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)

A series of 43 human gliomas, consisting of 30 glioblastomas, 7 anaplastic astrocytomas, 3 low grade astrocytomas, 2 ependymomas, and 1 oligodendroglioma, was studied for amplification of the epidermal growth factor receptor (EGFR) and mouse double minute 2 (MDM2) genes. DNA extracted from formalin-fixed, paraffin-embedded tissue sections was analyzed by differential PCR and the results were compared with slot blot examination of DNA extracted from frozen tissue from the same neoplasms. Twelve glioblastomas (40%) showed amplification of the EGFR gene, and overexpression of EGFR was evident in each of these tumors as indicated by the immunoperoxidase technique. Two of the tumors with EGFR gene amplification also revealed amplification of the MDM2 gene, while one additional glioblastoma revealed MDM2 amplification only. A 100% concordance in the detection of amplification was observed between differential PCR and slot blot analysis; consequently, these results indicate that differential PCR using DNA extracted from archival tissue sections is a reliable method of demonstrating gene amplifications in glial tumors.
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PMID:Reliability of differential PCR for the detection of EGFR and MDM2 gene amplification in DNA extracted from FFPE glioma tissue. 781 80

Although both spatial and temporal heterogeneity confound the description of the genetic events underlying glioma tumorigenesis, it is becoming evident that chromosome 17 loss and p53 inactivating mutations are probably involved early in the pathway of tumorigenesis of some, but not all, astrocytomas. Chromosome 10 loss and epidermal growth factor receptor amplification are seen predominantly in high-grade lesions, although they have not been shown to be independent prognostic indicators. Data is accumulating on the presence of a tumor suppressor gene on chromosome 9p, although the gene remains to be identified. The roles of chromosome 22 and the NF-2 tumor suppressor gene in the tumorigenesis of sporadic and familial meningiomas are discussed here, along with other nonrandom chromosomal alterations that are seen in both astrocytomas and meningiomas.
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PMID:Molecular genetics of astrocytomas and meningiomas. 786 78

Over the last decade, much has been learned about the genetic changes that occur in human neoplasia and how they contribute to the neoplastic state. Oncogenes and tumor suppressor genes have been identified, and many powerful molecular genetic techniques have emerged. Brain tumors have been intensively studied as part of this process. Specific and recurring genetic alterations have been identified and are associated with specific tumor types. In astrocytomas, for example, losses of genetic material on chromosomes 10 and 17 and amplification of the epidermal growth factor receptor gene seem important in pathogenesis, with the loss of chromosome 10 and the amplification of epidermal growth factor receptor being strongly associated with glioblastoma multiforme. Meningiomas, on the other hand, have usually lost part or all of chromosome 22. Brain tumors also express growth factors and growth factor receptors that may be important in promoting tumor growth and angiogenesis. These include epidermal growth factor, transforming growth factor-alpha, platelet-derived growth factor, the fibroblast growth factors, and vascular endothelial growth factor. In this article, we review the genetic aberrations that occur in the major types of brain tumors, including glial tumors, meningiomas, acoustic neuromas, medulloblastomas, primitive neuroectodermal tumors, and pituitary tumors. Wherever possible, clinical correlations have been made concerning the prognostic and therapeutic implications of specific aberrations. We also provide some background about the cytogenetic and molecular genetic techniques that have contributed to the description and understanding of these alterations and speculate as to some clinical and basic science issues that might be explored in the future.
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PMID:Genetic aberrations in human brain tumors. 800 71

Amplifications of cellular oncogenes and growth factor genes have previously been reported in gliomas. Here we have evaluated 21 gliomas for amplification of tumor related genes including NMYC, EGFR, TGFalpha, MET, CMYC, SRC, HRAS, NRAS, SEC, ROS1, JUN, and WNT1. Five amplifications were observed. The epidermal growth factor receptor (EGFR) gene was amplified in 4 glioblastomas. The oncogene MET was amplified in a glioblastoma which showed no EGFR gene amplification. Importantly, both genes are located on chromosome 7 and belong to a family with tyrosine kinase activity. There was no amplification found for TGFalpha which was previously reported to be amplified in gliomas. The finding of MET and EGFR independently amplified in glioma lends further support to a crucial role of chromosome 7 in the development of gliomas.
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PMID:Two independent amplification events on chromosome 7 in glioma: amplification of the epidermal growth factor receptor gene and amplification of the oncogene MET. 801 63

The role of the low-affinity neurotrophin receptor (p75NTR) in signal transduction is undefined. Nerve growth factor can activate the sphingomyelin cycle, generating the putative-lipid second messenger ceramide. In T9 glioma cells, addition of a cell-permeable ceramide analog mimicked the effects of nerve growth factor on cell growth inhibition and process formation. This signaling pathway appears to be mediated by p75NTR in T9 cells and NIH 3T3 cells overexpressing p75NTR. Expression of an epidermal growth factor receptor-p75NTR chimera in T9 cells imparted to epidermal growth factor the ability to activate the sphingomyelin cycle. These data demonstrate that p75NTR is capable of signaling independently of the trk neurotrophin receptor (p140trk) and that ceramide may be a mediator in neurotrophin biology.
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PMID:Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor. 807 74

Tumor cells from a spontaneously arising canine astrocytoma were isolated and cloned. Three clonally derived cell lines (DL3580 clone 1, DL3580 clone 2, and DL3580 clone 3) were developed and found to express glial fibrillary acidic protein (GFAP) as well as epidermal growth factor receptor (EGFR/c-erbB1). The cell lines were tumorigenic as subcutaneous xenografts or as intracranial implants in athymic mice, or both. Both the monolayer astrocytoma cells and the xenograft tumor cells from clone 2 were aneuploid, with a modal number of 84 chromosomes per metaphase; clones 1 and 3 were also aneuploid with modal numbers of 82 and 75/79, respectively. The histology of both the initial spontaneously occurring tumor in the dog and the intracranial astrocytoma in athymic mice demonstrated features of diffuse infiltration into normal brain. These newly developed canine glioma cell lines are karyotypically stable for 1 yr in culture and carry the same marker chromosomes as the parental lines. These glioma cell lines may serve as models for investigating mechanisms of glioma invasion into brain. Additionally, clonal cell lines with divergent properties isolated from the same tumor may assist in studies of the molecular basis of astrocytoma progression and heterogeneity.
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PMID:Tumorigenic, invasive, karyotypic, and immunocytochemical characteristics of clonal cell lines derived from a spontaneous canine anaplastic astrocytoma. 832 Jan 82

The development of a malignant tumor generally entails a series of events that damage the genome of a somatic cell and result in the malignant phenotype. These events chronicle the malignant progression of a tumor; a dynamic process in which more aggressive and growth-deregulated cell populations are constantly evolving. Gliomas, the most common primary tumors of brain, are known to become increasingly malignant with time. Within recent years, several details of the molecular genetic events associated in their progression have been determined. The earliest events of glioma progression include loss of genetic information from the long arms of chromosomes 13 or 22, or the short arm of chromosome 17 for which targeting of the TP53 (p53) gene has been indicated. Loss of a single complement of type I interferon (IFN) genes from 9p and loss of genetic information from 19q are seen in the tumors of intermediate malignancy grade. Events associated with the most malignant of glial tumors include loss of the second, type I IFN gene complement, loss of genetic information from chromosome 10, and gene amplification (most commonly the epidermal growth factor receptor, in 40% of cases). These findings have helped elucidate the events associated with glial tumorigenesis, and through the identification of specific genes, have provided a starting point for investigating the molecular biology of central nervous system neoplasia.
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PMID:Gene and chromosomal alterations associated with the development of human gliomas. 834 89

We have previously demonstrated antibody production to a glioma-associated variant form of the human epidermal growth factor receptor in rabbits that had received a synthetic peptide mimicking the unique primary structure of the variant protein as immunogen. We report here the response of mice, rabbits, goats, and macaques immunized by various protocols to this peptide. Titers to both peptide- and cell-elaborated variant receptor were measured, and the capacity to recognize the variant receptor in human tumor samples was determined. Within the range of species and strains investigated, we demonstrated a variable species-associated response to the peptide (rabbits > mice > goats > rats > macaques). Rabbits and a single goat produced specific, high titer antibody activity to the variant receptor protein following immunization with peptide alone. Murine titers to the parent protein were not appreciable following peptide immunization alone; additional immunization with variant receptor as expressed on cell membranes was used to boost this response.
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PMID:Investigation of a synthetic peptide as immunogen for a variant epidermal growth factor receptor associated with gliomas. 836 Mar 27

The incidence of primary brain tumors has increased dramatically among elderly North Americans during the past two decades. Numerous chromosomal abnormalities have been associated with these tumors; various subsets of these abnormalities are specific to certain types of brain tumors. Astrocytic gliomas may exhibit losses of genetic information from chromosomes 9p, 10q, 11p, 13q, 17p, or 22. Mutations of the p53 gene are found mostly in the malignant astrocytic forms and have been linked to malignant tumor transformation and progression. Functional and structural abnormalities of the neurofibromatosis 1 (NF1) gene and overexpression of the epidermal growth factor receptor have been associated with expression of the malignant glioma phenotype. Other less clearly defined abnormalities in astrocytomas include mutations of the retinoblastoma (RB) gene and overexpression of platelet-derived growth factor; transforming growth factor-alpha and -beta; the c-erb B-1, c-myc, ras, c-fos, and ros oncogenes; and insulin-like growth factor I and II. In other glioma tumors, p53 mutations are either infrequent, as in oligodendrogliomas, or absent, as in ependymomas. Occasionally, medulloblastomas exhibit p53 mutations and loss of genetic information from chromosomes 6q and 16q or expression of the c-erb B-2 oncogene. Loss of heterozygosity in chromosome 22 is the most frequent event in meningiomas, suggesting the presence of a tumor-suppressor gene in this chromosome.
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PMID:Epidemiology, cytogenetics, and molecular biology of brain tumors. 849 8

The effects of specific antibodies against growth factors and receptors on deoxyribonucleic acid (DNA) synthesis in two established human glioma cell lines, A172 and TM-1, were examined. Anti-platelet-derived growth factor (PDGF), anti-basic fibroblast growth factor (bFGF), and anti-epidermal growth factor receptor (EGF-R) antibodies inhibited thymidine incorporation by both cell lines in serum-free medium. Antibody specific to transforming growth factor-alpha only slightly suppressed DNA synthesis by both cell lines. Although the antiproliferative effects of anti-PDGF and anti-bFGF antibodies decreased in serum-supplemented medium, the effect of anti-EGF-R antibody was little changed. The combination of anti-PDGF, anti-bFGF, and anti-EGF-R antibodies significantly inhibited thymidine incorporation by the two cell lines even in serum-supplemented medium. This preliminary study suggests that simultaneous blockade of multiple autocrine loops may provide a new approach to the treatment of human malignant gliomas.
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PMID:Antiproliferative effect of multiple autocrine loop blockade in human malignant glioma cell lines. 853 26


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