多西紫杉醇作为晚期非小细胞肺癌的二线治疗药物的系统评价

目的系统评价多西紫杉醇作为晚期非小细胞肺癌二线治疗药物的疗效、不良反应、生存质量及给药方案。方法电子检索Medline（1991～2008．2）、Pubmed、CBMDisc等数据库，对符合纳入标准的研究，采用RevMan4．2软件进行Meta分析。结果共有8篇文献纳入研究。多西紫杉醇治疗晚期非小细胞肺癌疗效与支持性疗法相比，疾病进展期和中位生存期明显延长，分别是10．6周和6．7周（P〈0．001）、7．0月和4．6月（P〈0．001），1年生存率分别为37％和11％。不良反应研究中，3—4级血液学不良反应在多西紫杉醇组中发生率较高，其中高剂量组（100mg／m^2）发生率高于低剂量组（75mg／m^2）；3～4级非血液学不良反应，多西紫杉醇组和支持治疗组发生率相似。另外以长春瑞滨或异环磷酰胺为对照的研究显示，多西紫杉醇组反应率、疾病进展时间和生存率优于对照；4级血液学不良反应多西紫杉醇组高于对照组，其他3～4级非血液学不良反应的发生率无明显规律。生存质量评价（LCSS、QLQ—C30或QLQ—LC13）方面，患者自评和观察者评价均显示多西紫杉醇组优于支持治疗组。不同给药方案（3周给药和1周给药）的Meta分析结果可以看出不同给药方案在疾病控制率、反应率及1年生存率方面没有统计学差异（P〉0．05）；在嗜中性白细胞减少症、白细胞减少症的发生率上，1周给药组发生率均低于3周给药组（P〈0．01）；在非血液学不良反应如虚弱、恶心／呕吐的发生率上，不同给药方案没有统计学差异（P〉0．5）。结论多西紫杉醇可以认为是在晚期非小细胞肺癌的二线治疗中疗效确切的药物；不同的多西紫杉醇给药方案（3周vs1周），在疗效方面差异不明显，在不良反应发生率上略有差异，因此，在发生严重血液学不良反应的情况下，可以用1周给药代替3周给药进行治     

多西紫杉醇联合顺铂治疗晚期乳腺癌31例临床观察

目的观察多西紫杉醇联合顺铂方案治疗晚期乳腺癌的临床疗效和不良反应。方法晚期乳腺癌31例,其中包括既往应用蒽环类药物治疗18例,非蒽环类药物化疗13例。用多西紫杉醇75mg／m^2,第1天静滴,顺铂25mg／m^2。第1～3天静滴,21天为1周期,2周期后评价疗效。结果31例中CR3例,PR14例,总有效率为54．84％。主要不良反应为骨髓抑制、恶心呕吐和脱发,但均可耐受。结论多西紫杉醇联合顺铂治疗晚期乳腺癌疗效确切,副作用较轻可耐受。     

Clinical outcomes in a contemporary series of “young” patients with castration-resistant prostate cancer who were 60 years and younger

BackgroundThe prognosis of younger patients with prostate cancer is unclear, and the very few studies assessing those with metastatic castration-resistant prostate cancer (mCRPC) have mainly involved patients treated with older therapies. The aim of this observational study was to evaluate the clinical outcomes of a contemporary series of docetaxel-treated patients with mCRPC who were 60 years and younger.Patients and methodsWe retrospectively identified 134 patients who were 60 years and younger who were treated with docetaxel in 25 Italian hospitals and recorded their predocetaxel history of prostate cancer, their characteristics at the start of chemotherapy, and their postdocetaxel treatment history and outcomes.ResultsMost of the 134 consecutive patients with mCRPC received the standard 3-week docetaxel schedule; median progression-free survival (PFS) was 7 months, and 90 patients underwent further therapies after progression. The median overall survival (OS) from the start of docetaxel treatment was 21 months, but OS was significantly prolonged by the postprogression treatments, particularly those based on the new agents such as cabazitaxel, abiraterone acetate, or enzalutamide. OS was significantly shorter in the patients with a shorter interval between the diagnosis of prostate cancer and the start of docetaxel treatment; those who received hormonal treatment for a shorter period; those with shorter prostate-specific antigen doubling times; and those with lower hemoglobin levels, a worse performance status, and higher lactate dehydrogenase levels before starting treatment with docetaxel.ConclusionsThe findings of this first study of clinical outcomes in a contemporary series of younger patients with mCRPC showed that their survival is similar to that expected in unselected patients with mCRPC who were of any age.     

Mechanism of drug resistance identified in human lung adenocarcinoma cell line SPC-A1 selected for resistance to docetaxel

Objective  To investigate the mechanism of resistance to docetaxel in human lung cancer. Methods  Human lung carcinoma SPC-A1/Docetaxel cells were derived from parental SPC-A1 cells by continuous exposure to increasing concentration of docetaxel. The drug sensitivity was measured by MTT assay in vitro. The cDNA microarray identified a set of differentially expressed genes, and some genes were confirmed by RT-PCR. P-glycoprotein level was measured by flow cytometry analysis. Results  The results of drug sensitivity measured by MTT assay showed that SPC-A1/Docetaxel cells were 13.2-fold resistant to docetaxel and cross-resistant at varying levels to other drugs. The cDNA microarray results identified a set of differentially expressed genes, which showed 428 genes that were up-regulated and 506 genes that were down-regulated in SPC-A1/Docetaxel cells, and some genes were confirmed by RT-PCR. Flow cytometry analysis suggests expression of P-glycoprotein (P-gp) was more abundant in SPC-A1/Docetaxel cells than in the parental cells and docetaxel selection reduces the apoptotic response. Conclusion  The results suggest that docetaxel selection led to changes in gene expression that contribute to the multidrug resistance phenotype. This work was supported by a grant from the Postdoctor Research Project of Jiangsu Province (No.0602031B)     

表柔比星联合多西他赛或紫杉醇治疗乳腺癌效果差异分析

目的探讨表柔比星联合多西他赛或紫杉醇治疗乳腺癌的效果差异。方法选取2018年2月至2019年7月本院收治的86例乳腺癌患者,根据动态随机分组法将其分为对照组(n=43)和观察组(n=43),对照组采用表柔比星联合紫杉醇治疗,观察组采用表柔比星联合多西他赛治疗,比较两组临床缓解率、1年内复发率、生存时间以及不良反应发生率。结果两组患者临床缓解率差异经统计学软件检验显示无统计学意义(P>0.05);观察组1年内复发率和不良反应发生率低于对照组,生存时间长于对照组,差异经统计学软件检验显示有统计学意义(P<0.05)。结论表柔比星联合多西他赛或紫杉醇对乳腺癌的治疗效果相近,但联合多西他赛的不良反应风险更低,还可延长患者生存时间。     

Multifunctional silica nanoparticles for targeted delivery of hydrophobic imaging and therapeutic agents

This article reports the development of a multifunctional silica nanoparticle system for targeted delivery of hydrophobic imaging and therapeutic agents. Normally, silica nanoparticles have been widely used to deliver hydrophilic drugs such as doxorubicin while difficult to carry hydrophobic drugs. A strategy for loading hydrophobic drugs onto silica nanoparticles via covalent attachment was developed in this study as a universal strategy to solve this problem. Docetaxel, one of the most potent therapeutics for cancer treatment is selected as a model hydrophobic drug and quantum dots (QDs) are used as a model imaging agent. Such a multifunctional delivery system possesses high drug loading capacity, controlled drug release behavior and stable drug reservation. A mixed layer of polyethylene glycol conjugated phospholipids is formed on the nanoparticle surface to further enhance the biocompatibility and cell fusion capability of the delivery system. Folic acid as ligand is then conjugated onto the surface layer for targeting. Such a multifunctional system for targeting, imaging and therapy is characterized and evaluated in vitro. Fluorescent confocal microscopy is used to monitor the cellular uptake by specific cancer cells. Cytotoxicity studies are conducted by using MTT assay.     

Bivalent sequential binding of docetaxel to methyl-β-cyclodextrin

New docetaxel (Dtx) and cyclodextrin (CD) inclusion complexes having improved apparent water solubility (up to 9.98 mg mL⁻¹) were obtained from phase solubility diagrams. γ-CD and SBE-β-CD offered only poor solubility enhancements while considerable increases in apparent solubility were obtained with Me-β-CD (20%, w/w) and HP-β-CD (40%, w/w) (9.98 mg mL⁻¹ and 7.43 mg mL⁻¹, respectively). The complexation mechanism between Dtx and Me-β-CD was investigated by circular dichroism spectrometry, two-dimensional ¹H NMR (NOESY) in D₂O, isothermal titration calorimetry (ITC) and molecular docking calculations. Circular dichroism and NOESY confirmed the existence of non-covalent interactions between Dtx and Me-β-CD and suggested that the tert-butyl group (C₆-C₉) and two aromatic groups (C₂₄-C₂₉ and C₃₀-C₃₅) of Dtx interacted with the Me-β-CD molecules. The combination of ITC results to molecular docking calculations led to the identification of an unconventional sequential binding mechanism between Me-β-CD and Dtx. In this sequential binding, a Me-β-CD molecule first interacted with both tert-butyl and C₃₀-C₃₅ aromatic groups (K₁: 744 M⁻¹). Then a second Me-β-CD molecule interacted with the C₂₄-C₂₉ aromatic group (K₂: 202 M⁻¹). The entropy of the first interaction was positive, whereas a negative value of entropy was found for the second interaction. The opposite behavior observed for these two sites was explained by differences in the hydrophobic contact surface and functional group flexibility.     

培美曲塞与DP方案在非小细胞肺癌二线治疗中临床疗效观察

目的 比较DP 方案与培美曲塞在晚期非小细胞肺癌(NSCLC) 治疗中的近期疗效和毒副反应.方法 NSCLC 患者27例.分别接受DP方案和培美曲塞两种方案的治疗,其中培美曲塞组13例,DP组14例,治疗2个周期后分别评价疗效和毒副反应.结果 有效率培美曲塞组为23.1%,DP组为28.6%,差异无统计学意义(P>0....     

多西他赛联合卡培他滨治疗耐药性晚期乳腺癌疗效观察

目的观察及评价周剂量多西他赛联合卡培他滨治疗蒽环类药物耐药晚期乳腺癌的疗效和不良反应。方法46例经病理证实的蒽环类耐药性晚期乳腺癌患者,采用多西他赛联合卡培他滨方案化疗,多西他赛35mg／m^2、静脉滴注、d1、d8,卡培他滨1250mg／（m^2·d）,分2次口服、d1～d14,21d为1个周期,化疗周期数为2～8个周期,中位周期数4个,直至病情进展或不良反应无法耐受。结果46例患者中,完全缓解6例（13．0％）,部分缓解23例（50．0％）,稳定13例（28．9％）,疾病进展4例（8．7％）,有效率为63．0％。不良反应主要为胃肠道反应、骨髓抑制和手足综合征,患者均可耐受。结论周剂量多西他赛联合卡培他滨治疗蒽环类耐药性晚期乳腺癌的疗效确切及毒副反应轻,患者耐受性好,值得临床推广。