晚期非小细胞肺癌一线治疗进展

进入21世纪后,抗肿瘤新药培美曲塞的出现,给晚期非小细胞肺癌患者带来新的希望。Scagliotti等开展的JMDB这项Ⅲ期随机临床研究,对比了吉西他滨联合顺铂方案及培美曲塞联合顺铂方案一线治疗晚期非小细胞肺癌的疗效。     

培美曲塞联合顺铂治疗非小细胞肺癌的临床价值研究

目的:研究培美曲塞联合顺铂治疗非小细胞肺癌的临床价值.方法:随机选择70例我院收治的非小细胞肺癌患者,平均分成观察组与对照组,给予对照组多烯紫杉醇联合顺铂进行治疗,观察组采用培美曲塞联合顺铂进行治疗.结果:观察组治疗总有效率、不良反应发生率均优于对照组,P<0.05.结论:对非小细胞肺癌实施培美曲塞、顺铂联合治疗,不仅能提高临床治疗有效率,还能明显降低不良反应发生概率.     

培美曲塞二钠联合顺铂治疗非小细胞肺癌的疗效观察

目的观察培美曲塞二钠联合顺铂治疗非小细胞肺癌的疗效。方法选择本院收治的非小细胞肺癌患者60例,接受培美曲塞二钠联合顺铂治疗,并选取同期接受多西他赛联合顺铂治疗的45例患者。观察两组疗效与不良反应。结果两组疗效比较差异无统计学意义（P〉0.05）。观察组在胃肠道反应、感觉神经异常和肾功能异常方面发生率显著低于对照组,差异有统计学意义（P〈0.05）;且对照组不良反应多以Ⅲ～Ⅳ度为主。结论培美曲塞二钠联合顺铂治疗非小细胞肺癌效果显著,且显著降低不良反应,值得临床推广。     

PC和DC方案一线治疗晚期非小细胞肺癌的临床观察

目的比较培美曲塞（PEM）联合顺铂（DDP）与多西他赛（DOC）联合DDP治疗晚期非小细胞肺癌的临床疗效及不良反应。方法将30例晚期非小细胞肺癌（ⅢB～Ⅳ期）患者随机分为培美曲塞加顺铂组（PC组）和多西他赛加顺铂组（DC组）,每组15例。治疗2个周期后评价疗效及不良反应。结果 PC组疾病控制率为86.7%;DC组疾病控制率为80%。两组比较差异均无统计学意义（均P〉0.05）。PC组Ⅲ-Ⅳ度骨髓抑制及胃肠道反应显著低于DC组（P〈0.05）。结论培美曲塞联合顺铂治疗晚期非小细胞肺癌的疗效与多西他赛加顺铂的疗效相当,但不良反应发生率低,可作为晚期非小细胞肺癌患者的一线治疗。     

多西紫杉醇与培美曲塞分别联合顺铂对晚期非小细胞肺癌的疗效比较

目的比较多西紫杉醇联合顺铂和培美曲塞联合顺铂治疗晚期非小细胞肺癌的近期疗效和毒性反应。方法选择72例经病理学或细胞学确诊的晚期非小细胞肺癌患者,分两组进行化疗。PC组：培美曲塞500mg·m^-2第1天静脉滴注,顺铂75mg·m^-2第1～3天,21天为一周期;DP组：多西紫杉醇75mg·m^-2,第1天、第8天,静脉滴注1h,顺铂75mg·m^-2,分3天于第1～3天静脉滴注,21天为一周期。结果两组有效率、疾病控制率、一年生存率及临床受益反应等无显著统计学差异（P〉0.05）。DP组与PC组之间的无进展生存期有显著性差异（P〈0.05）。两组毒副反应的发生率差异无明显统计学意义（P〉0.05）。结论两种化疗方案治疗晚期非小细胞肺癌均具有较好的近期疗效,并发的毒副反应均可耐受。培美曲塞联合顺铂较多西紫杉醇联合顺铂疗效更好,可作为晚期非小细胞肺癌的首选治疗方案。     

培美曲塞联合顺铂不同途径治疗晚期非小细胞肺癌疗效观察

摘 要 目的： 研究培美曲塞联合顺铂不同给药途径治疗晚期非小细胞肺癌并发恶性胸腔积液的临床疗效与不良反应,为晚期非小细胞肺癌的临床治疗提供参考。方法: 老年晚期非小细胞肺癌并发恶性胸腔积液患者48例随机分为培美曲塞联合顺铂静脉滴注组(Ⅳ组) 和培美曲塞联合顺铂胸腔灌注组(IP组)。采用不同途径给药,评价比较两组疗效与药品不良反应。结果: 两组患者疗效比较,差异无统计学意义(P>0.05);IP组生活质量改善率明显高于IV组（P<0.05）,Ⅳ组的不良反应发生率明显高于IP 组( P<0.05)。结论:培美曲塞联合顺铂胸腔灌注治疗与全身化疗治疗晚期非小细胞肺癌并发恶性胸腔积液疗效相当,但胸腔灌注治疗较全身化疗治疗具有更好的安全性和耐受性。     

培美曲塞联合顺铂方案对晚期肺癌临床疗效观察

目的：探究培美曲塞联合顺铂治疗方案应用于晚期肺癌的临床疗效。方法：选取2012年1月～2015年3月我院收治的确诊为晚期非小细胞肺癌患者89例,随机分成对照组和实验组。对照组44例,采用吉西他滨联合顺铂方案治疗;实验组45例,采用培美曲塞联合顺铂方案治疗。统计评估两组临床疗效。结果：实验组在疾病控制率及有效率均显著高于对照组,差异具有统计学意义（P<0.05）;实验组药物毒副作用显著低于对照组,差异具有统计学意义（P<0.05）。结论：培美曲塞联合顺铂化疗方案应用于晚期非小细胞肺癌治疗,可取得良好的临床疗效,有效避免药物毒副作用,值得临床推广。     

培美曲塞联合顺铂治疗非小细胞肺癌的临床观察

目的探讨培美曲塞联合顺铂治疗非小细胞肺癌的临床效果。方法我院肿瘤科纳入60例非小细胞肺癌患者作为调查对象。随机分组后,对照组30例以吉西他滨联合顺铂化疗方案进行治疗;观察组30例以培美曲塞联合顺铂化疗方案进行治疗,每疗程21 d,2个疗程后对比疗效。结果观察组与对照组患者近期治疗效果比较可知,观察组治疗总有效率为90%,对照组治疗总有效率为73.3%,组间比较存在统计学意义(P<0.05)。结论培美曲塞联合顺铂治疗非小细胞肺癌近期效果明显,优于吉西他滨联合顺铂治疗。     

培美曲塞二钠联合顺铂治疗二线晚期非小细胞肺癌的临床观察

目的探讨培美曲塞二钠联合顺铂方案一线治疗失败的晚期非小细胞肺癌的疗效和毒性。方法15例既往化疗或靶向治疗失败的晚期非小细胞肺癌患者接受培美曲塞二钠联合顺铂方案化疗,其中培美曲塞二钠500mg/m2加入0.9%氯化钠注射液100ml静脉点滴超过10min;顺铂75mg/m^2。每21d重复,2周期评价疗效。结果15例患者中,部分缓解（PR）1例,进展（SD）8例,PD6例,总有效率6.6%,毒性反应主要为疲乏无力,占53.3%。白细胞下降占46.6%,恶心、呕吐占33.3%。结论培美曲塞二钠联合顺铂方案是一线治疗失败的晚期非小细胞肺癌的理想方案之一。     

培美曲塞辅助治疗晚期非小细胞肺癌的疗效和安全性分析

目的 探讨培美曲塞联合顺铂治疗晚期非小细胞肺癌的临床疗效与安全性.方法 选取医院收治的晚期非小细胞肺癌患者48例,随机均分为对照组和治疗组各24例,对照组采用西他赛联合柏顺化疗,治疗组采用美曲塞联合顺铂化疗.比较2组化疗效果和并发症发生率的差异.结果 治疗组患者完全缓解率和总缓解率均高于对照组,差异有统计学意义（P＞0.05）;治疗组患者并发症发生率显著低于对照组,差异有统计学意义（P＜0.05）.结论 美曲塞联合顺铂治疗晚期非小细胞肺癌疗效确切,并发症发生少于多西他赛联合柏顺治疗,值得临床推广使用.     

Effect of glutathione combined with cisplatin and oxaliplatin on the proliferation and apoptosis of lung carcinoma cell line

Reduced glutathione (GSH) is generally administered for patients with cancer to reduce the side-effects of anti-cancer drugs. However, whether its protective effects interfere with anti-carcinogenicity is still unclear. The aim of this study was to investigate the effect of exogenous GSH on effects of oxaliplatin (L-OHP) or cisplatin (CDDP) by observing the proliferation and apoptosis of lung carcinoma cell line A549. Cell proliferation was evaluated by sulforhodamine-B assay and morphological changes were observed by an inverted microscope. Cell cycle distribution and apoptosis rate were observed by flow cytometry (FCM). Results showed that GSH did not change the inhibiting effects of L-OHP and CDDP on A549 proliferation, and did not reduce the apoptosis induced by CDDP. The FCM analysis showed the GSH combined with the CDDP group had fewer cells in the S-phase and had an apoptotic peak, which was not significantly different from that of the CDDP alone group (p?>?0.05). These results indicated that GSH does not reduce the effects of L-OHP and CDDP to inhibit A549 growth in vitro, and doesn’t affect the apoptosis induced by CDDP.     

Induction of apoptosis by gallic acid in lung cancer cells

The apoptosis-inducing effect of gallic acid (3,4,5-trihydroxybenzoic acid) was investigated in four human lung cancer cell lines, SBC-3 (small cell carcinoma), EBC-1 (squamous cell carcinoma), A549 (adenocarcinoma) and SBC-3/CDDP (cisplatin-resistant subclone of SBC-3). Gallic acid induced apoptosis in a dose-dependent manner as evidenced by analyses of DNA fragmentation, changes in cell morphology and loss of viability. Fifty percent inhibitory concentration (IC50) values of gallic acid on the cell viability of SBC-3, EBC-1 and A549 were around 10, 20 and 60 microg/ml, respectively. The IC50 value for SBC-3/CDDP cells was almost the same as that of SBC-3, suggesting that susceptibility of cells to gallic acid-induced apoptosis is not altered by the acquisition of cisplatin resistance. The apoptotic process was effectively triggered by 30 min exposure to gallic acid. A caspase inhibitor and alpha-tocopherol effectively prevented the gallic acid-induced apoptosis, indicating the involvememt of caspase activation and oxidative processes during the course of apoptosis in gallic acid-treated cancer cells. These findings suggest the possible applicability of gallic acid in lung cancer therapy, especially to circumvent resistance to anti-cancer drugs.     

培美曲塞与多西他赛分别联合顺铂治疗晚期非小细胞肺癌的疗效观察

目的观察培美曲塞与多西他赛分别联合顺铂治疗晚期非小细胞肺癌的临床疗效和药物安全性。方法将95例晚期非小细胞肺癌患者随机分为两组,培关曲塞组48例,给予第1d静脉滴注培关曲塞500mg·m-2,第1~3d静脉滴注顺铂25mg．m-2;多西他塞组47例,给予第1、8d静脉滴注多西他赛75mg·m-2,第1—3d静脉滴注顺铂25nag·m-2。每3周为l周期,每2疗程评价临床疗效,观察不良反应的发生情况。结果培美曲塞组与多西他赛组的总缓解率分别为22．92％和17．02％．疾病控制率分别为52．08％和46．81％,差异均无统计学意义（P〉0．05）;但培关曲塞组不良反应如白细胞减少、贫血、血小板减少、恶心呕吐、肝功能异常的发生率明显低于多西他赛组（P〈0．01）。结论培美曲塞与多西他赛联合顺铂治疗非小细胞肺癌的疗效相当,但培关曲塞联合顺铂的毒副作用相对较低,患者耐受}生更好。     

microRNA-21促进人肺腺癌细胞A549对顺铂耐药性的研究

目的 研究microRNA-21(miR-21)对人肺腺癌细胞A549对于顺铂耐药性的影响及分子机制.方法 MTT法检测A549和顺铂耐药株A549/CDDP对于顺铂的敏感性,以及在A549细胞中过表达miR-21和在A549/CDDP细胞中抑制miR-21表达后对顺铂敏感性的影响;RT-PCR方法检测A549和A549/CDDP中miR-21表达情况;Western blotting检测PI3K/AKT,核因子-κB (NF-κB)信号通路的激活情况以及在过表达miR-21和抑制miR-21表达后细胞中AKT信号通路的活性变化情况.结果 相对于A549细胞,A549/CDDP对顺铂的敏感性有明显降低,而细胞中miR-21表达则明显增多.Western blotting结果表明:与A549细胞相比,A549/CDDP细胞PI3K/AKT通路被激活,NF-κB通路没有明显变化.过表达miR-21可以激活PI3K/AKT信号通路并提高A549细胞对顺铂的耐药性,相反地,抑制miR-21表达抑制了A549/CDDP细胞中的AKT通路的活化情况并降低了A549/CDDP细胞对顺铂的耐药性.结论 miR-21可以促进肺癌细胞A549对顺铂的耐药性,其机制与PI3K/AKT信号通路的激活有关.     

YM-155协同顺铂杀伤非小细胞肺癌细胞的机制研究

目的 探讨survivin小分子抑制剂YM-155对非小细胞肺癌顺铂化疗的协同治疗作用并研究其机制。方法 MTT法检测YM-155和顺铂对非小细胞肺癌细胞系A549的杀伤活性。Western blot试验检测A549细胞中survivin、细胞色素C、凋亡诱导因子、caspase-9和caspase-3的表达水平。流式细胞术检测A549细胞的线粒体膜电位和凋亡率。结果 YM-155能增强顺铂的抗肺癌活性,显著降低顺铂对A549细胞的半抑制浓度（IC₅₀）。YM-155处理能显著抑制A549细胞中survivin的表达。顺铂+YM-155组A549细胞的线粒体膜电位明显低于顺铂单治疗组。顺铂+YM-155组A549细胞的凋亡率,细胞色素C、凋亡诱导因子释放水平以及caspase-9、caspase-3活化水平均明显高于顺铂单治疗组。顺铂+YM-155+survivin质粒组A549细胞的相对细胞活力和线粒体膜电位明显高于顺铂+YM-155组。顺铂+YM-155+survivin质粒组A549细胞的凋亡率、细胞色素C、凋亡诱导因子释放水平以及caspase-9、caspase-3活化水平均明显低于顺铂+YM-155组。结论 YM-155通过抑制survivin的表达能够增强顺铂对非小细胞肺癌细胞线粒体途径凋亡的诱导活性。     

Myriocin induces apoptotic lung cancer cell death via activation of DR4 pathway

It has been known that myriocin inhibits melanoma growth. However, the effects and action mechanisms of myriocin on lung cancer cell growth have not been reported. In this study, we examined whether myriocin isolated from Mycelia sterilia inhibits cell growth of lung cancer cells (A549 and NCI-H460) as well as possible signaling pathways involved in cell growth inhibition. Different concentrations of myriocin inhibited the growth of lung cancer cells through the induction of apoptotic cell death. Consistent with cancer cell growth inhibition, myriocin induced the expression of death receptors (DRs) as well as p-JNK and p-p38 in both cell lines. Moreover, the combination of myriocin with DR4 ligand TRAIL, and other well known anti-tumor drugs (docetaxel and cisplatin) synergistically inhibited cancer cell growth, and induced DR4 expression. These results showed that myriocin inhibits lung cancer cells growth through apoptosis via the activation of DR4 pathways, and enhanced anti-cancer effects with well known drugs. Thus, our study indicates that myriocin could be effective for lung cancer cells as an anti-cancer drug and/or a conjunction agent with well known anti-cancers.     

Gallic Acid Hindered Lung Cancer Progression by Inducing Cell Cycle Arrest and Apoptosis in A549 Lung Cancer Cells via PI3K/Akt Pathway

This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.     

贝伐单抗辅助培美曲塞联合顺铂化疗治疗非小细胞肺癌的临床观察

目的：探讨贝伐单抗辅助培美曲塞联合顺铂化疗治疗非小细胞肺癌的临床应用价值。方法将2007年1月-2008年12月我院收治的240例进展期非小细胞肺癌患者纳入研究,随机分为观察组（给予贝伐单抗＋培美曲塞＋顺铂化疗）和对照组（给予培美曲塞＋顺铂化疗）,每组120例,观察和比较两组化疗后的近期疗效、远期疗效以及不良反应的发生情况。结果（1）观察组的客观有效率和疾病控制率均显著高于对照组,差异有统计学意义（P〈0.05）;（2）观察组患者的1年、3年、5年生存率均显著高于对照组,无进展生存时间和总生存时间均明显长于对照组,差异有统计学意义（P〈0.05）;（3）两组患者不良反应的发生率比较,差异无统计学意义（P〉0.05）。结论贝伐单抗辅助培美曲塞联合顺铂化疗方案有助于促进非小细胞肺癌的缓解,延长患者的生存时间,且不增加不良反应,具有积极的临床应用价值。     

川楝素下调ATF2蛋白的表达增强顺铂对肺癌细胞的凋亡诱导活性研究

目的 探讨川楝素辅助治疗是否能增强顺铂对肺癌细胞的凋亡诱导活性并研究其机制。方法 MTT法检测肺癌细胞系A549在顺铂和川楝素处理下的细胞活力。Western blot试验检测顺铂和川楝素对A549细胞ATF2磷酸化水平,Bcl-xl蛋白表达水平、细胞色素c释放水平、caspase-9和caspase-3活化水平的影响。流式细胞术检测A549细胞在顺铂和川楝素联合处理下的细胞凋亡率。结果 MTT试验结果显示,川楝素辅助治疗能明显提降低顺铂对A549的IC₅₀。Western blot试验结果显示川楝素处理能显著抑制A549细胞ATF2的表达和磷酸化。MTT试验结果显示,转染ATF2表达质粒显著抑制川楝素对顺铂的协同抗肺癌活性。Western blot和流式细胞试验结果显示,川楝素能显著抑制A549细胞中顺铂诱导的Bcl-xl表达水平的上调,进而促进A549细胞中顺铂诱导的细胞色素c的释放、caspase-9和caspase-3活化及A549细胞的凋亡水平。结论 川楝素通过抑制ATF2蛋白的磷酸化增强顺铂对肺癌细胞的凋亡诱导活性。     

Trichostatin A sensitizes cisplatin-resistant A549 cells to apoptosis by up-regulating death-associated protein kinase

Aim:

To investigate the apoptosis-inducing effect of trichostatin A (TSA) in the human lung adenocarcinoma cisplatin-resistant cell line (A549/CDDP) and to examine whether TSA can enhance sensitivity to cisplatin treatment and the underlying molecular mechanisms of such an enhancement.

Methods:

Cell viability was evaluated using the Neutral Red assay. Apoptosis was assessed using Hoechst 33258 staining and flow cytometry analysis. Protein expression was detected by Western blotting. To determine the role of Death-associated protein kinase (DAPK) in TSA-induced apoptosis in the A549/CDDP cell line, cells were transfected with pcDNA3.1(+)-DAPK, which has a higher expression level of DAPK compared to endogenous expression, and DAPK activity was inhibited by both over-expression C-terminal fragment of DAPK which may competitive binding DAPK substrates to inhibit the function of DAPK and RNA interference.

Results:

TSA induced apoptosis in both A549 cells and A549/CDDP cells. TSA enhanced the sensitivity of A549/CDDP cells to cisplatin, along with concomitant DAPK up-regulation. When DAPK was over-expressed, A549/CDDP cells became sensitive to cisplatin and the cytotoxicity of TSA could be increased. Moreover, the cytotoxicity of TSA could be alleviated by inhibition of DAPK activity by the expression of a recombinant C-terminal fragment of DAPK or RNA interference.

Conclusion:

TSA induced sensitivity to cisplatin treatment in cisplatin-resistant A549 cells. The up-regulation of DAPK is one of the mechanisms mediating sensitization to TSA-induced apoptosis in cisplatin-resistant cells.