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 f...