35 results on '"Zhao-Qian Liu"'
Search Results
2. Circular RNA screening from EIF3a in lung cancer
- Author
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Ma‐Sha Huang, Fu‐Qiang Yuan, Yang Gao, Jun‐Yan Liu, Yi‐Xin Chen, Chen‐Jing Wang, Bai‐Mei He, Hong‐Hao Zhou, and Zhao‐Qian Liu
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bioinformatics ,circular RNA ,EIF3a ,lung cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Eukaryotic initiation factor 3 (EIF3) is one of the largest and most complex translation initiation factors, which consists of 13 subunits named eukaryotic translation initiation factor 3 subunit A (EIF3a) to EIF3m. EIF3a is the largest subunit of EIF3. Previous studies suggested that EIF3a is a housekeeping gene, recent results have found that EIF3a is closely related to the tumorigenesis and drug resistance. Circular RNAs (circRNAs) derived from biologically important gene can play an important role in gene regulation. However, the mechanism underlying circRNAs’ biological functions is not well understood yet. In this work, we screened 31 EIF3a‐derived circRNAs, in which two circEIF3as were identified to be correlated with cisplatin drug sensitivity in lung cancer. Two circEIF3as were found involved in RNA‐binding proteins‐mediated biological processes and may be related to translational regulation according to bioinformatics analyses. CircEIF3as, the transcriptional initiation factor EIF3a transcribed circRNAs, are associated with both drug sensitivity and translation regulation. These findings mean that they may have a functional synergy effect with EIF3a or be valuable therapeutic targets for treatment like EIF3a. This is the first study that exploits circRNAs screening from EIF3a in lung cancer, our findings provide a novel perspective on the function of EIF3a and circEIF3as in lung cancer.
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- 2019
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- View/download PDF
3. The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients
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Di Xiao, Yu Guo, Xi Li, Ji-Ye Yin, Wei Zheng, Xin-Wen Qiu, Ling Xiao, Rang-Ru Liu, Sai-Ying Wang, Wei-Jing Gong, Hong-Hao Zhou, and Zhao-Qian Liu
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background. We aimed to investigate the distributive characteristics of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients. Methods. The distributions of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms were determined in 267 T2DM patients and 182 healthy subjects. Subsequently, 53 newly diagnosed patients who received metformin monotherapy were recruited to evaluate metformin efficacy. Results. No significant difference was found between T2DM patients and healthy subjects in SLC22A1 rs594709 and SLC47A1 rs2289669 allele frequencies and genotype frequencies. After metformin treatment, SLC22A1 rs594709 GG genotype patients showed a higher increase in FINS (p=0.015) and decrease in HOMA-IS (p=0.001) and QUICKI (p=0.002) than A allele carriers. SLC47A1 rs2289669 GG genotype patients had a higher decrease in TChol (p=0.030) and LDL-C (p=0.049) than A allele carriers. Among SLC22A1 rs594709 AA genotype, patients with SLC47A1 rs2289669 AA genotype showed a higher decrease in FBG (p=0.015), PINS (p=0.041), and HOMA-IR (p=0.014) than G allele carriers. However, among SLC22A1 rs594709 G allele carriers, SLC47A1 rs2289669 AA genotype patients showed a higher decrease in TChol (p=0.013) than G allele carriers. Conclusion. Our data suggest that SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients.
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- 2016
- Full Text
- View/download PDF
4. eIF3a‐PPP2R5A‐mediated ATM/ATR dephosphorylation is essential for irinotecan‐induced DNA damage response
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Chao Mei, Ze‐En Sun, Li‐Ming Tan, Jian‐Ping Gong, Xi Li, and Zhao‐Qian Liu
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DNA Repair ,Eukaryotic Initiation Factor-3 ,Humans ,Apoptosis ,Ataxia Telangiectasia Mutated Proteins ,Protein Phosphatase 2 ,Cell Biology ,General Medicine ,Caco-2 Cells ,Irinotecan ,DNA Damage - Abstract
The individual differences and pervasive resistance seriously hinder the optimization of irinotecan-based therapeutic effectiveness. Eukaryotic translation initiation factor 3a (eIF3a) plays a key role in tumour occurrence, prognosis and therapeutic response. This study focused on the role of eIF3a in irinotecan-induced DNA damage response.The cck8 cell viability and clone survival analyses were used to test the regulatory role of eIF3a on irinotecan sensitivity in HT29 and CACO2 cell lines in vitro. This regulatory role was also verified in vivo by conducting subcutaneous xenograft model. Irinotecan-induced DNA damage, cell cycle arrest and apoptosis were tested by flow cytometry analysis, TUNEL staining, western blot and comet assays. The immunofluorescence, co-IP, luciferase reporter assay, RIP and flow cytometric analyses were carried out to investigate the underline mechanism.We demonstrated that eIF3a continuously activates ATM/ATR signal by translationally inhibiting PPP2R5A, a phosphatase that directly dephosphorylates and inactivates ATM/ATR after DNA repair complete. Suppression of PPP2R5A resulted in chronic ATM/ATR phosphorylation and activation, impairing DNA repair and enhancing irinotecan sensitivity.Our study suggested eIF3a with a high potential to influence phenotypic functions, which may contribute substantially to the early identification of susceptible individuals and the provision of personalized medication to irinotecan-treated patients.
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- 2022
5. Analytics of the clinical implementation of pharmacogenomics testing in 12 758 individuals
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Zhi Li, Zhao-Qian Liu, Dong-Sheng Ouyang, Gang Zhou, Fan Xiao, Lei-Yun Wang, Hong-Hao Zhou, Rong Liu, Yang Wang, Qing Li, Yan Chen, Wei Zhang, Yan Zhan, Le-Dong Xiao, Howard L. McLeod, Ji-Ye Yin, and Xing-Liang Xiong
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China ,Medicine (General) ,business.industry ,MEDLINE ,Medicine (miscellaneous) ,Data science ,Letter to Editor ,Clopidogrel ,Pharmacogenomic Testing ,Cytochrome P-450 CYP2C19 ,R5-920 ,Analytics ,Vitamin K Epoxide Reductases ,Pharmacogenomics ,Humans ,Molecular Medicine ,Medicine ,Warfarin ,Precision Medicine ,business ,Cytochrome P-450 CYP2C9 - Published
- 2021
6. Circular RNA screening from EIF3a in lung cancer
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Chen-Jing Wang, Hong-Hao Zhou, Yi-Xin Chen, Bai-Mei He, Fu-Qiang Yuan, Ma-Sha Huang, Jun-Yan Liu, Yang Gao, and Zhao-Qian Liu
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0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Eukaryotic Initiation Factor-3 ,Computational biology ,Biology ,medicine.disease_cause ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Eukaryotic translation ,Circular RNA ,Translational regulation ,medicine ,Initiation factor ,Humans ,Radiology, Nuclear Medicine and imaging ,EIF3a ,Gene ,Original Research ,Regulation of gene expression ,Clinical Cancer Research ,circular RNA ,RNA, Circular ,bioinformatics ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Survival Analysis ,Housekeeping gene ,Gene Expression Regulation, Neoplastic ,lung cancer ,030104 developmental biology ,Treatment Outcome ,Oncology ,A549 Cells ,030220 oncology & carcinogenesis ,Cisplatin ,Carcinogenesis - Abstract
Eukaryotic initiation factor 3 (EIF3) is one of the largest and most complex translation initiation factors, which consists of 13 subunits named eukaryotic translation initiation factor 3 subunit A (EIF3a) to EIF3m. EIF3a is the largest subunit of EIF3. Previous studies suggested that EIF3a is a housekeeping gene, recent results have found that EIF3a is closely related to the tumorigenesis and drug resistance. Circular RNAs (circRNAs) derived from biologically important gene can play an important role in gene regulation. However, the mechanism underlying circRNAs’ biological functions is not well understood yet. In this work, we screened 31 EIF3a‐derived circRNAs, in which two circEIF3as were identified to be correlated with cisplatin drug sensitivity in lung cancer. Two circEIF3as were found involved in RNA‐binding proteins‐mediated biological processes and may be related to translational regulation according to bioinformatics analyses. CircEIF3as, the transcriptional initiation factor EIF3a transcribed circRNAs, are associated with both drug sensitivity and translation regulation. These findings mean that they may have a functional synergy effect with EIF3a or be valuable therapeutic targets for treatment like EIF3a. This is the first study that exploits circRNAs screening from EIF3a in lung cancer, our findings provide a novel perspective on the function of EIF3a and circEIF3as in lung cancer.
- Published
- 2019
7. LncRNA FOXD1‐AS1 acts as a potential oncogenic biomarker in glioma
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Yuan-Feng Gao, Zhao-Qian Liu, Zheng-Wen He, Hong-Hao Zhou, Wei Zhang, Xiao-Yuan Mao, Zhi-Bin Wang, Xi Li, Ji-Ye Yin, Jun-Yan Liu, and Tao Zhu
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0301 basic medicine ,lncRNAs ,Protein Array Analysis ,Apoptosis ,Biology ,Diagnosis, Differential ,Mice ,03 medical and health sciences ,0302 clinical medicine ,lncRNA FOXD1‐AS1 ,Peptide Initiation Factors ,Cell Line, Tumor ,Physiology (medical) ,Glioma ,miR‐339/342 ,microRNA ,medicine ,Animals ,Gene silencing ,Pharmacology (medical) ,RNA, Small Interfering ,Pharmacology ,Mice, Inbred BALB C ,Gene knockdown ,Oncogene ,Brain Neoplasms ,RNA-Binding Proteins ,Forkhead Transcription Factors ,Original Articles ,Transfection ,medicine.disease ,Xenograft Model Antitumor Assays ,3. Good health ,Antisense RNA ,MicroRNAs ,Psychiatry and Mental health ,030104 developmental biology ,Cancer research ,Original Article ,RNA, Long Noncoding ,eIF5a ,EIF5A ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Aims Altered activities of long noncoding RNAs (lncRNAs) have been associated with cancer development, and lncRNA FOXD1‐AS1 (FOXD1‐AS1) is the antisense transcript of the gene encoding for FOXD1, known for its role as an oncogene in several tumor types including glioma. However, the role of FOXD1‐AS1 in the differentiation and progression of glioma is not well known. Methods Expression profile chip and qPCR were used to screen and identify FOXD1‐AS1. Glioma cells were transfected with siRNA or eukaryotic expression vector to observe FOXD1‐AS1 function in vitro and in vivo. Dual luciferase reporter gene analysis, Western blot, and ChIRP‐MS were used to detect microRNAs and protein that combine with FOXD1‐AS1. Results FOXD1‐AS1 was upregulated and directly correlated with the glioma grade, and it was localized in both the nucleus and the cytoplasm of the glioma cell. FOXD1‐AS1 silencing caused tumor suppressive effects via inhibiting cell proliferation, migration, and apoptosis, while FOXD1‐AS1 overexpression resulted in opposite effects. Additionally, in vivo experiments showed that FOXD1‐AS1 knockdown reduced tumor volume and weight. More importantly, mechanical studies revealed that FOXD1‐AS1 targeted both miR339‐5p and miR342‐3p (miR339/342). Furthermore, protein eukaryotic translation initiation factor 5 subunit A (eIF5a) resulted a direct target of FOXD1‐AS1. Conclusions These data indicated that FOXD1‐AS1, a miR339/342 target, affected biological processes via protein eIF5a; thus, it might be considered as a new therapeutic target for glioblastoma.
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- 2019
8. Retracted : 9za plays cytotoxic and proapoptotic roles and induces cytoprotective autophagy through the PDK1/Akt/mTOR axis in non‐small‐cell lung cancer
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Hong-Hao Zhou, Xi Li, Xinan Yi, Zhao-Qian Liu, Gaoyun Hu, Fengying Huang, Rangru Liu, Danqi Liu, and Zhuo Chen
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0301 basic medicine ,Indoles ,Lung Neoplasms ,Cell Survival ,Physiology ,Clinical Biochemistry ,Antineoplastic Agents ,3-Phosphoinositide-Dependent Protein Kinases ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Autophagy ,medicine ,Humans ,Cytotoxic T cell ,Benzodioxoles ,Protein kinase A ,Lung cancer ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Aniline Compounds ,Molecular Structure ,Chemistry ,TOR Serine-Threonine Kinases ,Cancer ,Cell Biology ,Fibroblasts ,medicine.disease ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Phosphorylation ,Proto-Oncogene Proteins c-akt - Abstract
Non-small-cell lung cancer (NSCLC) is an aggressive subtype of pulmonary carcinomas with high mortality. However, chemotherapy drug resistance and high recurrence rates hinder the curative effect of platinum-based first-line chemotherapy, which makes it urgent to develop new antitumor drugs for NSCLC. 9za, a new candidate drug synthesized by our research group, has been verified with potent antilung cancer activity in preliminary experiments. However, the underlying molecular mechanism of 9za remains largely vague. This work revealed that 9za could play important cytotoxic and proapoptotic roles in NSCLC cells. Moreover, 9za could induce autophagy and promote autophagy flux. Interestingly, the cytotoxic and proapoptotic roles were significantly dependent on 9za-induced cytoprotective autophagy. That is, the coadministration of 9za with an autophagy inhibitor such as chloroquine or 3-methyladenine exhibited increased cytotoxic and proapoptotic effects compared with 9za treatment alone. In addition, 9za exposure suppressed the phosphorylation of phosphoinositide-dependent protein kinase 1 (PDK1), protein kinase B (Akt), mammalian targets of rapamycin (mTOR), p70 S6 kinase, and 4E binding protein 1 by a dose-dependent way, manifesting that the Akt/mTOR axis was implicated in 9za-induced autophagy. In addition, the overexpression of PDK1 resulted in increased phosphorylation of PDK1 and Akt and blocking of 9za-mediated autophagy. These data showed that the PDK1/Akt/mTOR pathway was involved in 9za-induced autophagy. Hence, this work provides a theoretical basis for exploiting 9za as a new antilung cancer candidate drug and hints that the combination of 9za with an autophagy inhibitor is a feasible alternative approach for the therapy of NSCLC.
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- 2019
9. Resistin facilitates metastasis of lung adenocarcinoma through the <scp>TLR</scp> 4/Src/ <scp>EGFR</scp> / <scp>PI</scp> 3K/ <scp>NF</scp> ‐κB pathway
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Rui-Jie Liu, Hong-Hao Zhou, Wei Zhang, Ji-Ye Yin, Jun-Yan Liu, Wei-Jing Gong, Di Xiao, Xi Li, Zhao-Qian Liu, Jia-Jia Cui, Wei Zhuo, and Chao Luo
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0301 basic medicine ,Cancer Research ,Lung Neoplasms ,endocrine system diseases ,Carcinogenesis ,Adenocarcinoma of Lung ,Adenocarcinoma ,migration ,Metastasis ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Resistin ,TLR4 ,Epidermal growth factor receptor ,Neoplasm Metastasis ,PI3K/AKT/mTOR pathway ,A549 cell ,Tumor microenvironment ,biology ,Chemistry ,NF-kappa B ,nutritional and metabolic diseases ,Original Articles ,U937 Cells ,General Medicine ,respiratory system ,invasion ,lung adenocarcinoma ,medicine.disease ,ErbB Receptors ,Toll-Like Receptor 4 ,src-Family Kinases ,030104 developmental biology ,Oncology ,A549 Cells ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Original Article ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Metastasis is the main cause of lung cancer-related death. The tumor microenvironment greatly contributes to tumor metastasis. Resistin, mainly secreted by tumor-associated macrophages in tumor tissues, is a 12.5-kDa cysteine-rich secretory protein that is found at significantly higher levels in the serum or plasma of cancer patients compared with healthy controls. In this study, we explored the expression and role of resistin in lung adenocarcinoma. Our study showed that resistin was strongly expressed in lung adenocarcinoma tissues and promoted the migration and invasion of lung adenocarcinoma cells in a dose-dependent manner. Toll-like receptor 4 (TLR4) was the functional receptor of resistin for migration and invasion in A549 cells. Src/epidermal growth factor receptor (EGFR) was involved in resistin-induced migration and invasion. Resistin increased the phosphorylation of EGFR through the TLR4/Src pathway. We also found that PI3K/nuclear factor (NF)-κB were the intracellular downstream effectors mediating resistin-induced migration and invasion. Taken together, our results suggested that resistin promoted lung adenocarcinoma metastasis through the TLR4/Src/EGFR/PI3K/NF-κB pathway.
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- 2018
10. Copper efflux transporters ATP7A and ATP7B: Novel biomarkers for platinum drug resistance and targets for therapy
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Ji-Ye Yin, Yue-Qin Li, Xiang-Ping Li, and Zhao-Qian Liu
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0301 basic medicine ,endocrine system diseases ,medicine.medical_treatment ,Clinical Biochemistry ,ATP7A ,chemistry.chemical_element ,Drug resistance ,medicine.disease_cause ,Biochemistry ,Cancer prognosis ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,Medicine ,Molecular Biology ,Chemotherapy ,business.industry ,Cancer ,Cell Biology ,medicine.disease ,Efflux transporters ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,business ,Carcinogenesis ,Platinum - Abstract
Platinum-based chemotherapy agents are widely used in the treatment of various solid malignancies. However, their efficacy is limited by drug resistance. Recent studies suggest that copper efflux transporters, which are encoded by ATP7A and ATP7B, play an important role in platinum drug resistance. Over-expressions of ATP7A and ATP7B are observed in multiple cancers. Moreover, their expressions are associated with cancer prognosis and treatment outcomes of platinum-based chemotherapy. In our review, we highlight the roles of ATP7A/7B in platinum drug resistance and cancer progression. We also discuss the possible mechanisms of platinum drug resistance mediated by ATP7A/7B and provide novel strategies for overcoming resistance. This review may be helpful for understanding the roles of ATP7A and ATP7B in platinum drug resistance. © 2018 IUBMB Life, 70(3):183-191, 2018.
- Published
- 2018
11. Nucleolar and spindle-associated protein 1 is a tumor grade correlated prognosis marker for glioma patients
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Yuan-Feng Gao, Ma-Sha Huang, Tao Zhu, Hong-Hao Zhou, Wei Zhang, Zhao-Qian Liu, Pan Xie, and Xi Li
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Adult ,Male ,0301 basic medicine ,Cell cycle checkpoint ,medicine.medical_treatment ,Apoptosis ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,Physiology (medical) ,Glioma ,Biomarkers, Tumor ,medicine ,Humans ,Gene silencing ,Pharmacology (medical) ,RNA, Messenger ,neoplasms ,Mitosis ,Survival analysis ,Cell Proliferation ,Pharmacology ,Chemotherapy ,Brain Neoplasms ,business.industry ,Cell Cycle ,Original Articles ,Middle Aged ,Prognosis ,medicine.disease ,Phenotype ,nervous system diseases ,Psychiatry and Mental health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,business ,Microtubule-Associated Proteins - Abstract
Aims Despite therapeutic advances in glioma management including surgery, radiation, and chemotherapy, the improvement of patient outcome is far from satisfactory. Nucleolar and spindle-associated protein 1 (NUSAP1) is an important functional protein during mitosis, and its abnormal expression is implicated in progression of different types of tumors. However, the role of NUSAP1 in gliomas remains unclear. Methods NUSAP1 expression in gliomas with different grades was investigated based on GEO glioma datasets. Kaplan-Meier survival analysis was used to evaluate its prognostic significance. In vitro assays were also performed to evaluate effects of NUSAP1 on malignant phenotypes of glioma cells by silencing NUSAP1. Results NUSAP1 expression was correlated not only with glioma grade but also with prognosis of glioma patients. NUSAP1 depletion suppressed proliferation of U251 cells by inducing cell cycle arrest at G2/M phase and apoptosis. NUSAP1 depletion rendered U251 cells impaired migratory ability as well. Conclusion NUSAP1 is a potential prognosis marker for glioma patients and therapeutic strategies targeting NUSAP1 might hold promise in improving glioma treatment.
- Published
- 2018
12. The association of genetic variations in DNA repair pathways with severe toxicities in NSCLC patients undergoing platinum‐based chemotherapy
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Wei Zhang, Xiang-Ping Li, Di Xiao, Hong-Hao Zhou, Ji-Ye Yin, Zhao-Qian Liu, Cheng-Ping Hu, Xiang Chen, Shiming Wang, Yi Zheng, Xiao-Ke Wen, Daru Lu, and Zheng Deng
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Male ,0301 basic medicine ,Cancer Research ,Candidate gene ,Lung Neoplasms ,DNA Repair ,Genotype ,Paclitaxel ,DNA repair ,Antineoplastic Agents ,Single-nucleotide polymorphism ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Carboplatin ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,medicine ,Humans ,Lung cancer ,Aged ,Leukopenia ,Middle Aged ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Toxicity ,Cohort ,Female ,medicine.symptom ,Pharmacogenetics - Abstract
Genetic variations in genes involved in repairing platinum-induced DNA lesions may contribute to the toxicity of platinum-based chemotherapy. The role of single nucleotide polymorphisms (SNPs) within DNA repair pathways in the occurrence of severe toxicity is not yet understood. Current studies prefer to do original works rather than analyze previously published data. Our study aimed to replicate associations between previously investigated SNPs and toxicities as well as to identify new genetic makers. We systematically examined the relevance of 97 SNPs in 54 candidate genes responsible for repairing DNA inter-strand and intra-strand crosslinks to severe toxicity in a discovery cohort of 437 NSCLC patients receiving platinum-based chemotherapy. Statistically significant SNPs were then assessed for replication in an independent validation cohort of 781 NSCLC patients. We found that 7 SNPs were significant at P
- Published
- 2017
13. Emerging roles ofRAC1in treating lung cancer patients
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Juan Chen, Xiao-Yuan Mao, Hong-Hao Zhou, Tao Zhu, Ting Zou, Zhao-Qian Liu, Xi Li, Qiu-Qi Li, and Ji-Ye Yin
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0301 basic medicine ,Cell growth ,Phagocytosis ,Cancer ,Guanosine ,Motility ,RAC1 ,Biology ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Breast cancer ,chemistry ,Genetics ,medicine ,Cancer research ,Lung cancer ,Genetics (clinical) - Abstract
The Ras-related C3 botulinum toxin substrate 1 (RAC1), a member of the Rho family of small guanosine triphosphatases, is critical for many cellular activities, such as phagocytosis, adhesion, migration, motility, cell proliferation, and axonal growth. In addition, RAC1 plays an important role in cancer angiogenesis, invasion, and migration, and it has been reported to be related to most cancers, such as breast cancer, gastric cancer, testicular germ cell cancer, and lung cancer. Recently, the therapeutic target of RAC1 in cancer has been investigated. In addition, some investigations have shown that inhibition of RAC1 can reverse drug-resistance in non-small cell lung cancer. In this review, we summarize the recent advances in understanding the role of RAC1 in lung cancer and the underlying mechanisms and discuss its value in clinical therapy.
- Published
- 2016
14. Effect of CYP2C9-VKORC1 interaction on warfarin stable dosage and its predictive algorithm
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Wei Zhang, Sheng-Lan Tan, Hui He, Xi Li, Fang Yang, Ji-Ye Yin, Jie Tang, Zhi Li, Zhao-Qian Liu, Han Yan, Rong Liu, Hong-Hao Zhou, Zhi-Yin Luo, Xiao-Ping Chen, and Xiao-Yuan Mao
- Subjects
Pharmacology ,Generalized linear model ,Statistics ,Warfarin ,medicine ,On warfarin ,Pharmacology (medical) ,Multiple linear regression analysis ,Biology ,Predictive analytics ,Algorithm ,medicine.drug ,CYP2C9 & VKORC1 - Abstract
This study aimed to identify the effect of CYP2C9-VKORC1 interaction on warfarin dosage requirement and its predictive algorithm by investigating four populations. Generalized linear model was used to evaluate the relationship between the interaction and warfarin stable dosage (WSD), whereas multiple linear regression analysis was applied to construct the WSD predictive algorithm. To evaluate the effect of CYP2C9-VKORC1 interaction on the predictive algorithms, we compared the algorithms with and without the interaction. The interaction was significantly associated with WSD in the Chinese and White cohorts (P values < 0.05). In the algorithms that considered the interaction, the predictive success rates improved by only 0.12% in the Chinese patients and by a maximum of 0.02% in the White patients under four different CYP2C9 classifications. Thus, VKORC1-CYP2C9 interaction can affect WSD. However, the discrepancy between the predictive results obtained using the predictive algorithm with and without CYP2C9-VKORC1 interaction was negligible and can therefore be disregarded.
- Published
- 2014
15. Association ofHMGB1andHMGB2genetic polymorphisms with lung cancer chemotherapy response
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Ji-Ye Yin, Chen-Yue Qian, Kamila Smieszkol, Juan Chen, Yu Zhang, Yi Zheng, Hui He, Xiang-Ping Li, Hong-Hao Zhou, Zi-Yu Chen, Zhao-Qian Liu, Ying Wang, and Yi-Lan Fu
- Subjects
Genetic Markers ,Male ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Genotype ,Physiology ,medicine.medical_treatment ,Antineoplastic Agents ,chemical and pharmacologic phenomena ,Single-nucleotide polymorphism ,Biology ,HMGB1 ,HMGB2 ,Carboplatin ,Physiology (medical) ,Internal medicine ,medicine ,HMGB2 Protein ,Humans ,HMGB1 Protein ,Lung cancer ,Pharmacology ,Chemotherapy ,Polymorphism, Genetic ,Middle Aged ,medicine.disease ,Potential biomarkers ,biology.protein ,Cancer research ,Female ,Cisplatin ,Chemotherapy response - Abstract
Summary The aim of the present study was to investigate the association of genetic polymorphisms in high mobility group box 1 and 2 (HMGB1 and HMGB2, respectively) with platinum-based chemotherapy responses in Chinese lung cancer patients. In total, 338 Chinese lung cancer patients (154 responders and 184 non-responders) were recruited to the study. All patients received at least two cycles of first-line platinum-based chemotherapy. Three tagging single nucleotide polymorphisms (SNPs) of HMGB1 and two tagging SNPs of HMGB2 were detected in patients. We found that rs1412125 and rs2249825 of HMGB1 were significantly associated with the platinum-based chemotherapy response in both recessive and genotypic models. In addition, rs1412125 showed significant association with platinum-based chemotherapy response for the subgroup of patients aged >55 years in additive, recessive and genotypic models. No significant associations were detected between other SNPs and the platinum-based chemotherapy response. The HMGB1 SNPs (rs1412125 and rs2249825) were associated with platinum-based chemotherapy responses in Chinese lung cancer patients. In conclusion, HMGB1 SNPs may serve as potential biomarkers for predicting the efficacy of platinum-based chemotherapy.
- Published
- 2014
16. Type 2 diabetes mellitus-related genetic polymorphisms in microRNAs and microRNA target sites (MicroRNAs中与2型糖尿病相关的基因多态性及microRNA靶位)
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Ji-Ye Yin, Wei-Jing Gong, Guang-feng Ming, Di Xiao, Hong-Hao Zhou, and Zhao-Qian Liu
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Genetics ,Untranslated region ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,nutritional and metabolic diseases ,MiRNA binding ,Regulatory sequence ,microRNA ,Genetic variation ,Gene expression ,Medicine ,Gene silencing ,business ,Gene - Abstract
MicroRNAs (miRNAs) are important endogenous regulators in eukaryotic gene expression and a broad range of biological processes. MiRNA-related genetic variations have been proved to be associated with human diseases, such as type 2 diabetes mellitus (T2DM). Polymorphisms in miRNA genes (primary miRNAs, precursor miRNAs, mature miRNAs, and miRNA regulatory regions) may be involved in the development of T2DM by changing the expression and structure of miRNAs and target gene expression. Genetic polymorphisms of the 3'-untranslated region (UTR) in miRNA target genes may destroy putative miRNA binding sites or create new miRNA binding sites, which affects the binding of UTRs with miRNAs, finally resulting in susceptibility to and development of T2DM. Therefore, focusing on studies into genetic polymorphisms in miRNAs or miRNA binding sites will help our understanding of the pathophysiology of T2DM development and lead to better health management. Herein, we review the association of genetic polymorphisms in miRNA and miRNA targets genes with T2DM development.
- Published
- 2014
17. Gene-Wide Tagging Study of the Association BetweenKCNT1Polymorphisms and the Susceptibility and Efficacy of Genetic Generalized Epilepsy in Chinese Population
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Yu Zhang, Zhao-Qian Liu, Hong-Hao Zhou, Xiang-Ping Li, Nan Lv, Qiang Tang, Ying Zhang, Dong-Li Hu, Jian Qu, Ji-Ye Yin, Xiao-Jing Xu, Zhi-Quan Yang, Hongyu Long, Bo Xiao, Boting Zhou, Hui He, and Xiao-Yuan Mao
- Subjects
Adult ,Male ,China ,Candidate gene ,Potassium Channels ,Adolescent ,Drug Resistance ,Nerve Tissue Proteins ,Autosomal dominant nocturnal frontal lobe epilepsy ,Drug resistance ,Potassium Channels, Sodium-Activated ,Biology ,Polymorphism, Single Nucleotide ,Young Adult ,symbols.namesake ,Physiology (medical) ,Genotype ,medicine ,Humans ,Genetic Predisposition to Disease ,Pharmacology (medical) ,Allele ,Child ,Genetic Association Studies ,Pharmacology ,Genetics ,Haplotype ,Original Articles ,medicine.disease ,Psychiatry and Mental health ,Bonferroni correction ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Multiple comparisons problem ,symbols ,Anticonvulsants ,Epilepsy, Generalized ,Female - Abstract
SUMMARY Aims: The causes of genetic generalized epilepsies (GGEs) are still uncertain now. Some studies found that the human potassium channel, subfamily T, member 1 (KCNT1) is the candidate gene causing malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy which are all rare genetic generalized epilepsies. The aims of this study were going to evaluate the association between KCNT1 common variations and the susceptibility and drug resistance of genetic generalized epilepsies in Chinese population. Methods: The allele-specific MALDI–TOF mass spectrometry method was used to assess 17 tagSNPs (tagged single-nucleotide polymorphisms) of KCNT1 in 284 healthy Chinese controls and 483 Chinese GGEs patients including 279 anti-epileptic drug-responsive patients and 204 drug-resistant patients. Results: Genotype distributions of all the selected tagSNPs were consistent with Hardy–Weinberg equilibrium in GGEs and healthy controls. None of the all 17 tagSNPs alleles were found to be related with the susceptibility and drug resistance of genetic generalized epilepsies. The frequencies of haplotype 5 and haplotype 1 were significantly lower in GGEs than that in healthy controls (2% vs. 4%, OR = 0.47 [0.27–0.94], P = 0.03) and obviously higher in drug-resistant patients than that in drug-response patients (6% vs. 3%, OR = 2.56 [1.23–5.35], P = 0.01). However, after the correction of multiple comparisons with Bonferroni’s method, we found that the above two haplotypes were not associated with the susceptibility and drug resistance in GGEs and healthy controls. Conclusion: This gene-wide tagging study revealed no association between KCNT1 17 common variations and susceptibility of GGEs or AEDs (anti-epileptic drugs) efficacy of genetic generalized epilepsies in Chinese population.
- Published
- 2013
18. A high-throughput inhibition screening of major human cytochrome P450 enzymes using anin vitrococktail and liquid chromatography-tandem mass spectrometry
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Hong-Hao Zhou, Yao Chen, Jing Yu, Zhao-Qian Liu, Ji-Ye Yin, Jian Qu, Chong-Zhen Qin, Zhi-Rong Tan, and Xian Ren
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Pharmacology ,CYP2D6 ,Chromatography ,CYP3A4 ,biology ,Chemistry ,Drug discovery ,Clinical Biochemistry ,Cytochrome P450 ,General Medicine ,Mass spectrometry ,Biochemistry ,Analytical Chemistry ,Liquid chromatography–mass spectrometry ,Drug Discovery ,Microsome ,biology.protein ,CYP2A6 ,Molecular Biology - Abstract
A sensitive and high-throughput inhibition screening liquid chromatography–mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of five probe metabolites (7-hydroxycoumarin, CYP2A6; 4-hydroxytolbutamide, CYP2C9; 4′-hydroxymephenytoin, CYP2C19; α-hydroxymetoprolol, CYP2D6; and 1-hydroxymidazolam, CYP3A4) for in vitro cytochrome P450 activity determination in human liver microsome and recombinant. All the metabolites and the internal standard, tramadol, were separated on a Waters 2695 series liquid chromatograph with a Phenomenex Luna C18 column (150 × 2.0 mm, 5 µm). Quality control samples and a positive control CYP inhibitor were included in the method. The IC50 values determined for typical CYP inhibitors were reproducible and in agreement with the literature. The method was selective and showed good accuracy (99.13–103.37%), and inter-day (RSD
- Published
- 2013
19. Association betweeneIF3αpolymorphism and severe toxicity caused by platinum-based chemotherapy in non-small cell lung cancer patients
- Author
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Ruixia Yuan, Zhao-Qian Liu, Lifang Han, Boting Zhou, Xiao-Jing Xu, Li Duan, Huaping Yang, Hong-Hao Zhou, Rui Ma, and Yingchun Zhao
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Pharmacology ,Cisplatin ,Oncology ,Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,non-small cell lung cancer (NSCLC) ,medicine.disease ,Carboplatin ,Nephrotoxicity ,chemistry.chemical_compound ,Ototoxicity ,chemistry ,Internal medicine ,Toxicity ,medicine ,Pharmacology (medical) ,Lung cancer ,business ,medicine.drug - Abstract
Aim Platinum-induced toxicity severely impedes successful chemotherapy in lung cancer patients. The nucleotide excision repair (NER) pathway is considered as one of the major factors contributing to platinum effects. Furthermore, genetic variances of the NER pathway influence platinum toxicity. eIF3α, over expressed in many malignancies, is an up-stream gene of NER and could regulate its activity. The purpose of this study was to investigate whether eIF3α polymorphism is associated with severe platinum toxicity in patients with non-small cell lung cancer (NSCLC). Methods Two hundred and eighty-two incident NSCLC patients, from three different institutions, were enrolled and followed up. These patients were diagnosed and histologically confirmed with non-small cell lung cancer. All patients accepted platinum based chemotherapy for at least two cycles. Twenty-two SNPs of eIF3α were detected in these patients. Results eIF3α Arg803Lys C > T polymorphism was associated with cisplatin-induced toxicity in NSCLC patients (P = 0.02, OR = 0.54, 95% CI 0.32, 93). T-carrier subjects presented better tolerance to platinum nephrotoxicity, but poorer tolerance to ototoxicity. Conclusion eIF3α Arg803Lys was associated with platinum toxicity in NSCLC patients and could be considered as a predictor for pretreatment evaluation in lung cancer patients.
- Published
- 2013
20. Rapid clinical induction of bupropion hydroxylation by metamizole in healthy Chinese men
- Author
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Zhao-Qian Liu, Dong-Li Hu, Xiao-Ping Chen, Hong-Hao Zhou, Zhi-Rong Tan, Wei Zhang, Wen-Jie Qin, Dan Wang, and Lan Fan
- Subjects
Pharmacology ,Bupropion ,Chemistry ,Analgesic ,Cmax ,Metamizole ,Pharmacokinetics ,Oral administration ,health services administration ,mental disorders ,behavior and behavior mechanisms ,medicine ,Pharmacology (medical) ,Antipyretic ,Active metabolite ,medicine.drug - Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Bupropion, an antidepressant and smoking cessation drug, is metabolized to its active metabolite, 4-hydroxybupropion, almost exclusively by CYP2B6. • Metamizole, a pyrazolone derivative with analgesic properties, was shown in an in vitro study to increase significantly the expression of CYP2B6 and bupropion hydroxylase activity. • The effect of metamizole on bupropion hydroxylation has not been investigated and drug interactions may occur between metamizole and bupropion. WHAT THIS PAPER ADDS • Oral administration of metamizole for 4 days significantly altered the pharmacokinetics of both bupropion and its active metabolite, 4-hydroxybupropion, and significantly increased the CYP2B6-catalyzed bupropion hydroxylation in all of the subjects. • Dosage adjustment of bupropion may be needed in patients when metamizole is concomitantly administered. AIMS This study aimed to investigate the effect of metamizole on bupropion hydroxylation related to different CYP2B6 genotype groups in healthy volunteers. METHODS Sixteen healthy male volunteers (6 CYP2B6*1/*1, 6 CYP2B6*1/*6 and 4 CYP2B6*6/*6) received orally administered bupropion alone and during daily treatment with metamizole 1500 mg day–1 (500 mg tablet taken three times daily) for 4 days. Serial blood samples were obtained up to 48 h after each bupropion dose. RESULTS After metamizole treatment relative to bupropion alone, the geometric mean ratios (GMRs) and 90% confidence interval (CI) of the AUC(0,∞) ratio of 4-hydroxybupropion over bupropion were 1.99 (1.57, 2.55) for the CYP2B6*1/*1 group, 2.15 (1.53, 3.05) for the CYP2B6*1/*6 group and 1.86 (1.36, 2.57) for the CYP2B6*6/*6 group. The GMRs and 90% CI of bupropion were 0.695 (0.622, 0.774) for AUC(0,∞) and 0.400 (0.353, 0.449) for Cmax, respectively. The corresponding values for 4-hydroxybupropion were 1.43 (1.28, 1.53) and 2.63 (2.07, 2.92). The t1/2 value was significantly increased for bupropion and decreased for 4-hydroxybupropion. The tmax values of bupropion and 4-hydroxybupropion were both significantly decreased. The mean percentage changes in pharmacokinetic parameters among the CYP2B6 genotype groups were not significantly different. CONCLUSIONS Oral administration of metamizole for 4 days significantly altered the pharmacokinetics of both bupropion and its active metabolite, 4-hydroxybupropion, and significantly increased the CYP2B6-catalyzed bupropion hydroxylation in all of the subjects. Cautions should be taken when metamizole is co-administered with CYP2B6 substrate drugs.
- Published
- 2012
21. Genetic polymorphism of copper transporter protein 1 is related to platinum resistance in Chinese non-small cell lung carcinoma patients
- Author
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Zhao-Qian Liu, Boting Zhou, Xiao-Jing Xu, Li Duan, Rui Ma, and Hong-Hao Zhou
- Subjects
Adult ,Male ,China ,Lung Neoplasms ,endocrine system diseases ,Physiology ,medicine.medical_treatment ,chemistry.chemical_element ,Antineoplastic Agents ,Platinum Compounds ,Drug resistance ,Treatment of lung cancer ,Biology ,Polymorphism, Single Nucleotide ,Carboplatin ,Asian People ,Carcinoma, Non-Small-Cell Lung ,Physiology (medical) ,Antineoplastic Combined Chemotherapy Protocols ,Carcinoma ,medicine ,Humans ,Cation Transport Proteins ,Genetic Association Studies ,Aged ,Copper Transporter 1 ,Pharmacology ,Cisplatin ,Chemotherapy ,Predictive marker ,Haplotype ,Middle Aged ,medicine.disease ,Survival Analysis ,female genital diseases and pregnancy complications ,chemistry ,Drug Resistance, Neoplasm ,Immunology ,Cancer research ,Female ,Platinum ,Biomarkers ,Follow-Up Studies ,medicine.drug - Abstract
1. Chemotherapeutic resistance to platinum-based anticancer drugs is a major obstacle in the successful treatment of lung cancer. Cellular uptake and platinum accumulation are considered the most important factors contributing to platinum resistance. The copper transporter family is the major plasma membrane transporter for platinum uptake. Copper transporter protein 1 (CTR1) plays an essential role in cisplatin influx and is closely related to platinum resistance by influencing platinum uptake and accumulation. The aim of the present study was to determine whether CTR1 polymorphisms are associated with platinum resistance in non-small cell lung carcinoma (NSCLC) patients. 2. A total of 282 incident Chinese Han NSCLC patients were enrolled in the study and followed up at three different institutions. All patients underwent at least two cycles of platinum-based chemotherapy. Twenty single-nucleotide polymorphisms of CTR1 were detected from genomic DNA samples. 3. Genetic polymorphisms of CTR1 at rs7851395 and rs12686377 were associated with platinum resistance in NSCLC patients. Patients with a GT haplotype presented with increased susceptibility to platinum resistance (P < 0.05), whereas an AG haplotype contributed to longer survival (P < 0.05). 4. In conclusion, a significant relationship was found between rs7851395 and rs12686377 polymorphisms and platinum resistance, as well as clinical outcomes, in Chinese NSCLC patients. Thus, CTR1 plays an essential role in platinum resistance and could be considered a predictive marker for the pretreatment evaluation of NSCLC patients.
- Published
- 2012
22. NeuroD1 A45T and PAX4 R121W polymorphisms are associated with plasma glucose level of repaglinide monotherapy in Chinese patients with type 2 diabetes
- Author
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Zhicheng Gong, Hong-Bin Lu, Xiao-Jing Xu, Zhao-Qian Liu, Qi Pei, Xing-Ping Dai, Ji-Ye Yin, Hong-Hao Zhou, Guang-Hua Lei, Jian Qu, Jie Shen, Gan Zhou, Qiong Huang, Min Dong, and Boting Zhou
- Subjects
Pharmacology ,medicine.medical_specialty ,Triglyceride ,Insulin ,medicine.medical_treatment ,Case-control study ,Type 2 Diabetes Mellitus ,Type 2 diabetes ,Biology ,medicine.disease ,Repaglinide ,chemistry.chemical_compound ,Insulin resistance ,Endocrinology ,Postprandial ,chemistry ,Internal medicine ,medicine ,Pharmacology (medical) ,medicine.drug - Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Repaglinide is an insulin secretagogue agent widely used in the treatment of type 2 diabetes mellitus (T2DM). Obvious interindividual differences in the therapeutic efficacy of and adverse reactions to repaglinide were observed in Chinese T2DM patients. • There are no reports showing the influence of genetic variations of NeuroD1/BETA2 A45T and PAX4 R121W on repaglinide response in Chinese T2DM patients. WHAT THIS STUDY ADDS • This study aimed to investigate the association of genetic polymorphisms of NeuroD1/BETA2 A45T and PAX4 R121W with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients. • The NeuroD1/BETA2 A45T and PAX4 R121W polymorphisms were correlated with repaglinide therapeutic efficacy in Chinese T2DM patients. AIMS We aimed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus (T2DM) patients. METHODS Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism. Forty-three patients with various genotypes were randomly selected to undergo 8 weeks of repaglinide treatment (3 mg day−1). Fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin, fasting and postprandial serum insulin (FINS, PINS), homeostasis model assessment for insulin resistance, serum triglyceride, total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment. RESULTS The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [13.45 vs. 6.82%, P < 0.01, odds ratios = 2.342 (1.365, 4.019), P= 0.002]. Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45T polymorphism showed higher FINS (13.46 ± 12.57 vs. 10.04 ± 7.09 mU l−1, P < 0.05) (11.67, 14.83 vs. 8.38, 11.37) and PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l−1, P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than individuals with the T allele. The PAX4 R121W R allele carriers had higher PINS (52.11 ± 40.93 vs. 68.66 ± 43.87 mU l−1, P < 0.05) (44.89, 58.35 vs. 55.35, 88.87) than subjects with the W allele. After repaglinide treatment, patients with the T allele of NeuroD1/BETA2 A45T polymorphisms had attenuated efficacy on fasting plasma glucose (−2.79 ± 2.14 vs.−0.99 ± 1.80 mmol l−1, P < 0.01) (−3.53, −1.84 vs.−1.99, −0.13) and postprandial plasma glucose (−6.71 ± 5.90 vs.−2.54 ± 3.39 mmol l−1, P < 0.01) (−9.28, −4.62 vs.−4.34, −0.84). Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postprandial plasma glucose than R/W genotypes (−6.53 ± 6.52 vs.−2.95 ± 1.17 mmol l−1, P < 0.05) (−8.20, −4.89 vs.−3.92, −1.20). CONCLUSIONS The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy.
- Published
- 2012
23. ABCC2 Polymorphisms and Haplotype are Associated with Drug Resistance in Chinese Epileptic Patients
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Jian Qu, Ying Chun Zhao, Qiang Tang, Zhao-Qian Liu, Guang-Hua Lei, Bo Ting Zhou, Ji-Ye Yin, Xiao-Jing Xu, and Hong Hao Zhou
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Pharmacology ,business.industry ,Multidrug resistance-associated protein 2 ,Body movement ,ATP-binding cassette transporter ,Drug resistance ,Carbamazepine ,Drug Resistant Epilepsy ,medicine.disease ,Efficacy ,Psychiatry and Mental health ,Epilepsy ,Physiology (medical) ,medicine ,Pharmacology (medical) ,business ,medicine.drug - Abstract
Epilepsy is a chronic neurological illness, in which abnormal electrical activity in the brain causes involuntary changes in body movement, function, sensation, or behavior [1]. The World Health Organization estimates that epilepsy affects approximately 50 million people worldwide. Now‐a‐days, we recognize that genetic factors play an even more important role in the pathogenesis of epilepsy and drug efficacy than previously appreciated [1, 2]. Approximately, every second epileptic patient became resistant to the initial drugs [3]. Why so many epileptic patients show resistance against the antiepileptic drugs (AEDs) is not well‐understood. Some potential mechanisms have been suggested with regard to the targets and transporters of the drugs. The voltage‐gated ion channels are targets of some AEDs; alternations in the composition and functionality of them may lead to resistance in epileptic patients [4, 5]. The overexpression of ATP‐binding cassette (ABC) efflux transporters in the blood‐brain barrier (BBB), causing low‐drug concentration at their target, may be a potential mechanism [6]. Seizures, exposure to some AEDs such as carbamazepine, and genetic factors may influence the expression of transporters [7, 8, 9]. Some ABC transporters such as multidrug resistance 1 (MDR1, p‐glycoprotein, ABCB1), and a group of multidrug resistance proteins (MRPs, ABCCs), have been shown to mediate AEDs in brain [7, 9, 10]. These transporters are expressed in endothelial cells, astrocytes, and neurons of human brain tissues [11]. Therefore, these transporters may influence the efficacy of AEDs. Initial observation of the relationship between ABCB1 3435C>T and drug resistant epilepsy was followed by a number of studies to evaluate the single nucleotide polymorphism (SNP) as a predictor of AED resistance [12, 13]. However, some studies have conversely suggested no association between ABCB1 polymorphisms and the response to AEDs [14, 15]. Leschziner et al. studied a cohort of 503 epilepsy patients and found no evidence to support that ABCB1 common variation influences drug withdrawal outcomes [16]. ABCC2 is one of the ABC efflux transporters, whose role in human brain tissues is not fully understood due to its low expression in normal brain tissues [17]. But some studies found that the expression of ABCC2 was upregulated in the brain tissues of epileptic patients [18, 19]. Moreover, in the ABCC2‐deficient rat model, it is found that ABCC2 is involved in carbamazepine efficacy [20]. Recently, a study found a significant association between ABCC2 V417I polymorphism and reduced oral bioavailability of talinolol [21]. Kin et al. found that the ABCC2 1249G>A, and ABCB1 3435C>T, 1236C>T, 2677G>T/A polymorphisms were not associated with AED resistance in Japanese epileptic patients [22]. The study of Ufer et al. showed that a higher risk of AED failure in ABCC2−24T allele carriers is possible due to upregulation of ABCB1, but the mechanism is unknown [23]. Overall, whether the polymorphisms of these genes are associated with AED resistance is still not clear. To clarify whether ABCC2 and ABCB1 genes are involved in drug resistance epilepsy, we investigated the effects of ABCB1 rs1045642 and ABCC2 rs717620, rs3740066, and rs2273697 polymorphisms on AED resistance in Chinese epileptic patients.
- Published
- 2012
24. Comprehensive analysis of the association of SCN1A gene polymorphisms with the retention rate of carbamazepine following monotherapy for new-onset focal seizures in the Chinese Han population
- Author
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Guo-Liang Li, Hong-Hao Zhou, Ding Liu, Zhao-Qian Liu, Xiao-Jing Xu, Boting Zhou, Jian Qu, Ji-Ye Yin, and Qiuhong Zhou
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Physiology ,Haploview ,Single-nucleotide polymorphism ,Pharmacology ,Gastroenterology ,Medication Adherence ,Cohort Studies ,Young Adult ,Epilepsy ,Asian People ,Seizures ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Child ,Genetic Association Studies ,Polymorphism, Genetic ,Maintenance dose ,business.industry ,Confounding ,Odds ratio ,Carbamazepine ,Middle Aged ,medicine.disease ,NAV1.1 Voltage-Gated Sodium Channel ,Female ,business ,Body mass index ,medicine.drug - Abstract
Summary The aim of the present study was to investigate whether single nucleotide polymorphisms (SNPs) in the sodium channel a subunit type 1 (SCN1A) gene affect the retention rate of carbamazepine (CBZ) used to treat seizures in Chinese Han patients with epilepsy. In total, 448 patients were genotyped for SNPs selected in the SCN1A gene. The tag SNPs were selected using Haploview version 4.2 software (http://www.broad.mit.edu/haploview/haploview, accessed 18 Sept 2009). Monotherapy with CBZ was administered to patients with new-onset focal seizures. In the present study, the retention rate of CBZ was defined as the percentage of patients with epilepsy who had continued with CBZ treatment in the preceding 3 months. Potential confounding variables were analysed to evaluate the risk factors for non-retention. When adjusted for potential confounding factors (e.g. age, sex, body mass index, seizure type etc.), the presence of the A allele of SNP rs3812718 predicted non-retention (P = 0.015; odds ratio (OR) = 3.122; 95% confidence interval (CI) = 1.823–4.893). Beyond 12 months of treatment in those that continued with CBZ (retention cohort), analysis of covariance indicated that the maintenance dose (P = 0.025) and serum CBZ levels (P = 0.021) were significantly higher in carriers of the rs3812718 AA genotype than in those with the GG genotype. The results of the present study indicate that the rs3812718 SNP in the SCN1A gene is significantly associated with the retention rate of CBZ monotherapy in Chinese Han patients with focal epilepsy.
- Published
- 2012
25. ABCC1 polymorphism Arg723Gln (2168G > A) is associated with lung cancer susceptibility in a Chinese population
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Qiong Huang, Zhao-Qian Liu, Xiao-Jing Xu, Ji-Ye Yin, Lifang Han, and Hong-Hao Zhou
- Subjects
Pharmacology ,Chinese population ,medicine.medical_specialty ,biology ,Physiology ,Odds ratio ,medicine.disease ,Gastroenterology ,Lung cancer susceptibility ,Confidence interval ,Multiple drug resistance ,Physiology (medical) ,Internal medicine ,Immunology ,medicine ,ABCC1 ,biology.protein ,Allele ,Lung cancer - Abstract
Summary 1. In a previous in vitro study, we showed that the Arg723Gln (2168G > A) polymorphism significantly ABCC1-induced multidrug resistance. The aim of the present study was to further investigate the association of this polymorphism with lung cancer susceptibility and chemotherapy response in a Chinese population. 2. A total of 77 lung cancer patients (54 men, 23 women) and 71 cancer-free controls (49 men, 22 women) were enrolled in the study. Genomic DNA was extracted from peripheral blood and all samples were genotyped using polymerase chain reaction-restriction fragment length polymorphism. 3. Individuals carrying the 723Gln (A) allele have a 3.4-fold increased risk (adjusted odds ratio (OR) 3.42; 95% confidence interval (CI) 1.29–9.06; P = 0.013) of lung cancer compared with wild-type individuals. Further stratified analysis indicated that older individuals (> 50 years) carrying the 723Gln (A) allele have the highest susceptibility to lung cancer (adjusted OR 4.10; 95% CI 1.25–13.48; P = 0.020). However, no substantial association was found between the Arg723Gln (2168G > A) polymorphism and chemotherapy response in Chinese lung cancer patients. 4. In conclusion, the Arg723Gln (2168G > A) polymorphism of ABCC1 appears to be a potential susceptibility marker for lung cancer in the Chinese population, especially in older people.
- Published
- 2011
26. NAMPT -3186C/T polymorphism affects repaglinide response in Chinese patients with Type 2 diabetes mellitus
- Author
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Ying-Zi Liu, Min Dong, Hong Bin Lu, Hong-Hao Zhou, Feifeng Sheng, Guang-Hua Lei, Jian Qu, Jing Wu, Zhao-Qian Liu, Xiao-Jing Xu, Qi Pei, and Xing-Ping Dai
- Subjects
Pharmacology ,medicine.medical_specialty ,endocrine system diseases ,Triglyceride ,Physiology ,business.industry ,Nicotinamide phosphoribosyltransferase ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Type 2 diabetes ,medicine.disease ,Repaglinide ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,chemistry ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,Genotype ,medicine ,business ,medicine.drug - Abstract
1. In the present study, we investigated the associations of nicotinamide phosphoribosyltransferase (NAMPT)-3186 C/T and -948G/T polymorphisms with the risk of Type 2 diabetes mellitus (T2DM) and their impact on the efficacy of repaglinide in Chinese Han T2DM patients. 2. In all, 170 patients with T2DM and 129 healthy controls were genotyped for NAMPT-948G>T and -3186C>T polymorphisms. Thirty-five patients with different NAMPT -3186 C/T genotypes and the same organic anion-transporting polypeptide 1B1 (OATP1B1521) T/C genotype were randomly selected to undergo 8 weeks preprandial repaglinide treatment (1 mg, three times daily). Serum fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), glycated haemoglobin (HbAlc), fasting serum insulin (FINS), post-prandial serum insulin (PINS), triglyceride (TG), total cholesterol (CHO), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined before and after repaglinide treatment. 3. After repaglinide treatment for 8 consecutive weeks, there were significantly decreases in PFG, PPG, HbAlc, CHO and LDL-C, and increases in FINS, HDL-C and the HDL-C : LDL-C ratio, in T2DM patients. The elevated PINS value in patients with CT genotypes was significantly lower than that in patients with the CC and TT genotypes (P T polymorphism is significantly associated with plasma levels of PINS and CHO in Chinese T2DM patients with repaglinide monotherapy.
- Published
- 2011
27. Novel Susceptibility Loci were Found in Chinese Genetic Generalized Epileptic Patients by Genome-wide Association Study
- Author
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Yu Zhang, Ji-Ye Yin, Zhao-Qian Liu, Hongyu Long, Bo Xiao, Wei Zhang, Ying Zhang, Xiao-Yuan Mao, Zhicheng Gong, Zhi-Bin Wang, Hong-Hao Zhou, Jian Qu, Boting Zhou, and Chen-Xue Mao
- Subjects
Adult ,Male ,Adolescent ,Genotype ,MEDLINE ,Genome-wide association study ,Polymorphism, Single Nucleotide ,Young Adult ,Epilepsy ,Asian People ,Gene Frequency ,Polymorphism (computer science) ,Physiology (medical) ,medicine ,Humans ,Genetic Predisposition to Disease ,Pharmacology (medical) ,Child ,Letter to the Editor ,Allele frequency ,Pharmacology ,Genetics ,business.industry ,medicine.disease ,Psychiatry and Mental health ,Susceptibility locus ,Epilepsy, Generalized ,Female ,business ,Genome-Wide Association Study - Published
- 2014
28. Nitric oxide and zinc homeostasis in pulmonary endothelium
- Author
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Zhao-Qian Liu, Karla J. Wasserloos, Claudette M. St. Croix, Rong Cao, Bruce R. Pitt, Hui-Hua Li, and Paula J. Bernal
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Cell signaling ,Kinase ,Effector ,General Neuroscience ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Nitric oxide ,Cell biology ,chemistry.chemical_compound ,History and Philosophy of Science ,Biochemistry ,chemistry ,Hypoxic pulmonary vasoconstriction ,Metallothionein ,Signal transduction ,Intracellular - Abstract
We have shown that zinc-thiolate moieties of the metal binding protein metallothionein (MT) are critical targets for nitric oxide (NO) with resultant increases in intracellular labile zinc. Such an NO-MT-Zn signaling pathway appears to participate in important cardiovascular functions associated with biosynthesis of NO including hypoxic vasoconstriction in the lung. Although downstream effector signaling molecules and critical contractile targets remain unclear, current investigations reveal a contributory role for zinc dependent protein kinases and cytoskeletal proteins in mediating hypoxic induced constriction of pulmonary endothelial cells.
- Published
- 2010
29. Effect of 393T>C Polymorphism of GNAS1 Gene on Dobutamine Response in Chinese Healthy Subjects
- Author
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Li-Jun Yang, Dong Guo, Lan Fan, Yan-Mei Mao, Zhao-Qian Liu, Sai-Ying Wang, Hong-Hao Zhou, Bi-Lian Chen, and Chun-Ting Han
- Subjects
Adult ,Male ,China ,medicine.medical_specialty ,Adolescent ,Genotype ,Adrenergic ,Blood Pressure ,Polymerase Chain Reaction ,Ventricular Function, Left ,Young Adult ,Double-Blind Method ,Heart Rate ,In vivo ,Dobutamine ,Internal medicine ,Heart rate ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,medicine ,Humans ,Pharmacology (medical) ,Pharmacology ,Polymorphism, Genetic ,Ejection fraction ,Dose-Response Relationship, Drug ,business.industry ,Adrenergic beta-Agonists ,Dose–response relationship ,Endocrinology ,Blood pressure ,Cardiology ,Female ,Receptors, Adrenergic, beta-1 ,business ,Polymorphism, Restriction Fragment Length ,Echocardiography, Stress ,medicine.drug - Abstract
The purpose of this study was to characterize the functional consequences of the 393T>C polymorphism of the GNAS1 gene in vivo. PCR-RFLP assays were used to identify GNAS1 and beta 1-adrenoceptor genotypes. The heart rate (HR), blood pressure, left ventricular fractional shortening (LVFS), and left ventricular ejection fraction (LVEF) were determined in different genotypes through a modified dobutamine stress echocardiography protocol. Our results showed that individuals with homozygous or heterozygous C393 had an increased cardiovascular agonistic response to dobutamine, and the increases from baseline in LVFS at the 3 dosage levels of dobutamine were 19.3% +/- 1.0% versus 32.0% +/- 2.9%, 36.7% +/- 3.1% versus 41.3% +/- 4.1%, and 51.7% +/- 3.3% versus 58.7% +/- 2.6% in T393 homozygotes and C393 homozygotes or heterozygotes, respectively (P = .026). Significant differences were also found between these 2 groups with the increases from baseline in LVEF (P = .007) and SBP (P = .048). In addition, there were significant differences in the increases from atopine in LVFS (P = .011), LVEF (P = .004), and SBP (P = .046) between the T393 homozygotes and C393 homozygotes or heterozygotes. The change of LVEF in C393 homozygous was higher than that in T393 homozygous at the dose of 40 microg/kg/min (28.9% +/- 4.0% vs 36.4% +/- 2.1%; 95% CI, 18.8%-38.9%; P = .046). These data suggested that the 393T>C polymorphism of GNAS1 was functionally relevant in vivo.
- Published
- 2009
30. Effects ofUCP2 -866 G/AandADRB3 Trp64Argon rosiglitazone response in Chinese patients with Type 2 diabetes
- Author
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Hai-Ling Liu, Qiong Huang, Hong-Hao Zhou, Zhao-Qian Liu, Jing Wu, Ji-Ye Yin, Hong Sun, and Min Yang
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Adolescent ,Genotype ,medicine.drug_class ,Type 2 diabetes ,Ion Channels ,Mitochondrial Proteins ,Rosiglitazone ,Young Adult ,Insulin resistance ,Asian People ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Hypoglycemic Agents ,Clinical Trials ,Uncoupling Protein 2 ,Pharmacology (medical) ,Thiazolidinedione ,Allele frequency ,Aged ,Aged, 80 and over ,Pharmacology ,Polymorphism, Genetic ,Adiponectin ,business.industry ,Middle Aged ,medicine.disease ,Endocrinology ,Postprandial ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Receptors, Adrenergic, beta-3 ,Female ,Thiazolidinediones ,business ,medicine.drug - Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Rosiglitazone is one of the thiazolidinedione medicines that is widely used in patients with Type 2 diabetes (T2DM); it acts by activation of peroxisome proliferator-activated receptor-γ. • There are no reports on the influence of genetic variations of UCP2 and ADRB3 on rosiglitazone response in Chinese T2DM patients. • The current study was designed to evaluate the relationship between the genetic polymorphisms of UCP2 –866G/A and ADRB3 Trp64Arg with susceptibility to T2DM development and the therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with T2DM. WHAT THIS STUDY ADDS • The genetic polymorphisms of UCP2 –866G/A and ADRB3 Trp64Arg are associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese T2DM patients. AIMS The aim of this study was to explore the impact of UCP2 and ADRB3 genetic polymorphisms on the therapeutic efficacy of rosiglitazone in Chinese Type 2 diabetes (T2DM) patients. METHODS A total of 199 T2DM patients and 155 healthy volunteers were enrolled to identify UCP2 –866 G/A genotypes, and 273 T2DM patients and 166 controls were genotyped for Trp64Arg of ADRB3 by polymerase chain reaction-restriction fragment length polymorphism assay. Nine patients with GG genotype and 27 with GA+AA genotype of UCP2 –866 G/A, 11 with Trp64Trp genotype and 25 with Trp64Arg genotype of ADRB3 received oral rosiglitazone as a single-agent therapy (4 mg day−1) for 12 weeks. Serum fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin (HbA1c), fasting serum insulin, postprandial serum insulin (PINS), triglycerol (TG), cholesterol, homeostasis model assessment for insulin resistance, leptin and adiponectin in all T2DM patients were determined before and after rosiglitazone treatment. RESULTS There were no differences in allele frequency of either ADRB3 Trp64Arg or UCP2 –866 G/A between T2DM patients and control subjects. The A allele carriers of UCP2 in the T2DM patients had significantly lower PINS (61.5 ± 34.3 vs. 41.6 ± 28.7 mU l−1, P < 0.01) (37.57, 59.16 vs. 34.82, 49.39) and low-density lipoprotein (LDL)-cholesterol compared with GG genotypes (3.4 ± 1.1 vs. 2.7 ± 1.1 mmol l−1, P < 0.05) (2.64, 3.52 vs. 2.66, 3.15). After rosiglitazone treatment for 12 consecutive weeks, we found that A allele carriers of UCP2 in the T2DM patients had smaller attenuated PINS (−3.82 ± 13.2 vs.−42.1 ± 30.7 mU l−1, P < 0.01) (9.45, 51.31 vs. 0.48, 11.88) and greater attenuated HbA1c (−1.85 ± 1.62 vs.−0.61 ± 0.80, P < 0.05) (0.14, 1.37 vs. 1.10, 2.38) compared with GG genotypes, and ADRB3 Trp64Arg had greater attenuated serum TG (−3.88 ± 2.77 vs.−0.24 ± 1.16 mmol l−1, P < 0.05) (−0.19, 2.74 vs. 1.19, 1.45) and smaller attenuated LDL-cholesterol (1.08 ± 1.36 vs.−0.36 ± 0.99, P < 0.01) (−1.26, 0.78 vs.−1.26, 0.79) as well as reduced enhanced adiponectin (1.57 ± 1.10 vs. 3.15 ± 2.12 mmol l−1, P < 0.05) (1.68, 4.08 vs.−9.18, 11.40) compared with ADRB3 Trp64Trp. CONCLUSION UCP2 –866 G/A and ADRB3 Trp64Arg polymorphisms are associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese T2DM patients.
- Published
- 2009
31. OATP1B1 POLYMORPHISM IS A MAJOR DETERMINANT OF SERUM BILIRUBIN LEVEL BUT NOT ASSOCIATED WITH RIFAMPICIN-MEDIATED BILIRUBIN ELEVATION
- Author
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Zhao-Qian Liu, An Wang, Yijing He, Lin-Yong Xu, Lan Fan, Qing Li, Sheng Deng, Wei Zhang, Hong-Hao Zhou, Yuan-Fei Huang, and Zhou Gan
- Subjects
Adult ,Male ,medicine.medical_specialty ,Genotype ,Organic anion transporter 1 ,Physiology ,Bilirubin ,Serum bilirubin level ,Organic Anion Transporters ,chemistry.chemical_compound ,In vivo ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Pharmacology ,Polymorphism, Genetic ,biology ,Liver-Specific Organic Anion Transporter 1 ,Organic anion-transporting polypeptide ,Endocrinology ,Biochemistry ,chemistry ,biology.protein ,Rifampin ,SLCO1B1 ,Rifampicin ,medicine.drug - Abstract
1. Elevated serum bilirubin levels are caused mainly by liver diseases, haematolysis, genetic defects and drug intake. Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene). The present study was performed to determine the association between SLCO1B1 gene polymorphisms and serum bilirubin levels in vivo. Moreover, the effects of administration of low-dose rifampicin on serum bilirubin levels in different SLCO1B1 genotypes was examined. 2. Serum bilirubin levels were examined in 42 healthy volunteers who had been analysed for SLCO1B1 genotype (seven, 13, 14 and eight with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and *15/*15, respectively). Among them, 24 subjects (seven, seven, eight and two with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and *15/*15, respectively) were selected to participate in an open-label, two-phase clinical trial. Each was given 450 mg rifampicin orally once daily at 2000 hours for 5 consecutive days. Serum bilirubin concentrations at 0800 hours on the 1st and 6th days were compared between the different SLCO1B1 genotypes. 3. In the 42 volunteers, the mean (+/-SD) serum UCB in both SLCO1B1*1b/*15 and *15/*15 groups was significantly higher than that in the SLCO1B1*1b/*1b group (11.07 +/- 2.31, 13.01 +/- 3.87 and 8.21 +/- 2.68 micromol/L, respectively; P = 0.009 and P < 0.001). Total bilirum (T.BIL) in both the SLCO1B1*1b/*15 and *15/*15 groups was significantly higher than that in the SLCO1B1*1b/*1b group (16.69 +/- 4.09, 20.71 +/- 5.12 and 13.06 +/- 5.12 micromol/L, respectively; P = 0.029 and P < 0.001). The direct bilirubin (D.BIL) in the SLCO1B1*15/*15 group was significantly higher than that in the SLCO1B1*1b/*1b group (7.69 +/- 1.81 vs 4.85 +/- 1.81 micromol/L, respectively; P = 0.001). Rifampicin significantly increased UCB, T.BIL and D.BIL concentrations in 24 healthy volunteers (17.68 +/- 5.96 vs 13.95 +/- 4.44 micromol/L (P = 0.040), 5.72 +/- 2.01 vs 4.35 +/- 1.50 micromol/L (P = 0.028) and 12.00 +/- 4.26 vs 9.61 +/- 3.15 micromol/L (P = 0.035), respectively). However, the extent of the increase in serum bilirubin caused by 450 mg rifampicin for 5 days was not affected by SLCO1B1 genotype. 4. Genetic polymorphism in SLCO1B1 is a major determinant of interindividual variability in the serum bilirubin level. SLCO1B1*15 carriers had higher baseline serum UCB, T.BIL and D.BIL levels compared with subjects with the SLCO1B1*1a/*1a and SLCO1B1*1b/*1b genotypes. SLCO1B1*15/*15 homozygotes are more susceptible to hyperbilirubinaemia. Serum bilirubin levels could be increased by low-dose rifampicin administration, but the extent of the increase was not associated with SLCO1B1 genotype.
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- 2007
32. Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide
- Author
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Hong-Hao Zhou, Zhao-Qian Liu, Wei-Xia Zhang, Lan Fan, Bang-Ning Yu, Yijing He, Dong-Li Hu, Zhi-Rong Tan, Qing Li, Wei Zhang, Chun-Ting Han, and Dan Wang
- Subjects
Adult ,Male ,Phenylalanine ,Cmax ,Organic Anion Transporters ,Nateglinide ,Single-nucleotide polymorphism ,Pharmacology ,Polymorphism, Single Nucleotide ,Diabetes mellitus genetics ,Pharmacokinetics ,Cyclohexanes ,Diabetes Mellitus ,medicine ,Humans ,Hypoglycemic Agents ,Pharmacology (medical) ,biology ,Liver-Specific Organic Anion Transporter 1 ,Repaglinide ,Meglitinide ,Pharmacogenetics ,biology.protein ,SLCO1B1 ,medicine.drug - Abstract
Aims Nateglinide is a meglitinide analogue with antidiabetic action. A recent study showed that SLCO1B1 (which codes the OATP1B1 gene, also known as OATP-C, OATP2) is a major determinant which markedly affects the pharmacokinetics of repaglinide. Our objective was to assess the association between single nucleotide polymorphisms (SNPs) of SLCO1B1 and the pharmacokinetics of nateglinide. Methods Seventeen healthy volunteers with different SLCO1B1 genotypes (11 with 521TT, four with 521TC and two with 521CC) were enrolled in this study. Each was given a single oral dose of 90 mg nateglinide. Plasma concentrations of nateglinide were measured up to 8 h by HPLC. Results The Cmax and AUC(0,∞) of nateglinide were 83% (P = 0.002) and 82% (P = 0.001) higher in the SLCO1B1521TC subjects (n = 4), and 76% (P = 0.016) and 108% (P = 0.001) higher in the SLCO1B1521CC subjects (n = 2) than in the SLCO1B1521TT subjects (n = 11), respectively. The t1/2 of nateglinide in SLCO1B1521CC subjects was 78% longer than that in 521TT subjects (P = 0.036). The difference in tmax values among the three genotypic groups was not statistically significant. Conclusions Our results suggest that OATP1B1-mediated hepatic uptake of nateglinide may be the prior step for its metabolism and elimination. SLCO1B1521T > C SNP might play an important role in the pharmacokinetics of nateglinide.
- Published
- 2006
33. Effect of the CYP2C19 oxidation polymorphism on fluoxetine metabolism in Chinese healthy subjects
- Author
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Xiao-Ping Chen, Zhao-Qian Liu, Song-Lin Huang, Hong-Hao Zhou, Zeneng Cheng, Chang-Hong Jiang, and Dong-Sheng Ouyang
- Subjects
Pharmacology ,medicine.medical_specialty ,Fluoxetine ,Cmax ,CYP2C19 ,Biology ,Endocrinology ,Pharmacokinetics ,Oral administration ,Polymorphism (computer science) ,Internal medicine ,medicine ,Pharmacology (medical) ,Reuptake inhibitor ,Pharmacogenetics ,medicine.drug - Abstract
Aims The study was designed to investigate whether genetically determined CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects. Methods A single oral dose of fluoxetine (40 mg) was administrated successively to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5–7 half-lives and fluoxetine, and norfluoxetine were determined by reversed-phase high performance liquid chromatography. Results Poor metabolizers (PMs) showed a mean 46% increase in fluoxetine peak plasma concentrations (Cmax, P
- Published
- 2001
34. Evidence for involvement of polymorphic CYP2C19 and 2C9 in theN-demethylation of sertraline in human liver microsomes
- Author
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Yan Shu, Nan He, Xue-Jun Zhao, Bing Zhu, Song-Lin Huang, Hong-Hao Zhou, Wei Wang, Zhao-Qian Liu, and Zhen-Hua Xu
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Pharmacology ,chemistry.chemical_classification ,Cytochrome P450 ,Metabolism ,Biology ,Isozyme ,Enzyme ,Biochemistry ,chemistry ,biology.protein ,Microsome ,Pharmacology (medical) ,Cytochrome P-450 CYP2C8 ,Drug metabolism ,Demethylation - Abstract
Aims The present study was designed to define the kinetic behaviour of sertraline N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P450 involved in this metabolic pathway. Methods The kinetics of the formation of N-demethylsertraline were determined in human liver microsomes from six genotyped CYP2C19 extensive (EM) and three poor metabolisers (PM). Selective inhibitors of and specific monoclonal antibodies to various cytochrome P450 isoforms were also employed. Results The kinetics of N-demethylsertraline formation in all EM liver microsomes were fitted by a two-enzyme Michaelis-Menten equation, whereas the kinetics in all PM liver microsomes were best described by a single-enzyme Michaelis-Menten equation similar to the low-affinity component found in EM microsomes. Mean apparent Km values for the high-and low-affinity components were 1.9 and 88 μm and V max values were 33 and 554 pmol min−1 mg−1 protein, respectively, in the EM liver microsomes. Omeprazole (a CYP2C19 substrate) at high concentrations and sulphaphenazole (a selective inhibitor of CYP2C9) substantially inhibited N-demethylsertraline formation. Of five monoclonal antibodies to various cytochrome P450 forms tested, only anti-CYP2C8/9/19 had any inhibitory effect on this reaction. The inhibition of sertraline N-demethylation by anti-CYP2C8/9/19 was greater in EM livers than in PM livers at both low and high substrate concentrations. However, anti-CYP2C8/9/19 did not abolish the formation of N-demethylsertraline in the microsomes from any of the livers. Conclusions The polymorphic enzyme CYP2C19 catalyses the high-affinity N-demethylation of sertraline, while CYP2C9 is one of the low-affinity components of this metabolic pathway.
- Published
- 1999
35. Association of eIF3 p170 expression with chemotherapy response of lung cancer and its effects on cisplatin sensitivity in lung carcinoma cells
- Author
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Jing Ting Zhang, Hai Tang Xie, Zhao-Qian Liu, Jie Shen, Hong Hao Zhou, and Ji-Ye Yin
- Subjects
Lung ,business.industry ,Cancer ,Cisplatin sensitivity ,Cell Biology ,General Medicine ,medicine.disease ,medicine.anatomical_structure ,Carcinoma ,medicine ,Cancer research ,Lung cancer ,business ,Chemotherapy response - Published
- 2008
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