scholarly journals Microtube Device for Selectin-Mediated Capture of Viable Circulating Tumor Cells from Blood

2012 ◽  
Vol 58 (5) ◽  
pp. 846-853 ◽  
Author(s):  
Andrew D Hughes ◽  
Jeff Mattison ◽  
Laura T Western ◽  
John D Powderly ◽  
Bryan T Greene ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Cancer ◽  
Capture Rate ◽  
Buffy Coat ◽  
Cellular Damage ◽  
Cancer Therapies ◽  
Microscale Flow ◽  
Coated Surface ◽  
Personalized Cancer

Abstract BACKGROUND Circulating tumor cells (CTCs) can be used clinically to treat cancer. As a diagnostic tool, the CTC count can be used to follow disease progression, and as a treatment tool, CTCs can be used to rapidly develop personalized therapeutic strategies. To be effectively used, however, CTCs must be isolated at high purity without inflicting cellular damage. METHODS We designed a microscale flow device with a functionalized surface of E-selectin and antibody molecules against epithelial markers. The device was additionally enhanced with a halloysite nanotube coating. We created model samples in which a known number of labeled cancer cells were suspended in healthy whole blood to determine device capture efficiency. We then isolated and cultured primary CTCs from buffy coat samples of patients diagnosed with metastatic cancer. RESULTS Approximately 50% of CTCs were captured from model samples. Samples from 12 metastatic cancer patients and 8 healthy participants were processed in nanotube-coated or smooth devices to isolate CTCs. We isolated 20–704 viable CTCs per 3.75-mL sample, achieving purities of 18%–80% CTCs. The nanotube-coated surface significantly improved capture purities (P = 0.0004). Experiments suggested that this increase in purity was due to suppression of leukocyte spreading. CONCLUSIONS The device successfully isolates viable CTCs from both blood and buffy coat samples. The approximately 50% capture rate with purities >50% with the nanotube coating demonstrates the functionality of this device in a clinical setting and opens the door for personalized cancer therapies.

Flow-Based Isolation and Neutralization of Circulating Tumor Cells

2009 ◽  
Author(s):  
Laura T. Western ◽  
Kuldeepsinh Rana ◽  
Michael R. King
Keyword(s):  
Cell Line ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Diagnostic Tool ◽  
Whole Blood ◽  
Metastatic Cancer ◽  
Capture Rate ◽  
Chemotherapeutic Agents ◽  
Leukemic Cells ◽  
Patient Treatment

Circulating tumor cells (CTC) have the potential to be used clinically as a diagnostic tool and a treatment tool in the field of oncology. As a diagnostic tool, CTC may be used to indicate the presence of a tumor before the tumor is large enough to cause noticeable symptoms. As a treatment tool, CTC isolated from patients may be used to test the efficacy of chemotherapy options to personalize patient treatment. One way for tumors to spread is through metastasis via the circulatory system. CTC are able to exploit the natural leukocyte recruitment process that is initially mediated by rolling on transient selectin bonds. Our capture devices take advantage of this naturally occurring recruitment step to isolate CTC from whole blood by flowing samples through selectin and antibody-coated microtubes. Whole blood was spiked with a known concentration of labeled cancer cells and then perfused through pre-coated microtubes. Microtubes were then rinsed to remove unbound cells and the number of labeled cells captured on the lumen was assessed. CTC were successfully captured from whole blood at a clinically relevant level on the order of 10 cells per mL. Combination tubes with selectin and antibody coated surface exhibited higher capture rate than tubes coated with selectin alone or antibody alone. Additionally, CTC capture was demonstrated with the KG1a hematopoietic cell line and the Du145 epithelial cell line. Thus, the in vivo process of selectin-mediated CTC recruitment to distant vessel walls can be used in vitro to target CTC to a tube lumen. The microtube device can also be used to capture CTC of hematopoietic and epithelial tumor origin and is demonstrated sensitivity down to the order of 10 CTC per mL. In a related study aimed at reducing the blood borne metastatic cancer load, we have shown that cells captured to a surface can be neutralized by a receptor-mediated biochemical signal (Rana et al. 2008). In the proposed method we have shown that using a combined selecting and TRAIL (TNF Related Apoptosis Inducing Ligand or Apo 2L) functionalized surface we are able to kill about 30% of the captured cells in a short duration of 1 hour whereas it took about 4 hours to kill the same proportion of cells without flow on a similarly functionalized. Here we have taken the approach a step further by showing that with very small doses of chemotherapeutic agents like Bortezomib, we can increase the kill rate of CTCs., thus allowing the device to function in senarios where the patient is undergoing treatment. We show here with leukemic cells that are treated with Bortezomib that we are able kill about 41% of the captured cells.

scholarly journals Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1385
Author(s):  
Hyeon-Yeol Cho ◽  
Jin-Ha Choi ◽  
Joungpyo Lim ◽  
Sang-Nam Lee ◽  
Jeong-Woo Choi
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Cancer ◽  
Cancer Prognosis ◽  
Optical Biosensors ◽  
Diagnosis And Prognosis ◽  
Noise Factors ◽  
Prediction Of Relapse

Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such as serum and hematopoietic cells. This review provides a selective overview of the recent progress in the design of microfluidic devices with optical sensing tools and their application in the detection and analysis of CTCs and their small malignant subset, circulating cancer stem cells (CCSCs). Moreover, discussion of novel strategies to analyze the differentiation of circulating cancer stem cells will contribute to an understanding of metastatic cancer, which can help clinicians to make a better assessment. We believe that the topic discussed in this review can provide brief guideline for the development of microfluidic-based optical biosensors in cancer prognosis monitoring and clinical applications.

scholarly journals Efficient Propagation of Circulating Tumor Cells: A First Step for Probing Tumor Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2784
Author(s):  
Jerry Xiao ◽  
Joseph R. McGill ◽  
Kelly Stanton ◽  
Joshua D. Kassner ◽  
Sujata Choudhury ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Success Rates ◽  
Breast Cancer Patients ◽  
Metastatic Cells ◽  
Healthy Donors

Circulating tumor cells (CTCs) represent a unique population of cells that can be used to investigate the mechanistic underpinnings of metastasis. Unfortunately, current technologies designed for the isolation and capture of CTCs are inefficient. Existing literature for in vitro CTC cultures report low (6−20%) success rates. Here, we describe a new method for the isolation and culture of CTCs. Once optimized, we employed the method on 12 individual metastatic breast cancer patients and successfully established CTC cultures from all 12 samples. We demonstrate that cells propagated were of breast and epithelial origin. RNA-sequencing and pathway analysis demonstrated that CTC cultures were distinct from cells obtained from healthy donors. Finally, we observed that CTC cultures that were associated with CD45+ leukocytes demonstrated higher viability. The presence of CD45+ leukocytes significantly enhanced culture survival and suggests a re-evaluation of the methods for CTC isolation and propagation. Routine access to CTCs is a valuable resource for identifying genetic and molecular markers of metastasis, personalizing the treatment of metastatic cancer patients and developing new therapeutics to selectively target metastatic cells.

scholarly journals Epithelial Mesenchymal Transition: A New Insight into the Detection of Circulating Tumor Cells

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Guislaine Barrière ◽  
Michel Tartary ◽  
Michel Rigaud
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
New Technologies ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Biological Marker ◽  
Molecular Characteristics ◽  
Mesenchymal Transition ◽  
Patient Will ◽  
Worse Prognosis

Many research groups reported on the relation between circulating tumor cells (CTCs) in peripheral blood and worse prognosis for metastatic cancer patients. These results are based on CTCs counting and did not take into account molecular characteristics of cells. To establish CTCs as a reliable and accurate biological marker, new technologies must be focused on CTC subpopulations: dedifferentiated circulating tumor cells (ddCTCs) arising from epithelial mesenchymal transition (EMT). To select and detect them, different methods have been proposed but none has still reached the goal. Technical progress and translational research are expected to establish CTCs as a real marker. Thus CTC evaluation profiling for each patient will lead to personalize followup and therapy.

Isolation and expansion of circulating tumor cells (CTC) from melanoma patients using a novel cell culture technique.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10614-10614 ◽  
Author(s):  
John R. McGregor ◽  
Wolfram E. Samlowski ◽  
Shweta Tharkar ◽  
Sreekanth Donepudi ◽  
Soldano Ferrone
Keyword(s):  
Cell Culture ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Molecular Study ◽  
Immunofluorescence Assay ◽  
Buffy Coat ◽  
Culture Technique ◽  
Blood Samples ◽  
Patients Âgés ◽  
Melanoma Patients

10614 Background: Identification of rare (>2-5) circulating tumor cells (CTC) in 7.5 ml blood by immunofluorescence assay (IFA) correlates with a poor prognosis in colon, breast, prostate and lung cancer. Changes in CTC count during treatment also predict the eventual patient progression and survival in these cancers. Existing assays do not detect melanoma CTC, however. In addition, isolation of viable CTC remains problematic. To overcome these limitations we attempted to develop novel melanoma CTC assays, using IFA and cell culture approaches. Methods: Blood samples were obtained from patients and controls following informed consent. The buffy coat (white cells + tumor) was isolated by Ficoll/Hypaque centrifugation, and split into 6 replicate cultures in proprietary TrueCells medium. After 21 days in culture, tumor colonies were counted, and stained for melanoma and leukocyte markers. Buffy coat cells from parallel blood samples were stained with a panel of CSPG4-specific mAb (a pan-melanoma marker) on ultraclean glass slides for analysis by immunofluorescence microscopy. Results: Blood samples were obtained from 16 melanoma patients, ages 28-87. Eight patients were men and 8 were women. CSPG4+ events (>2) were detected in 8/16 patients by IFA (range 0-52). In contrast, tumor cell colonies of >50 cells grew in 12 out of 16 patients with Stage 3 or 4 melanoma (range 0-1054), shown in Table. Cells isolated from CTC colonies produced melanin, stained for CSPG4 and other melanoma markers, but not for leukocyte markers. Control cultures grew no tumor colonies. Conclusions: Our pilot study shows that melanoma CTC can be identified by both IFA and cultured from blood in many patients with stage 3 or 4 melanoma. These CTC exhibited cytologic characteristics diagnostic of melanoma. The culture assay may represent a useful means of enumerating, isolating, and expanding viable melanoma CTC for further molecular study. [Table: see text]

scholarly journals Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer

2017 ◽  
Vol 77 (16) ◽  
pp. 4530-4541 ◽  
Author(s):  
Natali Gulbahce ◽  
Mark Jesus M. Magbanua ◽  
Robert Chin ◽  
Misha R. Agarwal ◽  
Xuhao Luo ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Whole Genome Sequencing ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Genome Sequencing ◽  
Metastatic Cancer ◽  
Whole Genome

Adhesion-based simple capture and recovery of circulating tumor cells using a blood-compatible and thermo-responsive polymer-coated substrate

RSC Advances ◽  
2016 ◽  
Vol 6 (92) ◽  
pp. 89103-89112 ◽  
Author(s):  
Takashi Hoshiba ◽  
Toshihiko Orui ◽  
Chiho Endo ◽  
Kazuhiro Sato ◽  
Ayano Yoshihiro ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Biology ◽  
Metastatic Cancer ◽  
Cancer Diagnostics ◽  
Cancer Drug ◽  
Coated Substrate ◽  
Anti Cancer ◽  
Biology Research

Circulating tumor cells (CTCs) have been a focus of study for metastatic cancer diagnostics, in in vitro anti-cancer drug screening to decide the chemotherapeutic course, and cancer biology research.

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