Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormally high expression of epidermal growth factor receptors (EGF-receptors) may contribute to the unregulated growth of some tumors. We here report the EGF-receptor numbers and the effects of epidermal growth factor (EGF) on two human cell lines. The glioblastoma cell line T-MG1 had 135,000 EGF-receptors per cell, was slightly growth stimulated by EGF and showed no obvious change in morphology after exposure to EGF. The carcinoma cell line T-CAR1, derived from a brain metastasis of a carcinoma of the adrenal cortex, had approximately 7 million EGF-receptors per cell. EGF had a significant antiproliferative effect on these cells and caused rounding and detachment of cells in adherent cultures. The cell lines may become useful in future studies concerning the role of the EGF-receptors in malignant growth.
 ...
PMID:Overexpression of the epidermal growth factor receptor gene in a human carcinoma cell line, derived from a brain metastasis. 278 42

A variety of tumors with different histologic types are included in a group of brain tumors. Although each histologic type of tumor has its own range of malignancy, the prognosis seems to be affected by several clinical, histologic and cell-biological factors. For example, relative survival rate of patients with glioblastoma is lower if the patient is older than 50 or 60 years. The leptomeningeal dissemination of glioma cells is a sign of poor prognosis. The presence of necrotic foci in the astrocytic tumors suggests shorter astrocytic tumors suggests shorter survival. Using a monoclonal antibody to bromodeoxyuridine (BrdU), the growth activity of the tumor can be estimated by BrdU labeling index (BrdU-LI, %). Higher BrdU-LI is correlated with more malignant histologic features in astrocytic tumors. In meningiomas, higher BrdU-LI is correlated with a more frequent or rapid recurrence of the tumor. The significance of growth factor receptors and oncogene of growth factor receptors and oncogene products as a cell-biologic marker of malignancy was investigated with an immunohistochemical method. Transferrin receptor was demonstrated in all tumors, and epidermal growth factor in about 40% of astrocytic tumors. The immunoreaction to c-myc oncogene product was detected in most astrocytic tumors; with higher intensity in anaplastic astrocytomas and glioblastomas than in low-grade astrocytomas. The role of these markers in the prognosis of brain tumors is, however, still unclear. Total or subtotal resection of glioblastoma results in longer resection of glioblastoma results in longer survival. Both postoperative radiotherapy and chemotherapy are effective. However, maintenance of chemotherapy longer than longer than 2 years does not significantly improve the prognosis.
 ...
PMID:[Factors affecting the prognosis of brain tumors]. 284 33

Two established human tumor cell lines, epidermoid carcinoma line A431 and glioblastoma line SF268, were studied to compare the interaction of each with epidermal growth factor (EGF). SF268 cells bound [125I] EGF with 35-40 fold higher affinity than did the A431 cells. The EGF binding sites of both lines were photoaffinity labeled using 2,4-NAPS-[125I] EGF, a photoreactive derivative of EGF. Extracts of photolysed cells analyzed by SDS-PAGE showed a difference between the two cell lines in the high molecular weight component corresponding to the EGF receptor. EGF in a dose range from 0.3-200 nM had no effect on thymidine incorporation by SF268 cells, whereas thymidine incorporation by A431 cells was markedly inhibited by EGF.
 ...
PMID:Epidermal growth factor receptors in the human glioblastoma cell line SF268 differ from those in epidermoid carcinoma cell line A431. 299 56

Type beta transforming growth factor (beta-TGF) is a potent regulator of cell growth and differentiation. The human glioblastoma cell line, T-MGI, was growth inhibited by beta-TGF under anchorage independent conditions. The antiproliferative effect of beta-TGF was potentiated to nearly total arrest by low doses of retinoic acid (RA) or tumor necrosis factor (TNF), while epidermal growth factor, platelet-derived growth factor, interleukin-2, and gamma interferon did not have this potentiating effect. The potentiation of the beta-TGF effect by RA and TNF could not be explained by modulation of the epidermal growth factor receptor, the beta-TGF receptor, or the TNF receptor. beta-TGF alone and in combination with RA or TNF were further tested on primary cultures from freshly resected human glioma biopsies (n = 13). There was great individual variation in sensitivity to beta-TGF, RA, or TNF. The astrocytoma and oligodendroglioma cells were inhibited to various degrees by beta-TGF or TNF, while most of the glioblastomas were not sensitive to these agents. Most of the biopsies were stimulated by RA. RA or TNF did not potentiate the growth inhibitory effect of beta-TGF on biopsy cells. We therefore think it unlikely that beta-TGF in combination with RA or TNF will be effective agents in the treatment of gliomas.
 ...
PMID:Effects of type beta transforming growth factor in combination with retinoic acid or tumor necrosis factor on proliferation of a human glioblastoma cell line and clonogenic cells from freshly resected human brain tumors. 316 58

The cell surface receptor for the mitogenic peptide epidermal growth factor (EGF) is involved in control of normal cell growth and may play a role in the genesis of human neoplasia such as squamous carcinoma and glioblastoma. Soft-agar growth and focus-formation experiments with NIH 3T3 mouse fibroblasts transfected with an expression plasmid demonstrated the ligand-dependent transforming potential of the human EGF receptor without structural alterations. Activation of overexpressed normal receptor alone appears to be sufficient for transformation of NIH 3T3 cells in vitro.
 ...
PMID:Ligand activation of overexpressed epidermal growth factor receptors transforms NIH 3T3 mouse fibroblasts. 325 24

The gene encoding the receptor for epidermal growth factor was amplified two- to fivefold in the human glioblastoma cell line SF268. The amplified gene gave rise to abundant quantities of receptor that bound EGF with a high affinity (Kd, 0.35 nM). The binding of ligand failed to elicit cellular DNA synthesis, however, and the receptor was enzymatically inactive. We presume that the amplified receptor gene carries a mutation(s) that affects several aspects of the receptor's function. Characterization of the mutation(s) may illuminate how structure dictates function in the receptor protein.
 ...
PMID:Amplified gene for the epidermal growth factor receptor in a human glioblastoma cell line encodes an enzymatically inactive protein. 326 68

The binding capacity for epidermal growth factor (EGF) was determined in 34 intracranial neoplasms (14 glioblastoma, seven low-grade gliomas, six meningiomas, and seven others) and four specimens of normal brain by using [I125]EGF. EGF binding and binding affinity of the sites in the tumour and brain samples were compared to placenta and rat liver. All specimens of normal brain were negative. Ten of 14 glioblastoma specimens contained EGF binding (level range 10-39,660 fmol/mg protein), however, ligand binding affinity was high in only three tumours. Only one of nine low-grade gliomas contained EGF binding activity. Five of six meningiomas contained EGF binding sites (level range 49-776 fmol/mg protein) and binding affinity was high in two. When present EGF binding activity was found in all cellular fractions except the cytosol. There were no clinical or histopathological features within major tumour groups that were predictive of either high or specific EGF binding activity. These preliminary studies have confirmed that EGF receptor-like activity is present in the particulate fractions of intracranial neoplasms of both mesenchymal and neuroctodermal origin. In a large proportion of these tumours the EGF binding affinity is low, suggesting either a less specific or truncated EGF binding site.
 ...
PMID:Epidermal growth factor binding in intracranial neoplasms: preliminary biochemical and clinicopathological findings. 326 5

By using Southern blot analysis, we found that in two cases of human glioblastoma multiforme, cells carried amplified c-erbB genes which bore short deletion mutations within the ligand-binding domain of the epidermal growth factor (EGF) receptor. The products of these mutated c-erbB genes were about 30 kilodalton (kDa) smaller than the normal 170-kDa EGF receptor, and the tumor cell membrane fractions containing the 140-kDa abnormal EGF receptor showed a significant elevation of tyrosine kinase activity without its ligand. In view of the similarity to the activated viral and cellular erbB genes in the avian system, these mutated and overexpressed EGF receptors might play a role in the onset or development of human glioblastoma cells.
 ...
PMID:Amplification of the structurally and functionally altered epidermal growth factor receptor gene (c-erbB) in human brain tumors. 338 99

We have examined the subcellular distribution and catalytic activity of c-Src tyrosine kinase after stimulation of A172 glioblastoma cells with peptide growth factors. Treatment of resting cells with platelet-derived growth factor resulted in an increase (3.5-fold) in the amount of c-Src protein associated with the cytoskeleton. In addition, an increase in specific c-Src kinase activity was observed in the cytoskeleton as well as in the cytosol and the membrane fraction. Similar effects on both c-Src redistribution and activity were seen after stimulation with epidermal growth factor. These data show that, like other signal transducing components, c-Src also becomes activated and associated to the cytoskeleton in response to growth factor stimulation.
 ...
PMID:Activation and translocation of c-Src to the cytoskeleton by both platelet-derived growth factor and epidermal growth factor. 753 Jul 20

Mutations in the receptor for the epidermal growth factor provide valuable insight into mechanisms of growth control. Oncogenic mutants of this receptor tyrosine kinase cause erythroid leukemia, fibrosarcoma, angiosarcoma, glioblastoma, and melanoma. Mutations in the avian protooncogene occur by retroviral mechanisms. Deletion of the ligand-binding domain results in erythroblastosis, while additional mutations in cytoplasmic structures broaden the disease potential to other cell types. A carboxyl-terminal structure of erbB oncogenes modulates growth responses in a complex, cell-specific manner; this tissue-specificity region appears to promote growth in erythroblasts and to produce trans-dominant inhibition in fibroblasts. Human glioblastoma multiforme frequently contains receptor mutations that are reminiscent of avian oncogenes. In hereditary melanoma of Xiphophorus, aberrant regulation of transcription by a recombinant promoter determines tissue-specific tumorigenesis. The diversity of oncogenic mutations raises important questions concerning the roles of several receptor structures. The extracellular domain inhibits the receptor when unoccupied by ligand, for example, through a mechanism that is unknown. The auto-phosphorylation sites are dispensable for transformation, so their function in neoplastic growth is unclear. The carboxyl-terminal region promotes or blocks transformation in different tissues, suggesting complex regulation by unknown cellular factors. These issues are critical to understanding of the mechanisms of receptor activation and tissue tropism for this family of oncogenes.
 ...
PMID:Tissue-specific transformation by oncogenic mutants of epidermal growth factor receptor. 771 Nov 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>