Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy, Том 1
Taken together the data presented in this review, and work by many other investigators, support the notion that DNA excision repair is important in a tumor cell's resistance to platinum compounds. Inhibition of this repair system by combination chemotherapy with the excision repair inhibitors HU and Ara-C produces synergistic cell kills and increased levels and persistance of DNA interstrand crosslinks. The studies with cis-DDP and ~-DDP in combination with UV induced thymine dimers suggest that there may be competition for DNA repair enzymes between the dimer and the platinum lesion. Whether the competing lesion is an intrastrand crosslink, interstrand crosslink, or platinum monoadduct (or all of these lesions) cannot be determined. The similarity between an intrastrand crosslink and a cyclobutane dimer suggests that these lesions may compete for repair. However, the increased peak levels of interstrand crosslinks, and increased persistence of these lesions at later time points suggest that this lesion may also be a substrate for the repair system. These observations may be of clinical relevance. Recently Dr. Kathy Albain of our institution has completed a Phase III I study using a 12 hour pretreatment with HU and Ara-C in patients prior to their cis-DDP therapy. She observed a significant number of responders in this trial (54). She is currently completing a second Phase IIII study substituting IV HU for the oral formulation. We anticipate initiating other clinical trials based upon these observations.
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Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy
Stephen B. Howell
Обмежений попередній перегляд - 2013
acid administration analogues anticancer antitumor activity Ara-C assay AT-II binding Biochem Biol Cancer Chemotherapy Cancer Res carboplatin carcinoma cells carrier ligand CDDP cell lines cellular chelate Chem chemotherapy cis-DDP cis-diamminedichloroplatinum(II cisplatin clearance clinical combination Compounds in Cancer concentration creatinine cytotoxicity DDTC DNA adducts DNA repair dose intensity drug effect etoposide gene GM-CSF guanine high dose high-dose cisplatin increased incubation infusion inhibition interaction interstrand crosslinks intraperitoneal kinase kinetics L-NDDP lesions leukemia levels ligand liposomes membrane Metal Coordination Compounds metallothionein mg/kg mg/m monoadducts mutation myelosuppression nephrotoxicity neuropathy neutropenia nucleobase observed oligonucleotides ototoxicity ovarian cancer ovarian carcinoma pharmacokinetic Pharmacol phase plasma plasmid platinated platinum platinum complexes platinum compounds platinum-DNA platinum(II Proc protein Pt-DNA rats reaction regimens renal replication response ribozyme sensitive sequence structure studies synthesis Table taxol therapy tissues toxicity trans-DDP treated treatment trials tumor tumor cells vitro vivo