Modelagem ecológica e manejo de populações de pragas: uma conexão possível e necessária para um mundo em transformação

Ecological modeling is an important tool for investigating dynamic behavior patterns in populations, trophic interactions, and behavioral ecology. However, the ecological patterns that reflect population oscillation trends are often not clearly visible without analytical instruments such as ecological models. Thus, ecological modeling plays a fundamental role in describing demographic processes that are important for population dynamics. Ecological models, besides making possible the visualization of ecological patterns, may also reveal patterns of population persistence in many trophic systems, including prey-predator or host-parasitoid relationships, interactions that are commonly present in integrated pest management programs. In this forum, we present the main ecological aspects important for model building and implementation of integrated pest management programs for insects. Particularly, in this study, we analyze the combination between host-parasitoid models and the concept of economic threshold level on a spatio-temporal scale. As a conclusion about the model combination, spatial structure is essential for models of this nature, since its introduction into the system significantly alters the economic threshold-level values.A modelagem ecológica é uma ferramenta importante para a investigação de padrões de comportamento dinâmico em populações, interações tróficas e também em ecologia comportamental. Contudo, os padrões ecológicos que refletem tendências de oscilação populacional muitas vezes não são claramente visíveis sem instrumentos analíticos, como os modelos ecológicos. Dessa forma, a modelagem ecológica exerce papel fundamental na descrição de processos demográficos importantes para a dinâmica populacional. Os modelos ecológicos, além de tornarem possível a visualização de padrões ecológicos, podem também revelar padrões de persistência populacional nos diversos sistemas tróficos, incluindo as relações presa-predador ou hospedeiro-parasitóide, interações comumente presentes em programas de manejo integrado de pragas. Neste fórum apresentamos os principais aspectos ecológicos importantes para a construção de modelos e implementação de programa de manejo de pragas em insetos. Em particular, analisamos a combinação entre modelos hospedeiro-parasitóide e o conceito de nível de dano em escala espaço-temporal. Como conclusão sobre a combinação de modelos, evidencia-se que a estrutura espacial é essencial para modelos desta natureza, já que sua introdução no sistema altera significativamente os valores de nível de dano econômico.CNPqFAPES

Bridging Scales: a Hybrid Model to Simulate Vascular Tumor Growth and Treatment Response

Cancer is a disease driven by random DNA mutations and the interaction of many complex phenomena. To improve the understanding and ultimately find more effective treatments, researchers leverage computer simulations mimicking the tumor growth in silico. The challenge here is to account for the many phenomena influencing the disease progression and treatment protocols. This work introduces a computational model to simulate vascular tumor growth and the response to drug treatments in 3D. It consists of two agent-based models for the tumor cells and the vasculature. Moreover, partial differential equations govern the diffusive dynamics of the nutrients, the vascular endothelial growth factor, and two cancer drugs. The model focuses explicitly on breast cancer cells over-expressing HER2 receptors and a treatment combining standard chemotherapy (Doxorubicin) and monoclonal antibodies with anti-angiogenic properties (Trastuzumab). However, large parts of the model generalize to other scenarios. We show that the model qualitatively captures the effects of the combination therapy by comparing our simulation results with previously published pre-clinical data. Furthermore, we demonstrate the scalability of the model and the associated C++ code by simulating a vascular tumor occupying a volume of 400mm3 using a total of 92.5 million agents

MODELAGEM HÍBRIDA EM TRÊS ESCALAS PARA O CRESCIMENTO TUMORAL

O crescimento tumoral é resultado de uma série de complexos fenômenos que ocorrem em múltiplas escalas de tempo e espaço. Neste trabalho, desenvolvemos um modelo híbrido que representa fenômenos do crescimento tumoral avascular que ocorrem nas escalas tecidual, celular e sub-celular. A dispersão de nutrientes e de fatores de crescimento ocorrem na escala do tecido. Na escala da célula, destacam-se as interações mecânicas entre células e entre os componentes do microambiente. Na escala sub-celular ocorre uma variedade de cascatas de reações moleculares que regulam as atividades celulares. Eventos que ocorrem em distintas escalas se inter-relacionam, de modo que o entendimento destes mecanismos é fundamental para a compreensão da doença e para o desenvolvimento de terapias. Experimentos computacionais são realizados para demonstrar o potencial uso da metodologia desenvolvida

Predicting response to combination evofosfamide and immunotherapy under hypoxic conditions in murine models of colon cancer

The goal of this study is to develop a mathematical model that captures the interaction between evofosfamide, immunotherapy, and the hypoxic landscape of the tumor in the treatment of tumors. Recently, we showed that evofosfamide, a hypoxia-activated prodrug, can synergistically improve treatment outcomes when combined with immunotherapy, while evofosfamide alone showed no effects in an in vivo syngeneic model of colorectal cancer. However, the mechanisms behind the interaction between the tumor microenvironment in the context of oxygenation (hypoxic, normoxic), immunotherapy, and tumor cells are not fully understood. To begin to understand this issue, we develop a system of ordinary differential equations to simulate the growth and decline of tumors and their vascularization (oxygenation) in response to treatment with evofosfamide and immunotherapy (6 combinations of scenarios). The model is calibrated to data from in vivo experiments on mice implanted with colon adenocarcinoma cells and longitudinally imaged with [18F]-fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) to quantify hypoxia. The results show that evofosfamide is able to rescue the immune response and sensitize hypoxic tumors to immunotherapy. In the hypoxic scenario, evofosfamide reduces tumor burden by $45.07 \pm 2.55$%, compared to immunotherapy alone, as measured by tumor volume. The model accurately predicts the temporal evolution of five different treatment scenarios, including control, hypoxic tumors that received immunotherapy, normoxic tumors that received immunotherapy, evofosfamide alone, and hypoxic tumors that received combination immunotherapy and evofosfamide. The average concordance correlation coefficient (CCC) between predicted and observed tumor volume is $0.86 \pm 0.05$. Interestingly, the model values to fit those five treatment arms was unable to accurately predict the response of normoxic tumors to combination evofosfamide and immunotherapy (CCC = $-0.064 \pm 0.003$). However, guided by the sensitivity analysis to rank the most influential parameters on the tumor volume, we found that increasing the tumor death rate due to immunotherapy by a factor of $18.6 \pm 9.3$ increases CCC of $0.981 \pm 0.001$. To the best of our knowledge, this is the first study to mathematically predict and describe the increased efficacy of immunotherapy following evofosfamide

Potent Antioxidant and Genoprotective Effects of Boeravinone G, a Rotenoid Isolated from Boerhaavia diffusa

Background and Aims: Free radicals are implicated in the aetiology of some gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. In the present study we investigated the antioxidant and genoprotective activity of some rotenoids (i.e. boeravinones) isolated from the roots of Boerhaavia diffusa, a plant used in the Ayurvedic medicine for the treatment of diseases affecting the gastrointestinal tract. Methods/Principal Findings: Antioxidant activity has been evaluated using both chemical (Electron Spin Resonance spectroscopy, ESR) and Caco-2 cells-based (TBARS and ROS) assays. DNA damage was evaluated by Comet assay, while pERK 1/2 and phospho-NF-kB p65 levels were estimated by western blot. Boeravinones G, D and H significantly reduced the signal intensity of ESR induced by hydroxyl radicals, suggesting a scavenging activity. Among rotenoids tested, boeravinone G exerted the most potent effect. Boeravinone G inhibited both TBARS and ROS formation induced by Fenton's reagent, increased SOD activity and reduced H 2O 2-induced DNA damage. Finally, boeravinone G reduced the levels of pERK 1 and phospho-NF-kB p65 (but not of pERK 2) increased by Fenton's reagent. Conclusions: It is concluded that boeravinone G exhibits an extraordinary potent antioxidant activity (significant effect in the nanomolar range). The MAP kinase and NF-kB pathways seem to be involved in the antioxidant effect of boeravinone G. Boeravinone G might be considered as lead compound for the development of drugs potentially useful against those pathologies whose aetiology is related to ROS-mediated injuries