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Habel N.,French Institute of Health and Medical Research | Habel N.,University Paris - Sud | Habel N.,University Paris Diderot | Vilalta M.,CSIC - Institute of Advanced Chemistry of Catalonia | And 11 more authors.
Oncogene | Year: 2014

Osteosarcoma is the most prevalent primary pediatric cancer-related bone disease. These tumors frequently develop resistance to chemotherapy and are highly metastatic, leading to poor outcome. Thus, there is a need for new therapeutic strategies that can prevent cell dissemination. We previously showed that CYR61/CCN1 expression in osteosarcoma cells is correlated to aggressiveness both in vitro and in vivo in mouse models, as well as in patients. In this study, we found that CYR61 is a critical contributor to the vascularization of primary tumor. We demonstrate that silencing CYR61, using lentiviral transduction, leads to a significant reduction in expression level of pro-angiogenic markers such as VEGF, FGF2, PECAM and angiopoietins concomitantly to an increased expression of major anti-angiogenic markers such as thrombospondin-1 and SPARC. Matrix metalloproteinase-2 family member expression, a key pathway in osteosarcoma metastatic capacity was also downregulated when CYR61 was downregulated in osteosarcoma cells. Using a metastatic murine model, we show that CYR61 silencing in osteosarcoma cells results in reduced tumor vasculature and slows tumor growth compared with control. We also find that microvessel density correlates with lung metastasis occurrence and that CYR61 silencing in osteosarcoma cells limits the number of metastases. Taken together, our data indicate that CYR61 silencing can blunt the malignant behavior of osteosarcoma tumor cells by limiting primary tumor growth and dissemination process. © 2015 Macmillan Publishers Limited. Source

Larrabide I.,Networking Biomedical Research Center on Bioengineering | Larrabide I.,University Pompeu Fabra | Kim M.,Networking Biomedical Research Center on Bioengineering | Kim M.,University Pompeu Fabra | And 9 more authors.
Medical Image Analysis | Year: 2012

Introduction: Minimally invasive treatment approaches, like the implantation of percutaneous stents, are becoming more popular every day for the treatment of intracranial aneurysms. The outcome of such treatments is related to factors like vessel and aneurysm geometry, hemodynamic conditions and device design. For this reason, having a tool for assessing stenting alternatives beforehand is crucial. Methodology: The Fast Virtual Stenting (FVS) method, which provides an estimation of the configuration of intracranial stents when released in realistic geometries, is proposed in this paper. This method is based on constrained simplex deformable models. The constraints are used to account for the stent design. An algorithm for its computational implementation is also proposed. The performance of the proposed methodology was contrasted with real stents released in a silicone phantom. Results: In vitro experiments were performed on the phantom where a contrast injection was performed. Subsequently, corresponding Computational Fluid Dynamics (CFD) analyzes were carried out on a digital replica of the phantom with the virtually released stent. Virtual angiographies are used to compare in vitro experiments and CFD analysis. Contrast time-density curves for in vitro and CFD data were generated and used to compare them. Conclusions: Results of both experiments resemble very well, especially when comparing the contrast density curves. The use of FVS methodology in the clinical environment could provide additional information to clinicians before the treatment to choose the therapy that best fits the patient. © 2010 Elsevier B.V. Source

Geers A.J.,University Pompeu Fabra | Geers A.J.,Networking Biomedical Research Center on Bioengineering | Larrabide I.,University Pompeu Fabra | Larrabide I.,Networking Biomedical Research Center on Bioengineering | And 5 more authors.
Journal of Biomechanics | Year: 2014

Computational fluid dynamics (CFD) simulations can be employed to gain a better understanding of hemodynamics in cerebral aneurysms and improve diagnosis and treatment. However, introduction of CFD techniques into clinical practice would require faster simulation times. The aim of this study was to evaluate the use of computationally inexpensive steady flow simulations to approximate the aneurysm's wall shear stress (WSS) field. Two experiments were conducted. Experiment 1 compared for two cases the time-averaged (TA), peak systole (PS) and end diastole (ED) WSS field between steady and pulsatile flow simulations. The flow rate waveform imposed at the inlet was varied to account for variations in heart rate, pulsatility index, and TA flow rate. Consistently across all flow rate waveforms, steady flow simulations accurately approximated the TA, but not the PS and ED, WSS field. Following up on experiment 1, experiment 2 tested the result for the TA WSS field in a larger population of 20 cases covering a wide range of aneurysm volumes and shapes. Steady flow simulations approximated the space-averaged WSS with a mean error of 4.3%. WSS fields were locally compared by calculating the absolute error per node of the surface mesh. The coefficient of variation of the root-mean-square error over these nodes was on average 7.1%. In conclusion, steady flow simulations can accurately approximate the TA WSS field of an aneurysm. The fast computation time of 6. min per simulation (on 64 processors) could help facilitate the introduction of CFD into clinical practice. © 2013 Elsevier Ltd. Source

Larrabide I.,Networking Biomedical Research Center on Bioengineering | Larrabide I.,University Pompeu Fabra | Villa-Uriol M.-C.,Networking Biomedical Research Center on Bioengineering | Villa-Uriol M.-C.,University Pompeu Fabra | And 23 more authors.
Computer Methods and Programs in Biomedicine | Year: 2012

Determining whether and how an intracranial aneurysm should be treated is a tough decision that clinicians face everyday. Emerging computational tools could help clinicians analyze clinical data and make these decisions. AngioLab is a single graphical user interface, developed on top of the open source framework GIMIAS, that integrates some of the latest image analysis and computational modeling tools for intracranial aneurysms. Two workflows are available: Advanced Morphological Analysis (AMA) and Endovascular Treatment Planning (ETP). AngioLab has been evaluated by a total of 62 clinicians, who considered the information provided by AngioLab relevant and meaningful. They acknowledged the emerging need of these type of tools and the potential impact they might have on the clinical decision-making process. © 2012 Elsevier Ireland Ltd. Source

Pashaei A.,University Pompeu Fabra | Pashaei A.,Networking Biomedical Research Center on Bioengineering | Romero D.,University Pompeu Fabra | Romero D.,Networking Biomedical Research Center on Bioengineering | And 5 more authors.
IEEE Transactions on Biomedical Engineering | Year: 2011

In this paper, we present a modeling methodology to couple the cardiac conduction system to cardiac myocytes through a model of Purkinje-ventricular junctions to yield fast and realistic electrical activation of the ventricles. A patient-specific biventricular geometry is obtained from processing computed tomography scan data. A one-manifold implementation of the fast marching method based on Eikonal-type equations is used for modeling heart electrophysiology, which facilitates the multiscale 1-D-3-D coupling at very low computational costs. The method is illustrated in in-silico experiments where we analyze and compare alternative pacing strategies on the same patient-specific anatomy. We also show very good agreement between the results from the proposed approach and more detailed and comprehensive biophysical models for modeling cardiac electrophysiology. The effect of atrioventricular delay on the distribution of activation time in myocardium is studied with two experiments. Given the reasonable computational times and realistic activation sequences provided by our method, it can have an important clinical impact on the selection of optimal implantation sites of pacing leads or placement of ablation catheters tip in the context of cardiac rhythm management therapies. © 2011 IEEE. Source

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