目的:了解胃肠道常见的B细胞淋巴瘤中含c a s p a s e募集结构域的膜相关鸟苷酸激酶蛋白1(caspase recruitment domain-containing membrane-associated guanylate kinase protein 1,CARMA1)表达与核因子κB(nuclear factorκB,NF-κB)...目的:了解胃肠道常见的B细胞淋巴瘤中含c a s p a s e募集结构域的膜相关鸟苷酸激酶蛋白1(caspase recruitment domain-containing membrane-associated guanylate kinase protein 1,CARMA1)表达与核因子κB(nuclear factorκB,NF-κB)表达的关系及其对淋巴瘤的影响.方法:筛选54例胃肠B细胞淋巴瘤,其中弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)34例、黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue,M A LT淋巴瘤)20例及21例胃肠淋巴组织反应性增生病例.Real-time PCR检测CARMA1mRNA,免疫组织化学染色检测肿瘤细胞的CARMA1、NF-κB/p65和NF-κB/p50蛋白表达.结果:CARMA1、NF-κB/p65和NF-κB/p50蛋白表达率在淋巴瘤组较淋巴组织反应性增生组病例明显增高(淋巴瘤:淋巴组织反应性增生CARMA1为75.9%∶47.6%,NF-κB/p65为48.2%∶14.3%,NF-κB/p50为38.9%∶9.5%,P=0.042,0.007,0.013).与MALT淋巴瘤比较,DLBCL病例中CARMA1 mRNA和蛋白高表达(DLBCL∶MALT淋巴瘤CARMA1 mRNA2-△△Ct为3.073∶1,CARMA1蛋白为88.2%∶55.0%),P值为0.019和0.020.CARMA1蛋白表达与NF-κB/p65和NF-κB/p50蛋白核表达有正相关关系(NF-κB/p65阴性组∶阳性组为67.9%∶84.6%,NF-κB/p50阴性组∶阳性组为78.8%∶71.4%),P值分别为0.030和0.031.CARMA1 mRNA在晚分期(Ⅲ和Ⅳ期)病例中表达水平高于早分期(Ⅰ和Ⅱ期)病例(晚分期∶早分期CARMA1 mRNA 2-△△Ct=4.416∶1),P=0.011,在消化管壁内浸润病例中CARMA1蛋白表达低于浸润至管壁外的病例(管壁内:管壁外66.7%∶91.7%),P=0.003.肿瘤细胞高增殖活性病例中CARMA1 mRNA和蛋白表达都显著升高(高增殖活性∶低增殖活性CARMA1 mRNA 2-△△Ct=2.885∶1 CARMA1蛋白为88.6%∶52.6%),P值分别为0.035,0.006.NF-κB/p65、NF-κB/p50蛋白在晚分期病例、肿瘤细胞高增殖活性病例中表达水平明显高于相应的比较组病例(晚分期∶早分期NF-κB/p65为68.2%∶34.4%,NF-κB/p50为54.5%∶28.1%,高增殖活性:低增殖活性NF-κB/p65为60.0%∶26.3%,NF-κB/p50为51.4%∶15.8%),P值分别为0.015和0.05,0.018和0.001.生存分析:淋巴瘤类型、临床分期、CARMA1蛋白及NF-κB/p65蛋白表达都是淋巴瘤独立的预后影响因子,4种因素的相对风险度接近.C A R M A1蛋白强阳性表达的所有淋巴瘤和DLBCL病例的生存状况较阴性和一般阳性表达(<50%)的相应病例差(P值为0.020,0.045).结论:胃肠MALT淋巴瘤和DLBCL中NF-κB持续活化可能与CARMA1蛋白高表达相关,推测CARMA1高表达通过活化NF-κB参与相关淋巴瘤的发生发展过程.展开更多
Dear Editor,Chemotherapy is one of major means for cancer treatments, and many of chemotherapeutic drugs are DNA damaging agents that reduce tumor growth through triggering cancer cell apoptosis or necrosis. Following...Dear Editor,Chemotherapy is one of major means for cancer treatments, and many of chemotherapeutic drugs are DNA damaging agents that reduce tumor growth through triggering cancer cell apoptosis or necrosis. Following DNA damage, ataxia telangiectasia mutated （ATM）, a protein kinase, was acti- vated and a cytosolic complex containing ATM, NEMO, RIP1 were formed （Biton and Ashkenazi, 2011）.展开更多
文摘目的:了解胃肠道常见的B细胞淋巴瘤中含c a s p a s e募集结构域的膜相关鸟苷酸激酶蛋白1(caspase recruitment domain-containing membrane-associated guanylate kinase protein 1,CARMA1)表达与核因子κB(nuclear factorκB,NF-κB)表达的关系及其对淋巴瘤的影响.方法:筛选54例胃肠B细胞淋巴瘤,其中弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)34例、黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue,M A LT淋巴瘤)20例及21例胃肠淋巴组织反应性增生病例.Real-time PCR检测CARMA1mRNA,免疫组织化学染色检测肿瘤细胞的CARMA1、NF-κB/p65和NF-κB/p50蛋白表达.结果:CARMA1、NF-κB/p65和NF-κB/p50蛋白表达率在淋巴瘤组较淋巴组织反应性增生组病例明显增高(淋巴瘤:淋巴组织反应性增生CARMA1为75.9%∶47.6%,NF-κB/p65为48.2%∶14.3%,NF-κB/p50为38.9%∶9.5%,P=0.042,0.007,0.013).与MALT淋巴瘤比较,DLBCL病例中CARMA1 mRNA和蛋白高表达(DLBCL∶MALT淋巴瘤CARMA1 mRNA2-△△Ct为3.073∶1,CARMA1蛋白为88.2%∶55.0%),P值为0.019和0.020.CARMA1蛋白表达与NF-κB/p65和NF-κB/p50蛋白核表达有正相关关系(NF-κB/p65阴性组∶阳性组为67.9%∶84.6%,NF-κB/p50阴性组∶阳性组为78.8%∶71.4%),P值分别为0.030和0.031.CARMA1 mRNA在晚分期(Ⅲ和Ⅳ期)病例中表达水平高于早分期(Ⅰ和Ⅱ期)病例(晚分期∶早分期CARMA1 mRNA 2-△△Ct=4.416∶1),P=0.011,在消化管壁内浸润病例中CARMA1蛋白表达低于浸润至管壁外的病例(管壁内:管壁外66.7%∶91.7%),P=0.003.肿瘤细胞高增殖活性病例中CARMA1 mRNA和蛋白表达都显著升高(高增殖活性∶低增殖活性CARMA1 mRNA 2-△△Ct=2.885∶1 CARMA1蛋白为88.6%∶52.6%),P值分别为0.035,0.006.NF-κB/p65、NF-κB/p50蛋白在晚分期病例、肿瘤细胞高增殖活性病例中表达水平明显高于相应的比较组病例(晚分期∶早分期NF-κB/p65为68.2%∶34.4%,NF-κB/p50为54.5%∶28.1%,高增殖活性:低增殖活性NF-κB/p65为60.0%∶26.3%,NF-κB/p50为51.4%∶15.8%),P值分别为0.015和0.05,0.018和0.001.生存分析:淋巴瘤类型、临床分期、CARMA1蛋白及NF-κB/p65蛋白表达都是淋巴瘤独立的预后影响因子,4种因素的相对风险度接近.C A R M A1蛋白强阳性表达的所有淋巴瘤和DLBCL病例的生存状况较阴性和一般阳性表达(<50%)的相应病例差(P值为0.020,0.045).结论:胃肠MALT淋巴瘤和DLBCL中NF-κB持续活化可能与CARMA1蛋白高表达相关,推测CARMA1高表达通过活化NF-κB参与相关淋巴瘤的发生发展过程.
文摘Dear Editor,Chemotherapy is one of major means for cancer treatments, and many of chemotherapeutic drugs are DNA damaging agents that reduce tumor growth through triggering cancer cell apoptosis or necrosis. Following DNA damage, ataxia telangiectasia mutated （ATM）, a protein kinase, was acti- vated and a cytosolic complex containing ATM, NEMO, RIP1 were formed （Biton and Ashkenazi, 2011）.
