目的探讨基底型乳腺癌中拓扑异构酶Ⅱα(topoisomeraseⅡalpha,TOP2A)基因的扩增或缺失状态。方法采用荧光原位杂交(fluorescence in situ hybridization,FISH)法对53例基底型乳腺癌和对照组33例管腔A型乳腺癌石蜡包埋标本进行TOP2A基...目的探讨基底型乳腺癌中拓扑异构酶Ⅱα(topoisomeraseⅡalpha,TOP2A)基因的扩增或缺失状态。方法采用荧光原位杂交(fluorescence in situ hybridization,FISH)法对53例基底型乳腺癌和对照组33例管腔A型乳腺癌石蜡包埋标本进行TOP2A基因检测。结果 53例基底型乳腺癌中,TOP2A基因异常者21例,其中扩增14例(4例为簇状扩增、10例为点状扩增)、缺失7例;TOP2A基因正常者32例。管腔A型乳腺癌TOP2A基因1例扩增、6例缺失。基底型乳腺癌中TOP2A基因异常的发生率高于管腔A型乳腺癌(P<0.05)。结论基底型乳腺癌中存在较高比例的TOP2A基因异常,可作为蒽环类化疗药物的治疗靶点。展开更多
目的研究原发性肝癌拓扑异构酶Ⅱα(Topoisom eraseⅡ,αToPoⅡα)的表达及临床意义,并探讨其与p53基因突变之间的关系。方法免疫组织化学法和W estern B lotting方法检测57例未经化疗过的原发性肝癌肿瘤组织和32例肝硬化组织ToPoⅡα...目的研究原发性肝癌拓扑异构酶Ⅱα(Topoisom eraseⅡ,αToPoⅡα)的表达及临床意义,并探讨其与p53基因突变之间的关系。方法免疫组织化学法和W estern B lotting方法检测57例未经化疗过的原发性肝癌肿瘤组织和32例肝硬化组织ToPoⅡα蛋白的表达,并用聚合酶链反应-单链构象多态性(PCR-SSCP)分析p53基因7、8外显子的突变。结果To-PoⅡα蛋白在肝癌组织中阳性率为87.7%(50/57),在肝硬化组织中阳性率为50%(16/32),两者有显著差异(P<0.05)。蛋白印迹结果显示肝癌组织中ToPoⅡα蛋白表达显著高于肝硬化组织(P<0.05),高分化肿瘤与中、低分化的肿瘤组织之间有显著差异(P<0.05),有转移的病人高于无转移者(P<0.05).等级相关分析显示ToPoⅡα蛋白的表达与p53基因突变呈正相关(r=0.914,P=0.001)。p53基因突变组ToPoⅡ蛋白的表达显著高于野生型组(P<0.01)。结论ToPoⅡα的检测可作为肝癌分化程度的特异指标,同时p53基因突变可能诱导ToPoⅡα蛋白的表达。展开更多
There is an urgent need for new agents with activity inplatinum -and taxane -resistant epi thelial ovarian can-cer.Exatecan mesylate is a novel top oisomerase I inhibitor with potent activity against ovaria n cancer i...There is an urgent need for new agents with activity inplatinum -and taxane -resistant epi thelial ovarian can-cer.Exatecan mesylate is a novel top oisomerase I inhibitor with potent activity against ovaria n cancer in vitro.A multicentre phase IIA study was cond ucted in patients with platinum -and taxaneresistant epit helial ovarian cancer.Fifty -seven patients with bidimensionally measurable o-varian cancer,previously exposed t o platinum and taxanes,whose disease had relapsed within 6months of platinum -containing chemotherapy were randomised to one of two intravenous schedules of exatecan m esylate;0.3mg /m 2 daily for 5days every 3weeks(Arm A )or 2.1mg /m 2 weekly for 3weeks out of 4(Arm B ).There were no re-sponses in the weekly arm and a radiological response rate of 5.3%(95%CI 0.3-21.8%)in the daily arm.Principal toxicities were myelosup pression and emesis.Grade 3/4neutropenia occurred in 29%of patients inArm A and 6%patients in Arm B.Seventyone percent of pa-tients in Arm A required red cell tran sfusions while on treatment.Exatecan is well tolerated in this poor prognosis group of patients but only has modest single agent activity when administered in a daily regimen.展开更多
文摘目的探讨基底型乳腺癌中拓扑异构酶Ⅱα(topoisomeraseⅡalpha,TOP2A)基因的扩增或缺失状态。方法采用荧光原位杂交(fluorescence in situ hybridization,FISH)法对53例基底型乳腺癌和对照组33例管腔A型乳腺癌石蜡包埋标本进行TOP2A基因检测。结果 53例基底型乳腺癌中,TOP2A基因异常者21例,其中扩增14例(4例为簇状扩增、10例为点状扩增)、缺失7例;TOP2A基因正常者32例。管腔A型乳腺癌TOP2A基因1例扩增、6例缺失。基底型乳腺癌中TOP2A基因异常的发生率高于管腔A型乳腺癌(P<0.05)。结论基底型乳腺癌中存在较高比例的TOP2A基因异常,可作为蒽环类化疗药物的治疗靶点。
文摘目的研究原发性肝癌拓扑异构酶Ⅱα(Topoisom eraseⅡ,αToPoⅡα)的表达及临床意义,并探讨其与p53基因突变之间的关系。方法免疫组织化学法和W estern B lotting方法检测57例未经化疗过的原发性肝癌肿瘤组织和32例肝硬化组织ToPoⅡα蛋白的表达,并用聚合酶链反应-单链构象多态性(PCR-SSCP)分析p53基因7、8外显子的突变。结果To-PoⅡα蛋白在肝癌组织中阳性率为87.7%(50/57),在肝硬化组织中阳性率为50%(16/32),两者有显著差异(P<0.05)。蛋白印迹结果显示肝癌组织中ToPoⅡα蛋白表达显著高于肝硬化组织(P<0.05),高分化肿瘤与中、低分化的肿瘤组织之间有显著差异(P<0.05),有转移的病人高于无转移者(P<0.05).等级相关分析显示ToPoⅡα蛋白的表达与p53基因突变呈正相关(r=0.914,P=0.001)。p53基因突变组ToPoⅡ蛋白的表达显著高于野生型组(P<0.01)。结论ToPoⅡα的检测可作为肝癌分化程度的特异指标,同时p53基因突变可能诱导ToPoⅡα蛋白的表达。
文摘There is an urgent need for new agents with activity inplatinum -and taxane -resistant epi thelial ovarian can-cer.Exatecan mesylate is a novel top oisomerase I inhibitor with potent activity against ovaria n cancer in vitro.A multicentre phase IIA study was cond ucted in patients with platinum -and taxaneresistant epit helial ovarian cancer.Fifty -seven patients with bidimensionally measurable o-varian cancer,previously exposed t o platinum and taxanes,whose disease had relapsed within 6months of platinum -containing chemotherapy were randomised to one of two intravenous schedules of exatecan m esylate;0.3mg /m 2 daily for 5days every 3weeks(Arm A )or 2.1mg /m 2 weekly for 3weeks out of 4(Arm B ).There were no re-sponses in the weekly arm and a radiological response rate of 5.3%(95%CI 0.3-21.8%)in the daily arm.Principal toxicities were myelosup pression and emesis.Grade 3/4neutropenia occurred in 29%of patients inArm A and 6%patients in Arm B.Seventyone percent of pa-tients in Arm A required red cell tran sfusions while on treatment.Exatecan is well tolerated in this poor prognosis group of patients but only has modest single agent activity when administered in a daily regimen.
