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Computational modeling of blood flow in the tumor vasculature

English title Computational modeling of blood flow in the tumor vasculature
Applicant Rüegg Curzio Roberto
Number 137357
Funding scheme SCOPES
Research institution Unité de Pathologie Faculté de Science et Médecine Université de Fribourg
Institution of higher education University of Fribourg - FR
Main discipline Pathophysiology
Start/End 01.06.2012 - 31.05.2015
Approved amount 135'000.00
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All Disciplines (2)

Discipline
Pathophysiology
Fluid Dynamics

Keywords (5)

Modélisation ; Cancer; Angiogenèse tumorale; Flux sanguin; Thérapie

Lay Summary (French)

Lead
Lay summary

La modélisation par ordinateur du flux sanguin des vaisseaux tumoraux

La circulation sanguine est essentielle pour de nombreux processus physiologiques, allant du développement embryonnaire, à la différenciation, et la réparation des tissus ainsi que pour des états pathologiques tels que l'inflammation et le cancer. Il existent deux types de flux sanguin : le flux laminaire et le flux turbulent. Le flux laminaire est le flux normal dans la plupart des vaisseaux, tandis que le flux turbulent apparaît dans des situations de débit, pression et architecture vasculaire anormales. Le type de flux à un impact sur les cellules endothéliales et sur la biodistribution des éléments contenus dans le sang. Par example, le flux laminaire protège les cellules endothéliales et est anti-inflammatoire, tandis que le flux turbulent active les cellules endothéliales et est pro-inflammatoire. Les vaisseaux tumoraux sont différents des vaisseaux normaux : Ils sont chaotiques, irrégulier et perfusé irrégulièrement. Malgré son rôle clé dans l’apport de nutriments et de médicaments à la tumeur, le flux sanguin à l'intérieur de vaisseaux tumoraux est mal connu.

Dans ce projet nous allons caractériser le flux sanguin à l’intérieur des tumeurs en associant des expériences de modélisation mathématique du flux sanguin par ordinateur à des expériences fonctionnelles dans des modèles expérimentaux. La modélisation mathématique du flux sanguin dans les vaisseaux tumoraux sera utilisé pour estimer l'impact sur la biologie des tumeurs et la biodistribution des médicaments.

Ce projet est développé en partenariat entre l'Université de Kragujevac et l'Université de Fribourg. L'Université de Kragujevac est le plus grand établissement d'enseignement et de recherche de la Serbie centrale. Un des nouveaux domaines de recherche et d'enseignement est la bio-ingénierie. Le Centre de bio-ingénierie dirigé par le professeur Nenad Filipovic dispose d'installations informatiques de pointe et des chercheurs très actifs. Il apporte à ce projet les compétences nécessaires pour la modélisation mathématique du flux sanguin. Le Département de médecine à la Faculté des sciences, de l'Université de Fribourg a une longue tradition dans la recherche et l'enseignement en sciences médicales de base. Le laboratoire de oncologie expérimentale et translationnelle dirigé par le professeur Curzio Rüegg est à la pointe dans le domaine de l’angiogenèse tumorale et des thérapies anticancéreuses. Il apporte à ce projet les compétences nécessaires pour les expériences d’angiogenèse tumorale.

Au delà des aspects purement scientifiques, ce projet a aussi pour but de développer un partenariat institutionnel en matière de recherche et de formation entre ces deux universités pour mettre en place un nouveau programme d'études dans la recherche expérimentale et la modélisation mathématique en biologie vasculaire. Des ateliers, des stages de formation et des cours d'été seront organisés pour les étudiants.

 

Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Publications

Publication
Computational modeling of shear forces and experimental validation of endothelial cell responses in an orbital well shaker system
Nenad Filipovic Kedar Ghimir Igor Saveljic Zarko Milosevic and Curzio Ruegg (2015), Computational modeling of shear forces and experimental validation of endothelial cell responses in an orbital well shaker system, in Comput Methods Biomech Biomed Engin, [Epub ahead of print](June 22), 1-10.
Modeling of liver metastatic disease with applied drug therapy
Nenad Filipovic Tijana Djukic Igor Saveljic Petar Milenkovic and Marija Djuric (2014), Modeling of liver metastatic disease with applied drug therapy, in Methods and Programs in Biomedicine , 115, 3, Pages, 2014(3), 162-170.

Collaboration

Group / person Country
Types of collaboration
University of Friibourg Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
University of Kragujevac Serbien (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Sixth international conference on tumor-host interaction and Angiogenesis Monte Verità, Ascona Individual talk Mechanisms of tumor dormancy and metastasis 17.05.2015 Ascona, Switzerland Rüegg Curzio Roberto;
Methodologies and Experimental Strategies in Angiogenesis Research Talk given at a conference Models of tumor angiogenesis 08.04.2015 Bordeaux, France Rüegg Curzio Roberto;
Computational modeling of blood flow in the tumor vasculature Talk given at a conference Computer modeling of angiogenesis and blood microcirculation 25.04.2014 Fribourg, Switzerland Filipovic Nenad;
“Computational modeling of blood flow in the tumor vasculature Talk given at a conference Tumor angiogenesis 25.04.2014 Fribourg, Switzerland Rüegg Curzio Roberto;
International Congress of Serbian Society of Mechanics Talk given at a conference Modeling of tumor response to therapy 03.06.2013 Vrnjacka Banja, Serbia, Serbien Filipovic Nenad;
Invited seminar Individual talk radiation-induced metastasis 04.03.2013 University of Oxford Oxford, UK,, Great Britain and Northern Ireland Rüegg Curzio Roberto;
Invited seminar Individual talk Tumor mircroenvironment and metastasis formation 05.02.2013 Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Switzerland, Switzerland Rüegg Curzio Roberto;
Invited seminar Individual talk Mechanisms of radiation-induced mateatsais 18.01.2013 IRA-CHUV-UNIL, Lausanne, Switzerland, Switzerland Rüegg Curzio Roberto;
invited seminar Individual talk Tumor mircroenvironment and metastasis formation 15.11.2012 Institute of Anatomy, University of Bern, Switzerland Rüegg Curzio Roberto;
Invited seminar Individual talk Tumor mircroenvironment and metastasis formation 12.10.2012 IRB, Bellinzona, Switzerland, Switzerland Rüegg Curzio Roberto;
Invited seminar Individual talk Mechanisms of radiation-induced mateatsais 04.09.2012 DKFZ Heidelberg and Mannheim University, Germany, Germany Rüegg Curzio Roberto;
Invited Seminar Individual talk Role of radiotherapy in cancer progression 30.08.2012 Lausanne, Switzerland Rüegg Curzio Roberto;


Self-organised

Title Date Place
Mathematical modeling and experimental models in vascular biology 02.02.2015 Fribourg, Switzerland
Computational modeling of blood flow in the tumor vasculature 07.07.2014 Kragujevac, Serbien

Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions MedAlumniDay Western Switzerland 2012

Abstract

Blood circulation is essential to many physiological processes, ranging from embryonic development, tissue growth, differentiation, homeostasis and repair as well as to many pathological conditions such as inflammation and cancer. Blood vessels characteristics and features of blood flow are intimately interconnected. Two extreme conditions of blood flow can be differentiated: laminar and turbulent flow. While laminar flow is the physiological condition in most vessels, turbulent flow appears under situations of abnormal vascular architecture, flow or pressure. Endothelial cells can sense laminar and turbulent flow: laminar flow induces endothelial cell quiescence and is anti-inflammatory, while turbulent flow causes endothelial cell activation, and is pro-inflammatory. Malignant tumors induce the formation of tumor-associated vessels that supply the growing tumor with nutrients, remove metabolic byproducts and they favor tumor cell escape to distant tissues. Tumor vessels are different from the vasculature of normal tissues in many respects. They are chaotic, irregular and heterogeneously perfused. The exact flow conditions inside tumor vessels and the impact on delivery of nutrient and therapeutic drugs to the tumor are only partially characterized. Mathematical modeling of perturbed blood flow as it occurs in tumor vessels can be used to estimate the impact on tumor biology and treatments and to propose hypotheses fro improved drug delivery to be tested experimentally. Modeling of such biological phenomena, however, is still a huge issue, which has to be addressed through mathematical and algorithmic approaches and validated by experimental approaches.The University of Kragujevac (UoK) is one of the youngest universities in Serbia (founded in 1960), located in Kragujevac, the city with the longest history of industry in Serbia. UoK has over 1000 professors and assistants and is the largest educational and research institution in region of Central Serbia. Various faculties and departments are offering wide and diversified study and research opportunities at both the undergraduate and the graduate levels, including Ph.D. training. One of the new scientific areas of research and teaching at UoK is bioengineering. The Center for Bioengineering at Faculty of Mechanical Engineering, headed by Prof. Nenad Filipovic, provides a very solid basis to achieve the research and educational goals aimed at in the project. It has advanced computing facilities and highly active researchers and it is carrying a number of international scientific projects in the field of material modeling and software development. The Department of Medicine, Faculty of Sciences, of the University of Fribourg (UNIFR) has a long-standing tradition in research and teaching in basic medical sciences. With the introduction of the 3rd year of medicine and the delivery of a bachelor degree in medicine, new specialties have been introduced and new professors recruited, including the Swiss partner of this application. The Swiss partner, Prof. Curzio Rüegg, is an expert in tumor angiogenesis, vascular biology and translational cancer research. Prof. Rüegg has a well-developed facility to perform experimental research in cancer and vascular biology. The two partners are already collaborating on a project aimed at modeling the role of shear in endothelial cell activation during vascular remodeling in cardiovascular diseases. The aim of this SCOPE proposal is to build on these complementary competencies to develop a Institutional Partnership in research and training between the UNIFR and the UoK in computer modeling in tumor angiogenesis. Specifically we propose to: •Develop a collaborative project involving compute modeling and experimental research in tumor angiogenesis, with particular emphasis on drug delivery•Organize workshops and training courses for students•Organize summer schools for students•Develop a new curriculum in experimental research and mathematical modeling of tumor angiogenesisCommunication and mutual understanding between experimental and computational scientists is crucial for a better understanding of the pathophysiology of tumor vessels. The organization of workshops, training courses, and summer schools where students and scientists from both experimental and computational research can meet and discuss is a first step toward the development of a joint new curriculum in the area of experimental and computer modeling at UNIFR and UoK.
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