目的观察索拉非尼治疗不可切除肝细胞肝癌的初步疗效和不良反应。方法选取符合人组标准的不可切除肝癌患者33例，口服索拉非尼，每次400mg，2次／d，治疗过程中根据不良反应发生情况调整剂量。每6～8周根据修订的RECIST标准评价疗效，...目的观察索拉非尼治疗不可切除肝细胞肝癌的初步疗效和不良反应。方法选取符合人组标准的不可切除肝癌患者33例，口服索拉非尼，每次400mg，2次／d，治疗过程中根据不良反应发生情况调整剂量。每6～8周根据修订的RECIST标准评价疗效，并记录不良反应，统计中位疾病进展时间（time to progression，TTP）和中位总生存时间（overall survival，OS）。结果33例患者中没有完全缓解和部分缓解者，疾病稳定11例，疾病进展22例，中位TTP为5．6个月（2．3～8．9个月）。BCLCB期较BCLCC期的患者中位TTP显著延长；体力状况越差，中位TTP越短；有肝外转移患者的中位TTP明显较无肝外转移患者短。总体不良反应发生率为75．8％，最常见的是手足皮肤反应、腹泻、高血压、皮疹。3级不良反应3例。结论索拉非尼能延长不可切除肝癌患者的中位疾病进展时间；肿瘤的分期越早，患者的肝功能及体力状况越好，接受索拉非尼治疗获益越好。展开更多
Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect o...Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor P J34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines （HepG2, Hep3B and HCC-LM3） treated with PJ34 （8 μmol/L） and SAHA （1 panol/L）, alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bear- ing subcutaneous HepG2 tumors were administered different groups of drugs （10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34＋25 mg/kg SAHA）, and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of P J34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34＋SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone （P〈0.05）. In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34＋SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of P J34 or SAHA alone （P〈0.05）. It was led to conclude that P J34 and SAHA can synergistically suppress the proliferation of liver cancer cells.展开更多
文摘目的观察索拉非尼治疗不可切除肝细胞肝癌的初步疗效和不良反应。方法选取符合人组标准的不可切除肝癌患者33例，口服索拉非尼，每次400mg，2次／d，治疗过程中根据不良反应发生情况调整剂量。每6～8周根据修订的RECIST标准评价疗效，并记录不良反应，统计中位疾病进展时间（time to progression，TTP）和中位总生存时间（overall survival，OS）。结果33例患者中没有完全缓解和部分缓解者，疾病稳定11例，疾病进展22例，中位TTP为5．6个月（2．3～8．9个月）。BCLCB期较BCLCC期的患者中位TTP显著延长；体力状况越差，中位TTP越短；有肝外转移患者的中位TTP明显较无肝外转移患者短。总体不良反应发生率为75．8％，最常见的是手足皮肤反应、腹泻、高血压、皮疹。3级不良反应3例。结论索拉非尼能延长不可切除肝癌患者的中位疾病进展时间；肿瘤的分期越早，患者的肝功能及体力状况越好，接受索拉非尼治疗获益越好。
基金supported by grants from the National Natural Science Foundation of China(No.81172293)the New Century Excellent Talent Foundation of Ministry of Education of China(No.NCET-04-0701)
文摘Summary： Poly （ADP-ribose） polymerase-1 （PARP-1） inhibitors and histone deacetylase （HDAC） in- hibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor P J34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines （HepG2, Hep3B and HCC-LM3） treated with PJ34 （8 μmol/L） and SAHA （1 panol/L）, alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bear- ing subcutaneous HepG2 tumors were administered different groups of drugs （10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34＋25 mg/kg SAHA）, and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of P J34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34＋SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone （P〈0.05）. In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34＋SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of P J34 or SAHA alone （P〈0.05）. It was led to conclude that P J34 and SAHA can synergistically suppress the proliferation of liver cancer cells.
