Vacuum ultraviolet （VUV） photoionization and dissociative photoionization of capecitabine and its metabolites, 51-deoxy-5-fiuorocytidine （5＇-DFCR） and 51-deoxy-5- fiuorouridine （5＇- DFUR）, were investigated wi...Vacuum ultraviolet （VUV） photoionization and dissociative photoionization of capecitabine and its metabolites, 51-deoxy-5-fiuorocytidine （5＇-DFCR） and 51-deoxy-5- fiuorouridine （5＇- DFUR）, were investigated with infrared laser desorption/tunable synchrotron VUV photoionization mass spectrometry. Molecular ions （M＋） with small amounts of fragments can be found for these compounds at relatively low photon energies, while more fragment ions would be produced by increasing the photon energies. （M-H2O）＋, （base＋H）＋, （base＋2H）＋, （base＋30）＋, （base＋60）＋, and sugar moiety were proposed for these nucleoside drugs with similar backbones. Decomposition channels for the major fragments were discussed in detail. Moreover, ab initio calculations were introduced to study the dehydration pathways of three fluoro-nucleosides. Corresponding appearance energies for the （M-H2O）＋ ions were computed.展开更多
AIM: To study the levels of 5-fluorouracail (5-FU) in plasma, liver and tumor in patients with hepatoceilular carcinoma after oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR). METHODS: Thirty-nine pat...AIM: To study the levels of 5-fluorouracail (5-FU) in plasma, liver and tumor in patients with hepatoceilular carcinoma after oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR). METHODS: Thirty-nine patients with hepatoceilular carcinoma were treated with oral 5'-DFUR for more than 4 d before operation. The contents of 5-FU in plasma, liver and tumor were measured by high performance liquid chromatography (HPLC) and apoptosis of tumor cells was evaluated by in-situ TUNEL after resection of tumor. RESULTS: The concentrations of 5-FU were 1.1 μg/mL, 5.6, 5.9, and 10.5 μg/g in plasma, the liver tissue, the center of tumor and the periphery of tumor, respectively. 5-FU concentration was significantly higher in the periphery of tumor than that in the liver tissue and the center of tumor (10.5±1.6 μg/g vs 5.6±0.8 μg/g, t = 21.38, P<0.05; 10.5±1.6 μg/g vs 5.9±0.9 μg/g, t = 20.07, P<0.05). 5-FU level was significantly lower in plasma than that in the liver and the tumor (1.1±0.3 μg/mL vs 5.6±0.8 μg/g, t = 19.63, P<0.05; 1.1±0.3 μg/mL vs 10.5±1.6 μg/g, t= 41.01, P<0.05). Apoptosis of tumor cells was significantly increased after oral 5'-DFUR compared to the control group without 5-DFUR treatment. CONCLUSION: There is a higher concentration of 5-FU distributed in the tumor compared with liver tissue and apoptosis of tumor cells is increased following oral 5'-DFUR compared with the control group. The results indicate that 5'-DFUR is hopeful as neo-adjuvant chemotherapy to prevent recurrence after resection of hepatoceilular carcinoma.展开更多
目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的s...目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的shRNA(shRNA-METTL5)转染TNBC细胞后,用CCK-8、集落形成、伤口愈合以及Transwell实验分别检测细胞增殖活性、迁移与侵袭,Western blot检测Wnt/β-catenin信号关键蛋白的表达。构建异种移植瘤模型,验证敲降METTL5对TNBC细胞在体内生长以及Wnt/β-catenin信号活性的影响。结果METTL5在TNBC肿瘤组织和细胞系中表达上调(P<0.01)。敲降METTL5可抑制TNBC细胞的增殖、迁移和侵袭并降低了Wnt/β-catenin信号分子β-catenin、细胞周期蛋白(Cyclin)D1、基质金属蛋白酶(MMP)-2和MMP-7的表达(均P<0.01)。体内实验显示,敲降METTL5减缓了移植瘤生长和Wnt/β-catenin信号活性。结论敲降METTL5能抑制TNBC细胞的增殖、迁移与侵袭,其作用可能与抑制Wnt/β-catenin信号通路有关。展开更多
目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结...目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结肠癌组织、正常结肠细胞系(NCM460)和结直肠癌细胞系(SW620、HCT116、HT29、Lovo和SW480)中的表达。将SCL6A9过表达质粒及阴性对照(SLC6A9 OE、Vector)转染HT29细胞,将SCL6A9小干扰RNA及阴性对照(SLC6A9 siRNA1#、siRNA2#和Scramble)转染SW620细胞。划痕愈合实验和Transwell实验检测各组细胞的迁移、侵袭能力。Western blot和细胞免疫荧光检测EMT相关蛋白E-cadherin、Vimentin的表达水平。利用CCK-8法和构建裸鼠移植瘤模型检测SLC6A9过表达对结直肠癌细胞5-FU药物敏感性的影响。结果:与正常结肠组织和NCM460细胞相比,SLC6A9在结肠癌组织和结直肠癌细胞系中低表达(均P<0.05)。SLC6A9过表达引起E-cadherin蛋白表达增加,Vimentin蛋白水平降低,抑制结直肠癌细胞的迁移、侵袭(P<0.05)。SLC6A9低表达引起E-cadherin蛋白表达降低,Vimentin蛋白水平增加,促进结直肠癌细胞的迁移、侵袭能力(P<0.05)。SLC6A9过表达提高了5-FU的药物敏感性,并使肿瘤生长缓慢,质量减轻(P<0.05)。而SLC6A9低表达降低了5-FU的药物敏感性(P<0.05)。结论:SLC6A9过表达能够抑制结直肠癌细胞的迁移、侵袭和EMT进程,并增强5-FU对结直肠癌细胞的药物敏感性。展开更多
文摘Vacuum ultraviolet （VUV） photoionization and dissociative photoionization of capecitabine and its metabolites, 51-deoxy-5-fiuorocytidine （5＇-DFCR） and 51-deoxy-5- fiuorouridine （5＇- DFUR）, were investigated with infrared laser desorption/tunable synchrotron VUV photoionization mass spectrometry. Molecular ions （M＋） with small amounts of fragments can be found for these compounds at relatively low photon energies, while more fragment ions would be produced by increasing the photon energies. （M-H2O）＋, （base＋H）＋, （base＋2H）＋, （base＋30）＋, （base＋60）＋, and sugar moiety were proposed for these nucleoside drugs with similar backbones. Decomposition channels for the major fragments were discussed in detail. Moreover, ab initio calculations were introduced to study the dehydration pathways of three fluoro-nucleosides. Corresponding appearance energies for the （M-H2O）＋ ions were computed.
文摘AIM: To study the levels of 5-fluorouracail (5-FU) in plasma, liver and tumor in patients with hepatoceilular carcinoma after oral administration of 5'-deoxy-5-fluorouridine (5'-DFUR). METHODS: Thirty-nine patients with hepatoceilular carcinoma were treated with oral 5'-DFUR for more than 4 d before operation. The contents of 5-FU in plasma, liver and tumor were measured by high performance liquid chromatography (HPLC) and apoptosis of tumor cells was evaluated by in-situ TUNEL after resection of tumor. RESULTS: The concentrations of 5-FU were 1.1 μg/mL, 5.6, 5.9, and 10.5 μg/g in plasma, the liver tissue, the center of tumor and the periphery of tumor, respectively. 5-FU concentration was significantly higher in the periphery of tumor than that in the liver tissue and the center of tumor (10.5±1.6 μg/g vs 5.6±0.8 μg/g, t = 21.38, P<0.05; 10.5±1.6 μg/g vs 5.9±0.9 μg/g, t = 20.07, P<0.05). 5-FU level was significantly lower in plasma than that in the liver and the tumor (1.1±0.3 μg/mL vs 5.6±0.8 μg/g, t = 19.63, P<0.05; 1.1±0.3 μg/mL vs 10.5±1.6 μg/g, t= 41.01, P<0.05). Apoptosis of tumor cells was significantly increased after oral 5'-DFUR compared to the control group without 5-DFUR treatment. CONCLUSION: There is a higher concentration of 5-FU distributed in the tumor compared with liver tissue and apoptosis of tumor cells is increased following oral 5'-DFUR compared with the control group. The results indicate that 5'-DFUR is hopeful as neo-adjuvant chemotherapy to prevent recurrence after resection of hepatoceilular carcinoma.
文摘目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结肠癌组织、正常结肠细胞系(NCM460)和结直肠癌细胞系(SW620、HCT116、HT29、Lovo和SW480)中的表达。将SCL6A9过表达质粒及阴性对照(SLC6A9 OE、Vector)转染HT29细胞,将SCL6A9小干扰RNA及阴性对照(SLC6A9 siRNA1#、siRNA2#和Scramble)转染SW620细胞。划痕愈合实验和Transwell实验检测各组细胞的迁移、侵袭能力。Western blot和细胞免疫荧光检测EMT相关蛋白E-cadherin、Vimentin的表达水平。利用CCK-8法和构建裸鼠移植瘤模型检测SLC6A9过表达对结直肠癌细胞5-FU药物敏感性的影响。结果:与正常结肠组织和NCM460细胞相比,SLC6A9在结肠癌组织和结直肠癌细胞系中低表达(均P<0.05)。SLC6A9过表达引起E-cadherin蛋白表达增加,Vimentin蛋白水平降低,抑制结直肠癌细胞的迁移、侵袭(P<0.05)。SLC6A9低表达引起E-cadherin蛋白表达降低,Vimentin蛋白水平增加,促进结直肠癌细胞的迁移、侵袭能力(P<0.05)。SLC6A9过表达提高了5-FU的药物敏感性,并使肿瘤生长缓慢,质量减轻(P<0.05)。而SLC6A9低表达降低了5-FU的药物敏感性(P<0.05)。结论:SLC6A9过表达能够抑制结直肠癌细胞的迁移、侵袭和EMT进程,并增强5-FU对结直肠癌细胞的药物敏感性。
