A three-dimensional fractal model of tumour vasculature

Tsafnat, Naomi; Tsafnat, Guy; Lambert, Tim D.

doi:10.1109/iembs.2004.1403250

Cited by 10 publications

(8 citation statements)

References 8 publications

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“…For chemotherapeutic drugs to reach tumor cells in vivo, they have to travel through the blood vessels [ 120 , 121 , 122 , 123 ]. Blood flow through a solid tumor is varied and disorganized [ 124 , 125 ]. Most blood vessels in tumors are dilated and “leaky” compared to those in normal tissues.…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Senthebane

Rowe

Thomford

et al. 2017

IJMS

336

330

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Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology. It is not surprising that the study of the tumor microenvironment is now considered to be as important as the study of tumor cells. Recent advances in technological and analytical methods, especially ‘omics’ technologies, has made it possible to identify specific targets in tumor cells and within the tumor microenvironment to eradicate cancer. Tumors need constant support from previously ‘unsupportive’ microenvironments. Novel therapeutic strategies that inhibit such microenvironmental support to tumor cells would reduce chemoresistance and tumor relapse. Such strategies can target stromal cells, proteins released by stromal cells and non-cellular components such as the extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro tumor biology models that recapitulate the in vivo tumor microenvironment such as multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being developed and are increasing our understanding of cancer cell-microenvironment interactions. This review offers an analysis of recent developments on the role of the tumor microenvironment in the development of chemoresistance and the strategies to overcome microenvironment-mediated chemoresistance. We propose a systematic analysis of the relationship between tumor cells and their respective tumor microenvironments and our data show that, to survive, cancer cells interact closely with tumor microenvironment components such as mesenchymal stem cells and the extracellular matrix.

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Section: Tumor Microenvironmentmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Senthebane

Rowe

Thomford

et al. 2017

IJMS

336

330

View full text Add to dashboard Cite

show abstract

“…Multimodels have been explored as an approach to computing the optimal therapy plan for these complex clinical treatments. 30 This treatment planning multimodel combines (1) a stochastic fractal model of tumor microvasculature, 31 (2) a probabilistic drug delivery and deposition model, and (3) a finite-element dose delivery model. While the models are all the same spatial scale, the temporal scales differ widely.…”

Section: Example Ii: a Multimodel Of Liver Cancer Treatmentmentioning

confidence: 99%

Computational Reasoning across Multiple Models

Tsafnat

Coiera

2009

Journal of the American Medical Informatics Association

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Computational support of clinical decisions frequently requires the integration of data in a variety of formats and from multiple sources and domains. Some impressive multiscale computational models of biological phenomena have been developed as part of the study of disease and healthcare systems. One can now contemplate harnessing these models arising from computational biology and using highly interconnected clinical data to support clinical decision-making. Indeed, understanding how to build computational systems able to reason across heterogeneous models and datasets is one of the major and perhaps foundational challenges of translational biomedical informatics. In this paper, the authors examine the use of multimodels (models composed of several daughter models) and explore three major research challenges to reasoning across multiple models: model selection, model composition, and computer aided model construction.

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“…Because of its pronounced randomness, the vascular architecture of myocardial and tumor tissue has been described under the auspices of fractal geometry (e.g., Bassingthwaighte et al, 1994;Beard and Bassingthwaighte, 2000;Gazit et al, 1997). In numerical simulations, self-similar and completely randomly randomized structures with a specified fractal dimension or other statistical measures can be generated by invasion percolation branching and random growth techniques (e.g., Tsafnat et al, 2004). The capillary network model considered in our numerical studies consists of a cascading sequence of bifurcating capillary segments forming a randomized fractal-tree structure similar to that observed in the kidney vasculature (Karshafian et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Numerical Simulation of Blood Flow Through Microvascular Capillary Networks

Pozrikidis

2009

Bull. Math. Biol.

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A numerical method is implemented for computing blood flow through a branching microvascular capillary network. The simulations follow the motion of individual red blood cells as they enter the network from an arterial entrance point with a specified tube hematocrit, while simultaneously updating the nodal capillary pressures. Poiseuille's law is used to describe flow in the capillary segments with an effective viscosity that depends on the number of cells residing inside each segment. The relative apparent viscosity is available from previous computational studies of individual red blood cell motion. Simulations are performed for a tree-like capillary network consisting of bifurcating segments. The results reveal that the probability of directional cell motion at a bifurcation (phase separation) may have an important effect on the statistical measures of the cell residence time and scattering of the tube hematocrit across the network. Blood cells act as regulators of the flow rate through the network branches by increasing the effective viscosity when the flow rate is high and decreasing the effective viscosity when the flow rate is low. Comparison with simulations based on conventional models of blood flow regarded as a continuum indicates that the latter underestimates the variance of the hematocrit across the vascular tree.

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A three-dimensional fractal model of tumour vasculature

Cited by 10 publications

References 8 publications

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Computational Reasoning across Multiple Models

Numerical Simulation of Blood Flow Through Microvascular Capillary Networks

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