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目的探讨多聚二磷酸腺苷核糖聚合酶(PARP)抑制剂奥拉帕尼用于治疗DNA修复缺陷的转移性膀胱尿路上皮肿瘤(MBUC)的临床应用。方法选取2015年2月至2015年9月于抚顺市中医院及盛京医院泌尿外科就诊的MBUC患者100例,根据第二代基因组测序、外显子和转录组分析以及数字PCR检测结果分为DNA修复正常组和DNA修复缺陷组,给予两组患者奥拉帕尼,隔日1次,每次400 mg。分别于治疗1周、2周、4周和8周末比较两组患者血清前列腺特异抗原(PSA)水平、血浆循环肿瘤细胞(CTC)数量,观察并记录两组总生存率和不良反应发生情况。结果 DNA修复缺陷组治疗1周、2周、4周和8周末,血清PSA水平分别为(25.18±10.31)、(16.58±6.47)、(13.26±5.49)和(11.46±6.47)ng/ml,每7.5 ml血浆中所含CTC数量分别为(85.25±2.55)、(80.35±2.25)、(78.38±3.26)和(75.25±3.45)个,均显著低于同时间点的DNA修复正常组,差异均具有统计学意义(P<0.05)。与治疗1周相比,DNA修复缺陷组治疗2周、4周和8周末血清PSA水平和CTC数量均显著降低,差异均具有统计学意义(P<0.05)。从治疗第2周开始,DNA修复缺陷组的总生存率显著高于同时间点的DNA修复正常组,差异均具有统计学意义(P<0.05)。但两组不良反应发生率相似,差异无统计学意义(P>0.05)。结论奥拉帕尼可显著降低DNA修复缺陷MBUC患者的血清PSA水平和血浆CTC数量,患者总生存率较高。
Objective To investigate the clinical application of orapamidine, a poly-ADP ribose polymerase (PARP inhibitor), in the treatment of metastatic bladder urothelial carcinoma (MBUC) deficient in DNA repair. Methods One hundred patients with MBUC who were treated in Department of Urology, Fushun Hospital of Traditional Chinese Medicine and Shengjing Hospital from February 2015 to September 2015 were selected and divided into two groups according to the second generation of genome sequencing, exon and transcriptome analysis and digital PCR test DNA repair normal group and DNA repair defect group, given two groups of patients Orapanib, every other day, 400 mg each time. The level of serum PSA and the number of circulating tumor cells (CTCs) in the two groups were compared at 1 week, 2 weeks, 4 weeks and 8 weeks after treatment. The overall survival and adverse reactions were observed and recorded. Results The levels of PSA in the DNA repair deficient group were (25.18 ± 10.31), (16.58 ± 6.47), (13.26 ± 5.49) and (11.46 ± 6.47) ng / ml at the end of the 1st, 2nd, 4th and 8th week, The number of CTC contained in each 7.5 ml plasma was (85.25 ± 2.55), (80.35 ± 2.25), (78.38 ± 3.26) and (75.25 ± 3.45), respectively, which were significantly lower than that of DNA repair normal group at the same time All were statistically significant (P <0.05). Compared with the 1-week treatment, the levels of PSA and CTC in the DNA repair deficient group at 2 weeks, 4 weeks and 8 weeks after treatment were significantly lower, with statistical significance (P <0.05). From the second week of treatment, the overall survival rate of DNA repair defect group was significantly higher than that of DNA repair normal group at the same time points, the differences were statistically significant (P <0.05). However, the incidence of adverse reactions was similar between the two groups, with no significant difference (P> 0.05). Conclusion Orapanib can significantly reduce the level of serum PSA and plasma CTC in patients with DNA repair-deficient MBUC. The overall survival rate is high.