AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.
Background Inhibition of tumor growth by endostatin has been shown to be an effective strategy in cancer therapy in mice However, its widespread application has been hampered by difficulties in a large scale productio...Background Inhibition of tumor growth by endostatin has been shown to be an effective strategy in cancer therapy in mice However, its widespread application has been hampered by difficulties in a large scale production of the recombinant endostatin protein, rapid loss bioactivity of the protein, and the cumbersome daily administration These limitations could be resolved by in vivo delivery and expression of the endostatin gene In this study, we observed the effect and advantage of endostatin gene therapy mediated by a recombinant adenoviral vector (Ad/hEndo) on the growth of hepatocellular carcinoma BEL 7402 xenografted tumors, comparison with recombinant endostatin protein Methods Hepatocellular carcinoma BEL 7402 cells were inoculated subcutaneously in the flank of Balb/c nude mice Nine days after tumor cell inoculation, animals were given a cycle of four courses of intra tumoral injections of Ad/hEndo of 5×10 8 pfu (low dose group) and 1×10 9 pfu (high dose group) at intervals of six days, respectively Recombinant human endostatin protein (rhEndo) was administrated daily subcutaneously at a dose of 10 mg·kg 1 ·d 1 at a site nearby the tumor for ten days The expression of endostatin mRNA in tumor tissue was analyzed by reverse transcription polymerase chain reaction (RT PCR) after Ad/hEndo injection Dynamic changes of concentration of endostatin protein in tumor tissue were quantitated by enzyme linked immunosorbent assay (ELISA) Results After 4 courses of treatment, the tumor growth rates of high dose treated group with 1×10 9 pfu of Ad/hEndo were inhibited by 42 26% compared with the Ad/ LacZ control group ( P =0 001) and by 46 26% compared with the NIH buffer control group ( P =0 003), respectively However, in this study, Ad/hEndo at low dose of 5×10 8 pfu failed to demonstrate significant inhibition of tumor growth, compared with control groups After daily administration of recombinant human endostatin protein (rhEndo) for 9 days, the ratio of T/C (rhEndo group versus PBS group) was less than 47% Howe展开更多
目的应用斑马鱼模型研究小金胶囊(麝香、木鳖子、制草乌等)的抗肿瘤作用。方法荧光标记的人乳腺癌细胞(michigan cancer foundation-7,MCF-7)移植入斑马鱼卵黄囊内建立移植瘤模型。小金胶囊以水溶液暴露移植瘤斑马鱼以评价其抗肿瘤作用...目的应用斑马鱼模型研究小金胶囊(麝香、木鳖子、制草乌等)的抗肿瘤作用。方法荧光标记的人乳腺癌细胞(michigan cancer foundation-7,MCF-7)移植入斑马鱼卵黄囊内建立移植瘤模型。小金胶囊以水溶液暴露移植瘤斑马鱼以评价其抗肿瘤作用,用转基因斑马鱼观察其对新生血管形成的抑制作用。吖啶橙染色后,图像分析法评价该药物的体内细胞凋亡诱导作用。结果 26.47、88.24、264.72μg/m L的小金胶囊对斑马鱼MCF-7移植瘤的抑制率分别为31.66%、54.35%、53.77%(P<0.01)。小金胶囊在高质量浓度(264.72μg/m L)下能显著抑制血管形成和诱导细胞凋亡,抑制率和诱导率分别为21.74%和28.92%(P<0.01)。结论小金胶囊能诱导细胞凋亡,抑制MCF-7移植瘤生长和新血管形成,具有潜在的抗肿瘤作用。展开更多
基金Supported by NIH Clinical Trial Registration,No.NCT00247728(this trial was cosponsored by Progen Industries Limited,Brisbane,Australia and Medigen Biotechnology Corporation,TaipeiTaiwan)to Chen PJ,Lai KL and Chang SSCTaiwan Liver Disease Consortium,the National Research Program for Biopharmaceuticals,and the National Science Council,Taiwan,NSC1002325-B-002-052NSC102-2325-B-002-079
文摘AIM: To demonstrate that administering heparanase inhibitor PI-88 at 160 mg/d is safe and promising in reducing hepatocellular carcinoma (HCC) recurrence for up to 3 year following curative resection.
文摘Background Inhibition of tumor growth by endostatin has been shown to be an effective strategy in cancer therapy in mice However, its widespread application has been hampered by difficulties in a large scale production of the recombinant endostatin protein, rapid loss bioactivity of the protein, and the cumbersome daily administration These limitations could be resolved by in vivo delivery and expression of the endostatin gene In this study, we observed the effect and advantage of endostatin gene therapy mediated by a recombinant adenoviral vector (Ad/hEndo) on the growth of hepatocellular carcinoma BEL 7402 xenografted tumors, comparison with recombinant endostatin protein Methods Hepatocellular carcinoma BEL 7402 cells were inoculated subcutaneously in the flank of Balb/c nude mice Nine days after tumor cell inoculation, animals were given a cycle of four courses of intra tumoral injections of Ad/hEndo of 5×10 8 pfu (low dose group) and 1×10 9 pfu (high dose group) at intervals of six days, respectively Recombinant human endostatin protein (rhEndo) was administrated daily subcutaneously at a dose of 10 mg·kg 1 ·d 1 at a site nearby the tumor for ten days The expression of endostatin mRNA in tumor tissue was analyzed by reverse transcription polymerase chain reaction (RT PCR) after Ad/hEndo injection Dynamic changes of concentration of endostatin protein in tumor tissue were quantitated by enzyme linked immunosorbent assay (ELISA) Results After 4 courses of treatment, the tumor growth rates of high dose treated group with 1×10 9 pfu of Ad/hEndo were inhibited by 42 26% compared with the Ad/ LacZ control group ( P =0 001) and by 46 26% compared with the NIH buffer control group ( P =0 003), respectively However, in this study, Ad/hEndo at low dose of 5×10 8 pfu failed to demonstrate significant inhibition of tumor growth, compared with control groups After daily administration of recombinant human endostatin protein (rhEndo) for 9 days, the ratio of T/C (rhEndo group versus PBS group) was less than 47% Howe
