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Circulating tumor cells (CTCs)are cancerous cells that shed from the primary tumor or metastases into the bloodstream. The currently clinical applicability of CTCs approved by the US Food and Drug Administration (FDA)is that CTCs can be prognostic biomarker for patients with metastatic breast cancer, prostate cancer and colorectal cancer. CTCs also have great potential in the prognosis assessment of other meta-static or localized tumors,as well as early screening of tumors,analysis of molecular profiling,guiding treat-ment decisions,and monitoring of treatment response. Currently,various studies are being carried out to further explore the clinical application of CTCs,and provide new strategies and new prospects for individualized and precise treatment of cancer patients.
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Liquid biopsy is a kind of popular and emerging pathological detection technology,which mainly includes the detection of circulating tumor cells,circulating tumor DNA and exosome.Recent studies show that liquid biopsy not only plays a potential advantage in early diagnosis of pancreatic cancer,but also has some guiding significance for prognosis and recurrence monitoring of pancreatic cancer.
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Liquid biopsy mainly focuses on tumor diagnosis,metastasis monitoring,individualized treatment monitoring,curative effect evaluation and prognostic judgment.The main targets include circulating tumor cells,circulating tumor DNA and exosomes.At present,the liquid biopsy target has been used in the clinical monitoring of some tumors,and has good clinical results,but there are still many cha-llenges.
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There are many ways to identify circulating tumor cells in the current.Fluorescence has a wide range of applications in the identification of circulating tumor cells.The labeled cells can be observed and counted more intuitively by labeling the tumor cells with fluorescent group containing antibodies,probes and aptamers,and cytokine,CD45 and fluorescence in situ hybridization are widely used in the identification of various circulating tumor cell related tests.In recent years,people have explored the feasibility of using fluorescent probes to directly identify circulating tumor cells.With the development of biopsy probes and optical sectioning imaging technology of confocal microscopy,it is possible to directly identify circulating tumor cells with fluorescent probes in the future.
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To investigate the effect of ultrasound-guided percutaneous injection of cinobufotalin or anhydrous ethanol in the treatment of portal vein tumor thrombus (PVTT) through a comparative analysis. MethodsA total of 56 patients with PVTT after liver cancer surgery, who were admitted to the 94th Hospital of PLA from October 2009 to December 2011, were enrolled. Among these patients, 27 underwent ultrasound-guided percutaneous injection of cinobufotalin (cinobufotalin group) and 29 underwent ultrasound-guided percutaneous injection of anhydrous ethanol (anhydrous ethanol group). The clinical outcome and survival time were compared between the two groups after treatment, and the levels of total bilirubin (TBil), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) before and after treatment were compared. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, the rank sum test was used for comparison of ranked data, and the Kaplan-Meier method was used for survival analysis. ResultsThe response rate showed no significant difference between the cinobufotalin group and the anhydrous ethanol group (63.0% vs 58.6%, χ2=0.111, P＞0.05). After treatment, the cinobufotalin group had significantly lower levels of TBil, ALT, and AST than the anhydrous ethanol group (t=2.24, 2.40, and 2.39, all P＜0.05). The 6-month, 1-year, and 2-year survival rates showed no significant differences between the cinobufotalin group and the anhydrous ethanol group (81.5%/63.0%/29.6% vs 82.8%/586%/31.0%, χ2=0.016, 0.111, and 0.013, all P＞0.05). ConclusionUltrasound-guided percutaneous injection of cinobufagin or anhydrous ethanol has similar short- and long-term effects in the treatment of PVTT and can inhibit the growth of tumor thrombus and prolong survival time, but cinobufagin is superior to anhydrous ethanol in the aspect of protecting liver function.
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Over the last two decades,we have seen many advances in the biological underpinnings of many kinds of cancers that have had a significant impact either directly or indirectly on the management and ultimately on the prognostic outcome of this disease.Next-generation sequencing studies have provided further evidence to support the notion4 that cancer is a disease characterized by Darwinian evolution.However,Ones often fail to obtain the information in different stages of the tumor before making treatment decision.This may be the major reason for treatment failures.Currently,circulating tumor cells (CTCs) is considered as aliquid biopsy.By detecting CTCs at different stages of tumor and obtaining the biological characteristics of CTCs,ones can get information about tumor evolution at different stages.It might provide effective basis for individual therapy to tumors,and promote the accuracy of tumor treatment.
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In consideration of a few patients with small cell lung cancer (SCLC) receiving surgery, it is difficult to obtain tumor samples, extremely restricting biomarker research by SCLC tissue samples. With the development of precise measurement techniques, liquid biopsy brings hope for SCLC biomarker research. As an alternative tumor tissue, circulating tumor cells (CTCs) are found frequently and abundant in peripheral blood of patients with SCLC. Related CTCs studies which conducted in patients with SCLC in recent years have found that CTCs have great significance in diagnosis and staging of SCLC, recurrence and metastasis monitoring, evaluation of therapeutic effect and prognosis, and individualized treatment. This paper reviews the detection and clinical application of CTCs in SCLC and explores its implication in individualized treatment strategy for SCLC.
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Circulating tumor cells (CTCs) is the source of tumor metastasis and recurrence. Many studies have suggested that tissue factor (TF) can be used as a novel marker of CTCs. This review focuses on the effects of TF on promotion of formation of CTC, activation of tumor cell proliferation, tumor cell survival, tumor angiogenesis and immune escape of tumor as well as its mechanisms; it also discusses the current status of TF/CTCs-targeted strategy in tumor treatment and the challenges faced, in hope of providing the theoretical basis for the application of TF/CTCs-targeted strategy in this field.
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Circulating tumor cells (CTCs) mediate distant metastasesof many kinds of cancer.The detection and characterization of CTC through different enrichment and isolation methods play important roles in assessing of prognosis, monitoring of therapy response and decision making of personalized treatment.With the development of continued research, detection of CTC may become a routine test for therapeutic decision making of cancer.
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Objective To explore the expression and significance of CD44 gastric cancer stem cell biomarker positive circulating tumor cells (CTC ) in peripheral blood of patients with gastric cancer . Methods From March 2010 to December 2012 ,45 patients with gastric cancer and 20 healthy individuals were enrolled .Peripheral blood samples of all the subjects were collected .The expression of CTC and CD44 postive CTC were detected by density gradient centrifugation method and double immunofluorescent staining .Chi‐square test and t‐test were performed for statistical analysis .Results CTC in peripheral blood of healthy controls were not detected .Among 45 patients with gastric cancer ,CTC were detected in 27 patients and 19 of them were CD44‐positive .The difference in positive rate of CTC expression was statistically significant between two groups (χ2 =10 .986 , P<0 .05) .Among 27 CTC‐positive patients , 19 were proximal gastric cancer and 16 of them were CD44‐positive;16 patients had lymph node metastasis and 14 of them were CD44‐positive;13 patients had distant metastasis and 12 of them were CD44‐positive;14 patients had recurrence and 13 of them were CD44‐positive .The CD44 positive CTC was correlated with tumor location ,lymph node metastasis ,distant metastasis and recurrence (χ2=5 .891 ,5 .527 ,5 .787 and 7 .052 ,respectively ,all P<0 .05) .Furthermore ,in 13 patients with recurrence and CD44 positive CTC ,the recurrence time was (10 .54 ± 5 .55) months which was shorter than that of one patients with CD44 negative CTC (19 months) ,and the difference was statistically significant (t= -3 .654 , P=0 .004) .Conclusions CTC which express cancer stem cell marker may be associated with recurrence and metastasis of gastric cancer .It has more important clinical significance to detect this subtype of CTC .
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Objective To assess the value of tumor marker immunostaining-FISH (TM-iFISH) technology on concen?trating and enumeration of tumor cells in CSF of lung cancer patients with leptomeningeal metastasis(LM). Methods Six cases of non-small cell lung cancer with leptomeningeal metastasis, which were diagnosed by CSF cytology or enhanced MRI scan, were selected. A total of 20 mL of CSF was collected in each case. TM-iFISH technology was employed to concen?trate and quantify circulating tumor cells in 7.5 mL CSF samples in each case while CSF cytology used 10 mL CSF samples in each case;Finally, the rest 2.5 mL CSF in each case was used for biochemistry assay. Results Ten CSF samples from 6 patients with non-small lung cancer with LM were assayed and tumor cells numbers ranging between 3 and 1 823 every 7.5 mL were found in 7 samples. On the other hand, CSF cytology examination only revealed tumor cells in 3 cases. Using CSF biochemical assay, higher than normal of protein level was found in 9 cases. TM-iFISH technology was employed again in 3 cases of patients who received treatment. Tumor cell count in CSF reduced in 2 out of the 3 cases. Conclusion TM-iFISH technology is a new method for detection and enumeration of tumor cells in the CSF in non-small cell lung cancer patients with leptomeningeal metastasis. This technology present diagnosis and curative values in lung cancer patients with leptomen?ingeal metastasis.
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Circulating tumor cells (CTCs) play pivotal roles for monitoring the tumor metastasis and prognosis.The nanotechnology provides a favourable platform for CTCs detection,and enables CTCs to be more promising for practical application.Meanwhile,the nanoscale device by virtue of nanotechnology has broad application prospects in eliminating CTCs and offers a new direction in the field of anti-cancer.
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Objective: To explore the clinical value of cytokeratin 19 (CK19) and human mammaglobin (hMAM) in the detection of circulating tumor cells (CTCs) in peripheral blood of patients with breast cancer. Methods: Expressions of CK19 and hMAM in blood were identified by real-time fluorescent quantitative PCR, and the correlations between CK19, hMAM and the clinicopathologic features were analyzed. Results: In breast cancer patients, the rates of diagnostic positive detection of individual CK19 or hMAM and the combination of these two biomarkers were 45.5% (20/44), 38.6% (17/44) and 56.8% (25/44), respectively. The expression of combined biomarkers was correlated with lymph node metastasis (P = 0.031). The rates of diagnostic positive detection of CK19, hMAM and the combination biomarkers were significantly higher in breast cancer patients prior to treatment than those in the healthy control group (P = 0.000 3, P = 0.000 1 and P = 0.000 1, respectively). After two-cycle chemotherapy, CTCs which were positive at baseline presented as negative in 5 stage III patients and 4 stage IV patients (P = 0.025 3 and P = 0.045 5). However, the number of CTCs-positive patients at stagesI-II decreased no matter using CK19, hMAM or CK19 plus hMAM as biomarker, leaving more CTCs-positive patients in combined biomarker group than that in single biomarker group, but there was no statistical significance. Conclusion: The combined panel of both hMAM and CK19 may serve as representative biomarkers for CTCs, thus it presents potentially significant value for monitoring early metastasis, therapeutic efficacy and prognosis for the patients with breast cancer. Copyright © 2014 by TUMOR.
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Circulating tumor cells (CTCs) play an important role in cancer recurrence and metastasis, which are the principal reasons to death. In recent studies, it has been reported that platelets are closely associated with CTCs for inducing epithelial-mesenchymal-like transition, pro-angiogenesis, tumor thrombus and immunosuppression, and they can accelerate the progression of tumor directly. This review summarizes that how platelets affect generation and metastasis of CTCs in order to find out new evidences and direction for treatment of cancer. Copyright © 2014 by TUMOR.
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The specificity of circulating tumor cell (CTC) such as epithelial-mesenchymal transition,fusion of bone marrow-derived cells,resistance anoikis determines the necessity of cell cultivating.The produced cell lines can provide good material basis for further research of malignant tumor metastasis,also provide individualized targeted therapy for patients with a new direction.
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Objective To investigate the expression of Circulating tumor cells ( CTCs ) in peripheral blood cells of patients with different stages of Small-Cell Lung Cancer ( SCLC) ,and to evaluate its significance in early diagnosis of lung cancer metastasis.Methods Thirty-five patients with SCLC ( 12 in limited stage and 23 in extensive stage ) and 25 patients with benign lung disease were recruited at the Shanghai Changhai Hospital from April 2011 to April 2013.Samples were prepared from 7.5 ml peripheral venous blood and collected in CellSave tubes.The CTC counts were determined using CellTracks AutoPrep fluorescence scanning system according to the manufacturers′instructions.The expression of CTCs in peripheral blood of SCLC patients and benign lung disease patients were analyzed.The expression of CTCs in different stages of SCLC was measured and compared.Furthermore, samples were prepared from 2 ml peripheral venous blood by centrifugation.The serum levels of NSE Neuron specific enolase were measured.The relationship between the expression of CTC and NSE was analyzed.Results CTCs positive rates in SCLC were significantly higher than in benign lung disease controls [ Positive rates of CTC≥1 were 80.0%and 12.0%(χ2 =27.003,P<0.000 1),CTC≥5 were 51.4%and 0 (χ2 =18.367,P<0.000 1), CTC≥10 were 34.3%and 0(χ2 =10.714,P<0.001),CTC≥50 were 17.1 and 0(P=0.036,P<0.05), respectively ].CTCs positive rates in SCLC extensive stage were significantly higher than limited-stage [Positive rates of CTC≥1 were 58.3% and 91.3%(P=0.033,P<0.05), CTC≥5 were 65.2% and 25.0%(P=0.035,P<0.05), respectively].The expression of CTCs was significantly correlated with NSE (r=0.743 7, P<0.000 1).Conclusion The expression of CTC in SCLC patients is significantly higher than those in control group , and is closely related to clinical stages , which may provide new clues to early predicting of SCLC metastasis and deterioration.
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Currently, it is considered that the tumor cells get abnormal activity by EMT (epithelial-mesenchymal transition) activation, inducing the generation and survival of CTCs (circulating tumor cells). After dissemination of CTCs through the blood, MET (mesenchymal-epithelial transition) occurs to form secondary tumor metastasis. Given that EMT is a key factor to induce CTCs to promote tumor metastasis, more and more attention was paid on CTCs in prognosis and targeted therapy of tumors. This review is mainly involved the current progress in the role of EMT in generation and survival of CTCs and the role of MET in metastasis formation from EMT-derived CTCs, and discusses the problem of the clinical application of detection of CTCs-EMT phenotype. Copyright © 2013 by TUMOR.
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As a useful supplement for TNM staging system of non-small cell lung cancer (NSCLC),circulating tumor cell (CTC) can better reflect the comprehensive condition of the patient.CTC plays an important potential role in monitoring curative effect of lung cancer,and has the effect of real-time detection.With the development of the CTC detection method and the improvement of sensitivity and specificity,clinical studies about CTC will provide more help for prognosis evaluation.
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Objective To establish a novel method for detecting circulating tumor cells (CTCs) in phripheral blood of lung cancer patients with high sensitivity and specificity.Methods Experimental study.42 cases of initial treatment patient who underwent resection and diagnosed to be non-small cell lung cancer by biopsy were studied,including 7 patients at stage Ⅰ,9 patients at stage Ⅱ,16 patients at stage Ⅲ and 10 patients at stage Ⅳ.As a control group,20 cases of healthy volunteers were selected.A series of experiments was conducted to determine the efficiency of tumor cells isolation,in which varied concentration (50,100,200,500,1000 cells) of A549 cells spiked into 2 ml peripheral blood drawn from healthy donors.The blood was removed of unwanted erythrocytes by lysis buffer,and made the rest of nucleated cells incubate with anti-EpCAM magnetic beads,then separated and enriched by a specific detector.All epithelia cells were retained on a slide because of a magnetic force and identified by H&E staining protocol.On the basis of cell recovery rate we calculated the sensitivity of tumor cells isolation.20 blood samples taken from healthy individuals were also detected to validate the specificity of this method.Samples of 42 patients with lung cancer were assayed for CTCs detection by above method.The correction of CTCs quantity with the patients' clinical features,for example,ages,gender,clinical stage,tumor size was analyzed in lung cancer patients by chi-square statistics.The correction of recovery cells with the spiked cells were assayed by linear correlation.Results The recovery rate was ranging from 68％ to 82％ by spiking varying numbers of A549 lung cancer cells into 2ml blood samples of healthy volunteers.Regression analysis of number of recovered vs.spiked A549 cells yielded a regression equation of Y =0.6419X + 8.8875.The number of CTCs detected has signification correlate with the cells spiked (R2 =0.9916,P ＜ 0.05),Eighteen of the 42 patients (43％) were found have CTCs in peripheral blood.The detection rate of lung cancer cells was 0 at stage Ⅰ,the detection rate of lung cancer cells was 11.1％ at stage Ⅱ,the detection rate of lung cancer cells was 62.5％ at stage Ⅲ and the detection rate of lung cancer cells was 70％ at stage Ⅳ.The positive rate of CTCs has no signification correlate with ages and gender of patients and tumor size (P ＞ 0.05),has signification with the clinical stage (P ＜ 0.05).None of the peripheral blood samples of the 20 healthy subjects analyzed was found to have CTCs.Conclusions This novel immunomagnetic separation technology is a sensitive and specific method,which provides a new tool allowing for feasible and specific detection of CTCs in lung cancer patients.The level of CTCs increases with the clinical stage and tumor size increased,which has important value to discover the early stage micrometastasis and redefine the clinical stage.But further multicenter and large sample clinical research are needed to confirm its clinical value.
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Objective To investigate the safety and efficacy of radical nephrectomy plus inferior vena cava thrombectomy,and to evaluate the efficacy of preoperative temporary inferior vena cava filter placement and intraoperative application of liver transplantation techniques to reveal the inferior vena cava in order to avoid tumor thrombosis shedding and embolism.Methods The data of 42 cases (January 2004 to December 2010) of renal cell carcinoma with subdiaphragmatic thrombus were analyzed retrospectively.All these patients underwent radical nephrectomy plus inferior vena cava thrombectomy.Patients were implanted temporary inferior vena cava filter as preoperative routine.Patients with the tumor thrombi behind the liver were applied liver transplant techniques to free and turn liver to the left in order to reveal inferior vena cava,block blood flow according to priority and then finish the inferior vena cava thrombectomy.The filter was removed postoperatively on the same day,and the patients were followed up as routine.Results The operation of the 42 cases was successful without symptomatic tumor thrombus embolism perioperatively,while 1 case died of severe postoperative lung infection.The average operation time was 220 min (130-320 min),blood loss was 750 ml (200-2500 ml),and 12 cases had blood transfusion with an average of 800 ml (400-2000 ml).Forty-one cases were followed up with an average period of 36 months (6-60 months).Among the 37 cases without preoperative tumor metastasis,15 cases had metastases and 22 cases had disease-free survival.Conclusions Nephrectomy and inferior vena cava thrombectomy could be safe and effective for renal cell carcinoma with subdiaphragmatic thrombosis.Preoperative temporary inferior vena cava filter placement and intraoperative application of liver transplantation techniques to reveal the inferior vena cava can be effective to prevent tumor thrombosis shedding and embolism and improve surgical safety.