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  • 1
    ISSN: 1432-0533
    Keywords: Key words Ki-67 labeling index ; Magnetic resonance imaging ; Optic nerve glioma ; p53 ; Pilocytic ¶astrocytoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pilocytic and diffuse astrocytomas difficult. We reviewed 22 cases of optic nerve gliomas, 19 of which were pilocytic astrocytomas (PA), and 3 of which were diffuse, non-pilocytic astrocytomas. The cases were evaluated for their clinical course, radiographic appearance, histologic grade, and proliferation indices as detected by MIB-1 (Ki-67) and p53 antibodies. Of the 19 PA, 14 showed no tumor growth by magnetic resonance imaging, and had Ki-67 and p53 labeling indices (LI) of 〈 1%. The other 5 PA exhibited aggressive behavior manifest by marked diffuse infiltrative tumor growth causing death in 2 patients, 1 of whom was diagnosed with neurofibromatosis type 1 (immunoperoxidase and radiographs not available), and marked local growth with an average time to growth of 39.3 months, a Ki-67 LI of 2–3%, and a p53 LI of 〈 1% in three others. Three of the five aggressive PA histologically demonstrated a finely reticulated pattern, a pattern that appears as an exaggeration or expansion of the normal neuroglia of the optic nerve, and may simulate a diffuse low-grade astrocytoma. Two demonstrated the coarsely reticulated pattern, with the biphasic and microcystic pattern typical of PA. Three diffuse astrocytomas (2 anaplastic astrocytomas and 1 glioblastoma) originated clinically and radiographically from the optic nerve, and revealed a Ki-67 LI of 2–12%, a p53 LI of 2–8%, and an average time to growth of 8 months. We conclude that the majority of PA of the optic nerve are non-aggressive, stabilize radiographically, and have Ki-67 and p53 LI 〈 1%. However, a subpopulation of PA has a propensity for aggressive behavior, and are identified by a Ki-67 LI of 2–3% and a p53 LI of 〈 1%. Diffuse astrocytomas have both Ki-67 and p53 LI 〉 2%. Thus, in cases of aggressive optic nerve tumors in which the histologic review of biopsy material cannot confidently confirm the diagnosis of pilocytic or diffuse fibrillary glioma, a p53 LI of 〉 1% appears to favor the diagnosis of diffuse astrocytoma.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Brain tumors ; Gliomas ; Chromosomes ; Karyotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The four permanent human glioma-derived cell lines reported here are the first such lines for which the karyotypes have been followed from the original biopsies through the establishment of the lines in culture. Although ploidy changes were seen, each line retained either distinctive marker chromosomes or the overall original chromosomal distribution allowing the origin of each line to be established with certainty. D-263 MG expresses glial fibrillary acidic protein, all lines except D-245 MG are tumorigenic in athymic mice, and each line displays a unique pattern with respect to in vitro growth parameters and expression of biochemically defined markers, oncofetal antigens and lymphoid-associated markers. D-245 MG and D-259 MG are able to grow in the absence of supplemental glutamine; glutamine synthetase was detected in these cell lines both by immunocytochemistry and by direct assay. Thus, the four permanent human glioma-derived cell lines described here are representative of glioma lines in their general characteristics. D-259 MG retains numerous double minute chromosomes (DMs), D-263 MG contains two marker chromosomes with breaks in 9p, and D-247 MG and D-245 MG with stemlines containing 96 and 89 chromosomes contain eight and six normal copies (respectively) of chromosome No. 7. The retention in these four cell lines of the most common chromosomal abnormalities seen in biopsies of malignant human gliomas provides the opportunity to investigate the meaning of these specific chromosomal changes.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 73 (1987), S. 309-312 
    ISSN: 1432-0533
    Keywords: Hydroxyurea ; Synchronize ; Glioma ; Chromosomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Karyotypic studies of human gliomas are often limited by a low mitotic index and the appearance of contracted chromosomes that do not exhibit clear banding patterns. The purpose of this study was to investigate the use of hydroxyurea (HU) as a synchronizing agent using established human glioma cell lines as a model system. HU was shown to reversibly inhibit cellular replication in glioma cell lines U-251 MG, D-245MG, D-247MG and D-263MG by flow cytometry on the basis of DNA content. Two-to sixfold increases were demonstrated in the mitotic index of HU-treated cultures exhibiting the greatest percentage of cells in the G2/M phases of the cell cycle. HU, therefore, promises to be an effective agent for use in short term cultures from biopsied human tumors to increase the quality of chromosome preparations in these tumors.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: GD2 ; Monoclonal antibodies ; Gliomas ; Ganglisides ; Medulloblastomas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Monoclonal antibodies (mAbs) recognizing the disialoganglioside II3(NeuAc)2GgOse3Cer (GD2) were produced by immunizing mice with the GD2-expressing neuroblastoma cell line LAN-1 and a prefusion boost with purified GD2 coupled to Salmonella minnesota. Two IgM mAbs were isolated which demonstrated high levels of reactivity (binding ratios in excess of 100) with GD2 by solid-phase radioimmunoassay and positivity in high-performance thin-layer chromatography (HPTLC) immunostain; only one (DMAb-20) was subsequently shown by analysis with a panel of defined ganglioside species to be specific for the minimum epitope of GD2, GalNAcβ1-4(NeuAcα2-8NeuAcα2-3)Gal-. DMAb-20 was used to evaluate the expression of GD2 by malignant glioma and medulloblastoma cell lines using cell surface radioimmunoassay, indirect membrane immunofluorescence, HPTLC immunostain, and densitometric analysis of extracted gangliosides from selected cell lines. Sixteen of 20 (80%) malignant glioma and 5 of 5 medulloblastoma cell lines reacted with DMAb-20; in agreement with previous studies, 5 of 5 neuroblastoma and 2 of 3 melanoma cell lines also reacted with DMAb-20. GD2 was proportionally increased in the glioma and medulloblastoma cell lines relative to levels in normal brain, as determined by densitometric analysis. In a phenotypic survey of malignant glioma biopsies, tumor cells in 24 of 30 (80%) cases stained positively with DMAb-20. Reactive astrocytes, both within and adjacent to tumors, were frequently intensely stained. Among the morphological variants of glioblastoma examined, the most intense staining with DMAb-20 was observed in neoplastic gemistocytes, with the weakest or absent staining in small cell glioblastomas. As GD2 is a commonly expressed surface antigen of gliomas and medulloblastomas, expression of which is retained in tissue culture, DMAb-20 will be useful in determining the functional role of GD2 in cell-cell interaction, adhesion, and invasion, and in defining altered growth control mechanisms of central nervous system neoplasms in in vitro models.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Malignant human gliomas ; Epidermal growth factor ; Epidermal growth factor receptor ; Monoclonal antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Epidermal growth factor (EGF) has been shown to stimulate DNA synthesis and cell division in normal glia. At least half of malignant human gliomas (MHG) express high levels of the EGF receptor (EGFR), which are above those detected in normal brain. The demonstration that antibodies against the EGFR inhibit the growth of squamous cell carcinoma line A-431, with large numbers of EGFR, in vitro and in vivo raises the possibility that these agents could be used therapeutically against malignant human gliomas either alone or conjugated to other agents. We have measured the growth effects of EGF and an anti-EGFR monoclonal antibody, 528 (Ab-528), on four well-characterized human malignant glioma cell lines, D-263 MG, D-247 MG, U-343 MGa Cl 2∶6, and D-37 MG, with 2.9×104, 1.5×105, 8.6×105 and 1.59×106 EGFRs per cell, respectively. EGF significantly increased cell number in D-263 MG and D-37 MG by 65% and 74%, respectively, had no effect on D-247 MG, and significantly decreased cell number in U-343 MGa Cl 2∶6 by 39%. U-343 MGa Cl 2∶6 growth was inhibited 19% by Ab-528, but Ab-528 had no effect on growth of the other MHG lines. Ab-528 significantly inhibited all EGF-mediated growth effects. These studies demonstrate that, although Ab-528 alone has little antiproliferative activity on MGH, it successfully competes with EGF to reduce the biological effects of EGF-EGFR binding. Therefore, this antibody could potentially be used to target radioisotopes to MHG via the EGFR for diagnosis and therapy.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0533
    Keywords: Key words Brain tumor ; Medulloblastoma ; Chromosome 17 ; Fluorescence in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Loss of portions of chromosome 17p, usually through the formation of i(17qp) is a well-known finding in medulloblastomas. Loss of heterozygosity (LOH) studies, however, occasionally demonstrate loss of the more distal portions of 17p, a pattern which is more consistent with a terminal deletion. Here we use a combination of routine karyotyping, fluorescence in situ hybridization (FISH) and LOH studies on four medulloblastoma cell lines and one xenograft to demonstrate the spectrum of chromosome 17 abnormalities which occur in these tumors. Cell line D-556 Med showed a typical dicentric i(17q) and cell line D-721 Med showed two normal copies of chromosome 17 by all methods. Cell line D-425 Med showed loss of terminal 17p by LOH, while the karyotype showed what appeared to be an i(17q). FISH and chromosome 17 painting, however, demonstrated that the abnormal chromosome 17 was actually formed through an unbalanced translocation involving two copies of chromosome 17, with breakpoints at p12 and q11-1, an explanation which reconciled the cytogenetic and LOH findings. Cell line D 581 Med had a terminal deletion at 17p11.2. The finding of two cells with i(17q) in this case by interphase FISH suggests that the terminal deletion arose from breakage of an i(17q). Finally, xenograft D 690 Med showed LOH for regions distal to 17p12, whereas karyotyping, FISH using probes on 17p, and chromosome 17 painting showed two intact copies of chromosome 17. This pattern can be explained by homologous recombination. These data support the concept that the critical deletion of 17p can occur through a variety of mechanisms in the medulloblastoma. The losses may occur through typical i(17q), as well as other mechanisms such as terminal deletions, possibly through breakage of i(17q), unbalanced translocations and homologous recombination.
    Type of Medium: Electronic Resource
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