autocrine system in which the cell produces its own growth factor. Several growth factors as well as their cellular receptors have been identified as productions of proto-oncogenes. Furthermore, these growth factors have been identified as mitogens in tumors of the central nervous system. The roles of growth factors including platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and its receptor. Insulin-like growth factors (IGFs), transforming growth factors (TGFs) and fibroblast growth factor (FGF) on the proliferation of brain tumors, especially glioma were reviewed. The activation of cellular proto-oncogenes resulting in the autocrine system of growth factors and their receptors offers the opportunity for therapeutic interference. Therapeutic efforts will be based on the concepts of neutralization of growth factors, antagonizing growth factors at their receptors, irreversibly blocking receptors, and interference with oncogene product synthesis. Specific antibody for growth factors or receptors will be able to inhibit the proliferation. Trapidil, an antagonist for PDGF, can inhibit the proliferation of a PDGF-producing glioma cell. We can assume that the further analysis of growth regulatory mechanism will allow the design of new therapeutic approaches.
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PMID:[Microbiological approach to the treatment of brain tumors]. 199 13

Anomalies of the epidermal growth factor receptor (EGFR) gene, including amplification, rearrangement, and overexpression, have been reported in malignant human gliomas in vivo. In vitro glioma cell lines coexpress EGFR and at least one of its ligands, transforming growth factor alpha, suggesting the existence of an autocrine growth stimulatory loop. We have studied the tumor tissue from 62 human glioma patients and examined the structure and quantity of the EGFR gene and its transcripts, as well as the quantity of the receptor protein. In addition we have examined the genes and transcripts coding for the pre-pro forms of epidermal growth factor and transforming growth factor alpha, the two endogenous EGFR ligands. EGFR gene amplification was detected in 16 of the 32 malignancy grade IV gliomas (glioblastoma) studied (50%), but only in 1 of 30 gliomas of lesser malignancy grade (I-III). All tumors with an amplified gene overexpressed EGFR mRNA. More than one-half (62.5%) of the glioblastomas with amplified EGFR genes also showed coamplification of rearranged EGFR genes and concomitant expression of aberrant mRNA species. Overexpression, without gene amplification, was observed in some of the low grade gliomas, and aberrant EGFR transcripts were also seen in some cases without gene amplification or detected gene rearrangements. mRNA expression for one or both of the pre-pro forms of the ligands was detected in every tumor studied. Thus, several mechanisms for the activation of the EGFR-mediated growth stimulating pathway are possible in human gliomas in vivo: expression of a structurally altered receptor that may have escaped normal control mechanisms; and/or auto-, juxta-, or paracrine stimulating mechanisms involving coexpression of receptor and ligands, with or without overexpression of the receptor.
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PMID:Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. 200 34

A positron-emitting isotope of bromine, 76Br, with a half-life of 16.2 h, was produced using the reaction natBr(p, xn)76Kr. Labelling of mouse epidermal growth factor (EGF) with 76Br was optimized, using the chloramine-T method, obtaining a maximal radiochemical yield of 53%. In tests with receptor-rich, cultured glioma cells, [76Br]EGF and [125I]EGF bound equally well. A study of the distribution and stability of [76Br]EGF and [125I]EGF in normal rat was carried out. The distribution of both radioisotopes was similar, however, the percentage of 76Br bound to the high molecular weight fraction in the plasma, liver and kidney was greater than that of 125I.
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PMID:Distribution and stability in the rat of a 76Br/125I-labelled polypeptide, epidermal growth factor. 202 1

Malignant glioma cells often have more epidermal growth factor (EGF) receptors than normal cells and targeting of toxic substances to the receptor might therefore be an attractive therapeutical approach. Radiation effects were analysed on human glioma cells growing as monolayers after exposure to 131I-EGF. Unspecific effects were analysed with 131I-BSA or after presaturation with nonradioactive EGF. The radiation effects were compared to the effects obtained by external 60Co gamma irradiation. Administration of the highest radioactive concentrations, 0.2-0.5 MBq/ml in the culture medium, corresponded, after 20 min incubation, to a binding of about 1.0-2.5 dpm/cell. Such an exposure to 131I decays gave effects on cell survival corresponding to about 2.5 Gy of external gamma irradiation. Somewhat less than half of this effect came from the specific bound radioactivity and the rest from nonbound radioactivity. When administrating lower concentrations of radioactivity both the binding and the radiation effects were smaller. The observations showed that it is possible to inactivate cell-proliferation of glioma cells with specific bound 131I-EGF. The possibilities to fractionate the treatments and of binding also other toxic agents than 131I to the EGF receptor are discussed.
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PMID:Effects of 131I-EGF on cultured human glioma cells. 208 35

To evaluate the role of protein kinase C-mediated pathways in the proliferation of malignant gliomas, this study examined the effect of a protein kinase C (PKC)-activating phorbol ester (12-O-tetradecanoyl-13-phorbol acetate or TPA) and a protein kinase C inhibitor (polymyxin B) on deoxyribonucleic acid (DNA) synthesis of malignant glioma cells in vitro. A serum-free chemically defined medium, MCDB 105, was employed for all studies. Two established human malignant glioma cell lines (T98G and U138), two rat glioma lines (9L and C6), and two low-passage human glioma lines (obtained from surgical specimens) were studied. With the exception of the C6 line, all tumors responded in a dose-dependent fashion to nanomolar concentrations of TPA with a median effective dose that varied from 0.5 ng/ml for the U138 glioma to 1 ng/ml for the T98G glioma. At optimal concentrations (5 to 10 ng/ml), TPA produced a two- to five-fold increase in the rate of DNA synthesis (p less than 0.05) as assessed by incorporation of 3H-thymidine. However, TPA had no additive effect on the mitogenic response produced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF). Inhibition of PKC using the antibiotic polymyxin B (20 micrograms/ml) abolished the TPA-induced mitogenic response in the five responsive lines tested. In two tumors (U138 and 9L), polymyxin B also eliminated EGF-, PDGF-, and serum-induced DNA synthesis as well as abolishing baseline DNA synthesis. These cells remained viable, however, as assessed by trypan blue exclusion; after removal of polymyxin B from the medium, they were able to resume DNA synthesis in response to TPA and serum. In the three other tumors (T98G and the two low-passage human glioma lines), growth factor-induced and serum-induced DNA synthesis were inhibited by approximately 25% to 85%. It is concluded that PKC-mediated pathways affect DNA synthesis in the human malignant glial tumors studied. The response of the glioma cells to TPA is similar to the responses seen in fetal astrocytes, but differs significantly from those reported for normal adult glial cultures. Because the response of the 9L glioma to TPA is similar to the responses seen in the human tumors, the 9L rat glioma model may prove useful for examining the role of PKC-mediated pathways in controlling glioma growth in vivo.
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PMID:Response of malignant glioma cell lines to activation and inhibition of protein kinase C-mediated pathways. 216 13

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