‘Go or Grow': the key to the emergence of invasion in tumour progression?

Uncontrolled proliferation and abnormal cell migration are two of the main characteristics of tumour growth. Of ultimate importance is the question what are the mechanisms that trigger the progression from benign neoplasms (uncontrolled/autonomous proliferation) to malignant invasive tumours (high migration). In the following, we challenge the currently prevailing view that the emergence of invasiveness is mainly the consequence of acquired cancer cell mutations. To study this, we mainly focus on the ‘glioblastoma multiforme' (GBM) tumour which is a particularly aggressive and invasive tumour. In particular, with the help of a simple growth model, we demonstrate that the short time required for the recurrence of a GBM tumour after a gross total resection cannot be deduced solely from a mutation-based theory. We propose that the transition to invasive tumour phenotypes can be explained on the basis of the microscopic ‘Go or Grow' mechanism (migration/proliferation dichotomy) and the oxygen shortage, i.e. hypoxia, in the environment of a growing tumour. We test this hypothesis with the help of a lattice-gas cellular automaton. Finally, we suggest possible therapies that could help prevent the progression towards malignancy and invasiveness of benign tumour

Body composition changes after covering on foot the Way of Saint James

Con este estudio, se pretende comprobar la existencia de cambios y variaciones en la composición corporal de un grupo de adultos después de la realización a pie de 5 etapas del Camino Primitivo de Santiago de Compostela que discurre por la Provincia de Lugo. En él participaron 22 personas de edades comprendidas entre los 21 y los 48 años, siendo el 22,72% varones y el 77,27% mujeres. Se realizaron medidas de bioimpedancia eléctrica con la TANITA BC-418 en dos momentos diferentes (antes y después de realizar las etapas del Camino de Santiago). Las modificaciones de las diferentes variables medidas se analizaron y trataron con el paquete estadístico SPSS 20.0. Los resultados encontrados muestran que con este tipo de trabajo aeróbico y esta duración, en cierta medida se modificó la composición corporal de los sujetos participantes. Sin embargo, se propone que para futuros estudios el tiempo de trabajo sea mayor y que la intensidad varíe, con el fin de comprobar si se obtienen más resultados significativosWith this research, we want to check body composition changes and variations in a group of adults after covering on foot 5 stages of the Primitive Way of Saint James, which runs through the Lugo province. This research involved 22 people between 21-48 years-old, 22.72% males and 77.27% females. Measurements were performed with the bio-impedance TANITA BC-418 at two different moments (before and after covering the Saint James` Way stages). Changes in different measured variables were analyzed and treated with the SPSS Statistics 20.0. Results show that, with this type of aerobic work and this duration, body composition of people involved had some changes. However, it is propose to increase work time and to vary intensity in future researches, with the intention of prove if more significant results are obtainedS

The Evolution of Robust Development and Homeostasis in Artificial Organisms

During embryogenesis, multicellular animals are shaped via cell proliferation, cell rearrangement, and apoptosis. At the end of development, tissue architecture is then maintained through balanced rates of cell proliferation and loss. Here, we take an in silico approach to look for generic systems features of morphogenesis in multicellular animals that arise as a consequence of the evolution of development. Using artificial evolution, we evolved cellular automata-based digital organisms that have distinct embryonic and homeostatic phases of development. Although these evolved organisms use a variety of strategies to maintain their form over time, organisms of different types were all found to rapidly recover from environmental damage in the form of wounds. This regenerative response was most robust in an organism with a stratified tissue-like architecture. An evolutionary analysis revealed that evolution itself contributed to the ability of this organism to maintain its form in the face of genetic and environmental perturbation, confirming the results of previous studies. In addition, the exceptional robustness of this organism to surface injury was found to result from an upward flux of cells, driven in part by cell divisions with a stable niche at the tissue base. Given the general nature of the model, our results lead us to suggest that many of the robust systems properties observed in real organisms, including scar-free wound-healing in well-protected embryos and the layered tissue architecture of regenerating epithelial tissues, may be by-products of the evolution of morphogenesis, rather than the direct result of selection

A seven-step guide to spatial, agent-based modelling of tumour evolution

Spatial agent-based models are increasingly used to investigate the evolution of solid tumours subject to localised cell-cell interactions and microenvironmental heterogeneity. Here we present a non-technical step by step guide to developing such a model from first principles, aimed at both aspiring modellers and other biologists and oncologists who wish to understand the assumptions and limitations of this approach. Stressing the importance of tailoring the model structure to that of the biological system, we describe methods of increasing complexity, from the basic Eden growth model up to off-lattice simulations with diffusible factors. We examine choices that unavoidably arise in model design, such as implementation, parameterisation, visualisation, and reproducibility. Each topic is illustrated with examples drawn from recent research studies and state of the art modelling platforms. We emphasise the benefits of simpler models that aim to match the complexity of the phenomena of interest, rather than that of the entire biological system

Evolutionary Games with Affine Fitness Functions: Applications to Cancer

We analyze the dynamics of evolutionary games in which fitness is defined as an affine function of the expected payoff and a constant contribution. The resulting inhomogeneous replicator equation has an homogeneous equivalent with modified payoffs. The affine terms also influence the stochastic dynamics of a two-strategy Moran model of a finite population. We then apply the affine fitness function in a model for tumor-normal cell interactions to determine which are the most successful tumor strategies. In order to analyze the dynamics of concurrent strategies within a tumor population, we extend the model to a three-strategy game involving distinct tumor cell types as well as normal cells. In this model, interaction with normal cells, in combination with an increased constant fitness, is the most effective way of establishing a population of tumor cells in normal tissue.Comment: The final publication is available at http://www.springerlink.com, http://dx.doi.org/10.1007/s13235-011-0029-

Biodiversidad de Myxomycetes en el Desierto de Monte (Argentina)

A biodiversity survey for myxomycetes was carried out in the Monte Desert (Argentina) and surrounding areas in November 2006 and late February and March 2007. Specimens were collected in seven different provinces (Catamarca, Jujuy, La Rioja, Salta, San Juan, San Luis and Tucumán), between 23º and 33º S latitude, and a total of 105 localities were sampled. Cacti and succulent plants were the most common type of substrate investigated, but shrubs and herbs characteristic of this biome were also included in the survey. Almost six hundred specimens of myxomycetes from 72 different species in 22 genera were collected either in the field, or from moist chamber cultures prepared with samples of plant material obtained from the same collecting sites. The results include 1 species new to science, Macbrideola andina three more species recently described based on material from this survey, 5 species cited for the first time for the Neotropics, 11 new records for South America and 38 new records for Argentina. Taxonomic comments on rare or unusual species are included and illustrated with photographs by LM and SEM. Data are presented on the development of some species and microenvironmental factors are discussed. An analysis of the biodiversity of myxomycetes in this area, and a comparison with other desert areas, are included.Con el objetivo de estudiar la biodiversidad de Myxomycetes en el Desierto de Monte (Argentina) y áreas circundantes, se realizó un muestreo en los meses de noviembre de 2006 y febrero y marzo de 2007. Se recolectaron especímenes en un total de 105 localidades pertenecientes a siete provincias (Catamarca, Jujuy, La Rioja, Salta, San Juan, San Luis y Tucumán), situadas entre los paralelos 23º y 33º de latitud sur. Los cactus y plantas suculentas fueron los tipos de sustratos más estudiados, pero también se analizaron arbustos y plantas herbáceas características de este bioma. Casi 600 especímenes de mixomicetes pertenecientes a 72 especies y 22 géneros fueron recolectados en el campo o se obtuvieron en el laboratorio, por cultivo en cámara húmeda, a partir de plantas procedentes de las mismas localidades. Los resultados incluyen una nueva especie, Macbrideola andina, otras tres recientemente descritas y basadas en material de este estudio, 5 especies que se citan por primera vez para el Neotrópico, 11 nuevos registros para América del Sur y 38 nuevos registros para Argentina. Se añaden comentarios taxonómicos e ilustraciones fotográficas, tanto con microscopía óptica como electró ni ca, de aquellas especies raras o poco comunes. Se discuten nuevos datos sobre el desarrollo de algunas especies y cómo influyen determinados factores microambientales. También se incluye un análisis de la biodiversidad de mixomicetes en esta zona árida y se compara con la obtenida en otros desiertos de América

A seven-step guide to spatial, agent-based modelling of tumour evolution

Spatial agent-based models are frequently used to investigate the evolution of solid tumours subject to localised cell-cell interactions and microenvironmental heterogeneity. As spatial genomic, transcriptomic and proteomic technologies gain traction, spatial computational models are predicted to become ever more necessary for making sense of complex clinical and experimental data sets, for predicting clinical outcomes, and for optimising treatment strategies. Here we present a nontechnical step by step guide to developing such a model from first principles. Stressing the importance of tailoring the model structure to that of the biological system, we describe methods of increasing complexity, from the basic Eden growth model up to off-lattice simulations with diffusible factors. We examine choices that unavoidably arise in model design, such as implementation, parameterisation, visualisation, and reproducibility. Each topic is illustrated with examples drawn from recent research studies and state of the art modelling platforms. We emphasise the benefits of simpler models that aim to match the complexity of the phenomena of interest, rather than that of the entire biological system. Our guide is aimed at both aspiring modellers and other biologists and oncologists who wish to understand the assumptions and limitations of the models on which major cancer studies now so often depend

Hippo Pathway Activity Influences Liver Cell Fate

SummaryThe Hippo-signaling pathway is an important regulator of cellular proliferation and organ size. However, little is known about the role of this cascade in the control of cell fate. Employing a combination of lineage tracing, clonal analysis, and organoid culture approaches, we demonstrate that Hippo pathway activity is essential for the maintenance of the differentiated hepatocyte state. Remarkably, acute inactivation of Hippo pathway signaling in vivo is sufficient to dedifferentiate, at very high efficiencies, adult hepatocytes into cells bearing progenitor characteristics. These hepatocyte-derived progenitor cells demonstrate self-renewal and engraftment capacity at the single-cell level. We also identify the NOTCH-signaling pathway as a functional important effector downstream of the Hippo transducer YAP. Our findings uncover a potent role for Hippo/YAP signaling in controlling liver cell fate and reveal an unprecedented level of phenotypic plasticity in mature hepatocytes, which has implications for the understanding and manipulation of liver regeneration

Cooperation among cancer cells: applying game theory to cancer

Cell cooperation promotes many of the hallmarks of cancer via the secretion of diffusible factors that can affect cancer cells or stromal cells in the tumour microenvironment. This cooperation cannot be explained simply as the collective action of cells for the benefit of the tumour because non-cooperative subclones can constantly invade and free-ride on the diffusible factors produced by the cooperative cells. A full understanding of cooperation among the cells of a tumour requires methods and concepts from evolutionary game theory, which has been used successfully in other areas of biology to understand similar problems but has been underutilized in cancer research. Game theory can provide insights into the stability of cooperation among cells in a tumour and into the design of potentially evolution-proof therapies that disrupt this cooperation