外周血中循环血管内皮细胞及血管内皮前体细胞的扩增与鉴定

目的证实外周血中循环血管内皮细胞(circulating endothelial cells,CECs)及血管内皮前体细胞(circulating endothelial precursors,CEPs)的存在,以及内皮前体细胞的增殖分化能力.方法应用流式细胞法检测57例肿瘤患者及15例正常人外周血中的CECs/CEPs.选择经造血干细胞动员的肿瘤患者,分离单个核细胞(mononuclear cells,MNCs),在VEGF、IGF及bFGF条件下培养血管内皮细胞,并应用透射电镜法对培养细胞进行鉴定.结果肿瘤患者外周血中CECs/CEPs含量分别为0.378±0.047%、0.059±0.013%,高于正常对照组.培养细胞透射电镜下可见Weibel-Palade小体,为血管内皮细胞的特异性标志.结论外周血中存在CECs/CEPs,在肿瘤患者体内存在血管内皮及其前体细胞的动员,循环血管内皮干/祖细胞可进一步分化成熟.     

肿瘤患者外周血循环血管内皮细胞数量与血清VEGF水平的关系

目的：分析实体瘤患者外周血中的循环血管内皮细胞（circulating endothelial cells, CECs）及血管内皮前体细胞(circulating endothelial precursors，CEPs)，并比较与正常人的差异。方法：流式细胞法检测57肿瘤患者及15例正常人外周血中的CECs和CEPs，ELISA法检测血清中血管生成相关因子VEGF和bFGF的表达水平。结果：肿瘤患者外周血CECs及CEPs分别为(0.378±0.047)%和(0.059±0.013)%，血清VEGF，bFGF分别为(295.58±59.56) ng/L和(28.73±7.40) ng/L，均高于正常对照组（P<0.05）。血管内皮及其前体细胞的数量与血清VEGF，bFGF水平相关。结论：实体瘤患者外周血中循环血管内皮及其前体细胞、血管内皮生长因子均高于正常人；VEGF和bFGF可能参与了血管内皮干/祖细胞的动员过程。     

肿瘤血管生成拟态的研究进展

肿瘤需要机体血液供应来满足生长的需要和进行播散。经典的血管生成理论认为：当实体肿瘤直径大于2mm时,需要诱导生成新的血管来获取血供,新的血管生成包括血管再生和血管形成两种方式,前者通过激活瘤体周围的宿主血管内皮细胞增生、迁移、芽生、向瘤组织内生长形成血管网;后者则是通过动员骨髓中血管内皮前体细胞,     

循环内皮细胞与肿瘤血管生成

循环内皮细胞（circulating endothelial cells，CECs）是指外周血中测得的血管内皮细胞（vascular endothelial cells，VEC）。20世纪70年代，Bou—vier和Hladovec在动物试验中发现了这种细胞，并提出了CECs的概念。CECs在正常人外周血中数量极少，而在动脉粥样硬化、糖尿病、红斑狼疮等疾病中明显增加。多项研究表明，CECs数量的增加与内皮细胞受损明显相关，因此被认为是判断血管内皮细胞损伤情况的最特异而直接的指标。     

血管内皮前体细胞与肿瘤血管发生

实体肿瘤的生长和演进依赖于肿瘤血管生成。肿瘤血管生成包括血管新生(angiogenesis)和血管发生(vasculogenesis),内皮前体细胞(endothelial progenitor cells,EPC)参与的肿瘤血管发生在肿瘤血管生成中起主要作用。EPC来源主要包括骨髓来源的EPC、血管壁定留EPC和成体干细胞经血管内皮分化形成的EPC,不同来源EPC参与的血管发生过程在肿瘤血管生成中起重要作用。其中,肿瘤干细胞作为肿瘤血管内皮前体细胞新来源的认识为研究肿瘤血管发生提供了新的思路。     

血管内皮生长因子在肿瘤血管生成的研究进展

人类肿瘤生长伴随血管生成早在一个多世纪前就被发现[1]。几十年对血管分子机制的研究,发现有很多种生长因子对肿瘤血管生成是有促进作用的,如血管内皮生长因子(VEGF)、成纤维生长因子(FGF)、血小板源性生长因子(PDGF)等,其中最重要的生长因子是VEGF[2],无论在生理     

循环内皮祖细胞及其与肿瘤关系的研究进展

内皮祖细胞(endothelial progenitor cell, EPC)是存在于骨髓和循环外周血的祖细胞亚群，具有在体内外分化为成熟内皮细胞的能力，参与血管发生和血管稳态。恶性肿瘤细胞产生多种细胞因子,使骨髓中的EPC动员至外周血,并募集到肿瘤组织的血管床,参与肿瘤血管生成、肿瘤生长和转移。外周血EPC水平与肿瘤的体积、抗新生血管治疗的反应性和预后等密切相关，因此EPC可作为肿瘤血管新生的生物标记物。EPC还可作为靶向肿瘤的细胞载体负载自杀基因、毒素或药物，为抗肿瘤治疗提供了新的途径。     

循环内皮祖细胞与肿瘤血管生成

恶性肿瘤细胞可产生多种细胞因子，可使骨髓中的内皮祖细胞(EPC)动员至外周血，并将这些细胞募集到肿瘤组织的血管床，参与肿瘤的血管生成。EPC有望成为抗肿瘤血管生成的靶点或肿瘤基因治疗的载体。     

非小细胞肺癌化疗中循环内皮祖细胞的检测

背景与目的:循环内皮祖细胞(circulating endothelial progenitor cells,cEPCs)在血管新生和肿瘤生长中具有重要作用.本研究旨在了解化疗对非小细胞肺癌(non-small cell lung cancer,NSCLC)患者cEPCs的影响.方法:35例晚期NSCLC紫杉醇联合顺铂化疗过程中,分别于化疗前1天、化疗开始后第7天、第15天和第42天用流式细胞仪检测外周血cEPCs数量.cEPCs的分子标志物定义为CD34+/CD133+/VEGFR-2+.结果:化疗周期的不同时间点外周血cEPCs数量存在差异.化疗后第15天cEPCs最多(F=4.36,P=0.006),化疗获益者化疗后cEPCs减少(t=4.35,P＜0.001),疾病进展者cEPCs增加(t'=5.35,P=0.001),cEPCs数量变化与化疗疗效相关(t=0.641,P＜0.001).化疗获益者治疗前的cEPCs数量低于化疗无效者(t=4.46,P＜0.001).结论:NSCLC的化疗疗效与cEPCs数量密切相关.     

循环内皮祖细胞与肿瘤血管生成

恶性肿瘤细胞可产生多种细胞因子,可使骨髓中的内皮祖细胞(EPC)动员至外周血,并将这些细胞募集到肿瘤组织的血管床,参与肿瘤的血管生成.EPC有望成为抗肿瘤血管生成的靶点或肿瘤基因治疗的载体.     

循环内皮细胞和放射性神经损伤的关系

背景与目的:放射性神经损伤是影响头颈部肿瘤放疗后生存质量的重要因素。本研究探讨大鼠不同剂量脑照射后不同时期神经行为和循环内皮细胞(circulatingendothelialcellsCECs)数量的变化。方法:108只SD大鼠信封法随机分成3组,用60Co单次照射大鼠脑,A组为空白对照组,B组为10Gy组,C组为30Gy组。Morris水迷宫分别对照射后7天、1个月和6个月的大鼠进行神经行为检测,水迷宫试验结束后心脏取血计数CECs。结果:照射7天后,3组大鼠Morris水迷宫的游泳潜伏期、平台象限时间、穿过平台区域次数比较无差异;照射1个月和6个月后Morris水迷宫B、C组较A组及C组较B组潜伏期延长,平台象限时间缩短,穿过平台区域次数减少,差异有统计学意义;CECs数量在1周和1个月时B、C组较A组及C组较B组有明显增高,差异有统计学意义,6个月时3组CECs数量之间无差异。在B组和C组1周时CECs数量和6个月时潜伏期相关(rB=0.97,rC=0.95)。结论:循环内皮细胞数量改变与损伤严重程度相关。     

循环肿瘤细胞检测技术的研究进展

循环肿瘤细胞（circulating tumor cells,CTCs）是导致发生肿瘤远处转移和复发的必要前提。随着靶向治疗的不断进步,对于无法取得肿瘤组织的晚期癌症患者,CTCs可作为一种肿瘤组织替代物指导患者治疗方案的选择。精确计数以及分子生物学分析对于肿瘤患者的预后判断、疗效评价以及个体化治疗均有重要的指导作用。随着CTCs检测技术不断发展,CTCs检测的准确性明显提高。本文针对CTCs的检测技术进行综述。      

循环肿瘤细胞的富集与检测研究进展

肿瘤的复发和转移是导致死亡的主要原因。循环肿瘤细胞(CTCs)与肿瘤的转移密切相关。 CTCs因其表面分子的多样性可为临床诊断、预后和个性化治疗提供丰富的信息。CTCs富集方法极 为重要,其表面分子的检测以及临床应用都受到富集方法的制约。目前,CTCs富集检测方法日新月 异,本文针对CTCs富集检测方法作一综述。     

Meta-Analysis of Circulating Endothelial Cells and Circulating Endothelial Progenitor Cells as Prognostic Factors in Lung Cancer

Background: The aim of this study was to analyze the prognostic implications of pretreatment circulatingendothelial cells (CECs) and circulating endothelial progenitor cells (CEPCs) for the survival of patients withlung cancer. Materials and Methods: Relevant literature was identified using Medline and EMBASE. Patientclinical characteristics, overall survival (OS) and progression-free survival (PFS) together with CEC andCEPC positive rates before treatment were extracted. STATA 12.0 was used for our analysis and assessment ofpublication bias. Results: A total of 13 articles (8 for CEC and 5 for CEPC, n=595 and n=244) were pooled forthe global meta-analysis. The odds ratio (OR) for OS predicted by pretreatment CECs was 1.641 [0.967, 2.786],while the OR for PFS was 1.168 [0.649, 2.100]. The OR for OS predicted by pretreatment CEPCs was 12.673[5.274, 30.450], while the OR for PFS was 4.930 [0.931, 26.096]. Subgroup analyses were conducted accordingto clinical staging. Odds ratio (OR) showed the high level of pretreatment CECs only correlated with the OSof patients with advanced lung cancer (stage III-IV). Conclusions: High counts of CECs seem to be associatedonly with worse 1-year OS in patients with lung cancer, while high level of pretreatment CEPCs correlate withboth worse PFS and OS.     

Parallel Evaluation of Circulating Tumor DNA and Circulating Tumor Cells in Metastatic Colorectal Cancer

Background

Tissue biopsy is the gold standard for tumor genotyping, but it is an invasive procedure providing a single snapshot into tumor heterogeneity. Liquid biopsy approaches, encompassing the analysis of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs), have been proposed as an alternative, with the potential of providing a comprehensive portrait of the tumor molecular landscape. In metastatic colorectal cancer (mCRC), both CTCs and ctDNA analysis have been investigated, but comparative analyses are limited.

Biologic markers of angiogenesis: circulating endothelial cells in patients with advanced malignancies treated on phase I protocol with metronomic chemotherapy and celecoxib

Preclinical studies demonstrate anti-angiogenic activity of low doses of chemotherapy; selective cox-2 inhibitors are also inhibitors of angiogenesis. Animal data indicates the presence of circulating endothelial cells (CEC), tumor-derived activated endothelial cells (AEC) and endothelial cell progenitors (ECP). Bone marrow-derived ECP have been shown to be incorporated into tumor vasculature. We conducted two combination Phase I studies of celecoxib with either cyclophosphamide or etoposide. Exploratory correlative studies were performed to evaluate the detectability of CEC, AEC and ECP in patients treated with these anti-angiogenic combinations. Patients were treated with oral cyclophosphamide at 50 mg daily or etoposide at 50 mg daily. Celecoxib was given at 400 mg twice daily. Blood samples were collected on days 0, 7, 28 and monthly until disease progression. Blood from healthy volunteers was collected on days 0 and 28. Peripheral mononuclear cells (PMNC) were isolated and stained with fluorescent antibodies and analyzed utilizing 5-color flow cytometry. Forty-four heavily pretreated patients (20 F; 24 M) with various solid tumors were enrolled. Median age was 65 (23-72). Therapy was well tolerated. No responses were seen. Six patients had stable disease for at least 16 weeks. The longest duration on therapy is 420 days in a patient with metastatic thymoma. Pre-therapy CEC were detected in cancer patients and normal controls with mean concentrations of 0.47 cells/uL and 0.14 cells/uL, respectively. Mean ECP in patients and controls were 0.09 cells/ uL and 0.03 cells/uL, respectively. No AEC were detected. No consistent changes were seen in CEC or ECP during therapy. The combinations of oral cyclophosphamide or etoposide at 50 mg daily with celecoxib at 400 mg twice daily are well tolerated with occasional prolonged disease stabilizations observed. CEC and ECP are detectable in cancer patients but their levels did not change significantly during therapy with our regimen. Further evaluation of CEC and ECP in patients treated with clinically more active anti-angiogenic therapies would be of interest.     

循环肿瘤细胞检测的研究新进展

循环肿瘤细胞的检测有助于发现早期肿瘤患者的微转移、重新确定临床分期、监测术后患者肿瘤复发与转移、评估预后、选择个体化的治疗策略。本文综述了近年来免疫细胞化学法、逆转录聚合酶链反应、流式细胞术、免疫磁珠富集检测法检测循环肿瘤细胞的研究新进展。     

肺癌循环肿瘤细胞的研究进展

转移和复发是肺癌患者死亡的主要原因。研究发现循环肿瘤细胞(circula tingtumo rcells,CTCs)在肺癌转移和复发中起着重要作用。而且随着靶向治疗的不断进步,对于晚期无法取得肺癌实体组织的患者,CTCs作为一种肺癌组织替代物可以决定治疗方案。所以CTCs在早期发现肺癌患者的微转移、检测肿瘤复发、评估预后和选择个体化治疗方案方面有着重要作用。本文针对CTCs的研究进展及肺癌领域的应用进行综述。