Wang Xiaobin, Wang Huihan, Song Yongsheng
Department of Urinary Surgery (II), Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Department of Hematology (II), Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Oncol Lett. 2019 Jan;17(1):201-208. doi: 10.3892/ol.2018.9617. Epub 2018 Oct 24.
The clinical efficacy and mechanism of Pralatrexate (PTX) combined with Palbociclib Isethionate (PAL) in the treatment of bladder cancer patients was investigated. A retrospective analysis of medical records of 82 bladder cancer patients admitted to Shengjing Hospital of China Medical University from February 2015 to February 2018 was performed. Patients treated with PTX combined with PAL served as study group (42 cases) and patients with conventional GC (gemcitabine plus cisplatin) chemotherapy regimen were the control group (40 cases). Changes in liver function indexes before and after treatment were observed, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil). RT-qPCR was used for detection of relative expression levels of serum dihydrofolate reductase (DHFR) and vascular endothelial growth factor (VEGF) before and after treatment in the two groups. The clinical efficacy after treatment and adverse reactions during treatment were observed in the two groups. There was no significant difference in the clinical remission rate (RR) nor in the serum ALT, AST, ALP and TBil levels between the study and the control groups (P>0.05). Concentrations of serum ALT, AST, ALP and TBil were significantly higher than those before treatment in both groups (P<0.05). Serum ALT, AST, ALP and TBil concentrations in study group were significantly lower than those in control group (P<0.05). There was no significant difference in the incidence of thrombocytopenia and leukopenia between the two groups (P>0.05). There was no significant difference in relative expression levels of serum DHFR mRNA and VEGF mRNA before treatment between the study and control groups (P>0.05). Those after treatment were significantly lower than those before treatment in both groups (P<0.05), and those after treatment in study group were significantly lower than those in control group (P<0.05). PTX combined with PAL can reduce adverse reactions of nausea and vomiting and liver function impairment during treatment and suppress tumor neovascularization. This is achieved possibly by inhibiting expression levels of DHFR and VEGF, thereby killing cancer cells. PTX combined with PAL may become a new method for the treatment of bladder cancer patients. DHFR and VEGF are expected to become novel therapeutic targets for the treatment of bladder cancer.
研究了普拉曲沙（PTX）联合依西美坦帕博西尼（PAL）治疗膀胱癌患者的临床疗效及机制。对2015年2月至2018年2月在中国医科大学盛京医院收治的82例膀胱癌患者的病历进行回顾性分析。接受PTX联合PAL治疗的患者作为研究组（42例），采用传统GC（吉西他滨加顺铂）化疗方案的患者作为对照组（40例）。观察治疗前后肝功能指标的变化，包括谷丙转氨酶（ALT）、谷草转氨酶（AST）、碱性磷酸酶（ALP）和总胆红素（TBil）。采用RT-qPCR检测两组治疗前后血清二氢叶酸还原酶（DHFR）和血管内皮生长因子（VEGF）的相对表达水平。观察两组治疗后的临床疗效及治疗期间的不良反应。研究组与对照组的临床缓解率（RR）以及血清ALT、AST、ALP和TBil水平均无显著差异（P>0.05）。两组血清ALT、AST、ALP和TBil浓度均显著高于治疗前（P<0.05）。研究组血清ALT、AST、ALP和TBil浓度显著低于对照组（P<0.05）。两组血小板减少症和白细胞减少症的发生率无显著差异（P>0.05）。研究组与对照组治疗前血清DHFR mRNA和VEGF mRNA的相对表达水平无显著差异（P>0.05）。两组治疗后均显著低于治疗前（P<0.05），且研究组治疗后显著低于对照组（P<0.05）。PTX联合PAL可降低治疗期间恶心、呕吐等不良反应及肝功能损害，并抑制肿瘤新生血管形成。这可能是通过抑制DHFR和VEGF的表达水平，从而杀死癌细胞来实现的。PTX联合PAL可能成为治疗膀胱癌患者的一种新方法。DHFR和VEGF有望成为治疗膀胱癌的新型治疗靶点。
