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Renal cell carcinoma is one of the common malignant tumors in genitourinary cancer.20％-30％ of patients have distant metastases.However,current biomarkers used for diagnosis,recurrence monitoring,and prognosis assessment are still uncertain.Circulating tumor cells (CTCs) are tumor cells that are detached from the primary tumor or metastases,and invade and presenting in peripheral blood vessels.Therefore,CTCs is regarded as a key step in the process of tumor metastasis.However,current studies on CTCs of renal cell carcinoma are facing with problems such as inconsistent detection methods and limited clinical applications.This article reviews the progress in the detection and clinical application of CTCs of renal cell carcinoma.
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Objective To establish a new method to measure the elastic modulus of living circulating tumor cells (CTCs) by micropipette aspiration. Methods Living CTCs were enriched by commercial microfluidic chips and identified individually using EpCAM antibody under fluorescence microscope. The elastic modulus of CTCs was measured using micropipette aspiration and compared with cancer cell lines. Results For the elastic modulus of different cancer cell lines, heterogeneity was found not only between the different types of cancer cell lines but also inside the same cell line. The CTCs in breast cancer had a smaller elasticity modulus compared with MCF-7 cancer cell line. Conclusions This method can measure the elastic modulus of living CTCs, which provides cell mechanics data for studying the relationship between physical properties of CTCs and diagnosis of cancers, as well as developing the physical biomarkers of tumor cells.
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Objective@#To discuss the application experience and predictive value of circulating tumor cells for urothelial carcinoma.@*Methods@#The clinical data of 96 patients with urothelial carcinoma treated by Beijing Cancer Hospital Urologic Department between September 2017 and September 2019 were analyzed retrospectively to evaluate relationship between the number of CTCs and pathological outcome. The mean age of the entire cohort was 62(40-87)years, with 74 males and 22 females. There were 13 cases of upper urinary tract tumors (pyelocarcinoma and ureteral carcinoma), 83 cases of bladder carcinoma, and 12 cases of lymph node metastasis. There were 77 cases of primary onset and 19 cases of recurrence. 68 cases in single focus group and 28 cases in multiple group. There were 29 cases in non infiltrative Ta stage, 42 cases in infiltrative lamina propria T1 stage, 16 cases in infiltrative muscle T2 stage, and 9 cases in extra-muscular≥T3 stage. At least 3ml of peripheral blood was collected after fasting for at least 8 hours, After cleavage and centrifugation, immunomagnetic beads were added, folate probe was added, and then amplification was carried out. Then the copy number of CTCs in each ml of blood was calculated. Logistic linear regression was used to analyze the risk factors of lymph node metastasis.@*Results@#The mean CNC of all patients was 12.3±7.3; the mean CNC of ≤62 years old group was 10.8±4.2; the mean CNC of >62 years old group was 13.7±9.2; the mean CNC of initial cases was 11.5±5.3; the mean CNC of recurrent cases was 15.5±12.2. Age (P=0.135) and frequency of onset (P=0.087) had no effect on the number of CTCs. The average CNC of single focus group was 10.5±5.2, multiple focus group was 16.5±9.7, Ta stage group was 8.2±2.3, T1 stage group was 12.0±4.4, T2 stage group was 16.4±6.8, and ≥T3 stage group was 19.5±16.6. The number of lesions (P<0.001) was significantly correlated with pathological T stage (P<0.001) and the number of CTCs. Univariate regression analysis showed that T stage (P<0.001) and the number of CTCs (P=0.02) might be correlated with lymph node metastasis; multivariate analysis showed that only T stage could be used as an independent predictor of lymph node metastasis (P=0.002).@*Conclusions@#CTCs can be used to predict lymph node metastasis of urothelial carcinoma.
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Objective To discuss the application experience and predictive value of circulating tumor cells for urothelial carcinoma.Methods The clinical data of 96 patients with urothelial carcinoma treated by Beijing Cancer Hospital Urologic Department between September 2017 and September 2019 were analyzed retrospectively to evaluate relationship between the number of CTCs and pathological outcome.The mean age of the entire cohort was 62(40-87)years,with 74 males and 22 females.There were 13 cases of upper urinary tract tumors (pyelocarcinoma and ureteral carcinoma),83 cases of bladder carcinoma,and 12 cases of lymph node metastasis.There were 77 cases of primary onset and 19 cases of recurrence.68 cases in single focus group and 28 cases in multiple group.There were 29 cases in non infiltrative Ta stage,42 cases in infiltrative lamina propria T1 stage,16 cases in infiltrative muscle T2 stage,and 9 cases in extramuscular≥T3 stage.At least 3ml of peripheral blood was collected after fasting for at least 8 hours,After cleavage and centrifugation,immunomagnetic beads were added,folate probe was added,and then amplification was carried out.Then the copy number of CTCs in each ml of blood was calculated.Logistic linear regression was used to analyze the risk factors of lymph node metastasis.Results The mean CNC of all patients was 12.3 ±7.3;the mean CNC of ≤62 years old group was 10.8 ±4.2;the mean CNC of ＞62 years old group was 13.7 ±9.2;the mean CNC of initial cases was 11.5 ±5.3;the mean CNC of recurrent cases was 15.5 ± 12.2.Age (P =0.135) and frequency of onset (P =0.087) had no effect on the number of CTCs.The average CNC of single focus group was 10.5 ± 5.2,multiple focus group was 16.5 ± 9.7,Ta stage group was 8.2 ±2.3,T1 stage group was 12.0 ±4.4,T2 stage group was 16.4 ±6.8,and ≥T3 stage group was 19.5 ± 16.6.The number of lesions (P ＜ 0.001) was significantly correlated with pathological T stage (P ＜ 0.001) and the number of CTCs.Univariate regression analysis showed that T stage (P ＜ 0.001) and the number of CTCs (P =0.02) might be correlated with lymph node metastasis;multivariate analysis showed that only T stage could be used as an independent predictor of lymph node metastasis (P =0.002).Conclusions CTCs can be used to predict lymph node metastasis of urothelial carcinoma.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with high morbidity and mortality and poor prognosis. The main reason for poor prognosis are difficulties in early diagnosis, common recurrence and metastasis after surgery. Therefore, early diagnosis and postoperative monitoring of HCC are particularly important to improve the overall prognosis of HCC patients. Circulating tumor cells (CTCs) are malignant tumor cells in blood circulation, which play an important role in tumor inva-sion and metastasis. As a"liquid biopsy"technique, CTC test can be performed in real-time and allows repeated monitoring of tumor cells in peripheral blood, which has great clinical application value in early tumor diagnosis, postoperative dynamic monitoring, and prognosis evaluation. In this article, the research progress of CTCs at home and abroad was retrospectively illustrated, and their detec-tion methods, research, and clinical applications for diagnosis, prognosis, and other aspects of HCC patients were systematically re-viewed.
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Hepatocellular carcinoma (HCC) is one of the most common malignant tumors.The prognosis of HCC patients is very poor due to the facts that vascular invasion and distance metastasis may occur in the earlier phase of the cancer.Therefore,it is very important to make earlier diagnosis and timely monitoring post-operatively to ensure the longer survival of HCC patients.Detection of circulating tumor cells (CTCs),as an liquid biopsy,which can detect the tumor cells timely and repeatedly in the circulation,plays an important role in the earlier diagnosis,treatment,monitoring,and making individualized therapeutic plan,etc.In this article,we retrospectively reviewed the current literatures to evaluate the values of CTCs in the diagnosis,therapy,and surveillance of HCC patients in order to guide the clinical practice.
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Circulating tumor cells (CTCs) are cancer cells that fall off from the primary tumor and enter into the blood circulation system. CTCs detection will contribute to diagnosing tumor in its early stage, monitoring the relapse and metastasis, evaluating the prognosis. In this review, the recent progress and the application in diagnosis and treatment of CTCs detection methods in lung cancer were summarized.
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Objective To establish a novel method using a nano microfluidic chip to detect circulating tumor cells (CTCs) in peripheral blood in gallbladder carcinoma,and to study the relationship between CTCs with clinicopathology and prognosis in these patients.Methods The peripheral blood samples of 51 patients with gallbladder carcinoma were collected from June 2014 to January 2017.The CTCs from peripheral blood samples were detected by a novel nano microfluidic chip.This study aimed to study the correlation between CTCs with the clinical and pathological features.The significance of CTCs on prognosis in patients with gallbladder carcinoma was also analyzed.Results The positive rate of CTCs in the peripheral blood of gallbladder carcinoma patients was 43.1％ (22/51).There were significant correlations between CTCs with liver metastasis (P ＜ 0.05) and Nevin staging (P ＜ 0.05).The 1-and 2-year overall survival (OS) in patients with CTCs were 70.7％ and 35.3％,and the 1-and 2-year OS in patients without CTCs were 92.0％ and 56.1％.There was a significant difference in the 2-year OS (P ＜ 0.05) but no significant difference in the 1-year OS between the 2 groups of patients (P ＞ 0.05).Conclusions Peripheral blood CTCs in patients with gallbladder carcinoma were efficaciously detected by a novel nano microfluidic chip.Peripheral blood CTCs was closely related to the Nevin staging and liver metastasis.CTCs could serve as a potential prognostic indicator in patients with gallbladder carcinoma.
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Circulating tumor cells (CTCs) are cancer cells that fall off from the primary tumor and enter into the blood circulation system. CTCs detection will contribute to diagnosing tumor in its early stage, monitoring the relapse and metastasis, evaluating the prognosis. In this review, the recent progress and the application in diagnosis and treatment of CTCs detection methods in lung cancer were summarized.
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Objective To estimate the diagnostic vaule of circulating tumor cells (CTCs) detection for epithelial ovarian cancer,and investigate the relationship between the presence of CTCs and the clinic pathologic characteristics of epithelial ovarian cancer patients.Methods Quantification of CTCs were performed using immunomagnetic bead based negative enrichment combined with flow cytometry in 65 patients with epithelial ovarian cancer,21 patients with benign ovarian diseases,and 10 healthy subjects.The differences among groups were analyzed by the Kruskal-Wallis H test (multi group comparison) and the Mann-Whitney U test (two group comparison),and the chi-square test was used in the positive rate comparison,the receiver operating characteristic (ROC) curve was established.The relationship between CTCs and clinic pathologic characteristics of epithelial ovarian cancer patients were analyzed.Results The receiver operating characteristic analysis showed the cut off value was 4.5 (＞ 4),the AUC was 0.806,and sensitivity,specificity and positive value (PPV) were 55.4 ％,96.8 ％ and 97.3 ％ respectively,in detecting patients with ovarian carcinoma malignancy.Quantification of CTCs in epithelial ovarian cancer was correlated with FIGO stages or distance metastasis (all P＜0.05),but not with patient age,histological types,pathologic differentiation,amount of ascites,tumor size and lymph node metastasis (all P＞0.05).Conclusion The detection of peripheral CTCs has a certain diagnosis value in epithelial ovarian cancer,especially with related to FIGO stages and distant metastasis.
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Objective To establish a cell level-based negative enrichmen technique to detect circulating tumor cells (CTCs) in the peripheral blood of patients with epithelial ovarian cancer.Methods The colon cancer SKOV-3 cells were mixed with 2 ml whole blood from healthy donors at different ratio.Quantification of CTCs was performed using immunomagnetic bead based negative enrichment combined with immunofluorescence antibody method.The method was evaluated the recovery rate of target cells,Samples of 32 patients with ovarian cancer and 10 controls were assayed for CTCs detection by above method.Results ①The recovery rate was ranging from 64％ ～80％ by spiking varying numbers of SKOV-3 into 2 ml blood samples of healthy volunteers.Regression analysis of number of recovered SKOV-3 cells yielded a regression equation of Y=0.782X-1.408 and a coefficient of determination of R2 =0.998.②Did not detect CK8/18-+ circulating tumor cells in 10 controls,and CK8/18+ circulating tumor cells in 18 cases of 32 Patients with ovarian cancer.The positive rate of CK 8/18 + circulating tumor cells was significantly differences between the two groups (x2 =7.681,P＜0.01).③The presence ofCTCs was significantly correlated with distant metastasis (x2 =5.776,P＜0.05).Conclusion The method of immunomagnetic bead based negative enrichment combined with immunofluorescence antibody technique for CTCs detection in peripheral blood of patients with ovarian cancer has a clinical value of application and extension.
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Objective To realize the high-efficient capture of circulating tumor cells (CTCs) in the blood of tumor patients by analytic modeling and optimization on the herringbone micro-fluidic chip. Methods By simulating the fluid flow within the herringbone chip with Fluent 15.0 and calculating the capture efficiency with MATLAB to understand how geometric parameters (the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height), flow rates and flow directions (forward flow, reverse flow) affected the cell-surface contact for capture of the CTCs, the capture efficiency was predicted and then validated by experiments. Results The herringbone micro-fluidic chip could achieve the optimal capture rate when the herringbone groove width, spacing between herringbone grooves, herringbone groove height and channel height were 75, 125, 70 and 30 μm, respectively, at a flow rate of 1 mL/h with forward direction. Conclusions In this study, cell capture in different micro-fluidic chips was simulated by the method of computational fluid dynamics. The statistic model of capture efficiency is established by MATLAB and optimized to quickly screen a group of physical parameters for high-efficient cell capture. These optimized micro-fluid chip parameters are validated by experiment, which can realize the high-efficient capture of CTCs.
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Aims: Circulating tumor cells (CTCs) have significant diagnostic value for cancer patients. We report a label-free, simple and rapid microchannel filter type device for isolation of known metastatic cancer cells based on their mechano-physical properties like size and deformability. Study Design: Metastatic renal cancer cells were highly elastic and squeezed through microchannels much smaller than their size. Using a reverse-selectivity approach, the number of microchannels and their dimensions were varied to optimize and reduce the shear stress on tumor cells such that these did not pass through filtering channels. Place and Duration of Study: Department of Electrical Engineering and Department of Bioengineering, University of Texas at Arlington, USA, between June 2012 and March 2013. Methodology: A microfluidic filter type device was fabricated using soft lithography in polydimethylsiloxane (PDMS). The device consisted of one inlet and one outlet connected via 400 microchannels. First of all human derived renal cancer cells were suspended in 1X PBS solution and passed through these microchannels and capture efficiency of the device was calculated. The dimensions of microchannels were varied in order to increase efficiency. Eventually cancer cells were spiked in rat blood and isolated from the mixture. Results: For different dimensions of microchannels capture efficiencies of the devices were calculated. First device consisted of microchannels of 20 μm x 10 μm (Device-1) and the capture efficiency was 31.04±2.5%. Then dimensions were varied to 10 μm x 10 μm (Device-2), 10 μm x 5 μm (Device-3), and 5 μm x 5 μm (Device-4) and capture efficiencies increased to 45.18±1.85%, 70.96±2.39% and 78.36±4.29%, respectively. Rat blood was used as negative control in Device-3 and Device-4 and blood cells were able to pass the microchannels. Finally renal cancer cells were spiked in rat blood and isolated from red blood cells and white blood cells. Conclusion: A novel microdevice is fabricated to detect metastatic renal cancer cells based on their size and deformability. The efficiency of the device is more than 78%. This microfluidic channel device does not require preprocessing of blood (except dilution) or tagging/modification of cells and can be implemented for primary screening of cancer.
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ObjectiveTo explore the relationship between circulating tumor cells(CTCs) in the peripheral blood of patients with esophageal squamous cell carcinoma(ESCC) and the physiopathological characteristics of esophageal neoplasms.MethodsUsing negative selection system,we depleted red blood cells(RBCs) in red blood cell lysis buffer,depleted white blood cells (WBCs) with Miltenyi magnetic beads and enriched the rare cells from ESCC patients'peripheral blood.Immunofluorence staining (IF) was adopted to identify CTCs.ResultsCirculating tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma was closely related to cell differentiation grade,the invasion of primary cancer,lymph node status,P-TNM stages,and was rarely related to the sex,age or the location of tumor.ConclusionThe results suggest that circulating tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma may express the development of esophageal cancer and may be served as a tumor marker to evaluate the biological behavior of esophageal cancer.