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1.
循环肿瘤细胞(CTCs)来源于原发肿瘤脱落并进入血液循环系统的癌细胞,其检测有助于肿瘤的筛查和早期诊断、肺癌分期、复发转移监测、个体化治疗。由于其在静脉血的稀有性,导致其在临床上应用的局限性。比较肺癌动、静脉血中CTCs含量有望打破这种局限。肺癌动脉血中的CTCs含量可能大大高于静脉血,检测动脉CTCs或可大幅度提高C...  相似文献   

2.
目的评价肝细胞癌(HCC)患者循环肿瘤细胞(CTCs)监测对手术切除HCC的意义。方法选取行手术治疗的HCC患者60例,应用基于生物素化去唾液酸糖蛋白受体(ASGPR)的循环HCC细胞分离/鉴定系统及免疫组织化学技术(IHC)于术前、术后第1天及第7天检测外周静脉血中CTCs阳性率,分析不同时期CTCs阳性率的差异及术前CTCs阳性率与患者临床资料的关系,Kaplan-Meier生存曲线分析CTCs阳性率与患者预后的关系。结果术后第7天CTCs阳性率显著低于术前及术后第1天(P<0. 05)。术前CTCs阳性患者肿瘤直径、数量及血管浸润率均显著高于阴性患者(P<0. 05),而年龄、性别、甲胎蛋白(AFP)浓度、乙肝表面抗原(Hbs Ag)水平、肿瘤分化程度、Child分级差异无统计学意义(P>0. 05),术前CTCs阳性患者预后总生存时间显著短于阴性患者(P<0. 05)。结论 CTCs可在一定程度上反映HCC患者病情进展,并可作为预测患者预后的指标之一。  相似文献   

3.
目的探讨非小细胞肺癌循环肿瘤细胞(CTCs)定量检测方法。方法CD45免疫磁珠阴性分选组20侧,CD326免疫磁珠阳性分选组25例,均为明确诊断的非小细胞肺癌患者。磁性分离富集后肺静脉与外周静脉血标本应用多参数流式细胞仪对CTCs进行定量检测。结果阴性分选由于只能去除CD45阳性细胞,回收目的细胞纯度低。阳性分选组中25例术中肺静脉血CTCs定量检测阳性率为64%(16/25),外周静脉血CTCs阳性率40%(10/25,P〈0.05)。结论免疫磁珠富集联合流式细胞分析检测CTCs的敏感性和特异性较高。  相似文献   

4.
目的分析外周血循环肿瘤细胞(CTCs)数目与老年晚期非小细胞肺癌(NSLCL)患者疗效及预后的相关性。方法选择50例老年晚期NSCLC患者为研究对象,全部患者入院后接受多西他赛+顺铂的方案化疗,化疗6个周期后评价疗效,化疗结束后随访1年,将发生远处转移及死亡者作为预后不良组,分别于入院时、化疗结束时、随访结束时,抽取患者肘正中静脉血7.5 ml,检测其CTCs阳性率,对比不同化疗效果及不同预后患者的CTCs阳性率,并分析CTCs阳性情况与疗效、预后的相关性。结果全部50例老年晚期NSCLC患者均接受化疗治疗,在化疗6个周期后,完全缓解、部分缓解、进展、稳定例数分别为1例、15例、9例、25例,有效率为32.00%。50例患者化疗期间均无死亡病例,化疗结束随访1年,50例患者中12例发生远处转移,10例死亡,预后不良22例。化疗实施前50例患者基线评估CTCs阳性率为40.00%,化疗6个周期后,其CTCs阳性率为26.00%(13/50),较化疗前降低,且化疗后CTCs阳性率多见于病情进展或稳定患者,差异有统计学意义(P<0.05);随访1年后,预后不良组CTCs阳性率明显高于预后良好组,差异有统计学意义(P<0.05);经Spearman相关性分析检验发现,外周血CTCs阳性率与老年NSCLC患者疗效、预后均呈负相关(r=-0.487、-0.301,P均<0.001)。结论外周血CTCs在老年晚期NSCLC中的表达情况与患者化疗效果、远处转移及死亡风险密切相关,可将外周血CTCs阳性数目与肿瘤标志物联合使用,为老年晚期NSCLC患者的疗效及预后评估提供依据。  相似文献   

5.
目的:研究甲磺酸阿帕替尼三线及三线以上治疗晚期非小细胞肺癌的临床疗效及循环肿瘤细胞(CTCs)在预后评价中的意义。方法:回顾性分析2016年2月-2018年10月于聊城市人民医院就诊的晚期非小细胞肺癌患者126例病例资料。所有患者给予口服甲磺酸阿帕替尼500 mg/次,每日1次,28 d为1个周期,2周期后观察临床效果...  相似文献   

6.
肝癌在恶性肿瘤死亡顺位中仅次于胃癌、食道癌而居第三位〔1〕。尽管针对肝癌已有诸多治疗措施,但由于大多数患者诊断延迟,发现时已达中晚期,导致肝癌患者治疗后的预后较差,而根本原因即是肿瘤的复发与转移〔2〕。目前所能发现的肿瘤转移灶大多数是通过计算机断层扫描(CT)、磁共振成像(MRI)或正电子发射计算机断层显像(PET-CT)等影像检测手段,但此时往往进入了肿瘤晚期。循环肿瘤细胞(CTCs)是指由原发肿瘤或转移灶通过血管侵犯而侵入癌症患者外周血液中的肿瘤细胞〔3〕。早在1869年,Ashworth就在1例乳腺癌患者尸检过程中发现了外周血中存在肿瘤细胞,随着近年来分子生物学及检测技术的发展,CTCs成为肿瘤早期转移及治疗术后复发领域研究的热点〔4,5〕。已知,CTCs在乳腺癌、肺癌、前列腺癌及结直肠癌复发及预后的预测中起着重要作用,但其在肝癌中的研究应用还远不及这些肿瘤类型。本文着重探讨肝癌CTCs的检测及其对肝癌复发及转移的预测作用。  相似文献   

7.
目的评估用内镜超声引导下细针抽吸术(EUS-FNA)于胰腺癌门静脉采血检测循环肿瘤细胞(CTCs)的安全性及有效性。方法该研究为一项前瞻性单中心临床研究,纳入5例胰腺癌患者,行EUS-FNA门静脉采血。以外周血CTCs为对照,采用阴性免疫磁珠联合FISH法和叶酸受体阳性CTCs检测试剂盒检测门静脉血和外周血CTCs的细胞含量。结果5例患者EUS-FNA下门静脉采血均成功。1例出现血液凝集,未能进行CTCs检测。4例患者进行检测,3例门静脉血和外周血检测到CTCs。其中门静脉血CTCs细胞含量为(10.5±4.0)FU/3.7 mL,外周血CTCs含量为(11.4±4.2)FU/3.7 mL,两组比较差异无统计学意义(P>0.05)。术中术后无感染、腹腔出血和休克等并发症。结论内镜超声引导下胰腺癌门静脉血CTCs测定是一项安全可行的方法,可有助于胰腺癌早期转移的预估和治疗方案的选择。  相似文献   

8.
目的探究多西他赛与奈达铂联合放疗对老年食管癌患者的临床疗效、血清指标及肿瘤循环细胞(CTCs)的影响。方法 92例老年食管癌患者随机分为观察组和对照组各46例;对照组给予单纯放疗,观察组同期给予多西他赛与奈达铂化疗;比较两组临床疗效、治疗前后的血清癌胚抗原(CEA)、鳞状细胞癌抗原(SCC)、Cyfra21-1及外周血CTCs阳性率,观察两组的不良反应。结果观察组和对照组总有效率分别为84. 78%、65. 21%,差异有统计学意义(P0. 05)。治疗后两组血清CEA、SCC及Cyfra21-1水平均显著降低(P0. 05),且观察组CEA、SCC及Cyfra21-1水平显著低于对照组(P0. 05);治疗后两组CTCs阳性率显著低于治疗前,观察组CTCs阳性率显著低于对照组(P0. 05);观察组白细胞下降及恶心呕吐明显高于对照组(P0. 05),其余不良反应无显著差异(P0. 05),所有不良反应经对症处理后均可耐受。结论多西他赛与奈达铂联合放疗能提高老年食管癌临床疗效,降低血清CEA、SCC、Cyfra21-1水平,减少CTCs阳性表达,毒副作用较单纯放疗略有增加,但患者均可耐受。  相似文献   

9.
[摘要] 目的 探讨直肠癌患者围手术期外周血循环肿瘤细胞(CTCs)的变化情况及其对患者预后的影响。方法 选择2015-09~2016-12广西壮族自治区人民医院胃肠外科收治的直肠癌患者30例,采用随机数字表法将其分为腹腔镜手术组和开腹手术组,每组15例。采用CanpatrolTM 2代技术对患者手术前后的外周血CTCs进行分型检测。术后随访22~33个月,分析两组患者手术前后的CTCs水平变化,术前各分型CTCs与疾病特征的关联性以及手术前后CTCs对患者预后的影响。结果 腹腔镜手术组术后总CTCs水平较术前显著降低(P<0.05)。腹腔镜手术组术前混合型CTCs水平显著高于开腹手术组(P<0.05),但术后两组差异无统计学意义(P>0.05)。两组手术前后间质型CTCs和上皮型CTCs水平比较差异均无统计学意义(P>0.05),且同组手术前后比较差异亦无统计学意义(P>0.05)。间质型阴性组肿瘤直径≤3 cm的人数比例显著高于间质型阳性组(P<0.05)。术前总CTCs、混合型CTCs、上皮型CTCs情况与患者年龄、性别、T分期、N分期及肿瘤直径的关联性不显著(P>0.05)。3例术后CTCs阴性者在随访过程中均未发生死亡;27例术后CTCs 阳性者在随访过程中出现死亡4例,术后CTCs阴性者的生存情况显著优于阳性者(log-rank检验: χ2=6.553,P=0.031)。2例术前CTCs阴性者在随访过程中均未死亡,28例术前CTCs阳性者在随访过程中出现死亡4例,术前CTCs阴性者的生存情况显著优于阳性者(log-rank检验: χ2=5.245,P=0.027)。结论 外周血CTCs可用于直肠癌患者预后评价,指导临床治疗。  相似文献   

10.
肿瘤细胞表现的高度异质性严重困扰着肿瘤临床诊断和治疗.因此,肿瘤分子分型及其指导个体化治疗一直是肿瘤研究领域的热点.循环肿瘤细胞(circulating tumor cells,CTCs)作为具有肿瘤代表性的"液体活检"样本,允许多次、实时、非侵入性获取,是指导个体化肿瘤诊疗的绝佳标本.目前认为,基于分子鉴定检测少数更具存活力和侵袭性的CTCs比单独CTCs计数更有价值.而在肿瘤转移过程中C T C s表现的多种生物学特性及其分子机制都可被用于分型,并且可能成为个体化肿瘤诊疗的靶点.本文综述近年来关于CTCs分子鉴定的研究进展,以及CTCs分子分型指导个体化诊疗的研究现状,提出相关领域今后的研究方向.  相似文献   

11.
This study aimed to explore the dynamics of circulating tumor cells (CTCs) and CD8+ T cells in stage II–III non-small cell lung cancer patients with CTCs in different programmed death-ligand 1 (PD-L1) status treated with radiotherapy and evaluate the correlation between CTCs and CD8+ T cells.This study was a retrospective study which reviewed 69 stage II–III non-small cell lung cancer patients underwent postoperative radiotherapy and peripheral blood tests of CTCs and T lymphocyte were available before radiation, 1 week after radiation and 1 month after radiation.In this study, 25 patients had PD-L1 positive CTCs and 44 patients had PD-L1 negative CTCs. The CTCs count was significantly decreased compared with baseline in patients with different PD-L1 status CTCs at 1 week and 1 month after radiotherapy. The proportion of CD8+ T cells was significantly increased at 1 month after radiotherapy compared with baseline in the total population (mean change, 7.24 ± 2.12; P < .05) and patients with PD-L1 negative CTCs (mean change, 7.17 ± 2.65; P < .05). One month after radiotherapy, the proportion of CD8+ T cells was negatively correlated with the CTCs count in the total population (r = −0.255, P = .034) and PD-L1 negative patients (r = –0.330, P = .029). In patients with PD-L1 negative CTCs, the CTCs count 1 week after radiotherapy (hazard ratio, 0.150 [95% confidence intervals., 0.027–0.840], P = .031) and the proportion of CD8+ T cells 1 month after radiotherapy (hazard ratio, 7.961 [95% confidence intervals, 1.028–61.68], P = .047) were independent prognostic factors for disease recurrence.After radiotherapy, only PD-L1-negative patients had a significant increase in the CD8+ T cell levels, while it was negatively correlated with CTCs count and was an independent prognostic factors of disease recurrence.  相似文献   

12.
AIM To analyse the long-term prognostic impact of circulating tumour cells(CTCs) in gastric cancer patients who underwent surgery. METHODS A 7.5-m L peripheral vein blood sample was obtained from each patient with treatment-negative gastric adenocarcinoma before surgery. OBP-401, a telomerasespecific, replication-selective, oncolytic adenoviral agent carrying the green fluorescent protein gene, was used to label CTCs. Correlations between the number of CTCs and clinical end points were evaluated. RESULTS The median follow-up period of the surviving patients with gastric cancer was 60 mo. The CTC number tended to increase concomitantly with disease progression. The overall survival of patients with more than five CTCs in 7.5-m L of peripheral blood was lower than that of patients with five or less CTCs, although the difference was not significant(P = 0.183). A significant difference in relapse-free survival was found between patients with more than five and those with five or less CTCs(P = 0.034).CONCLUSION A lower number of CTCs was correlated with higher relapse-free survival rates in patients. Detection of CTCs using OBP-401 may be useful for predicting prognosis in gastric cancer.  相似文献   

13.
14.
HER-2 gene amplification can be acquired as breast cancer progresses   总被引:16,自引:0,他引:16       下载免费PDF全文
Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2-negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin) therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2-positive tumors, the HER-2/chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 +/- 2.72 vs. 2.8 +/- 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.  相似文献   

15.
Rare circulating tumor cells (CTCs) present in the bloodstream of patients with cancer provide a potentially accessible source for detection, characterization, and monitoring of nonhematological cancers. We previously demonstrated the effectiveness of a microfluidic device, the CTC-Chip, in capturing these epithelial cell adhesion molecule (EpCAM)-expressing cells using antibody-coated microposts. Here, we describe a high-throughput microfluidic mixing device, the herringbone-chip, or "HB-Chip," which provides an enhanced platform for CTC isolation. The HB-Chip design applies passive mixing of blood cells through the generation of microvortices to significantly increase the number of interactions between target CTCs and the antibody-coated chip surface. Efficient cell capture was validated using defined numbers of cancer cells spiked into control blood, and clinical utility was demonstrated in specimens from patients with prostate cancer. CTCs were detected in 14 of 15 (93%) patients with metastatic disease (median = 63 CTCs/mL, mean = 386 ± 238 CTCs/mL), and the tumor-specific TMPRSS2-ERG translocation was readily identified following RNA isolation and RT-PCR analysis. The use of transparent materials allowed for imaging of the captured CTCs using standard clinical histopathological stains, in addition to immunofluorescence-conjugated antibodies. In a subset of patient samples, the low shear design of the HB-Chip revealed microclusters of CTCs, previously unappreciated tumor cell aggregates that may contribute to the hematogenous dissemination of cancer.  相似文献   

16.
BackgroundRecently, circulating tumor-cell-associated white blood cell (CTC-WBC) clusters have been reported to have prognostic value in some cancers. The prognostic role of CTC-WBC clusters in lung cancer has not yet been elucidated. Very little information is available about the biological characteristics of CTC-WBC clusters.MethodsA total of 82 patients with non-small cell lung cancer (NSCLC) were included in this study, and 61 patients with advanced-stage disease were closely followed-up. All patients had blood drawn prior to treatment. Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) platform was used to isolate and identify CTCs and CTC-WBC clusters. Kaplan-Meier survival analysis and Cox regression analysis were applied to assess patient progression-free survival (PFS). Further, qualitative and quantitative analyses the size and ploidy characteristics of CTC-WBC clusters.ResultsFirstly, CTC‐WBC clusters appeared more in the advanced (stage III and IV) stage (P=0.043) than in the early stage. Furthermore, the multivariable analysis (Cox proportional hazards model) revealed that the high‐CTC (≥7/6 mL) group and CTC‐WBC clusters (≥1/6 mL) positive group both had significantly worse PFS, with a hazard ratio (HR) of 2.89 [95% confidence interval (CI): 1.36–6.17, P=0.006] and 2.18 (95% CI: 1.07–4.43, P=0.031), respectively. In the conjoint analysis, compared to patients with <7 CTCs/6 mL without CTC-WBC clusters, patients with ≥7 CTCs/6 mL with CTC-WBC clusters had the highest risk of progression (HR =7.13, 95% CI: 2.51–20.23, P<0.001). In addition, the presence of ≥3-cell CTC-WBC clusters in patients may indicate a shorter PFS (P<0.05) and a higher risk of progression (HR =2.90, 95% CI: 1.06–7.89, P=0.037). Furthermore, compared with the characteristics of the total CTCs, almost all of the CTCs that could recruit WBCs were large cells (≥5 µm) and exhibited polyploidy (≥ tetraploid) (both P<0.01).ConclusionsThe presence of CTC-WBC clusters was an independent prognostic factor for advanced NSCLC. The joint analysis of CTCs and CTC-WBC clusters could provide additional prognostic value to the enumeration of CTCs alone. Besides, most of the CTCs in CTC‐WBC clusters were large polyploid cells.  相似文献   

17.
Circulating tumor cells (CTCs) enter peripheral blood from primary tumors and seed metastases. The genome sequencing of CTCs could offer noninvasive prognosis or even diagnosis, but has been hampered by low single-cell genome coverage of scarce CTCs. Here, we report the use of the recently developed multiple annealing and looping-based amplification cycles for whole-genome amplification of single CTCs from lung cancer patients. We observed characteristic cancer-associated single-nucleotide variations and insertions/deletions in exomes of CTCs. These mutations provided information needed for individualized therapy, such as drug resistance and phenotypic transition, but were heterogeneous from cell to cell. In contrast, every CTC from an individual patient, regardless of the cancer subtypes, exhibited reproducible copy number variation (CNV) patterns, similar to those of the metastatic tumor of the same patient. Interestingly, different patients with the same lung cancer adenocarcinoma (ADC) shared similar CNV patterns in their CTCs. Even more interestingly, patients of small-cell lung cancer have CNV patterns distinctly different from those of ADC patients. Our finding suggests that CNVs at certain genomic loci are selected for the metastasis of cancer. The reproducibility of cancer-specific CNVs offers potential for CTC-based cancer diagnostics.As a genomic disease, cancer involves a series of changes in the genome, starting from primary tumors, via circulating tumor cells (CTCs), to metastases that cause the majority of mortalities (13). These genomic alterations include copy number variations (CNVs), single-nucleotide variations (SNVs), and insertions/deletions (INDELs). Regardless of the concentrated efforts in the past decades, the key driving genomic alterations responsible for metastases are still elusive (1).For noninvasive prognosis and diagnosis of cancer, it is desirable to monitor genomic alterations through the circulatory system. Genetic analyses of cell-free DNA fragments in peripheral blood have been reported (46) and recently extended to the whole-genome scale (79). However, it may be advantageous to analyze CTCs, as they represent intact functional cancer cells circulating in peripheral blood (10). Although previous studies have shown that CTC counting was able to predict progression and overall survival of cancer patients (11, 12), genomic analyses of CTCs could provide more pertinent information for personalized therapy (13). However, it is difficult to probe the genomic changes in DNA obtainable from the small number of captured CTCs. To meet this challenge, a single-cell whole-genome amplification (WGA) method, multiple annealing and looping-based amplification cycles (MALBAC) (14), has been developed to improve the amplification uniformity across the entire genome over previous methods (15, 16), allowing precise determination of CNVs and detection of SNVs with a low false-positive rate in a single cell. Here, we present genomic analyses of CTCs from 11 patients (SI Appendix, Table S1) with lung cancer, the leading cause of worldwide cancer-related deaths. CTCs were captured with the CellSearch platform using antibodies enrichment after fixation, further isolated with 94% specificity (Materials and Methods), and then subjected to WGA using MALBAC before next-generation sequencing.  相似文献   

18.
AIM:To investigate the feasibility of separation and cultivation of circulating tumor cells(CTCs)in pancreatic cancer(Pa C)using a filtration device.METHODS:In total,24 Pa C patients who were candidates for surgical treatment were enrolled into the study.Peripheral blood samples were collected before an indicated surgery.For each patient,approximately8 m L of venous blood was drawn from the antecubitalveins.A new size-based separation Meta Cell?technology was used for enrichment and cultivation of CTCs in vitro.(Separated CTCs were cultured on a membrane in FBS enriched RPMI media and observed by inverted microscope.The cultured cells were analyzed by means of histochemistry and immunohistochemistry using the specific antibodies to identify the cell origin.RESULTS:CTCs were detected in 16 patients(66.7%)of the 24 evaluable patients.The CTC positivity did not reflect the disease stage,tumor size,or lymph node involvement.The same percentage of CTC positivity was observed in the metastatic and non-metastatic patients(66.7%vs 66.7%).We report a successful isolation of CTCs in Pa C patients capturing proliferating cells.The cells were captured by a capillary action driven size-based filtration approach that enabled cells cultures from the viable CTCs to be unaffected by any antibodies or lysing solutions.The captured cancer cells displayed plasticity which enabled some cells to invade the separating membrane.Further,the cancer cells in the“bottom fraction”,may represent a more invasive CTC-fraction.The CTCs were cultured in vitro for further downstream applications.CONCLUSION:The presented size-based filtration method enables culture of CTCs in vitro for possible downstream applications.  相似文献   

19.
AIM To compare the capacity of newly developed epidermal growth factor receptor(EGFR)-targeted immune magnetic liposomes(EILs) vs epithelial cell adhesion molecule(Ep CAM) immunomagnetic beads to capture colorectal circulating tumor cells(CTCs).METHODS EILs were prepared using a two-step method, and the magnetic and surface characteristics were confirmed. The efficiency of capturing colorectal CTCs as well as the specificity were compared between EILs and Ep CAM magnetic beads. RESULTS The obtained EILs had a lipid nanoparticle structure similar to cell membrane. Improved binding with cancer cells was seen in EILs compared with the method of coupling nano/microspheres with antibody. The binding increased as the contact time extended. Compared with Ep CAM immunomagnetic beads, EILs captured more CTCs in peripheral blood from colorectal cancer patients. The captured cells showed consistency with clinical diagnosis and pathology. Mutation analysis showed same results between captured CTCs and cancer tissues. CONCLUSION EGFR antibody-coated magnetic liposomes show high efficiency and specificity in capturing colorectal CTCs.  相似文献   

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