糖皮质激素抗支气管哮喘治疗的药物基因组学研究进展

支气管哮喘(简称哮喘)是全世界范围儿童最常见的慢性呼吸道疾病.糖皮质激素是哮喘治疗中最有效最常见的药物.临床发现哮喘患者对糖皮质激素的治疗反应存在个体差异和不良反应.药物基因组学研究发现,糖皮质激素通路及相关通路基因、药物代谢酶基因、哮喘易感基因的单核苷酸多态性与糖皮质激素在哮喘治疗中的反应有关.文中主要综述了近年糖皮质激素抗哮喘治疗的药物基因组学研究进展.     

Major partial response to crizotinib,a dual MET/ALK inhibitor,in a squamous cell lung (SCC) carcinoma patient with de novo c-MET amplification in the absence of ALK rearrangement

The initial radiotherapy of a 73 years old Caucasian male patient with advanced squamous cell lung carcinoma was terminated due to severe pericarditis. Subsequently, the tumor sample was analyzed for possible targets with comprehensive molecular diagnostics. EGFR, KRAS and PIK3CA genes were wild type, ALK and ROS1 were negative for rearrangement, but c-MET was amplified by fluorescent in situ hybridization. The kinase inhibitor crizotinib is already in clinical use for the treatment of ALK positive non-small cell lung cancers, but it is also known to be a potent c-MET inhibitor. The patient was treated with the standard dose of twice a day 250 mg crizotinib as a monotherapy. Major partial response to therapy was confirmed by chest CT and PET/CT after 8 weeks on therapy. C-MET expression is associated with poor prognosis and resistance to EGFR inhibitors. This case may indicate that c-MET tyrosine kinase inhibitors can be an effective targeted treatment option for squamous cell carcinoma patients, and future clinical trials should be expanded for this patient group as well.     

药物基因组学在个体化医疗中的应用进展和实例

目的：介绍药物基因组学目前在国外临床应用的进展和实例．促进其在我国临床实践中的应用．提高个体化医疗的水平。方法：本文根据美国FDA批准的60多个包含药物基因组学信息的药品说明书,结合我们临床用药实际和目前可及的基因检测手段．对药物基因组学在个体化医疗中的实际应用情况进行总结,供临床药师和医师在治疗中尝试、应用或参考。结果与结论：基于基因多态性检测技术的药物基因组学已经广泛应用于临床,在提高药物疗效．降低药物毒副作用,调整药物剂量方面发挥了重要的作用,开辟了个体化医疗的新局面。     

Frequency of CYP3A4, CYP3A5, CYP2C9 , and CYP2C19 variant alleles in patients receiving clopidogrel that experience repeat acute coronary syndrome

The presence of cytochrome P450 (CYP) variant alleles may reduce the activation of the prodrug clopidogrel to its active state. This research evaluated the frequency of variant alleles in the genes coding for CYP3A4, CYP3A5, CYP2C9, and CYP2C19 enzymes in patients on clopidogrel therapy and experiencing repeat acute coronary syndrome (ACS) compared to a control group with a matching ethnic composition. Real-time polymerase chain reaction was used for allelic discrimination. Complete data were obtained for 92 patients enrolled over a 3-month period. There were no significant differences in the presence of the examined CYP3A4, CYP3A5, CYP2C9, or CYP2C19 variant alleles between the two groups. The present data indicate that patients currently receiving clopidogrel therapy who present with repeat ACS do not have higher frequency of the examined variant alleles compared to a control group.     

人类白细胞抗原基因多态性与药物不良反应研究进展

药物不良反应已成为危害人类健康的重要公共卫生问题.人类白细胞抗原基因(HLA)是目前已知的人类最复杂基因系统.近年来研究发现,人类白细胞抗原基因多态性与药物不良反应之间有着很强的遗传相关性,且部分研究成果在临床已得到很好地应用.本文就人类白细胞抗原基因多态性与药物不良反应之间的研究及其临床应用进行阐述.     

应用细胞系模型研究药物基因组学的进展

随着人类基因组计划的完成,药物基因组学逐渐成为后基因组时代中发展最迅猛的学科之一.以前绝大部分药物基因组学的研究都是对临床病例数据进行分析,而近些年越来越多的研究者开始使用细胞系模型研究药物基因组学.该文拟就药物基因组学的发展与该领域中细胞系模型的使用情况及该模型与临床病例相比的优、缺点进行综述,旨在探讨细胞系模型是否可以成为药物基因组学研究的一个有效工具,并最终促进新药开发和临床个体化用药的发展.     

Frequencies of genetic polymorphisms related to triptans metabolism in chronic migraine

Chronic migraine (CM) prevalence ranges around 1–5%. Most of these patients usually treat their acute attacks with triptans, whose efficacy is extremely variable. A genetic basis for migraine is evident and many susceptibility genes have been described, as well as gene polymorphisms possibly implied in therapy response. Several factors could be involved in the evolution of episodic migraine into a chronic form, such as natural history, psychiatric comorbidity, and the individual’s response to therapy. During a study aimed at detecting connections between genotype and response to triptans administration, we characterized a CM population for polymorphisms in the genes coding for monoamine oxidase A, g-protein beta 3 and the cytochromes CYP3A4 and CYP1A2. Alleles and genotypes distributions were compared with known frequencies of healthy Caucasian populations. A significant association with CM was found for the long allele of monoamine oxidase A 30 bp VNTR and CYP1A2*1F variant. Such genomic analysis is part of an integrated platform able to evaluate different levels of metabolic pathways of drugs in CM and their influence in the chronicization process.