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9 results on '"Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)"'

1. Variations on the theme of podosomes: A matter of context

Author

IJsbrand M. Kramer, Elisabeth Génot, Florian Alonso, Pirjo Spuul, Thomas Daubon, Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Tallinn University of Technology (TTÜ), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier

Subjects
0301 basic medicine, Basement membrane, Microenvironment, Podosome, Angiogenesis, [SDV]Life Sciences [q-bio], Cell, Antigen presentation, Gene Expression, Neovascularization, Physiologic, Context (language use), Biology, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, Invasion, Mechanosensing, Cell Movement, medicine, Macrophage, Molecular Biology, Antigen Presentation, Macrophages, Cell Membrane, Dendritic Cells, Cell Biology, [SDV] Life Sciences [q-bio], Endothelial stem cell, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Podosomes, Endothelium, Vascular, Neuroscience, Signal Transduction
Abstract

International audience; Extensive in vitro studies have described podosomes as actin-based structures at the plasma membrane, connecting the cell with its extracellular matrix and endowed with multiple capabilities. Contractile actin-myosin cables assemble them into a network that constitutes a multifaceted cellular superstructure taking different forms - with common characteristics - but manifesting different properties depending on the context of study. Their morphology and their role in cell functioning and behavior are therefore now apprehended in in vivo or in vitro situations relevant to physiological processes. We focus here on three of them, namely: macrophage migration, antigen presentation by dendritic cells and endothelial cell sprouting during angiogenesis to highlight the characteristics of podosomes and their functioning shaped by the microenvironment.

Published
2019

2. Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma

Author

Emmanuel Chamorey, Wilfried Souleyreau, Alain Ravaud, Xingkang He, Papa Diogop Ndiaye, Lindsay S. Cooley, Sandy Giuliano, Nathalie M. Mazure, Benoit Beuselinck, Jessica Zucman-Rossi, Damien Ambrosetti, Patrick Auberger, Anais Hagege, Nathalie Rioux-Leclercq, Renaud Schiappa, Julien Parola, Karim Bensalah, Delphine Borchiellini, Stéphanie Torrino, Gilles Pagès, Andreas Bikfalvi, Yihai Cao, Nicolas Nottet, Baharia Mograbi, Jean-Christophe Bernhard, Annelies Verbiest, Maeva Dufies, mazure, nathalie, Centre Scientifique de Monaco (CSM), Laboratoire International Associé Réponse des Organismes et Populations face au Stress Environnemental - Université Côte d’Azur - Centre Scientifique de Monaco (LIA ROPSE), Université Côte d’Azur - Centre Scientifique de Monaco, University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Karolinska Institutet [Stockholm], Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de pharmacologie moléculaire et cellulaire (IPMC), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), CHU Pontchaillou [Rennes], CHU Bordeaux [Bordeaux], Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Universitaire de Nice (CHU Nice), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)

Subjects
0301 basic medicine, Life Sciences & Biomedicine - Other Topics, Embryo, Nonmammalian, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Cell Cycle Proteins, Drug resistance, Metastasis, Cohort Studies, Tumour biomarkers, Mice, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Biology (General), Neoplasm Metastasis, Zebrafish, Sunitinib, Kinase, Kidney Neoplasms, 3. Good health, Up-Regulation, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, Gene Expression Regulation, Neoplastic, Cancer therapeutic resistance, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Female, General Agricultural and Biological Sciences, Life Sciences & Biomedicine, medicine.drug, QH301-705.5, Mice, Nude, Protein Serine-Threonine Kinases, PLK1, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Targeted therapies, Downregulation and upregulation, In vivo, Cell Line, Tumor, Proto-Oncogene Proteins, medicine, Animals, Humans, Biology, Carcinoma, Renal Cell, Cell Proliferation, Science & Technology, business.industry, medicine.disease, Clear cell renal cell carcinoma, 030104 developmental biology, Drug Resistance, Neoplasm, Cancer research, business, Tumour angiogenesis
Abstract

Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients., Dufies et al. find high Plk1 expression levels in aggressive clear cell renal cell carcinoma and discover that Plk1 is transcriptionally upregulated in a manner dependent on HIF-2. They also find that high Plk1 expression is correlated to a poor prognosis and resistance to tyrosine kinase inhibitor against VEGF receptor, suggesting a critical role for hypoxia/HIF-2-induced Plk1 in disease progression.

Published
2020

3. The tumor organismal environment: Role in tumor development and cancer immunotherapy

Author

Lothar C. Dieterich, Andreas Bikfalvi, CCSD, Accord Elsevier, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cancer immunotherapy, Neoplasms, Tumor organismal environment, medicine, Tumor Microenvironment, Humans, Tumor growth, Tumor microenvironment, Cancer, Immunotherapy, medicine.disease, Macroenvironment, 3. Good health, [SDV] Life Sciences [q-bio], Haematopoiesis, 030104 developmental biology, Lymphatic system, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research
Abstract

International audience; Tumor immunotherapy has resulted in dramatic effects in some cancer types, including curing of previously untreatable patients. However, the response rates are typically very heterogenous, with some patients showing dramatic responses whereas others do not or only barely respond. Consequently, there has been an ever-increasing research effort to better understand the factors that govern immunotherapy responsiveness and efficiency in order to identify predictive biomarkers and novel therapeutic targets. Clearly, traits of the tumor cells as well as aspects of the tumor microenvironment (TME) play an important role in this regard. However, a growing tumor not only interacts with cells in its immediate vicinity, but also reciprocally communicates with the entire host organism (and its microbiota). Thus, systemic influences on tumor growth and progression are likely to be similarly important as the microenvironment. In this review, we focus on various aspects of the "tumor organismal environment" (TOE), namely the lymphatic, the hematopoietic, the microbial, the neurogenic and the metabolic environment, and discuss their impact on tumor growth and immunotherapy.

Published
2019

4. Patients Lung Derived Tumoroids (PLDTs) to model therapeutic response

Author

Delphine Fessart, Geraldine Siegfried, Jacques Robert, Hugues Begueret, Abdel-Majid Khatib, Fabienne Soulet, Thomas Grenier, Inaki Begiristain, Frédéric Delom, Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), UNICANCER, This work was supported by grants from the 'Région Nouvelle-Aquitaine'. FD was supported by grants from the 'Fondation ARC pour la Recherche sur le Cancer'. DF has been supported by the 'Agence Nationale de la Recherche (ANR)'. TG was supported by the 'SIRIC Brio'., Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jonchère, Laurent

Subjects
0301 basic medicine, Oncology, Drug, medicine.medical_specialty, Lung Neoplasms, media_common.quotation_subject, Primary Cell Culture, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Internal medicine, Tumor Microenvironment, medicine, Animals, Humans, Lung cancer, Lung, Molecular Biology, media_common, Tumor microenvironment, Radiation, business.industry, Cell Biology, medicine.disease, Precision medicine, Xenograft Model Antitumor Assays, Anticancer drug, Three-dimensional culture, 3. Good health, Tumoroids, 030104 developmental biology, medicine.anatomical_structure, Lung cancer cell, 030220 oncology & carcinogenesis, Chemotherapeutic drugs, Drug Screening Assays, Antitumor, business, Ex vivo
Abstract

International audience; Preclinical lung cancer models are essential for a basic understanding of lung cancer biology and its translation into efficient treatment options for affected patients. Lung cancer cell lines and xenografts derived directly from human lung tumors have proven highly valuable in fundamental oncology research and anticancer drug discovery. Both models inherently comprise advantages and caveats that have to be accounted for. Recently, we have enabled reliable in vitro culture techniques from lung cancer biopsies as Patients Lung Derived Tumoroids (PLDTs). This breakthrough provides the possibility of high-throughput drug screening covering the spectrum of lung cancer phenotypes seen clinically. We have adapted and optimized our in vitro three-dimensional model as a preclinical lung cancer model to recapitulate the tumor microenvironment (TME) using matrix reconstitution. Hence, we developed directly PLDTs to screen for chemotherapeutics and radiation treatment. This original model will enable precision medicine to become a reality, allowing a given patient sample to be screened for effective ex vivo therapeutics, aiming at tailoring of treatments specific to that individual. Hence, this tool can enhance clinical outcomes and avoid morbidity due to ineffective therapies.

Published
2020

5. The Multiple Layers of the Tumor Environment

Author

Nicolas Larmonier, Lucie Laplane, Andreas Bikfalvi, Thomas Pradeu, Dorothée Duluc, Institut d'Histoire et de Philosophie des Sciences et des Techniques (IHPST), Université Paris 1 Panthéon-Sorbonne (UP1)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Immunology from Concept and Experiments to Translation (ImmunoConcept), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 637647,H2020,ERC-2014-STG,IDEM(2015), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématopoïèse normale et pathologique (U1170 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Université Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris), Steele Children's Research Center, University of Arizona, and Mecanismes Moleculaires de l'Angiogenese

Subjects
0301 basic medicine, tumor organismal environment, Cancer Research, Angiogenesis, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Computational biology, Biology, [SHS]Humanities and Social Sciences, [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, 03 medical and health sciences, angiogenesis, Neoplasms, medicine, Humans, [SDV.BDD]Life Sciences [q-bio]/Development Biology, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Tumor microenvironment, [SHS.PHIL]Humanities and Social Sciences/Philosophy, Cancer, medicine.disease, Combined Modality Therapy, 3. Good health, niche, immune system, 030104 developmental biology, Oncology, Disease Progression, Neoplastic Stem Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, sense organs, Construct (philosophy)
Abstract

International audience; The notion of tumor microenvironment (TME) has been brought to the forefront of recent scientific literature on cancer. However, there is no consensus on how to define and spatially delineate the TME. We propose that the time is ripe to go beyond an all-encompassing list of the components of the TME, and to construct a multilayered view of cancer. We distinguish six layers of environmental interactions with the tumor and show that they are associated with distinct mechanisms, and ultimately with distinct therapeutic approaches.

Published
2018
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6. The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors

Author

Boyé, K, Pujol, N, D Alves, I, Chen, YP, Daubon, T, Lee, YZ, Dedieu, S, Constantin, M, Bello, L, Rossi, M, Bjerkvig, R, Sue, SC, Bikfalvi, A, Billottet, C., Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), National Tsing Hua University [Hsinchu] (NTHU), University of Bergen (UiB), Luxembourg Institute of Health (LIH), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano [Milano] (UNIMI), DAUBON, Thomas, Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), and École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Receptors, CXCR3, Science, [SDV]Life Sciences [q-bio], Chick Embryo, Article, Mice, stomatognathic system, immune system diseases, Cell Movement, Spheroids, Cellular, Tumor Cells, Cultured, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Neoplasm Invasiveness, lcsh:Science, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Brain Neoplasms, Cell Membrane, hemic and immune systems, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, stomatognathic diseases, Protein Transport, HEK293 Cells, lcsh:Q, Glioblastoma, Low Density Lipoprotein Receptor-Related Protein-1, Protein Binding
Abstract

CXCR3 plays important roles in angiogenesis, inflammation, and cancer. However, the precise mechanism of regulation and activity in tumors is not well known. We focused on CXCR3-A conformation and on the mechanisms controlling its activity and trafficking and investigated the role of CXCR3/LRP1 cross talk in tumor cell invasion. Here we report that agonist stimulation induces an anisotropic response with conformational changes of CXCR3-A along its longitudinal axis. CXCR3-A is internalized via clathrin-coated vesicles and recycled by retrograde trafficking. We demonstrate that CXCR3-A interacts with LRP1. Silencing of LRP1 leads to an increase in the magnitude of ligand-induced conformational change with CXCR3-A focalized at the cell membrane, leading to a sustained receptor activity and an increase in tumor cell migration. This was validated in patient-derived glioma cells and patient samples. Our study defines LRP1 as a regulator of CXCR3, which may have important consequences for tumor biology., The chemokine receptor CXCR3-A is expressed in high grade glioma. Here the authors show that CXCR3-A interacts with LPR1, a protein highly expressed in glioma, and this interaction regulates the trafficking of the receptor ultimately impacting on tumour cell migration.

Published
2017

7. The therapeutic response in Gorham's syndrome to the beta-blocking agent propranolol is correlated to VEGF-A, but not to VEGF-C or FLT1 expression

Author

Baud, Jessica, Lomri, Abderrahim, Graber, Denis, Bikfalvi, Andreas, Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Service de pédiatrie [Hôpital Saint-Louis, La Rochelle], This work was supported by funding from the « Institut National de la Santé et de la Recherche médicale (INSERM) »., and Bodescot, Myriam

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Medicine(all), Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-1, Adolescent, Neovascularization, Pathologic, Biochemistry, Genetics and Molecular Biology(all), Gorham’s syndrome, Adrenergic beta-Antagonists, Vascular Endothelial Growth Factor C, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Case Report, Propranolol, VEGF, Treatment Outcome, Humans, Female, Osteolysis, Essential, Angiogenesis, Lymphangiogenesis
Abstract

Background Gorham’s syndrome is a rare illness of unknown etiology. It is characterized by a local proliferation of blood or lymphatic vessels that in bones leads to progressive resorption and destruction. The cause of the disease is not elucidated, and therapeutic options remain limited. Case presentation We report herein the case of a young female Caucasian patient aged 18 years with diffuse Gorham syndrome. In tissue specimens angiogenesis and massive lymphangiogenesis as well as the expression of vascular endothelial growth factor-A (VEGF-A) and neuropilins was observed. Lymphangiogenesis is a prominent feature of the disease and a number of lymphatic markers were found to be expressed, however only VEGF-A, but not vascular endothelial growth factor-C (VEGF-C) was found to be elevated in the circulation. Circulating levels of soluble VEGF receptor-1 were also not elevated. Furthermore, the patient responded favorably and the disease was stabilized following treatment with the beta-blocking agent Propranolol alone which acts on VEGF-A alone, but not on soluble VEGF receptor-1 levels. Conclusion This suggests that the disease is dependent on VEGF-A, but on neither VEGF-C, the major driver of lymphangiogenesis, nor FLT1. Furthermore, Propranolol acts on VEGF-A but not FLT1 expression. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1259-9) contains supplementary material, which is available to authorized users.

Published
2014

8. A computational framework for gene regulatory network inference that combines multiple methods and datasets

Author

Philipp Antczak, Anna Stincone, Sarah Durant, Francesco Falciani, Andreas Bikfalvi, Rita Gupta, Roy Bicknell, School of Biosciences, University of Birmingham [Birmingham], Institute of Biomedical Research, Mecanismes Moleculaires de l'Angiogenese, Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), The work described in this paper was funded by the CRUK grant C8504/A9488 and partially funded by the BBSRC grant BBC5151041. AS is a recipient of a Darwin Trust PhD fellowship and PA is a recipient of a BBSRC PhD studentship., BMC, Ed., and Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Hydrogen-Ion Concentration, Time Factors, Gene regulatory network, Inference, Multiple methods, computer.software_genre, 0302 clinical medicine, Structural Biology, Gene regulatory network inference, Neoplasms, MESH: Gene Silencing, MESH: Neoplasms, Gene Regulatory Networks, MESH: Stress, Physiological, lcsh:QH301-705.5, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Gene Regulatory Networks, Genetics, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Escherichia coli, Applied Mathematics, Systems Biology, Methodology Article, Hydrogen-Ion Concentration, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, Modeling and Simulation, MESH: Systems Biology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Reverse engineering, MESH: Cell Line, Tumor, Systems biology, Biology, Machine learning, Models, Biological, 03 medical and health sciences, Stress, Physiological, Modelling and Simulation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Cell Line, Tumor, Escherichia coli, Humans, Gene Silencing, Molecular Biology, 030304 developmental biology, MESH: Humans, business.industry, MESH: Time Factors, Ode, MESH: Models, Biological, lcsh:Biology (General), Time course, Artificial intelligence, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer, 030217 neurology & neurosurgery
Abstract

Background Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective. Results This paper presents a new method for network inference, which uses multi-objective optimisation (MOO) to integrate multiple inference methods and experiments. We illustrate the potential of the methodology by combining ODE and correlation-based network inference procedures as well as time course and gene inactivation experiments. Here we show that our methodology is effective for a wide spectrum of data sets and method integration strategies. Conclusions The approach we present in this paper is flexible and can be used in any scenario that benefits from integration of multiple sources of information and modelling procedures in the inference process. Moreover, the application of this method to two case studies representative of bacteria and vertebrate systems has shown potential in identifying key regulators of important biological processes.

Published
2011

9. Computational Modelling of Metastasis Development in Renal Cell Carcinoma

Author

Olivier Saut, Etienne Baratchart, Wilfried Souleyreau, Emeline J. Ribot, Lindsay S. Cooley, Sebastien Benzekry, Andreas Bikfalvi, Raphael Pineau, Thierry Colin, Modélisation Mathématique pour l'Oncologie (MONC), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), The authors would like to thank the PlanCancer from the National Cancer Institute (INCA) and the National Institute of Health and Medical Research (INSERM) for financial support of this project (MetaSys grant to A.B and T.C). L.C,(Post-doctoral fellowship) and E.B. (PhD Fellowship) were supported by the MetaSys Grant. This work is part of the PhD thesis project of E.B. This study has been carried out within the frame of the LABEX TRAIL, ANR-10-LABX-0057 with financial support from the French State, managed by the French National Research Agency (ANR) in the frame of the 'Investments for the future' Programme IdEx (ANR-10-IDEX-03-02)., MetaSys and MIMOSA, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], Université Sciences et Technologies - Bordeaux 1 (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), and Baratchart, Etienne

Subjects
Multiple tumours, Metastatic lesions, QH301-705.5, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Models, Biological, Metastatic tumours, Metastasis, Mice, Cellular and Molecular Neuroscience, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Renal cell carcinoma, Genetics, medicine, Carcinoma, Animals, metastasis, Computer Simulation, Neoplasm Metastasis, Biology (General), Carcinoma, Renal Cell, Molecular Biology, Ecology, Evolution, Behavior and Systematics, cancer modelling, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Ecology, medicine.diagnostic_test, Computational Biology, Magnetic resonance imaging, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Kidney Neoplasms, 3. Good health, Computational Theory and Mathematics, Modeling and Simulation, Immunology, Cancer research, Female, Research Article
Abstract

The biology of the metastatic colonization process remains a poorly understood phenomenon. To improve our knowledge of its dynamics, we conducted a modelling study based on multi-modal data from an orthotopic murine experimental system of metastatic renal cell carcinoma. The standard theory of metastatic colonization usually assumes that secondary tumours, once established at a distant site, grow independently from each other and from the primary tumour. Using a mathematical model that translates this assumption into equations, we challenged this theory against our data that included: 1) dynamics of primary tumour cells in the kidney and metastatic cells in the lungs, retrieved by green fluorescent protein tracking, and 2) magnetic resonance images (MRI) informing on the number and size of macroscopic lesions. Critically, when calibrated on the growth of the primary tumour and total metastatic burden, the predicted theoretical size distributions were not in agreement with the MRI observations. Moreover, tumour expansion only based on proliferation was not able to explain the volume increase of the metastatic lesions. These findings strongly suggested rejection of the standard theory, demonstrating that the time development of the size distribution of metastases could not be explained by independent growth of metastatic foci. This led us to investigate the effect of spatial interactions between merging metastatic tumours on the dynamics of the global metastatic burden. We derived a mathematical model of spatial tumour growth, confronted it with experimental data of single metastatic tumour growth, and used it to provide insights on the dynamics of multiple tumours growing in close vicinity. Together, our results have implications for theories of the metastatic process and suggest that global dynamics of metastasis development is dependent on spatial interactions between metastatic lesions., Author Summary We used mathematical modelling to formalize the standard theory of metastatic initiation, under which secondary tumours, after establishment in a distant organ, grow independently from each other and from the primary tumour. When calibrated on the experimental data of primary tumour and total metastatic burden in the lungs in an animal model of renal cell carcinoma, the initial model predicted a size distribution of metastatic foci that did not fit with observations obtained experimentally using magnetic resonance imaging (which provided size and number of macro-metastases). The model predicted an increase in the number of lesions, but of smaller size when compared to the data. This led us to revise the standard theory and to propose two hypotheses in order to explain the observations: 1) small metastatic foci merge into larger ones and/or 2) circulating tumour cells may join already established tumours. We then derived a spatial model of tumour growth in order to explore the quantitative implications of tumours merging on global tumour growth and estimated the numbers of required metastatic foci to obtain the observed metastatic volumes.

Published
2015

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