AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the im...AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.展开更多
31 cases of atherosclerosis (AS) were treated with Jiang Zhi Tong Mai Fang ([symbol: see text], formula of JZTMF), and its effect was compared with 30 cases treated with lovastatin in the control group. Clinically, th...31 cases of atherosclerosis (AS) were treated with Jiang Zhi Tong Mai Fang ([symbol: see text], formula of JZTMF), and its effect was compared with 30 cases treated with lovastatin in the control group. Clinically, the JZTMF formula showed an effect of regulating blood lipids, and therefore it was antiatherosclerotic. The mechanism is, probably, restoration of the function of endothelial cells (EC) by increasing the synthesis of 6-keto-PGF1 alpha and decreasing the release of endothelin (ET) as evidenced in the experimental study.展开更多
目的:比较研究槲皮素与芦丁对离体大鼠胸主动脉环的作用及其可能的途径。方法:采用累积加药法,检测槲皮素和芦丁对去氧肾上腺素(pheny lephrine,PE)预收缩的胸主动脉环张力的影响。结果:槲皮素对离体大鼠内皮完整和去内皮的胸主动脉环...目的:比较研究槲皮素与芦丁对离体大鼠胸主动脉环的作用及其可能的途径。方法:采用累积加药法,检测槲皮素和芦丁对去氧肾上腺素(pheny lephrine,PE)预收缩的胸主动脉环张力的影响。结果:槲皮素对离体大鼠内皮完整和去内皮的胸主动脉环均有浓度依赖性的舒张作用,而芦丁对PE预收缩血管的舒张作用是内皮依赖性的。槲皮素和芦丁对内皮完整的胸主动脉环的最大舒张反应分别为(77.20±6.11)%和(44.28±7.48)%,但两者对内皮完整的胸主动脉环最大舒张的半数有效浓度无明显差异。用一氧化氮合酶抑制剂L-NAM E(0.1 mm o l/L)预处理后,可阻断芦丁诱导的舒张血管作用,但不能阻断槲皮素引起的舒张血管作用;用鸟苷酸环化酶抑制剂亚甲蓝(10μm o l/L)预处理后,两者的血管舒张作用均被阻断。用环氧合酶抑制剂吲哚美辛(10μm o l/L)预处理后可减弱槲皮素诱导的舒张血管作用,但不能阻断芦丁引起的舒张血管作用。结论:槲皮素的舒血管作用强于芦丁,槲皮素可能是通过鸟苷酸环化酶和环氧合酶途径产生非内皮依赖性的血管舒张作用,而芦丁可能是通过NO-鸟苷酸环化酶途径产生内皮依赖性的血管舒张作用。展开更多
To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endot...To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endothelin 1 induced proliferation of cultured vascular smooth muscle cells (VSMCs) of rats in vitro . The 3H TdR incorporation decreased by 16.8%～37.4% in H 2S treated VSMCs as compared with the controls ( P <0.01). The inhibitory effect was found to be associated with reduced activity of MAPK. The authors also observed that endogenous H 2S levels markedly increased in vessels of rats with either endotoxic shock or septic shock [H 2S level (pmol·min -1 ·mg -1 ):tail artery (16.18±2.06) vs (8.12±0.55);mesenteric artery (10.17±1.11) vs (6.19 ±0.55);pulmonary artery(11.38±1.24) vs (5.27±0.51); aorta(6.21±0.48) vs (4.10± 0.28), P < 0.01 ]. The above findings suggested that H 2S might play an important role in the regulation of cardiovascular pathophysiologic events.展开更多
基金Supported by a faculty research grant of Yonsei University College of Medicine for 2002,No.2002-06
文摘AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.
文摘31 cases of atherosclerosis (AS) were treated with Jiang Zhi Tong Mai Fang ([symbol: see text], formula of JZTMF), and its effect was compared with 30 cases treated with lovastatin in the control group. Clinically, the JZTMF formula showed an effect of regulating blood lipids, and therefore it was antiatherosclerotic. The mechanism is, probably, restoration of the function of endothelial cells (EC) by increasing the synthesis of 6-keto-PGF1 alpha and decreasing the release of endothelin (ET) as evidenced in the experimental study.
文摘目的:比较研究槲皮素与芦丁对离体大鼠胸主动脉环的作用及其可能的途径。方法:采用累积加药法,检测槲皮素和芦丁对去氧肾上腺素(pheny lephrine,PE)预收缩的胸主动脉环张力的影响。结果:槲皮素对离体大鼠内皮完整和去内皮的胸主动脉环均有浓度依赖性的舒张作用,而芦丁对PE预收缩血管的舒张作用是内皮依赖性的。槲皮素和芦丁对内皮完整的胸主动脉环的最大舒张反应分别为(77.20±6.11)%和(44.28±7.48)%,但两者对内皮完整的胸主动脉环最大舒张的半数有效浓度无明显差异。用一氧化氮合酶抑制剂L-NAM E(0.1 mm o l/L)预处理后,可阻断芦丁诱导的舒张血管作用,但不能阻断槲皮素引起的舒张血管作用;用鸟苷酸环化酶抑制剂亚甲蓝(10μm o l/L)预处理后,两者的血管舒张作用均被阻断。用环氧合酶抑制剂吲哚美辛(10μm o l/L)预处理后可减弱槲皮素诱导的舒张血管作用,但不能阻断芦丁引起的舒张血管作用。结论:槲皮素的舒血管作用强于芦丁,槲皮素可能是通过鸟苷酸环化酶和环氧合酶途径产生非内皮依赖性的血管舒张作用,而芦丁可能是通过NO-鸟苷酸环化酶途径产生内皮依赖性的血管舒张作用。
文摘To explore the possibility of hydrogen sulfide (H 2S) as a messenger molecule in cardiovascular system, the authors discovered that H 2S (5×10 -5 -5×10 -4 mol·L -1 )exerted an effect on inhibiting endothelin 1 induced proliferation of cultured vascular smooth muscle cells (VSMCs) of rats in vitro . The 3H TdR incorporation decreased by 16.8%～37.4% in H 2S treated VSMCs as compared with the controls ( P <0.01). The inhibitory effect was found to be associated with reduced activity of MAPK. The authors also observed that endogenous H 2S levels markedly increased in vessels of rats with either endotoxic shock or septic shock [H 2S level (pmol·min -1 ·mg -1 ):tail artery (16.18±2.06) vs (8.12±0.55);mesenteric artery (10.17±1.11) vs (6.19 ±0.55);pulmonary artery(11.38±1.24) vs (5.27±0.51); aorta(6.21±0.48) vs (4.10± 0.28), P < 0.01 ]. The above findings suggested that H 2S might play an important role in the regulation of cardiovascular pathophysiologic events.
