Colorectal cancer （CRC） is caused by a series of genetic or epigenetic changes, and in the last decade there has been an increased awareness that there are multiple forms of colorectal cancer that develop through di...Colorectal cancer （CRC） is caused by a series of genetic or epigenetic changes, and in the last decade there has been an increased awareness that there are multiple forms of colorectal cancer that develop through different pathways. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and most of hereditary nonpolyposis cancers. Tumors with a high frequency of microsatellite instability tend to be diploid, to possess a mucinous histology, and to have a surrounding lymphoid reaction. They are more prevalent in the proximal colon and have a fast pass from polyp to cancer. Nevertheless, they are associated with longer survival than stage-matched tumors with microsateUite stability. Resistance of colorectal cancers with a high frequency of microsatellite instability to 5-fluorouracilbased chemotherapy is well established. Silencing the MLH1 gene expression by its promoter methylation stops the formation of MLH1 protein, and prevents the normal activation of the DNA repair gene. This is an important cause for genomic instability and cell proliferation to the point of colorectal cancer formation. Better knowledge of this process will have a huge impact on colorectal cancer management, prevention, treatment and prognosis.展开更多
OBJECTIVE To detect the differences in gene expression of nonhomologous end-joining pathway including Ku70, Ku80, ERCC4, lig4 and DNA-PKcs between human primary gliomas and normal brain tissues, and furthermore, to ex...OBJECTIVE To detect the differences in gene expression of nonhomologous end-joining pathway including Ku70, Ku80, ERCC4, lig4 and DNA-PKcs between human primary gliomas and normal brain tissues, and furthermore, to explore the underlying mechanism for the expression alteration.METHODS The expression levels of Ku70, Ku80, ERCC4, lig4 and DNA-PKcs in 36 specimens of glioma and 12 specimens of normal brain tissue were measured using SYBR green-based real- time quantitative PCR. Methylation of DNA-PKcs was detected through methylation-specific PCR （MSP）.RESULTS There was no significant difference in expression of Ku70, Ku80, ERCC4 and lig4 between human primary gliomas and normal brain tissues （P 〈 0.05）, while DNA-PKcs were significantly up-regulated （P = 0.002）. The expression of DNA- PKcs was significantly higher in patients with grade III and IV diseases compared to patients with grade II disease or in normal brain tissues （P 〈 0.05）. Moreover, glioma tissue showed weaker methvlation than normal brain tissue.CONCLUSION The up-regulation of the DNA-PKcs may be associated with pathogenesis of glioma. Demethylation of DNA- PKcs promoter is an important reason for its up-regulation.展开更多
死亡相关蛋白激酶（death—associated protein kinase．DAPK）是一种钙离子和钙调素依赖的丝氨酸和苏氨酸蛋白激酶，它参与IFN-γ、TNF-α、Fas等诱导的细胞凋亡过程，具有促进凋亡的功能。近年来，DAPK与肿瘤发生、发展的关系引起人...死亡相关蛋白激酶（death—associated protein kinase．DAPK）是一种钙离子和钙调素依赖的丝氨酸和苏氨酸蛋白激酶，它参与IFN-γ、TNF-α、Fas等诱导的细胞凋亡过程，具有促进凋亡的功能。近年来，DAPK与肿瘤发生、发展的关系引起人们的广泛关注，尤其是其基因启动子区的甲基化与表达的缺失。在恶性血液病中，所有的伯基特淋巴瘤、84％的B细胞淋巴瘤、70％的多发性骨髓瘤、10％～30％的急性髓系白血病均有DAPK过甲基化。我们观察了骨髓增生异常综合征（MDS）患者骨髓单个核细胞（MNC）中DAPK基因启动子区过甲基化及其mRNA表达情况，并分析了其与临床特征的关系。展开更多
文摘Colorectal cancer （CRC） is caused by a series of genetic or epigenetic changes, and in the last decade there has been an increased awareness that there are multiple forms of colorectal cancer that develop through different pathways. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and most of hereditary nonpolyposis cancers. Tumors with a high frequency of microsatellite instability tend to be diploid, to possess a mucinous histology, and to have a surrounding lymphoid reaction. They are more prevalent in the proximal colon and have a fast pass from polyp to cancer. Nevertheless, they are associated with longer survival than stage-matched tumors with microsateUite stability. Resistance of colorectal cancers with a high frequency of microsatellite instability to 5-fluorouracilbased chemotherapy is well established. Silencing the MLH1 gene expression by its promoter methylation stops the formation of MLH1 protein, and prevents the normal activation of the DNA repair gene. This is an important cause for genomic instability and cell proliferation to the point of colorectal cancer formation. Better knowledge of this process will have a huge impact on colorectal cancer management, prevention, treatment and prognosis.
文摘OBJECTIVE To detect the differences in gene expression of nonhomologous end-joining pathway including Ku70, Ku80, ERCC4, lig4 and DNA-PKcs between human primary gliomas and normal brain tissues, and furthermore, to explore the underlying mechanism for the expression alteration.METHODS The expression levels of Ku70, Ku80, ERCC4, lig4 and DNA-PKcs in 36 specimens of glioma and 12 specimens of normal brain tissue were measured using SYBR green-based real- time quantitative PCR. Methylation of DNA-PKcs was detected through methylation-specific PCR （MSP）.RESULTS There was no significant difference in expression of Ku70, Ku80, ERCC4 and lig4 between human primary gliomas and normal brain tissues （P 〈 0.05）, while DNA-PKcs were significantly up-regulated （P = 0.002）. The expression of DNA- PKcs was significantly higher in patients with grade III and IV diseases compared to patients with grade II disease or in normal brain tissues （P 〈 0.05）. Moreover, glioma tissue showed weaker methvlation than normal brain tissue.CONCLUSION The up-regulation of the DNA-PKcs may be associated with pathogenesis of glioma. Demethylation of DNA- PKcs promoter is an important reason for its up-regulation.
文摘死亡相关蛋白激酶（death—associated protein kinase．DAPK）是一种钙离子和钙调素依赖的丝氨酸和苏氨酸蛋白激酶，它参与IFN-γ、TNF-α、Fas等诱导的细胞凋亡过程，具有促进凋亡的功能。近年来，DAPK与肿瘤发生、发展的关系引起人们的广泛关注，尤其是其基因启动子区的甲基化与表达的缺失。在恶性血液病中，所有的伯基特淋巴瘤、84％的B细胞淋巴瘤、70％的多发性骨髓瘤、10％～30％的急性髓系白血病均有DAPK过甲基化。我们观察了骨髓增生异常综合征（MDS）患者骨髓单个核细胞（MNC）中DAPK基因启动子区过甲基化及其mRNA表达情况，并分析了其与临床特征的关系。
