27 research outputs found
Use of Genetically Altered Mice to Investigate the Role of Nuclear Factor-Kappa B Activation and Cytokine Gene Expression in Sepsis-Induced ARDS
The information needs and sources of primary health care workers in the Upper East Region of Ghana
THE EFFECTS OF COLORED TEXTURED SOYBEAN PROTEIN (TSP) ON SENSORY AND PHYSICAL ATTRIBUTES OF GROUND BEEF PATTIES
Mind the gap: selling revolution, marginality and spectacle in post-revolutionary Nicaragua
Conjunctive Therapy of Cisplatin With the OCT2 Inhibitor Cimetidine: Influence on Antitumor Efficacy and Systemic Clearance
The organic cation transporter 2 (OCT2) regulates uptake of cisplatin in proximal tubules and inhibition of OCT2 protects against severe cisplatin-induced nephrotoxicity. However, it remains uncertain whether potent OCT2 inhibitors such as cimetidine can influence the antitumor properties and/or disposition of cisplatin. Using an array of preclinical assays, we found that cimetidine had no effect on the uptake and cytotoxicity of cisplatin in ovarian cancer cells with high OCT2 mRNA levels (IGROV-1). Moreover, the antitumor efficacy of cisplatin in mice bearing luciferase-tagged IGROV-1 xenografts was unaffected by cimetidine (P = 0.39). Data obtained in 18 patients receiving cisplatin (100 mg/m(2)) in a randomized crossover fashion with or without cimetidine (800 mg×2) revealed that cimetidine did not alter exposure to unbound cisplatin, a marker of antitumor efficacy (4.37 vs 4.38 μg×h/mL; P = 0.86). These results support the future clinical exploration of OCT2 inhibitors as specific modifiers of cisplatin-induced nephrotoxicity