凋落是一种程序性细胞死亡,一种有规律的细胞死亡形式,有别于激发性细胞死亡。程序性细胞死亡的细胞具如下特征:细胞皱缩、染色质凝聚、细胞膜呈典型的外突。在 DNA 水平上,通过 Mg<sup>2+</sup>/Ca<sup>2+</sup&...凋落是一种程序性细胞死亡,一种有规律的细胞死亡形式,有别于激发性细胞死亡。程序性细胞死亡的细胞具如下特征:细胞皱缩、染色质凝聚、细胞膜呈典型的外突。在 DNA 水平上,通过 Mg<sup>2+</sup>/Ca<sup>2+</sup>相关的核酸内切酶,裂解为180个碱基对大小的若干片断。在无胞浆成分溢出的情况下。展开更多
目的评价信迪利单抗对比安慰剂联合化疗(顺铂加紫杉醇或顺铂加5-氟尿嘧啶)作为不可切除的局部晚期、复发或转移性食管鳞癌一线治疗的效果。设计多中心、随机、双盲、Ⅲ期临床研究。背景2018年12月14日至2021年4月9日,国内66家研究中心,...目的评价信迪利单抗对比安慰剂联合化疗(顺铂加紫杉醇或顺铂加5-氟尿嘧啶)作为不可切除的局部晚期、复发或转移性食管鳞癌一线治疗的效果。设计多中心、随机、双盲、Ⅲ期临床研究。背景2018年12月14日至2021年4月9日,国内66家研究中心,国外13家研究中心。受试者659例未曾接受过系统性治疗的成年(≥18岁)晚期或转移性食管鳞癌患者。干预受试者按1∶1的比例随机分组,每3周接受1次信迪利单抗或安慰剂(体重<60 kg者3 mg/kg,体重>60 kg者200 mg)与顺铂75 mg/m2和紫杉醇175 mg/m2的联合治疗。本研究经修订,允许研究者选择顺铂联合紫杉醇或顺铂联合5-氟尿嘧啶(800 mg/m2,第1~5天连续输注给药)化疗方案。主要结局指标所有患者和程序性细胞死亡配体1(PD-L1)表达联合阳性评分≥10的患者总生存期。结果659例患者随机分配至信迪利单抗(n=327)或安慰剂(n=332)联合化疗组。659例患者中有616例(93%)接受了信迪利单抗或安慰剂与顺铂和紫杉醇联合治疗,有43例(7%)接受了信迪利单抗或安慰剂与顺铂和5-氟尿嘧啶联合治疗。期中分析显示,在所有患者(中位总生存期16.7 vs 12.5个月,风险比0.63,95%可信区间0.51~0.78;P<0.001)和联合阳性评分≥10的患者(17.2 vs 13.6个月,0.64,0.48~0.85;P=0.002)中,信迪利单抗联合化疗组的总生存期均优于安慰剂联合化疗组。与安慰剂联合化疗相比,信迪利单抗联合化疗显著延长了所有患者(7.2 vs 5.7个月,0.56,0.46~0.68;P<0.001)和联合阳性评分≥10患者(8.3 vs 6.4个月,0.58,0.45~0.75;P<0.001)的无进展生存期。信迪利单抗联合化疗组出现治疗相关不良事件的患者人数为321/327例(98%),安慰剂联合化疗组为326/332例(98%)。在信迪利单抗联合化疗组和安慰剂联合化疗组中,3级及以上治疗相关不良事件的发生率分别为60%(196/327)和55%(181/332)。结论与安慰剂相比,信迪利单抗联合顺铂加紫杉醇作为一�展开更多
MicroRNA-21(miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors.Through functional suppression,miR-21 is implicated in practically every walk of oncogenic life:t...MicroRNA-21(miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors.Through functional suppression,miR-21 is implicated in practically every walk of oncogenic life:the promotion of cell proliferation,invasion and metastasis,genome instability and mutation,inflammation,replicative immortalization,abnormal metabolism,angiogenesis,and evading apoptosis,immune destruction,and growth suppressors.In particular,miR-21 is strongly involved in apoptosis.In this article,we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis.This suggests that miR-21 is an oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21.展开更多
文摘凋落是一种程序性细胞死亡,一种有规律的细胞死亡形式,有别于激发性细胞死亡。程序性细胞死亡的细胞具如下特征:细胞皱缩、染色质凝聚、细胞膜呈典型的外突。在 DNA 水平上,通过 Mg<sup>2+</sup>/Ca<sup>2+</sup>相关的核酸内切酶,裂解为180个碱基对大小的若干片断。在无胞浆成分溢出的情况下。
文摘目的评价信迪利单抗对比安慰剂联合化疗(顺铂加紫杉醇或顺铂加5-氟尿嘧啶)作为不可切除的局部晚期、复发或转移性食管鳞癌一线治疗的效果。设计多中心、随机、双盲、Ⅲ期临床研究。背景2018年12月14日至2021年4月9日,国内66家研究中心,国外13家研究中心。受试者659例未曾接受过系统性治疗的成年(≥18岁)晚期或转移性食管鳞癌患者。干预受试者按1∶1的比例随机分组,每3周接受1次信迪利单抗或安慰剂(体重<60 kg者3 mg/kg,体重>60 kg者200 mg)与顺铂75 mg/m2和紫杉醇175 mg/m2的联合治疗。本研究经修订,允许研究者选择顺铂联合紫杉醇或顺铂联合5-氟尿嘧啶(800 mg/m2,第1~5天连续输注给药)化疗方案。主要结局指标所有患者和程序性细胞死亡配体1(PD-L1)表达联合阳性评分≥10的患者总生存期。结果659例患者随机分配至信迪利单抗(n=327)或安慰剂(n=332)联合化疗组。659例患者中有616例(93%)接受了信迪利单抗或安慰剂与顺铂和紫杉醇联合治疗,有43例(7%)接受了信迪利单抗或安慰剂与顺铂和5-氟尿嘧啶联合治疗。期中分析显示,在所有患者(中位总生存期16.7 vs 12.5个月,风险比0.63,95%可信区间0.51~0.78;P<0.001)和联合阳性评分≥10的患者(17.2 vs 13.6个月,0.64,0.48~0.85;P=0.002)中,信迪利单抗联合化疗组的总生存期均优于安慰剂联合化疗组。与安慰剂联合化疗相比,信迪利单抗联合化疗显著延长了所有患者(7.2 vs 5.7个月,0.56,0.46~0.68;P<0.001)和联合阳性评分≥10患者(8.3 vs 6.4个月,0.58,0.45~0.75;P<0.001)的无进展生存期。信迪利单抗联合化疗组出现治疗相关不良事件的患者人数为321/327例(98%),安慰剂联合化疗组为326/332例(98%)。在信迪利单抗联合化疗组和安慰剂联合化疗组中,3级及以上治疗相关不良事件的发生率分别为60%(196/327)和55%(181/332)。结论与安慰剂相比,信迪利单抗联合顺铂加紫杉醇作为一�
基金supported by the Diabetes and Obesity Center funded by NCRR/NIH(P20RR024489)the Center for Environmental Genomics and Integrated Biology fundedby NIEHS/NIH(P30ES014443)+1 种基金the Scientist Development Grant from American Heart Association(0830288N)a R01 grant from National Institutes of Health(CA138688)
文摘MicroRNA-21(miR-21) is frequently up-regulated in cancer and the majority of its reported targets are tumor suppressors.Through functional suppression,miR-21 is implicated in practically every walk of oncogenic life:the promotion of cell proliferation,invasion and metastasis,genome instability and mutation,inflammation,replicative immortalization,abnormal metabolism,angiogenesis,and evading apoptosis,immune destruction,and growth suppressors.In particular,miR-21 is strongly involved in apoptosis.In this article,we reviewed the experimentally validated targets of miR-21 and found that two thirds are linked to intrinsic and/or extrinsic pathways of cellular apoptosis.This suggests that miR-21 is an oncogene which plays a key role in resisting programmed cell death in cancer cells and that targeting apoptosis is a viable therapeutic option against cancers expressing miR-21.
