K-ras is a member of ras gene family which is involved in cell survival,proliferation and differentiation.When a mutation occurs in ras gene,the activation of Ras proteins may be prolonged to induce oncogenesis.Howeve...K-ras is a member of ras gene family which is involved in cell survival,proliferation and differentiation.When a mutation occurs in ras gene,the activation of Ras proteins may be prolonged to induce oncogenesis.However,the relationship between K-ras mutation and clinical outcomes in pancreatic cancer patients treated with chemotherapy agents is still under debate.In this study,we constructed five pAcGFP1-C3 plasmids for different types of K-ras gene(WT,G12V,G12R,G12D,and G13D)and stably transfected human pancreatic cancer Bxpc-3 cells with these genes.The wild type and mutant clones showed a comparable growth and expression of K-Ras-GFP fusion protein.The expression of some K-ras mutations resulted in a reduced sensitivity to gefitinib,5-FU,docetaxel and gemcitabine,while showed no effects on erlotinib or cisplatin.Moreover,compared with the wild type clone,K-Ras downstream signals(phospho-Akt and/or phospho-Erk)were increased in K-ras mutant clones.Interestingly,different types of K-ras mutation had non-identical K-Ras downstream signal activities and drug responses.Our results are the first to reveal the relationship between different K-ras mutation and drug sensitivities of these anti-cancer drugs in pancreatic cancer cells in vitro.展开更多
文摘目的 比较集中带量采购(简称“集采”)替格瑞洛仿制药和原研药用于行支架辅助弹簧圈栓塞术颅内动脉瘤患者的有效性和安全性。方法 纳入2020年1月至2021年11月行支架辅助弹簧圈栓塞术的颅内动脉瘤病例181例,根据使用替格瑞洛品种的不同分为集采前组(n=93)和集采后组(n=88)。比较2组在住院期间的二磷酸腺苷(ADP)抑制率和ADP抑制率的达标率,随访并比较2组术后出院6个月的改良Rankin量表(mRS)评分、格拉斯哥预后量表(GOS)评分、缺血事件和出血事件发生率。结果集采后组和集采前组住院期间的ADP抑制率[(59.01±29.05)%vs(62.35±27.62)%]和ADP抑制率的达标率(60.00%vs64.86%)比较,差异均无统计学意义(P>0.05)。集采后组和集采前组术后6个月的缺血事件发生率(5.88%vs 4.71%)、出血事件发生率(18.82%vs 15.29%)、GOS评分(4.89±7.05 vs 4.85±7.12)和mRS评分(0.50±0.21 vs 0.62±0.24)比较,差异均无统计学意义(P>0.05)。结论 对于行支架辅助弹簧圈栓塞术的颅内动脉瘤患者,集采替格瑞洛仿制药和原研药的有效性和安全性相当。
基金supported by National Natural Science Foundation of China(81102459)the Fundamental Research Funds for the Central Universities,Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources(Guangxi Normal University)+1 种基金Ministry of Education of China(CMEMR2012-B07)Doctoral Fund of Ministry of Education of China(20130071110069)
文摘K-ras is a member of ras gene family which is involved in cell survival,proliferation and differentiation.When a mutation occurs in ras gene,the activation of Ras proteins may be prolonged to induce oncogenesis.However,the relationship between K-ras mutation and clinical outcomes in pancreatic cancer patients treated with chemotherapy agents is still under debate.In this study,we constructed five pAcGFP1-C3 plasmids for different types of K-ras gene(WT,G12V,G12R,G12D,and G13D)and stably transfected human pancreatic cancer Bxpc-3 cells with these genes.The wild type and mutant clones showed a comparable growth and expression of K-Ras-GFP fusion protein.The expression of some K-ras mutations resulted in a reduced sensitivity to gefitinib,5-FU,docetaxel and gemcitabine,while showed no effects on erlotinib or cisplatin.Moreover,compared with the wild type clone,K-Ras downstream signals(phospho-Akt and/or phospho-Erk)were increased in K-ras mutant clones.Interestingly,different types of K-ras mutation had non-identical K-Ras downstream signal activities and drug responses.Our results are the first to reveal the relationship between different K-ras mutation and drug sensitivities of these anti-cancer drugs in pancreatic cancer cells in vitro.
