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. METHODS: A total ...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. METHODS: A total of 143 patients(83.1% of the 172 participants in the phase Ⅱ study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase Ⅱ trial. Safety parameters and the following efficacy endpoints were investigated:(1) time to recurrence;(2) diseasefree survival; and(3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group:(1) the recurrence-free rate increased from 50% to 63%, and(2) time to recurrence at the 36 th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate(11 out of 54 patients). Additionally, subgroup analyses of patients with(1) multiple tumors or a single tumor ≥ 2 cm; and(2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage(56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.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. METHODS: A total of 143 patients(83.1% of the 172 participants in the phase Ⅱ study) participated in the follow-up study. Of these patients, 50 had received no treatment, 48 had received 160 mg/d PI-88, and 45 had received 250 mg/d PI-88 during the phase Ⅱ trial. Safety parameters and the following efficacy endpoints were investigated:(1) time to recurrence;(2) diseasefree survival; and(3) overall survival. RESULTS: PI-88 at 160 mg/d delayed the onset and frequency of HCC recurrence, and provided a clinically significant survival advantage for up to 3 years after treatment compared with those of the control group:(1) the recurrence-free rate increased from 50% to 63%, and(2) time to recurrence at the 36 th percentile was postponed by 78%. The efficacy of administering PI-88 at 250 mg/d was confounded by a high dropout rate(11 out of 54 patients). Additionally, subgroup analyses of patients with(1) multiple tumors or a single tumor ≥ 2 cm; and(2) hepatitis B or C revealed that administering PI-88 at 160 mg/d conferred the most significant survival advantage(56.8% improvement in disease-free survival, P = 0.045) for patients with both risk factors for recurrence. CONCLUSION: Administering PI-88 at 160 mg/d is a safe and well-tolerated dosage that may confer significant clinical benefits for patients with HCC.
文摘目的探讨硫酸化寡聚多糖PI-88对食管鳞癌细胞株TE-13增殖和细胞侵袭行为的影响。方法培养中的TE-13细胞分为A组、B组和C组。A组用15μg·m L-1PI-88处理,B组用30μg·m L-1PI-88处理;C组用等体积0.9%氯化钠处理。用噻唑蓝(MTT)比色法检测0.5,1,2,4,8,16,32μg·m L-1PI-88对TE-13细胞增殖活性的影响。用Matrigel侵袭试验研究检测15或30μg·m L-1PI-88处理后对食管鳞癌细胞株TE-13细胞侵袭力的影响。结果 7个浓度组PI-88作用于TE-13细胞72 h,各组细胞存活抑制率差异无统计学意义(P>0.05)。Matrigel侵袭实验结果:A、B、C 3组侵袭细胞数差异有统计学意义(P<0.01),各组间比较差异均有统计学意义(A vs B,P<0.05;B vs C,P<0.01;A vs C,P<0.01)。结论 PI-88在一定浓度范围内对TE-13细胞生长无明显影响,但可抑制TE-13细胞侵袭能力,并且其抑制作用随剂量增大而增强。
