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文献翻译带练13 Pharmacodynamics(PD) biomarker
Blood-derived samples are the most commonly used tissue surrogates for PD biomarker analysis within clinical trials. This is predominantly due to the ease with which serial samples can be collected, processed, and stored for future analysis. For cancer therapies, blood-borne markers of cell apoptosis and/or necrosis in plasma or serum are often measured to provide an indication of an antitumor effect. Cytokeratin 18 (CK-18) is an example of a well-established blood-borne biomarker of epithelial cell necrosis and/or apoptosis.The amount of circulating full-length and caspase-cleaved CK-18 across the course of chemotherapy treatment can be measured in serum or plasma samples collected across treatment cycles using enzyme-linked immunoassays.
参考答案：在临床试验中，血液样本是药效学生物标志物分析中最常用的组织替代物。主要原因是可以方便地收集、处理和存储系列样品以供将来分析。对于癌症治疗，血浆或血清中细胞凋亡和/或坏死的血源性标记物经常被测量，以提供抗肿瘤作用的指示。细胞角蛋白18是一种公认的上皮细胞坏死和/或凋亡的血源性生物标志物。在整个化疗过程中，可以通过酶联免疫分析法检测整个治疗周期收集的血清或血浆样本中循环的全长和被含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)酶切的细胞角蛋白18的含量。
miRNAs are small noncoding RNAs (18–25 nucleotides) that are negative regulators of gene expression.The ability to measure the expression of these molecules in a variety of tissues and bodily fluids, in addition to the discovery that unique miRNA signatures can classify different cancers,has led to huge interest in their potential as biomarkers. Circulating miRNAs have been described as possible noninvasive diagnostic, prognostic, and predictive biomarkers in oncology.As a prognostic tool, Some in their initial discovery of stable miRNAs in the circulation, reported that high miR-21 expression in serum was associated with improved relapse-free survival time in patients with diffuse large B-cell lymphoma.
参考答案：miRNAs是小型非编码RNA(18-25个核苷酸)，是基因表达的负调控因子。测量这些分子在各种组织和体液中的表达，以及独特的miRNA信号可以对不同的癌症进行分类，这使得人们对它们作为生物标志物的潜力产生了巨大的兴趣。在肿瘤学中，循环miRNAs被描述为可能的非侵入性诊断、预后和预测性生物标志物。作为一种预后工具，一些研究者在首次发现循环中稳定的miRNAs时报道，血清中miR-21的高表达与弥漫性大B细胞淋巴瘤患者无复发(生存时间)的改善相关。
文献翻译带练14 Cytochrome P450 2D6 (CYP2D6) Genetic Polymorphism
Cytochrome P450 2D6 (CYP2D6) is a member of the cytochrome P450 (CYP) superfamily. This large superfamily of enzymes is involved in the biotransformation of drugs and other xenobiotics, as well as in the metabolism of endogenous compounds such as steroid hormones.CYP2D6 is involved in the biotransformation of several commonly used drugs including antipsychotics, antidepressants, analgesics,β -blockers and antiarrhythmics. Among CYP isoforms, CYP2D6 gene is considered as the most polymorphic. More than 105 different alleles have been identified so far. Unlike other better conserved CYP isoforms (e.g. such as CYP3A4), many CYP2D6 alleles encode enzymes that have reduced or no function compared with the wild-type enzyme.
参考答案：细胞色素P450 2D6 (CYP2D6)是细胞色素P450 (CYP)超家族成员之一。这个巨大的酶超家族参与药物和其他外源性物质的生物转化，以及内源性化合物(如类固醇激素)的代谢。CYP2D6参与几种常用药物的生物转化，包括抗精神病药、抗抑郁药、止痛药、β -阻滞剂和抗心律失常药。在CYP亚型中，CYP2D6基因被认为是多态性最强的。到目前为止，已经发现了超过105种不同的等位基因。与其他更保守的CYP亚型(如CYP3A4)不同，许多CYP2D6等位基因编码的酶与野生型酶相比功能减少或没有功能。
it is shown that CYP2D6 poor metabolizers (PMs) may be less efficient at synthesizing endogenous morphine compared with other metabolizers. In contrast, ultra-rapid metabolizers (UMs) may be more efficient than other metabolizers at synthesizing endogenous morphine, thus strengthening endogenous pain modulation. Additionally, for codeine and tramadol that are bioactivated by CYP2D6, PMs may undergo no metabolite formation, leading to inadequate analgesia. Conversely, UMs may experience quicker analgesic effects but be prone to higher mu-opioid-related toxicity. The literature suggested the potential usefulness of the determination of CYP2D6 polymorphisms in elucidating serious adverse events and in preventing subsequent inappropriate selection or doses of codeine and tramadol.
参考答案：研究表明，CYP2D6弱代谢者(PMs)在内源性吗啡合成方面的效率可能低于其他代谢者。相比之下，超快速代谢者(UMs)在合成内源性吗啡方面可能比其他代谢者更有效，从而加强内源性疼痛调节。此外，对于被CYP2D6生物激活的可待因和曲马多，弱代谢者可能不会产生代谢产物，导致镇痛不足。相反，UMs可能会经历更快的镇痛作用，但更容易出现更高的mu-**类药物相关毒性。文献表明CYP2D6多态性的测定在阐明严重不良事件和防止随后不适当地选择或使用不合适剂量的可待因和曲马多方面具有潜在的作用。