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Tumor microenvironment in a real-life model of tumor spheroids
No full textTumors are complex bio-systems and cell
growth is coupled to the chemical modifications of the
extracellular microenvironment. Tumor cells and their
microenvironment, therefore, constitute an evolving cellular
ecosystem and a detailed understanding of the underlying
dynamics might provide insights into tumor development and
resistance to therapy. Here we present a real-life computer
program for the simulation of multicell tumor spheroids.
Simulation results compare quite well with experimental
data and yields unique view of tumor microenvironment
Physical and Computational Issues in a Simulation of Multicellular Tumor Spheroids
No full textWe have developed a computer program which
simulates the growth and development of multicellular tumor
spheroids. The program implements a basic description of
the metabolism, growth and proliferation of single cells, a full
3-dimensional geometry, and handles the complex problem of
diffusion and transport of nutrients and metabolites into and
out of cells, and in their surrounding environment. Here we
discuss some of the challenging computational problems that
arise in the implementation of this biophysical model
Numerical simulation of tumor spheroid dynamics
No full textWhile mosts cells are polarized and give rise to complex structures as they grow, some cells, like those found in several tumors, are unpolarized, and produce spherical, or almost-spherical structures.Tumorspheroidsmaybegrowninvitroandyieldusefulinformationontumordy- namics, but growth requires long times (months) and is not easily controlled. We are now developing a novel numerical engine to simulate the growth of unpolarized cells and to study spheroidtumorgrowthinsilico.Herewesketchthestructureofthesimulatorandreporton some of the very rst results obtained with this approach
Proliferation and Death in a Binary Environment: A Stochastic Model of Cellular Ecosystems
No full textThe activation, growth and death of animal cells are accompanied by changes in the chemical composition of the surrounding environment. Cells and their microscopic environment constitute therefore a cellular ecosystem whose time-evolution determines processes of interest for either biology (e.g. animal development) and medicine (e.g. tumor spreading, immune response). In this paper, we consider a general stochastic model of the interplay between cells and environmental cellular niches. Niches may be either favourable or unfavourable in sustaining cell activation, growth and death, the state of the niches depending on the state of the cells. Under the hypothesis of random coupling between the state of the environmental niche and the state of the cell, the rescaled model reduces to a set of four non-linear differential equations. The biological meaning of the model is studied and illustrated by fitting experimental data on the growth of multicellular tumor spheroids. A detailed analysis of the stochastic model, of its deterministic limit, and of normal fluctuations is provided
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Emergent properties of tumor microenvironment in a real-life model of multicell tumor spheroids.
Full text linkMulticellular tumor spheroids are an important in vitro model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
A phenomenological approach to the simulation of metabolism and proliferation dynamics of large tumour cell populations
No full textA major goal of modern computational biology is to simulate the collective behaviour of large
cell populations starting from the intricate web of molecular interactions occurring at the
microscopic level. In this paper we describe a simplified model of cell metabolism, growth
and proliferation, suitable for inclusion in a multicell simulator, now under development
(Chignola R and Milotti E 2004 Physica A 338 261–6). Nutrients regulate the proliferation
dynamics of tumour cells which adapt their behaviour to respond to changes in the
biochemical composition of the environment. This modelling of nutrient metabolism and cell
cycle at a mesoscopic scale level leads to a continuous flow of information between the two
disparate spatiotemporal scales of molecular and cellular dynamics that can be simulated with
modern computers and tested experimentally
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