非小细胞肺癌循环肿瘤细胞检测进展

肺癌是世界范围内发病率最高的恶性肿瘤, 约有18%的癌症相关死亡与肺癌有关。循环肿瘤细胞(CTCs)的出现可看做是肿瘤细胞播散入血的直接体现, 而这正是导致非小细胞肺癌患者预后较差的最重要因素之一。检测外周血中循环肿瘤细胞有望成为诊断肺癌的辅助方法, 使肺癌患者得到最佳的个体化治疗。研究者们已尝试多种不同的方法从外周血中分离CTCs。虽然有关CTCs检测的研究众多, 但不同检测方法的敏感度、特异性及重复性限制了其临床意义, 本文就现有的各项技术进行综述。      

循环肿瘤细胞检测在预测非小细胞肺癌化疗疗效中的应用

目的 探讨循环肿瘤细胞检测在预测非小细胞肺癌化疗疗效中的应用.方法 选择非小细胞肺癌患者(肺Ca组)共25例,另选择慢性阻塞性疾病患者(COPD组)25例作为对比研究.入院后及化疗2个周期后分别采集所有参与研究的人员静脉血7.5 ml,利用密度梯度离心法富积循环肿瘤细胞,分析其与临床特征及化疗疗效的关系.结果 肺Ca组循环肿瘤细胞阳性率达72.00％,而COPD组阳性率为0,差异具有统计学意义(P<0.05).循环肿瘤细胞阳性表达与NSCLC病理类型、患者性别、年龄、吸烟情况等均无明显关系(P>0.05),仅与癌症分期相关(P<0.05).2个周期的化疗结束,发现对循环肿瘤细胞数目的评价与实体肿瘤疗效标准评价大致吻合,差异不具备统计学意义(P>0.05).相关分析发现这两种评价方法 呈负相关关系(γ=-0.465 P=0.021).结论 循环肿瘤细胞的存在与非小细胞肺癌的临床分期及化疗疗效有密切关系,可以用来预测非小细胞肺癌的转归.     

非小细胞肺癌的术前化疗

我科从1985年3月至1988年9月,对59例中晚期非小细胞肺癌,进行了术前大剂量PVE(C)联合化疗,治疗结果报告如下: 全部病例均经病理组织学或细胞学诊断证实。年龄26—69岁;男43例,女16例;Ⅰ期1例,Ⅱ期27例,Ⅲ期31例;鳞癌42例,腺癌17例。 本组对拟行手术治疗的病例均常规行术前化疗,部分不很适宜手术治疗的病例亦先行化疗,部分治疗有效病例再行手术。     

重组人血管内皮抑素联合化疗治疗晚期非小细胞肺癌

目的　观察重组人血管内皮抑素（恩度）联合化疗治疗晚期非小细胞肺癌（ＮＳＣＬＣ）的疗效及安全性。方法　１１例复治的晚期ＮＳＣＬＣ患者,接受恩度联合化疗治疗。恩度１５ｍｇ／天,连续１４天给药,间歇７天重复;同时,联合既往未使用或既往治疗病灶稳定的化疗药物。２１天为１周期,２周期评价疗效。结果　本组１１例患者均可评价客观疗效和毒副反应。有效率（ＲＲ）为１８.１８％,疾病控制率（ＤＣＲ）为８１.８２％;生活质量（ＱＯＬ）改善者４例（３６.４％）,稳定者５例（４５.４％）,下降２例（１８.２％）。主要毒副反应与化疗药物有关,包括白细胞减少２例（１８.１８％）,恶心呕吐２例（１８.１８％）。与恩度有关的心脏毒副反应１例（９％）,主要表现为疲乏感。出现皮肤一过性斑丘疹１例（９％）。结论　恩度联合化疗治疗晚期ＮＳＣＬＣ可以改善和稳定患者的生活质量,恩度与部分化疗药物有协同作用,安全性好。     

晚期非小细胞肺癌循环血管内皮细胞水平的研究

目的分析晚期非小细胞肺癌(NSCLC)患者治疗前后外周血中循环血管内皮细胞(CEC)的变化,探讨CEC在NSCLC中的应用价值。方法采用NP方案联合内皮抑素(治疗组)及单用NP方案(对照组)治疗晚期NSCLC 67例,流式细胞法检测治疗前后外周血CEC数量及细胞角蛋白(CK)水平。结果治疗组临床有效率为44．4％,对照组为27．3％(P=0．176);治疗组临床受益率为80．0％,对照组为50．0％(P=0．012)。治疗组肿瘤进展时间(TTP)为146．7 d,对照组为91．1 d (P=0．061)。当TTP的cut-off值>170时,两组TTP比较,差异有统计学意义(cut-off值=170,P= 0．034;cut-off值=180,P=0．009)。治疗组CEC平均下降(0．29±0．47)％,对照组平均下降(0．01±0．43)％(P=0．033)。全部患者治疗前CEC与CK水平呈正相关(r=0．381,P=0．013),治疗后亦呈正相关(r=0．450,P=0．004)。结论化疗联合血管靶向治疗晚期NSCLC优于单用化疗,CEC是一个较好的预测疗效的指标。     

血管内皮生长因子在人非小细胞肺癌中表达的临床研究

血管内皮生长因子 (ＶＥＧＦ)为一种能特异性促使内皮细胞激活、增殖及直接参与血管增生的糖蛋白 ,与肿瘤的发生、发展和转移关系密切。我们应用免疫组织化学法研究了ＶＥＧＦ在肺癌中的表达水平 ,现将结果报告如下。一、材料与方法1 材料 :取自我院胸外科 1993～ 1995年之间未经化疗和放疗手术切除的部分非小细胞肺癌共 99例。男性 75例 ,女性 2 4例 ;年龄 2 6～ 78岁 ;平均年龄 5 5 3岁。标本用 10 %中性福尔马林固定 ,石腊包埋 ,制成 4μｍ厚切片。经ＨＥ染色组织学观察 :鳞癌 2 8例 ,腺癌 5 7例 ,其他 14例。病理分级按ＷＨＯ标准 ,Ｇ1…     

晚期非小细胞肺癌的解救化疗

化疗在非小细胞肺癌（NSCLC）综合治疗中的作用日益受到重视，临床上辅助化疗与新辅助化疗渐趋增多，但晚期与复发的患者仍是主要对象。80年代确定的顺铂（DDP）为基础的化疗治疗晚期NSCLC患者有效率（RR）提高达50％左右，且能改善中位生存期（MST），从4月增到7月－8月。90年代出现一些新药，如：紫杉醇（Taxol,TAX)与紫杉特尔（Docetaxel,DOC)、氟胞苷（Gemcitabine,GEM)、伊利特肯（Irinotecan,CPT-11)和去甲长春花碱（Vinorelbine,NVB)等单用RR＞20％，与DDP或卡铂（CBP）联合应用，MST可达9月－10月，1年生存率亦有提高。然而，有些患者，特别是老人与肾功能不良者；不能耐受含DDP方案者，特别是老人与肾功能不良者；不能耐受含DDP方案者；或经含铂的第一线方案治疗失败者；患者活动状况（PS）差或病变恶化者需要交替方案。近年来，积极探索以非铂为基础的解求方案渐趋增加，以期应用新抗癌药，单剂、序贯或组成非铂的联合化疗，力求延长生存期，导致最小的不良反应，控制疾病症状和改善生活质量（QOL）。     

血管内皮生长因子在非小细胞肺癌中表达及意义

[目的]研究血管内皮生长因子(VEGF)在非小细胞肺癌(NSCLC)中的表达及意义.[方法]应用SABC免疫组化方法检测60例NSCLC中VEGF表达.[结果]NSCLC中VEGF阳性率为61.67%,明显高于癌旁正常组织(8.00%),P＜0.01.NSCLC中VEGF表达与临床分期及淋巴结转移显著相关.VEGF表达阴性组1、3、4年生存率分别为86.74%、64.05%、64.05%,而阳性组则分别为85.4%、43.64%、19.05%,经Log-Rank检验,差异有显著性(P＜0.05).[结论]VEGF在非小细胞肺癌血管形成及发展中起重要作用,并有助于预测肺癌患者的预后.     

非小细胞肺癌辅助化疗研究进展

近年来,非小细胞肺癌(NSCLC)术后辅助化疗的Ⅲ期随机临床试验结果已陆续报道,术后辅助化疗逐渐被接受,已成为Ⅱ～ⅢA期非小细胞肺癌综合治疗的重要措施之一.本文就NSCLCⅢ期随机临床试验结果作一综述.     

非小细胞肺癌微血管计数与血管内皮生长因子表达

目的　探讨血管内皮生长因子 (VEGF)在非小细胞肺癌 (NSCLC)浸润和转移中的作用。方法　应用免疫组化法检测 6 5例癌组织中VEGF蛋白的表达及微血管计数 (MVC)。结果　NSCLC组织中VEGF阳性表达率为 83 .1%(5 4/ 6 5 ) ,有转移组癌组织中VEGF阳性表达比例 (10 0 %,44/ 44)以及MVC(5 8.90± 31.45 )均显著高于无转移组 (47.6 %,10 / 2 1;2 1.44± 12 .77) (P <0 .0 1) ;Ⅲ期肺癌VEGF表达阳性率 (10 0 %,2 9/ 2 9)以及MVC(6 0 .2 4± 2 8.2 9)亦显著高于Ⅰ和Ⅱ期肺癌 (6 9.4%,2 5 / 36 ;19.5 3± 16 .2 7) (P <0 .0 1)。VEGF表达强度与MVC间有密切关系。在不同组织学类型及肿瘤直径间VEGF阳性率和MVC均未见显著性差异 (P >0 .0 5 )。结论　VEGF可能在NSCLC浸润和转移过程中发挥重要作用 ,检测VEGF表达及MVC有助于判断NSCLC转移及预测患者预后。     

Circulating endothelial and endothelial progenitor cells in non-small-cell lung cancer

New treatments have recently been introduced for treating non-small-cell lung cancer. Chemotherapeutic agents, such as pemetrexed, and targeted therapies, such as bevacizumab, erlotinib or gefitinib, have extended treatment options for selected histological subgroups. Antiangiogenic treatments, either associated with conventional chemotherapeutic drugs or given alone as maintenance therapy, constitute an active clinical research field. However, not all lung cancer patients benefit from antiangiogenic compounds. Moreover, tumour response assessment is often difficult when using these drugs, since targeted therapies generally do not cause rapid and measurable tumour shrinkage but, rather, long stabilisations and slight density changes on imaging tests. The finding of clinical or biological factors that might identify patients who will better benefit from these treatments, as well as identifying surrogate markers of tumour response and prognosis, is an issue of great interest. In that sense, different research lines have investigated the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. Circulating endothelial (CECs) and endothelial progenitor cells (CEPCs) are of prognostic value in different types of cancers, and relevant data are published about their potential usefulness as predictors of response to chemotherapy and antiangiogenic treatments. In this review, we discuss the data available on the role of CECs and CEPCs as prognostic factors and as surrogate markers of treatment response in non-small-cell lung cancer.     

晚期肺癌患者的抑郁状态在化疗过程中的变化

目的：观察晚期肺癌患者的抑郁状态在化疗过程中的变化。方法：应用Zung＇s抑郁自评量表,对可评价的111例住院的晚期肺癌患者在化疗前、中、后进行抑郁情绪的评估。结果：化疗中患者的抑郁人数比化疗前增多（P〉0.05）,出现Ⅲ-Ⅳ度化疗不良反应的晚期肺癌患者发生抑郁的人数较仅出现Ⅰ-Ⅱ度化疗不良反应的肺癌患者发生抑郁的人数要多（P〈0.05）;化疗后病情有缓解的晚期肺癌患者中的抑郁人数较化疗后病情是稳定或有进展的肺癌患者抑郁的人数要少（P〈0.05）。结论：较严重的化疗不良反应有可能会增加晚期肺癌患者抑郁的发生;肿瘤病情的缓解有可能会改善晚期肺癌患者的抑郁状态。     

晚期肺癌患者的抑郁状态在化疗过程中的变化

目的:观察晚期肺癌患者的抑郁状态在化疗过程中的变化。方法:应用Zung’s抑郁自评量表,对可评价的111例住院的晚期肺癌患者在化疗前、中、后进行抑郁情绪的评估。结果:化疗中患者的抑郁人数比化疗前增多(P>0.05),出现Ⅲ-Ⅳ度化疗不良反应的晚期肺癌患者发生抑郁的人数较仅出现Ⅰ-Ⅱ度化疗不良反应的肺癌患者发生抑郁的人数要多(P<0.05);化疗后病情有缓解的晚期肺癌患者中的抑郁人数较化疗后病情是稳定或有进展的肺癌患者抑郁的人数要少(P<0.05)。结论:较严重的化疗不良反应有可能会增加晚期肺癌患者抑郁的发生;肿瘤病情的缓解有可能会改善晚期肺癌患者的抑郁状态。     

Tailor-made chemotherapy for non-small cell lung cancer patients

The selection of the most effective chemotherapy treatment based on evaluation of biomarkers, that is, 'tailor-made chemotherapy', can improve the clinical outcome of non-small cell lung cancer patients, including early-stage tumors with a high metastatic potential and advanced-stage tumors with a low proliferation rate. Therefore, treatment would be chosen according to which drugs would be most effective in combating specific tumors. For example: 5-fluorouracil-derived agents would be used for tumors with a low expression of thymidylate synthase; gefitinib and erlotinib for tumors with epidermal growth factor receptor (EGFR) mutations or increased EGFR gene copy numbers; cisplatin and carboplatin for tumors with a low expression of excision repair cross complementing-1; and gemcitabine for tumors with a low expression of ribonucleotide reductase. The remaining populations of non-small cell lung cancers require chemotherapy using other drugs based on an evaluation of other targeted molecules.     

Circulating numbers of endothelial progenitor cells in patients with gastric and breast cancer

Angiogenic factors like VEGF or G-CSF were reported to mobilize endothelial progenitor cells (EPCs) from the bone marrow. These EPCs were shown to be incorporated in the neovessels of developing tumors. Although the concentrations of angiogenic factors in the peripheral blood were reported to be elevated in cancer patients, the number of circulating EPCs has not been previously investigated. In this study, the number of EPCs circulating in the blood in 16 healthy controls and 71 newly diagnosed cancer patients was examined by a culture assay of peripheral blood mononuclear cells. The number of circulating EPCs was not found to be increased in cancer patients, although the plasma levels of VEGF were elevated. It is suggested that VEGF, at concentrations typical of those observed in the blood of cancer patients, does not mobilize EPCs into the peripheral blood.     

Circulating endothelial progenitor cells correlate to stage in patients with invasive breast cancer

Tumor growth and metastasis is dependent on the formation and assembly of new blood vessels, a process known as neo-angiogenesis. Both pre-existing and circulating vascular cells have been shown to contribute to the assembly of tumor neo-vessels in specific tumors. Mobilization of endothelial progenitor cells (EPCs) from the bone marrow constitutes a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be increased in certain malignant states. However, the role of circulating EPCs in breast cancer is largely unknown. We recruited twenty-five patients with biopsy-proven invasive breast cancer at Weill Cornell Breast Center to participate in a pilot study investigating the correlation of circulating EPCs to extent of disease and initiation of chemotherapy. For each patient, a baseline sample was drawn before systemic treatment, and for seventeen of those patients, a second sample was taken after the first round of chemotherapy. Levels of peripheral blood EPCs, as defined by co-expression of CD133 and VEGFR2, were quantified by flow cytometry. Breast cancer patients with stage III & IV disease had statistically higher levels of circulating EPCs than did patients with stage I & II disease (median = 165,000 EPCs/5 × 10⁶MNCs vs. median = 6,920 EPCs/5 × 10⁶MNCs, respectively, P < 0.0001). In addition, in late-stage patients, levels of EPCs demonstrated a statistically significant drop after initiation of chemotherapy (median = 162,500 EPCs/5 × 10⁶MNCs [pre] vs. median = 117,500 EPCs/5 × 10⁶MNCs [post], P = 0.01). These results suggest that circulating EPCs may serve as a potential tumor biomarker in breast cancer and that EPCs may represent a plausible target for future therapeutic intervention.     

Circulating endothelial progenitor cells

Angiogenesis research investigates the formation of new blood vessels in wound healing, tumour growth and embryonic development. Circulating, bone marrow-derived endothelial progenitor cells (EPCs) were first described 8 years ago, yet the exact nature of these endothelial precursor cells remains unclear. The contributions of circulating EPCs to angiogenesis in tumours, ischaemic injury and other diseases as well as their usefulness in the repair of wounded hearts and limbs remain under intense investigation.     

尼妥珠单抗联合化疗治疗晚期非小细胞肺癌

目的 评价尼妥珠单抗联合化疗治疗晚期非小细胞肺癌(NSCLC)的价值.方法 回顾性分析2009年1月至2010年10月采用尼妥珠单抗联合化疗的37例晚期NSCLC患者的临床资料.其中Ⅲb期12例,Ⅳ期25例.采用尼妥珠单抗联合铂类为基础的化疗方案24例,尼妥珠单抗联合非铂类药物的化疗方案13例.尼妥珠单抗联合化疗作为一线方案患者10例,二线方案23例,三线方案4例.结果 37例患者共计化疗137个周期,平均每例3.7个周期.其中完全缓解(CR)1例,部分缓解(PR)9例,稳定(SD)16例,进展(PD)11例,有效率(RR)为27.0%,临床获益率(CBR)为70.3%.主要毒副反应为骨髓抑制和胃肠道反应,仅有1例患者出了Ⅰ度座疮样皮疹.结论 尼妥珠单抗联合化疗治疗晚期NSCLC患者可提高疗效,且耐受性良好.

Abstract：

Objective To evaluate the role of nimotuzumab in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods The clinical data of 37 NSCLC patients who received nimotuzumab in combination with chemotherapy in Tianjin Medical University Cancer Hospital from January 2009 to October 2010 were retrospectively reviewed. Of the thirty-seven patients, 12patients were in stage Ⅲ B, 25 patients in stage Ⅳ. Twenty-four patients recived platinum-based chemotherapy in combination with nimotuzumab, 13 patients recived nonplatinum-based chemotherapy in combination with nimotuzumab. Ten patients received nimotuzumab in combination with chemotherapy as first-line regimen, 23 patients as second-line regimen, 4 patients as third-line regimen. Results Of the 37advanced NSCLC patients who received nimotuzumab in combination with chemotherapy, the total number ofchemotherapy were 137 cycles, the mean number was 3.7 cycles. One patient had complete remission (CR), 9 patients had partial remission (PR), 16 cases had stable disease (SD), and 11 patients hadprogressive disease (PD). The response rate (RR) was 27% and clinical benefit rate (CBR) was 70.3%.The main side effects were bone marrow suppression and gastrointestinal reactions. Grade I acneiform rash was found in one patient. Conclusion The regimen of nimotuzumab in combination with chemotherapy can improve the response rate and was well tolerated in patients with advanced non-small cell lung cancer.     

血管内皮生长因子对非小细胞肺癌血道转移的影响

目的 探讨血管内皮生长因子（VEGF）含量对非小细胞肺癌（NSCLC）血道转移的影响。方法 外周血中细胞角蛋白（CK）阳性细胞经磁性细胞分选技术分离后,采用细胞学、免疫组化及免疫荧光染色对其中的肺癌细胞进行特性分析。外周血肺癌细胞含量按已建立的流式细胞仪检测方法作定量分析。VEGF含量采用ELISA测定。结果 外周血肺癌细胞具有明显的核异型,表达端粒酶逆转录酶（hTERT)及上皮细胞标志CK,可被抗人NSCLC特异性单抗S5A10－2染色,但不表达白细胞抗原CD34及CD45。154例NSCLC患者中,外周血肺癌细胞阳性44例,阳性率为28．6％。癌细胞阳性率与病期进展相关。NSCLC患者血浆VEGF含量显著高于健康人及肺部良性疾患者。VEGF含量与肺腺癌的病期进展密切相关。在血循环癌细胞阳性NSCLC患者中,VEGF含量增高者,癌细胞数量显著高于VEGF不增高者。结论 NSCLC患者血浆VEGF明显增高,在血循环癌细胞阳性的患者中,VEGF高表达可促使癌细胞血道转移,表现为血循环癌细胞数量明显增加。