The Akt signal transduction pathway controls most hallmarks of cancer. Activation of the Akt cascade promotes a malignant phenotype and is also widely implicated in drug resistance. Therefore, the modulation of Akt ac...The Akt signal transduction pathway controls most hallmarks of cancer. Activation of the Akt cascade promotes a malignant phenotype and is also widely implicated in drug resistance. Therefore, the modulation of Akt activity is regarded as an attractive strategy to enhance the efficacy of cancer therapy and irradiation. This pathway consists of phosphatidylinositol 3 kinase(PI3K), mammalian target of rapamycin, and the transforming serine-threonine kinase Akt protein isoforms, also known as protein kinase B. DNA-targeted agents, such as platinum agents, taxanes, and antimetabolites, as well as radiation have had a significant impact on cancer treatment by affecting DNA replication, which is aberrantly activated in malignancies. However, the caveat is that they may also trigger the activation of repairing mechanisms, such as upstream and downstream cascade of Akt survival pathway. Thus, each target can theoretically be inhibited in view of improving the potency of conventional treatment. Akt inhibitors, e.g., MK-2206 and perifosine, or PI3K modulators, e.g., LY294002 and Wortmannin, have shown some promising results in favor of sensitizing the cancer cells to the therapy in vitro and in vivo, which have provided the rationale for incorporation of these novel agents into multimodality treatment of different malignancies. Nevertheless, despite the acceptable safety profile of some of these agents in the clinical studies, with regard to the efficacy, the results are still too preliminary. Hence, we need to wait for the upcoming data from the ongoing trials before utilizing them into the standard care of cancer patients.展开更多
目的:研究东北红豆杉心材的化学成分。方法:采用硅胶柱色谱、制备薄层色谱和制备型高效液相色谱等手段对化学成分进行分离和纯化,用现代核磁技术对化合物进行结构鉴定。结果:从东北红豆杉心材分离得到10个化合物,分别鉴定为taxin ine(1)...目的:研究东北红豆杉心材的化学成分。方法:采用硅胶柱色谱、制备薄层色谱和制备型高效液相色谱等手段对化学成分进行分离和纯化,用现代核磁技术对化合物进行结构鉴定。结果:从东北红豆杉心材分离得到10个化合物,分别鉴定为taxin ine(1),taxusin(2),-βsitosterol(3),1-βhydroxybaccatin I(4),2,α5,α10β-triace-toxy-14β-(2-′m ethyl)butanoyloxy-4(20),11-taxad iene(5),2,α5,α10-βtriacetoxy-14-β(2-′m ethyl-3-′hydroxy-butanoy-loxy)-4(20),11-taxad iene(yunnanxane)(6),9,α10,β13α-triacetoxy-5-αc innamoyltaxa-4(20),11-d iene(7),2-deace-toxytaxin ine J(8),taxezop id ine G(9),2,α7,β9,α10,β13-αpentaacetoxyl-taxa-4(20),11-d ien-5-ol(5-dec innamoyltaxi-n ine J)(10)。结论:化合物4,6,10是首次从该植物中分离得到。展开更多
目的紫杉烷联合铂类及氟尿嘧啶类联合铂类均是食管癌的标准治疗方案,但二者之间的优劣尚不明确。本研究旨在应用荟萃分析方法比较紫杉烷联合铂类(taxane plus platinum,TP)与氟尿嘧啶类联合铂类(taxane plus platinum,FP)的同步放化疗...目的紫杉烷联合铂类及氟尿嘧啶类联合铂类均是食管癌的标准治疗方案,但二者之间的优劣尚不明确。本研究旨在应用荟萃分析方法比较紫杉烷联合铂类(taxane plus platinum,TP)与氟尿嘧啶类联合铂类(taxane plus platinum,FP)的同步放化疗治疗不可切除食管癌的临床疗效及安全性。方法检索PubMed、Embase、中国知网和万方数据库,检索时间截止至2018-12-18,收集所有对比TP与FP的同步放化疗治疗不可切除食管癌的队列研究或者随机对照试验。根据纽卡斯尔-渥太华量表(Newcastle-Ottawa scale,NOS)及Cochrane系统评价手册5.0对纳入的研究进行质量评价。采用RevMan5.3软件对相应的指标进行荟萃分析。结果36个研究共纳入3167例患者进行分析,其中随机对照试验20个,队列研究16个。TP的同步放化疗在完全缓解(OR=0.50,95%CI为0.41~0.62,P<0.001)、客观缓解率(OR=0.45,95%CI为0.37~0.55,P<0.001)、疾病控制率(OR=0.45,95%CI为0.32~0.64,P<0.001)、无进展生存期(HR=0.72,95%CI为0.63~0.82,P<0.001)及总生存期(HR=0.78,95%CI为0.69~0.88,P<0.001)方面均优于FP的同步放化疗。TP的同步放化疗在食管鳞癌患者中的疗效同样明显优于FP的同步放化疗。TP的同步放化疗Ⅲ~Ⅳ度白细胞减少的发生率(OR=1.91,95%CI为1.37~2.67,P<0.001)要高于FP的同步放化疗,其Ⅲ~Ⅳ度恶心/呕吐(OR=0.53,95%CI为0.32~0.86,P=0.01)及放射性食管炎(OR=0.52,95%CI为0.39~0.70,P<0.001)的发生率要低于FP的同步放化疗。结论TP同步放化疗治疗不可切除食管癌或者食管鳞癌疗效要优于FP同步放化疗,且增加的不良反应在可耐受范围之内。展开更多
文摘The Akt signal transduction pathway controls most hallmarks of cancer. Activation of the Akt cascade promotes a malignant phenotype and is also widely implicated in drug resistance. Therefore, the modulation of Akt activity is regarded as an attractive strategy to enhance the efficacy of cancer therapy and irradiation. This pathway consists of phosphatidylinositol 3 kinase(PI3K), mammalian target of rapamycin, and the transforming serine-threonine kinase Akt protein isoforms, also known as protein kinase B. DNA-targeted agents, such as platinum agents, taxanes, and antimetabolites, as well as radiation have had a significant impact on cancer treatment by affecting DNA replication, which is aberrantly activated in malignancies. However, the caveat is that they may also trigger the activation of repairing mechanisms, such as upstream and downstream cascade of Akt survival pathway. Thus, each target can theoretically be inhibited in view of improving the potency of conventional treatment. Akt inhibitors, e.g., MK-2206 and perifosine, or PI3K modulators, e.g., LY294002 and Wortmannin, have shown some promising results in favor of sensitizing the cancer cells to the therapy in vitro and in vivo, which have provided the rationale for incorporation of these novel agents into multimodality treatment of different malignancies. Nevertheless, despite the acceptable safety profile of some of these agents in the clinical studies, with regard to the efficacy, the results are still too preliminary. Hence, we need to wait for the upcoming data from the ongoing trials before utilizing them into the standard care of cancer patients.
文摘目的:研究东北红豆杉心材的化学成分。方法:采用硅胶柱色谱、制备薄层色谱和制备型高效液相色谱等手段对化学成分进行分离和纯化,用现代核磁技术对化合物进行结构鉴定。结果:从东北红豆杉心材分离得到10个化合物,分别鉴定为taxin ine(1),taxusin(2),-βsitosterol(3),1-βhydroxybaccatin I(4),2,α5,α10β-triace-toxy-14β-(2-′m ethyl)butanoyloxy-4(20),11-taxad iene(5),2,α5,α10-βtriacetoxy-14-β(2-′m ethyl-3-′hydroxy-butanoy-loxy)-4(20),11-taxad iene(yunnanxane)(6),9,α10,β13α-triacetoxy-5-αc innamoyltaxa-4(20),11-d iene(7),2-deace-toxytaxin ine J(8),taxezop id ine G(9),2,α7,β9,α10,β13-αpentaacetoxyl-taxa-4(20),11-d ien-5-ol(5-dec innamoyltaxi-n ine J)(10)。结论:化合物4,6,10是首次从该植物中分离得到。
文摘目的紫杉烷联合铂类及氟尿嘧啶类联合铂类均是食管癌的标准治疗方案,但二者之间的优劣尚不明确。本研究旨在应用荟萃分析方法比较紫杉烷联合铂类(taxane plus platinum,TP)与氟尿嘧啶类联合铂类(taxane plus platinum,FP)的同步放化疗治疗不可切除食管癌的临床疗效及安全性。方法检索PubMed、Embase、中国知网和万方数据库,检索时间截止至2018-12-18,收集所有对比TP与FP的同步放化疗治疗不可切除食管癌的队列研究或者随机对照试验。根据纽卡斯尔-渥太华量表(Newcastle-Ottawa scale,NOS)及Cochrane系统评价手册5.0对纳入的研究进行质量评价。采用RevMan5.3软件对相应的指标进行荟萃分析。结果36个研究共纳入3167例患者进行分析,其中随机对照试验20个,队列研究16个。TP的同步放化疗在完全缓解(OR=0.50,95%CI为0.41~0.62,P<0.001)、客观缓解率(OR=0.45,95%CI为0.37~0.55,P<0.001)、疾病控制率(OR=0.45,95%CI为0.32~0.64,P<0.001)、无进展生存期(HR=0.72,95%CI为0.63~0.82,P<0.001)及总生存期(HR=0.78,95%CI为0.69~0.88,P<0.001)方面均优于FP的同步放化疗。TP的同步放化疗在食管鳞癌患者中的疗效同样明显优于FP的同步放化疗。TP的同步放化疗Ⅲ~Ⅳ度白细胞减少的发生率(OR=1.91,95%CI为1.37~2.67,P<0.001)要高于FP的同步放化疗,其Ⅲ~Ⅳ度恶心/呕吐(OR=0.53,95%CI为0.32~0.86,P=0.01)及放射性食管炎(OR=0.52,95%CI为0.39~0.70,P<0.001)的发生率要低于FP的同步放化疗。结论TP同步放化疗治疗不可切除食管癌或者食管鳞癌疗效要优于FP同步放化疗,且增加的不良反应在可耐受范围之内。
