The WNT/-catenin and phosphoinositide 3-kinase(PI3K/AKT) signaling cascades both have been implicated in the formation and progression of colorectal cancer.Oncogenic PI3K/AKT signaling suppresses the activity of forkh...The WNT/-catenin and phosphoinositide 3-kinase(PI3K/AKT) signaling cascades both have been implicated in the formation and progression of colorectal cancer.Oncogenic PI3K/AKT signaling suppresses the activity of forkhead box O3a(FOXO3a) transcription factor through phosphorylation leading to its nuclear exclusion.Inhibition of the PI3K/AKT signaling by PI3K or AKT inhibitors results in the translocation of FOXO3a to the nucleus,and is considered to be a promising therapeutic strategy for many cancers including colon cancer.Now,however,a new study in Nature Medicine has revealed a nuclear interaction of-catenin with FOXO3a as a promoter of metastatic progression in colon cancer.The work has important implications for the treatment of colon cancers,suggests a companion biomarker strategy to enable a personalized medicine approach,and offers an alternative therapeutic strategy to overcome resistance to PI3K and AKT inhibitors.展开更多
目的探究前列腺癌中叉形头转录因子的O亚型-3(FOXO3a)、胰岛素样生长因子-Ⅱm RNA结合蛋白3(IMP3)的表达及临床意义。方法收集62例前列腺癌标本、53例良性前列腺增生患者标本,使用HE染色观察两组前列腺腺体形态变化,RT-PCR法测定前列腺...目的探究前列腺癌中叉形头转录因子的O亚型-3(FOXO3a)、胰岛素样生长因子-Ⅱm RNA结合蛋白3(IMP3)的表达及临床意义。方法收集62例前列腺癌标本、53例良性前列腺增生患者标本,使用HE染色观察两组前列腺腺体形态变化,RT-PCR法测定前列腺组织中FOXO3a、IMP3 m RNA的表达,免疫组化法检测前列腺组织中FOXO3a、IMP3蛋白表达,分析FOXO3a、IMP3蛋白表达与临床病理参数的关系,采用Kaplan-Meier对5年生存情况进行分析,Log-Rank法检测组间生存差异。结果 HE染色显示前列腺癌组织腺体结构混乱,大小形态不规则,腺体消失。前列腺癌中FOXO3a m RNA表达量低于前列腺增生组织,IMP3 m RNA表达量高于前列腺增生组织,差异有统计学意义(P<0.05)。前列腺癌中FOXO3a蛋白阳性表达率低于前列腺增生组织,IMP3蛋白阳性表达率高于前列腺增生组织,差异有统计学意义(P<0.05)。FOXO3a表达与病理分期、浸润程度、淋巴结转移存在一定关系(P<0.05),IMP3表达与病理分期、病理分级存在一定关系(P<0.05)。FOXO3a阳性表达者、IMP3阴性表达者5年内生存率高于FOXO3a阴性、IMP3阳性表达,生存曲线对比,差异均有统计学意义(χ~2=9.190,P=0.002;χ~2=7.269,P=0.007)。结论 FOXO3a在前列腺癌中低表达,IMP3高表达,提示在前列腺的发展中发挥重要作用,可作为治疗效果、病情程度以及预后的参考指标。展开更多
文摘The WNT/-catenin and phosphoinositide 3-kinase(PI3K/AKT) signaling cascades both have been implicated in the formation and progression of colorectal cancer.Oncogenic PI3K/AKT signaling suppresses the activity of forkhead box O3a(FOXO3a) transcription factor through phosphorylation leading to its nuclear exclusion.Inhibition of the PI3K/AKT signaling by PI3K or AKT inhibitors results in the translocation of FOXO3a to the nucleus,and is considered to be a promising therapeutic strategy for many cancers including colon cancer.Now,however,a new study in Nature Medicine has revealed a nuclear interaction of-catenin with FOXO3a as a promoter of metastatic progression in colon cancer.The work has important implications for the treatment of colon cancers,suggests a companion biomarker strategy to enable a personalized medicine approach,and offers an alternative therapeutic strategy to overcome resistance to PI3K and AKT inhibitors.
文摘目的探究前列腺癌中叉形头转录因子的O亚型-3(FOXO3a)、胰岛素样生长因子-Ⅱm RNA结合蛋白3(IMP3)的表达及临床意义。方法收集62例前列腺癌标本、53例良性前列腺增生患者标本,使用HE染色观察两组前列腺腺体形态变化,RT-PCR法测定前列腺组织中FOXO3a、IMP3 m RNA的表达,免疫组化法检测前列腺组织中FOXO3a、IMP3蛋白表达,分析FOXO3a、IMP3蛋白表达与临床病理参数的关系,采用Kaplan-Meier对5年生存情况进行分析,Log-Rank法检测组间生存差异。结果 HE染色显示前列腺癌组织腺体结构混乱,大小形态不规则,腺体消失。前列腺癌中FOXO3a m RNA表达量低于前列腺增生组织,IMP3 m RNA表达量高于前列腺增生组织,差异有统计学意义(P<0.05)。前列腺癌中FOXO3a蛋白阳性表达率低于前列腺增生组织,IMP3蛋白阳性表达率高于前列腺增生组织,差异有统计学意义(P<0.05)。FOXO3a表达与病理分期、浸润程度、淋巴结转移存在一定关系(P<0.05),IMP3表达与病理分期、病理分级存在一定关系(P<0.05)。FOXO3a阳性表达者、IMP3阴性表达者5年内生存率高于FOXO3a阴性、IMP3阳性表达,生存曲线对比,差异均有统计学意义(χ~2=9.190,P=0.002;χ~2=7.269,P=0.007)。结论 FOXO3a在前列腺癌中低表达,IMP3高表达,提示在前列腺的发展中发挥重要作用,可作为治疗效果、病情程度以及预后的参考指标。
