Is the allee effect relevant in cancer evolution and therapy?

Most models of cancer assume that tumor cells populations, at low densities, grow exponentially to be eventually limited by the available amount of resources such as space and nutrients. However, recent pre-clinical and clinical data of cancer onset or recurrence indicate the presence of a population dynamics in which growth rates increase with cell numbers. Such effect is analogous to the cooperative behavior in an ecosystem described by the so called Allee effect. In this work, we study the consequences of the Allee effect on cancer growth via the properties of dynamical models incorporating the Allee effect, and the implications that the occurrence of such effect has for the choice of the more appropriate therapy. Some simulations will be presented in which the model is used to fit data from in vitro experiments and clinical trials

Perception of intense precipitation events by public opinion

International audienceA survey of four years of local newspapers over the island of Sardinia was conducted. Articles were compared against meteorological observations in order to understand how efficiently intense precipitation events are perceived. The comparison showed that, on a wide and heterogeneous area, public opinion perceives correctly 44% of events and its perception is unbiased. If, however, the focus is placed upon urban areas, the ability to perceive grows to 66%, but an "overperception" of 33% arises. If focus is finally placed upon rural areas, skills worsen, several events are missed and a significant negative bias is detected

Cancer development: a population theoretical perspective

In the history of life, immune system and cancer have been engaged in an evolutionary arms race driven by the twin forces of mutation and selection. Ideally therapies should be a resolutive weapon, but, despite great progresses during the last 50 years or so, the race still goes on. The aim of this paper is to present a mathematical model, which can be used as in silico laboratory, to provide some indication on the effectiveness of therapies. Here we focus on two cancer populations competing for resources and subjected to the action of two types of immune system cells: thus the model results in a system of 4 differential equation that is analytically and computationally studied to elucidate its properties and emerging behaviors. At the beginning, some speci.c subsystems are analyzed and the effects of different therapies simulated; in particular .rst the system comprising a single cancer and immune cells type is considered and next the case of two cancer clones in absence of the immune cells. The complete model is then presented, which yields a rich variety of behaviors; in particular it is shown that for strong intertumoral competition, and high recognition levels by the immune system, stable stationary states are replaced by sustained oscillations. Finally some conclusion about therapy effectiveness are drawn, based on the results of simulations

How combination therapies shape drug resistance in heterogeneous tumoral populations

Treatment of cancer relies increasingly on combination therapies to overcome cancer resistance, but the design of successful combined protocols is still an open problem. In order to provide some indications on the effectiveness of medical treatments, results from in silico experiments are presented based on a mathematical model comprising two cancer populations competing for resources and with different susceptibilities to the action of immune system cells and therapies. The focus is on the effects of therapies that affect the rate of cancer growth, as in case of chemotherapy, used alone or in combination with immunotherapy, which boost the action of the immune system. Simulations show that a standard dose chemotherapy is effective when the sensitive clone has a marked competitive advantage, whereas combination of immuno- and chemotherapy works better in all the other cases. These results stress the importance to take into account competitive interactions among cancer clones to decide which therapeutic strategy should be adopted. Next the analysis is extended to protocols involving a drug holiday, i.e. periods in which no drug is administered. Finally, the model has been adapted to investigate combination therapies for non-small cell lung cancer: simulation results show that administration of standard dose of Erlotinib (a tyrosine kinase inhibitor), alone, has quite the same effect as a low-dose combination therapy, but the latter produces a slower increase of resistant cells

A Mathematical Study of the Influence of Hypoxia and Acidity on the Evolutionary Dynamics of Cancer

Hypoxia and acidity act as environmental stressors promoting selection for cancer cells with a more aggressive phenotype. As a result, a deeper theoretical understanding of the spatio-temporal processes that drive the adaptation of tumour cells to hypoxic and acidic microenvironments may open up new avenues of research in oncology and cancer treatment. We present a mathematical model to study the influence of hypoxia and acidity on the evolutionary dynamics of cancer cells in vascularised tumours. The model is formulated as a system of partial integro-differential equations that describe the phenotypic evolution of cancer cells in response to dynamic variations in the spatial distribution of three abiotic factors that are key players in tumour metabolism: oxygen, glucose and lactate. The results of numerical simulations of a calibrated version of the model based on real data recapitulate the eco-evolutionary spatial dynamics of tumour cells and their adaptation to hypoxic and acidic microenvironments. Moreover, such results demonstrate how nonlinear interactions between tumour cells and abiotic factors can lead to the formation of environmental gradients which select for cells with phenotypic characteristics that vary with distance from intra-tumour blood vessels, thus promoting the emergence of intra-tumour phenotypic heterogeneity. Finally, our theoretical findings reconcile the conclusions of earlier studies by showing that the order in which resistance to hypoxia and resistance to acidity arise in tumours depend on the ways in which oxygen and lactate act as environmental stressors in the evolutionary dynamics of cancer cells

A model for the formation and evolution of traffic jams

In this paper, we establish and analyze a traffic flow model which describes the formation and dynamics of traffic jams. It consists of a pressureless gas dynamics system under a maximal constraint on the density and is derived through a singular limit of the Aw-Rascle model. From this analysis, we deduce the particular dynamical behavior of clusters (or traffic jams), defined as intervals where the density limit is reached. An existence result for a generic class of initial data is proved by means of an approximation of the solution by a sequence of clusters. Finally, numerical simulations are produced

La Separazione mediante HPLC dei due fenoli isomeri Timolo (p-isopropil-m-cresolo) e Carvacrolo (p-isopropil-o-cresolo)

A method is described for the separation by HPLC of two isomer phenols thymol and carvacrol. Satisfactory resu1ts have been obtained by using a chromatographic column μ Bondapak ,C18 and a solvent system constitued by acetonitrile (40%) and water (60%). The flow rate was 1,5 ml/min. The use of this technique permits determination and dosage of these two phenols in essential oils

Risk factors associated with <i>Helicobacter pylori</i> infection among children in a defined geographic area

Factors influencing the pattern of Helicobacter pylori infection among children living in adjacent urban and rural areas of northern Sardinia, Italy, were compared. The seroprevalence of H. pylori infection was 22% (625 of 2810 children) in the study population and was significantly higher among children in rural areas (37%) than in urban areas (13%) (odds ratio [OR], 3.8; 95% confidence interval [CI], 3.2–4.7; P &lt;.005). This difference was consistent within each age group. In rural areas, children who had dogs were at greatest risk for H. pylori infection (OR, 1.8; 95% CI, 1.3–2.6; P &lt;.05). No association was seen between H. pylori sero-positivity and a history of breast-feeding. Urban children attending day care centers had a higher prevalence of infection (17%) than did those who never attended (12%) (OR, 1.5; 95% CI, 1.1–2.0; P &lt;.05). The epidemiology of H. pylori infection is complex; even within the same geographic area, different factors influence acquisition of H. pylori infection

Gender specific profiles of white coat and masked hypertension impacts on arterial structure and function in the SardiNIA study

Background: There is no definite consensus on the CV burden associated to Masked hypertension (MH) or White Coat Hypertension (WCH)-conditions that can be detected by out-of-office blood pressure measurements (24 hour Ambulatory Blood Pressure Monitoring, 24 h ABPM). Methods: We investigated the association of WCH and MH with arterial aging, indexed by a range of parameters of large artery structure and function in 2962 subjects, taking no antihypertensive medications, who are participating in a large community-based population of both men and women over a broad age range (14-102 years). Results: The overall prevalence of WCH was 9.5% and was 5.0% for MH, with 54.9% of subjects classified as true normotensive and 30.6% as true hypertensive. Both WCH and MH were associated with a stiffer aorta, a less distensible and thicker common carotid artery, and greater central BP than true normotensive subjects. Notably, the profile of arterial alterations in WCH and MH did not significantly differ from what was observed in true hypertensive subjects. The arterial changes accompanying WCH and MH differed in men and women, with women showing a greater tendency towards concentric remodeling, greater parietal wall stress, and PWV than men. Conclusion: Both WCH, and MH are associatedwith early arterial aging, and therefore, neither can be regarded as innocent conditions. Future studies are required to establish whether measurement of arterial aging parameters in subjects with WCH or MHwill identify subjects at higher risk of CV events and cognitive impairment, who may require more clinical attention and pharmacological intervention