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Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

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Chinese Journal of Cancer 2017年第6期36卷 267-273页

作者： Jun-Yan Liu Chen-Yue Qian Yuan-Feng Gao Juan Chen Hong-Hao Zhou ji-ye yin Xiangya School of Medicine Central South University Department of Clinical Pharmacology Xiangya HospitalCentral South University Institute of Clinical Pharmacology Hunan Key Laboratory of PharmacogeneticsCentral South University Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study

Background:Chemotherapy toxicity is a serious problem from which non-small cell lung cancer(NSCLC) patients *** mismatch repair(MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC *** this study,we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC ***:A total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this *** was evaluated in each patient after two cycles of chemotherapy.A total of 44 single nucleotide polymorphisms were selected to investigate their associations with platinum-based chemotherapy ***:MutS homolog 2[MSH2) rs6544991[odds ratio(OR) 2.98,95%confidence interval(CI) 1.20-7.40,P = 0.019]was associated with gastrointestinal toxicity in the dominant model;MSH3 rs6151627(OR 2.38,95%CI 1.23-4.60,P = 0.010),rs6151670(OR 2.05,95%CI 1.07-3.93,P = 0.031),and rs7709909(OR 2.38,95%CI 1.23-4.64,P = 0.010)were associated with hematologic toxicity in the dominant ***,MSH5 rs805304 was significantly associated with overall toxicity(OR 2.21,95%CI 1.19-4.09,P = 0.012),and M5H5 rs707939 was significantly associated with both overall toxicity(OR 0.42,95%CI 0.23-0.76,P = 0.004) and gastrointestinal toxicity(OR 0.44,95%CI 0.20-0.96,P = 0.038) in the dominant ***:Genetic polymorphisms in the MMR pathway are potential clinical markers for predicting chemotherapy toxicity in NSCLC patients.

关键词：非小细胞肺癌药物毒性基因多态性错配修复化疗患者 DNA 单核苷酸多态性

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Associations of genetic polymorphisms of the transporters organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATE1),and ATP-binding cassette subfamily C member 2(ABCC2) with platinum-based chemotherapy response and toxicity in non-small cel

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Chinese Journal of Cancer 2016年第11期35卷 604-616页

作者： Chen-Yue Qian Yi Zheng ying Wang Juan Chen Jun-Yan Liu Hong-Hao Zhou ji-ye yin Zhao-Qian Liu Department of Clinical Pharmacology Xiangya HospitalCentral South Uni-versityChangsha 410008HunanP.R.China. Institute of Clinical Pharmacol-ogy Hunan Key Laboratory of PharmacogeneticsCentral South UniversityChangsha 410078HunanP.R.China. Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study Hengyang 421001HunanP.R.China. Key Laboratory of Hunan Province for Traditional Chinese Medicine in Obstetrics&Gynecology Research The Maternal and Child Health Hospital of Hunan ProvinceChangsha 410008HunanP.R.China. The affiliated Cancer Hospital of Xiangya School of Medicine Central South UniversityChangsha 410008HunanP.R.China. Xiangya School of Medicine Central South UniversityChangsha 410008HunanP.R.China.

Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this *** important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum *** study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC ***:A total of 403 Chinese NSCLC patients were recruited for this *** patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based *** tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was *** single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and ***:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor ***:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC *** registration Chinese Clinical Trial Registry

关键词： OCT2 MATE1 ABCC2 Non-small cell lung cancer Platinum-based chemotherapy

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Effect of cholesterol metabolism on hepatolithiasis

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World Journal of Gastroenterology 2025年第1期31卷 157-162页

作者： Lin Zheng Zi-Yu ye Jun-ji Ma Department of Gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesNo.215 Heping West RoadShijiazhuang 050000Hebei ProvinceChina

Surgical intervention is currently the primary treatment for hepatolithiasis;how-ever,some patients still experience residual stones and high recurrence rates after *** metabolism seems to play an important role in hepatoli-thiasis pathogenesis.A high cholesterol diet is one of the significant reasons for the increasing incidence of ***,regular diet and appropriate medical intervention are crucial measures to prevent hepatolithiasis and reduce recurrence rate after *** dietary cholesterol and drugs that increase cholesterol stone solubility are key therapeutic approaches in treating *** article discusses the cholesterol metabolic pathways related to the pathogenesis of hepatolithiasis,as well as food intake and targeted therapeutic drugs.

关键词： Hepatolithiasis Cholesterol metabolism High-fat diet 3-hydroxy-3-methylglutaryl-coenzyme A reductase Interlobular bile duct

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非小细胞肺癌患者DNA错配修复基因多态与铂类化疗药物毒副反应的关系

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癌症 2018年第2期37卷 82-88页

作者： Jun-Yan Liu Chen-Yue Qian Yuan-Feng Gao Juan Chen Hong-Hao Zhou ji-ye yin 中南大学湘雅医学院中南大学湘雅医院临床药理研究所中南大学临床药理研究所湖南省遗传药理学重点实验室湖南省分子靶标新药研究协同创新中心

背景与目的化疗毒性是一个令非小细胞肺癌(non-small cell lung cancer, NSCLC)患者深受困扰的严重问题。在NSCLC患者中,错配修复(mismatch repair, MMR)系统与铂类化疗药物的毒性相关。本研究旨在探讨NSCLC患者MMR通路的基因多态性与... 详细信息

背景与目的化疗毒性是一个令非小细胞肺癌(non-small cell lung cancer, NSCLC)患者深受困扰的严重问题。在NSCLC患者中,错配修复(mismatch repair, MMR)系统与铂类化疗药物的毒性相关。本研究旨在探讨NSCLC患者MMR通路的基因多态性与铂类化疗药物毒性的关系。方法本研究共纳入220例中国肺癌患者,他们曾接受过至少两个周期的铂类化疗药物治疗。两个化疗周期后,对每个患者的毒性反应进行评价。我们选择了44个单核苷酸多态性研究它们与铂类化疗药物毒性的关系。结果在显性模型中,人类错配修复基因2(MutS homolog 2, MSH2)rs6544991[优势比(OR)=2.98, 95%置信区间(CI):1.20–7.40, P=0.019]与胃肠道毒性有关;MSH3 rs6151627(OR=2.38, 95%CI:1.23–4.60, P=0.010)、rs6151670(OR=2.05, 95%CI:1.07–3.93, P=0.031)和rs7709909(OR=2.38, 95%CI:1.23–4.64, P=0.010)与血液学毒性有关。此外,MSH5 rs805304与整体毒性显著相关(OR=2.21, 95%CI:1.19–4.09, P=0.012),MSH5 rs707939与整体毒性(OR=0.42, 95%CI:0.23–0.76, P=0.004)和胃肠道毒性(OR=0.44, 95%CI:0.20–0.96, P=0.038)均显著相关。结论 MMR通路的基因多态性是潜在的预测NSCLC患者化疗毒性的临床标志物。

关键词： DNA错配修复肺癌化疗毒性铂类药物

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Perfluoropentane-based oxygen-loaded nanodroplets reduce microglial activation through metabolic reprogramming

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Neural Regeneration Research 2025年第4期20卷 1178-1191页

作者： Wanxian Luo Chuanhui Xu Linxi Li Yunxiang ji yezhong Wang yingjia Li Yongyi ye Department of Medicine Ultrasonics Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience Department of NeurosurgeryThe Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina

Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s *** perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory ***,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly *** this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s *** suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in ***,the neurotoxic effects were mitigated,which alleviated neuronal ***,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic *** further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1α***,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.

关键词： metabolic reprogramming microglia microglial migration nanotherapy neurodegenerative diseases neuroinflammation oxygen-loaded nanodroplets Parkinson’s disease perfluoropentane ultra-performance liquid chromatography–mass spectrometry

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Mechanisms of eIF3a action on therapeutic sensitivity in lung cancer patients receiving platinum-based chemotherapy

Mechanisms of eIF3a action on therapeutic sensitivity in lun...

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湖南省首届生理—药理科学青年论坛

作者： ji-ye yin,jie Shen,Xiao-jing Xu,Zhao-Qian Liu Institute of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics, Central South University Xiangya School of Medicine,Changsha,Hunan 410078

＜正＞Objcetive Platinum resistance is still one of the major obstacles in successful chemotherapy of lung cancer *** lesion is the major mechanism of action of many drugs,such as platinum and anthracyclines. Therefor...

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Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao jianjian Chu Tinglin Zhang Tong yin Yuankai Gu Wendanqi Liang Wenbo ji jianhua Zhuang Yan Liu jie Gao You yin Department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

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Repaglinide-irbesartan drug interaction: effects of SLCO1B1 polymorphism on repaglinide pharmacokinetics and pharmacodynamics in Chinese population

Repaglinide-irbesartan drug interaction: effects of SLCO1B1 ...

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2016年中国药学大会暨第十六届中国药师周

作者： Qi PEI Xi LI ji-ye yin Guo-ping YANG Shi-kun LIU Yi ZHENG Pan XIE Cheng-xian GUO Mi LUO Hong-hao ZHOU Zhao-qian LIU Department of Pharmacy The Third Xiangya HospitalCentral South University Department of Clinical Pharmacology Xiangya HospitalCentral South University Institute of Clinical Pharmacology Central South UniversityHunan Key Laboratory of Pharmacogenetics

Aim: On account of the potential inhibition of OATP1 B1（organic anion transporting polypeptide） by Angiotensin II receptor blockers（ARBs） and the effects of SLCO1 B1（solute carrier organic anion transporter family member） polymorphism, the aim of current study is to assess the impact of ARBs on the pharmacokinetics（PK） and pharmacodynamics（PD） of repaglinide in Chinese healthy volunteers with different SLCO1 B1 genotypes. Methods: The in vitro study was conducted on irbesartan, valsartan, olmesartan and losartan by using HEK293 cells transfected with OATP1 B1. Data on drug interactions between repaglinide and irbesartan from 21 healthy Chinese-Han male volunteers were collected and ***: IC50 from in vitro study suggested irbesartan was the most potent inhibitor of OATP1 B1 transporter. Clinical data from single dose of repaglinide indicated SLCO1 B1 c.521 T＞C polymorphism influenced the PK and PD of repaglinide in healthy Chinese-Han male volunteers. In subjects with SLCO1 B1 c.521 TT genotype, irbesartan comedication increased the exposure of repaglinide. In details, the peak plasma concentration [Cmax] increased 84%（P=0.003） and the area under the curve of plasma concentration 0-8 h [AUC0-8] increased 34%（P=0.004）, while the minimum blood glucose concentration [Cmin] decreased 33.8%（P=0.005）. No significant change was observed in repaglinide exposure in subjects with SLCO1 B1 c.521 TC genotype in presence or absence of irbesartan. Conclusion: SLCO1 B1 c.521 T＞C polymorphism affects the PK of repaglinide in Chinese population. Irbesartan increased repaglinide exposure in subjects with SLCO1 B1 c.521 TT genotype, but not SLCO1 B1 c.521 TC genotype.

关键词： repaglinide irbesartan drug-drug interaction SLCO1B1 polymorphism pharmacokinetics pharmacodynamics

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Effects of SLC30A8 polymorphisms on repaglinide response in type 2 diabetes mellitus

Effects of SLC30A8 polymorphisms on repaglinide response in ...

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湖南省首届生理—药理科学青年论坛

作者： Qiong Huang,ji-ye yin,Hong-Hao Zhou,Zhao-Qian Liu~* 1 Institute of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics, Central South University,Changsha,Hunan 410078,P.R.China.

＜正＞Objective Several genome-wide association studies（GWASs） identified the SLC30A8 polymorphisms to be associated with type 2 diabetes mellitus（T2DM） in European ancestry *** rs13266634 and rs16889462 nonsynony...

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Neural Regeneration Research 2025年第2期20卷 366-377页

作者： Samuel Abokyi Dennis Yan-yin Tse School of Optometry The Hong Kong Polytechnic UniversityKowloonHong Kong Special Administrative RegionChina Research Center for SHARP Vision The Hong Kong Polytechnic UniversityKowloonHong Kong Special Administrative RegionChina Center for Eye and Vision Research Sha TinHong Kong Special Administrative RegionChina

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their *** comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor *** meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal *** review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal *** impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing *** vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal ***,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and *** retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in *** cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering pro

关键词： age-related macular degeneration anti-aging interventions autophagy calorie restriction diabetic retinopathy exercise glaucoma neuromodulation phagocytosis photoreceptor outer segment degradation retinal aging transcription factor EB

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