目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显...目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子14和23,再对PCR产物进行DNA测序分析。结果所有ICP患者及对照组外周血DNA经PCR均扩增出目的片段,外显子14和23均未发现有突变。结论云南临沧佤族、傣族ICP的发生可能与MDR3基因外显子14和23突变无关。展开更多
目的:探索妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子6和9突变与ICP发病的关系。方法:从云南省临沧地区各少数民族自治县29例ICP患者及32例正常孕妇及患者家属组的外周血中提取DNA,聚合酶链反...目的:探索妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子6和9突变与ICP发病的关系。方法:从云南省临沧地区各少数民族自治县29例ICP患者及32例正常孕妇及患者家属组的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子6和9,PCR产物进行DNA测序分析。结果:所有ICP患者及对照组PCR均扩增出目的片段,且外显子6存在多态性位点C158T,外显子9存在突变位点G581A,但两组的基因频率无明显差异。结论:云南省临沧少数民族地区ICP的发生可能与MDR3外显子6和9的突变无关。展开更多
Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretio...Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.展开更多
Aim:This study investigated the ATP binding cassette(ABC)transporter(ABCA1,ABCB1,ABCB3,ABCC2 and ABCG2)expression in high grade serous ovarian cancer(HGSOC)tissues,cell lines and primary cells to determine their poten...Aim:This study investigated the ATP binding cassette(ABC)transporter(ABCA1,ABCB1,ABCB3,ABCC2 and ABCG2)expression in high grade serous ovarian cancer(HGSOC)tissues,cell lines and primary cells to determine their potential relationship with acquired chemotherapy resistance and patient outcome.Methods:ABC transporter mRNA and protein expression(ABCA1,ABCB1,ABCB3,ABCC2 and ABCG2)was assessed in publicly available datasets and in a tissue microarray(TMA)cohort of HGSOC at diagnosis,respectively.ABC transporter mRNA expression was also assessed in chemosensitive ovarian cancer cell lines(OVCAR-5 and CaOV3)versus matching cell lines with acquired carboplatin resistance and in primary HGSOC cells from patients with chemosensitive disease at diagnosis(n=10)as well as patients with acquired chemotherapy resistance at relapse(n=6).The effects of the ABCA1 inhibitor apabetalone in carboplatin-sensitive and-resistant cell lines were also investigated.Results:High ABCA1 mRNA and protein expression was found to be significantly associated with poor patient outcome.ABCA1 mRNA and protein levels were significantly increased in ovarian cancer cell lines(OVCAR-5 CBPR and CaOV3 CBPR)with acquired carboplatin resistance.ABCA1 mRNA was significantly increased in primary HGSOC cells obtained from patients with acquired chemotherapy resistance.Apabetalone treatment reduced ABCA1 protein expression and increased the sensitivity of both parental and carboplatin-resistant ovarian cancer cells to carboplatin.Conclusion: These results suggest that inhibiting ABCA1 transporter may be useful in overcoming acquired chemotherapy resistance and improving outcome for patients with HGSOC.展开更多
文摘目的探讨妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子14和23突变与ICP的关系。方法从云南临沧地区29例佤族、傣族ICP患者及32例正常孕妇的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子14和23,再对PCR产物进行DNA测序分析。结果所有ICP患者及对照组外周血DNA经PCR均扩增出目的片段,外显子14和23均未发现有突变。结论云南临沧佤族、傣族ICP的发生可能与MDR3基因外显子14和23突变无关。
文摘目的:探索妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregancy,ICP)患者MDR3基因外显子6和9突变与ICP发病的关系。方法:从云南省临沧地区各少数民族自治县29例ICP患者及32例正常孕妇及患者家属组的外周血中提取DNA,聚合酶链反应(PCR)扩增MDR3基因外显子6和9,PCR产物进行DNA测序分析。结果:所有ICP患者及对照组PCR均扩增出目的片段,且外显子6存在多态性位点C158T,外显子9存在突变位点G581A,但两组的基因频率无明显差异。结论:云南省临沧少数民族地区ICP的发生可能与MDR3外显子6和9的突变无关。
基金Supported by NIH,No.UG3TR003289 to Soto-Gutierrez A.
文摘Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.
文摘Aim:This study investigated the ATP binding cassette(ABC)transporter(ABCA1,ABCB1,ABCB3,ABCC2 and ABCG2)expression in high grade serous ovarian cancer(HGSOC)tissues,cell lines and primary cells to determine their potential relationship with acquired chemotherapy resistance and patient outcome.Methods:ABC transporter mRNA and protein expression(ABCA1,ABCB1,ABCB3,ABCC2 and ABCG2)was assessed in publicly available datasets and in a tissue microarray(TMA)cohort of HGSOC at diagnosis,respectively.ABC transporter mRNA expression was also assessed in chemosensitive ovarian cancer cell lines(OVCAR-5 and CaOV3)versus matching cell lines with acquired carboplatin resistance and in primary HGSOC cells from patients with chemosensitive disease at diagnosis(n=10)as well as patients with acquired chemotherapy resistance at relapse(n=6).The effects of the ABCA1 inhibitor apabetalone in carboplatin-sensitive and-resistant cell lines were also investigated.Results:High ABCA1 mRNA and protein expression was found to be significantly associated with poor patient outcome.ABCA1 mRNA and protein levels were significantly increased in ovarian cancer cell lines(OVCAR-5 CBPR and CaOV3 CBPR)with acquired carboplatin resistance.ABCA1 mRNA was significantly increased in primary HGSOC cells obtained from patients with acquired chemotherapy resistance.Apabetalone treatment reduced ABCA1 protein expression and increased the sensitivity of both parental and carboplatin-resistant ovarian cancer cells to carboplatin.Conclusion: These results suggest that inhibiting ABCA1 transporter may be useful in overcoming acquired chemotherapy resistance and improving outcome for patients with HGSOC.
