The topology of gene expression space for a set of 12 cancer types is studied by means of an entropy-like magnitude, which allows the characterization of the regions occupied by tumor and normal samples. The comparison indicates that the number of available states in gene expression space is much greater for tumors than for normal tissues, suggesting the irreversibility of the progression to the tumor phase. The entropy is nearly constant for tumors, whereas exhibits a higher variability in normal tissues, probably due to tissue differentiation. In addition, we show an interesting correlation between the fraction of available states and the overlapping between the tumor and normal sample clouds, interpreted as a way of reducing the decay rate to the tumor phase in more ordered or structured tissues.
A prospective study was performed on neurosurgical samples from 18 patients to evaluate the use of Full-Field Optical Coherence Tomography (FF-OCT) in brain tumor diagnosis. FF-OCT captures en face slices of tissue samples at 1\mum resolution in 3D with a typical 200\mum imaging depth. A 1cm2 specimen is scanned at a single depth and processed in about 5 minutes. This rapid imaging process is non-invasive and 30 requires neither contrast agent injection nor tissue preparation, which makes it particularly well suited to medical imaging applications. Temporal chronic epileptic parenchyma and bra…
Cancer is a disease of cellular regulation, often initiated by genetic mutation within cells, and leading to a heterogeneous cell population within tissues. In the competition for nutrients and growth space within the tumors the phenotype of each cell determines its success. Selection in this process is imposed by both the microenvironment (neighboring cells, extracellular matrix, and diffusing substances), and the whole of the organism through for example the blood supply. In this view, the development of tumor cells is in close interaction with their increasingly changing environment: the mo…
This paper concerns multiphase models of tumor growth in interaction with a surrounding tissue, taking into account also the interplay with diffusible nutrients feeding the cells. Models specialize in nonlinear systems of possibly degenerate parabolic equations, which include phenomenological terms related to specific cell functions. The paper discusses general modeling guidelines for such terms, as well as for initial and boundary conditions, aiming at both biological consistency and mathematical robustness of the resulting problems. Particularly, it addresses some qualitative properties such…
Background: A fundamental problem in cancer research is identifying the cell type that is capable of sustaining neoplastic growth and its origin from normal tissue cells. Recent investigations of a variety of tumor types have shown that phenotypically identifiable and isolable subfractions of cells possess the tumor-forming ability. In the present paper, using two lineage-related human melanoma cell lines, primary melanoma line IGR39 and its metastatic derivative line IGR37, two main observations are reported. The first one is the first phenotypic evidence to support the origin of melanoma can…
This paper presents the development of a vascularized breast tumor and healthy or tumorigenic liver microenvironments-on-a-chip connected in series. This is the first description of a vascularized multi tissue-on-a-chip microenvironment for modeling cancerous breast and cancerous/healthy liver microenvironments, to allow for the study of dynamic and spatial transport of particles. This device enables the dynamic determination of vessel permeability, the measurement of drug and nanoparticle transport, and the assessment of the associated efficacy and toxicity to the liver. The platform is utili…
Starting from kinetic transport equations and subcellular dynamics we deduce a multiscale model for glioma invasion relying on the go-or-grow dichotomy and the influence of vasculature, acidity, and brain tissue anisotropy. Numerical simulations are performed for this model with multiple taxis, in order to assess the solution behavior under several scenarios of taxis and growth for tumor and endothelial cells. An extension of the model to incorporate the macroscopic evolution of normal tissue and necrotic matter allows us to perform tumor grading.
Single-walled carbon nanotubes (SWNTs) with five different C13/C12 isotope compositions and well-separated Raman peaks have been synthesized and conjugated to five targeting ligands in order to impart molecular specificity. Multiplexed Raman imaging of live cells has been carried out by highly specific staining of cells with a five-color mixture of SWNTs. Ex vivo multiplexed Raman imaging of tumor samples uncovers a surprising up-regulation of epidermal growth factor receptor (EGFR) on LS174T colon cancer cells from cell culture to in vivo tumor growth. This is the first time five-color multip…
A new mathematical model and numerical approach are proposed for the simulation of fluid and chemical exchanges between a growing capillary network and the surrounding tissue, in the context of tumor-induced angiogenesis. Thanks to proper modeling assumptions the capillaries are reduced to their centerline: a well posed mathematical model is hence worked out, based on the coupling between a three-dimensional and a one-dimensional equation (3D-1D coupled problem). Also the application of a PDE-constrained optimization formulation is here proposed for the first time for angiogenesis simulations.…
Solute transport is modeled using mixture theory, applied to the nanoparticle accumulation and concentration decay in the tissue space for different vascular configurations. A comparison of a single capillary configuration (SBC) with two parallel cylindrical blood vessels (2 BC) and a lymph vessel parallel to a blood vessel (BC_LC) embedded in the tissue cylinder is performed for five solute molecular weights between 0.1 kDa and 70 kDa. We found that the presence of a second capillary reduces the extravascular concentration compared to a single capillary and this reduction is enhanced by the p…
Metastatic tumors often invade healthy neighboring tissues by forming multicellular finger-like protrusions emerging from the cancer mass. To understand the mechanical context behind this phenomenon, we here develop a minimalist fluid model of a self-propelled, growing biological tissue. The theory involves only four mechanical parameters and remains analytically trackable in various settings. As an application of the model, we study the evolution of a 2D circular droplet made of our active and expanding fluid, and embedded in a passive non-growing tissue. This system could be used to model th…
Primary tumors often emerge within genetically altered fields of premalignant cells that appear histologically normal but have a high chance of progression to malignancy. Clinical observations have suggested that these premalignant fields pose high risks for emergence of secondary recurrent tumors if left behind after surgical removal of the primary tumor. In this work, we develop a spatio-temporal stochastic model of epithelial carcinogenesis, combining cellular reproduction and death dynamics with a general framework for multi-stage genetic progression to cancer. Using this model, we investi…
The transformation of the regular vasculature in normal tissue into a highly inhomogeneous tumor specific capillary network is described by a theoretical model incorporating tumor growth, vessel cooption, neo-vascularization, vessel collapse and cell death. Compartmentalization of the tumor into several regions differing in vessel density, diameter and in necrosis is observed for a wide range of parameters in agreement with the vessel morphology found in human melanoma. In accord with data for human melanoma the model predicts, that microvascular density (MVD, regarded as an important diagnost…
Epileptogenic lesions have higher concentrations of sodium than does normal brain tissue. Such lesions are palpably recognized by a surgeon and then excised in order to eliminate epileptic seizures with their associated abnormal electrical behavior. Here we study the frequency-dependent electrical conductivities of lesion-laden tissues excised from the brains of epilepsy patients. The low-frequency (< 1000 Hz) conductivity of biological tissue primarily probes extracellular solvated sodium-cations traveling parallel to membranes within regions bounded by blockages. This conductivity rises mono…
University of Jordan（约旦大学）；King Abdullah II School for IT（阿卜杜拉二世信息技术学院）
Effective ultrasound tissue characterization is usually hindered by complex tissue structures. The interlacing of speckle patterns complicates the correct estimation of backscatter distribution parameters. Nakagami parametric imaging based on localized shape parameter mapping can model different backscattering conditions. However, performance of the constructed Nakagami image depends on the sensitivity of the estimation method to the backscattered statistics and scale of analysis. Using a fixed focal region of interest in estimating the Nakagami parametric image would increase estimation varia…
Here, we investigate how competition in the Eden model is affected by short range dispersal and the requirement that site updates occur only after several updates of the same site have been attempted previously. The latter models the effect of tissue or media resistance to invasion. We found that the existence of tissue intensifies 'Natural Selection' and de-accelerating 'Genetic Drift', both to a limited extent. More interestingly, our results show that short-range migration can eliminate Genetic demixing and conceal Natural Selection.
Towards Machine Learning-based Quantitative Hyperspectral Image Guidance for Brain Tumor Resection
University of British Columbia（不列颠哥伦比亚大学）；University Hospital of Münster（明斯特大学医院）；Macquarie University（麦考瑞大学）；Hokkaido Medical Center, National Hospital Organization（国立医院机构北海道医疗中心）
Background: Radiotherapy outcomes are usually predicted using the Linear Quadratic model. However, this model does not integrate complex features of tumor growth, in particular cell cycle regulation. Methods: In this paper, we propose a multiscale model of cancer growth based on the genetic and molecular features of the evolution of colorectal cancer. The model includes key genes, cellular kinetics, tissue dynamics, macroscopic tumor evolution and radiosensitivity dependence on the cell cycle phase. We investigate the role of gene-dependent cell cycle regulation in the response of tumors to th…
We propose a mechanism for tumor growth emphasizing the role of homeostatic regulation and tissue stability. We show that competition between surface and bulk effects leads to the existence of a critical size that must be overcome by metastases to reach macroscopic sizes. This property can qualitatively explain the observed size distributions of metastases, while size-independent growth rates cannot account for clinical and experimental data. In addition, it potentially explains the observed preferential growth of metastases on tissue surfaces and membranes such as the pleural and peritoneal l…
By means of a recently-proposed metric or structural derivative, called scale-q-derivative approach, we formulate differential equation that models the cell death by a radiation exposure in tumor treatments. The considered independent variable here is the absorbed radiation dose D instead of usual time. The survival factor, Fs, for radiation damaged cell obtained here is in agreement with the literature on the maximum entropy principle, as it was recently shown and also exhibits an excellent agreement with the experimental data. Moreover, the well-known linear and quadratic models are obtained…
We study multicellular tumor spheroids by introducing a new three-dimensional agent-based Voronoi/Delaunay hybrid model. In this model, the cell shape varies from spherical in thin solution to convex polyhedral in dense tissues. The next neighbors of the cells are provided by a weighted Delaunay triangulation with in average linear computational complexity. The cellular interactions include direct elastic forces and cell-cell as well as cell-matrix adhesion. The spatiotemporal distribution of two nutrients -- oxygen and glucose -- is described by reaction-diffusion equations. Viable cells cons…
We deduce a model for glioma invasion making use of DTI data and accounting for the dynamics of brain tissue being actively degraded by tumor cells via excessive acidity production, but also according to the local orientation of tissue fibers. Our approach has a multiscale character: we start with a microscopic description of single cell dynamics including biochemical and/or biophysical effects of the tumor microenvironment, translated on the one hand into cell stress and corresponding forces and on the other hand into receptor binding dynamics; these lead on the mesoscopic level to kinetic eq…
