Exploration of organoid in breast cancer related research / 生物工程学报

Breast cancer is the most common cancer in women. At present, the in vivo model and traditional cell culture are mainly used in breast cancer researches. However, as high as 90% clinical trials are failed for drugs explored by the above two methods, due to the inherent species differences between humans and animals, as well as the differences in the tissue structure between organs and cells. Therefore, organoid three-dimensional culture is emerging. As a new tumor research model, organoid, a three-dimensional cell complex with spatial structure, has broad application prospects, such as precision medicine, organ transplantation, establishment of refractory disease model, gene therapy and drug research and development. Therefore, organoid is considered as one of the ideal carriers for life science research in the future. Breast cancer, a heterogeneous disease with complex phenotypes, has a low survival rate. Breast cancer organoid can reproduce many key features of human breast cancer, thus, the construction of organoid biological library of breast cancer will provide a new platform for studying the occurrence, development, metastasis and drug resistance mechanism of breast cancer. In this review, we systematically introduce the culture conditions of organoids and their application in breast cancer related research, and the application prospect of organoids.

Advances of the mode of clinical pharmacy care in the era of precision medicine / 医学研究生学报

Precision medicine has become a new mode of modern medicine, and personalized medication is the important embodiment of clinical application of precision medicine. The advances of life science technologies greatly facilitated precision medicine, and also promoted the shift of the mode of clinical pharmacy care from rational drug use and individualized medication to precision medication. To achieve"one person, one mode" clinical dosage regimens,it is necessary to rely on the supports of advanced life science technologies and precisely analyzing and accurately characterizing the biomarker clusters related to individual differences among patients, pathological differences of disease, and disease progression. This article illustrated the recent advances in the application of pharmacokinetics/pharmacodynamics, omics technology and liquid biopsy to the design of dosage regimen, prediction of therapeutic effect and adverse drug reactions, etc. in the era of precision medicine. Furthermore, the development direction of the new model of clinical pharmaceutical care faced on the precision medicine is prospected.

Based on CYP2C19 Genotype of Clopidogrel and Ticagrelor Treatment of Acute Coronary Syndromes Individualized Drug Analysis / 中国药学杂志

OBJECTIVE: To investigate the adverse events of CYP2C19 gene polymorphism on clopidogrel and ticagrelor in the treatment of acute coronary syndrome and provide reference for clinical individualized medication. METHODS: The total of 1 086 patients with acute coronary syndrome were selected as the subjects in the cardiovascular department of Zhengzhou Central Hospital Affiliated to Zhengzhou University from March 2015 to March 2018. The patients were grouped according to whether they agreed to do the CPY2C19 gene test or not. The patients who didn′t carry out CYP2C19 gene testing were given routine dosage(Group A,75 mg clopidogrel and 100 mg aspirin). The CYP2C19 genotype was detected by real-time fluorescence quantitative PCR for patients in group B,group C and group D. According to the genotype,patients were divided into three groupsgroup B(super fast metabolism and fast metabolism, 75 mg clopidogrel and 100 mg aspirin), group C(intermediate metabolism,150 mg clopidogrel dosage and 100 mg aspirin),group D(slow metabolism, 150 mg clopidogrel dosage and 100 mg aspirin or 180 mg ticagrelor and 100 mg aspirin). The incidence of major adverse events and minor adverse events were compared among the four groups. RESULTS: There was significant differences in the incidence of major adverse events and stent thrombosis among group A, group B, group C and group D(P<0.05). The incidence of stent thrombosis in group A was significantly higher than that in group B and group C, respectively(all P<0.05). There were significant differences in the incidence of target vessel reconstruction and cardiogenic readmission among the four groups (all P<0.05). The target vessel reconstruction in group A was significantly higher than that in group B and group C(P<0.01). The cardiogenic readmission in group A was significantly higher than that in group B, group C and group D(all P<0.01). Compared with group D1, the incidence of secondary adverse events,stent thrombosis,target vessel reconstruction and cardiogenic readmission in group D1 were significantly higher than those in group C(all P<0.05 ). Compared with D1 group, the incidence of cardiogenic readmission in group D1 was significantly higher than that in group D2 ( P<0.05 ), but the incidence of bleeding was high in group D2. CONCLUSION: The CPY2C19 gene detection for individualized administration to patients with acute coronary syndrome can significantly reduce the incidence of adverse events, which is of great guiding significance. It is necessary to pay attention to the occurrence of bleeding events for patients with ultra-fast metabolic.

Regulation of drug metabolism and toxicity by multiple factors of genetics, epigenetics, lncRNAs, gut microbiota, and diseases: a meeting report of the 21International Symposium on Microsomes and Drug Oxidations (MDO)

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

Brief Analysis of Aspirin Resistance and Its Implications / 中国药学杂志

OBJECTIVE: Individuals taking aspirin but who fail to appropriately respond to the medication may remain at higher risk of thrombotic events. To provide reference for rational use of aspirin and reduce the risk of adverse reactions, clinical pharmacists need to comprehend the status of aspirin resistance. METHODS: We have reviewed, analyzed, and summarized domestic and foreign literatures published in the last five years that are related to aspirin resistance. RESULTS: The term "aspirin resistance" still has no standard accepted definition in the literature. Researchers focus on molecular insights into the mechanisms of aspirin resistance. The absolute as well as relative contributions of various factors to the phenomenon of aspirin resistance are the subject of current research. There are diverse platelet function testing methods and each has its strengths and weaknesses, which will greatly increase the difficulty of selection. CONCLUSION: In order to have a comprehensive assessment and interpretation of laboratory data, clinical pharmacists need to understand the research progress of aspirin resistance, which will promote personalized medication of aspirin.

Aspirin, Cardiovascular and Cerebrovascular Diseases / 中国生化药物杂志

Cardiovascular and cerebrovascular diseases is the most fatal diseases in the world.The prevention and treatment of cardiovascular and cerebrovascular diseases are both basic and clinical focus.Aspirin has been used as a prevention medicine in cardiovascular and cerebrovascular diseases for over a century, which is the longest one in history.Aspirin use is estimated at 100 billion tablets annually as an analgesic, antipyretic and antiplatelet drugs.However, there are still many new findings about aspirin, such as aspirin resistance and aspirin hydrolase.This paper reviews the current research advances and future directions of aspirin in cardiovascular and cerebravascwlar diseases, mainly focuses on aspirin resistance and personalized medication.

Individualized use of clopidogrel based on CYP2C19 genotype / 中国药学杂志

OBJECTIVE: To explore the impact of CYP2C19 genotype on major adverse cardiac events (MACE) in coronary disease patients receiving clopidogrel treatment, and provide reference for rational use of clopidogrel in clinic. METHODS: Coronary disease patients hospitalized in the Vasculocardiology Department of our hospital from Apr to Sep 2014 were enrolled, CYP2C19 genotype was detected by pyrosequencing method, and the MACE caused by clopidogrel treatment was studied. RESULTS: Among the 174 enrolled cases, CYP2C19*2 and CYP2C19*3 mutant alleles were observed in 96 patients (55.17%). Compared with patients with wild type, the mutant alleles carriers had higher risk of MACE (47.92% vs 11.54%, P<0.05). Compared with clopidogrel monotherapy, combined antiplatelet therapy with clopidogrel and aspirin lowered the risk of MACE (35.84% vs 62.79%, P<0.05). CONCLUSION: It is suggested that CYP2C19*2 and CYP2C19*3 mutant alleles carriers receive higher dosage of clopidogrel, or use combined antiplatelet therapy or other antiplatelet drugs.