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  • 1
    Electronic Resource
    Electronic Resource
    Absence of cross-resistance between two alkylating agents: BCNU vs bifunctional galactitol (1989)
    Springer
    Cancer chemotherapy and pharmacology 24 (1989), S. 311-313 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dianhydrogalactitol (DAG) increased the life span of both BCNU-sensitive and-resistant L1210 tumorbearing mice. However, the BCNU-resistant strain showed slightly lower sensitivity against DAG, which could be overcome by an increase in drug dose of ca. 20%. The somewhat lower sensitivity was proportional to a slightly reduced DNA cross-linking formation induced by DAG in BCNU-resistant cells. The amount of DNA cross-links was determined by measurement of the 1,6-di(guaninyl)-galactitol content of DNA. The slight reduction in cross-links is not attributable to DNA repair but rather to other factors that seem to prevent the formation of DNA-drug adducts. The absence of cross-resistance is explained by different kinds of DNA damage caused by the two alkylating agents and the presumably different defense mechanisms developed by cells against these lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00304764
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Do metallothioneins affect the response to treatment in testis cancers? (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 31-36 
    Details
    ISSN: 1432-1335
    Keywords: Key words Metallothionein ; Immunohistochemistry ; Testicular germ cell tumors ; Response to treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Data on the involvement of elevated metallothionein (MT) expression in resistance to some of the commonly used anticancer treatments are scattered and conflicting. This encouraged us to examine further the contribution of metallothionein expression to the development of this resistance phenotype. Patients and methods: Formalin-fixed, paraffin-embedded blocks of primary untreated germ cell testicular tumor specimens, obtained from 77 patients following radical orchiectomy, were examined for their MT expression using monoclonal antibody and immunohistochemistry. Clinical staging, the chemotherapeutic schedule and evaluation of response to treatment (defining objective response) were performed according to UICC criteria. Results: All tumor types, including seminomas and nonseminomas, expressed MT, regardless of their histology and clinical stage. The immunoreactivity of MT showed a significant positive correlation with the clinical sensitivity of cancer to antitumor therapy (P = 0.0001). Conclusion: In patients with germ cell testicular tumors, high MT expression, as detected by immunohistochemistry, predicts a better response rate to chemotherapy whereas tumors lacking or demonstrating low MT expression show a worse prognosis. These data do not support the hypothesis that MT overexpression contributes to cisplatinum resistance, at least in this tumor type.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050130
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  • 3
    Electronic Resource
    Electronic Resource
    Severe depletion of cellular thiols and glutathione-related enzymes of a carmustine-resistant L1210 strain associates with collateral sensitivity to cyclophosphamide (1993)
    Springer
    Cancer chemotherapy and pharmacology 33 (1993), S. 85-88 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cyclophosphamide (CPA) increased the life span of both carmustine (BCNU)-resistant (L1210/BCNU) and BCNU-sensitive L1210 (L1210/0) leukaemic mice; their sensitivity to CPA, however, was extremely different. The BCNU-resistant strain was much more sensitive (collaterally) to CPA than was its sensitive counterpart. The collateral sensitivity was accompanied by a severe reduction in the activity of glutathione-related enzymes and in protein thiol (SH) and non-protein SH levels in BCNU-resistant cells. The activity of glutathione reductase (GSSG-R) was 2 times higher in the L1210/0 cells than in the L1210/BCNU cells. Glutathione-S-transferase (GST) was also almost 2 times more active in the sensitive cells than in the resistant strain. To develop resistance against CPA with a single treatment (60 mg/kg) per passage, the L1210/BCNU strain needed 26 passages, whereas the L1210/0 strain required significantly fewer. The resistance developed against CPA was associated with a moderate elevation of thiols in the L1210/CPA cells, whereas this elevation was approximately 3 times more pronounced in the L1210/BCNU/CPA cells. The severely reduced activity of GST in the L1210/BCNU strain was markedly increased when these cells were made resistant to CPA; the GSSG-R activity, however, remained low, suggesting an irreversible injury of this enzyme by BCNU.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686029
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  • 4
    Electronic Resource
    Electronic Resource
    Benzamide potentiation of the cytotoxicity of bifunctional galacticol in resistant P388 leukemia correlates with inhibition of DNA ligase II (1992)
    Springer
    Cancer chemotherapy and pharmacology 30 (1992), S. 325-329 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Benzamide (BA) enhances the cytotoxicity of 1,2:5,6-dianhydrogalactitol (DAG) in resistant P388 leukemia cell lines but not in the sensitive parent line. To examine the reason for this difference in response, we carried out an alkaline elution assay using proteinase K to study DNA interstrand cross-linking. At early time points, equal concentrations of DAG produced the same level of interstrand cross-linking (ICL) in the resistant and sensitive P388 leukemic cells, although marked differences were observed in their cytotoxicity toward the two cell lines. In the sensitive cells, neither the amount of DNA cross-linking nor the cytotoxicity changed during the observation period (38 h) in either the presence or the absence of BA. In contrast, the elution rate of the DNA of DAG-treated resistant cells increased with time and had reached the control levels by 38 h. However, when these cells were postincubated with BA for 38 h, the elution rate of DNA was much faster than that observed for the untreated resistant cells, indicating an accumulation of DNA singlestrand breaks (SSB). The SSB accumulation caused by BA was associated with an inhibition of the activity of ligase II enzyme, which was stimulated when resistant cells were treated with DAG alone. The potentiating effect of BA on the resistant cells can thus be related to the inhibiting action of BA on the DNA-rejoining enzyme, ligase II. The lack of sensitization by BA of the DAG-treated parent cell line may be attributable to the absence of DNA-SSB formation, which is necessary for ligase II activation through the stimulation of poly(ADP-ribose) synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686304
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Piperazin-Derivate, I. Alkyl-, Aryl-, Aralkyl-piperazin-Derivate (1967)
    Weinheim : Wiley-Blackwell
    Berichte der deutschen chemischen Gesellschaft 100 (1967), S. 3045-3051 
    Details
    ISSN: 0009-2940
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Nach einem neuen Verfahren wurden die Aryl-, Aralkyl- und Alkyl-piperazine 1-14 her-gestellt und der Ablauf der Reaktion untersucht. Aus 1.4-Bis-[1-methyl-2-phenyl-äthyl]-piperazin (3) wurden geometrische und optische Isomere gewonnen.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cber.19671000930
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