Novel application of pluronic lecithin organogels (PLOs) for local delivery of synergistic combination of docetaxel and cisplatin to improve therapeutic efficacy against ovarian cancer

The synergistic combination of docetaxel (DTX) and cisplatin (CIS) by local drug delivery with a pluronic lecithin organogel (PLO) to facilitate high drug concentrations at tumor sites and less nonspecific distribution to normal organs is thought to be beneficial in chemotherapy. In this study, using Capryol-90 (C90) with the addition of lecithin as the oil phase was developed to carry DTX, which was then incorporated into a PLO-containing CIS to formulate a dual-drug injectable PLO for local delivery. An optimal PLO composite, P₁₃L_0.15O_1.5, composed of PF127:lecithin:C90 at a 13:0.15:1.5 weight ratio was obtained. The sol–gel transition temperature of P₁₃L_0.15O_1.5 was found to be 33?°C. Tumor inhibition studies illustrated that DTX/CIS-loaded P₁₃L_0.15O_1.5 could efficiently suppress tumor growth by both intratumoral and peritumoral injections in SKOV-3 xenograft mouse model. Pharmacokinetic studies showed that subcutaneous administration of P₁₃L_0.15O_1.5 was able to sustain the release of DTX and CIS leading to their slow absorption into the systemic circulation resulting in lower area under the plasma concentration curve at 0–72?h (AUC_0–72) and maximum concentration (C_max) values but longer half-life (T_1/2) and mean residence time (MRT) values. An in vivo biodistribution study showed lower DTX and CIS concentrations in organs compared to other treatment groups after IT administration of the dual drug-loaded P₁₃L_0.15O_1.5. It was concluded that the local co-delivery of DTX and CIS by PLOs may be a promising and effective platform for local anticancer drug delivery with minimal systemic toxicities.     

多西他赛一线治疗老年晚期非小细胞肺癌临床分析

目的观察多西他赛单药一线治疗老年晚期非小细胞肺癌的临床疗效。方法72例老年晚期非小细胞肺癌初治患者以国产多西他赛（商品名：奥名润）50～60mg／m2,溶于生理盐水250ml中,第1、8天给药,21d为一周期,每完成2周期化疗后评价疗效,有效及稳定病例完成4周期,随访疾病进展至患者死亡。结果72例可评价病例中,总有效率为26．4％,疾病控制率为52．8％,中位无进展生存期3．2个月,中位生存期8．4个月,1年、2年生存率分别为33．9％、18．6％。全组患者的性别、ECOG评分和临床分期3项指标在治疗后的中位生存期方面差异有统计学意义（P〈0．05）。不良反应以粒细胞减少、乏力和脱发为主,分别为52．78％、36．11％和43．06％。结论国产多西他赛单药治疗老年晚期非小细胞肺癌显示了较好的疗效,患者安全性及耐受性较好,值得临床推广使用。     

表柔比星联合奥沙利铂、多西他赛治疗晚期胃癌的临床研究

目的：探讨表柔比星联合奥沙利铂、多西他赛治疗晚期胃癌的疗效及安全性。方法：26例晚期胃癌患者接受如下方案治疗：表柔比星50mg·（m^2）^-1,静脉注射,第1天;多西他赛30mg·（m^2）^-1,静脉滴注1小时,第1天,第8天;奥沙利铂85mg·（m^2）^-1,静脉滴注2小时,第1天;每21天重复。中位治疗5周期。结果：26例患者CR2例（7.69%）,PR10例（38.46%）,SD9例（34.15%）,PD5例（19.23%）,RR46.15%,DC80.30%,中位TTP6.1个月,1年生存率50%。结论：表柔比星联合奥沙利铂、多西他赛治疗晚期胃癌效果好,不良反应可以耐受。     

Synthesis and in vitro studies of gold nanoparticles loaded with docetaxel

The aim of these studies was to synthesize, characterize and evaluate the efficacy of pegylated gold nanoparticles (AuNPs) that differed in their PEG molecular weight, using PEG 550 and PEG 2000. The synthesis of the gold nanoparticles was carried out by modified Brust method with a diameter of 4–15 nm. The targeting agent folic acid was introduced by the covalent linkage. Finally, the anti-cancer drug docetaxel was encapsulated by the AuNPs by non covalent adsorption. The nanoparticles were characterized by transmission electron microscopy and used for in vitro studies against a hormone-responsive prostate cancer cell line, LnCaP. The loaded nanoparticles reduced the cell viability in more than 50% at concentrations of 6 nM and above after 144 h of treatment. Moreover, observation of prostate cancer cells by optical microscopy showed damage to the cells after exposure to drug-loaded AuNPs while unloaded AuNPs had much less effect.     

多西紫杉醇联合卡培他滨在进展期胃癌中的疗效观察

目的：探讨多西紫杉醇联合卡培他滨在进展期胃癌中的疗效。方法：选取2007年1月~2010年12月于本院进行化疗的140例进展期胃癌患者为研究对象,将其随机分为对照组（奥沙利铂、亚叶酸钙联合氟尿嘧啶组）70例和观察组（多西紫杉醇联合卡培他滨组）70例,后将两组患者治疗2个周期的总有效率及不良反应发生率进行统计及比较。结果：观察组的治疗总有效率（77.14%）明显高于对照组（54.29%）,而不良反应发生率（恶心呕吐为51.43%,骨髓抑制为34.29%,其他为22.86%）却低于对照组（恶心呕吐为68.57%,骨髓抑制为34.29%,其他为22.86%）,P均〈0.05,差异均有统计学意义。结论：多西紫杉醇联合卡培他滨在进展期胃癌中的疗效较好,安全性也较受肯定,较为可取。     

多西他赛单药治疗老年复发卵巢上皮癌临床观察

目的：观察多西他赛单药治疗老年复发卵巢上皮癌的疗效、生活质量改变以及不良反应。方法：28例经病理学或细胞学确诊的老年复发卵巢上皮癌患者（≥60岁）,应用多西他赛100mg·（m^2）^-1,静脉滴注,第1天给药,每21天为1周期;对照组给予最佳支持治疗（BSC）。结果：多西他赛治疗组有效率（RR）为32.1%,中位缓解时间为16.5个月,中位肿瘤进展时间（TTP）为11.6个月,中位生存期（OS）为22.4个月;对照组有效率（RR）为0%,中位TTP为5.3个月,中位OS为11.8个月。治疗组治疗后生存质量较治疗前及对照组均有明显提高（P〈0.01）。治疗组药物不良反应较轻,无因不良反应需停药者。结论：多西他赛单药治疗老年复发卵巢上皮癌患者疗效确切,不良反应较轻,耐受性较好。     

KIFC1 induces resistance to docetaxel and is associated with survival of patients with prostate cancer

Objectives

Prostate cancer (PCa) is a common malignancy worldwide. Docetaxel has been an important treatment option for patients with metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients with CRPC treated with docetaxel eventually become refractory. In the present study, we analyzed the expression and distribution of kinesin family member C1 (KIFC1) in human PCa by immunohistochemistry and examined the effect of inhibiting KIFC1 expression on docetaxel resistance.

扶正肺瘤方联合DP方案治疗晚期非小细胞肺癌临床研究

目的：观察扶正肺瘤方治疗晚期非小细胞肺癌的临床疗效。方法：将符合诊断标准和纳入标准的50例非小细胞肺癌晚期患者随机分为观察组和对照组,对照组仅给予DP化疗方案（多西紫杉醇联合顺氯氨铂）,观察组在DP方案化疗基础上联合扶正肺瘤方内服,观察2个疗程（3周为1个疗程）后,比较用药前后患者中医临床症状、肿瘤情况和患者生存质量,评估临床疗效。结果：观察组在中医证候疗效方面效果明显好于对照纽,差异具有统计学意义（P〈0．05）;观察组病灶稳定率为76％,明显高于对照组,差异具有统计学意义（P〈0．05）;观察组的近期治疗客观有效率大于对照组,但两组比较,差异无统计学意义（P〉0．05）;FACT—L生存质量观察提示：观察组明显好于对照组,差异具有统计学意义（P〈0．05）。结论：扶正肺瘤方联合DP方案化疗对缓解晚期非小细胞肺癌在改善中医症状方面疗效明显,并能提高患者生存质量及病灶稳定率。     

调强放疗联合同期多西他赛加顺铂化疗治疗局部晚期非小细胞肺癌

目的：探讨调强放疗（IMRT）联合同期多西他赛加顺铂化疗治疗局部晚期非小细胞肺癌（NSCLC）的疗效。方法：将2012年1月～2014年12月收治的晚期NSCLC患者分为实验组（60例）和对照组（60例）,实验组采用IMRT联合同期多西他赛加顺铂化疗治疗,对照组采用三维适形放疗联合同期多西他赛加顺铂化疗治疗。统计两组的疗效、不良反应情况、生活改善程度,利用卡方检验分析相关数据。结果：实验组的有效率和一年生存率分别为76.67%和78.33%,明显高于对照组的60.00%和56.67%（P＜0.05）。实验组发生放射性食管炎和放射性肺炎的概率明显低于对照组（P＜0.05）。治疗后,实验组生活质量良好的患者占68.33%,比对照组（56.67%）高出11.66%。结论：IMRT联合同期多西他赛加顺铂化疗治疗局部晚期NSCLC的疗效明确,可以提高一年生存率减少不良反应。