转移性循环肿瘤细胞的特征

循环肿瘤细胞（circulating tumor cells,CTCs）是肿瘤转移的潜在种植者。这些引起肿瘤转移的CTCs具有干性、转化、簇群、亲器官性和变形等特征,最终在靶器官形成转移灶。研究CTCs的特征可能揭开肿瘤转移的机制。     

肺癌中循环肿瘤细胞的检测

 循环肿瘤细胞为肿瘤复发转移的重要原因,检测循环肿瘤细胞能早期发现肿瘤的转移及复发,同时也将有助于判断疾病预后、指导治疗。循环肿瘤细胞检测通常包含有筛选和分离技术如免疫磁性分选技术和逆转录聚合酶链反应等。随着检测技术的发展出现了将筛选和分析技术合为一体的循环肿瘤细胞检测芯片。     

乳腺癌循环肿瘤细胞检测及其研究进展

循环肿瘤细胞(CTC)为肿瘤发生转移的重要原因.检测CTC能早期发现肿瘤的转移及复发.在乳腺癌中,CTC检测与其他检测方式相比有较高的可重复性和敏感性,并能更早地提供预后信息.     

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。      

上皮间质型循环肿瘤细胞在小细胞肺癌转移中的研究进展

小细胞肺癌（Small Cell Lung Cancer,SCLC）约占肺癌的20%,确诊时大约60%~70%患者已经处于晚期。与非小细胞肺癌相比,其生物学行为更差,恶性程度高,病情发展迅速,更易早期转移。目前,局限期和广泛期的小细胞肺癌治疗以全身化疗为主,小细胞肺癌患者对化疗敏感,但极易发生耐药,容易复发和转移,生存率低[1-2]。肿瘤转移是导致肿瘤患者死亡的最直接原因。目前,     

循环肿瘤细胞的检测及其临床应用

循环肿瘤细胞(CTC)可反映肿瘤的侵袭性.尽管许多检测及计数CTC的方法如磁性激活的细胞筛选、免疫细胞化学法、反转录聚合酶链式反应、流式细胞术开展了很久,直到最近这些方法才具有可行性.临床检测结果强烈提示,在某些肿瘤中,CTC的检测和计数可以用来预测预后、选择个体化治疗并可能作为评估治疗反应性的早期指标.     

循环肿瘤细胞的异质性在转移性乳腺癌中的作用研究进展

循环肿瘤细胞（CTC）的计数可以预测转移性乳腺癌的预后,但其改善患者预后的能力在临床试验中尚未得到证实。目前研究专注于CTC的分子表征,作为肿瘤组织的“替代物”以非侵入性地方式评估癌症基因组表达及其在治疗过程中的演变。CTC中存在上皮-间质转化过程（EMT）,其特点为上皮标志物的缺失。EMT过程可以存在于侵袭性及耐药性较强的细胞,其计数和表征,能够引起肿瘤的复发和进展,具有较高的临床价值。本文深入探讨循环肿瘤细胞的异质性及在转移性乳腺癌上皮-间质转化过程中的作用。使其成为乳腺癌患者监测转移和预后的常规的检测指标,并有助于明确转移的机制,更有望发现乳腺癌转移治疗的新靶点。     

Twist 对EMT 调控在循环肿瘤细胞监测与抗癌药物评价中的临床意义*

肿瘤细胞的上皮间质可塑性变化包括上皮- 间质化（epithelial-mesenchymal transition ,EMT ）和间质- 上皮转化（mesenchymal-epithelial transition,MET ）的可逆过程,在循环肿瘤细胞（circulating tumor cells ,CTCs）形成、转归及肿瘤转移过程中起到重要作用。Twist在人横纹肌肉瘤、乳腺癌、胃癌等多种肿瘤中过表达,肿瘤细胞中Twist与多种信号通路连接,形成复杂的网状环路参与调控CTCs中EMT/MET的发生并促进肿瘤细胞向远处转移。因此,通过监测CTCs中Twist本身以及所调控的上皮- 间质表型分子标志物的变化,不仅可以增加肿瘤标志物CTCs的检出率,提供肿瘤临床分期及预后评估的直接证据;而且,对于评估多种抗肿瘤药物的疗效及耐药机制均具有重要的临床意义。     

乳腺癌循环肿瘤细胞检测方法的研究进展

目的:对乳腺癌循环肿瘤细胞(CTC)检测方法进行简要总结和评述.方法:以乳腺肿瘤和CTC为关键词,检索1995-01-2010-05 PubMed、MEDLINE、EMBASE、Science Direct、Springer、CNKI和维普数据库的相关文献.纳入标准:关于CTC检测方法的文献.根据纳入标准符合分析文献39篇.结果:伴随近年生物学技术的飞速发展,CTC的检测敏感性和特异性显著提高.目前,CTC检测方法多由富集分离和标记鉴定两部分组成.Cell Search系统和实时定量逆转录聚合酶链反应法是目前最常用的CTC检测方法,前者特异性较好、可获取形态学信息并可计数,后者敏感性更高.结论:CTC检测方法众多,但尚缺乏公认的检测标志和标准的检测流程.进一步提高CTC的检测效率有助于加深对其应用价值的认识.     

循环肿瘤细胞株的建立

循环肿瘤细胞(CTC)具有的特异性(上皮间质转化、与骨髓来源细胞的融合、抗失巢凋亡)决定了将其作为原代目标进行培养的必要性,所培养出的细胞株将为进一步研究恶性肿瘤的转移机制提供良好的物质基础,为患者的靶向治疗提供个体化的新方向.     

Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma

Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been recently investigated in several cancer types, but their respective clinical significance remains to be determined. In our prospective study, we compared the detection rate and the prognostic value of these two circulating biomarkers in patients with metastatic uveal melanoma. GNAQ/GNA11 mutations were characterized in archived tumor tissue. Using a highly sensitive and mutation‐specific bidirectional pyrophosphorolysis‐activated polymerization (bi‐PAP) technique, GNAQ c.626A>T, GNAQ c.626A>C and GNA11 c.626A>T copy numbers were quantified in plasma from 12 mL of blood. CTCs were detected at the same time in 7.5 mL of blood by the CellSearch® technique. Patient characteristics and outcome were prospectively collected. CTCs (≥1) were detected in 12 of the 40 included patients (30%, range 1–20). Among the 26 patients with known detectable mutations, ctDNA was detected and quantified in 22 (84%, range 4–11,421 copies/mL). CTC count and ctDNA levels were associated with the presence of miliary hepatic metastasis (p = 0.004 and 0.03, respectively), with metastasis volume (p = 0.005 and 0.004) and with each other (p < 0.0001). CTC count and ctDNA levels were both strongly associated with progression‐free survival (p = 0.003 and 0.001) and overall survival (p = 0.0009 and <0.0001). In multivariate analyses, ctDNA appeared to be a better prognostic marker than CTC. In conclusion, ctDNA and CTC are correlated and both have poor prognostic significance. CTC detection can be performed in every patient but, in patients with detectable mutations, ctDNA was more frequently detected than CTC and has possibly more prognostic value.     

肝细胞癌患者循环血肿瘤细胞的检测、分型鉴定及其临床意义

目的 通过对肝细胞癌(hepatocellular carcinoma,HCC)患者外周循环血肿瘤细胞(circulating tumor cells,CTCs)的检测及亚型鉴定,分析其与HCC临床分期的关系及对手术预后的影响.方法 采用CanPatrolTM CTC-二代捕获技术联合RNA多重原位杂交分析(RNA in situ hybridisation,RNA-ISH),检测112例可手术切除HCC患者术前1～2 d与术后8～10 d外周循环血中的肿瘤细胞,并根据上皮-间叶转化(epithelial-mesenchymal transition,EMT)相关标志物的表达情况对其进行分型鉴定.同时,抽取20名健康志愿者的外周血作对照.结果 112例HCC患者术前1～2 d检测出CTCs101例(90.18％),20名健康志愿者的外周血中未检测到CTCs.根据EMT相关标志物的表达情况,将检测出的CTCs分为上皮型CTCs、上皮为主型CTCs、上皮/间叶混合型CTCs、间叶为主型CTCs及间叶型CTCs.其中CTC总数及间叶型CTC的比例与HCC的巴塞罗那肝癌临床(barcelona clinic liver cancer,BCLC),分期密切相关.当以CTC总数等于16作为临界点时,预测患者术后极早期复发的敏感性为55.3％,特异性为92.3％,曲线下面积(area under the curve,AUC)为0.74;当以间叶型CTC的比例等于2％作为临界点时,预测患者术后极早期复发的敏感性为80.9％,特异性为69.2％,AUC为0.748.CTC总数≥16且间叶型CTC的比例≥2％组的患者中位无瘤生存期为3.5个月,明显低于单纯CTC总数≥16或间叶型CTC的比例≥2％组(7个月)和CTC总数＜16且间叶型CTC的比例＜2％组(13.5个月),差异有统计学意义(P＜0.05).112例HCC患者术后8～10 d CTC总数较术前有所下降,但间叶型CTC的比例较术前增多.术后出现间叶型CTC的比例增多的患者无瘤生存期短于间叶型CTC的比例下降(或不变)的患者,其预后也较差(P＜0.05).对10例患者进行术后连续定期CTCs变化的动态监测直至复发,发现其中8例患者于出现临床可见复发病灶前的1～2个月,CTCs就可出现逐渐增多的趋势.结论 HCC患者外周血CTC阳性率高,CTCs能被检测出存在于早期HCC患者外周血中,提示HCC的播散转移是早期事件;术前高CTC总数或高间叶型CTC的比例以及术后出现间叶型CTC的比例增多的患者,其复发时限较短,预后较差.术后动态监测CTCs变化,对HCC极早期复发的预测具有一定的临床意义.     

Detection and characterization of invasive circulating tumor cells derived from men with metastatic castration‐resistant prostate cancer

The Vitatex cell‐adhesion matrix (CAM) platform allows for isolation of invasive circulating tumor cells (iCTCs). Here we sought to determine the utility of prostate‐specific membrane antigen (PSMA) as a metastatic castration‐resistant prostate cancer (mCRPC) iCTC biomarker, to identify solitary cells and clusters of iCTCs expressing either epithelial, mesenchymal, or stem cell markers, and to explore the feasibility of iCTC epigenomic analysis. CTCs were isolated and enumerated simultaneously using the Vitatex and CellSearch platforms in 23 men with mCRPC. CAM‐avid iCTCs were identified as nucleated cells capable of CAM uptake, but without detectable expression of hematopoietic lineage (HL) markers including CD45. iCTCs were enumerated immunocytochemically (ICC) and by flow cytometry. Whole‐genome methylation status was determined for iCTCs using the Illumina HumanMethylation27 BeadChip. Thirty‐four samples were collected for iCTC analysis. A median of 27 (range 0–800) and 23 (range 2–390) iCTCs/mL were detected by ICC and flow, respectively. In a subset of 20 samples, a median of seven CTCs/mL (range 0–85) were detected by the CellSearch platform compared to 26 by the CAM platform. iCTC clusters were observed in 17% of samples. iCTCs expressing PSMA as well as markers of EMT and stemness were detectable. The iCTC methylation profile highly resembled mCRPC. More CTCs were recovered using the CAM platform than the CellSearch platform, and the CAM platform allowed for the detection of iCTC clusters, iCTCs expressing EMT and stem‐cell markers, and characterization of the iCTC methylome. Correlation with clinical data in future studies may yield further insight into the functional significance of these findings.     

Detection of circulating tumor cells: Advances and critical concerns

Metastasis is the main cause of cancer-related death and the major challenge in cancer treatment. Cancer cells in circulation are termed circulating tumor cells (CTCs). Primary tumor metastasis is likely due to CTCs released into the bloodstream. These CTCs extravasate and form fatal metastases in different organs. Analyses of CTCs are clarifying the biological understanding of metastatic cancers. These data are also helpful to monitor disease progression and to inform the development of personalized cancer treatment-based liquid biopsy. However, CTCs are a rare cell population with 1–10 CTCs per ml and are difficult to isolate from blood. Numerous approaches to detect CTCs have been developed based on the physical and biological properties of the cells. The present review summarizes the progress made in detecting CTCs.     

循环肿瘤细胞的检测及其在乳腺癌患者中的临床应用

由于循环肿瘤细胞（ｃｉｒｃｕｌａｔｉｎｇｔｕｍｏｒｃｅｌｌ,ＣＴＣ）能够反映肿瘤侵袭与转移,检测ＣＴＣ也就在成为肿瘤界研究的热点。外周血ＣＴＣ非常少,仅能通过肿瘤特异性抗原来检测。本综述主要介绍了ＣＴＣ的富集、检测过程、常用标记物及其在乳腺癌患者中的临床应用。     

纳米技术在循环肿瘤细胞中的研究进展

循环肿瘤细胞(CTC)对于监测肿瘤复发及判断预后具有重要意义.纳米技术为检测CTC提供了良好的平台,使CTC的应用具有广阔的发展前景.同时,利用纳米技术设计杀灭CTC的纳米装置在清除CTC方面有广阔的应用前景,为肿瘤治疗提供了新的研究方向.     

Detection and enumeration of circulating tumor cells based on their invasive property

Circulating tumor cells (CTCs) are in limited numbers and heterogeneous, making their detection, isolation, and enumeration a major challenge. To overcome these difficulties, we developed a novel method to detect and enumerate CTCs with invasive property. Our assay consists of three simple steps: enrichment, Matrigel invasion assay, and immunostaining. We have validated this method using mouse xenograft tumor models and confirmed its utility in human cancer patients. Our method does not require special equipment and antigen expression for CTC selection, is less likely to be affected by the heterogeneity of the CTCs, and could be applicable to virtually all cancers. Most important, our method enumerates invasive CTCs, which may allow more accurate correlations with clinical outcome and treatment response compared with other CTC detection methods.     

Detection of circulating carcinoma cells by telomerase activity

Telomerase has been shown to be a marker of epithelial cancer cells. We developed a method that allows the detection of circulating carcinoma cells in the blood of cancer patients. Circulating epithelial cells are harvested from peripheral blood mononuclear cells by immunomagnetic separation using BerEP4-coated beads. A telomeric repeat amplification protocol (TRAP)-ELISA is then used to measure telomerase in harvested epithelial cells. This method is specific and sensitive as demonstrated by experiments using BerEP4-positive and negative cell lines. Whereas we never found telomerase activity in harvested epithelial cells (HEC) samples from 30/30 healthy donors, we have detected telomerase activity in HEC from 11/15 (73%) patients with stage IIIB or IV non-small cell lung cancer (NSCLC) patients and from 8/11 (72%) stage C or D (Dukes classification) colon cancer patients. This non-invasive method could be of great value as a diagnostic or prognostic marker, or for monitoring cancer progression.