Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases

Allard, W. Jeffrey; Matera, Jeri; Miller, Michael Craig; Repollet, Madeline; Connelly, Mark C.; Rao, Chinthalapally V.; Tibbe, Arjan G.J.; Uhr, Jonathan W.; Terstappen, Leon W.M.M.

doi:10.1158/1078-0432.ccr-04-0378

Cited by 2,290 publications

(2,139 citation statements)

References 24 publications

Supporting

Mentioning

1,985

Contrasting

Unclassified

Order By: Relevance

“…EpCAM is a surface marker that is widely expressed by different tumor cells and has been used to separate tumor cells in diagnostic settings for many years already. 17,23 EpCAM antibody functionalized beads were assembled using Protein A (or Protein A/G hybrid)-coated magnetic clusters with cluster diameters of 50 nm, 200 nm, 300 nm, 1 μm, and 4 μm (according to the manufacturer; Figure 1a). Transmission electron micrographs of the 300-nm clusters show a uniform size and shape of the particles (Figure 1b).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Removal of Cells from Body Fluids by Magnetic Separation in Batch and Continuous Mode: Influence of Bead Size, Concentration, and Contact Time

Bohmer

Demarmels

Tsolaki

et al. 2017

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

ABSTRACT:The magnetic separation of pathogenic compounds from body fluids is an appealing therapeutic concept. Recently, removal of a diverse array of pathogens has been demonstrated using extracorporeal dialysis-type devices. The contact time between the fluid and the magnetic beads in such devices is limited to a few minutes. This poses challenges, particularly if large compounds such as bacteria or cells need to be removed. Here, we report on the feasibility to remove cells from body fluids in a continuous dialysis type of setting. We assessed tumor cell removal efficiencies from physiological fluids with or without white blood cells using a range of different magnetic bead sizes (50−4000 nm), concentrations, and contact times. We show that tumor cells can be quantitatively removed from body fluids within acceptable times (1−2 min) and bead concentrations (0.2 mg per mL). We further present a mathematical model to describe the minimal bead number concentration needed to remove a certain number of cells, in the presence of competing nonspecific uptake. The present study paves the way for investigational studies to assess the therapeutic potential of cell removal by magnetic blood purification in a dialysis-like setting.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Removal of Cells from Body Fluids by Magnetic Separation in Batch and Continuous Mode: Influence of Bead Size, Concentration, and Contact Time

Bohmer

Demarmels

Tsolaki

et al. 2017

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…The CellSearch system relies on EpCAMs and cytokeratin for cell identification and enumeration, respectively. The CTC detection rates range from 11% to 57% in different tumors types (Allard et al, 2004). As EpCAM and cytokeratin are not expressed in a fair proportion of CTCs, this method has had to be continuously improved.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Sun

Liang

Wang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4′,6‐diamidino‐2‐phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45‐/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2–5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7–7.3, p < 0.001) were both associated with shorter disease‐free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2–6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8–8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.

show abstract

“…Assessment of CTC using CellSearch has been cleared by the Food and Drug Administration as a prognostic indicator, in conjunction with other clinical methods, for patients with metastatic breast, prostate, and colorectal cancers. Studies in metastatic breast, colorectal, and prostate cancer showed that patients about to start new lines of chemotherapy could be divided into groups with favourable and unfavourable prognosis on the basis of the number of CTCs measured with the analytically valid CellSearch system(Veridex, Raritan, NJ, USA) [3,[5][6][7][8][9][10][11][12][13]20]. When studying the association between the number of CTCs and evolution of the disease, researchers generally use a single cutpoint to identify favorable and unfavorable response groups, such as 5 CTCs for MBC [3,4,14], three for metastatic colorectal cancer [11], and five for castration resistant prostate cancer [7].…”

Section: Discussionmentioning

confidence: 99%

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer

Botteri

Sandri

Bagnardi

et al. 2009

Breast Cancer Res Treat

View full text Add to dashboard Cite

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer. Breast Cancer Research and Treatment, Springer Verlag, 2009, 122 (1), pp.211-217. <10.1007/s10549-009-0668-7>. EPIDEMIOLOGYModeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer Abstract Circulating tumor cell (CTC) count has been shown to be an independent predictor of progression in metastatic breast, prostate, and colorectal cancer. A cutpoint is generally used to identify favorable and unfavorable response groups. In this study, we propose an approach in which the number of CTCs is analyzed as a continuous predictor, to detect the shape of the relationship between CTCs and prognosis of metastatic breast cancer. We evaluated the association of baseline CTC with progression-free survival (PFS) and overall survival (OS) in a series of 80 patients treated for advanced breast cancer at the European Institute of Oncology, Milan. The association between CTCs and prognosis was analyzed with standard categorical survival analysis and spline regression models. At baseline, median age was 55 years; 33 patients were newly diagnosed with metastatic breast cancer (41%), while 28 (35%) and 19 (24%) were pretreated with one and two previous chemotherapy lines, respectively. After a median follow-up of 28 months, 76 disease progressions and 44 deaths were observed. Kaplan-Meier curves showed a clear association between CTCs and PFS (P-value 0.03) and OS (Pvalue \ 0.01). Patients with no CTC at baseline had a significantly better prognosis. When analyzing the CTCs as a continuous variable, we found an increase in risk with increasing number of CTCs, for both PFS and OS. The increase rate lessened after approximately 5 CTCs. CTCs represent a robust prognostic factor in the metastatic breast cancer setting. A nonlinear increase in risk of both progression and death with increasing number of CTCs was observed, with a lessening increase after approximately 5 CTCs. If distinct prognostic groups are to be identified, women with no CTC could plausibly represent a distinct favorable one.

show abstract

Tumor Cells Circulate in the Peripheral Blood of All Major Carcinomas but not in Healthy Subjects or Patients With Nonmalignant Diseases

Cited by 2,290 publications

References 24 publications

Removal of Cells from Body Fluids by Magnetic Separation in Batch and Continuous Mode: Influence of Bead Size, Concentration, and Contact Time

Removal of Cells from Body Fluids by Magnetic Separation in Batch and Continuous Mode: Influence of Bead Size, Concentration, and Contact Time

Prognostic impact of circulating tumor cells in patients with ampullary cancer

Modeling the relationship between circulating tumour cells number and prognosis of metastatic breast cancer

Contact Info

Product

Resources

About