scholarly journals A Hydrodynamic Approach To Cancer

2015 ◽  
Author(s):  
Alexander Pinkowski ◽  
Walter Lilienblum

Abstract This is the pre-print version of a paper submitted to Technische Mechanik (ISSN 0232-3869) Hydrodynamic analysis suggests that the injection of drag-reducing agents (DRA) in nanomolar concentrations may hinder metastasizing of circulating tumor cells and serve this way as a complementary post-operative treatment for cancer patients. Our conclusion is based on the following considerations: - Tumor cells need an extra nutrient supply in order to survive and grow. - The attachment of circulating tumor cells therefore tends to occur at sites in the human circulatory system characterized by localized turbulence, which enhances the mass transfer of nutrients, e.g., at sites of vessel branching and bending with plasma skimming. - Also obstacles to blood flow, such as plaques (atherosclerosis), tumors, and red blood cell (RBC) rouleaux, produce local vortices that increase mass transfer, i.e., food supply. - DRA have the ability to smooth (laminarise) localized turbulence in the circulatory system and to reduce mass transfer. - Depriving tumor cells of their required nutrient levels will reduce the probability of creating metastatic tumors, and may lead to their starvation-induced death. In the first part of our essay we demonstrate how flow constrictions decrease mean blood flow velocity, wall shear rates, and Reynolds numbers respectively, and increase the friction factor. Experimentally derived apparent viscosity data from literature will be used to determine the probability of RBC rouleaux formation. This is of importance since RBC rouleaux are typically associated with turbulent blood flow patterns. An increase in apparent viscosity at low flow rates will be attributed to the formation of RBC rouleaux. In part two we discuss the application of the Lockhart/Martinelli method to determine the pressure drop in blood vessels. The objective is to determine a mass transfer coefficient characterizing the mass transfer between the center and the wall of both healthy and cancerous blood vessels. This coefficient indicates the nutrient supply available to tumor cells under different flow conditions and shows the effect of DRA. Our hydrodynamic approach contrasts with previous studies of the possible benefits of DRA injection, which were focused on improving blood supply. We emphasize the reduction of the mass transfer rate as a tool to withhold turbulence induced supplementary food supply to tumor cells. Due to the possibility of unexpected side effects when using DRA (including their mechanical degradation products) animal models are indispensable before clinical trials.

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245536
Author(s):  
Alessandra Marrella ◽  
Arianna Fedi ◽  
Gabriele Varani ◽  
Ivan Vaccari ◽  
Marco Fato ◽  
...  

Metastasis represents a dynamic succession of events involving tumor cells which disseminate through the organism via the bloodstream. Circulating tumor cells (CTCs) can flow the bloodstream as single cells or as multicellular aggregates (clusters), which present a different potential to metastasize. The effects of the bloodstream-related physical constraints, such as hemodynamic wall shear stress (WSS), on CTC clusters are still unclear. Therefore, we developed, upon theoretical and CFD modeling, a new multichannel microfluidic device able to simultaneously reproduce different WSS characterizing the human circulatory system, where to analyze the correlation between SS and CTC clusters behavior. Three physiological WSS levels (i.e. 2, 5, 20 dyn/cm2) were generated, reproducing values typical of capillaries, veins and arteries. As first validation, triple-negative breast cancer cells (MDA-MB-231) were injected as single CTCs showing that higher values of WSS are correlated with a decreased viability. Next, the SS-mediated disaggregation of CTC clusters was computationally investigated in a vessels-mimicking domain. Finally, CTC clusters were injected within the three different circuits and subjected to the three different WSS, revealing that increasing WSS levels are associated with a raising clusters disaggregation after 6 hours of circulation. These results suggest that our device may represent a valid in vitro tool to carry out systematic studies on the biological significance of blood flow mechanical forces and eventually to promote new strategies for anticancer therapy.


2012 ◽  
Vol 36 (1) ◽  
pp. 58-62
Author(s):  
Catherine Loudon ◽  
Elizabeth C. Davis-Berg ◽  
Jason T. Botz

A physical model was used in a laboratory exercise to teach students about countercurrent exchange mechanisms. Countercurrent exchange is the transport of heat or chemicals between fluids moving in opposite directions separated by a permeable barrier (such as blood within adjacent blood vessels flowing in opposite directions). Greater exchange of heat or chemicals between the fluids occurs when the flows are in opposite directions (countercurrent) than in the same direction (concurrent). When a vessel loops back on itself, countercurrent exchange can occur between the two arms of the loop, minimizing loss or uptake at the bend of the loop. Comprehension of the physical principles underlying countercurrent exchange helps students to understand how kidneys work and how modifications of a circulatory system can influence the movement of heat or chemicals to promote or minimize exchange and reinforces the concept that heat and chemicals move down their temperature or concentration gradients, respectively. One example of a well-documented countercurrent exchanger is the close arrangement of veins and arteries inside bird legs; therefore, the setup was arranged to mimic blood vessels inside a bird leg, using water flowing inside tubing as a physical proxy for blood flow within blood vessels.


PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e85143 ◽  
Author(s):  
Gunjan Gakhar ◽  
Vicente N. Navarro ◽  
Madelyn Jurish ◽  
Guang Yu. Lee ◽  
Scott T. Tagawa ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1734 ◽  
Author(s):  
Feiyu Chen ◽  
Zhangfeng Zhong ◽  
Hor-Yue Tan ◽  
Ning Wang ◽  
Yibin Feng

Hepatocellular carcinoma (HCC) is ranked as the sixth most common cancer around the world. With the emergence of the state-of-the-art modalities lately, such as liver transplantation, image-guided ablation, and chemoembolization, the death rate is still high due to high metastasis rate after therapy. Observation by biannual ultrasonography allows effective diagnosis at an early stage for candidates with no extrahepatic metastasis, but its effectiveness still remains unsatisfactory. Developing a new test with improved effectiveness and specificity is urgently needed for HCC diagnosis, especially for patients after first line therapy. Circulating tumor cells (CTCs) are a small sub-population of tumor cells in human peripheral blood, they release from the primary tumor and invade into the blood circulatory system, thereby residing into the distal tissues and survive. As CTCs have specific and aggressive properties, they can evade from immune defenses, induce gene alterations, and modulate signal transductions. Ultimately, CTCs can manipulate tumor behaviors and patient reactions to anti-tumor treatment. Given the fact that in HCC blood is present around the immediate vicinity of the tumor, which allows thousands of CTCs to release into the blood circulation daily, so CTCs are considered to be the main cause for HCC occurrence, and are also a pivotal factor for HCC prognosis. In this review, we highlight the characteristics and enrichment strategies of CTCs, and focus on the use of CTCs for tumor evaluation and management in patients with HCC.


2015 ◽  
Vol 39 (2) ◽  
pp. 91-95 ◽  
Author(s):  
Aleš Škorjanc ◽  
Gregor Belušič

In the present study, a preparation of frog skin was presented, which can be used to demonstrate the basic concepts of blood flow regulation in a very clear and attractive way to high school and university students. In a freshly euthanized Xenopus, a patch of abdominal skin was exposed from the internal side and viewed with a USB microscope while it remained connected to a functioning circulatory system. In this way, it was possible to obtain sharp images of arteries and veins and to visualize blood flow. This allows students to learn about the functional differences between arteries and veins and about the complexity of hemodynamics as well as the particularities of the amphibian pulmocutaneous circulation. Students can then quantitatively estimate the effect of norepinephrine and epinephrine on the diameter of blood vessels by simply superfusing the skin patch with a series of solutions of the two substances. They can also test the effect of α-adrenergic receptor blockers, used to treat high blood pressure, on the norepinephrine-induced muscle tonus of blood vessels.


2022 ◽  
Vol 15 (1) ◽  
pp. 75
Author(s):  
Chaithanya Chelakkot ◽  
Hobin Yang ◽  
Young Kee Shin

Shedding of cancer cells from the primary site or undetectable bone marrow region into the circulatory system, resulting in clinically overt metastasis or dissemination, is the hallmark of unfavorable invasive cancers. The shed cells remain in circulation until they extravasate to form a secondary metastatic lesion or undergo anoikis. The circulating tumor cells (CTCs) found as single cells or clusters carry a plethora of information, are acknowledged as potential biomarkers for predicting cancer prognosis and cancer progression, and are supposed to play key roles in determining tailored therapies for advanced diseases. With the advent of novel technologies that allow the precise isolation of CTCs, more and more clinical trials are focusing on the prognostic and predictive potential of CTCs. In this review, we summarize the role of CTCs as a predictive marker for cancer incidence, relapse, and response to therapy.


2020 ◽  
Vol 21 (7) ◽  
pp. 2323 ◽  
Author(s):  
Denis V. Voronin ◽  
Anastasiia A. Kozlova ◽  
Roman A. Verkhovskii ◽  
Alexey V. Ermakov ◽  
Mikhail A. Makarkin ◽  
...  

Flow cytometry nowadays is among the main working instruments in modern biology paving the way for clinics to provide early, quick, and reliable diagnostics of many blood-related diseases. The major problem for clinical applications is the detection of rare pathogenic objects in patient blood. These objects can be circulating tumor cells, very rare during the early stages of cancer development, various microorganisms and parasites in the blood during acute blood infections. All of these rare diagnostic objects can be detected and identified very rapidly to save a patient’s life. This review outlines the main techniques of visualization of rare objects in the blood flow, methods for extraction of such objects from the blood flow for further investigations and new approaches to identify the objects automatically with the modern deep learning methods.


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1111
Author(s):  
Jerry Xiao ◽  
Paula R. Pohlmann ◽  
Claudine Isaacs ◽  
Benjamin A. Weinberg ◽  
Aiwu R. He ◽  
...  

Circulating tumor cells (CTCs) are single cells or clusters of cells within the circulatory system of a cancer patient. While most CTCs will perish, a small proportion will proceed to colonize the metastatic niche. The clinical importance of CTCs was reaffirmed by the 2008 FDA approval of CellSearch®, a platform that could extract EpCAM-positive, CD45-negative cells from whole blood samples. Many further studies have demonstrated the presence of CTCs to stratify patients based on overall and progression-free survival, among other clinical indices. Given their unique role in metastasis, CTCs could also offer a glimpse into the genetic drivers of metastasis. Investigation of CTCs has already led to groundbreaking discoveries such as receptor switching between primary tumors and metastatic nodules in breast cancer, which could greatly affect disease management, as well as CTC-immune cell interactions that enhance colonization. In this review, we will highlight the growing variety of isolation techniques for investigating CTCs. Next, we will provide clinically relevant context for CTCs, discussing key clinical trials involving CTCs. Finally, we will provide insight into the future of CTC studies and some questions that CTCs are primed to answer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hongyi Zhang ◽  
Xiaoyan Lin ◽  
Yuan Huang ◽  
Minghong Wang ◽  
Chunmei Cen ◽  
...  

Circulating Tumor Cells (CTCs) are cancer cells that split away from the primary tumor and appear in the circulatory system as singular units or clusters, which was first reported by Dr. Thomas Ashworth in 1869. CTCs migrate and implantation occurs at a new site, in a process commonly known as tumor metastasis. In the case of breast cancer, the tumor cells often migrate into locations such as the lungs, brain, and bones, even during the early stages, and this is a notable characteristic of breast cancer. Survival rates have increased significantly over the past few decades because of progress made in radiology and tissue biopsy, making early detection and diagnosis of breast cancer possible. However, liquid biopsy, particularly that involving the collection of CTCs, is a non-invasive method to detect tumor cells in the circulatory system, which can be easily isolated from human plasma, serum, and other body fluids. Compared to traditional tissue biopsies, fluid sample collection has the advantages of being readily available and more acceptable to the patient. It can also detect tumor cells in blood earlier and in smaller numbers, possibly allowing for diagnosis prior to any tumor detection using imaging methods. Because of the scarcity of CTCs circulating in blood vessels (only a few CTCs among billions of erythrocytes and leukocytes), thorough but accurate detection methods are particularly important for further clinical applications.


2018 ◽  
Vol 116 ◽  
pp. 51-59 ◽  
Author(s):  
Wen-Hui Weng ◽  
I-Lin Ho ◽  
Chi-Chia Pang ◽  
Sow-Neng Pang ◽  
Tung-Ming Pan ◽  
...  

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