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

Culturing human central nervous system tumors has been difficult compared to other neoplasms. We report improved success rates for establishing short term human brain tumor cultures using a modified tissue processing technique. Eighty-seven brain tumor specimens (56 glioblastomas, 8 mid grade astrocytomas, 8 oligodendrogliomas, 15 other) were obtained from June 1988 to March 1997. The first twenty-three samples were processed by dissection, partial enzyme dissociation, and filtration through a tissue culture sieve. Subsequent samples were processed identically except tumor cells were centrifuged on a density gradient prior to plating. Successful cultures were defined as those surviving greater than three passages in tissue culture and growing to sufficient numbers (>10(6) cells) to allow freezing. Success rate was 42% (10/23) using standard processing methods and 86% (55/64) with the addition of density gradient centrifugation. Glial fibrillary acidic protein (GFAP) and vimentin staining, karyotypes, and growth curves were obtained for representative glioma cultures. All cultures tested were positive for vimentin (29/29) while 62% (18/29) were positive for GFAP. Of four cultures karyotyped (two glioblastomas, two oligodendrogliomas), all but one oligodendroglioma culture exhibited clonal cytogenetic abnormalities. These immunohistochemical and karyotypic results are consistent with the malignant glial origin of these cells. Of note, low passage human glioma cultures grew slower and exhibited more contact inhibition than immortalized human glioblastoma cell lines. Nevertheless, this simple method for establishing short term human brain tumor cultures should aid in further developing human brain tumor pre-clinical models as well as enhancing clinical applications dependent on in vitro human brain tumor cell growth adjust.
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PMID:Improved technique for establishing short term human brain tumor cultures. 1044 65

Chordoid glioma of the third ventricle was recently reported as a novel tumor entity of the central nervous system with characteristic clinical and histopathological features (Brat et al., J Neuropathol Exp Neurol 57: 283-290, 1998). Here, we report on a histopathological, immunohistochemical and molecular genetic analysis of five cases of this rare neoplasm. All tumors were immunohistochemically investigated for the expression of various differentiation antigens, the proliferation marker Ki-67, and a panel of selected proto-oncogene and tumor suppressor gene products. These studies revealed a strong expression of GFAP, vimentin, and CD34. In addition, most tumors contained small fractions of neoplastic cells immunoreactive for epithelial membrane antigen, S-100 protein, or cytokeratins. The percentage of Ki-67 positive cells was generally low (<5%). All tumors showed immunoreactivity for the epidermal growth factor receptor and schwannomin/merlin. There was no nuclear accumulation of the p53, p21 (Waf-1) and Mdm2 proteins. To examine genomic alterations associated with the development of chordoid gliomas, we screened 4 tumors by comparative genomic hybridization (CGH) analysis. No chromosomal imbalances were detected. More focussed molecular genetic analyses revealed neither aberrations of the TP53 and CDKN2A tumor suppressor genes nor amplification of the EGFR, CDK4, and MDM2 proto-oncogenes. Our data strongly support the hypothesis that chordoid glioma of the third ventricle constitutes a novel tumor entity characterized by distinct morphological and immunohistochemical features, as well as a lack of chromosomal and genetic alterations commonly found in other types of gliomas or in meningiomas.
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PMID:Chordoid glioma of the third ventricle: immunohistochemical and molecular genetic characterization of a novel tumor entity. 1051

Rats developed mixed gliomas, oligodendrogliomas, and a few astrocytomas in response to transplacental ethylnitrosourea. The neoplastic cell composition of mixed gliomas must be defined; this study required a 20-80% admixture of neoplastic astrocytes and oligodendroglia for the diagnosis of mixed glioma. A battery of immunoantibodies, including Leu-7, S-100, and vimentin, were helpful in classifying rat gliomas, and the histologic features of each tumor type are described. Other brain tumor characteristics that may decide the outcome of carcinogenicity studies include incidence, multiplicity, latency, fatality, size, and malignancy. The size of tumors was determined by measuring their 3-dimensional volumes. Brain tumor volume was found to be highly correlated with malignancy and fatality. Systematic evaluation of the malignancy of brain tumors is an important but often overlooked adjunct method of measuring the effectiveness of a carcinogen. A system to estimate malignancy, one that grades 9 tumor characteristics and weights, each according to clinical outcome, was developed. It was found that mixed gliomas grew larger, had a shorter latency, and were significantly more malignant than were other gliomas.
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PMID:Evaluation of ENU-induced gliomas in rats: nomenclature, immunochemistry, and malignancy. 1066 7

Keratin intermediate filaments (Ifs) are specific for epithelial cell differentiation. This study demonstrates the presence of keratin in two recently established human glioblastoma cell lines 8-MG-BA and 42-MG-BA. Immunofluorescence staining was performed on cells within passage 230 to 235 using monoclonal pan-cytokeratin antibodies. The cells were analyzed during several DIV at different cell density. Keratin-positive stained cells reached 5 to 7% in 8-MG-BA and less than 0.1% in 42-MG-BA cell line. The presence of keratin-positive cells was independent on cell density and days in vitro. Keratin-positive cells appeared unevenly distributed in both cell lines. They were observed as single or areas of keratin-positive cells. The morphological features of keratin-positive and keratin-negative cells were similar. The results are discussed with respect to previous studies on glial fibrillary acidic protein (GFAP) and vimentin to show the heterogeneity of IFs expression in glioma cell lines.
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PMID:Heterogeneity of keratin intermediate filaments expression in human glioma cell lines. 1073 69

Permanent glioma cell lines are invaluable tools in understanding the biology of glioblastomas. The present study reports the establishment of a clonal human cell line, GBM6840, derived from a biopsy of paediatric cerebellar glioblastoma multiforme. GBM6840 had a doubling time of 32 h and grew as a monolayer of large round cells that retained immunopositivity for glial fibrillary acidic protein and vimentin. Karyotypic analysis revealed a modal chromosome number of 68 and polysomies of chromosomes 3, 5 and 20, as well as the presence of 3-4 marker chromosomes. GBM6840 also showed anchorage-independent growth in soft agar and tumour formation in nude mice. The p16(CDKN2A) gene was transcriptionally silenced by hypermethylation, consistent with the lack of protein expression observed in the original tumour and cultured cells. Western blot analysis revealed normal protein expression of pRb and CDK4. It appears that p16 is the major component altered in the cell cycle pathway and may confer these cells unrestrained proliferation potential. Neither EGFR gene amplification nor over-expression of the protein was detected in the cultured cells. Over-expression of the p53 protein was observed in the majority of cells, despite undetectable mutation (exons 5-8) in the gene. One allele of the PTEN gene was found to be mutated during in vitro cultivation. Telomerase activity was demonstrated in the cultured cells but not in the original tumour, supporting the hypothesis that telomerase is required for the in vitro immortalization process.
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PMID:Establishment and characterization of a human cell line from paediatric cerebellar glioblastoma multiforme. 1073 64

Herpes simplex virus thymidine kinase (HSV-tk) gene transfer and ganciclovir (GCV) administration have been suggested for the treatment of malignant gliomas. To understand tissue responses and possible ways to improve the treatment effect, we studied tumor growth, tissue reactions, and survival time after HSV-tk/GCV treatment in a syngeneic BT4C rat glioma model by mixing various ratios of stably transfected HSV-tk-expressing BT4C-tk glioma cells with wild-type BT4C glioma cells (percentage of BT4C-tk cells: 0%, 1%, 10%, 30%, 50%, and 100%), followed by injection into BDIX rat brains (n = 79). With the exception of some animals with end-stage tumors, very little astroglia or microglia reactivity was detected in the wild-type tumors as analyzed by immunocytochemistry using glial fibrillary acid protein (GFAP)-, vimentin-, human histocompatibility leukocyte antigen-DR-, OX-42-, and CD68-specific monoclonal antibodies. After 14 days of GCV treatment, tumors induced with > or = 10% BT4C-tk cells showed a significant reduction in tumor size (P < .05) and prolonged survival time (P < .01). Astrogliosis, as indicated by a strong GFAP and vimentin immunoreactivity, was seen in the tumor scar area. GFAP and vimentin reactivity was already present after the GCV treatment in tumors induced with 1% BT4C-tk cells. Much less human histocompatibility leukocyte antigen-DR-positive microglia was seen in the treated animals, indicating low microglia reactivity and immunoactivation against the tumor. However, GCV-treated tumors were positive for apoptosis, indicating that apoptosis is an important mechanism for cell death in the BT4C-tk glioma model. Our results suggest that > or = 10% transfection efficiency is required for a successful reduction in BT4C glioma tumor size with HSV-tk/GCV treatment in vivo. Tissue reactions after 14 days of GCV treatment are characterized by astrogliosis and apoptosis, whereas microglia response and immunoactivation of the brain cells appear to play a minor role. Stimulation of the microglia response by gene transfer or other means might improve the efficacy of the HSV-tk/GCV treatment in vivo.
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PMID:Herpes simplex virus thymidine kinase gene therapy in experimental rat BT4C glioma model: effect of the percentage of thymidine kinase-positive glioma cells on treatment effect, survival time, and tissue reactions. 1076 47

S100A1 and S100B are members of a multigenic family of Ca(2+)-binding proteins of the EF-hand type highly abundant in astrocyte and striated muscle cells that have been implicated in the Ca(2+)-dependent regulation of several intracellular activities including the assembly and disassembly of microtubules and type III intermediate filaments. In the present work we tested S100A1 and S100B for their ability to cause microtubule and/or intermediate filament disassembly in situ using triton-cytoskeletons obtained from U251 glioma cells and rat L6 myoblasts. Our results indicate that: (i) both proteins cause a Ca(2+)-dependent disassembly of cytoplasmic microtubules in a dose-dependent manner; (ii) the S100A1- and S100B-inhibitory peptide, TRTK-12, blocks the S100A1 and S100B effects on microtubules; (iii) S100A1Delta88-93, an S100A1 mutant lacking the C-terminal extension, does not affect microtubule stability; and (iv) no obvious S100A1- or S100B-dependent intermediate filament disassembly could be observed under the experimental conditions used in the present study, but S100A1- and S100B-dependent microtubule disassembly results in a tendency of vimentin intermediate filaments to aggregate into bundles and/or to condense. Together, these results suggest that S100A1 and S100B probably cause microtubule disassembly by interacting with the microtubule wall, and that the two proteins do not affect intermediate filament stability via interaction with preformed intermediate filaments, in agreement with previous biochemical investigation. Our present data lend support to the possibility that S100A1 and S100B might have a role in the in vivo regulation of the state of assembly of microtubules in a Ca(2+)-regulated manner and, potentially, on microtubule-based activities in astrocytes and myoblasts. Also, these data suggest that the both S100 proteins use their C-terminal extension for interacting with microtubules.
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PMID:Effects of S100A1 and S100B on microtubule stability. An in vitro study using triton-cytoskeletons from astrocyte and myoblast cell lines. 1097 40

Nucleoside diphosphate kinases (Nm23/NDPK) are enzymes functional in cell proliferation, differentiation, development, tumor progression, and metastasis. Nevertheless, no consensus exists about the molecular mechanism by which Nm23/NDPK isoforms exert their role in these processes. We investigated the expression of the rat Nm23-R1/NDPKbeta and Nm23-R2/NDPKalpha isoforms, homologues of the human Nm23-H1/NDPK A and Nm23-H2/NDPK B proteins, respectively, upon cAMP-induced differentiation of rat C6 glioma cells and demonstrated a differential interaction with intermediate filaments. Semiquantitative RT-PCR, immunoblotting, and flow cytometry showed a constitutive expression of both Nm23 isoforms. After induction of differentiation in C6 cells with cAMP analogs or isoproterenol, a dose-dependent 2- and 2.5-fold upregulation of the Nm23-R1 mRNA and protein, respectively, was observed. In contrast, the expression of Nm23-R2 remained unchanged. Localization of both isoforms with confocal laser scanning microscopy demonstrated a punctate reticular staining pattern for both Nm23 isoforms in the cytosol and processes of the cells which was particularly intense in the perinuclear region. In addition, while Nm23-R2 was colocalized and coimmunoprecipitated with vimentin in nondifferentiated cells, both isoforms were associated with GFAP in differentiated cells. The significance of these findings in relation to a possible function of Nm23 isoforms in cell proliferation, differentiation, and tumor-associated mechanisms is discussed.
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PMID:Nucleoside diphosphate kinase beta (Nm23-R1/NDPKbeta) is associated with intermediate filaments and becomes upregulated upon cAMP-induced differentiation of rat C6 glioma. 1108 83

Chordoid glioma is a rare neoplasm occurring in the third ventricle and, as the name implies, having a chordoid appearance. It is currently considered a glial neoplasm of uncertain histogenesis with distinct clinicopathologic features. We report three cases of chordoid glioma with a focus on the ultrastructural appearance. The patients were two men and one woman aged, respectively, 34, 40, and 43 years. Immunohistochemically, all tumors showed strong and diffuse reactivity for glial fibrillary acidic protein and vimentin, whereas immunoreactivity for epithelial membrane antigen and cytokeratin was focal. Ultrastructurally, they showed features of ependymal differentiation for the presence of an apical pole with microvilli and a basal pole characterized, as in normal ependyma, by many hemidesmosomelike structures connecting cell membranes to the underlying basal lamina. Constant features were a submicroscopic cell body zonation (i.e., perinuclear, intermediate, subapical, and apical regions) and the presence of secretory granules. These findings were similar to those described for the secretory ependymal cells of the subcommissural organ, a small structure located in a dorsocaudal region of the third ventricle that undergoes regression after birth in humans. Our observations suggest that chordoid glioma may represent a subtype of ependymoma whose cells resemble the highly specialized ependyma of the subcommissural organ.
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PMID:Chordoid glioma of the third ventricle: an ultrastructural study of three cases with a histogenetic hypothesis. 1122 12

Glial fibrillary acidic protein (GFAP), vimentin (Vi) and cytokeratin (CK) intermediate filament (IF) proteins were studied in glioblastoma cell line GL-15. The immunofluorescence staining revealed strong positive staining for vimentin in all cultured cells. Approximately 20% of analyzed cells showed strong and 50% moderate intensity of staining for GFAP. About 3% of all cells were positively stained with a mixture of anti-CK monoclonal antibodies. The expression of all IF was not in relation to the cell density or days in vitro after passage. The double immunofluoresce revealed that all CK-positive cells express GFAP and vimentin. This study demonstrates the heterogeneity of the clonal GL-15 glioma cell line which consists in three immunocytochemically distinct cell types: Vi+/GFAP-/CK-, Vi+/GFAP+/CK-, and Vi+/GFAP+/CK+. These findings give further evidence about the expression of non-glial IF in cultured glioma cells.
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PMID:Co-expression of GFAP, vimentin and cytokeratins in GL-15 glioblastoma cell line. 1126 60


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