Synergy of Irofulven in combination with various anti-metabolites, enzyme inhibitors, and miscellaneous agents in MV522 lung carcinoma cells: marked interaction with gemcitabine and 5-fluorouracil
作者： Michael J. Kelner , Trevor C. McMorris , Rafael J. Rojas , Leita A. Estes , Pharnuk Suthipinijtham
DOI: 10.1007/S10637-008-9113-8
关键词:
摘要: The novel agent Irofulven (HMAF, NSC 683863) has demonstrated significant antitumor activity against solid tumors in various xenograft models and human clinical trials. potential of combining irofulven with 72 different anti-metabolite, enzyme inhibiting, miscellaneous agents was investigated this study. lung carcinoma MV522 cell line its corresponding model were used to evaluate the combination these agents. select anti-metabolites, notably cytidine or adenine-derived agents, displayed strong synergistic both vitro vivo studies. Agents demonstrating interaction included gemcitabine, cyclocytidine, cytarabine, fludarabine phosphate, cladribine, 5-fluorouracil. Other inhibitors, a variety failed interact beneficially when administered irofulven. therapeutic is enhanced considerably combined anti-metabolite further evaluation combinations warranted. may stem from actions including inhibition nucleotide excision repair (NER) pathway, topoisomerase I activity, caspase-dependent independent induction apoptosis.
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