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)

Epidermal growth factor, EGF, and 131I or 125I-labelled tyrosine were conjugated to the sugar polymer dextran. The conjugates bound to EGF-receptor rich human glioma cells in culture and the binding was mainly receptor specific because cells presaturated with nonradioactive EGF gave strongly reduced binding. The 131I labelled conjugates were used in tests on cellular retention and therapeutical effects. 131I activity delivered to the cells as EGF-dextran-tyrosine-131I remained cell-associated for much longer periods of time than 131I activity delivered by only EGF. The amount of cell-associated 131I activity was nearly constant for up to 25 hours. The 131I labelled conjugate gave, after a one hour incubation period for binding followed by a 25 hour incubation in nonradioactive medium, a good therapeutical effect. This effect, which corresponded to about 3.0 Gy of external 60Co radiation, was due to the specifically bound 131I. The comparatively small effects of nonbound 131I in the culture medium, present only during the first incubation hour, were measured in control experiments with presaturated receptors and were corrected for in the evaluation of the EGF-receptor mediated effects. Control experiments showed that neither nonradioactive EGF nor non-radioactive EGF-dextran conjugates gave measurable effects on clonogenic growth. The results obtained were promising and the possibilities to use EGF-dextran conjugates for therapy should be further examined.
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PMID:Effects of EGF-dextran-tyrosine-131I conjugates on the clonogenic survival of cultured glioma cells. 128 Dec 25

A strategy for improved treatment of malignant gliomas grade III-IV is presented. The strategy can briefly be described as surgical removal of the bulky tumor, high precision external irradiation of small brain volumes over and near the primary tumor area with high doses from proton beams, and thereafter treatment of spread cells with toxic radionuclides. Proton beams suitable for this are under development. The clinical effects of high single doses on malignant gliomas grade III-IV are presently tested with conventional gamma radiation. Targeting of spread glioma cells with toxic radionuclides tagged to epidermal growth factor, EGF, or to EGF-dextran is presently tested in experimental systems and can, in the near future, be tested in combination with local high doses of external proton radiation. The possibilities to combine proton beams with EGF-guided neutron capture therapy will be considered in a longer perspective.
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PMID:Strategy for planned radiotherapy of malignant gliomas: postoperative treatment with combinations of high dose proton irradiation and tumor seeking radionuclides. 131 Sep 61

We established and characterized two cell lines derived from glioblastoma multiforme. Both cell lines exhibited tumor cell morphology and growth kinetics and showed variable expression of glial fibrillary acidic protein (GFAP), S-100, fibronectin and vimentin. Cytofluorimetrical analysis of tumor samples showed a diploid DNA distribution, whereas permanent culture cells evolved to the hyperdiploid DNA content. Karyotype studies revealed cytogenetical abnormalities described in glial tumors including gain of chromosome 7, loss of chromosome 10 and presence of double minutes (DMs). Enhanced expression of Ha-ras and c-myc genes resulted from high p-21 and p-62 levels. The contemporary presence of TGF-alpha and EGF-Rc transcripts suggested an autocrine mechanism in the cell lines growth.
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PMID:Establishment and characterization of two cell lines derived from human glioblastoma multiforme. 132 Mar 58

Significant advances have recently been made in a number of areas concerning central nervous system (CNS) neoplasia. Particularly salient are the following: (1) gene amplification is related to increasing grade of human glioma malignancy and occurs in approximately 40% of the most common and most malignant variety of glioma, glioblastoma multiforme (GBM), (2) by far the most commonly amplified gene in glioblastomas is the epidermal growth factor receptor (EGFR) gene, which is amplified in about one third of GBMs, (3) a small percentage of GBMs amplify N-myc or the novel sequence gli, (4) the EGFR gene is rearranged in at least half of gliomas in which it is amplified, and (5) EGFR gene rearrangement results in external domain deletions that yield truncated EGF receptors. Antibodies specific for the mutant EGF receptor fusion junction have been successfully produced and provide stimulating new potential avenues for tumor imaging and therapy. For pediatric CNS neoplasms, only medulloblastoma has been investigated in adequate numbers; a small percentage exhibit amplification of either the N-myc or c-myc genes.
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PMID:Amplified cellular oncogenes in neoplasms of the human central nervous system. 137 22

Here I discuss quantitative and qualitative activation of several receptor-type molecules in tumor cells. Recently we have shown that EGF-R gene is frequently mutated in human glioblastoma. Mutant EGF-R had a 801-bp deletion within the ligand binding domain, and showed a ligand-independent, constitutive elevation of tyrosine kinase activity. This EGF-R mutation is detected only in glioma and associated with gene amplification, suggesting a relationship in the molecular mechanism between deletion mutation and initiation of gene amplification in these cases. Secondly I have shown an activation of mouse CD43 gene by amplification and rearrangement in erythroleukemia cell lines. Intracellular domain of CD43 has no kinase domain but a highly conserved structure among mammals, probably interacting with intracellular signal transducers. Recently CD43 has been demonstrated to be specifically associated with a cell-adhesion molecule ICAM-1. Thus, CD43-ICAM-1 system might be a new type of cytokine system which regulate cell-proliferation through cell-cell interaction. In addition, activation of EpoR and v-mpl is also discussed.
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PMID:[Membrane receptors and cell transformation]. 143 60

Recombinant tumor necrosis factor alpha (rTNF alpha; optimal dose 1000 U/ml) significantly increased the density of epidermal growth factor receptor (EGF-R) in three of four glioma cell lines in culture as determined by binding analysis of anti-EGF-R monoclonal antibody (mAb) 425. Since enhancement of EGF-R expression by rTNF-alpha was inhibited when cells were treated with the protein synthesis inhibitor cycloheximide, the effects of rTNF alpha may be protein-synthesis-dependent. The dose of rTNF alpha that was optimal for up-regulation of EGF-R on glioma cells did not inhibit the growth of these cells. 125I-labeled mAb 425 lysed glioma cells in culture following its internalization into the cells. After glioma cells had been treated with rTNF alpha, the growth-inhibitory effects of the mAb were significantly enhanced, probably a reflection of the increase in EGF-R density on the tumor cell surfaces. The rTNF alpha effects were specific to the EGF-R and did not affect unrelated glioma-associated antigens. In our previous clinical trials, 125I-labeled mAb 425 showed immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with 125I-labeled mAb 425 and rTNF alpha.
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PMID:Enhancement of epidermal growth factor receptor expression on glioma cells by recombinant tumor necrosis factor alpha. 156 13

Human epidermal growth factor receptor (EGFr) gene amplification, rearrangements and expression were studied in tumours of the human nervous system. EGFr gene amplification was studied in 46 brain tumours. Gene expression was analysed by northern blot in 37 tumours and binding of its protein to EGF in 27 tumours. The EGFr gene was simultaneously amplified (with arrangements in 12.5% of gliomas) and overexpressed in 53% (9/17) of malignant gliomas, but never in meningiomas. In five high grade gliomas, amplification was always associated with a high level of receptors. However, since high amounts of EGF receptors found in one glioma were not the result of gene amplification, several systems of deregulation in EGFr production may exist and could be located at translational and/or post-translational levels.
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PMID:EGF receptor amplification and expression in human brain tumours. 156 59

Malignant human glioma D-298 MG amplifies a rearranged epidermal growth factor receptor (EGFR) gene (c-erbB proto-oncogene), resulting in an in-frame deletion of 83 amino acids in domain IV of the extracellular domain of the EGFR. EGF and transforming growth factor-a (TGF-a) bound to the mutant EGFR with high affinity and enhanced the intrinsic mutant EGFR kinase activity. The mutant EGFR was capable of transducing EGF-stimulated glioma cell proliferation and invasiveness in an in vitro three-dimensional spheroid model. The deletion-mutant EGFR in D-298 MG is capable of being activated by growth factor; this suggests that overexpression of this mutant EGFR protein rather than structural alteration may be the more significant biologic event.
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PMID:Deletion-mutant epidermal growth factor receptor in human gliomas: effects of type II mutation on receptor function. 167

Targeting of toxic substances to the epidermal growth factor, EGF, receptor might be an attractive therapeutic approach because of the increased receptor-expression in some human tumours such as, for example, malignant gliomas and squamous lung carcinomas. Radiation effects of [131I]EGF on human malignant glioma cells growing as monolayers were analysed in this study. The cells were, in all cases, incubated for 25 min with about 350 kBq/ml [131I]EGF, which gave a total binding of 3.2-3.5 kBq/10(5) cells. The rapid release of activity from the cells caused by the normal degradation of EGF was inhibited by incubation with 30 microM chloroquine or 5 mM lidocaine added to the cell culture medium. These substances are, at these concentrations, known to inhibit proteolytic processes in lysosomes. No effects of the inhibitors alone were observed on cell growth and clonogenic survival. Inhibition of EGF degradation by chloroquine or lidocaine resulted in a significantly prolonged association of 131I with the test cells. About 70% of the initially bound radioactivity remained in the cells giving, after 6 h, a binding of 2.1-2.5 kBq/10(5) cells. A 6 h exposure to the radiation from 131I decays, mediated mainly by specifically bound EGF, gave a survival value of about 50%. Such an effect corresponds to a treatment of 2.5 Gy 60Co gamma-radiation. This is promising considering that, when monolayers are applied, only a very small fraction of the released energy from the 131I decays is deposited in the cells. Effects from non-receptor bound [131I]EGF were analysed after presaturation of the receptors with non-radioactive EGF, and gave no or very small changes in survival.
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PMID:Influence of chloroquine and lidocaine on retention and cytotoxic effects of [131I]EGF: studies on cultured glioma cells. 167 89

Some gliomas, melanomas and squamous carcinomas have large numbers of EGF receptors which could, in these cases, be used for targeting with toxic agents. We investigated whether EGF could be conjugated to dextran, which is a suitable carrier for toxic agents, without losing its ability to bind to the receptor. Dextran of 20 kDa molecular weight was activated with I-cyano-4-dimethylamino pyridinium tetrafluoroborate (CDAP) yielding highly active pyridinium-isourea derivatives. EGF was coupled to the activated dextran through the amino terminus and glycine was added to block residual activity. The EGF-dextran conjugate was, after purification on Sephadex G25 and Sephacryl 200 columns, tested for its receptor binding properties on human malignant glioma, U343MGaC12:6, cells. The conjugate inhibited binding of 125I-EGF in a competitive assay, showing that the binding was receptor-specific. Dextran conjugated with glycine, without EGF, had no inhibitory effect. The conjugate was radio-labelled either on the EGF part with 125I or on the dextran part with 3H-glycine, and the internalization patterns were compared to the internalization of 125I-EGF. The radioactivity of the conjugates remained cell-associated for more than 20 hr, regardless of whether the radioactivity was on the EGF or on the dextran part, while the radioactivity of unconjugated EGF rapidly disappeared from the cells. Most of the cell-associated radioactivity was, at all analysed time intervals, located intracellularly. Thus, it seems promising to use dextran, conjugated with EGF, as a carrier of, for example, toxic radioactive nuclides.
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PMID:Binding of epidermal growth factor-dextran conjugates to cultured glioma cells. 170 55


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