Tacrolimus (FK506) is a calcineurin inhibitor with a narrow therapeutic index that exhibits large interindividual variation. Seventy-eight kidney transplant patients treated with tacrolimus were recruited to study the correlation of dose adjusted trough level (level/dose; L/D) of tacrolimus with CYP3A5 and ABCB1 genotypes, as well as the mRNA copy number of ABCB1 in blood. Patients were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T) and CYP3A5 (G6986A), while ABCB1 mRNA transcript copy number was determined by absolute quantification (real-time PCR) in 46 patients. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus L/D in kidney-transplant patients. Significantly higher L/D was observed among non-expressors (2.85, 95%: 2.05-3.70 (ng·mL(-1))/(mg·kg(-1))) as compared with the expressors (1.15, 95%: 0.95-1.80 (ng·mL(-1))/(mg·kg(-1))) of CYP3A5 (Mann-Whitney U test; P < 0.001). No correlation was observed between L/D and the ABCB1 genotypes. A significant inverse correlation of blood ABCB1 mRNA level with L/D was demonstrated (Spearman's Rank Order correlation; P = 0.016, rs = -0.348). However, in multiple regression analysis, only CYP3A5*3 genotype groups were found to be significantly correlated with tacrolimus L/D (P < 0.001). These findings highlight the importance of CYP3A5*3 pharmacogenotyping among kidney-transplant patients treated with tacrolimus, and confirm the role of blood cell P-glycoprotein in influencing the L/D for tacrolimus.
Vitamin E is made up of two substances, tocopherols (TOCs) and tocotrienols (TCTs). These substances are present in four different subtypes namely alpha, beta, delta and gamma and these subtypes differs in their chemical structures. Vitamin E has been made known to exert anticancer effects for decades-long ago. This vitamin, which is also a well-known lipid-soluble antioxidant, has been extensively studied and its effects on cancer cells progressions are widely reported. These include its effects on the progressions of the breast, cervix, colon, liver, lung, pancreas, prostate, skin, and stomach cancers. Despite the widely available reports on vitamin E as an anticancer, the particular reports on the effects of this vitamin for reproduction in ovarian cancer are remarkably limited. Hence, this review is written to provide a summary of the reported effects from the studies published between the year 2010-2020 and the possible future research on vitamin E in ovarian cancer. This review will contribute to a more organized finding on the effects of vitamin E and ovarian cancer.
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