新型雌激素受体 GPR30在非小细胞肺癌中的表达

目的：研究 GPR30与 ERα、ERβ、HER2、HER3在非小细胞肺癌中的表达及相关性,并分析 GPR30和ERβ与临床病理特征之间的关系。方法：采用免疫组织化学方法检测60例术后非小细胞肺癌组织样本中GPR30、ERα、ERβ、HER2、HER3的表达。结果：GPR30表达在有淋巴结转移、腺癌、低分化、III 期肿瘤中明显高于无淋巴结转移、鳞癌、中高分化、I - II 期肿瘤,差异有统计学意义（P <0.05）。ERβ表达在腺癌中显著高于鳞癌（P <0.05）。GPR30表达与 ERβ和 HER3呈中度正相关（r =0.607,P =0.000;r =0.510,P =0.000）。结论：GPR30与 ERβ或 HER2- HER3的信号途径可能存在相关性,共同参与非小细胞肺癌的发生发展。     

非小细胞肺癌中上皮钙粘附素的表达及其意义

目的研究上皮钙粘附素(epithelialcadherin,E-cad)在非小细胞肺癌(non-smallcelllungcancer,NSCLC)中的表达,探讨E-cad与NSCLC的组织类型、病理分级、TNM分期及淋巴结转移的关系。方法应用免疫组织化学SABC法检测65例原发性NSCLC,20例癌旁组织中E-cad蛋白的表达水平。结果20例正常肺组织均阳性表达,且均匀分布于膜表面。NSCLC中E-cad表达不均匀,阳性率为32.3%,与正常组比较差异有显著性(P<0.05)。但与组织类型无关(P>0.05),与病理分级、TNM分期及淋巴结转移显著相关(P<0.05)。结论E-cad与NSCLC的发生发展呈显著负相关,低表达者预示预后不良。     

吉西他滨与放疗联合治疗非小细胞肺癌

吉西他滨是一种嘧啶核苷类似物,具有抗瘤谱广、毒副反应轻等特点,被广泛地应用于非小细胞肺癌、乳腺癌、膀胱癌、胰腺癌等各种实体瘤治疗领域中。本文综述吉西他滨联合放疗治疗局部晚期非小细胞肺癌的研究进展。     

NSCLC中EGFR基因突变与表达关系研究

目的 研究非小细胞肺癌组织表皮生长因子受体(EGFR)基因突变和蛋白表达的相关性.方法 随机选择北京协和医院胸外科2009年6月至2011年5月收治的非小细胞肺癌(non- small cell lung cancer,NSCLC)患者的石蜡包埋肺癌组织标本71例,分别以直接测序法和免疫组织化学染色法取得表皮生长因子受...     

Expression of telomeric repeat binding factor 1 in non-small cell lung cancer

BACKGROUND AND OBJECTIVES: Telomeric repeat binding factor 1 (TRF1) is crucial for forming and maintaining the protective telomeric structure. However, the relationship between TRF1 and non-small cell lung cancer(NSCLC) is not well understood. With this background, we investigated the expressions of the mRNA encoded by the TRF1 gene in cancer tissue and the paired non-cancerous tissue. We also examined whether TRF1 expression is correlated with histopathological features. METHODS: From October 2004 to August 2005, 40 patients with NSCLCs had undergone curative operations, including 29 males and 11 females. There were 20 cases of squamous cell carcinoma and 20 cases of adenocarcinoma. We measured the expression of TRF1 mRNA using RT-PCR on 40 surgically resected specimens and the paired non-cancerous tissues. RESULTS: TRF1 mRNA was significantly downregulated in cancer tissue compared with the paired non-cancerous tissue. Additionally, the expression of TRF1 mRNA was significantly associated with the grade of tumor differentiation. No significant difference of TRF1 mRNA level was found between sexes, or among different T-status, clinical stages, pathological subtypes, and lymph node metastasis. CONCLUSIONS: Downregulation of TRF1 mRNA expression appeared in lung cancer tissue. TRF1 may play a significant role in cell differentiation in NSCLC.     

miR-302b在非小细胞肺癌中的表达及意义

目的:探讨miR-302b在人非小细胞肺癌组织中的表达及与临床病理特征的关系。方法:采用实时荧光定量PCR（qRT-PCR）检测65例非小细胞肺癌组织和52例癌旁组织miR-302b的表达,分析其与临床病理特征之间的关系。结果:miR-302b在非小细胞肺癌组织中的表达明显低于癌旁组织（P<0.05）。与患者淋巴转移以及分化程度明显相关（P<0.05）。结论:miR-302b在非小细胞肺癌中低表达,提示其可能发挥抑癌基因的功能。     

盖诺联合化疗治疗非小细胞肺癌近期疗效观察

目的：观察国产去甲长春花碱（盖诺）联合顺铂化疗治疗非小细胞肺癌的疗效和安全性。方法：用NP方案：盖诺25mg/m^2 d 1、8,DDP 80－100mg/m^2 d 1。21天为1周期,至少治疗2周期。治疗28例非小细胞肺癌。结果：OR：46．4％,初治OR高达50．0％,复治为25．0％;毒副作用以白细胞减少和恶心、呕吐为常见。结论：盖诺联合顺铂治疗非小细胞肺癌疗效明显,耐受性好。     

非小细胞肺癌过继细胞免疫治疗的研究进展

目前非小细胞肺癌发病率高,预后差,需要研究新的治疗方法。肿瘤的发生、发展和转移与人体免疫系统密切相关,过继输注免疫细胞是免疫治疗的一种方法,能够显著提高机体免疫系统的抗肿瘤效应。过继输注的免疫细胞多样,如 LAK、TIL、NK、γδ T、CIK、CTL 等,通过输注不同的免疫细胞或联合其他治疗介导靶细胞凋亡,可增强抗肿瘤效应。本文介绍各种免疫细胞的抗肿瘤的机制并回顾近几年治疗非小细胞肺癌的相关试验研究。     

美伐他汀诱导人非小细胞肺癌细胞凋亡及其分子机制的研究

目的:研究美伐他汀对非小细胞肺癌细胞(nod-small-cell lung cancer,NSCLC)诱导凋亡及其分子机制。方法:应用MTT法检测美伐他汀对A549、NCI-H520细胞株的体外增殖作用,应用流式细胞仪,透射电镜,研究美伐他汀对A549、NCI-H520细胞株的细胞周期阻滞和诱导调亡的作用,应用流式细胞术和RT-PCR检测P21蛋白、P21 mRNA、XIAP mRNA的表达,以研究细胞周期阻滞和诱导调亡的机制。结果:MTT试验表明:美伐他汀对A549、NCI-H520增殖有明显的抑制作用,且表现为剂量依赖性和时间依赖性;流式细胞学显示:美伐他汀诱导A549、NCI-H520细胞G0／G1期阻滞;Annexin V结果证实美伐他汀可诱导A549、NCI-H520细胞凋亡,而且凋亡率随剂量的增加而增加。美伐他汀对A549、NCI-H520细胞P21 mRNA及P21总蛋白的表达无影响,但可使P21细胞膜蛋白的表达下降。美伐他汀作用后XIAP mRNA的表达下降,加入外源性甲羟戊酸可完全逆转美伐他汀的上述作用。结论:美伐他汀通过抑制甲羟戊酸合成途径诱导NSCLC细胞G0／G1阻滞,抑制增殖,诱导细胞凋亡,其机制可能与抑制P21蛋白异戊二烯化和下调XIAP mRNA的表达有关。     

IEP方案治疗晚期非小细胞肺癌

目的评估异环磷酰胺(IFO)、足叶乙甙(Vp-16)、顺铂(DDP)联合化疗对晚期非小细胞肺癌的疗效及毒副反应.方法用IEP方案治疗晚期非小细胞肺癌64例.结果完全缓解(CR)6例,部分缓解(PR)27例,稳定(NC)25例,进展(PD)5例.总有效率51.6%,毒性反应主要是骨髓抑制、消化反应、脱发.结论 IEP方案治疗晚期非小细胞肺癌疗效较好,毒副反应可以耐受,可作为治疗晚期非小细胞肺癌的一线方案.     

Whole blood FPR1 mRNA expression predicts both non‐small cell and small cell lung cancer

While long‐term survival rates for early‐stage lung cancer are high, most cases are diagnosed in later stages that can negatively impact survival rates. We aim to design a simple, single biomarker blood test for early‐stage lung cancer that is robust to preclinical variables and can be readily implemented in the clinic. Whole blood was collected in PAXgene tubes from a training set of 29 patients, and a validation set of 260 patients, of which samples from 58 patients were prospectively collected in a clinical trial specifically for our study. After RNA was extracted, the expressions of FPR1 and a reference gene were quantified by an automated one‐step Taqman RT‐PCR assay. Elevated levels of FPR1 mRNA in whole blood predicted lung cancer status with a sensitivity of 55% and a specificity of 87% on all validation specimens. The prospectively collected specimens had a significantly higher 68% sensitivity and 89% specificity. Results from patients with benign nodules were similar to healthy volunteers. No meaningful correlation was present between our test results and any clinical characteristic other than lung cancer diagnosis. FPR1 mRNA levels in whole blood can predict the presence of lung cancer. Using this as a reflex test for positive lung cancer screening computed tomography scans has the potential to increase the positive predictive value. This marker can be easily measured in an automated process utilizing off‐the‐shelf equipment and reagents. Further work is justified to explain the source of this biomarker.     

康莱特联合GP方案治疗晚期非小细胞肺癌临床疗效观察

目的:观察康莱特联合GP方案(吉西他滨+顺铂)治疗晚期非小细胞肺癌患者的有效性.方法:将72例晚期非小细胞肺癌患者随机分为试验组和对照组,对照组予GP方案化疗,试验组予GP化疗方案+康莱特联合治疗,比较两组治疗有效率、对生活质量影响及肿瘤标志物水平.结果:两组间治疗有效率相当,差异无统计学意义(P>0.05);试验组KPS评分改善优于对照组,差异有统计学意义(P<0.05);试验组肿瘤标志物水平低于对照组.结论:康莱特联合GP方案化疗不影响晚期非小细胞肺癌患者治疗有效率,但可降低患者血清糖链抗原CA-125、神经烯醇化酯酶(NSE)水平,明显改善患者生活质量.     

非小细胞肺癌中 AKAP12基因的表达与甲基化研究

目的：探讨 AKAP12基因甲基化与非小细胞肺癌发生发展的关系。方法：采用实时荧光定量 PCR 检测43例非小细胞肺癌患者组织中 AKAP12基因 mRNA 的 RQ 值。应用 MSP 法检测其甲基化状态,分析 RQ值、甲基化状态与临床因素的关系。结果：非小细胞肺癌 AKAP12的 RQ 值与正常组织比较差异具有统计学意义。非小细胞肺癌 AKAP12甲基化阳性率与正常组织之间差异具有统计学意义。非小细胞肺癌组织中AKAP12 mRNA 的 RQ 值在病理分型、临床分期、分化程度方面差异具有显著性。AKAP12基因甲基化在病理分型及临床分期方面比较差异具有统计学意义。非小细胞肺癌组织中甲基化组的 mRNA RQ 值较非甲基化组低,差异具有统计学意义。结论：AKAP12基因甲基化与非小细胞肺癌的发生发展可能有关。     

The validation of estrogen receptor 1 mRNA expression as a predictor of outcome in patients with metastatic non‐small cell lung cancer

The prognostic role of estrogen receptors in lung cancer is not validated. Results from patients with early stage non‐small lung cancer patients indicate a prognostic role of estrogen receptor 1 (ESR1) mRNA expression in these patients. Automated RNA extraction from paraffin and RT‐quantitative PCR was used for evaluation of tumoral ESR1 and progesterone receptor (PGR) mRNA expression. The test cohort consisted of 31 patients with advanced or metastatic non‐small cell lung cancer (NSCLC) patients, treated in a first‐line registry trial. For validation, 53 patients from a randomized multicentre first‐line study with eligible tumor samples were evaluated. There was no significant correlation of ESR1 expression with clinical characteristics. ESR1 high expression was of significant positive prognostic value in the training set with a median overall survival (OS) of 15.9 versus 6.2 months for high versus low ESR1 expression patients (p = 0.0498, HR 0.39). This could be confirmed in the validation cohort with a median OS of 10.9 versus 5.0 months in ESR1 high versus low patients, respectively (p = 0.0321, HR 0.51). In the multivariate analysis adjusted for histological subtype, gender, age and performance status, ESR1 expression remained an independent prognostic parameter for survival in both cohorts. In contrast to ESR1, PGR expression was not able to separate prognostic groups or to predict outcome significantly (for OS; p = 0.94). Our study shows that ESR1 mRNA as assessed by qPCR represents a reliable method for detecting ESR1 expression in NSCLC and that ESR1 expression is an independent prognostic factor in metastatic NSCLC.     

Role for dipeptidyl peptidase IV in tumor suppression of human non small cell lung carcinoma cells

Lung cancer is the leading cause of cancer death. Lung cancers produce a variety of mitogenic growth factors that stimulate tumor cell proliferation and migration. The cell surface protease, dipeptidyl peptidase IV (DPPIV), is involved in diverse biologic functions, including peptide-mediated cellular growth and differentiation. DPPIV is expressed in various normal tissues, including lung tissue, and its expression is lost in many types of human cancers. DPPIV expression and its enzymatic activity are detected in normal bronchial and alveolar epithelium but different histologic subtypes of lung carcinomas lose DPPIV expression. To investigate the role of DPPIV in lung carcinoma, we examined the expression of DPPIV at both mRNA and protein levels in non small cell lung cancer (NSCLC) cell lines and normal human bronchial epithelial cells. DPPIV expression was detectable in normal lung epithelial cells, but was absent or markedly reduced in all NSCLC cell lines at both mRNA and protein levels. Restoration of DPPIV expression in NSCLC cells resulted in profound morphologic changes, inhibition of cell proliferation, anchorage-independent growth, in vitro cell migration and tumorigenicity in nude mice. DPPIV reexpression also correlated with increased p21 expression, leading to induction of apoptosis and cell cycle arrest in G1 stage. These effects were accompanied by increased expression of cell surface proteins, fibroblast-activating protein (Fapalpha) and CD44 that are associated with suppression of tumor growth and metastasis. Thus, DPPIV functions as a tumor suppressor, and its downregulation may contribute to the loss of growth control in NSCLC cells.     

GP方案治疗晚期非小细胞肺癌疗效观察

目的观察GP方案治疗晚期非小细胞肺癌的疗效与毒性反应。方法60例符合条件的患者接受下述联合方案化疗2周期,吉西他滨1250mg/m2iv d1、8,顺铂25 mg/m2iv d1~3,至少2周期进行评价。结果本组患者总有效率为46.67%;III期及IV期与复发转移者比较疗效均无显著性差别;鳞癌与腺癌比较疗效无显著性差异。毒性反应以骨髓抑制为主,III~IV度白细胞减少发生率61.82%,其中粒细胞减少性发热30.91%。其它不良反应耐受性良好。结论GP方案是治疗晚期非小细胞肺癌有效、耐受性良好的方案。     

Kras基因突变的非小细胞肺癌靶向治疗进展

肺癌占恶性肿瘤死因的第一位,其中非小细胞肺癌（NSCLC）占绝大多数。已发现三分之一的NSCLC和Kras基因突变直接相关,故针对Kras突变的靶向治疗是近年来肺癌研究的热点。本文从抑制Kras膜定位、直接抑制Kras、抑制其下游信号和抑制Kras突变的协同致死因子四个方面对目前的研究进展做一简要概论。     

肺癌VEGF表达的免疫组化定量分析与预后的相关研究

目的 :探讨非小细胞肺癌 (NSCLC)肿瘤组织 (VEGF)表达程度与其组织学类型、淋巴结转移及预后的关系。方法 :对随访的 74例NSCLC术后病例采用免疫组化方法检测肿瘤组织切片中VEGF蛋白表达程度 ,并经图象分析系统对VEGF表达程度进行定量测定。结果 :肺腺癌组和淋巴结转移组中的VEGF表达程度分别比肺鳞癌组和淋巴结无转移组明显增高 ,差异具有显著意义 (P <0 0 5～ 0 0 1)。在腺癌中 ,淋巴结转移组的VEGF表达程度比淋巴结无转移组显著增高 (P <0 0 5 )。单变量生存分析显示 ,VEGF高表达组与VEGF低表达组相比 ,前者生存时间明显下降 ,具有显著性差异 (P <0 0 1)。结论 :NSCLC肿瘤组织VEGF表达程度与其肿瘤的生物学行为及预后密切相关。     

Clinical evaluation of microRNA expression profiling in non small cell lung cancer

Deregulation of miRNAs expression levels has been detected in many human tumor types, and recent studies have demonstrated the critical roles of miRNAs in cancer pathogenesis. Numerous recent studies have shown that miRNAs are rapidly released from tissues into the circulation in many pathological conditions. The high relative stability of miRNAs in biofluids such as plasma and serum, and the ability of miRNA expression profiles to accurately classify discrete tissue types and disease states have positioned miRNAs as promising non-invasive new tumor biomarkers. In this study, we used liquid bead array technology (Luminex) to profile the expression of 320 mature miRNAs in a pilot testing group of 19 matched fresh frozen cancerous and non-cancerous tissues from NSCLC patients. We further validated our results by RT-qPCR for differentially expressed miRNAs in an independent group of 40 matched fresh frozen tissues, 37 plasma samples from NSCLC patients and 28 healthy donors.