AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genist...AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genistein analogues were prepared by difluoromethylation and alkylation, and human gastric cancer cell lines AGS and SGC-7901 cultured in vitro were treated with various concentrations of genistein and genistein analogues. The cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were incubated by DFOG at different concentrations. The growth inhibitory effects were evaluated using MTT and clonogenic assay. The distribution of the phase in cell cycle was analyzed using flow cytometric analysis with propidium iodide staining. The expression of the transcription factor forkhead box M1 (FOXM1) was analyzed by reverse transcription-polymerase chain reaction and Western blotting. The expression levelsof CDK1, Cdc25B, cyclin B and p27KIP1 protein were detected using Western blotting. RESULTS: Nine of the genistein analogues had more effective antitumor activity than genistein. Among the tested analogues, DFOG possessed the strongest activity against AGS and SGC-7901 cells in vitro. DFOG significantly inhibited the cell viability and colony formation of AGS and SGC-7901 cells. Moreover, DFOG efficaciously arrested the cell cycle in G2/M phase. DFOG decreased the expression of FOXM1 and its downstream genes, such as CDK1, Cdc25B, cyclin B, and increased p27KIP1 at protein levels. Knockdown of FOXM1 by small interfering RNA before DFOG treatment resulted in enhanced cell growth inhibition in AGS cells. Up-regulation of FOXM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition in AGS cells. CONCLUSION: DFOG inhibits the growth of human gastric cancer cells by down-regulating the FOXM1 expression.展开更多
特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability metho...特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability method,CP)和界面流法(Interface Current method,IC)等。本文从方法理论以及数值计算两方面将MOC、CP和IC进行比较分析,评估其在pin-by-pin计算中的能力。同时在MOC计算中,不同的参数选择会对计算成本和计算精度产生影响,因此有必要进行敏感性分析以寻求最佳参数。本文首先将三种计算方法从原理上进行比较分析,再基于2D C5G7-MOX基准题完成了数值计算及MOC参数敏感性初步分析。计算结果表明:MOC在计算精度、计算效率和内存开销上均优于CP和IC。MOC的计算耗时和内存开销分别为23.9 min和37.5 MB,与参考解的相对误差仅为6.04×10^(-4)。而CP和IC的计算耗时分别为MOC的56.7倍和15.6倍,内存开销分别为MOC的407.7倍和32.8倍。进一步通过参数敏感性分析发现:网格划分对计算内存开销以及计算时间的影响最大,而极角的选择对计算精度的影响最大,并且给出一组综合优化建议参数:网格划分6×6,极角为GAUS且数目为2,方位角个数为30。该组参数的计算耗时为45.4 min,内存开销为264.7 MB,相对误差为5.9×10^(-5),归一化后的栅元均方根误差为0.002 55。展开更多
基金National Natural Science Foundation of China, No. 81172375Hunan Provincial Natural Science Foundation, No. 03JJY5009
文摘AIM: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms. METHODS: A series of genistein analogues were prepared by difluoromethylation and alkylation, and human gastric cancer cell lines AGS and SGC-7901 cultured in vitro were treated with various concentrations of genistein and genistein analogues. The cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were incubated by DFOG at different concentrations. The growth inhibitory effects were evaluated using MTT and clonogenic assay. The distribution of the phase in cell cycle was analyzed using flow cytometric analysis with propidium iodide staining. The expression of the transcription factor forkhead box M1 (FOXM1) was analyzed by reverse transcription-polymerase chain reaction and Western blotting. The expression levelsof CDK1, Cdc25B, cyclin B and p27KIP1 protein were detected using Western blotting. RESULTS: Nine of the genistein analogues had more effective antitumor activity than genistein. Among the tested analogues, DFOG possessed the strongest activity against AGS and SGC-7901 cells in vitro. DFOG significantly inhibited the cell viability and colony formation of AGS and SGC-7901 cells. Moreover, DFOG efficaciously arrested the cell cycle in G2/M phase. DFOG decreased the expression of FOXM1 and its downstream genes, such as CDK1, Cdc25B, cyclin B, and increased p27KIP1 at protein levels. Knockdown of FOXM1 by small interfering RNA before DFOG treatment resulted in enhanced cell growth inhibition in AGS cells. Up-regulation of FOXM1 by cDNA transfection attenuated DFOG-induced cell growth inhibition in AGS cells. CONCLUSION: DFOG inhibits the growth of human gastric cancer cells by down-regulating the FOXM1 expression.
文摘特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability method,CP)和界面流法(Interface Current method,IC)等。本文从方法理论以及数值计算两方面将MOC、CP和IC进行比较分析,评估其在pin-by-pin计算中的能力。同时在MOC计算中,不同的参数选择会对计算成本和计算精度产生影响,因此有必要进行敏感性分析以寻求最佳参数。本文首先将三种计算方法从原理上进行比较分析,再基于2D C5G7-MOX基准题完成了数值计算及MOC参数敏感性初步分析。计算结果表明:MOC在计算精度、计算效率和内存开销上均优于CP和IC。MOC的计算耗时和内存开销分别为23.9 min和37.5 MB,与参考解的相对误差仅为6.04×10^(-4)。而CP和IC的计算耗时分别为MOC的56.7倍和15.6倍,内存开销分别为MOC的407.7倍和32.8倍。进一步通过参数敏感性分析发现:网格划分对计算内存开销以及计算时间的影响最大,而极角的选择对计算精度的影响最大,并且给出一组综合优化建议参数:网格划分6×6,极角为GAUS且数目为2,方位角个数为30。该组参数的计算耗时为45.4 min,内存开销为264.7 MB,相对误差为5.9×10^(-5),归一化后的栅元均方根误差为0.002 55。
