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3D bioprinted breast cancer model reveals stroma-mediated modulation of extracellular matrix and radiosensitivity

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Bioactive Materials 2024年第12期42卷 316-327页

作者： Theo Desigaux Leo Comperat Nathalie Dusserre Marie-Laure Stachowicz Malou Lea Jean-William Dupuy Anthony Vial Michael Molinari Jean-Christophe Fricain Francois Paris Hugo Oliveira univ.bordeaux Tissue Bioengineering INSERM U1026F-33000BordeauxFrance INSERM U1026 ART BioPrintF-33000BordeauxFrance univ.bordeaux Bordeaux ProteomeF-33000BordeauxFrance univ.bordeaux CNRSINSERMTBM-CoreUS5UAR 3427OncoProtF-33000BordeauxFrance univ.bordeaux CNRSBordeaux INPCBMNUMR 5248F-33600PessacFrance Services d’Odontologie et de Sante Buccale CHU BordeauxF-33000BordeauxFrance CRCINA INSERMCNRSUniv.NantesF-44000NantesFrance Institut de Cancerologie de l’Ouest F-44800Saint HerblainFrance

Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor ***,we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human *** findings unveil the functional maturation of this millimeter-sized model,showcasing the development of a hypoxic cancer core and an increased surface *** was also driven by the presence of cancer-associated fibroblasts(CAF)that induced elevated microvascular-like structures *** modulation was concomitant to extracellular matrix remodeling,with high levels of collagen and matricellular proteins deposition by CAF,simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic ***,our bioprinted model faithfully reproduced response to treatment,further modulated by ***,CAF played a protective role for cancer cells against radiotherapy,facilitating increased paracrine *** model holds promise as a platform to decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology.

关键词： Bioprinting Cancer microenvironment Extracellular matrix

Pivotal Role of PGE_2 and IL-10 in the Cross-Regulation of Dendritic Cell-Derived Inflammatory Mediators

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Cellular & Molecular Immunology 2006年第4期3卷 271-277页

作者： Hedi Harizi Norbert Gualde CNRS UMR 5540 bordeaux Université Bordeaux 2France

Exposure to pathogens induces antigen-presenting cells （APC） such as macrophages and dendritic cells （DC） to produce various endogenous mediators, including arachidonic acid （AA）-derived eicosanoids, cytokines, and nitric oxide （NO）. Many secreted products of activated APC can act by themselves in an autocrine manner and modulate their function. Moreover, the cross-interaction between endogenous bioactive molecules regulates the function of professional APC with important consequences for their ability to activate and sustain immune and inflammatory responses, and to regulate immune homeostasis. Although neglected for many years when compared to their role in cardiovascular homeostasis, cancer and inflammation, the importance of eicosanoids in immunology is becoming more defined. The role of prostaglandin （PG） E2 （PGE2）, one of the best known and most well studied eicosanoids, is of particular interest. It modulates the activities of professional DC by acting on their differentiation, maturation and their ability to secrete cytokines. Uniquely among haematopoietic cytokines, interleukin-10 （IL-10） is a pleiotropic molecule that displays both immunostimulatory and immunoregulatory activities. IL-10 has attached much attention because of its anti-inflammatory properties. It modulates expression of cytokines, soluble mediators and cell surface molecules by cells of myeloid origin, particularly macrophages and DC. We previously reported that PGE2 is a potent inducer of IL-10 in bone marrow-derived DC （BM-DC）, and PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype. BM-DC may be considered as an important model to study complex interactions between endogenous mediators, and autocrine IL-10 plays a pivotal role in the crossregulation of AA-derived lipid mediators, cytokines, and NO, with critical effects on immune and inflammatory responses.

关键词： BM-DC IL-10 PGE2 feed-back regulation cytokine inflammation

NetPrune:A sparklines visualization for network pruning

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Visual Informatics 2023年第2期7卷 85-99页

作者： Luc-Etienne Pommé Romain Bourqui Romain Giot Jason Vallet David Auber univ.bordeaux CNRSBordeaux INPINRIALaBRIUMR 5800F-33400 TalenceFrance

Current deep learning approaches are cutting-edge methods for solving classification *** transfer learning techniques allows applying large generic model to simple tasks whereas simpler models could be *** models raise the major problem of their memory consumption and processor usage and lead to a prohibitive ecological *** that paper,we present a novel visual analytics approach to interactively prune those networks and thus limit that *** technique leverages a novel sparkline matrix visualization technique as well as a novel local metric which evaluates the discriminatory power of a filter to guide the pruning process and make it *** assess the well-founded of our approach through two realistic case studies and a user *** both of them,the interactive refinement of the model led to a significantly smaller model having similar prediction accuracy than the original one.

关键词： Explainable pruning Guided Fine-tuning Visualization Deep learning

Color and Shape efficiency for outlier detection from automated to user evaluation

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Visual Informatics 2022年第2期6卷 25-40页

作者： Loann Giovannangeli Romain Bourqui Romain Giot David Auber univ.bordeaux CNRSBordeaux INPINRIALaBRIUMR 5800F-33400 TalenceFrance

The design of efficient representations is well established as a fruitful way to explore and analyze complex or large *** these representations,data are encoded with various visual attributes depending on the needs of the representation *** make coherent design choices about visual attributes,the visual search field proposes guidelines based on the human brain’s perception of ***,information visualization representations frequently need to depict more data than the amount these guidelines have been validated ***,the information visualization community has extended these guidelines to a wider parameter *** paper contributes to this theme by extending visual search theories to an information visualization *** consider a visual search task where subjects are asked to find an unknown outlier in a grid of randomly laid out *** are defined by color and shape features for the purpose of visually encoding categorical *** experimental protocol is made of a parameters space reduction step(i.e.,sub-sampling)based on a machine learning model,and a user evaluation to validate hypotheses and measure capacity *** results show that the major difficulty factor is the number of visual attributes that are used to encode the *** redundantly encoded,the display heterogeneity has no effect on the *** encoded with one attribute,the difficulty depends on that attribute heterogeneity until its capacity limit(7 for color,5 for shape)is ***,when encoded with two attributes simultaneously,performances drop drastically even with minor heterogeneity.

关键词： Visual search Outlier detection User evaluation Deep learning Automated evaluation

A red wine polyphenolic extract reduces the activation phenotype of cultured human liver myofibroblasts

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World Journal of Gastroenterology 2008年第14期14卷 2194-2199页

作者： Véronique Neaud Jean Rosenbaum INSERM U889 Bordeaux F-33076 France univ.rsity Victor Segalen bordeaux 2 Bordeaux F-33076 France

AIM: To test the effect of a standardized red wine polyphenolic extract (RWPE) on the phenotype of human liver myofibroblasts in culture. METHODS: Human myofibroblasts grown from liver explants were used in this study. Cell proliferation was measured with the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Signaling events were analyzed by western blot with phosphospecific antibodies. Matrix-metalloproteinase activity was measured with gel zymography. RESULTS: We found that cell proliferation was dose-dependently decreased by up to 90% by RWPE while cell viability was not affected. Exposure to RWPE also greatly decreased the phosphorylation of ERK1/ERK2 and Akt in response to stimulation by the mitogenic factor platelet-derived growth factor BB (PDGF-BB). Finally, RWPE affected extracellular matrix remodeling by decreasing the secretion by myofibroblasts of matrix-metalloproteinase-2 and of tissue inhibitor of matrix- ***: Altogether, RWPE decreases the activation state of liver myofibroblasts. The identification of the active compounds in RWPE could offer new therapeutic strategies against liver fibrosis.

关键词： Liver fibrosis Myofibroblasts Hepatic stellate cells Wine Phosphorylation Proliferation

Optical coherence tomography angiography at the acute phase of optic disc edema

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Eye and Vision 2018年第1期5卷 144-150页

作者： Marie-Bénédicte Rougier Mélanie Le Goff Jean-François Korobelnik Service d’Ophtalmologie CHU de BordeauxBordeauxFrance bordeaux Population Health Research Center Team LEHAUniversity BordeauxINSERMUMR 1219F-33000 BordeauxFrance

Background:The differential diagnosis of optic disc edema at the acute phase can be *** angiography(OCTA)is a new technology allowing the visualization of the peripapillary vascular network and optic disc *** peripapillary network alterations of glaucoma and chronic non-arteritic anterior ischemic optic neuropathy(NAION)were ***,no OCTA studies on acute optic disc edema from various *** aim of this project was to use OCTA to demonstrate the vascular changes the optic nerve head of various types of optic disc edema at the acute ***:In this retrospective study,patients with non-arteritic anterior ischemic optic neuropathy(NAION),papillitis or papilledema were *** patient was imaged using the AngioPlex^(TM)CIRRUS^(TM)HD-OCT device(model 5000,Carl Zeiss Meditec,Inc.,Dublin,USA)with a scanning area of 6×6 mm^(2) centered on the optic disc.A morphological analysis of the peripapillary network was *** some patients with unilateral optic disc edema,a quantitative analysis was performed using a swept-source OCT-A system(PLEX®Elite 9000,Carl Zeiss Meditec,Inc.,Dublin,USA).Vessel perfusion density and flux index of the peripapillary area were ***:Eight eyes with NAION(4 patients),12 eyes with papillitis(6 patients)and 25 eyes with papilledema(13 patients)were *** apparent disappearance or moderate pattern alteration of the peripapillary capillary vessels were observed in patients with NAION or papillitis,*** papilledema,the capillaries at the surface of the optic disc were dilated and tortuous,but no peripapillary network pattern changes were *** quantitative analysis did not show any difference of peripapillary network between NAION and healthy *** papillitis,the flux index was higher in inflammatory eyes compared to the healthy eyes in average(p=0.03).Conclusion:At the acute phase,the morphological analysis of OCT-A appeared to be more useful than the q

关键词： Optical coherence tomography angiography Optic nerve head Edema NAION Microvascular network And morphology

Genotype phenotype classification of hepatocellular adenoma

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World Journal of Gastroenterology 2007年第19期13卷 2649-2654页

作者： Paulette Bioulac-Sage Jean Frédéric Blanc Sandra Rebouissou Charles Balabaud Jessica Zucman-Rossi CHU bordeaux Hpital Pellegrin Department of Pathology Bordeaux F-33076 France Charles Balabaud Inserm U889 Bordeaux F-33076 GREF univ.Victor Segalen bordeaux 2 Bordeaux F-33076 France Charles Balabaud CHU Bordeaux Hpital Saint André Department of Hepatology Bordeaux F-33075 France Inserm U674 CEPH Univ Paris 7 Paris F-75010 France CHU bordeaux Hpital Saint André Department of Hepatology Bordeaux F-33075 France

Studies that compare tumor genotype with phenotype have provided the basis of a new histological/molecular classification of hepatocellular adenomas. Based on two molecular criteria （presence of a TCFI/HNF1α or β-catenin mutation）, and an additional histological criterion （presence or absence of an inflammatory infiltrate）, subgroups of hepatocellular adenoma can be defined and distinguished from focal nodular hyperplasia. Analysis of 96 hepatocellular adenomas performed by a French collaborative network showed that they can be divided into four broad subgroups： the first one is defined by the presence of mutations in TCF1 gene inactivating the hepatocyte nuclear factor 1 （HNF1α）, the second by the presence of β-catenin activating mutations; the category without mutations of HNF1α or β-catenin is further divided into 2 subgroups depending on the presence or absence of inflammation. Therefore, the approach to the diagnosis of problematic benign hepatocytic nodules may be entering a new era directed by new molecular information. It is hoped that immunohistological tools will improve significantly diagnosis of liver biopsy in our ability to distinguish hepatocellular adenoma from focal nodular hyperplasia （FNH）, and to delineate clinically meaningful entities within each group to define the best clinical management. The optimal care of patients with a liver nodule will benefit from the recent knowledge coming from molecular biology and the combined expertise of hepatologists, pathologists, radiologists, and surgeons.

关键词： Hepatocellular adenoma HNF1α mutation β-catenin mutation Inflammatory adenoma Telangiectatic adenoma Maturity-onset diabetes of theyoung Hepatocyte nuclear factor 1 CTNNB1 Focal nodular hyperplasia

Reciprocal crosstalk between dendritic cells and natural killer cells under the effects of PGE2 in immunity and immunopathology

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Cellular & Molecular Immunology 2013年第3期10卷 213-221页

作者： Hedi Harizi Laboratory of Immunology Mixed Research Unit 5540 Bordeaux 2 University Bordeaux France

The reciprocal activating crosstalk between dendritic cells （DCs） and natural killer （NK） cells plays a pivotal role in regulating immune defense against viruses and tumors. The cytokine-producing capacity, Th-cell polarizing ability and chemokine expression, migration and stimulatory functions of DCs are regulated by activated NK cells. Conversely, the innate and effector functions of NK cells require close interactions with activated DCs. Cell membrane-associated molecules and soluble mediators, including cytokines and prostaglandins （PGs）, contribute to the bidirectional crosstalk between DCs and NK cells. One of the most well-known and well-studied PGs is PGE2. Produced by many cell types, PG E2 has been shown to affect various aspects of the immune and inflammatory responses by acting on all components of the immune system. There is emerging evidence that PGE2 plays crucial roles in DC and NK cell biology. Several studies have shown that DCs are not only a source of PGE2, but also a target of its immunomodulatory action in normal immune response and during immune disorders. Although NK cells appear to be unable to produce PGE2, they are described as powerful PGE2-responding cells, as they express all PGE2 E-prostanoid （EP） receptors. Several NK cell functions （lysis, migration, proliferation, cytokine production） are influenced by PGE2. This review highlights the effects of PGE2 on DC- NK cell crosstalk and its subsequent impact on immune regulations in normal and immunopathological processes.

关键词： DC-NK cell crosstalk immunopathology NSAIDs PGE2

Evaluation of left atrial remodelling following percutaneous left atrial appendage closure

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Journal of Geriatric Cardiology 2017年第8期14卷 496-500页

作者： Zakaria Jalal Xavier Iriart Marie-Lou Dinet Olivier Comeloup Xavier Pillois Hubert Cochet Jean-Benoit Thambo Department of Paediatric and Adult Congenital Cardiology Bordeaux University Hospital Pessac France Electrophysiology and Heart Modeling Institute IHU Lirye Fondation Bordeaux UniversitO Pessac-Bordeaux France Centre de recherche Cardio-Thoracique de bordeaux INSERM Bordeaux France Department of Radiology Bordeaux University Hospital Pessac France

Atrial fibrillation prevalence is increasing with age, reaching up to 5% of patients older than 65 years, and is associated with 20%-30% of stroke episodes in that population.

关键词： Atrial fibrillation Left atrial appendage Left atrial remodeling Percutaneous closure