9 results on '"Tanguy, Julie"'
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2. HSPB5 Inhibition by NCI-41356 Reduces Experimental Lung Fibrosis by Blocking TGF-β1 Signaling
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Tanguy, Julie, primary, Boutanquoi, Pierre-Marie, additional, Burgy, Olivier, additional, Dondaine, Lucile, additional, Beltramo, Guillaume, additional, Uyanik, Burhan, additional, Garrido, Carmen, additional, Bonniaud, Philippe, additional, Bellaye, Pierre-Simon, additional, and Goirand, Françoise, additional
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- 2023
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3. In Vivo Nuclear Imaging of Hypoxia as Predictive Biomarkers and follow up the Response to Anti-VEGF Therapies in Idiopathic Pulmonary Fibrosis
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Tanguy, Julie and STAR, ABES
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Hypoxie ,Diagnostic tool ,Ipf ,Fpi ,Outil diagnostique ,Anti-VEGF ,Imagerie nucléaire ,Hypoxia ,Nuclear imaging ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology - Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal disease of unknown origin. In France, it is one of the most common interstitial pathologies (IP) and affects 4,400 new people each year. IPF is characterized by dysregulated healing mechanisms that lead to the accumulation of large amounts of collagen in the lung tissue and cause disorganization of the alveolar architecture. It results in progressive deterioration of the respiratory function, leading in a few years to chronic respiratory failure and then to death. Idiopathic pulmonary fibrosis has a lower survival rate than many cancers with a median survival of 2 to 5 years from diagnosis. This pathology whose main risk factor, in addition to genetic and environmental factors (cigarettes, pollution, etc.), remains age, rarely occurs before the age of 60. Despite the therapeutic advances made in recentyears in the field of fibrosis, IPF remains an incurable and lethal disease. The late management of patients, the complexity of the diagnosis and the lack of therapeutic solutions or early diagnosis strategies are all issues that explain the mortality associatedwith this pathology. Today, the identification of signaling pathways and key cellular actors involved in IPF development remains crucial in order, on the one hand, to develop new treatments and, on the other hand, to identify new tools for earlier diagnoses. In this context, the study of the roles of heat shock proteins HSPB5 and HSP90 in idiopathic pulmonary fibrosis as well as markers of hypoxia could provide new therapeutic and diagnostic targets. IPF imaging is in practice limited to high-resolution computed tomography (HRCT). This examination is often insufficient for a definitive diagnosis of the disease and has a limited impact on the therapeutic decision and management of IPF patients. Pulmonary hypoxia is an important feature of IPF, but its role in disease progression remains unknown. Thus, using a preclinical model of bleomycin-induced pulmonary fibrosis, we have determined in vivo that hypoxia imaging with 18F-FMISO could constitute a predictive biomarker of disease progression and treatment efficacy compared to another clinically used marker 18F-FDG. We have also shown in vivo in our mouse model that inhibition of HSPB5, a low molecular weight heat shock protein known to be involved in the development of fibrosis, using NCI-41356 allows to reduce fibrosis by modulating the expression of several pro-fibrotic factors including TGF-Beta;. In addition, we have also demonstrated that targeting the extracellular HSP90 protein overexpressed in plasma as well as in fibrotic tissues of IPF patients could constitute a potential theranostic tool for fibrosis.In conclusion, this thesis work has made it possible to characterize a potential early and predictive radiopharmaceutical tracer of the evolution of pulmonary fibrosis as well as the anti-fibrotic role of a chemical inhibitor of the canonical TGF-Beta; pathway. Furthermore, we hope that our results concerning the HSP90 protein will make it possible to envisage the theranostic use of recombinant antibodies against HSP90 in the context of IPF., La fibrose pulmonaire idiopathique (FPI) est une maladie chronique, évolutive et mortelle d'origine inconnue. En France, elle figure parmi les pathologies interstitielles (PI) les plus fréquentes et touche 4400 nouvelles personnes chaque année. La FPI est caractérisée par des mécanismes de cicatrisation dérégulés qui induisent l'accumulation de grandes quantités de collagène dans le tissu pulmonaire et provoquent une désorganisation de l'architecture alvéolaire. Elle se manifeste par une détérioration progressive de la fonction respiratoire, conduisant en quelques années à une insuffisance respiratoire chronique puis au décès. Le taux de survie de la fibrose pulmonaire idiopathique est inférieur à celui de nombreux cancers avec une survie médiane de 2 à 5 ans à partir du diagnostic. Cette pathologie, dont le principal facteur de risque outre les facteurs génétiques et environnementaux (cigarette, pollution, etc.) reste l’âge, se manifeste rarement avant 60 ans. Malgré les avancées thérapeutiques récentes réalisées dans le domaine de la fibrose, la FPI reste une maladie incurable et létale. La prise en charge tardive des patients, la complexité du diagnostic et le manque de solutions thérapeutiques et diagnostiques précoces sont autant de points qui expliquent la mortalité associée à cette pathologie. Aujourd’hui, il reste crucial de continuer à identifier les acteurs cellulaires et moléculaires du développement de la FPI afin, d’une part, de développer de nouveaux traitements inhibiteurs et d’autre part, de mettre au point de nouveaux outils diagnostiques plus précoces. Dans ce contexte, l’étude du rôle des protéines de choc thermique HSPB5 et HSP90 dans la FPI ainsi que des marqueurs de l’hypoxie pourraient apporter de nouvelles solutions thérapeutiques et diagnostiques. L'imagerie de la FPI est en pratiquelimitée à la tomodensitométrie à haute résolution (HRCT). Cet examen reste souvent insuffisant pour un diagnostic définitif de la maladie et a un impact limité sur la décision thérapeutique et la prise en charge des patients. L'hypoxie pulmonaire est une caractéristique importante de la FPI, mais son rôle sur la progression de la maladie reste méconnu. Ainsi à l’aide d’un modèle préclinique de fibrose pulmonaire induite par la bléomycine nous avons déterminé in vivo que l’imagerie de l'hypoxie au 18FFMISOpouvait constituer un biomarqueur prédictif de la progression de la maladie et de l'efficacité des traitements par rapport à un autre marqueur utilisé en clinique le 18F-FDG. Nous avons également montré in vivo dans notre modèle murin que l’administration d’un inhibiteur (le NCI-41356) de HSPB5, une protéine de choc thermique de bas poids moléculaire connue pour être impliquée dans le développement de la fibrose, permet de réduire la fibrose en modulant l’expression de plusieurs facteurs pro-fibrotiques dont le TGF-Beta;. De plus, nous avons montré qu’inhiber la protéine HSP90, surexprimée à la fois au niveau circulant et au sein des tissus fibrotiques des patients atteints de FPI, présente un potentiel intérêt théranostique.En conclusion, ce travail de thèse a permis de caractériser un potentiel traceur radiopharmaceutique précoce et prédictif de l’évolution de la fibrose pulmonaire ainsi que le rôle anti-fibrotique d’un inhibiteur chimique de la voie canonique du TGF-Beta;. Par ailleurs nous espérons que nos résultats concernant la protéine HSP90 pourraient permettre d’envisager l’utilisation théranostique d’anticorps recombinant dirigés contre HSP90 dans le contexte de la FPI.
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- 2022
4. Extracellular Heat Shock Proteins as Therapeutic Targets and Biomarkers in Fibrosing Interstitial Lung Diseases
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Tanguy, Julie, primary, Pommerolle, Lenny, additional, Garrido, Carmen, additional, Kolb, Martin, additional, Bonniaud, Philippe, additional, Goirand, Françoise, additional, and Bellaye, Pierre-Simon, additional
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- 2021
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5. Role of Extracellular HSP27 in pulmonary fibrosis
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Pommerolle, Lenny, primary, Burgy, Olivier, additional, Dondaine, Lucile, additional, Boutanquoi, Pierre-Marie, additional, Beltramo, Guillaume, additional, Tanguy, Julie, additional, Loriod, Sabrina, additional, Garrido, Carmen, additional, Bonniaud, Philippe, additional, and Goirand, Françoise, additional
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- 2020
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6. [18F]FMISO PET/CT imaging of hypoxia as a non-invasive biomarker of disease progression and therapy efficacy in a preclinical model of pulmonary fibrosis: comparison with the [18F]FDG PET/CT approach.
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Tanguy, Julie, Goirand, Françoise, Bouchard, Alexanne, Frenay, Jame, Moreau, Mathieu, Mothes, Céline, Oudot, Alexandra, Helbling, Alex, Guillemin, Mélanie, Bonniaud, Philippe, Cochet, Alexandre, Collin, Bertrand, and Bellaye, Pierre-Simon
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COMPUTED tomography , *PULMONARY fibrosis , *IDIOPATHIC pulmonary fibrosis , *DISEASE progression , *BIOMARKERS , *POSITRON emission tomography computed tomography - Abstract
Purpose: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor outcome and limited therapeutic options. Imaging of IPF is limited to high-resolution computed tomography (HRCT) which is often not sufficient for a definite diagnosis and has a limited impact on therapeutic decision and patient management. Hypoxia of the lung is a significant feature of IPF but its role on disease progression remains elusive. Thus, the aim of our study was to evaluate hypoxia imaging with [18F]FMISO as a predictive biomarker of disease progression and therapy efficacy in preclinical models of lung fibrosis in comparison with [18F]FDG. Methods: Eight-week-old C57/BL6 mice received an intratracheal administration of bleomycin (BLM) at day (D) 0 to initiate lung fibrosis. Mice received pirfenidone (300 mg/kg) or nintedanib (60 mg/kg) by daily gavage from D9 to D23. Mice underwent successive PET/CT imaging at several stages of the disease (baseline, D8/D9, D15/D16, D22/D23) with [18F]FDG and [18F]FMISO. Histological determination of the lung expression of HIF-1α and GLUT-1 was performed at D23. Results: We demonstrate that mean lung density on CT as well as [18F]FDG and [18F]FMISO uptakes are upregulated in established lung fibrosis (1.4-, 2.6- and 3.2-fold increase respectively). At early stages, lung areas with [18F]FMISO uptake are still appearing normal on CT scans and correspond to areas which will deteriorate towards fibrotic lesions at later timepoints. Nintedanib and pirfenidone dramatically and rapidly decreased mean lung density on CT as well as [18F]FDG and [18F]FMISO lung uptakes (pirfenidone: 1.2-, 2.9- and 2.6-fold decrease; nintedanib: 1.2-, 2.3- and 2.5-fold decrease respectively). Early [18F]FMISO lung uptake was correlated with aggressive disease progression and better nintedanib efficacy. Conclusion: [18F]FMISO PET imaging is a promising tool to early detect and monitor lung fibrosis progression and therapy efficacy. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Pirates ! - La légende du drapeau noir
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Proust Tanguy, Julie and Proust Tanguy, Julie
- Abstract
Jadis barbare, hors-la-loi, source de terreur et de cruauté ; aujourd’hui, symbole de liberté, de résistance et d’aventure. Comment expliquer une telle évolution ? Embarquez sous le pavillon noir pour découvrir les distorsions de la légende de ces bandits qui, après avoir parcouru les sept mers, hantent désormais le cyber-espace...
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- 2016
8. L'Antiquité romaine : 80 mots-clés pour découvrir l'histoire, la culture et la vie quotidienne à Rome. Ed. 1
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Proust Tanguy, Julie and Proust Tanguy, Julie
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Ce guide vivant en 80 mots-clés vise à faire (re)découvrir au lecteur l'Antiquité et surtout à compléter une approche parfois approximative de la Rome antique. En abordant l'histoire, la politique, l'économie mais aussi les mythes, l'éducation et les divertissements, il permet de comprendre pourquoi nous nourrissons toujours une certaine fascination pour les ruines et les textes antiques. Ecrit par une spécialiste, cet ouvrage complet vous montrera enfin comment la civilisation romaine a façonné certains aspects de notre quotidien, de notre culture et de notre imaginaire.
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- 2016
9. CD206 + macrophages are relevant non-invasive imaging biomarkers and therapeutic targets in experimental lung fibrosis.
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Pommerolle L, Beltramo G, Biziorek L, Truchi M, Dias AMM, Dondaine L, Tanguy J, Pernet N, Goncalves V, Bouchard A, Monterrat M, Savary G, Pottier N, Ask K, Kolb MRJ, Mari B, Garrido C, Collin B, Bonniaud P, Burgy O, Goirand F, and Bellaye PS
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Background: Interstitial lung diseases (ILDs) include a large number of diseases associated with progressive pulmonary fibrosis (PPF), including idiopathic pulmonary fibrosis (IPF). Despite the rarity of each of the fibrotic ILDs individually, they cumulatively affect a considerable number of patients. PPF is characterised by an excessive collagen deposition leading to functional decline., Objectives: Therapeutic options are limited to nintedanib and pirfenidone which are only able to reduce fibrosis progression. CD206-expressing M2 macrophages are involved in fibrosis progression, and whether they may be relevant therapeutic targets or biomarkers remains an open question., Results: In our study, CD206
+ lung macrophages were monitored in bleomycin-induced lung fibrosis in mice by combining flow cytometry, scRNAseq and in vivo molecular imaging using a single photon emission computed tomography (SPECT) radiopharmaceutical,99m Tc-tilmanocept. The antifibrotic effect of the inhibition of M2 macrophage polarisation with a JAK inhibitor, tofacitinib, was assessed in vivo. We demonstrate that CD206-targeted in vivo SPECT imaging with99m Tc-tilmanocept was able to accurately detect and quantify the increase in CD206+ macrophages from early to advanced stages of experimental fibrosis and ex vivo in lung biopsies from patients with IPF. CD206-targeted imaging also specifically detected a decrease in CD206+ lung macrophages on nintedanib and tofacitinib treatment. Importantly, early in vivo imaging of CD206+ macrophages allowed the prediction of experimental lung fibrosis progression as well as nintedanib and tofacitinib efficacy., Conclusions: These findings indicate that M2 macrophages may be relevant theranostic targets for personalised medicine for patients with PPF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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