scholarly journals Mass Action Kinetic Model of Apoptosis by TRAIL-Functionalized Leukocytes

2018 ◽  
Author(s):  
Emily E. Lederman ◽  
Michael R. King
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prolonged Exposure ◽  
Mass Action ◽  
New Approach ◽  
Membrane Bound ◽  
Soluble Trail ◽  
Kinetics Of ◽  
Coupled Reaction

1 AbstractBackgroundMetastasis through the bloodstream contributes to poor prognosis in many types of cancer. A unique approach to target and kill colon, prostate, and other epithelial-type cancer cells in the blood has been recently developed that causes circulating leukocytes to present the cancer-specific, liposome-bound Tumor Necrosis Factor (TNF)-related apoptosis inducing ligand (TRAIL) on their surface along with E – selectin adhesion receptors. This approach, demonstrated both in vitro with human blood and in mice, mimics the cytotoxic activity of natural killer cells. The resulting liposomal TRAIL-coated leukocytes hold promise as an effective means to neutralize circulating tumor cells that enter the bloodstream with the potential to form new metastases.ResultsThe computational biology study reported here examines the mechanism of this effective signal delivery, by considering the kinetics of the coupled reaction cascade, from TRAIL binding death receptor to eventual apoptosis. In this study, a collision of bound TRAIL with circulating tumor cells (CTCs) is considered and compared to a prolonged exposure of CTCs to soluble TRAIL. An existing computational model of soluble TRAIL treatment was modified to represent the kinetics from a diffusion-limited 3D reference frame into a 2D collision frame with advection and adhesion to mimic the E – selectin and membrane bound TRAIL treatment. Thus, the current model recreates the new approach of targeting cancer cells within the blood. The model was found to faithfully reproduce representative observations from experiments of liposomal TRAIL treatment under shear. The model predicts apoptosis of CTCs within 2 hr when treated with membrane bound TRAIL, while apoptosis in CTCs treated with soluble TRAIL proceeds much more slowly over the course of 10 hrs, consistent with previous experiments. Given the clearance rate of soluble TRAIL in vivo, this model predicts that the soluble TRAIL method would be rendered ineffective, as found in previous experiments.ConclusionThis study therefore indicates that the kinetics of the coupled reaction cascade of liposomal E – selectin and membrane bound TRAIL colliding with CTCs can explain why this new approach to target and kill cancer cells in blood is much more effective than its soluble counterpart.

scholarly journals The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1119
Author(s):  
Ivonne Nel ◽  
Erik W. Morawetz ◽  
Dimitrij Tschodu ◽  
Josef A. Käs ◽  
Bahriye Aktas
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Hematopoietic Cells ◽  
Surrogate Marker ◽  
Clinical Samples ◽  
Breast Cancer Patients ◽  
Shape Restoration

Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection.

The Clinical Application of Circulating Tumor Cells and DNAs as Prognostic and Predictive Biomarkers in Gastrointestinal Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Sara Memarpour ◽  
Ghazaleh Khalili-Tanha ◽  
Awa Alizadeh Ghannad ◽  
Masoud Sharifian Razavi ◽  
Mona Joudi ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Biology ◽  
Predictive Biomarkers ◽  
Invasive Approach ◽  
New Approach ◽  
Non Invasive ◽  
Gi Cancer ◽  
Gi Cancers ◽  
Tumor Dna

: Gastrointestinal (GI) cancer is one of the most common cancers globally. Genetic and epigenetic mechanisms are involved in its pathogenesis. The conventional methods for diagnosis and screening for GI cancers are often invasive and have other limitations. In the era of personalized medicine, a novel non-invasive approach called liquid biopsy has been introduced for the detection and management of GI cancers, which focuses on the analysis of circulating tumor cells (CTCs) and circulating cell-free tumor DNA (ctDNA). Several studies have shown that this new approach allows for an improved understanding of GI tumor biology and will lead to an improvement in clinical management. The aim of the current review is to explore the clinical applications of CTCs and ctDNA in patients with GI cancer.

A Microfluidic Platform for On-Chip Analysis of Circulating Tumor Cells

2021 ◽  
Author(s):  
Jeff Darabi ◽  
Joseph Schober
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Automated Image Analysis ◽  
Rare Cancer ◽  
On Chip ◽  
Chip Analysis ◽  
Selection Of

Abstract Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.

Circulating Tumor Cells: Diagnostic and Therapeutic Applications

2018 ◽  
Vol 20 (1) ◽  
pp. 329-352 ◽  
Author(s):  
Eric Lin ◽  
Thong Cao ◽  
Sunitha Nagrath ◽  
Michael R. King
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Poor Prognosis ◽  
Experimental Therapeutics ◽  
Next Generation ◽  
Therapeutic Applications

Metastasis contributes to poor prognosis in many types of cancer and is the leading cause of cancer-related deaths. Tumor cells metastasize to distant sites via the circulatory and lymphatic systems. In this review, we discuss the potential of circulating tumor cells for diagnosis and describe the experimental therapeutics that aim to target these disseminating cancer cells. We discuss the advantages and limitations of such strategies and how they may lead to the development of the next generation of antimetastasis treatments.

Vita-Assay™ Method of Enrichment and Identification of Circulating Cancer Cells/Circulating Tumor Cells (CTCs)

2016 ◽  
pp. 107-119 ◽  
Author(s):  
Shaun Tulley ◽  
Qiang Zhao ◽  
Huan Dong ◽  
Michael L. Pearl ◽  
Wen-Tien Chen
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Circulating Cancer Cells

Abstract OT1-3-02: The treat CTC trial – A new approach targeting circulating tumor cells (CTC) in early breast cancer (EBC)

2013 ◽  
Author(s):  
B Rack ◽  
C Messina ◽  
S Litiere ◽  
C Dittrich ◽  
D Mavroudis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Early Breast Cancer ◽  
New Approach

New approach to terahertz sensing offers detection of circulating tumor cells

Scilight ◽  
2017 ◽  
Vol 2017 (18) ◽  
pp. 180003
Author(s):  
Meeri Kim
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
New Approach ◽  
Terahertz Sensing

Continuously capturing circulating cancer cells

2019 ◽  
Vol 11 (489) ◽  
pp. eaax1730
Author(s):  
Rajan P. Kulkarni
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Circulating Cancer Cells

A wearable apheresis device allows for continuous and specific capture of circulating tumor cells.

scholarly journals AZD1775 Increases Sensitivity to Olaparib and Gemcitabine in Cancer Cells with p53 Mutations

Cancers ◽  
2018 ◽  
Vol 10 (5) ◽  
pp. 149 ◽  
Author(s):  
Xiangbing Meng ◽  
Jianling Bi ◽  
Yujun Li ◽  
Shujie Yang ◽  
Yuping Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Gynecologic Cancer ◽  
Cell Cycle Checkpoints ◽  
Ovarian Cancer Cells ◽  
Tumor Suppressor P53 ◽  
New Approach ◽  
Dna Damaging Agents ◽  
Recurrent Gynecologic Cancer

Tumor suppressor p53 is responsible for enforcing cell cycle checkpoints at G1/S and G2/M in response to DNA damage, thereby allowing both normal and tumor cells to repair DNA before entering S and M. However, tumor cells with absent or mutated p53 are able to activate alternative signaling pathways that maintain the G2/M checkpoint, which becomes uniquely critical for the survival of such tumor cells. We hypothesized that abrogation of the G2 checkpoint might preferentially sensitize p53-defective tumor cells to DNA-damaging agents and spare normal cells with intact p53 function. The tyrosine kinase WEE1 regulates cdc2 activity at the G2/M checkpoint and prevents entry into mitosis in response to DNA damage or stalled DNA replication. AZD1775 is a WEE1 inhibitor that overrides and opens the G2/M checkpoint by preventing WEE1-mediated phosphorylation of cdc2 at tyrosine 15. In this study, we assessed the effect of AZD1775 on endometrial and ovarian cancer cells in the presence of two DNA damaging agents, the PARP1 inhibitor, olaparib, and the chemotherapeutic agent, gemcitabine. We show that AZD1775 alone is effective as a therapeutic agent against some p53 mutated cell models. Moreover, the combination of AZD1775 with olaparib or gemcitabine is synergistic in cells with mutant p53 and constitutes a new approach that should be considered in the treatment of advanced and recurrent gynecologic cancer.

scholarly journals Chemically modified plastic tube for high volume removal and collection of circulating tumor cells

2015 ◽  
Author(s):  
Angelo Gaitas ◽  
Gwangseong Kim
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
High Volume ◽  
Blood Stream ◽  
Plastic Tube ◽  
Chemically Modified ◽  
Stage Of Development ◽  
Flow Through

In this preliminary effort, we use a commercially available and chemically modified tube to selectively capture circulating tumor cells (CTCs) from the blood stream by immobilizing human anti-EpCAM antibodies on the tube's interior surface. We describe the steps required to modify a tube into a cancer cell capturing device. Using these simple modifications, at this proof-of-concept stage of development, we were able to capture about 85% of cancer cells from suspension and 44% of cancer cells from spiked whole blood, the capture percentage being dependent on the tube's length and the number of cancer cells present. Previous work by other researchers has focused on extracting small blood volumes and capturing CTCs with complicated micro-fluidic devices for diagnostic purposes. In addition, prior results of other researchers point to a possible reduction in metastasis achieved by removing CTCs from the bloodstream. We believe that with the utilization of appropriate tube lengths and procedures, we can ensure capture and removal of nearly the entire CTC population in whole blood. Following whole blood flow through the tube, the tube can be trypsinized to release the captured live CTCs for further analysis and testing.

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