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

We investigated the biochemical changes which accompanied the development and reversion of methionine dependence in a human glioma cell line GaMg. This cell line attained a higher proliferation rate and more malignant morphology with increasing passages in vitro. Early passages (P10, P25, and P45) were able to grow in a methionine-deficient medium supplemented with homocysteine (Met-Hcy+), while a later passage (P60) had lost this ability, i.e., it had become methionine-dependent. From P60 cells, a methionine-independent revertant (P60R) was established by exposing the cells to 5-aza-2-deoxycytidine, followed by culture in a Met-Hcy+ medium. In these genetically related cell lines, we investigated homocysteine remethylation and the functional state of cobalamin-dependent methionine synthase, the enzyme responsible for remethylation of homocysteine to methionine. The methionine synthase activity in cell extracts was similar in all cell sublines. Intact cell methionine biosynthesis and nitrous oxide-dependent homocysteine export reflect homocysteine remethylation in cells cultured in a Met-Hcy+ and methionine-containing (Met+Hcy-) medium, respectively. Both of these parameters, as well as the cellular content of the substrate 5-methyltetrahydrofolate, and the cofactor methylcobalamin, in addition to adenosylcobalamin, were high in P10, declined progressively in P45 and P60, and were restored in P60R. P25 cells had some unique features among the methionine-independent phenotypes because both homocysteine remethylation and the level of 5-methyltetrahydrofolate were low in Met+Hcy- medium. The maximal homocysteine export rate in the presence of nitrous oxide, which reflects the overall transmethylation rate, was high in P60 and even higher in P60R compared to the lower passages. The basis for development of methionine dependence during culture of this glioma cell line seems related to the combined effects of reduced methionine biosynthesis and an increased overall transmethylation rate. The single parameter which most closely correlated to the ability to use homocysteine for growth was methylcobalamin. These data support a model for methionine dependence, which implies impaired provision of cobalamin to methionine synthase.
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PMID:Development and reversion of methionine dependence in a human glioma cell line: relation to homocysteine remethylation and cobalamin status. 806 55

The expression of beta 2-adrenergic receptors is up-regulated by glucocorticoids. In contrast, beta 1-adrenergic receptors display glucocorticoid-induced down-regulation. In rat C6 glioma cells, which express both of these subtypes of beta-adrenergic receptors, the synthetic glucocorticoid dexamethasone stimulates no change in the total beta-adrenergic receptor content, but rather shifts the beta 1:beta 2 ratio from 80:20 to 50:50. Radioligand binding and immunoblotting demonstrate a sharp decline in beta 1-adrenergic receptor expression. Metabolic labelling of cells with [35S]-methionine in tandem with immunoprecipitation by beta 1-adrenergic-receptor-specific antibodies reveals a sharp decline in the synthesis of the receptor within 48 h for cells challenged with glucocorticoid. Steady-state levels of beta 1-adrenergic-receptor mRNA declined from 0.47 to 0.26 amol/microgram of total cellular RNA within 2 h of dexamethasone challenge, as measured by DNA-excess solution hybridization. The stability of receptor mRNA was not influenced by glucocorticoid; the half-lives of the beta 1- and beta 2-subtype mRNAs were 1.7 and 1.5 h respectively. Nuclear run-on assays revealed the basis for the down-regulation of receptor expression, i.e. a sharp decline in the relative rate of transcription for the beta 1-adrenergic-receptor gene in nuclei from dexamethasone-treated as compared with vehicle-treated cells. These data demonstrate transcriptional suppression as a molecular explanation for glucocorticoid-induced down-regulation of beta 1-adrenergic receptors.
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PMID:Glucocorticoids down-regulate beta 1-adrenergic-receptor expression by suppressing transcription of the receptor gene. 809 90

When cisplatin is administered in the form of a cisplatin-methionine substitution complex, high doses of cisplatin can be tolerated with no obvious signs of renal toxicity. We have demonstrated that male Wistar rats receiving a single i.p. dose of cisplatin-methionine at a 1:5 ratio (by weight) did not exhibit cisplatin-induced nephrotoxicity, while cisplatin administered alone at an identical concentration (6 mg/kg) resulted in marked renal toxicity in all animals treated. Using renal cortical slices prepared from untreated rats, we demonstrated that cisplatin, but not cisplatin-methionine, inhibited the accumulation of 14C-tetraethylammonium (TEA). This observation suggests that cisplatin, unlike cisplatin-methionine, is a substrate for the organic base transport system. In addition, cisplatin alone was more cytotoxic to C6 glioma cells in vitro than the cisplatin-methionine complex. Exposure of C6 glioma cells to cisplatin-methionine, however, resulted in a 50%-60% reduction in 3H-thymidine incorporation at cisplatin:methionine ratios up to 1:10. These results indicate that cisplatin-methionine is significantly cytotoxic yet lacks cisplatin-associated renal toxicity and may, therefore, have a role in the treatment of human malignancies.
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PMID:The nephrotoxicity, cytotoxicity and renal handling of a cisplatin-methionine complex in male Wistar rats. 817 19

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

The authors examined 50 patients with cerebral glioma with use of positron emission tomography (PET) and L-[methyl]-[11C]methionine to assess the grade of malignancy and the extent of cerebral glioma. Carbon-11 methionine was highly accumulated in the lesion in 31 of 32 patients with high-grade glioma and 11 of 18 patients with low-grade glioma. The rate of uptake of C-11 methionine in high-grade glioma was significantly higher than in low-grade glioma (P < .001). However, in individual cases it was difficult to evaluate the grade of malignancy only from the degree of C-11 methionine accumulation. In most cases, the area of increased accumulation of C-11 methionine did not correspond to the abnormalities seen at computed tomography (CT). Surgical intervention confirmed that methionine PET delineated the extent of cerebral glioma more clearly than did CT. The authors concluded that methionine PET has greater utility in assessing the extent rather than the grade of malignancy of cerebral glioma.
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PMID:Cerebral glioma: evaluation with methionine PET. 841 53

The aim of this investigation was to assess the capacity of MR imaging to identify the tumour components of cerebral gliomas and thus to grade and delineate these tumours. A comparative analysis between MR examinations and histopathologic whole-brain sections was performed in 5 brain specimens from patients with malignant glial tumours. All cases were examined with MR imaging in vitro. In 2 cases a close comparison with the MR examination in vivo was also possible. The homogeneous hypercellular tumour core was not an isolated entity with typical signal characteristics in any sequence used. However, the tumour core was better observed in T2WI than in T1WI or PDWI, its signal characteristics both in vitro and in vivo being more hypointense than the peritumoural oedema. The use of image subtraction and T2 maps in combination with T2WI increased our capacity to correctly distinguish the most malignant part, compared with using each of these methods separately. In all cases, benign-looking tumour cells were found in the most peripheral aspects of the peritumoural oedema. These cells were not separately identified by any MR sequence or MR imaging method used. In 4 of the 5 cases of malignant glial tumours, we found isolated tumour cells and even larger tumour cell areas, though consisting of benign-looking cells, in areas that were visualized as normal in all sequences and MR imaging methods used. In all cases the necroses were heterogeneous. This heterogeneity was best reflected in the T2WI. Necroses were the most conspicuous tumour components in cases of malignant glioma and best reflected the underlying heterogeneous histopathology. A comparison between contrast-enhanced CT, Gd-DTPA-enhanced MR imaging and positron emission tomography (PET) with 11C-L-methionine was performed in 14 patients. In all patients except one, the area of increased 11C-L-methionine accumulation on PET, indicating viable tumour tissue, was the same size as, or larger than the extension of the contrast enhancement on both CT and MR. Contrast-enhanced MR and CT gave similar results as regards tumour extension. The increase in signal intensity 5 min post-contrast tended to be greater in the high-grade than in the low-grade tumour group. In order to evaluate the short- and long-term effects of formalin fixation on T1 and T2 of cerebral grey and white matter, MR imaging was also performed in 5 whole-brain specimens from patients with no known brain disease.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:MR imaging in cerebral gliomas analysis of tumour tissue components. 849 82

We previously showed that gangliosides inhibit DNA synthesis in Swiss 3T3 cells stimulated with platelet-derived growth factor (PDGF) in a dose-responsive manner. This correlated with the inhibitory effects of several gangliosides (except GM3) on tyrosine phosphorylation of the PDGF receptor (PDGFR). [35S]Methionine-labeled Swiss 3T3 cells were incubated either with or without gangliosides and stimulated with PDGF, and proteins were cross-linked with bis(sulfosuccinimidyl) suberate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that two protein bands (170 and 350 kDa) were specifically immunoprecipitated with an anti-PDGFR antibody. Using both Swiss 3T3 and human glioma U-1242MG cells, western blots with anti-PDGFR and anti-phosphotyrosine antibodies confirmed that these bands were the PDGFR monomer and dimer, respectively, and that phosphotyrosine was present in these bands only after cells were stimulated with PDGF. Of the gangliosides tested, GM1, GM2, GD1a, GD1b, GD3, and GT1b, but not GM3, inhibited the formation of the 350-kDa band. These results demonstrate that all gangliosides tested, except GM3, probably inhibit PDGF-mediated growth by preventing dimerization of PDGFR monomers. Loss of more complex gangliosides in human gliomas would permit unregulated activation of the PDGFR, contributing to uncontrolled growth stimulation. We propose that ganglioside inhibition of receptor dimerization is a novel mechanism for regulating and coordinating several trophic factor-mediated cell functions.
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PMID:Gangliosides inhibit platelet-derived growth factor-stimulated receptor dimerization in human glioma U-1242MG and Swiss 3T3 cells. 851 85

In the present study we investigated the frequency of p16 gene exon 2 mutations in 35 malignant gliomas, using either direct sequencing of the PCR products or cloning into the pCRII vector and sequencing of the cloned PCR products. No mutations were detected during direct sequencing of the PCR products. However, after sequencing of individual clones, we found multiple mutations in 5 tumors involving codons 73(GCC to ACC, Ala to Thr), 76 (GCC to GTC, Ala to Val), 85(GCT to ACT, Ala to Thr), 98(CAC to TAC, His to Tyr), 102 (GCG to GTG, Ala to Val), 106 (GTG to ATG, Val to Met), 107 (CGC to TGC, Arg to Cys), 127 (GCA to GTA, Ala to Val), 128 (CGG to TGG, Arg to Trp) and 136 (GGC to GAC, Gly to Asp). Mutations were found only in glioblastomas and were either C to T or G to A transitions. Each mutation was detected in a small percentage of tumor cells (1.3-22%) using individual colony sequencing and southern hybridization with mutant oligonucleotides, consistent with the heterogenous cell population of glioblastomas. The presence of p16 gene mutations only in glioblastomas suggests that they are late events in glioma development.
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PMID:Mutations of the p16 gene in gliomas. 855

Gliomas represent the largest group of primary brain tumors in adults. The astrocytic variants are the most common and the adult forms are histologically stratified into three malignancy grades. Of these glioblastoma is the most common and the most malignant; it has also been best studied by molecular genetics and cytogenetics. Double-minute chromosomes, known to represent amplified genes, are found in 50% of glioblastomas. Amplified genes are not detected in the most benign of the astrocytomas. Many genes have been shown to be amplified in more than single cases of gliomas and these include EGFR, CDK4, SAS, MDM2, GLI, PDGFAR, MYC, N MYC, MYCL1, MET, GADD153, and KIT. The most commonly amplified genes in glioblastomas are EGFR (in approximately 40%), CDK4, and SAS (in approximately 15%). The remainder of the genes are amplified at lower frequency. The best mapped amplicon in gliomas involves the 12q13-14 region. The amplicon is of undetermined size, encompasses a number of genes, and may be rearranged. It occurs in 15% of glioblastomas and almost always includes the CDK4 and SAS genes, in about 10% of tumors the MDM2 gene, and at lower frequency GLI, GADD153, and A2MR. All but A2MR are overexpressed if amplified. The amplified EGFR gene is frequently rearranged, resulting in changes in the regions of the transcript that codes for the extracellular domain. The resultant receptor is constitutively activated. These findings provide examples of the impact the use of modern molecular biological techniques has had on our understanding of oncogenic mechanisms in gliomas.
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PMID:Gene amplification in human gliomas. 858 64

A 37-year-old male with mixed glioma was treated with combined radio- and chemotherapy. The amino acid metabolism of the tumor site and normal brain was followed by positron emission tomography using [11C]methionine ([11C]Met). The accumulation of [11C]Met in the tumor decreased during therapy and slightly increased 7 months after completion of the therapy, but then decreased markedly. However, computed tomography revealed no notable changes. The contralateral gray matter also showed a gradual decrease of [11C]Met accumulation. These findings indicate that reduction of amino acid metabolism in the tumor continues after radiochemotherapy although neuroimaging reveals no further morphological changes. Such therapy also has long-term effects on normal brain tissue.
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PMID:Serial positron emission tomography imaging of changes in amino acid metabolism in low grade astrocytoma after radio- and chemotherapy-- Case report. 865 32


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