AIM:To determine whether expression of certain enzymes related to 5-fluorouracil(5-FU)metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma(CCA).METHODS:The histoculture drug response assay(HDRA)was performe...AIM:To determine whether expression of certain enzymes related to 5-fluorouracil(5-FU)metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma(CCA).METHODS:The histoculture drug response assay(HDRA)was performed using surgically resected CCA tissues.Tumor cell viability was determined morphologically with hematoxylin and eosin-and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues.The mRNA expression of thymidine phosphorylase(TP),orotate phosphoribosyl transferase(OPRT),thymidylate synthase(TS),and dihydropyrimidine dehydrogenase(DPD)was determined with realtime reverse transcriptase-polymerase chain reaction.The levels of gene expression and the sensitivity to 5-FU were evaluated.RESULTS:Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital,Khon Kaen University from 2007 to 2009.HDRA was used to determine the response of these CCA tissues to 5-FU.Based on the dose-response curve,200μg/mL 5-FU was selected as the test concentration.The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU.When the relationship between TP,OPRT,TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined,only OPRT mRNA expression was significantly correlated with the response to 5-FU.The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group(0.41±0.25 vs 0.22±0.12,P<0.05).CONCLUSION:OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA.Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.展开更多
目的探讨内脂素-烟酰胺磷酸核糖转移酶(Nampt)轴在卵巢上皮癌进展中的作用及对患者预后的影响。方法采用免疫组化方法检测Nampt在卵巢上皮癌及正常卵巢组织内的表达,ELISA方法测定血清内脂素浓度,并分析其与临床病理特征及患者总体生存...目的探讨内脂素-烟酰胺磷酸核糖转移酶(Nampt)轴在卵巢上皮癌进展中的作用及对患者预后的影响。方法采用免疫组化方法检测Nampt在卵巢上皮癌及正常卵巢组织内的表达,ELISA方法测定血清内脂素浓度,并分析其与临床病理特征及患者总体生存期的关系。结果卵巢上皮癌患者血清内脂素浓度显著高于卵巢良性肿瘤患者及正常对照人群,内脂素诊断卵巢上皮癌的曲线下面积(area under curve,AUC)为0.744,界值5.95 ng/mL。卵巢上皮癌患者血清内脂素与T、N、FIGO分期相关(P<0.05)且与CA125呈正相关性(rs=0.389,P=0.001)。Nampt在卵巢上皮癌组织中阳性表达率显著升高,且与FIGO分期、血清内脂素水平相关(P<0.05)。卵巢上皮肿瘤细胞Nampt蛋白表达与患者血清内脂素水平呈正相关性(rs=0.55,P<0.001)。卵巢上皮癌患者1年、3年、5年生存率分别为98.6%、74.3%、34.3%。生存分析显示,卵巢上皮癌患者生存期与T、N、FIGO分期及血清内脂素、肿瘤细胞Nampt表达有关,且FIGO分期、肿瘤细胞Nampt表达是影响患者预后的独立因素(P<0.05)。结论卵巢上皮癌患者血清内脂素、癌组织中Nampt高表达以及T、N、FIGO分期与患者总体生存期有关,且Nampt高表达、FIGO分期是独立影响因素。这提示内脂素-Nampt轴促进卵巢上皮癌进展并影响患者预后。展开更多
基金Supported by The Research Team Strengthening Grant,National Genetic Engineering and Biotechnology Center,National Science and Technology Development Agency,ThailandThe Liver Fluke and Cholangiocarcinoma Research Center,Faculty of Medicine,Khon Kaen University,Thailand(to Chaiyagool J)
文摘AIM:To determine whether expression of certain enzymes related to 5-fluorouracil(5-FU)metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma(CCA).METHODS:The histoculture drug response assay(HDRA)was performed using surgically resected CCA tissues.Tumor cell viability was determined morphologically with hematoxylin and eosin-and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues.The mRNA expression of thymidine phosphorylase(TP),orotate phosphoribosyl transferase(OPRT),thymidylate synthase(TS),and dihydropyrimidine dehydrogenase(DPD)was determined with realtime reverse transcriptase-polymerase chain reaction.The levels of gene expression and the sensitivity to 5-FU were evaluated.RESULTS:Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital,Khon Kaen University from 2007 to 2009.HDRA was used to determine the response of these CCA tissues to 5-FU.Based on the dose-response curve,200μg/mL 5-FU was selected as the test concentration.The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU.When the relationship between TP,OPRT,TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined,only OPRT mRNA expression was significantly correlated with the response to 5-FU.The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group(0.41±0.25 vs 0.22±0.12,P<0.05).CONCLUSION:OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA.Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.
文摘目的探讨内脂素-烟酰胺磷酸核糖转移酶(Nampt)轴在卵巢上皮癌进展中的作用及对患者预后的影响。方法采用免疫组化方法检测Nampt在卵巢上皮癌及正常卵巢组织内的表达,ELISA方法测定血清内脂素浓度,并分析其与临床病理特征及患者总体生存期的关系。结果卵巢上皮癌患者血清内脂素浓度显著高于卵巢良性肿瘤患者及正常对照人群,内脂素诊断卵巢上皮癌的曲线下面积(area under curve,AUC)为0.744,界值5.95 ng/mL。卵巢上皮癌患者血清内脂素与T、N、FIGO分期相关(P<0.05)且与CA125呈正相关性(rs=0.389,P=0.001)。Nampt在卵巢上皮癌组织中阳性表达率显著升高,且与FIGO分期、血清内脂素水平相关(P<0.05)。卵巢上皮肿瘤细胞Nampt蛋白表达与患者血清内脂素水平呈正相关性(rs=0.55,P<0.001)。卵巢上皮癌患者1年、3年、5年生存率分别为98.6%、74.3%、34.3%。生存分析显示,卵巢上皮癌患者生存期与T、N、FIGO分期及血清内脂素、肿瘤细胞Nampt表达有关,且FIGO分期、肿瘤细胞Nampt表达是影响患者预后的独立因素(P<0.05)。结论卵巢上皮癌患者血清内脂素、癌组织中Nampt高表达以及T、N、FIGO分期与患者总体生存期有关,且Nampt高表达、FIGO分期是独立影响因素。这提示内脂素-Nampt轴促进卵巢上皮癌进展并影响患者预后。
