RESUMEN
A 53-year-old woman with papillary thyroid cancer treated with 800 mg sorafenib therapy rapidly experienced grade 3 toxicities. Dosing was reduced in a step-wise manner with several treatment discontinuations down to 200 mg every 2 days but severe toxicities continued. Plasma drug monitoring showed high exposure, even at low dose. Dosing was then further reduced at 200 mg every 3 days and tolerance was finally acceptable (i.e., grade 1 toxicity) with stable disease upon RECIST imaging. Pharmacogenetic investigations showed polymorphisms affecting both UGT1A9 (UGT1A9-rs3832043) and nuclear receptor PXR (NR1I2-rs3814055, NR1I2-rs2472677 and NR1I2-rs10934498), possibly resulting in downregulation of liver metabolizing enzymes of sorafenib (i.e., CYP and UGT). Patient's clearance (0.48 l/h) estimated by Bayesian approach was consistently lower than usually described. This is the first time that, in addition to mutations affecting UGT1A9, genetic polymorphisms of NR1I2 have possibly been associated with both plasma overexposure and severe toxicities upon sorafenib intake.
Asunto(s)
Antineoplásicos/toxicidad , Polimorfismo de Nucleótido Simple , Sorafenib/toxicidad , Cáncer Papilar Tiroideo/tratamiento farmacológico , Neoplasias de la Tiroides/tratamiento farmacológico , Antineoplásicos/sangre , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Femenino , Glucuronosiltransferasa/genética , Humanos , Hígado/efectos de los fármacos , Hígado/enzimología , Persona de Mediana Edad , Pruebas de Farmacogenómica , Receptor X de Pregnano/genética , Índice de Severidad de la Enfermedad , Sorafenib/sangre , Cáncer Papilar Tiroideo/sangre , Neoplasias de la Tiroides/sangre , UDP Glucuronosiltransferasa 1A9RESUMEN
CdS/CdSe/CdS quantum-dot quantum-well heterostructures with the different thicknesses of CdSe well layers were synthesized by using the colloidal chemical method. The absorption, photoluminescence and Raman scattering spectra of CdS cores, and CdS/CdSe, CdS/CdSe/CdS structures were investigated. A comparative study of their optical properties confirmed the formation of CdSe well and exterior CdS shell. Raman spectra of the nanostructures exhibit the quantum confinement of the optical phonons and the appearance of the surface phonons. It was found that the temperature dependence of the photoluminescence emission energy is described by Varshni relation with the different temperature coefficients for CdS/CdSe and CdS/CdSe/CdS structures. Upconversion luminescence was observed at low temperatures. The optical and vibrational properties of quantum-dot quantum-well heterostructures have been discussed.
