miR-30a通过靶向调控ZEB2抑制非小细胞肺癌的迁移与侵袭

目的:探讨miR-30a在非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞中的表达情况及miR-30a在肺癌细胞迁移和侵袭过程中的作用及其机制。方法:采用qRT-PCR检测miR-30a在不同NSCLC细胞株中的表达情况;采用脂质体2000转染miR-30a mimics和E盒结合锌指蛋白2（E-box binding zinc finger protein 2,ZEB2） siRNA;通过qRT-PCR检验miR-30a mimics和ZEB2 siRNA的转染效率及转染后ZEB2 mRNA的表达水平变化;Western blot检测转染miR-30a mimics和ZEB2 siRNA后ZEB2蛋白表达情况;采用双荧光素酶报告实验验证miR-30a和ZEB2的相互作用机制;划痕实验和Transwell小室侵袭实验检测上调miR-30a和干扰ZEB2对A549细胞迁移和侵袭能力的影响。结果:实验结果显示,与正常人支气管上皮细胞相比,在不同NSCLC细胞株中miR-30a的表达呈不同程度下调;NSCLC细胞转染miR-30a mimics和ZEB2 siRNA后均获得满意的转染效果:miR-30a mimics和ZEB2 siRNA明显降低了NSCLC细胞中ZEB2的mRNA和蛋白的表达水平,组间差异具有统计学意义。双荧光素酶报告实验验证miR-30a对ZEB2 3' UTR具有直接调控作用。细胞迁移实验和侵袭实验结果显示,与Blank组和NC组相比,miR-30a过表达组和ZEB2基因沉默组的A549细胞迁移和侵袭能力均明显降低,说明miR-30a mimics和ZEB2 siRNA均对A549细胞细胞迁移和侵袭有抑制作用。结论:上调miR-30a的表达水平可以负调控ZEB2转录后表达水平,通过抑制上皮-间质转化(epithelial-mesenchymal transition,EMT)的进程来抑制肺癌细胞的转移和侵袭。     

甘草酸通过调控miR-142/ZEB1 分子轴影响非小细胞肺癌HCC827 和A549 细胞的恶性生物学行为

目的：探讨甘草酸（GA）通过调控miR-142/锌指E 盒结合的同源盒蛋白1（ZEB1）分子轴对非小细胞肺癌（NSCLC）HCC827 和A549 细胞增殖、侵袭和迁移的影响。方法：HCC827 和A549 细胞培养和转染完成后,分成4 组：NC组（未经转染+3mmol/L GA）、miR-142 inhibitor 组（敲降miR-142+3 mmol/L GA）、pcDNA3.1-ZEB1 组（过表达ZEB1+3 mmol/L GA）和pcDNA3.1-ZEB1+miR-142 mimic 组（过表达ZEB1 及miR-142+3 mmol/L GA）。采用qPCR检测不同浓度GA处理后HCC827 和A549 细胞中miR-142 的表达水平,WB实验检测HCC827 和A549 细胞中ZEB1 蛋白的表达水平,采用MTT和Transwell 检测HCC827 和A549细胞的增殖、侵袭和迁移能力,采用双荧光素酶报告基因检测miR-142 与ZEB1 的靶向关系。结果：GA显著抑制HCC827 和A549 细胞的增殖、侵袭和迁移,且显著上调miR-142 的表达水平（P<0.05 或P<0.01）;miR-142 通过靶向结合ZEB1 的3''-UTR 区域下调ZEB1 的表达水平（P<0.05 或P<0.01）;进一步实验证实,GA通过上调miR-142 抑制ZEB1 的表达水平,进而抑制HCC827 和A549 细胞增殖、侵袭和迁移（P<0.05 或P<0.01）。结论：GA能够抑制NSCLC HCC827 和A549 细胞增殖、侵袭和迁移,其机制为GA通过上调miR-142对ZEB1 的抑制作用,从而抑制HCC827和A549 细胞的恶性生物学行为。     

miR-21靶向Atg5对非小细胞肺癌A549细胞自噬调控促进细胞增殖、迁移和侵袭的实验研究

目的  探讨miR-21通过靶向作用自噬相关靶基因5（Atg5）调控非小细胞肺癌（NSCLC）自噬的作用机制及其在A549细胞增殖、迁移及侵袭中的作用。方法  无义核酸序列NC（NC组）、miR-21 模拟物（miR-21 mimics组）、miR-21抑制物（miR-21 抑制组）分别转染A549细胞, CCK-8检测细胞增殖情况;划痕实验检测细胞迁移能力; Transwell侵袭实验检测细胞侵袭能力。双荧光素酶报告实验验证miR-21和Atg5之间的靶向关系。Western blotting检测LC3B-II、p62和Atg5蛋白的表达。结果  与NC组比较,miR-21 mimics组细胞增殖、迁移、侵袭能力均上调,miR-21 抑制组细胞增殖、迁移、侵袭能力均下调（P＜0.05）。双荧光素酶报告实验结果显示,miR-21显著抑制野生型Atg5 3’-UTR质粒转染细胞的荧光素酶活性（P＜0.05）,但对突变型Atg5 3’-UTR的基因报告质粒与miR-21 mimics共转染之后,并未对荧光素酶活性产生影响。NC组LC3B-II蛋白表达量为1.24±0.059,低于miR-21 mimics组的1.98±0.077,高于miR-21抑制组的0.52±0.021（P＜0.05）;NC组p62蛋白表达量为0.62±0.021,高于miR-21 mimics组的0.45±0.020,低于miR-21抑制组的0.79±0.031（P＜0.05）;NC组Atg5蛋白表达量为1.17±0.025,高于miR-21 mimics组的0.38±0.014,低于miR-21抑制组的1.40±0.039（P＜0.05）。与NC组比较, 3-MA处理降低miR-21 mimics转染诱导的A549细胞增殖能力（P＜0.05）;划痕实验和Transwell实验表明,3-MA处理抑制了miR-21mimics转染诱导的A549细胞的迁移和侵袭,差异有统计学意义（P＜0.05）。结论  miR-21靶向Atg5调控NSCLC自噬促进细胞增殖、迁移和侵袭。     

miR-1269a 在食管癌组织中的表达及其对KYSE30 细胞恶性生物学行为的影响

[摘要] 目的：探讨miR-1269a 在食管癌组织中的表达及其对KYSE30 细胞恶性生物学行为的影响,并研究其可能的作用机制。方法：选取90 例在河北医科大学第四医院通过手术切除的食管癌组织标本,并收集正常食管永生化上皮细胞和食管癌细胞系,应用qPCR 实验检测癌组织和细胞系miR-1269a 的表达水平。将miR-1269a 的mimics 和inhibitor 分别转染食管癌细胞KYSE30 后,用MTS、Transwell 和克隆形成实验分别检测miR-1269a 对KYSE30 细胞增殖、侵袭、迁移和克隆形成能力的影响。通过生物信息学软件预测miR-1269a 的靶基因,并通过WB实验和双荧光素酶报告基因实验验证miR-1269a 对靶基因的调控作用。转染SOX6 质粒后,采用MTS、Transwell 和克隆形成实验分别检测SOX6 对KYSE30 细胞的增殖、侵袭、迁移和克隆形成能力的影响,并利用回复实验进一步验证结果。结果：食管癌组织中miR-1269a 的表达水平显著高于癌旁组织（P<0.05）;与正常食管上皮细胞相比,食管癌细胞系中miR-1269a 的表达水平显著升高（P<0.05 或P<0.01）。miR-1269a mimics 转染组KYSE30 细胞的增殖、侵袭、迁移和克隆形成能力显著高于mimics NC组（P<0.05 或P<0.01）;inhibitor 转染组KYSE30 细胞的增殖、侵袭、迁移和克隆形成能力显著低于inhibitor NC组（P<0.05 或P<0.01）。miR-1269a 可与SOX6 的3’UTR区相结合,且过表达miR-1269a 后,KYSE30细胞的SOX6 表达水平和荧光素酶报告基因的活性均显著降低（P<0.05）。回复实验表明,高表达miR-1269a 可以促进食管癌细胞增殖、侵袭和迁移（P<0.05 或P<0.01）,同时高表达SOX6 后,miR-1269a 的促进作用出现部分逆转。结论：miR-1269a 在食管癌组织和细胞系中表达上调,能够促进KYSE30 细胞的增殖、迁移、侵袭和克隆形成等恶性生物学行为,其机制可能是通过抑制靶基因SOX6 实现的。     

过表达miR-497靶向细胞周期蛋白E1抑制肺癌A549细胞的上皮间质转化

目的：探讨过表达 miR-497 靶向细胞周期蛋白 E1（cyclin E1,CCNE1）对肺癌 A549 细胞上皮间质转化（epithelialmesenchymal transition,EMT）的影响。方法：常规培养人肺癌A549细胞,细胞实验分为正常组（不加干预）、对照组（转染miR497 mimics-NC）、实验组（转染miR-497 mimics）。采用Transwell小室实验、免疫荧光染色、qPCR、Western blotting法分别检测各组细胞迁移和侵袭能力、蛋白间质标志物α-SMA和上皮标志物E-cadherin的表达、miR-497和CCNE1的表达水平,荧光素酶基因基因报告实验验证miR-497和CCNE1的靶向关系。结果：与对照组和正常组相比,实验组A549细胞迁移和侵袭的数量明显减少（均P<0.05）,细胞的间质标志物α-SMA的绿色荧光强度明显减弱（[ 36.95±5.81）vs（98.69±2.36）、（97.94±2.63）,均P<0.05],上皮标志物E-cadherin的绿色荧光强度明显增强（[ 388.41±10.93）vs（100.95±6.37）、（102.55±3.18）,均P<0.05],miR-497 的表达明显升高（均P<0.05）,CCNE1的表达均明显下降（均P<0.05）。miR-497能够靶向调控CCNE1的表达。结论：在肺癌A549细胞中miR-497能够靶向调控CCNE1的表达,上调miR-497的表达后能明显抑制A549细胞迁移和侵袭能力,影响EMT相关蛋白的表达。     

miR-145通过靶向抑制SMAD3的表达抑制非小细胞肺癌细胞侵袭能力

目的:探讨miR-145靶向调控SMAD3的表达对非小细胞肺癌细胞侵袭能力的影响。方法:采用qRT-PCR检测miR-145和SMAD3在30例非小细胞肺癌组织和癌旁组织中的表达水平并分析其相关性。利用靶基因预测网站预测miR-145的潜在靶基因SMAD3,利用双荧光素酶报告基因实验验证。利用细胞转染实验对非小细胞肺癌A549细胞进行了miR-145 mimics、miR-145 inhibitor、siRNA SMAD3及其相关对照的细胞转染,采用Transwell实验检测转染后A549细胞侵袭能力的变化。使用Western blot检测上调或下调miR-145表达对A549细胞中SMAD3蛋白表达的影响。结果:qRT-PCR结果显示,非小细胞肺癌组织中miR-145低表达,SMAD3高表达,且两者表达水平呈负相关。靶基因预测及验证实验结果显示miR-145可以与SMAD3 的 3'-UTR特异性结合,SMAD3是miR-145的靶基因。Western blot 结果显示,转染miR-145 mimics可以显著降低SMAD3蛋白的表达水平（P<0.001）,转染miR-145 inhibitor则显著提高SMAD3蛋白的表达水平（P<0.01）。Transwell体外侵袭实验结果显示,与对照组相比,转染miR-145 mimic显著降低了A549细胞的侵袭能力（P<0.001）,转染miR-145 inhibitor显著提高了A549细胞的侵袭能力（P<0.05）;与对照组相比,敲低SMAD3的表达A549细胞的侵袭能力减弱（P<0.001）;与单独敲低SMAD3相比,共同转染siRNA SMAD3和miR-145 mimics A549细胞的侵袭能力减弱（P<0.05）,共同转染siRNA SMAD3和miR-145 inhibitor A549细胞的侵袭能力无显著差异（P>0.05）。结论:miR-145在非小细胞肺癌组织中低表达,miR-145通过靶向抑制SMAD3的表达发挥对非小细胞肺癌细胞侵袭能力的抑制作用,为临床综合治疗提供了新的作用靶点。     

p53通过促进miR-145的表达抑制肺腺癌A549细胞的干细胞特性

目的： 探讨P53 抑制肺腺癌A549细胞干细胞特性及其机制。方法： 收集2014年3月至2015年12月解放军第85医院胸外科手术切除的30例非小细胞肺癌（non-small cell lung carcinoma, NSCLC）患者癌组织及癌旁组织,采用Real-time PCR检测NSCLC组织和癌旁组织中miR-145的表达。构建人P53 基因的真核表达载体（pcDNA3.1-P53）和突变载体\[pcDNA3.1-P53 R273H(CGT-CAT)\],设计靶向P53基因的siRNA,分别转染A549细胞;细胞分为对照转染组（Vector或NC-siRNA）和实验组（Flag-P53或P53-siRNA）;Western blotting检测P53蛋白过表达和干扰效率,Real-time PCR检测OCT4和miR-145的表达,荧光双报告基因和Western blotting技术检测证实A549细胞中干细胞多能性调节基因（OCT4）为miR-145的靶标分子。结果： NSCLC组织中miR-145的表达水平明显低于癌旁组织\[(2.31±0.13) vs (3.51±0.27),P<0.01\];P53明显促进A549细胞中miR-145的表达\[(1.84±0.14) vs (1.00±0.00),P<0.01\];miR-145 mimics显著抑制A549细胞中pGL3-OCT4-3′-UTR活性(P<001)和OCT4蛋白表达水平(P<0.05),而转染miR-145抑制剂可进一步增加OCT4表达水平,且逆转P53对A549细胞的干细胞特性的抑制作用。结论：P53通过促进miR-145表达下调OCT4表达,进而明显抑制A549细胞的干细胞特性,该结果为肺腺癌的临床诊断和治疗提供了新途径。     

miR-1290通过抑制干扰素调节因子-2调控非小细胞肺癌的增殖

  目的  探讨微小RNA-1290（miR-1290）在非小细胞肺癌（non-small cell lung cancer,NSCLC）组织中的表达及其相关调控机制。  方法  采用实时荧光定量PCR检测成都市双流区第一人民医院2014年6月至2017年6月41例NSCLC患者癌组织、癌旁组织以及NSCLC细胞株A549、H460及正常支气管上皮细胞BEAS-2B中miR-1290表达;qPCR、Western blot检测癌组织、癌旁组织IRF2 mRNA和蛋白表达;将A549和H460细胞分为miR-1290 mimic组（转染miR-1290 mimic）、miR-1290 inhibit组（转染miR-1290 inhibit）和miR- 1290 NC组（不转染）。分别于转染24、48、72、96 h后采用CCK-8法检测细胞增殖能力,平板克隆形成实验检测细胞克隆形成数,Transwell小室检测细胞侵袭数,双荧光素酶报告基因实验检测miR-1290与干扰素调节因子-2（interferon regulatory factor,IRF2）3′-UTR结合情况,qPCR检测不同miR-1290表达水平的A549和H460细胞IRF2 mRNA表达。  结果  癌组织miR-1290相对表达量明显高于癌旁组织,IRF2 mRNA和蛋白相对表达量明显低于癌旁组织,差异具有统计学意义（P < 0.05）;NSCLC组织miR-1290表达与IRF2 mRNA、蛋白表达呈显著负相关（P < 0.05）。NSCLC患者中,淋巴结转移者miR-1290表达明显高于无淋巴结转移者,Ⅲ/Ⅳ期患者miR-1290表达明显高于Ⅰ/Ⅱ期,差异具有统计学意义（P < 0.05）。转染72、96 h后,A549和H460细胞miR-1290 mimic组增殖能力明显高于miR- 1290 NC组,miR-1290 inhibit组增殖能力明显低于miR-1290 NC组,差异具有统计学意义（P < 0.05）。A549和H460细胞中miR-1290 mimic组细胞克隆数和侵袭细胞数明显高于miR-1290 NC组,miR-1290 inhibit组克隆数和侵袭细胞数明显低于miR-1290 NC组,差异具有统计学意义（P < 0.05）。双荧光素酶报告基因实验显示miR-1290能与IRF2 3′-UTR结合,明显降低荧光值（P < 0.05）。A549和H460细胞中,miR-1290 mimic组IRF2相对表达量明显低于miR-1290 NC组,miR-1290 inhibit组IRF2相对表达量明显高于miR-1290 NC组,差异具有统计学意义（P < 0.05）。  结论  miR-1290在NSCLC组织和细胞中高表达,miR-1290可能通过与IRF2结合,促进肿瘤细胞的增殖和侵袭。      

miR-372-3p 在膀胱癌组织中的表达及其对膀胱癌细胞增殖、迁移与侵袭的影响

目的：检测miR-372-3p 在膀胱癌组织和转染miR-372-3p mimics 膀胱癌细胞中的表达,研究miR-372-3p 对膀胱癌5637 和T24 细胞增殖、迁移与侵袭的影响。方法：采集2016 年3 月至2017 年1 月武汉中心医院收治的6 例膀胱癌患者癌及癌旁组织（距离肿瘤边缘>5 cm）,qPCR检测膀胱癌及癌旁组织miR-372-3p 表达。采用脂质体转染法将miR-372-3p mimics 或者miRNC转入膀胱癌5637 和T24 细胞。用qPCR和Western blotting 检测转染miR-372-3p mimics 和miR-NC膀胱癌细胞miR-372-3p 和ATAD2 mRNA和蛋白E-cadherin、N-cadherin 蛋白的表达,流式细胞术检测细胞周期分布,MTT法和集落形成实验检测细胞增殖和集落形成能力,划痕实验和Transwell 侵袭实验检测细胞的迁移和侵袭能力。结果：膀胱癌组织miR-372-3p mRNA的表达显著低于癌旁组织（0.65±0.56 vs 1.76±0.34,P<0.01）。和转染miR-NC膀胱癌细胞相比,转染miR-372-3p mimics 膀胱癌细胞的miR-372-3p mRNA表达显著增加,ATAD2 mRNA和蛋白的表达显著降低,E-cadherin 蛋白表达上调,N-cadherin 蛋白表达下调,细胞周期明显阻滞,细胞集落形成和增殖能力显著降低,细胞迁移数和侵袭数减少。结论：miR-372-3p 的低表达可能与膀胱癌的发生发展有关,其通过靶向调控ATAD2 抑制膀胱癌细胞的增殖、迁移和侵袭能力,可能成为膀胱癌生物治疗的新靶标。     

miR-211通过靶向下调SATB2表达促进非小细胞肺癌细胞的增殖、迁移与侵袭

目的:探讨miR-211及SATB2基因在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织和细胞中的表达情况,探究miR-211在NSCLC细胞增殖、迁移和侵袭过程中的作用及其相关机制。方法:双荧光素酶报告系统验证miR-211和SATB2的相互作用机制;qRT-PCR检测miR-211和SATB2在NSCLC组织及癌旁组织中的表达情况;向A549细胞中转染miR-211 mimics、miR-211 inhibitor和pcDNA3.1-SATB2,检验转染效率及转染后A549细胞中SATB2 mRNA和蛋白表达水平;采用CCK-8实验和Transwell小室分别检测miR-211和SATB2表达变化对A549细胞增殖、迁移和侵袭能力的影响。结果:双荧光素酶报告系统结果提示SATB2 3' UTR是miR-211直接结合的靶位点。NSCLC组织中miR-211表达上调,SATB2表达下调,两者表达呈线性负相关(P＜0.05)。转染miR-211 mimics显著下调A549细胞中SATB2 mRNA和蛋白的表达水平(P＜0.05);转染miR-211 inhibitor和pcDNA3.1-SATB2使A549细胞中SATB2 mRNA和蛋白的表达水平增高(P＜0.05)。CCK-8实验显示,相较于对照组,miR-211过表达组的A549细胞增殖率显著增加(P＜0.05),miR-211抑制组和SATB2过表达组的A549细胞增殖能力下降(P＜0.05)。Transwell小室实验结果显示,与对照组相比,miR-211抑制组和SATB2过表达组的A549细胞迁移和侵袭能力明显降低(P＜0.05)。在miR-211过表达组共转染SATB2过表达,使miR-211介导的对A549细胞增殖、迁移及侵袭的促进作用受到抑制。结论:下调miR-211的表达可以增加NSCLC细胞中SATB2转录及转录后表达水平,从而抑制肺癌细胞的增殖、迁移和侵袭能力。     

Invasive adenocarcinoma of the lung is associated with the upper lung regions

Objectives

We postulated that ventilation–perfusion (V/Q) relationships within the lung might influence where lung cancer occurs. To address this hypothesis we evaluated the location of lung adenocarcinoma, by both tumor lobe and superior–inferior regional distribution, and associated variables such as emphysema.

Materials and Methods

One hundred fifty-nine cases of invasive adenocarcinoma and adenocarcinoma with lepidic features were visually evaluated to identify lobar or regional tumor location. Regions were determined by automated division of the lungs into three equal volumes: (upper region, middle region, or lower region). Automated densitometry was used to measure radiographic emphysema.

Results

The majority of invasive adenocarcinomas occurred in the upper lobes (69%), with 94% of upper lobe adenocarcinomas occurring in the upper region of the lung. The distribution of adenocarcinoma, when classified as upper or lower lobe, was not different between invasive adenocarcinoma and adenocarcinoma with lepidic features (formerly bronchioloalveolar cell carcinoma, P = 0.08). Regional distribution of tumor was significantly different between invasive adenocarcinoma and adenocarcinoma with lepidic features (P = 0.001). Logistic regression analysis with the outcome of invasive adenocarcinoma histology was used to adjust for confounders. Tumor region continued to be a significant predictor (OR 8.5, P = 0.008, compared to lower region), whereas lobar location of tumor was not (P = 0.09). In stratified analysis, smoking was not associated with region of invasive adenocarcinoma occurrence (P = 0.089). There was no difference in total emphysema scores between invasive adenocarcinoma cases occurring in each of the three regions (P = 0.155). There was also no difference in the distribution of region of adenocarcinoma occurrence between quartiles of emphysema (P = 0.217).

Conclusion

Invasive adenocarcinoma of the lung is highly associated with the upper lung regions. This association is not related to smoking, history of COPD, or total emphysema. The regional distribution of invasive adenocarcinoma may be due to V/Q relationships or other local factors.     

小细胞肺癌与非小细胞肺癌的CT特征对比研究

目的:比较小细胞肺癌与非小细胞癌的CT表现,探讨小细胞肺癌的CT特征.方法:140例患者经肺穿刺活检病理结果分为小细胞肺癌组(35例)与非小细胞肺癌组(105例),分析两组患者的CT特征.结果:两组CT表现特征对比,在病灶长径与支气管关系、有无毛刺、是否存在胸膜凹陷、是否累及纵隔大血管、是否存在远处转移、是否累及叶、段支气管方面差异有统计学意义(P＜0.01).结论:小细胞肺癌的CT表现特点为病灶与支气管长径多平行,周边光滑、毛刺少见,常累及叶支气管、甚至累及段支气管,胸膜凹陷少见,常累及纵隔大血管等.     

Small cell lung cancer transformation from EGFR-mutated lung adenocarcinoma: A case report and literatures review

Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have markedly improved the response of non-small cell lung cancer (NSCLC) with EGFR-mutant patients. However, these patients inevitably come cross acquired resistance to EGFR-TKIs. The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with EGFR-TKIs is rare, which leads to resistance to EGFR-TKIs.

The present case concerns a case of a 38-year-old man presenting with cough and dyspnea. Radical resection was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient suffered pleural metastasis after successful treatment with surgery and adjuvant treatment. So, erlotinib was administered with 18 months. Because of enlarged pleural nodule, repeat biopsy identified an SCLC and chemotherapy was started. However, despite the brief success of chemotherapy, our patient suffered brain metastasis.

Our case emaphsizes both the profile of transformation from NSCLC to SCLC and the importance of repeat biopsy dealing with drug resistance. We also summarize the clinical characteristics, mechanisms, predictors of SCLC transformation, treatment after transformation and other types of transformation to SCLC.     

葫芦素E对非小细胞肺癌细胞的生长抑制作用

目的:体外观察葫芦素E（cucurbitacin E,CuE）对非小细胞肺癌细胞系A549增殖的影响及分子作用机制。方法:采用MTT法检测不同浓度 CuE（0、1、10、100以及1000nmol/L）处理A549细胞24、48和72小时后的细胞增殖情况。流式细胞仪检测CuE对A549细胞凋亡的影响。 Western blot法检测被处理细胞中p-STAT3、p-Raf-1、p-MEK1/2、p-ERK1/2、Bcl-2、Fas蛋白表达水平的变化。结果:CuE可显著抑制A549细胞的增殖（P＜0.05）,且呈时间和浓度依赖性。流式细胞仪检测显示随着CuE作用浓度的逐渐升高（0、100、200、400nmol/L）,A549细胞凋亡率由（4.63±0.70）%分别提高到（6.80±0.10）%、（20.53±0.49）%、（24.57±0.55）%,差异有统计学意义（P均<0.05）。Western blot结果显示CuE处理A549细胞,可降低p-STAT3、p-Raf-1、p-MEK1/2、p-ERK1/2、Bcl-2蛋白表达水平,增强Fas蛋白表达水平,且上述作用随CuE浓度升高而增强。结论:CuE可显著抑制A549细胞的增殖并诱导凋亡,其作用机制与阻断STAT3和Raf/MEK/ERK信号通路,同时激活Fas信号通路有关。     

Clear cell tumor of the lung

Clear cell tumor of the lung is a rare benign tumor. We report herein a case of clear cell tumor of the lung. A 45 year-old woman with a round mass lesion of approximately 2 cm diameter on chest X-ray underwent a thoracotomy. Pathologic examination revealed sheets of large round or polygonal cells with clear cytoplasm and immunoreactive positivity for HMB-45 and vimentin. Investigation with abdominal CT scans showed no evidence of renal disease, and the tumor was diagnosed as clear cell tumor of the lung.     

Toward an early diagnosis of lung cancer: an autoantibody signature for squamous cell lung carcinoma

Serum‐based diagnosis offers the prospect of early lung carcinoma detection and of differentiation between benign and malignant nodules identified by CT. One major challenge toward a future blood‐based diagnostic consists in showing that seroreactivity patterns allow for discriminating lung cancer patients not only from normal controls but also from patients with non‐tumor lung pathologies. We addressed this question for squamous cell lung cancer, one of the most common lung tumor types. Using a panel of 82 phage‐peptide clones, which express potential autoantigens, we performed serological spot assay. We screened 108 sera, including 39 sera from squamous cell lung cancer patients, 29 sera from patients with other non‐tumor lung pathologies, and 40 sera from volunteers without known disease. To classify the serum groups, we employed the standard Naïve Bayesian method combined with a subset selection approach. We were able to separate squamous cell lung carcinoma and normal sera with an accuracy of 93%. Low‐grade squamous cell lung carcinoma were separated from normal sera with an accuracy of 92.9%. We were able to distinguish squamous cell lung carcinoma from non‐tumor lung pathologies with an accuracy of 83%. Three phage‐peptide clones with sequence homology to ROCK1, PRKCB1 and KIAA0376 reacted with more than 15% of the cancer sera, but neither with normal nor with non‐tumor lung pathology sera. Our study demonstrates that seroreactivity profiles combined with statistical classification methods have great potential for discriminating patients with squamous cell lung carcinoma not only from normal controls but also from patients with non‐tumor lung pathologies. © 2008 Wiley‐Liss, Inc.     

Enhancement of artificial lung metastases by misonidazole

The effect of treatment with the hypoxic cell radiosensitizer misonidazole on the formation of artificial lung metastases was examined. Both single treatments with large doses of misonidazole and fractionated treatments with smaller doses of misonidazole were found to increase the number of lung tumors developing after intravenous injection of EMT6 mouse mammary carcinoma cells. The immunologic and physiologic effects of the nitroimidazole were postulated to be responsible for the enhancement of lung tumor formation.     

Expression of BCRP gene in the normal lung tissue and lung cancer

The development of multidrug resistance during chemotherapy was found to be correlated with over-expression of two transmembrane xenobiotic transporter protein, P-glycoprotein (Pgp) and the multidrug resistance protein (MRP).[1(6] Because the discordance between drug efflux and P-glycoprotein expression in human leukemic cells and unclear drug resistance exhibited during chemotherapy in advanced breast cancer patients, a alternative multidrug resistance transporter might be existed and has b…     

非小细胞肺癌脑转移的研究进展

非小细胞肺癌脑转移的治疗对肿瘤学家是一种挑战。虽然近年脑转移研究有所进展,但生存率并不乐观。本文阐述非小细胞肺癌脑转移的临床特点、诊断方法、预后因素以及治疗进展。脑转移最常见的症状为因颅内压力增高所致的头痛。评价脑转移时,头颅MRI较CT优越。最常用的预后标准是肿瘤放射治疗组(RTOG)的RPA分级。关于全脑放疗、立体定向放射外科、手术以及化疗治疗脑转移的作用仍存在争议。全脑放疗常作为脑转移的标准治疗方案。SRS对单一或多个脑转移灶的治疗可代替外科切除。许多数据证明化疗有较好的颅内作用,这引起全身化疗治疗脑转移的研究热点。确立预后因素和其他临床特点后,才能制定最适合个体患者的治疗。     

Immunotherapy – new perspective in lung cancer

Lung carcinoma is associated with a high mortality worldwide, being the leading cause of cancer death. It is mainly classified into squamous non-small cell lung cancer (NSCLC), non-squamous NSCLC, and small cell lung cancer. However, such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment. Therapies can be used in adjuvant and palliative settings. Regarding immunotherapy, it has been widely tested in both first or subsequent palliative lines. In this sense, drugs such as pembrolizumab, nivolumab, atezolizumab, ipilimumab, avelumab, and durvalumab have been assessed in large studies. Some of these trials have also studied these medicines in adjuvant and in maintenance therapy. In recent years, advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed. Immunotherapy has increased the overall survival in squamous NSCLC, non-squamous NSCLC, and small cell lung cancer. However, it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support. In order to show how immunotherapy is being applied in the treatment of lung carcinoma, we reviewed the main studies in adjuvant and palliative scenarios. What is the better scheme? What is the better combination? What is the better dose? When should we use immunotherapy? Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency? Some of these questions have already been answered, while others require more investigations.