25,515 research outputs found
Modelling the response of vascular tumours to chemotherapy: A multiscale approach
An existing multiscale model is extended to study the response of a vascularised tumour to treatment with chemotherapeutic drugs which target proliferating cells. The underlying hybrid cellular automaton model couples tissue-level processes (e.g. blood flow, vascular adaptation, oxygen and drug transport) with cellular and subcellular phenomena (e.g. competition for space, progress through the cell cycle, natural cell death and drug-induced cell kill and the expression of angiogenic factors). New simulations suggest that, in the absence of therapy, vascular adaptation induced by angiogenic factors can stimulate spatio-temporal oscillations in the tumour's composition.\ud
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Numerical simulations are presented and show that, depending on the choice of model parameters, when a drug which kills proliferating cells is continuously infused through the vasculature, three cases may arise: the tumour is eliminated by the drug; the tumour continues to expand into the normal tissue; or, the tumour undergoes spatio-temporal oscillations, with regions of high vascular and tumour cell density alternating with regions of low vascular and tumour cell density. The implications of these results and possible directions for future research are also discussed
Maternal fish consumption, fatty acid levels and angiogenic factors: The Generation R Study
Introduction Angiogenic factors, such as placental growth factor (PlGF) and soluble Flt-1 (sFlt-1), are key regulators of placental vascular development. Evidence from in vitro studies indicates that fatty acids can affect angiogenesis. We investigated the associations of maternal fish consumption and fatty acids levels with angiogenic factors during pregnancy, and in cord blood in a large population-based prospective cohort. Methods First trimester fish consumption was assessed among 3134 pregnant women using a food-frequency questionnaire. Plasma fatty acid levels were measured in second trimester. Plasma PlGF and sFlt-1 were measured in first and second trimester and in cord blood. Associations of fish consumption or fatty acid levels with angiogenic factors were assessed by multivariable linear regression analyses. Results There were no consistent associations of total fish or lean fish consumption with levels of PlGF, sFlt-1, or sFlt-1/PlGF ratio. Neither fatty fish nor shellfish were associated with angiogenic factors. Plasma omega-3 polyunsaturated fatty acids, which are the main type of fatty acids in fish, were inconsistently associated with angiogenic factors in second trimester and cord blood. Yet, higher levels of arachidonic acid, an omega-6 polyunsaturated fatty acid, were associated with lower levels of PlGF and sFlt-1. Discussion We found no consistent associations of fish consumption or fatty acids levels with angiogenic factors in a population with low fish consumption. Studies including populations with higher fish consumption are required to fully grasp the potential effects of maternal fish consumption on placental angiogenesis
The zebrafish xenograft platform-A novel tool for modeling KSHV-associated diseases
Kaposi\u27s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic, but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the firs
Angiogenesis and Lymphangiogenesis of Gastric Cancer
Tumor angiogenesis is the result of an imbalance between positive and negative angiogenic factors released by tumor and host cells into the microenvironment of the neoplastic tissue. The stroma constitutes a large part of most solid tumors, and cancer-stromal cell interactions contribute functionally to tumor growth and metastasis. Activated fibroblasts and macrophages in tumor stroma play important roles in angiogenesis and tumor progression. In gastric cancer, tumor cells and stromal cells produce various angiogenic factors, including vascular endothelial growth factor, interleukin-8, platelet-derived endothelial cell growth factor, and angiopoietin. In addition, Helicobacter pylori infection increases tumor cell expression of metastasis-related genes including those encoding several angiogenic factors. We review the current understanding of molecular mechanisms involved in angiogenesis and lymphangiogenesis of human gastric cancer
Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights
There is an ongoing debate on the therapeutic potential of vaso-modulatory
interventions against glioma invasion. Prominent vasculature-targeting
therapies involve functional tumour-associated blood vessel deterioration and
normalisation. The former aims at tumour infarction and nutrient deprivation
medi- ated by vascular targeting agents that induce occlusion/collapse of
tumour blood vessels. In contrast, the therapeutic intention of normalising the
abnormal structure and function of tumour vascular net- works, e.g. via
alleviating stress-induced vaso-occlusion, is to improve chemo-, immuno- and
radiation therapy efficacy. Although both strategies have shown therapeutic
potential, it remains unclear why they often fail to control glioma invasion
into the surrounding healthy brain tissue. To shed light on this issue, we
propose a mathematical model of glioma invasion focusing on the interplay
between the mi- gration/proliferation dichotomy (Go-or-Grow) of glioma cells
and modulations of the functional tumour vasculature. Vaso-modulatory
interventions are modelled by varying the degree of vaso-occlusion. We
discovered the existence of a critical cell proliferation/diffusion ratio that
separates glioma invasion re- sponses to vaso-modulatory interventions into two
distinct regimes. While for tumours, belonging to one regime, vascular
modulations reduce the tumour front speed and increase the infiltration width,
for those in the other regime the invasion speed increases and infiltration
width decreases. We show how these in silico findings can be used to guide
individualised approaches of vaso-modulatory treatment strategies and thereby
improve success rates
Maternal fish consumption, fatty acid levels and angiogenic factors: The Generation R Study
AbstractIntroductionAngiogenic factors, such as placental growth factor (PlGF) and soluble Flt-1 (sFlt-1), are key regulators of placental vascular development. Evidence from in vitro studies indicates that fatty acids can affect angiogenesis. We investigated the associations of maternal fish consumption and fatty acids levels with angiogenic factors during pregnancy, and in cord blood in a large population-based prospective cohort.MethodsFirst trimester fish consumption was assessed among 3134 pregnant women using a food-frequency questionnaire. Plasma fatty acid levels were measured in second trimester. Plasma PlGF and sFlt-1 were measured in first and second trimester and in cord blood. Associations of fish consumption or fatty acid levels with angiogenic factors were assessed by multivariable linear regression analyses.ResultsThere were no consistent associations of total fish or lean fish consumption with levels of PlGF, sFlt-1, or sFlt-1/PlGF ratio. Neither fatty fish nor shellfish were associated with angiogenic factors. Plasma omega-3 polyunsaturated fatty acids, which are the main type of fatty acids in fish, were inconsistently associated with angiogenic factors in second trimester and cord blood. Yet, higher levels of arachidonic acid, an omega-6 polyunsaturated fatty acid, were associated with lower levels of PlGF and sFlt-1.DiscussionWe found no consistent associations of fish consumption or fatty acids levels with angiogenic factors in a population with low fish consumption. Studies including populations with higher fish consumption are required to fully grasp the potential effects of maternal fish consumption on placental angiogenesis
Directional control of angiogenesis to produce a designed multiscale micro-vascular network with bioprinting
Department of Biomedical EngineeringThe biomimetic vascular network is a key element in regeneration of viable, functional and scalable artificial tissues. In this study, we developed a multiscale vascular network that can be patterned freely by using bioprinting technology. An endothelialized channel of several hundred micrometer scale was directly printed. The micro-vascular network consisting of tubular structures of several tens of micrometers was generated through the direction control of angiogenic sprouting using the chemotaxis effect. For this purpose, human umbilical vein endothelial cells (HUVEC) and angiogenic factor secreting cells, normal human dermal fibroblasts (NHDF), were co-patterned at 1 to 2 mm intervals using water soluble bio-ink and alginate based bio-ink, respectively. Then, a bridge pattern connecting the two patterned gels was made with fibrin gel. After printing, an endothelialized channel of about 800 ??m was formed by selective removal of water soluble bio-ink. The angiogenic sprouting was induced at about 200 ??m/day along the bridge pattern from the channel. It was also possible to fabricate a multiscale micro-vascular network with diagonal, wave and branch shapes using bridge patterns of various designs. In this study, we investigated the functionality of hepatocytes by co-culturing mouse primary hepatocytes after fabricating a vascular construct with hepatic lobule-shaped pattern to confirm the utility of the constructed process. As a result, we could confirm largely improved albumin and urea secretion. Based on these results, we confirmed that the tissue specific multiscale vascular network could be constructed. This technique should provide a useful tool for the development of functional and scalable vascularized tissues.clos
Role of genetic polymorphisms in tumour angiogenesis
Angiogenesis plays a crucial role in the development, growth and spread of solid tumours. Pro- and anti-angiogenic factors are abnormally expressed in tumours, influencing tumour angiogenesis, growth and progression. Polymorphisms in genes encoding angiogenic factors or their receptors may alter protein expression and/or activity. This article reviews the literature to determine the possible role of angiogenesis-related polymorphisms in cancer. Further research studies in this potentially crucial area of tumour biology are proposed
Long-time behavior of an angiogenesis model with flux at the tumor boundary
This paper deals with a nonlinear system of partial differential equations
modeling a simplified tumor-induced angiogenesis taking into account only the
interplay between tumor angiogenic factors and endothelial cells. Considered
model assumes a nonlinear flux at the tumor boundary and a nonlinear
chemotactic response. It is proved that the choice of some key parameters
influences the long-time behaviour of the system. More precisely, we show the
convergence of solutions to different semi-trivial stationary states for
different range of parameters.Comment: 17 page
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