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)

Epidemiological studies on intracranial tumors have suggested that the observed familial aggregation of a proportion of gliomas may be due to inherited predisposition to their development. In the Li-Fraumeni syndrome (LFS) associated with germ-line mutations of the p53 gene, nervous-system tumors are observed with increased frequency. However, the contribution of germ-line p53 mutation to the incidence of brain tumors has not been investigated. In order to address this point, we have performed 2 independent investigations. First, we have examined an unselected series of brain tumors. Whenever the presence of a p53 mutation in the tumor was observed, the possible germ-line origin of the mutation was investigated. Germ-line p53 mutations were also analyzed in constitutional DNA of patients with gliomas that had been selected for an unusual personal or familial history of cancer. Germ-line p53 mutations were detected in 1 out of 80 unselected cases and in 3 out of 15 selected cases (20%). We conclude that germ-line p53 mutation may contribute to a small fraction of gliomas that develop in the general population. The presence of a personal or familial history of cancer in a patient with glioma should prompt the search for a germ-line p53 mutation. However, the low frequency of p53 germ-line mutation suggests that alterations of this gene may not account for most familial cases of gliomas.
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PMID:Incidence of germ-line p53 mutations in patients with gliomas. 855 Feb 39

In this study, we demonstrated that tumor necrosis factor (TNF)-alpha inhibited the viability of rat glioma (C6) cells and induced apoptosis but did not affect the viability of rat newborn brain, mainly astroglial cells. The antitumor activity of TNF-alpha against C6 cells was partially inhibited by actinomycin D and cycloheximide, suggesting that it is possibly dependent upon new ribonucleic acid and protein synthesis. The results of immunoblotting assay demonstrated that TNF-alpha decreased the expression of mutant p53 protein but induced the expression of wild-type p53 in C6 cells during apoptosis. We suggest that TNF-alpha may activate the function of wild-type p53 protein by the suppression of mutant p53, at least indirectly, and induce p53-dependent apoptosis in glioma cells.
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PMID:Tumor necrosis factor-alpha induces p53-dependent apoptosis in rat glioma cells. 855 6

This study examines the relationship between p53 immunostaining and direct sequencing of polymerase chain reaction (PCR) products in 61 gliomas. Glioma tissues obtained from patients at surgery were analyzed immunohistochemically with the monoclonal antibody PAb1801 to detect p53 protein abnormalities. Amplified p53 cDNA from these samples was analyzed by direct sequencing. Four grades of p53 immunostaining were evaluated: grade 0 = no labeling, grade 1 = less than 5% labeled cells, grade 2 = 5-30% labeled cells, and grade 3 = more than 30% labeled cells. Twenty-six of 36 glioblastomas, 14 of 23 anaplastic gliomas, and none of two low-grade gliomas had positive p53 immunoreactivity. Direct sequencing of PCR-amplified p53 cDNA revealed that 10 glioblastomas, 11 anaplastic gliomas, and no low-grade gliomas had mutations. Comparison of p53 immunostaining and sequencing data revealed that among all the gliomas, mutations were found in three of 21 with p53 grade 0, one of 16 with p53 grade 1, seven of nine with p53 grade 2, and 10 of 15 with p53 grade 3. These results indicate a good correlation between the p53 immunostaining and sequencing data when the percentage of abnormal cells within the tumor was greater than 5% (p53 grades 2 and 3). However, the correlation was poor when the percentage of abnormal cells was less than 5% (p53 grade 1) because of the limited sensitivity of sequencing techniques. Thus, p53 immunostaining may be more accurate in detecting p53 alterations when the percentage of abnormal cells is small; however, in rare cases, p53 immunostaining may fail to detect mutations confirmed by sequencing.
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PMID:Correlation of p53 immunoreactivity and sequencing in patients with glioma. 856 60

Neoplastic transformation occurs in all glial cell types of the human nervous system, producing a wide variety of clinico-pathological entities and morphological variants. Astrocytomas are most common and span an unusually wide spectrum, ranging from the slowly growing juvenile pilocytic astrocytoma to the highly malignant glioblastoma multiforme. Diffusely infiltrating astrocytomas of the cerebral hemispheres show an inherent tendency for progression towards a more malignant phenotype. This change is morphologically categorized in histologic grading schemes (e.g., WHO Grade II to IV) and is associated with the sequential acquisition of genetic alterations, including mutations in the p53 and homozygous deletions of the p16 tumour suppressor genes. Loss of heterozygosity on chromosomes 10 and 19q as well as amplification of the EGF receptor are largely restricted to malignant gliomas and thus considered late events in astrocytoma progression. Gliomas often show phenotypic expression of different glial cell lineages (e.g., oligoastrocytoma). Recent studies suggest that the occurrence of mixed gliomas is not indicative of a polyclonal origin but rather reflects altered gene expression, leading to a change in the balance of growth factors influencing glioma differentiation.
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PMID:Histopathology, classification, and grading of gliomas. 858 58

Mutation of the p53 gene is among the most common lesions in a variety of human tumors, including those of the central nervous system. In most instances, mutation of one p53 allele is followed by loss of the remaining wild-type allele, resulting in cells with a complete absence of functional wild-type p53 protein. However, in some situations, such as at initiation of spontaneously arising gliomas or as the germline configuration of patients with the Li-Fraumeni syndrome, cells clearly carry both wild-type and mutant p53 alleles. These observations lead to the hypothesis that p53 mutations can give rise to loss of tumor suppressor functions as well as to gain of oncogenic transformation capabilities. In this review, we define the types of mutations that occur in the p53 gene in various glial tumors, contrast that with the spectra described in other human tumor types, and discuss the biochemistry and physiology of the p53 protein and its ability to regulate and be regulated by other gene products. We use this information to propose roles for p53 in the initiation and progression of human gliomas.
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PMID:The p53 gene and its role in human brain tumors. 858 66

The past few years have seen remarkable progress in understanding the molecular genetic basis of glioma formation. Affected oncogenes and tumor suppressor genes have been identified and putative tumor suppressor loci have been mapped. These studies have illustrated distinct molecular pathways for different glial neoplasms. We summarize the findings of an ongoing study initiated to characterize human gliomas on a molecular basis. The data are compiled from 150 astrocytic, oligodendroglial, and mixed gliomas that were assessed for genomic alterations characteristic of these neoplasms, i.e., loss of portions of chromosomes 1p, 9p, 10, 17p, 17q, and 19q, mutations of the p53 tumor suppressor gene, and amplification of the EGF receptor (EGFR) gene. Our findings support the hypothesis that distinct genetic pathways result in the formation of astrocytic and oligodendroglial neoplasms of different malignancy grades, and that glioblastoma multiforme may be subdivided into genetically distinct subsets. Such findings may not only lead to a better understanding of neoplastic transformation in glial cells, but may also have a major impact on clinical neuro-oncology.
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PMID:Molecular pathways in the formation of gliomas. 858 67

One event that accompanies glioma progression is the upregulation of angiogenesis. Low-grade gliomas are moderately vascularized tumors whereas high-grade gliomas show prominent microvascular proliferations and areas of high vascular density. To analyze the molecular mechanisms underlying glioma angiogenesis, we studied the expression of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptors VEGFR-1 and VEGFR-2 during normal brain development and glioma-induced angiogenesis. Our results suggest a paracrine control of angiogenesis and endothelial cell proliferation that is tightly regulated and transient in the embryonic brain, switched off in the normal adult brain, and turned on in tumor cells (VEGF) and the host vasculature (VEGFR-1 and -2) during tumor progression. It is unknown how VEGF and VEGF receptors are upregulated during glioma angiogenesis, but there is recent evidence that VEGF as well as endogenous inhibitors of angiogenesis could be under control of the tumor suppressor genes p53 and VHL.
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PMID:Angiogenesis in malignant gliomas. 858 68

Experimental studies in rodents using chemical carcinogens and viral oncogenes show a high susceptibility to malignant transformation. Analytical epidemiological studies have revealed an increased risk of human brain tumor development in association with certain occupations but, with the exception of therapeutic X-irradiation, attempts to identify a specific exposure or causative environmental agent have so far been unsuccessful. Thus, endogenous mutations and genetic factors may play a more important role. This view is supported by recent studies on the nature of DNA alterations in human brain tumors. More than 70% of p53 mutations observed during glioma progression are G:C-->A:T transitions, predominantly at CpG sites, i.e. likely to be produced by deamination of 5-mcC or related spontaneous mechanisms. No specific mutations or mutational hot spots were found which could be suggestive of environmental carcinogens operative in the etiology of human brain tumors. A similar pattern of mutation is found in colon cancer, sarcomas, and lymphomas, i.e. neoplasms with largely unknown etiology. This is similarly true for p53 germline mutations which again show a strong preference for G:C-->A:T transitions at CpG sites.
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PMID:Genetic and environmental factors in the etiology of human brain tumors. 859 15

The p53 tumor-suppressor gene is the most commonly mutated gene in cancer. However, p53 gene alterations are infrequent in renal-cell cancer (RCC). Bcl-2 has been shown to inhibit apoptosis triggered by wild-type p53 and an inverse correlation between Bcl-2 expression and p53 mutation has been observed in breast cancer and glioma. To characterize the expression of bcl-2 in RCC and its relationship to the p53 status, we analyzed 25 RCCs by immunohistochemistry for Bcl-2 and p53, Southern hybridization for bcl-2, and PCR-SSCP and sequencing for p53. Positive Bcl-2 staining was detected in 17 of 25 RCCs, whereas positive p53 staining was seen in only 1. Amplification of bcl-2 or p53 mutation was not detected in any of the tumors. Bcl-2 protein was expressed in all 7 RCC cell lines examined. Only one of the 7 lines had p53 mutation. These results suggest that overexpression of bcl-2, rather than p53 mutation, may prevent apoptosis during RCC development.
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PMID:Frequent expression of Bcl-2 in renal-cell carcinomas carrying wild-type p53. 862 Dec 51

Chemotherapeutic agent-induced DNA cleavage gives rise to apoptosis in a subpopulation of SK-N-SH human neuroblastoma cells; the remaining cells undergo Schwann cell-like differentiation. Like other neural crest and primitive neurectodermal tumor-derived cell lines, SK-N-SH cultures contain cells of neural (N-type) and epithelial (substrate-adherent, or S-type) phenotypes. Using isolated N-type and S-type cells from neuroblastoma, medulloblastoma, melanoma and glioma cell lines, we demonstrate that the determinants of the response to DNA cleavage are intrinsic properties of the cell. Furthermore, using a series of analogues of enediyne deoxyribonucleic acid (DNA) cleaving agents, we show that the molecular target of these agents is likely to be the same in N- and S-type cells, implying that the difference in response characteristics is a function of different distal pathways that are triggered by DNA cleavage. We demonstrate that the concentration of the DNA damaging agent used, and not the specific characteristics of the damage it produces, is the trigger for production of the cellular response. Response type does not correlate with previously published values for expression of the apoptosis modulators Bcl-2, Bcl-XL, wildtype p53, or, in medulloblastoma lines, p75.
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PMID:Determinants of the response of neuroblastoma cells to DNA damage: the roles of pre-treatment cell morphology and chemical nature of the damage. 862 28


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