Search Results - (Author, Cooperation:D. D. Bigner)

Showing 1 - 17 results of 17, query time: 0.26s Refine Results
  1. 1
    Staff View
    Publication Date:
    2011-07-02
    Publisher:
    American Association for the Advancement of Science (AAAS)
    Print ISSN:
    0036-8075
    Electronic ISSN:
    1095-9203
    Topics:
    Biology
    Chemistry and Pharmacology
    Computer Science
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Adaptor Proteins, Signal Transducing/*genetics/metabolism ; Carcinoma, Neuroendocrine/*genetics/pathology/physiopathology ; Cell Nucleus/metabolism ; Central Nervous System Neoplasms/*genetics/pathology/physiopathology ; Chromatin Assembly and Disassembly ; DNA Helicases/*genetics/metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Mutant Proteins/genetics/metabolism ; Mutation ; Nuclear Proteins/*genetics/metabolism ; Pancreatic Neoplasms/*genetics/pathology/physiopathology ; Phenotype ; Telomere/*physiology/ultrastructure
    Published by:
    http://www.aaas.org/

    Latest Papers from Table of Contents or Articles in Press
  2. 2
    Staff View
    Publication Date:
    2015-03-13
    Publisher:
    Nature Publishing Group (NPG)
    Print ISSN:
    0028-0836
    Electronic ISSN:
    1476-4687
    Topics:
    Biology
    Chemistry and Pharmacology
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Animals ; Antigens, Neoplasm/immunology ; CD4-Positive T-Lymphocytes/drug effects/immunology ; Cancer Vaccines/administration & dosage/*immunology/therapeutic use ; Cell Movement/drug effects ; Chemokine CCL3/*immunology ; Dendritic Cells/cytology/*drug effects/immunology ; Female ; Glioblastoma/drug therapy/*immunology/pathology/*therapy ; Humans ; Immunotherapy/methods ; Lymph Nodes/cytology/drug effects/immunology ; Mice ; Mice, Inbred C57BL ; Phosphoproteins/chemistry/genetics/immunology ; Substrate Specificity ; Survival Rate ; Tetanus Toxoid/*administration & dosage/*pharmacology/therapeutic use ; Treatment Outcome ; Viral Matrix Proteins/chemistry/genetics/immunology
    Published by:
    http://www.nature.com/

    Latest Papers from Table of Contents or Articles in Press
  3. 3
    P. A. Northcott ; D. J. Shih ; J. Peacock ; L. Garzia ; A. S. Morrissy ; T. Zichner ; A. M. Stutz ; A. Korshunov ; J. Reimand ; S. E. Schumacher ; R. Beroukhim ; D. W. Ellison ; C. R. Marshall ; A. C. Lionel ; S. Mack ; A. Dubuc ; Y. Yao ; V. Ramaswamy ; B. Luu ; A. Rolider ; F. M. Cavalli ; X. Wang ; M. Remke ; X. Wu ; R. Y. Chiu ; A. Chu ; E. Chuah ; R. D. Corbett ; G. R. Hoad ; S. D. Jackman ; Y. Li ; A. Lo ; K. L. Mungall ; K. M. Nip ; J. Q. Qian ; A. G. Raymond ; N. T. Thiessen ; R. J. Varhol ; I. Birol ; R. A. Moore ; A. J. Mungall ; R. Holt ; D. Kawauchi ; M. F. Roussel ; M. Kool ; D. T. Jones ; H. Witt ; L. A. Fernandez ; A. M. Kenney ; R. J. Wechsler-Reya ; P. Dirks ; T. Aviv ; W. A. Grajkowska ; M. Perek-Polnik ; C. C. Haberler ; O. Delattre ; S. S. Reynaud ; F. F. Doz ; S. S. Pernet-Fattet ; B. K. Cho ; S. K. Kim ; K. C. Wang ; W. Scheurlen ; C. G. Eberhart ; M. Fevre-Montange ; A. Jouvet ; I. F. Pollack ; X. Fan ; K. M. Muraszko ; G. Y. Gillespie ; C. Di Rocco ; L. Massimi ; E. M. Michiels ; N. K. Kloosterhof ; P. J. French ; J. M. Kros ; J. M. Olson ; R. G. Ellenbogen ; K. Zitterbart ; L. Kren ; R. C. Thompson ; M. K. Cooper ; B. Lach ; R. E. McLendon ; D. D. Bigner ; A. Fontebasso ; S. Albrecht ; N. Jabado ; J. C. Lindsey ; S. Bailey ; N. Gupta ; W. A. Weiss ; L. Bognar ; A. Klekner ; T. E. Van Meter ; T. Kumabe ; T. Tominaga ; S. K. Elbabaa ; J. R. Leonard ; J. B. Rubin ; L. M. Liau ; E. G. Van Meir ; M. Fouladi ; H. Nakamura ; G. Cinalli ; M. Garami ; P. Hauser ; A. G. Saad ; A. Iolascon ; S. Jung ; C. G. Carlotti ; R. Vibhakar ; Y. S. Ra ; S. Robinson ; M. Zollo ; C. C. Faria ; J. A. Chan ; M. L. Levy ; P. H. Sorensen ; M. Meyerson ; S. L. Pomeroy ; Y. J. Cho ; G. D. Bader ; U. Tabori ; C. E. Hawkins ; E. Bouffet ; S. W. Scherer ; J. T. Rutka ; D. Malkin ; S. C. Clifford ; S. J. Jones ; J. O. Korbel ; S. M. Pfister ; M. A. Marra ; M. D. Taylor
    Nature Publishing Group (NPG)
    Published 2012
    Staff View
    Publication Date:
    2012-07-27
    Publisher:
    Nature Publishing Group (NPG)
    Print ISSN:
    0028-0836
    Electronic ISSN:
    1476-4687
    Topics:
    Biology
    Chemistry and Pharmacology
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Carrier Proteins/genetics ; Cerebellar Neoplasms/*classification/*genetics/metabolism ; Child ; DNA Copy Number Variations/genetics ; Gene Duplication/genetics ; Genes, myc/genetics ; Genome, Human/*genetics ; Genomic Structural Variation/*genetics ; Genomics ; Hedgehog Proteins/metabolism ; Humans ; Medulloblastoma/*classification/*genetics/metabolism ; NF-kappa B/metabolism ; Nerve Tissue Proteins/genetics ; Oncogene Proteins, Fusion/genetics ; Proteins/genetics ; RNA, Long Noncoding ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Translocation, Genetic/genetics
    Published by:
    http://www.nature.com/

    Latest Papers from Table of Contents or Articles in Press
  4. 4
    Staff View
    Publication Date:
    2010-12-18
    Publisher:
    American Association for the Advancement of Science (AAAS)
    Print ISSN:
    0036-8075
    Electronic ISSN:
    1095-9203
    Topics:
    Biology
    Chemistry and Pharmacology
    Computer Science
    Medicine
    Natural Sciences in General
    Physics
    Keywords:
    Adult ; Cerebellar Neoplasms/*genetics/metabolism ; Child ; DNA Copy Number Variations ; DNA-Binding Proteins/genetics/metabolism ; *Genes, Neoplasm ; Genes, Tumor Suppressor ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Histones/metabolism ; Humans ; Medulloblastoma/*genetics/metabolism ; Methylation ; MicroRNAs/genetics ; *Mutation ; Neoplasm Proteins/genetics/metabolism ; Oligonucleotide Array Sequence Analysis ; Point Mutation ; Sequence Analysis, DNA ; Signal Transduction
    Published by:
    http://www.aaas.org/

    Latest Papers from Table of Contents or Articles in Press
  5. 5
    Staff View
    Publication Date:
    2018-08-02
    Publisher:
    The American Association for Cancer Research (AACR)
    Print ISSN:
    1078-0432
    Electronic ISSN:
    1557-3265
    Topics:
    Medicine
    Published by:
    http://www.aacr.org/

    Latest Papers from Table of Contents or Articles in Press
  6. 6
    Staff View
    Publication Date:
    2018-09-05
    Publisher:
    The American Association for Cancer Research (AACR)
    Print ISSN:
    1078-0432
    Electronic ISSN:
    1557-3265
    Topics:
    Medicine
    Published by:
    http://www.aacr.org/

    Latest Papers from Table of Contents or Articles in Press
  7. 7
    McComb, R. D. ; Jones, T. R. ; Pizzo, S. V. ; Bigner, D. D.
    Springer
    Published 1982
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Endothelial cell ; Factor VIII/von Willebrand factor ; Glial fibrillary acidic protein ; Hemangioblastoma ; Immunohistochemistry
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary The histogenesis of hemangioblastoma stromal cells is unresolved. Ultrastructural observations suggest that the stromal cells, endothelial cells, and pericytes that compose this neoplasm are all derived from angiogenic mesenchyme. The expression of factor VIII/von Willebrand factor (FVIII/vWF), a specific marker for endothelial cells, and of glial fibrillary acidic protein (GFAP), a specific marker for glial cells, was examined in 16 hemangioblastomas using the peroxidase-antiperoxidase immunohistochemical method. Endothelial cell staining for FVIII/vWF was intense in 14 tumors, weak in one, and absent in another. There was no stromal cell staining in any of the neoplasms. Process-bearing, GFAP-positive cells were observed near the tumor margin in 13 cases, and deeper in the neoplasm in 8. In two of these tumors there were also occasional GFAP-positive cells that lacked processes and had a vacuolated cytoplasm. Virtually all of the GFAP-positive cells were interpreted as trapped astrocytes rather than stromal cells. The lack of expression of FVIII/vWF by the stromal cells indicates that they are antigenically distinct from endothelial cells. Several alternatives for stromal cell histogenesis remain open. The stromal cells may be derived from endothelial cells that have undergone antigenic loss, or from angiogenic mesenchymal cells that do not express FVIII/vWF. Alternatively, the stromal cells may originate from nonangiogenic mesenchymal cells derived from the mesoderm or neuroectoderm.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00690637

    Articles: DFG German National Licenses
  8. 8
    Staff View
    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
    URL:
    http://dx.doi.org/10.1007/BF00687431

    Articles: DFG German National Licenses
  9. 9
    Staff View
    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
    URL:
    http://dx.doi.org/10.1007/BF00687952

    Articles: DFG German National Licenses
  10. 10
    Ridder, L. I. ; Laerum, O. D. ; Mørk, S. J. ; Bigner, D. D.
    Springer
    Published 1987
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Human glioblastomas ; Invasion ; Organ culture ; Tumorigenicity
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Five established cell lines derived from human anaplastic astrocytomas or glioblastoma multiforme were tested for invasiveness into precultured chick heart fragments in vitro. Four of the cell lines (U118 MG, D54 MG, U373 MG and A172) were strongly invasive into the heart tissue. A fifth cell line, U251 MG sp, which was only tumorigenic at doses of greater than 1×108 cells in athymic mice, was non-invasive in vitro. One line, A172, was invasive but not tumorigenic in athymic mice, although a related invasive subline, D54 MG, at later passage levels was tumorigenic even at low cell doses. Invasion of the glioma cells was characterized by progressive and irreversible replacement of the precultured chick heart tissue. Both by light and transmission electron microscopy, a similar pattern of invasion was observed as earlier found with experimental rat glioma cells in the same system. Some human cell lines established from human gliomas retain invasive properties after a prolonged culture period in vitro.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00691091

    Articles: DFG German National Licenses
  11. 11
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Neuroectodermal tumor cells ; Monoclonal antibody ; Ganglioside ; GD3
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary Seven monoclonal antibodies (mAbs) reactive with ganglioside II3(NeuAc)2-LacCer (GD3) were generated; four of these mAbs (DMAb-21, DMAb-22, DMAb-23, and DMAb-24) by immunizing mice with GD3 adsorbed to Salmonella minnesota and the remaining three (DMAb-7, DMAb-8, and DMAb-17) with melanoma line SK-MEL 28, which contains 1.4 nmol sialic acid of GD3 per mg protein. The specificities of the mAbs were defined by high-performance thin-layer chromatography (HPTLC) immunostain and solid-phase radioimmunoassay (SP-RIA) with a panel of purified gangliosides. DMAb-7 and DMAb-8 reacted with GD3, IV3(NeuAc)2nLcOse4Cer(3′,8′-LD1), and very weakly with IV3(NeuAc)2II3NeuAc-GgOse4Cer (GTla), but not with II3NeuAc-LacCer (GM3), II3NeuAcGgOse3Cer(GM2), II3NeuAc-GgOse4Cer(GM1), II3NeuAc, IV3NeuAcGgOse4Cer (GD1a), II3(NeuAc)2GgOse3(GD2), II3(NeuAc)2GgOse4Cer (GD1b), IV3NeuAcII3(NeuAc)2, GgOse4Cer(GT1b), suggesting the binding epitope to be a terminal tetrasaccharide NeuAcα2-8NeuAcα2-3Galβ1-4(Glc or GlcNAc). DMAb-7 and DMAb-8 were used to investigate the expression of GD3 on cultured human tumor cells of neuroectodermal origin. Thirteen of 19 gliomas, 3 of 5 medulloblastomas, 5 of 5 neuroblastomas, 2 of 2 melanomas, and 1 of 3 teratomas were shown to react with DMAb-8 and/or DMAb-7 by cell surface-RIA (CS-RIA) and immunofluorescence (IF) assays. HPTLC and densitometric analysis confirmed these results, as positive immunostains in the GD3 region were obtained with oligoganglioside fractions from 9 glioma, 1 medulloblastoma, 2 neuroblastoma, 1 melanoma, and 1 teratoma cell line. Glioma cell line U-105 MG and medulloblastoma cell line Daoy contain GD3 as shown by HPTLC immunostain analysis of extracts, although GD3 was undetectable on the cell surface as determined by CS-RIA and IF. There was no detectable GD3 found in gangliosides isolated from cell lines U-373 MG, D-54 MG, TE-671, and PA-1, which were negative for both DMAb-7 and DMAb-8 by CS-RIA and IF assay. Our results provide evidence that GD3 is expressed extensively with significant quantitative heterogeneity on cultured human neuroectodermal tumor cells including glioma, medulloblastoma, neuroblastoma, and melanoma.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00294668

    Articles: DFG German National Licenses
  12. 12
    Staff View
    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
    URL:
    http://dx.doi.org/10.1007/s004010051134

    Articles: DFG German National Licenses
  13. 13
    Staff View
    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
    URL:
    http://dx.doi.org/10.1007/BF00310922

    Articles: DFG German National Licenses
  14. 14
    Biegel, J. A. ; Leslie, D. S. ; Bigner, D. D. ; Bigner, S. H.
    Springer
    Published 1987
    Staff View
    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
    URL:
    http://dx.doi.org/10.1007/BF00686628

    Articles: DFG German National Licenses
  15. 15
    Staff View
    ISSN:
    1432-0533
    Keywords:
    Ganglioside ; Medulloblastoma ; Xenograft
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Summary The ganglioside patterns of medulloblastomas have never been established; in this study we report the ganglioside profile of the human medulloblastoma cell line TE-671 grown as a xenograft in nude mice. Gangliosides were isolated and structurally analyzed by fast atom bombardment mass spectometry following permethylation. Identification of individual gangliosides was also performed by immunostaining of high-performance thin-layer chromatography-separated bands. Total ganglioside levels of 0.20 μmol/g of tissue were obtained, consistent with those reported for human glioma cell lines grown as xenografts; predominant monosialogangliosides of TE-671 xenografts were II3-α-NeuAc-LacCer (GM3) and II3-α-NeuAc-GgOse3 Cer (GM2) but there were also relatively large proportions of IV3-α-NeuAc-LcOse4Cer (3′-isoLM1), IV3-α-NeuAc-nLcOse4Cer (3′-LM1) and a further ganglioside of the neolactoseries with an extra lactosamine moiety. The only oligosialoganglioside detected was IV3, II3-α-NeuAc2-GgOse4Cer (GD1a).
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00687580

    Articles: DFG German National Licenses
  16. 16
    Staff View
    ISSN:
    1432-0843
    Keywords:
    Key words BCNU ; Chemotherapy ; Drug resistance ; Gliomas ; O6-benzylguanine
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Medicine
    Notes:
    Abstract  The prognosis for patients with malignant gliomas continues to be dismal. The high degree of resistance of gliomas to nitrosourea-based chemotherapy is one major factor in poor treatment outcome. The identification of O 6-alkylguanine-DNA alkyltransferase (AGAT) as a major determinant of nitrosourea resistance has resulted in the development of several agents to inactivate this repair protein and counteract tumor cell resistance. However, a major problem in preclinical trials has been the marked nitrosourea dose limitations imposed by the prior administration of AGAT-depleting agents. We investigated the AGAT depletion and selective enhancement of BCNU activity of intraarterial (i.a.) O 6-benzylguanine (O 6BG) in the human malignant glioma xenograft D-456 MG growing intracranially (i.c.) in athymic rats. Whereas i.a. O 6BG at 2.5 mg/kg produced 100% inhibition of D-456 MG AGAT i.c. activity 8 h after administration, intraperitoneal (i.p.) O 6BG at this dose produced only 40% inhibition, requiring dose escalation to 10 mg/kg to produce 100% AGAT depletion. Prior administration of i.p. O 6BG (10 mg/kg) and i.a. O 6BG (2.5 mg/kg) limited maximum tolerated intravenous (i.v.) BCNU doses (37.5 mg/kg when given alone) to 6.25 and 25 mg/kg, respectively. Higher doses of BCNU alone or in combination with O 6BG produced histopathologic evidence of cerebral and hepatic toxicity. Therapy experiments revealed a significantly improved median survival for rats treated with O 6BG i.a. (2.5 mg/kg) plus BCNU i.v. (25 mg/kg, days 61 and 59 in duplicate experiments) compared with saline (day 21, P=0.001), O 6BG i.a. or i.p. (days 22 and 23, P=0.001), BCNU i.v. (37.5 mg/kg, day 29, P=0.001), and O 6BG i.p. (10 mg/kg) plus BCNU i.v. (6.25 mg/kg, day 37, P〈0.001). Therefore, O 6BG i.a., by virtue of rapid AGAT depletion and selective uptake into i.c. tumors, offers significant potential for regional chemomodulation of AGAT-mediated nitrosourea resistance in malignant human gliomas with concomitant reduction of systemic toxicity.
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/s002800050577

    Articles: DFG German National Licenses
  17. 17
    Wilfong, R. F. ; Bigner, D. D. ; Wechsler, W.
    Springer
    Published 1972
    Staff View
    ISSN:
    1432-1904
    Source:
    Springer Online Journal Archives 1860-2000
    Topics:
    Biology
    Chemistry and Pharmacology
    Natural Sciences in General
    Type of Medium:
    Electronic Resource
    URL:
    http://dx.doi.org/10.1007/BF00617927

    Articles: DFG German National Licenses