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  • 1
    Electronic Resource
    Electronic Resource
    Differential modulation of chemosensitivity to alkylating agents and platinum compounds by DNA repair modulators in human lung cancer cell lines (2000)
    Springer
    Journal of cancer research and clinical oncology 126 (2000), S. 198-204 
    Details
    ISSN: 1432-1335
    Keywords: Key words DNA repair ; Resistance modifier ; Drug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Modulation of DNA repair represents one strategy to overcome cellular drug resistance to alkylating agents and platinum compounds. The effects of different known DNA repair modulators such as O 6-benzylguanine (6 μg/ml), fludarabine (25 ng/ml), aphidicolin (8.5 ng/ml), pentoxifylline (1.4 μg/ml) and methoxamine (12.4 μg/ml) on the cytotoxicity of mafosfamide, chlorambucil, 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU), cisplatin and carboplatin were tested in human lung cancer cell lines. Methods: Chemosensitivity of the human adenocarcinoma cell line MOR/P and the cisplatin-resistant subline MOR/CPR as well as the large-cell lung cancer cell line L23/P and its cisplatin-resistant counterpart L23/CPR were evaluated by the MTT colorimetric assay. Results: O 6-benzylguanine, an inhibitor of O 6-alkylguanine-DNA alkyltransferase, significantly sensitised MOR/P and MOR/CPR cells to the cytotoxic effect of BCNU. Fludarabine, methoxamine and aphidicolin did not change the chemosensitivity of the parental and cisplatin-resistant cell lines to any cytotoxic drug tested. Interestingly, O 6-benzylguanine enhanced the chemoresistance of parental and cisplatin-resistant cell lines to platinum compounds. Also, pentoxifylline increased resistance of the MOR cell lines to mafosfamide. Conclusions: Modulation of DNA repair elicits not only chemosensitisation but may also enhance cellular resistance to DNA-affine drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050033
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  • 2
    Electronic Resource
    Electronic Resource
    Cytotoxicity of adriamycin, idarubicin, and vincristine in acute myeloid leukemia: Chemosensitization by verapamil in relation to P-glycoprotein expression (1992)
    Springer
    Annals of hematology 65 (1992), S. 206-212 
    Details
    ISSN: 1432-0584
    Keywords: P-glycoprotein ; Drug resistance ; MTT assay ; Acute myeloid leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 4-day colorimetric tetrazolium dye (MTT) assay was used to assess the cytotoxicity of adriamycin (ADM), vincristine (VCR), and idarubicin (IDA) in blasts isolated from 37 patients with newly diagnosed and pretreated acute myeloid leukemia (AML). The effect of verapamil (VRP) as a chemosensitizer was studied in relation to the expression of the membrane efflux pump P-glycoprotein (PGP) as determined by a semiquantitative flow-cytometric procedure. A slight positive correlation was found between the fraction of cells expressing PGP and the ID50 values for ADM and VCR, but not between cellular PGP content and sensitivity to IDA. The overall data showed no significant sensitization effect of VRP. However, in specimens with more than 10% cells expressing PGP, 2μM VRP sensitized cells to ADM and VCR significantly. The median of sensitization ratios (SRs), i.e., the ratios of cytotoxic drug ID50 in the absence/presence of VRP, were 1.89 and 2.0, respectively. No sensitizing effect of VRP on the cytotoxicity of IDA was observed. Related to the clinical status, the median fraction of PGP-positive blasts was elevated fourfold in pretreated patients (n=16) in comparison to patients with de novo AML (n=19). No differences in ID50 values were observed between newly diagnosed and pretreated patients. However, SRs for ADM and VCR were higher in samples of pretreated patients compared with de novo AML. PGP-mediated cellular drug resistance may thus be circumvented in leukemic blasts by application of chemosensitizers or, potentially, alternative anthracyclines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01703946
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  • 3
    Electronic Resource
    Electronic Resource
    Isolation of rapidly labelled nuclear RNA of high specific activity from human leukaemic cells (1973)
    Springer
    Journal of molecular medicine 51 (1973), S. 677-679 
    Details
    ISSN: 1432-1440
    Keywords: Human Leukaemia ; 32P-orthophosphate ; nuclear RNA ; Menschliche Leukämie ; 32P-Orthophosphat ; nucleare RNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es werden Methoden zur Präparation von nuklearer RNA hoher spezifischer Aktivität aus menschlichen Leukämiezellen beschrieben. Das Inkubationsmedium basiert auf Hepes-Puffer und der Verwendung von dialysiertem Kalbsserum zur Verbesserung der Bedingungen für den32P-Orthophosphat-Einbau in die hochmolekulare Kern-RNA. Die erreichten spezifischen Aktivitäten erlauben detaillierte Nucleotid- und Oligonucleotidanalysen der verschiedenartigen Ribonucleinsäurespezies in menschlichen Leukämiezellen.
    Notes: Summary Methods are presented which provide the preparation of highly labelled nuclear RNA from cells of the different forms of human leukaemia. An incubation medium is described that is based on Hepes buffer and on the use of exhaustively dialyzed fetal calf serum offering suitable conditions for the uptake of32P-orthophosphate into the RNA of leukaemic nuclei. The specific activities reached may allow more detailed nucleotide and oligonucleotide analyses of the various RNA species present in human leukaemic cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01468172
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  • 4
    Electronic Resource
    Electronic Resource
    Differences in nuclear RNA labelling patterns of BURKITT lymphoma, leukaemic lymphosarcoma and various human leukaemias (1973)
    Springer
    Journal of molecular medicine 51 (1973), S. 680-684 
    Details
    ISSN: 1432-1440
    Keywords: BURKITT lymphoma ; leukaemic lymphosarcoma ; chronic myelotic leukaemia (CML) ; acute myeloblastic leukaemia (AML) ; chronic lymphocytic leukaemia (CLL) ; 32P-orthophosphate ; nuclear RNA ; Burkitt-Lymphom ; leukämische Lymphosarcomatose ; akute myeloische Leukämie (AML) ; chronischmyeloische Leukämie (CML) ; chronisch-lymphatische Leukämie (CLL) ; 32P-Orthophosphat ; nucleare RNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Aus Zellen des Burkitt-Lymphoms, eukämischer Lymphosarcomatose, chronisch-lymphatischer Leukämie, chronisch-myeloischer und akuter myeloischer Leukämie wurden nach sechsstündiger32P-Markierung in einem phosphatarmen Medium Zellkerne mit Hilfe des Zitronensäure-Verfahrens isoliert und die nucleare RNA mit der heißen Phenol-SDS-Methode extrahiert. Nach Fraktionierung der kernspezifischen Nucleinsäuren über Zucker-Dichtegradienten fanden sich markante Unterschiede in der32P-Radioaktivitätsverteilung. Insbesondere war eine differente Markierung der nuclearen 45S RNA, welche als Vorläufer ribosomaler 28S und 18S RNA gilt, festzustellen. Die niedrigsten spezifischen Aktivitäten des ribosomalen Vorläufers fanden sich bei der CML, die höchsten bei AML, leukämischem Lymphosarkom und Burkitt-Tumor. Bemerkenswert erscheint die aktive Synthese präribosomaler (45S/35S) RNA in Zellen der CLL, deren DNA-Syntheserate äußerst niedrig ist. Zur Klärung der Frage, ob die im Nucleolus der unreifen Zellen gebildeten hochmolekularen Nucleinsäuren quantitative oder qualitative Unterschiede zwischen myeloischen und lymphatischen Zellen aufweisen, sind strukturchemische Untersuchungen im Gange.
    Notes: Summary Nuclear RNA was isolated from citric acid nuclei derived from AML, CML, CLL, leukaemic lymphosarcoma and BURKITT lymphoma cells after 6 hours incubation with32P-orthophosphate in a phosphate-free medium. In fractionations on sucrose density gradients, marked differences were found in the distribution of the32P-radioactivity mainly in the 45S fraction containing the ribosomal precursor RNA. The lowest specific activities of nuclear 45S RNA were found in CML; very high labelling accurred in cells of AML, leukaemic lymphosarcoma and BURKITT lymphoma. In CLL cells which are known for lack in DNA synthesis, pre-ribosomal 45S and 35S RNA were labelled to a remarkable extent. Studies are in progress in order to define possible differences in nuclear RNA structures between lymphocytic and granulocytic cell lines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01468173
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