Purpose: Several case reports suggest sorafenib exposure and sorafenib-induced hyperbilirubinemia may be related to a (TA) 5/6/7 repeat polymorphism in UGT1A1 Ã 28 (UGT, uridine glucuronosyl transferase Enzymes and Transporters genotyping platform was applied to DNA obtained from six patients, which revealed the ABCC2-24C>T genotype cosegregated with sorafenib AUC phenotype. Sorafenib exposure was related to plasma bilirubin increases in patients carrying 1 or 2 copies of UGT1A1 Ã 28 alleles (n ¼ 12 and n ¼ 5; R 2 ¼ 0.38 and R 2 ¼ 0.77; P ¼ 0.032 and P ¼ 0.051, respectively). UGT1A1 Ã 28 carriers showed two distinct phenotypes that could be explained by ABCC2-24C>T genotype and are more likely to experience plasma bilirubin increases following sorafenib if they had high sorafenib exposure.Conclusions: This pilot study indicates that genotype status of UGT1A1, UGT1A9, and ABCC2 and serum bilirubin concentration increases reflect abnormally high AUC in patients treated with sorafenib.
This review provides an overview of the pharmacogenetics of membrane transporters including selected ABC transporters (ABCB1, ABCC1, ABCC2, and ABCG2) and OATPs (OATP1B1 and OATP1B3). Membrane transporters are heavily involved in drug clearance and alters drug disposition by actively transporting substrate drugs between organs and tissues. As such, polymorphisms in the genes encoding these proteins may have significant effects on the absorption, distribution, metabolism and excretion of compounds, and may alter pharmacodynamics of many agents. This review discusses the techniques used to identify substrates and inhibitors of these proteins and subsequently to assess the effect of genetic mutation on transport, both in vitro and in vivo. A comprehensive list of substrates for the major drug transporters is included. Finally, studies linking transporter genotype with clinical outcomes are discussed.
Objective.-To compare the perioperative morbidity and survival between abdominal radical hysterectomy (ARH) and robotic radical hysterectomy (RRH). Methods.-A retrospective cohort of patients undergoing radical hysterectomy for cervical cancer from 2010 to 2016 was identified. Patients with stage IB1 cervical cancer were included and were grouped by ARH vs. RRH. Tumor characteristics, perioperative complications, recurrence rate, progression-free survival (PFS), and overall survival (OS) were compared between groups. Results.-105 patients were identified; 56 underwent ARH and 49 underwent RRH. Those who had ARH were more likely to have lesions that were ≥2 cm (62% vs. 39%, p = 0.02) and that were higher grade (p = 0.048). Other tumor characteristics were similar between groups. There was no difference in perioperative complication rates between groups. Additionally, there were no differences in recurrence risk (RR) (14% vs. 24%, p = 0.22), progression-free survival (PFS) (p = 0.28), or overall survival (OS) (p = 0.16). However, in those with tumors ≥2 cm there was a higher risk of recurrence in the overall cohort (30% vs. 8%, p = 0.006), and a shorter PFS in the RRH *
An important form of positive behavioral support is the use of predictor strategies that prevent the occurrence of problem behavior. Teaching students to follow a personalized schedule is one type of predictor strategy. This article describes how to teach students to use personalized schedules. We review relevant research, describe one method for encouraging schedule use, and recommend directions for future research about the use of schedules as a predictor strategy.
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