C609T Polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin

Background Amrubicin hydrochloride (AMR) is a key agent for lung cancer. NADPH quinone oxidoreductase 1 (NQO1) metabolizes the quinone structures contained in both amrubicin (AMR) and amrubicinol (AMR-OH). We hypothesized that NQO 1 C609T polymorphism may affect AMR-related pharmacokinetics and clinical outcomes. Methods Patients received AMR doses of 30 or 40 mg/m 2 /day on days 1–3. Plasma sampling was performed 24 hours after the first and third AMR injections. Concentrations of AMR and AMR-OH were determined by HPLC and the NQO 1 C609T polymorphism was assayed by RT-PCR. Results A total of 35 patients were enrolled. At a dose of 40 mg/m 2 , the T/T genotype exhibited a tendency toward a relationship with decrease concentrations of AMR-OH on days 2 and 4. The genotype also showed a significant decrease of hematological toxicities ( P < 0.05). Conclusions NQO 1 C609T polymorphism had a tendency of correlation with the plasma concentrations of AMR-OH, and thereby had significant correlations with hematologic toxicities

Ablation of KS in microglia accelerated the early phase pathogenesis in a mouse model.

<p>(A) The lifespan of SOD1^G93A was 164.7±18.2 days (n = 43), while that of SOD1^G93AGlcNAc6ST-1^−/− was 158.7±13.2 days (n = 76) (p = 0.007). (B) Body weight loss of SOD1^G93A began at 124.7±12.2 days, while it began at 118.4±11.9 days in SOD1^G93AGlcNAc6ST-1^−/− (p = 0.005). A decrease in rotarod performance at (C) 15 rpm and (D) 20 rpm of SOD1^G93A began at 141.4±18.2 days and 121.6±24.5 days, respectively. In SOD1^G93AGlcNAc6ST-1^−/− mice, these onset times were accelerated to 125.2±14.2 (p<0.001) days and 112.5±18.1 days (p = 0.003), respectively.</p