The biological activity of cisplatin and dibromodulcitol in combination therapy
| Autor: | J Fürész, András Jeney, Karoly Lapis, Ilona Kovalszky, RE Durand, Erzsébet Rásó |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Combination therapy DNA damage Biology Mice Mitolactol In vivo Antineoplastic Combined Chemotherapy Protocols Tumor Cells Cultured medicine Animals Cytotoxic T cell Neoplasm Metastasis Cytotoxicity Melanoma Cisplatin Leukemia P388 Body Weight Drug Synergism DNA Neoplasm In vitro Mice Inbred C57BL Oncology Mechanism of action Mice Inbred DBA Mice Inbred CBA Cancer research Drug Screening Assays Antitumor medicine.symptom Neoplasm Transplantation Research Article DNA Damage medicine.drug |
| Zdroj: | British Journal of Cancer Scopus-Elsevier |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.1995.63 |
| Popis: | The efficacy and modes of action of dibromodulcitol (DBD) and cisplatin (CDDP) were studied in several model systems. Combination treatments produced a longer survival time in mice bearing P388 solid lymphomas than either of the drugs alone. In the human metastatic melanoma HT-168 xenograft model the combined application of DBD and CDDP was also very effective, inducing a reduction in the number and volume of metastatic nodules. For V79 spheroids, DBD was mainly cytotoxic against the internal, quiescent cells, whereas cisplatin primarily killed cells in the proliferating, external regions of the spheroids. When combined, the drugs appeared to act synergistically throughout the spheroids. Studies on plasmid DNA showed that CDDP primarily generates cross-links, whereas single-strand breaks were dominant after DBD treatment. Upon using an assay for cleavage by restriction nuclease, antagonistic action of DBD and CDDP in combination may occur, nevertheless more strand breaks were always observed in these samples. These results suggest that the efficacy of combined DBD and CDDP is in part a result of 'spatial cooperation' by the drugs (i.e. affecting different cells) and in part the result of DNA damage produced by the combination treatments. |
| Databáze: | OpenAIRE |
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