血管内皮生长因子和新生血管在非小细胞肺癌中的表达及其意义

目的研究血管内皮生长因子（vascular endothelial growth factor, VEGF）和新生血管在不同分期非小细胞肺癌（non-small cell lung cancer,NSCLC）中的表达及其相互关系. 方法共收集79例原发性NSCLC手术标本和12例尸检正常肺组织,用免疫组织化学法（S-P法）检测,用免疫组化图象分析系统进行结果处理. 结果非小细胞肺癌中VEGF和新生血管的表达水平与正常肺组织相比差异具有显著性（P〈0.05）;Ⅰ期与Ⅱ期及Ⅲ期之间相比,VEGF和新生血管的表达水平差异同样具有显著性,并且随分期越晚表达越强（P〈0.05）;不同细胞类型之间的差异无显著性（P〉0.05）.结论 VEGF的表达水平与新生血管的表达成正相关.     

Survivin在非小细胞肺癌组织中的表达及其与临床病理特征的关系

目的探讨Survivin在非小细胞肺癌（NSCLC）组织中的表达及其与临床病理特征的关系。方法应用免疫组织化学SP方法，检测100例NSCLC组织中Survivin的表达。选取已知Survivin阳性表达的10例胃癌石蜡标本作为阳性对照，10例正常肺组织作为阴性对照，以非免疫兔血清替代Survivin作为替代对照，以PBS缓冲液替代Survivin作为空白对照。采用Y2检验分析Survivin的表达状态与患者的年龄、性别，癌组织学类型、分化程度、p-TNM分期、淋巴结转移，患者生存期的关系。结果Survivin在NSLCC组织中的阳性表达率为63．0％（63／100），不同p-TNM分期、不同生存期、淋巴结有转移和无转移的NSCLC组织中Survivin阳性表达率比较有非常显著性差异（P〈0．01），患者不同年龄，不同性别，不同的癌组织学类型和分化程度，Survivin表达阳性率互相比较，均无显著性差异（P〉0．05）。结论Survivin表达阳性的NSLCC患者预后不良，Survivin的表达可作为判断NSLCC患者预后的1个指标。     

热、化疗联合治疗晚期非小细胞肺癌初探

背景与目的晚期非小细胞肺癌化疗有效率低,而热、化疗联合已在多种实体瘤的治疗中取得良好效果。本研究旨在探讨热疗与化疗联合治疗晚期非小细胞肺癌的可行性及近期疗效。方法51例晚期非小细胞肺癌患者入选,其中热化疗组(HC组)22例,单纯化疗组(C组)29例,均给予NP(长春瑞滨 顺铂)或GP(吉西他滨 顺铂)方案化疗2个周期。热化疗组使用13.8MHz局部射频热疗机同步进行热疗,每周2次,共12次。结果热化疗组有效率为22.7%,单纯化疗组为13.8%(P>0.05);热化疗组临床受益率为68.2%,而单纯化疗组为34.5%(P<0.05)。两组患者治疗前后KPS评分的变化无统计学意义。结论初步观察到热、化疗联合治疗晚期非小细胞肺癌有良好的耐受性和较好的近期疗效,值得进一步研究。     

TP与NP方案治疗晚期非小细胞肺癌的疗效比较

目的 :观察盐酸拓扑替康 +顺铂 (TP方案 )与重酒石酸长春瑞滨 (诺维本 ) +顺铂 (NP方案 )分别治疗晚期非小细胞肺癌(NSCLC)的临床疗效和不良反应。方法 :将50例NSCLC患者随机分为TP方案组 (21例 )和NP方案组 (29例 )。治疗周期均为21d ,2个治疗周期后评价疗效。结果 :TP、NP方案组有效率分别为52.4 %、51.7 % ,中位生存期分别为9.2mo、8 6mo ,均无显著性差异 (P>0.05)。NP方案组不良反应程度及发生率均高于TP方案组 ,但两组比较均无显著性差异 (P>0.05)。结论 :2种方案临床疗效相近 ,不良反应相似 ,耐受性均较好。     

生脉注射液联合健择加顺铂治疗晚期非小细胞肺癌的临床观察

目的观察生脉注射液联合健择加顺铂方案治疗晚期非小细胞肺癌的临床效果及其减毒增效作用。方法将52例晚期非小细胞肺癌患者随机分为中药加化疗组和单纯化疗组各26例。化疗组予健择1000mg／m^2第1、8天30min静滴，顺铂75mg／m^2第1天静滴，21d为1个周期；中药加化疗组于化疗前3d生脉注射液60ml加入5％GS500ml静滴。每天1次连用3周，两个周期后按照WHO实体瘤近期客观疗效评定标准进行评价。结果中药加化疗组和单纯化疗组近期有效率为46．15％和42．31％，中药加化疗组的Karnorfsky评分增加9例，单纯化疗组增加3例，中药加化疗组体重明显增加，外周血白细胞及血小板下降和贫血发生率明显较单纯化疗组低。结论生脉注射液能提高健择加顺铂方案化疗患者的生存质量，改善临床症状，减轻化疗后骨髓抑制。     

非小细胞肺癌间质炎性细胞TAMs、MCs与趋化因子IL-8、MCP-1、MIP-1的相互影响

目的测定非小细胞肺癌MVC和间质中TAMs、MCs计数以及趋化因子IL-8、MCP-1、MIP-1 mRNA的表达，探讨其间相互关系。方法用免疫组化ABC法测定40例非小细胞肺癌组织石蜡切片标本中MV和TAMs、MCs计数。以原位杂交法检测上述标本中IL-8、MCP-1、MIP-1 mRNA的表达情况。分析MV、TAMs、MCs计数和趋化因子阳性表达之间的相互关系。结果40例非小细胞肺癌组织中MV、TAMs、MCs计数和IL-8、MCP-1、MIP-1阳性表达之间以及它们相互之间均存在着密切的正相关。结论非小细胞肺癌间质炎性细胞TAMs、MCs和趋化因子IL-8、MCP-1、MIP-1能够相互协同，共同促进肿瘤血管生成。     

Analysis of glutamine dependency in non-small cell lung cancer: GLS1 splice variant GAC is essential for cancer cell growth

One of the hallmarks of cancer is metabolic deregulation. Many tumors display increased glucose uptake and breakdown through the process of aerobic glycolysis, also known as the Warburg effect. Less studied in cancer development and progression is the importance of the glutamine (Gln) pathway, which provides cells with a variety of essential products to sustain cell proliferation, such as ATP and macromolecules for biosynthesis. To this end Gln dependency was assessed in a panel of non-small cell lung cancer lines (NSCLC). Gln was found to be essential for the growth of cells with high rates of glutaminolysis, and after exploring multiple genes in the Gln pathway, GLS1 was found to be the key enzyme associated with this dependence. This dependence was confirmed by observing the rescue of decreased growth by exogenous addition of downstream metabolites of glutaminolysis. Expression of the GLS1 splice variant KGA was found to be decreased in tumors compared with normal lung tissue. Transient knock down of GLS1 splice variants indicated that loss of GAC had the most detrimental effect on cancer cell growth. In conclusion, NSCLC cell lines depend on Gln for glutaminolysis to a varying degree, in which the GLS1 splice variant GAC plays an essential role and is a potential target for cancer metabolism-directed therapy.     

Ultra-micro samples can be used for mRNA quantification of lung cancer biomarkers

Background Isolating sufficient material for molecular testing remains challenging in non-small cell lung cancer (NSCLC). The use of new ultra-microsamples (uMS) is proven sufficient for DNA and mRNA detection, but whether uMS are useful for quantifying mRNA expression is unknown. We investigated if uMS from lung cancer patients can be used to generate quantitative data on mRNA expression. Methods uMS were collected from primary tumors and lymph nodes from patients suspected of having lung cancer. mRNA was isolated, reverse-transcribed into cDNA and quantified with quantitative PCR assays for hepatocyte growth factor receptor (MET), hepatocyte growth factor (HGF), epidermal growth factor receptor (EGFR) and amphiregulin (AREG) mRNA. The fraction of tumor cells to normal cells was estimated in each sample. Results MET, HGF, EGFR, and AREG expression were evaluated in 90 samples (30 containing cancer cells and 60 without cancer cells). MET and EGFR expression were negligible in samples without cancer cells. In samples containing cancer cells, MET and EGFR could be quantified in 13 samples each. Adjustment for tumor-cell fraction made it possible to obtain a quantitative result for the tumor-cell mRNA expression of MET and EGFR. In contrast, AREG and HGF were expressed in samples without tumor cells. These samples were used to establish the AREG and HGF mRNA expression in normal cells. Seven out of 14?AR-positive and two out of eight HGF-positive samples with tumor cells were above a cut-off of the mean?+?2SD established in samples without tumor cells. Conclusion We demonstrate that uMS contain high-quality mRNA, and quantitative studies can be performed when the tumor-cell fraction is considered.     

miR-135b reverses chemoresistance of non-small cell lung cancer cells by downregulation of FZD1

BackgroundNon-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance.MethodsTo identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3′-untranslated region (3′-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay.ResultsCompared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3′-UTR of FZD1.ConclusionThe amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.