The Role of Platinum Complexes in Combined Modality Therapy

摘要: Platinum complexes are one of the most important classes antitumor agents to enter clinic in last 30 yr. Cisplatin (cis-diamminedichloroplatinum II), first a group platinum complexes, was shown by Rosenberg et al. (1) possess antibiotic activity and subsequent studies (2) have murine tumor models. In 1972 National Cancer Institute introduced cisplatin into clinical trials. is water-soluble inorganic square planar coordination complex containing central atom surrounded two chlorine atoms ammonia moieties (Fig. 1). characterized slow rates ligand substitution reactions compared with other metal (3–5). Because involved drugs binding DNA, intracellular nucleophiles such as glutathione may compete DNA for reaction (6). also bind metallothioneins, cytosolic proteins molecular weight 6000–7000 that contain 20 cysteine residues (7). The primary mechanism inhibition growth appears be synthesis (8,9). cis configuration chloride leaving groups favors formation intrastrand crosslinks (10–14). Recently, crystal structure double-stranded decamer single interstrand crosslink formed between opposite guanine 5′-GC sequence solved (15). another study using short oligodeoxyribonucleotides duplexes (10 base pairs) AGCGA/TCGCT, strands labile at 37°C rearranged an (16). Thus, frequency specific adducts could locally transiently altered cell nucleus during some phase (or phases) cycle different from those modified cell-free media (17). inhibit transcription elongation both prokaryotic eukaryotic RNA polymerases (18) thus more lethal than frequent