非小细胞肺癌体外化疗药物敏感性与GRP78表达的相关性

背景和目的 糖调节蛋白78（GRP78）在乳腺癌细胞中表达增高并与其对化疗药物的耐药性有关，而非小细胞肺癌（NSCLC）中GRP78的表达与其对化疗药物的耐药性是否相关，研究较少。本研究拟探讨NSCLC对8种化疗药物的体外敏感性与GRP78表达的相关性。方法 采用四噻唑蓝（MTT）法对52例手术切除的新鲜NSCLC组织进行8种化疗药物体外敏感性检测；采用免疫组织化学方法检测其GRP78的表达水平。采用Spearman相关分析对NSCLC的耐药性与GRP78表达的相关性进行分析。结果 52例NSCLC对紫杉醇（PTX）、阿霉素（ADM）、卡铂（CBP）、拓扑替康（TPT）、长春瑞滨（NVB）、长春新碱（VCR）、顺铂（DDP）和鬼臼乙叉苷（VP-16）8种化疗药物的耐药率分别为42．31％、57．69％、63．46％、65．38％、67．31％、73．08％、78．85％、90．38％，其中14例表现为完全耐药。GRP78的表达水平随着肺癌恶性程度的提高而增加，且其高表达与肺癌细胞对VP-16、ADM、VCR和TPT的耐药具有相关性（P〈0．05）。结论 MTT法体外化疗药物敏感性实验对NSCLC的治疗具有一定的指导作用，GRP78对判定NSCLC的恶性程度及其耐药性具有一定的参考意义。     

RNA干扰技术抗非小细胞肺癌作用的体内实验研究

目的 探讨体外化学合成表皮牛长因子受体(EGFR)基因序列特异性双链RNA(dsRNA)在体内诱导非小细胞肺癌(NSCLC)细胞出现序列特异性基因沉默的町行性.方法 体外化学合成EGFR序列特异性dsRNA(dsRNA-EGFR),结合脂质体Lipofectamine 2000转染肺腺癌细胞株SPC-A1后,将200 μl细胞悬液接种于裸鼠,建立荷瘤鼠模型,计箅肿瘤抑制率.采用免疫组织化学技术、Western blot技术和实时逆转录聚合酶链反应(real-time RT-PCR),检测肿瘤组织中EGFR蛋白和mRNA的表达水平.结果 dsRNA-EGFR可显著抑制体内肿瘤生长,肿瘤抑制率为75.0%,并可将EGFR蛋白表达水平降低53.6%、mRNA表达水平降低32.3%.结论 dsRNA-EGFR在体内可有效抑制NSCLC细胞中EGFR蛋白和mRNA的表达水平,抑制肿瘤生长.     

Role of pemetrexed in non-small cell lung cancer

Pemetrexed was approved for the treatment of relapsed or chemotherapy refractory non-small cell lung cancer patients, as it produced similar response and survival outcomes and less toxicity as compared to taxotere. Pemetrexed in combination with platinum analogs or with gemcitabine or vinorelbine, produce equivalent responses and overall survival results compared to combinations of platinum analogs with other drugs. The role of bevacizumab and the inhibitors of epithelial growth factor receptor also should be evaluated in selected patients with NSCLC treated with pemetrexed combinations. Further increases in drug dose may be possible using transfer of drug resistance genes in hematopoietic stem cells.     

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.     

Current treatment landscape for oligometastatic non-small cell lung cancer

The management of patients with advanced non-small cell lung carcinoma (NSCLC) has undergone major changes in recent years. On the one hand, improved sensitivity of diagnostic tests, both radiological and endoscopic, has altered the way patients are staged. On the other hand, the arrival of new drugs with antitumoral activity, such as targeted therapies or immunotherapy, has changed the prognosis of patients, improving disease control and prolonging survival. Finally, the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body. All of these advances have impacted the treatment of patients with advanced lung cancer, especially in a subgroup of these patients in which all of these treatment modalities converge. This poses a challenge for physicians who must decide upon the best treatment strategy for each patient, without solid evidence for one optimal mode of treatment in this patient population. The aim of this article is to review, from a practical and multidisciplinary perspective, published evidence on the management of oligometastatic NSCLC patients. We evaluate the different alternatives for radical ablative treatments, the role of primary tumor resection or radiation, the impact of systemic treatments, and the therapeutic sequence. In short, the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.     

长链非编码RNA HOTTIP 通过调控细胞凋亡水平促进非小细胞肺癌增殖

背景与目的：探索非小细胞肺癌(non-small cell lung cancer,NSCLC)有效的早期诊断及预后标志物具有重要的科学意义和临床价值。长链非编码RNA(lncRNA)在肿瘤中的作用逐渐引起研究者的关注。本研究拟分析lncRNA HOTTIP在NSCLC中的表达情况及对NSCLC细胞增殖水平的影响和机制。方法：采用实时定量PCR(quantitative real-time PCR,qRT-PCR)检测方法检测54例NSCLC组织及其对应癌旁组织的HOTTIP表达情况,分析NSCLC组织HOTTIP表达与临床病理参数的相关性;MTT方法检测肺癌细胞增殖水平,流式细胞术检测凋亡率的改变;蛋白［质］印迹法(Western blot)检测目的基因的蛋白表达变化。结果：与癌旁组织比较,HOTTIP在肺癌组织中的表达率明显增加,差异有统计学意义(P<0.05)。HOTTIP表达与患者淋巴结转移和TNM分期相关。转染HOTTIP siRNA至A549肺癌细胞后,结果显示,与未转染组和阴性质粒转染组相比,转染siRNA-HOTTIP 的A549细胞HOTTIP 表达明显降低;HOTTIP表达下调后细胞增殖速度减慢,凋亡率增加,凋亡相关蛋白Bax的表达增加,Bcl-2表达减少。结论：HOTTIP是一种新的NSCLC生物标志物,可作为潜在的治疗新靶点。     

State of the art in therapy for non-small cell lung cancer

The treatment of lung cancer has changed rapidly over the last few years and now more than ever a multi-disciplinary approach is vital to patient care. Surgical resection remains the mainstay of treatment for patients with operable disease. Recent studies have clearly demonstrated the survival benefits of adjuvant chemotherapy and this is now considered the standard of care. Despite efforts to improve early detection the majority of patients present with advanced lung cancer. The combination of radiation and chemotherapy should be considered for patients with locally advanced disease. Chemotherapy and the newer generation of molecularly targeted agents, provide quality of life benefits and modest gains in survival for patients with metastatic disease. Though there is room for improvement there is no justification for the therapeutic nihilism once surrounding the treatment of lung cancer.     

局部晚期非小细胞肺癌外科治疗中的气道重建

背景与目的部分局部晚期非小细胞肺癌患者需要采取不同的气道重建方式，以彻底切除病变并最大限度保存肺功能。本研究旨在探讨气道重建中的外科相关问题。方法回顾分析研究2003年1月～2005年6月2206例肺癌手术中100例气道重建患者的临床资料，其中鳞癌42例，腺鳞癌23例，腺癌11例，粘液表皮样癌5例，腺样囊性癌4例，类癌3例及其它混合散在分布类型12例。ⅠB期34例，ⅡB期23例，ⅢA期23例，ⅢB期20例。主要手术方式包括：右上叶袖状切除42例，右下叶袖状切除1例，左上叶袖状切除24例，左下叶袖状切除4例。两叶袖状切除8例，隆凸成形重建17例，肺叶袖状切除合并肺动脉成形4例。结果97例患者为完全性切除（R0），3例为不完全性切除（R1）。术后5例出现并发症，分别为肺部感染2例，胸腔感染1例，支气管胸膜瘘1例，肺泡胸膜瘘1例，并发症发生率为5％。术后住院日为4～27日（中位11日）。99例治愈出院，肺部感染导致死亡1例，手术死亡率为1％。结论对局部晚期非小细胞肺癌采取适当的气道重建方式，符合外科手术原则，可取得较满意的治疗效果。对血管、气管、支气管的处理技巧是手术获得成功的关键。     

非小细胞肺癌的潜在生物标记物:长链非编码RNA

非小细胞肺癌是常见的肺癌类型之一,筛选可用于诊断、治疗和预后判断的生物标志物是近年来非小细胞肺癌研究的热点之一。我们已知,基因和表观遗传学改变是非小细胞肺癌发展的重要因素,近期研究发现,基因组的非蛋白质编码区域可以作为各种RNA的转录模板,统称为非编RNA。包括长链非编码RNA在内的非编码RNA,在多种细胞功能中发挥了重要作用。研究表明,长链非编码RNA的表达异常与肿瘤的发生关系密切,包括非小细胞肺癌。在本篇综述中,我们将总结长链非编码RNA作为非小细胞肺癌潜在生物标志物的最新研究进展。     

蛞蝓对人肺鳞癌、肺腺癌细胞抑癌作用初探

 在对肺鳞癌、乳腺癌、原发性肝癌、直肠癌手术切除标本和肺腺癌胸膜侵犯胸水中的癌细胞进行双层琼脂克隆培养和药敏试验的同时, 进行3H－胸腺嘧啶掺入试验(3H-TdR), 结果显示蛞蝓对肺鳞癌、肺腺癌细胞有明显的抑制作用:对肺鳞癌细胞的3H－TdR摄入抑制率93.08%, 与顺铂(93.33%相当；对肺腺癌克隆集落抑制率65.24%, 3H-TdR摄入抑制率46.21%, 比顺铂的34.77%和15.23%显著增高, 这一结果, 为今后进一步研究蛞蝓的抗癌作用提供了体外抑瘤的实验依据。     

肺癌神经内分泌分化与术后生存关系探讨

目的 探讨非小细胞肺癌神经内分泌(NSCLC—NE)分化与患者手术后生存关系。方法 收集1997年4月至1999年4月98例肺癌手术切除病理标本，采用免疫组化标记特异性烯醇化酶(NSE)及突触素(SY)，并按强弱区分为“ 、 、 ”。对同一手术病例标本采用电镜观察特异性NE颗粒。术后病例随访36月，最长60月。采用Cox多因素风险模型分析NSCLC-NE分化与患者术后生存的关系。结果 91例为非小细胞肺癌。非小细胞肺癌NF阳性表达率为63．7％(58/91)，其中NSE阳性表达54例(59．3％)，SY阳性表达22例(24．1％)，电镜观察NE持异性颗粒30例(33．0%)。结合免疫组化和电镜观察，NSCLC-NE分化44例(48．4％)。Cox模型多因素分析结果表明NSCLC-NE分化者术后生存时间明显缩短(P=0.048)。术后生存与肺癌细胞分化程度(P=0．006)、病理分期(P=0．001)、NE表达强弱(P=0．054)有密切关系。结论 NSCLC-NE分化与肿瘤细胞分化和患者术后生存有关。采用NE标志物标记肿瘤，并观察其强弱改变．对术后评估具有较重要的参考意义，可作为为临床判断患者预后指标之一。     

SPARC expression and prognostic value in non-small cell lung cancer

Secreted protein,acidic and rich in cysteine(SPARC) is expressed in numerous types of tumors and is suggested to have prognostic value.Moreover,because of its strong affinity for albumin,and hence albumin-bound drugs,SPARC has increasingly become a focus for research.In this study,we aimed to determine SPARC expression in patients with non-small cell lung cancer(NSCLC) and investigate the association of SPARC with disease prognosis.Tissue microarrays were constructed with specimens from 105 patients with NSCLC treated at Sun Yat-sen University Cancer Center,and immunohistochemical analysis was performed on these tissue microarrays to assess SPARC expression.Our results showed that SPARC expression status did not significantly relate with age,gender,and tumor stage.However,SPARC was expressed more frequently in squamous cell carcinoma than in adenocarcinoma(75% vs.43.5%,P = 0.004).Patients with smoking history had higher SPARC expression than non-smokers(68.2% vs.33.3%,P = 0.002).In both univariate and multivariate analyses,SPARC was a prognostic factor of overall survival(HR = 0.32;95% CI:0.16-0.65) but not disease-free survival.Our study indicates that SPARC expression is higher in squamous cell carcinoma than in adenocarcinoma in NSCLC.Most notably,SPARC can be used as a prognostic factor for NSCLC.     

厄洛替尼治疗化疗后进展的晚期非小细胞肺癌的近期疗效观察

目的 观察厄洛粹尼治疗化疗后进展的晚期非小细胞肺癌(NSCLC)的疗效和不良反应.方法 化疗后进展的12例晚期NSCLC患者,口服厄洛替尼150 mg/d,1个月后进行疗效评价.疾病无进展者继续服用,之后每月对接受治疗者进行疗效评价,并密切观察不良反应.结果 12例患者均可评价疗效,其中完全缓解1例,部分缓解2例,疾病无变化4例,疾病进展5例;有效率为25.0%(3/12),疾病控制率为58.3%(7/12),临床受益率为41.7%(5/12).厄洛替尼治疗的主要不良反应为皮疹和腹泻,全组无一例患者因不能耐受不良反应而终止治疗.结论 厄洛替尼对化疗后进展的晚期NSCLC具有一定的疗效,且不良反应轻,患者能够耐受.     

非小细胞肺癌放化综合治疗的前瞻性随机研究

目的 对比观察非小细胞肺癌单纯放疗和放化综合治疗的疗效。方法 从１９９５年１月 到１９９７年１２月,将符合入组条件的８２例非小细胞肺癌患者随机分为放疗组和化放疗综合治疗组。其中完成治疗计划的有７４例,３５例属单纯放疗组,３９例属化放疗综合治疗组。综合治疗组中２１例为增敏化疗（氟脲嘧啶、顺铂）,在放疗的第１、４周给药;１８例为联合方案化疗,在放疗前、中、后进行,最少两周期,药物为卡铂、顺铂、足叶乙甙     

非小细胞肺癌EGFR-TKIs耐药——小细胞肺癌转化的机制和治疗

肺癌是当前死亡率最高的恶性肿瘤之一。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）明显提高了晚期非小细胞肺癌（NSCLC）患者的生活质量,延长了生存期。EGFR基因优势突变的NSCLC患者临床获益明显,然而由于耐药产生,患者的中位无进展生存期（PFS）仅1年左右。最近,有文献报道EGFR TKIs耐药的机制之一是NSCLC转化为小细胞肺癌（SCLC）。本文对这种现象进行了分析总结,探讨了其转化的可能机制。根据EGFR-TKIs耐药后的处理方法和病理表型转化患者的治疗报道,探讨NSCLC EGFR-TKIs耐药后转化为SCLC患者的治疗策略。     

TELOMERASE ACTIVITY OF FIBROBRONCHOSCOPIC BRUSHING CELLS IN NON－SMALL CELL LUNG CANCER

Telomerase is a ribonucleoprotein enzyme that uses its own integral RNA as a template for synthesis of the telomeric DNA. The cells containing thisenzyme can escape from natural telomeric shortening and acquire infinite growth potentiality. Findings in recent studies showed that telomerase was activated in almost all malignant tumor tissues which suggests that the activation of telomerase is the critical procedure in oncogenesis. We studied telomerase activity in bronchial exfoliated cells f…     

长链非编码RNA HOTAIR对非小细胞肺癌迁移和侵袭能力的影响

目的 探讨长链非编码RNA HOTAIR在非小细胞肺癌（NSCLC）组织及4株细胞系（A549、SPC-A1、SK-MES-1和16HBE）中的表达,并分析其对细胞侵袭和迁移能力的影响。方法通过定量反转录PCR（qRT-PCR）检测HOTAIR在38例NSCLC组织及4株细胞系中的表达水平,并进一步利用过表达和RNA干扰技术探讨HOTAIR的生物学功能。通过分别转染pcDNA-HOTAIR或si-HOTAIR来上调或下调HOTAIR的表达,以空载体（pcDNA3.1-NC）和阴性对照（si-NC）作为对照组,用qRT-PCR检测转染效率。用MTT法和Transwell法评估异常表达的HOTAIR对NSCLC细胞增殖、迁移和侵袭能力的影响。结果 38例NSCLC组织中HOTAIR相对表达水平为24.48±59.55。与正常支气管上皮细胞系16HBE相比,HOTAIR在SPC-A1和SK-MES-1细胞中相对高表达,而在A549细胞中相对低表达。转染HOTAIR siRNA 48h后,A549和SPC-A1细胞中HOTAIR表达下调;转染pcDNA3.1 HOTAIR 48h后,A549细胞中HOTAIR表达上调。MTT实验显示,通过RNAi技术来抑制HOTAIR的表达,对NSCLC细胞的增殖能力无明显影响。Transwell实验显示,通过转染si-HOTAIR来下调HOTAIR表达可抑制癌细胞的迁移和侵袭（P＜0.05）;相反,过表达HOTAIR可以显著促进癌细胞的迁移和侵袭（P＜0.05）。结论 HOTAIR在NSCLC中异常高表达,能显著增强NSCLC细胞的迁移和侵袭能力,提示可能与不良预后相关。     

吉西他滨联合卡铂治疗晚期非小细胞肺癌

目的　观察吉西他滨联合卡铂治疗晚期非小细胞肺癌的疗效及毒副反应。方法　 41例晚期非小细胞肺癌患者给予吉西他滨与卡铂联合治疗 ,吉西他滨 10 0 0mg/m2 ,静脉滴注第 1、8、15天 ,卡铂AUC 5 ,静脉滴注第 1天 ,2 8天为一周期 ,每例患者治疗 2周期以上。结果　全组完全缓解 2例 ,部分缓解 18例 ,稳定15例 ,进展 6例 ,总有效率为 48.8%。初治组有效率为 5 5 .6% ,复治组为 43 .5 % (P >0 .0 5 )。全组中位生存期 11.8月 ,1年生存率为 49%。KPS评分增加者占 70 .7% ( 2 9/4 1)。最常见的毒副反应为骨髓抑制 ,Ⅲ～Ⅳ度白细胞和血小板下降发生率分别为 3 4.1%和 2 9.3 % ,其余毒副反应均轻微 ,可耐受。结论　吉西他滨联合卡铂一线治疗或二线治疗晚期非小细胞肺癌均有较好的疗效 ,毒性可以耐受。     

Adjuvant chemotherapy for non-small cell lung cancer

Nearly half of all patients who undergo surgical resection of localized non-small cell lung cancer (NSCLC) will develop and ultimately die of recurrent disease. The postoperative radiotherapy (PORT) meta-analysis showed adjuvant thoracic radiotherapy to have a detrimental effect on survival in this patient population. A meta-analysis of early trials of adjuvant chemotherapy by the Non-Small Cell Lung Cancer Collaborative Group showed that while chemotherapy with alkylating agents was also detrimental, chemotherapy with cisplatin-based adjuvant chemotherapy was associated with an improved hazard ratio for death (HR = 0.87), equating to a 5 percent survival benefit at 5 years. However, the result was not statistically significant (p = 0.08). Recently, results have been reported for several large Phase III trials of adjuvant chemotherapy which differed with respect to the stage of resected disease included, the type of chemotherapy used and the use of post-operative radiotherapy. Three trials (IALT, JBR 10, and ANITA) that utilized cisplatin-based doublets showed a significantly positive survival benefit of adjuvant chemotherapy in patients with Stage II-IIIA NSCLC. The magnitude of this benefit, which was suggested to be 4-5 percent at 5 years in the meta-analysis and by the IALT study, may be as large as 8-15 percent as indicated by more recent studies with modern platinum-based doublet chemotherapy. These data indicate that medically fit patients with resected Stage II-IIIA NSCLC should be offered adjuvant chemotherapy with a modern cisplatin-based doublet.