培美曲塞治疗晚期非小细胞肺癌近期疗效分析

Objective:The aim of our study was to observe the efficacy and toxicity of 50 cases of advanced non-small cell lung cancer (NSCLC) patients treated by pemetrexed.Methods:Fifty patients,including 29 females and 21 males,with a median age 62 years (35–82 years),13 of whom were treated with pemetrexed only and the left 37 cases were treated with pemetrexed combined with platinum in the Department of Oncology,Renmin Hospital of Wuhan University from June 2006 to March 2009.Single agent regimen:patients received pemetrexed 500 mg/m2 on day 1 with every 21 days.Combination regimen:patients received pemetrexed 500 mg/m2 on day 1 and carboplatin 300 mg/m2 on day 1 or cisplatin 35 mg/m2 on day 1 to day 3 or nedaplatin 80 mg/m2 on day 1 by intravenous infusion with 21 days as one cycle.RECIST 1.0 standard was used to evaluate the clinical efficiency,and the WHO toxicity standard was used to evaluate toxic reaction,and the QOL was used to evaluate the quality of life.Results:All patients were given 162 cycles (at least 2 cycles,at most 6 cycles) and the response rate of all the patients were evaluated.There were 2 complete remission (CR),7 partial remission (PR),22 stable disease (SD) and 19 progressive disease (PD) in the group,the overall response rate was (RR) was 18.0% and disease control rate (DCR) 62.0%.The quality of life improvement rate reaches 58.0%.The major toxic reaction included neutropenia,thrombocytopenia,hypemia,nausea,and vomiting.Most of the severity of these effects was grade I–II and well tolerated.Conclusion:Chemotherapy with pemetrexed or pemetrexed combined with platinum in the treatment of advanced non-small cell lung cancer is effective,safe and well-tolerable,which can improve quality of life of the patient.     

Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells

Abstract

Combination therapy using anticancer drugs and nucleic acid is a more promising strategy to overcome multidrug resistance in cancer and to enhance apoptosis. In this study, lipid-polymer hybrid nanoparticles (LPNs), which contain both pemetrexed and miR-21 antisense oligonucleotide (anti-miR-21), have been developed for treatment of glioblastoma, the most aggressive type of brain tumor. Prepared LPNs have been well characterized by particle size distribution and zeta potential measurements, determination of encapsulation efficiency, and in vitro release experiments. Morphology of LPNs was determined by transmission electron microscopy. LPNs had a hydrodynamic size below 100?nm and exhibited sustained release of pemetrexed up to 10?h. Encapsulation of pemetrexed in LPNs increased cellular uptake from 6% to 78%. Results of confocal microscopy analysis have shown that co-delivery of anti-miR-21 significantly improved accumulation of LPNs in the nucleus of U87MG cells. Nevertheless, more effective cytotoxicity results could not be obtained due to low concentration of anti-miR-21, loaded in LPNs. We expect that the effective drug delivery systems can be obtained with higher concentration of anti-miR-21 for the treatment of glioblastoma.     

培美曲塞二钠的合成研究进展

介绍了合成新型抗癌药物培美曲塞二钠的两种方法。一种是以对溴苯甲酸为起始原料经酯化、缩合、溴代、环合、成盐等反应合成目标化合物,总收率达13．9％。另一是对碘苯甲酸甲酯与3-丁烯醇反应后溴代得4-（3-溴-4-氧代丁基）苯甲酸甲酯,与2,4-二氨基-6-羟基嘧啶反应后,再经水解得重要中间体2-氨基-4-氧代-5-[2-（4-羧基苯基）乙基]-4,7-二氢-3H-吡咯并（2,3-d）嘧啶,最后与L-谷氨酸二乙酯盐酸盐酰化、水解得培美曲塞二钠,总收率为16％。     

艾迪注射液对培美曲塞联合奈达铂治疗晚期非小细胞肺癌的增效作用

目的: 探讨艾迪注射液对培美曲塞联合奈达铂治疗晚期非小细胞肺癌是否有增效作用。方法: 将86例晚期非小细胞肺癌患者分为研究组和对照组,每组43例。对照组采用培美曲塞联合奈达铂治疗。研究组在对照组基础上,给予艾迪注射液治疗。对比两组的临床疗效,并检测两组患者治疗前后血清免疫指标变化,包括CD3+、CD4+、CD4+/CD8+、IgM、IgA、IgG,观察治疗过程中两组患者不良反应的发生情况。结果: 研究组的控制率及有效率高于对照组,但差异无统计学意义（P>0.05）;对照组治疗后的CD3+、CD4+、CD4+/CD8+、IgA、IgG较治疗前均明显降低（P<0.05）;研究组治疗后的CD3+、CD4+、CD4+/CD8+、IgA、IgG明显高于对照组,差异有统计学意义（P<0.05）;研究组胃肠道反应、白细胞减少、肝肾功能异常的发生程度明显低于对照组,差异有统计学意义（P<0.05）。结论:艾迪注射液对培美曲塞联合奈达铂治疗晚期非小细胞肺癌具有增效减毒的作用。     

4-(4-甲酯基苯基)丁醛的合成

以对溴苯甲酸为原料,经酯化后与3-丁烯-1-醇偶联,再与亚硫酸氢钠反应形成磺酸钠盐,经盐酸酸化后得4-(4-甲酯基苯基)丁醛。总收率可达37.3%。     

高效液相色谱法测定培美曲塞二钠中间体的有关物质

目的建立高效液相色谱法(HPLC)测定培美曲塞二钠中间体有关物质的方法。方法采用Agilent Extend-C18色谱柱(4.6 mm×250 mm,5μm),流动相为乙腈-0.0265 mol/L磷酸二氢钾(32:68),检测波长254 nm,柱温25℃,流速1.0 mL/min。结果培美曲塞二钠中间体在2.51~25.1 mg/mL范围内线性关系良好(r=0.9999),精密度试验中总杂质含量的RSD为0.25%(n=18)。结论本法简便、快速、专属性强、精密度好,可作为培美曲塞二钠中间体的有关物质控制方法。