Analysis Of Topoisomerase (Top) Expression In Peripheral Blood Mononuclear Cell (Pbmcs) From Patients (Pts) Undergoing Chemotherapy (Cht) For Solid Tumors(St).

2124 Background: Clinical experience demonstrated the efficacy of combined drug regimens, including inhibitors of DNA replication and anti-TOP. Aim of this study was the time-course evaluation of TOP mRNA expression in PBMCs from PTS undergoing CHT for histologically proven ST in order to optimise combination regimens including TOP inhibitors. Methods: We analysed TOP1, TOP2A, TOP2B mRNA levels in PBMCs from 33 PTS (18 M and 15 F, median age 63) by quantitative real-time RT-PCR. Measurements were performed at 0 h, before the beginning of the first CHT dose administration, and at +2, +3, +6 and +24 h. Drugs included gemcitabine, oxaliplatin, 5-fluorouracile and methotrexate, either alone or in combination. Results: 28 PTS showed a significant increase of TOP expression at 2–3 h from the beginning of treatment with a subsequent restoration of baseline values at 6 h. In particular, TOP1 mRNA levels increased from 120% to 1,400% of baseline values, TOP2A increased 200%–730% from baseline and TOP2B increased from 130%–12,000% of baseline. Among the variety of drugs tested, 5-fluorouracile (in monotherapy or in association with oxaliplatin or methotrexate) and gemcitabine were the most effective in inducing TOP expression. Conclusions: we demonstrated that anti-tumour drugs acting on cell replication and/or metabolism induce TOP1, TOP2A, TOP2B expression with a pick at 2–3 h from treatment. These results are of interest in the designing combined chemotherapy schedules including topoisomerase inhibitors. No significant financial relationships to disclose.