IBM Tivoli Risk Manger与Check Point Next Generation相集成,产品交叉认证以实现无缝互操作性。互联网安全领域的全球领先厂商——Check Point软件技术有限公司日前宣布,它将通过更紧密地集成Check Point Next Generation安全解决方案...IBM Tivoli Risk Manger与Check Point Next Generation相集成,产品交叉认证以实现无缝互操作性。互联网安全领域的全球领先厂商——Check Point软件技术有限公司日前宣布,它将通过更紧密地集成Check Point Next Generation安全解决方案和IBM的自动化安全管理软件。展开更多
In this work, the most detrimental missense mutations of Madl protein that cause various types of cancer were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed...In this work, the most detrimental missense mutations of Madl protein that cause various types of cancer were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed. Out of 13 missense mutations, I Mutant 2.0, SIFT and PolyPhen programs identified 3 variants that were less stable, deleterious and damaging respectively. Subsequently, modeling of these 3 variants was performed to understand the change in their conformations with respect to the native Madl by computing their root mean squared deviation （RMSD）. Furthermore, the native protein and the 3 mutants were docked with the binding partner Mad2 to explain the substrate binding efficiencies of those detrimental missense mutations. The docking studies identified that all the 3 mutants caused lower binding affinity for Mad2 than the native protein. Finally, normal mode analysis determined that the loss of binding affinity of these 3 mutants was caused by altered flexibility in the amino acids that bind to Mad2 compared with the native protein. Thus, the present study showed that majority of the substrate binding amino acids in those 3 mutants displayed loss of flexibility, which could be the theoretical explanation of decreased binding affinity between the mutant Madl and Mad2.展开更多
局部晚期头颈部鳞状细胞癌(locally advanced head and neck squamous cell carcinoma,LA-HNSCC)虽经手术、放疗和化疗的综合治疗,疗效仍不尽如人意,40%~60%的患者治疗后会发生局部复发或远处转移,5年生存率不超过50%。近年来免疫检查...局部晚期头颈部鳞状细胞癌(locally advanced head and neck squamous cell carcinoma,LA-HNSCC)虽经手术、放疗和化疗的综合治疗,疗效仍不尽如人意,40%~60%的患者治疗后会发生局部复发或远处转移,5年生存率不超过50%。近年来免疫检查点抑制剂(immune checkpoint inhibitor,ICI)为复发/转移的头颈部鳞癌(recurrent or metastatic head and neck squamous cell carcinoma,R/M HNSCC)患者带来了生存获益,也成为国内外指南的一线推荐。基于免疫检查点抑制剂的安全性与有效性,大量临床研究围绕局部晚期头颈部鳞癌的免疫新辅助治疗策略,包括免疫单药或联合化疗、靶向、放疗等展开深入探讨,以期提高病理缓解率,继而改善总生存率。该文就免疫治疗在局部晚期头颈部鳞癌新辅助的研究现状和进展做一综述,希望对临床决策提供参考。展开更多
文摘IBM Tivoli Risk Manger与Check Point Next Generation相集成,产品交叉认证以实现无缝互操作性。互联网安全领域的全球领先厂商——Check Point软件技术有限公司日前宣布,它将通过更紧密地集成Check Point Next Generation安全解决方案和IBM的自动化安全管理软件。
文摘In this work, the most detrimental missense mutations of Madl protein that cause various types of cancer were identified computationally and the substrate binding efficiencies of those missense mutations were analyzed. Out of 13 missense mutations, I Mutant 2.0, SIFT and PolyPhen programs identified 3 variants that were less stable, deleterious and damaging respectively. Subsequently, modeling of these 3 variants was performed to understand the change in their conformations with respect to the native Madl by computing their root mean squared deviation （RMSD）. Furthermore, the native protein and the 3 mutants were docked with the binding partner Mad2 to explain the substrate binding efficiencies of those detrimental missense mutations. The docking studies identified that all the 3 mutants caused lower binding affinity for Mad2 than the native protein. Finally, normal mode analysis determined that the loss of binding affinity of these 3 mutants was caused by altered flexibility in the amino acids that bind to Mad2 compared with the native protein. Thus, the present study showed that majority of the substrate binding amino acids in those 3 mutants displayed loss of flexibility, which could be the theoretical explanation of decreased binding affinity between the mutant Madl and Mad2.
文摘局部晚期头颈部鳞状细胞癌(locally advanced head and neck squamous cell carcinoma,LA-HNSCC)虽经手术、放疗和化疗的综合治疗,疗效仍不尽如人意,40%~60%的患者治疗后会发生局部复发或远处转移,5年生存率不超过50%。近年来免疫检查点抑制剂(immune checkpoint inhibitor,ICI)为复发/转移的头颈部鳞癌(recurrent or metastatic head and neck squamous cell carcinoma,R/M HNSCC)患者带来了生存获益,也成为国内外指南的一线推荐。基于免疫检查点抑制剂的安全性与有效性,大量临床研究围绕局部晚期头颈部鳞癌的免疫新辅助治疗策略,包括免疫单药或联合化疗、靶向、放疗等展开深入探讨,以期提高病理缓解率,继而改善总生存率。该文就免疫治疗在局部晚期头颈部鳞癌新辅助的研究现状和进展做一综述,希望对临床决策提供参考。
