微管类药物在转移、耐药的癌症治疗中发挥重要的作用。然而,临床上出现微管类药物耐药现象,需要研究者研发具有新作用模式、新机制的分子来克服耐药问题。多靶点药物分子策略是近年来针对复杂性疾病及耐药问题发展起来的一种药物分子设...微管类药物在转移、耐药的癌症治疗中发挥重要的作用。然而,临床上出现微管类药物耐药现象,需要研究者研发具有新作用模式、新机制的分子来克服耐药问题。多靶点药物分子策略是近年来针对复杂性疾病及耐药问题发展起来的一种药物分子设计策略。本文在替巴尼布林基础上,结合课题组前期研究,开展微管蛋白(tubulin)及原癌基因酪氨酸蛋白激酶Src(proto-oncogene tyrosine protein kinase Src,c-Src)双靶点抑制剂研究。从增加饱和碳原子比率(fraction of sp^(3)-hybridized carbon atoms,Fsp^(3))角度出发,合成16个目标化合物,并通过核磁共振氢谱、碳谱和质谱对其结构进行表征;采用噻唑蓝(MTT)法评价了化合物对宫颈癌细胞(HeLa)和肝癌细胞(HepG2)两种细胞株的生长抑制活性,并通过免疫荧光和流式细胞术评价化合物22对微管和细胞周期的影响。结果显示2-咪唑啉酮不适合替代替巴尼布林中的吡啶结构,化合物22对HeLa和HepG2的半数生长抑制浓度分别为45和51 nmol·L^(-1),并且能够破坏微管结构,将细胞周期阻滞于G2/M期。化合物22可作为先导物开展进一步深入研究。展开更多
Multiple-Point Simulation(MPS)is a geostatistical simulation technique commonly used to model complex geological patterns and subsurface heterogeneity.There have been a great variety of implementation methods develope...Multiple-Point Simulation(MPS)is a geostatistical simulation technique commonly used to model complex geological patterns and subsurface heterogeneity.There have been a great variety of implementation methods developed within MPS,of which Patch-Based Simulation is a more recently developed class.While we have witnessed great progress in Patch-Based algorithms lately,they are still faced with two challenges:conditioning to point data and the occurrence of verbatim copy.Both of them are partly due to finite size of Training image,from which a limited size of pattern database is constructed.To address these questions,we propose a novel approach that we call Generative-Patched-Simulation(GPSim),which is based on Generative Adversarial Networks(GAN).With this method,we are able to generate sufficient(in theory an infinite)number of new patches based on the current pattern database.As demonstrated by the results on a simple 2D binary image,this approach shows its potential to address the two issues and thus improve Patch-based Simulation methods.展开更多
文摘微管类药物在转移、耐药的癌症治疗中发挥重要的作用。然而,临床上出现微管类药物耐药现象,需要研究者研发具有新作用模式、新机制的分子来克服耐药问题。多靶点药物分子策略是近年来针对复杂性疾病及耐药问题发展起来的一种药物分子设计策略。本文在替巴尼布林基础上,结合课题组前期研究,开展微管蛋白(tubulin)及原癌基因酪氨酸蛋白激酶Src(proto-oncogene tyrosine protein kinase Src,c-Src)双靶点抑制剂研究。从增加饱和碳原子比率(fraction of sp^(3)-hybridized carbon atoms,Fsp^(3))角度出发,合成16个目标化合物,并通过核磁共振氢谱、碳谱和质谱对其结构进行表征;采用噻唑蓝(MTT)法评价了化合物对宫颈癌细胞(HeLa)和肝癌细胞(HepG2)两种细胞株的生长抑制活性,并通过免疫荧光和流式细胞术评价化合物22对微管和细胞周期的影响。结果显示2-咪唑啉酮不适合替代替巴尼布林中的吡啶结构,化合物22对HeLa和HepG2的半数生长抑制浓度分别为45和51 nmol·L^(-1),并且能够破坏微管结构,将细胞周期阻滞于G2/M期。化合物22可作为先导物开展进一步深入研究。
文摘Multiple-Point Simulation(MPS)is a geostatistical simulation technique commonly used to model complex geological patterns and subsurface heterogeneity.There have been a great variety of implementation methods developed within MPS,of which Patch-Based Simulation is a more recently developed class.While we have witnessed great progress in Patch-Based algorithms lately,they are still faced with two challenges:conditioning to point data and the occurrence of verbatim copy.Both of them are partly due to finite size of Training image,from which a limited size of pattern database is constructed.To address these questions,we propose a novel approach that we call Generative-Patched-Simulation(GPSim),which is based on Generative Adversarial Networks(GAN).With this method,we are able to generate sufficient(in theory an infinite)number of new patches based on the current pattern database.As demonstrated by the results on a simple 2D binary image,this approach shows its potential to address the two issues and thus improve Patch-based Simulation methods.
