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23 results on '"Isabelle, Brochériou"'

1. In vitro analysis of carotid lesions using a preliminary microwave sensor to detect vulnerable plaques: Correlation with histology, Duplex ultrasound examination, and computed tomography scanner: The Imaging and Microwave Phenotyping Assessment of Carotid stenosis Threat (IMPACT) study

Author

Rania Shahbaz, PhD, Etienne Charpentier, MD, Maharajah Ponnaiah, PhD, Frédérique Deshours, PhD, Hamid Kokabi, PhD, Isabelle Brochériou, MD, PhD, Gilles Le Naour, PhD, Alban Redheuil, MD, PhD, Fabien Koskas, MD, PhD, and Jean-Michel Davaine, MD, PhD

Subjects
Carotid plaque stability, Stroke, Microwave, Duplex US, Risk assessment, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective: Progress in best medical treatment have made identification of best candidates for carotid surgery more difficult. New diagnostic modalities could be helpful in this perspective. Microwaves (MWs) can quantify dielectric properties (complex relative permittivity) of biological tissues and MW technology has emerged as a promising field of research for distinguishing abnormal tissues from healthy ones. We here evaluated the ability of a dedicated MW sensor developed in our laboratory to identify vulnerable carotid lesions. Methods: We included 50 carotid lesions in this study. The plaques were analyzed and classified preoperatively by ultrasound (US) examination, computed tomography angiography and tested postoperatively using a MW sensor. Histopathological analysis was used as a gold standard to separate vulnerable plaques (VPs) from nonvulnerable plaques (NVPs). Results: VPs were more frequently types 2 or 3 plaques (on US examination), had a greater proportion of low (

Published
2024
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2. Datasets for gene expression profiles of head and neck squamous cell carcinoma and lung cancer treated or not by PD1/PD-L1 inhibitors

Author

Jean-Philippe Foy, Andy Karabajakian, Sandra Ortiz-Cuaran, Maxime Boussageon, Lucas Michon, Jebrane Bouaoud, Dorssafe Fekiri, Marie Robert, Kim-Arthur Baffert, Geneviève Hervé, Pauline Quilhot, Valéry Attignon, Angélique Girod, André Chaine, Mourad Benassarou, Philippe Zrounba, Christophe Caux, François Ghiringhelli, Sylvie Lantuejoul, Carole Crozes, Isabelle Brochériou, Maurice Pérol, Jérôme Fayette, Chloé Bertolus, and Pierre Saintigny

Subjects
Head and neck cancer, Non-small cell lung cancer, Transcriptome profile, Biomarker, Immunotherapy, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.

Published
2022
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4. Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients

Author

Jean-Philippe Foy, Andy Karabajakian, Sandra Ortiz-Cuaran, Maxime Boussageon, Lucas Michon, Jebrane Bouaoud, Dorssafe Fekiri, Marie Robert, Kim-Arthur Baffert, Geneviève Hervé, Pauline Quilhot, Valéry Attignon, Angélique Girod, André Chaine, Mourad Benassarou, Philippe Zrounba, Christophe Caux, François Ghiringhelli, Sylvie Lantuejoul, Carole Crozes, Isabelle Brochériou, Maurice Pérol, Jérôme Fayette, Chloé Bertolus, and Pierre Saintigny

Subjects
Cancer Research, Lung Neoplasms, Phenotype, Oncology, Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Gene Expression Profiling, Programmed Cell Death 1 Receptor, Cetuximab, Humans, Immune Checkpoint Inhibitors, B7-H1 Antigen
Abstract

Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours.Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors.A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis.The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.

Published
2022

5. Supplementary Data from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Supplemental figures 1-10

Published
2023

6. Supplementary Table 5 from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Supplementary Table 5: Difference in gene expression between Immune High (IH) and Immune Low (IL) subgroups from the validation dataset (n=20, Coulouarn et al, Carcinogenesis, 2012) (33).

Published
2023

7. Supplementary Table 3 from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Supplementary Table 3: Difference in gene expression between IH1 and IH2 subtypes IH: Immune - High

Published
2023

8. Supplementary Table 1 from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Supplementary Table 1: Difference in gene expression between IL and IH subtypes

Published
2023

9. Supplementary Table 6 from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Supplementary Table 6: Difference in gene expression between Immune High 1 (IH1) and Immune High 2 (IH2) subgroups in the validation dataset (n=20, Coulouarn et al, Carcinogenesis, 2012) (33).

Published
2023

10. Supplementary Table 8 from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Supplementary Table 8: Molecular alterations identified in cHCC-CCA

Published
2023

11. Supplementary Table 7 from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Supplementary Table 7: Difference in gene expression between Immune Low 1 (IL1) and Immune Low 2 (IL2) subgroups in the validation dataset (n=20, Coulouarn et al. Carcinogenesis. 2012) (33).

Published
2023

12. Supplementary Table 4 from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Supplementary Table 4: Difference in gene expression between IL1 and IL2 subtypes IL: Immune - Low

Published
2023

13. Data from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

Author

Julien Calderaro, Valérie Paradis, Fouad Lafdil, Christophe Tournigand, Jean-Michel Pawlotsky, Jessica Zucman-Rossi, Sebastien Mulé, Manon Allaire, Jean Charles Nault, Audrey Rapinat, David Gentien, Thi Lan Tran, Hong Son Trinh, Van To Ta, Van Ky Le, Alexis Laurent, Vincent Leroy, Patrick Soussan, Daniele Sommacale, Isabelle Brochériou, Frédéric Charlotte, Olivier Scatton, Raffaele Brustia, Hélène Regnault, Alain Luciani, Luca di Tommaso, Giuliana Amaddeo, Rami Rhaiem, Camille Boulagnon-Rombi, Anaïs Pujals, Loetitia Favre, Jérémy Augustin, Aurélie Beaufrère, Pascale Maille, Stefano Caruso, and Cong Trung Nguyen

Abstract

Purpose:Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome.Experimental Design:We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of IHC stainings. Genetic alterations were investigated using targeted next-generation sequencing.Results:Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an “immune-high” (IH) subtype (57% of the cases) and an “immune-low” (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (P < 0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Quantification of immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival.Conclusions:We have identified a subgroup of cHCC-CCA that displays features of an ongoing intratumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.

Published
2023

14. Blocking TGF-β Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRβ+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats.

Author

Agnieszka A Pozdzik, Laetitia Giordano, Gang Li, Marie-Hélène Antoine, Nathalie Quellard, Julie Godet, Eric De Prez, Cécile Husson, Anne-Emilie Declèves, Volker M Arlt, Jean-Michel Goujon, Isabelle Brochériou-Spelle, Steven R Ledbetter, Nathalie Caron, and Joëlle L Nortier

Subjects
Medicine, Science
Abstract

The platelet-derived growth factor receptor β (PDGFRβ)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target.In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ) inhibition in a rat model of AAN.Neutralizing anti-TGFβ antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily.At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro.The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation.

Published
2016
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15. Platelet-activating factor acetylhydrolase and transacetylase activities in human aorta and mammary artery

Author

Demokritos C. Tsoukatos, Isabelle Brochériou, Vassilios Moussis, Christina P. Panopoulou, Elena D. Christofidou, Stamatis Koussissis, Socratis Sismanidis, Ewa Ninio, and Stavros Siminelakis

Subjects
atherosclerosis, macrophages, smooth muscle cells, lipoproteins, atherogenesis, oxidized LDL, Biochemistry, QD415-436
Abstract

Platelet-activating factor (PAF), the potent phospholipid mediator of inflammation, is involved in atherosclerosis. Platelet-activating factor-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF bioactivity, possesses both acetylhydrolase and transacetylase activities. In the present study, we measured acetylhydrolase and transacetylase activities in human atherogenic aorta and nonatherogenic mammary arteries. Immunohistochemistry analysis showed PAF-AH expression in the intima and the media of the aorta and in the media of mammary arteries. Acetylhydrolase and transacetylase activities were (mean ± SE, n = 38): acetylhydrolase of aorta, 2.8 ± 0.5 pmol/min/mg of tissue; transacetylase of aorta, 3.3 ± 0.7 pmol/min/mg of tissue; acetylhydrolase of mammary artery, 1.4 ± 0.3 pmol/min/mg of tissue (P < 0.004 as compared with acetylhydrolase of aorta); transacetylase of mammary artery, 0.8 ± 0.2 pmol/min/mg of tissue (P < 0.03 as compared with acetylhydrolase of mammary artery). Lyso-PAF accumulation and an increase in PAF bioactivity were observed in the aorta of some patients. Reverse-phase HPLC and electrospray ionization mass spectrometry analysis revealed that 1-O-hexadecyl-2 acetyl-sn glycero-3-phosphocholine accounted for 60% of the PAF bioactivity and 1-O-hexadecyl-2-butanoyl-sn-glycerol-3-phosphocholine for 40% of the PAF bioactivity. The nonatherogenic properties of mammary arteries may in part be due to low PAF formation regulated by PAF-AH activity. In atherogenic aortas, an imbalance between PAF-AH and transacetylase activity, as well as lyso-PAF accumulation, may lead to unregulated PAF formation and to progression of atherosclerosis.

Published
2008
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16. IgA Nephropathy Associated with Trifluridine/Tipiracil: A Case Report

Author

Liliane Ngango, Geoffroy Desbuissons, Philippe Fournier, and Isabelle Brochériou

Subjects
Chemotherapy, medicine.medical_specialty, Kidney, business.industry, medicine.medical_treatment, Trifluridine, macromolecular substances, medicine.disease, Gastroenterology, Nephrotoxicity, Nephropathy, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Refractory, Internal medicine, medicine, Hemodialysis, business, medicine.drug, Tipiracil
Abstract

Kidney diseases during chemotherapy treatment are variable, with different manifestations depending on the drugs used. Trifluridine/tipiracil is a treatment used in refractory metastatic digestive cancers. Its renal toxicity is poorly described. We report here the onset of a severe IgA nephropathy requiring hemodialysis which occurred several weeks after trifluridine/tipiracil treatment.

Published
2020

17. Blocking TGF-β Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRβ+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats

Author

Joëlle Nortier, Jean Michel Goujon, Anne-Emilie Decleves, Nathalie Quellard, Cécile Husson, Gang Li, Eric De Prez, Laetitia Giordano, M. H. Antoine, Agnieszka Pozdzik, Volker M. Arlt, Nathalie Caron, Isabelle Brochériou-Spelle, Julie Godet, Steven R. Ledbetter, Department of Nephrology - Dialysis and Renal Transplantation, Hôpital Erasmes, Hulunber Grassland Ecosystem Observation and Research Station (IARRP), Institute of Agricultural Resources and regional Planning-Chinese Academy of Agricultural Sciences (CAAS), Service d’Anapathomopathologie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Département d'Anatomocytopathologie, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), and Steichen, Clara

Subjects
0301 basic medicine, Male, Cell signaling, Time Factors, Physiology, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Psychologie appliquée, lcsh:Medicine, Smad Proteins, Mitochondrion, Signal transduction, Biochemistry, Epithelium, Kidney Tubules, Proximal, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Animal Cells, Transforming Growth Factor beta, Medicine and Health Sciences, Homeostasis, Receptor, lcsh:Science, Myofibroblasts, Energy-Producing Organelles, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Connective Tissue Cells, Kidney, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Acute kidney injury, Signaling cascades, Sciences bio-médicales et agricoles, Acute Kidney Injury, 3. Good health, Cell biology, Mitochondria, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Connective Tissue, Aristolochic Acids, Anatomy, Cellular Types, Cellular Structures and Organelles, Myofibroblast, Biologie, Research Article, Blotting, Western, Aristolochic acid, Biology, Bioenergetics, Models, Biological, Cell Line, Mitochondrial Proteins, Receptor, Platelet-Derived Growth Factor beta, 03 medical and health sciences, Growth factor receptor, Growth Factors, medicine, Animals, Humans, Rats, Wistar, Biology and life sciences, Endocrine Physiology, lcsh:R, Endothelial Cells, Kidneys, Epithelial Cells, Renal System, Fibroblasts, medicine.disease, Fibrosis, Antibodies, Neutralizing, 030104 developmental biology, Proteostasis, Biological Tissue, chemistry, TGF-beta signaling cascade, Immunology, lcsh:Q, Pericytes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology
Abstract

Background: The platelet-derived growth factor receptor β (PDGFRβ)+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target. Aims: In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN) and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ) inhibition in a rat model of AAN. Materials and Methods: Neutralizing anti-TGFβ antibody (1D11) and its control isotype (13C4) were administered (5 mg/kg, i.p.) at Days -1, 0, 2 and 4; AA (15 mg/kg, sc) was injected daily. Results: At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema) in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR) pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro. Conclusions: The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2016

18. Liste des collaborateurs

Author

Victor Aboyans, Pierre Abraham, Isabelle Aïchoun, Jean-Noël Albertini, Laurence Amar, Myriam Ammi, Michel Azizi, Richard Azzaoui, Michel Alain Bartoli, Jean-Michel Baud, François Becker, Lavinia Belaye, Gudrun Böge, Christian Boissier, Vanina Bongard, Christophe Bonnin, Patrick Bouilly, Carine Boulon, Pierre Boutouyrie, Luc Bressollette, Sophie Brizzi, Isabelle Brochériou, Alessandra Bura-Rivière, Patrice Cacoub, Luca Calanca, Patrick-Henri Carpentier, Xavier Chaufour, Bertrand Chavent, Laurent Chiche, Bénédicte Clin-Godard, Serge Cohen, Joël Constans, Thibaut Couture, Michel Dadon, Anne Daoudal, Michel Dauzat, Michèle Depairon, Ileana Desormais, Anne Blanchet Deverly, Monika Di Rienzo-Ambrozkiewicz, Ambroise Duprey, Clarisse Éveno-Saunier, Dominique Fabre, Jean-Pierre Favre, Béatrice Ferrari, Claire-Lise Fogeron, Michael Frank, Jean-Philippe Galanaud, Damien Garrigues, Valentine Gautier, Simon Gestin, Pascal Giordana, Yann Gouëffic, Nicolas Grenier, Jean-Louis Guilmot, Thibaut Guiraut, Caroline Haase-Ruby, Stéphan Haulon, Fabien Heller, Adrien Hertault, Hassan Houmaida, Vincent Jaquinandi, Elixène Jean-Baptiste, Adrien Kaladji, Hakim Khettab, Rémi Klotz, Fabien Koskas, Philippe Lacroix, Marc Lambert, Jean-Pierre Laroche, Vincent Larrue, Marc Laskar (†), Claude Laurian, Isabelle Lazareth, Claire Le Hello, Benoit Lebas, Anne Long, François Luizy (†), Jean-Luc Magne, Guillaume Mahé, Romain Martin, Teresa Martin-Gonzalez, Mario Maufus, Lucia Mazzolai, Emmanuel Messas, Olivier Meyrignac, Dominique Midy, Tristan Mirault, Wassim Mokaddem, Fatima-Zohra Mokrane, Philippe Patra (†), Antonia Pérez-Martin, Gilles Pernod, Francis Pesteil, Antoine Petermann, Nicole Petrissans-Ferrando, Jean Picquet, Augustin Pirvu, Marc-Antoine Pistorius, Jean-Noël Poggi, Agathe de Préville, Pascal Priollet, Philippe Quéhé, Isabelle Quéré, Paul Revel-Mouroz, Hervé Rousseau, David Saadoun, Brigitte Sandrin-Berthon, Hélène Sanson, Gabrielle Sarlon-Bartoli, Bernadette Satger, Iris Schuster, Christophe Seinturier, Damien Sene, Patricia Senet, Marie-Antoinette Sevestre, Salma Siddique, Jonathan Sobocinski, Rafaelle Spear, Muriel Sprynger, Éric Steinmetz, Dominique Stephan, Denis Wahl, Paul Wade Wennberg, Cécile Yelnik, and Stéphane Zuily

Published
2016

19. Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN

Author

Mohamad, Zaidan, Benjamin, Terrier, Agnieszka, Pozdzik, Thierry, Frouget, Nathalie, Rioux-Leclercq, Christian, Combe, Sébastien, Lepreux, Aurélie, Hummel, Laure-Hélène, Noël, Isabelle, Marie, Bruno, Legallicier, Arnaud, François, Antoine, Huart, David, Launay, Gilles, Kaplanski, Frank, Bridoux, Philippe, Vanhille, Raifah, Makdassi, Jean-François, Augusto, Philippe, Rouvier, Alexandre, Karras, Chantal, Jouanneau, Marie-Christine, Verpont, Patrice, Callard, Fabrice, Carrat, Olivier, Hermine, Jean-Marc, Léger, Xavier, Mariette, Patricia, Senet, David, Saadoun, Pierre, Ronco, Isabelle, Brochériou, Patrice, Cacoub, Emmanuelle, Plaisier, Thierry, Zénone, CHU Necker - Enfants Malades [AP-HP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [APHP], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Nephrology - Dialysis and Renal Transplantation, Hôpital Erasmes, Laboratory of Experimental Nephrology - Department of Biochimie, Université Libre de Bruxelles [Bruxelles] (ULB), Service de néphrologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre de compétences des microangiopathies thrombotiques, Université Bordeaux Segalen - Bordeaux 2, Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'Anatomie et Cytologie Pathologique [Rouen], Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de Médecine Interne et d'Immunologie clinique, Centre National de Référence Maladies rares-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de médecine interne et néphrologie, CH Valenciennes, Université d'Angers - Faculté de médecine (UA UFR Médecine), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université d'Angers (UA), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), CHU Saint-Antoine [APHP], Centre de référence des mastocytoses, Service d'Hématologie Adulte, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Immunologie - Immunopathologie - Immunothérapie (I3), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Sorbonne Universités, Service de Néphrologie et Dialyses [CHU Tenon], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] ( DHU - I2B ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Libre de Bruxelles [Bruxelles] ( ULB ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Laboratoire d'Immunologie ( EA 2686 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Centre National de Référence Maladies rares-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Université d'Angers - Faculté de médecine ( UA UFR Médecine ), Université d'Angers ( UA ) -CHU Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Département de santé publique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie - Immunopathologie - Immunothérapie ( I3 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Anatomopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université libre de Bruxelles (ULB), Service de néphrologie [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne [CHU Rouen], Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Tenon [AP-HP], CHU Saint-Antoine [AP-HP], Centre de référence des mastocytoses (CEREMAST), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
Male, medicine.medical_specialty, Pathology, Cyclophosphamide, Glomerulonephritis, Membranoproliferative, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Lymphoproliferative disorders, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Internal medicine, medicine, Humans, Cause of death, Retrospective Studies, 030203 arthritis & rheumatology, Proteinuria, [ SDV ] Life Sciences [q-bio], business.industry, General Medicine, membranoproliferative GN, Middle Aged, medicine.disease, Prognosis, Cryoglobulinemia, 3. Good health, Lymphoma, Regimen, Nephrology, histopathology, Rituximab, Female, medicine.symptom, business, Immunosuppressive Agents, medicine.drug
Abstract

International audience; Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m2. Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m2 with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death

Published
2015

20. [IgG4-related systemic disease and renal involvement]

Author

Isabelle, Brochériou

Subjects
Plasma Cells, Retroperitoneal Fibrosis, Complement System Proteins, Autoimmune Diseases, Diagnosis, Differential, Glomerulonephritis, Neutrophil Infiltration, Adrenal Cortex Hormones, Hypergammaglobulinemia, Immunoglobulin G, Pancreatitis, Chronic, Humans, Nephritis, Interstitial, Immunosuppressive Agents
Published
2012

21. [Fatal cardiac failure following antibiotic treatment]

Author

Peter, Dorfmüller, Olivier, Chosidow, Jean-François, Trouillet, Pascal, Leprince, Frédérique, Capron, and Isabelle, Brochériou

Subjects
Adult, Heart Failure, Inflammation, Myocarditis, Necrosis, Fatal Outcome, Myocardium, Edema, Humans, Female, Genital Diseases, Female, Anti-Bacterial Agents
Published
2009

22. Atherogenic properties of LDL particles modified by human group X secreted phospholipase A2 on human endothelial cell function

Author

Sonia‐Athina Karabina, Isabelle Brochériou, Gilles Le Naour, Monique Agrapart, Hervé Durand, Michael Gelb, Gérard Lambeau, Ewa Ninio, Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie pathologique [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departements of Chemistry and Biochemistry, Seattle University [Seattle], Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), 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), INSERM, Marie Curie Individual Fellowship, FRM, CNRS, ARC, NIHG, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Nice Sophia Antipolis (1965 - 2019) (UNS)

Subjects
030204 cardiovascular system & hematology, Biochemistry, MESH: Atherosclerosis, chemistry.chemical_compound, 0302 clinical medicine, MESH: Endothelial Cells, 0303 health sciences, biology, Cell adhesion molecule, Arteries, Endothelial stem cell, Protein Transport, Low-density lipoprotein, MESH: Cell Adhesion Molecules, MESH: Phospholipases A, Biotechnology, MESH: Cholesterol, LDL, MESH: Protein Transport, Phospholipid, Phospholipases A, Cell Line, Veins, MESH: Cell Adhesion, 03 medical and health sciences, Phospholipase A2, Genetics, Cell Adhesion, Group X Phospholipases A2, Humans, RNA, Messenger, Cell adhesion, Molecular Biology, MESH: Arteries, 030304 developmental biology, MESH: RNA, Messenger, MESH: Humans, MESH: Veins, Cholesterol, Macrophages, Endothelial Cells, MESH: Macrophages, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cholesterol, LDL, Atherosclerosis, MESH: Cell Line, Phospholipases A2, chemistry, biology.protein, Cell Adhesion Molecules, Lipoprotein
Abstract

Increasing evidence suggests that secreted phospholipases A2 (sPLA2s) play an important role in the pathophysiology of atherosclerosis. Among sPLA2s, the human group X (hGX) enzyme has the highest catalytic activity toward phosphatidylcholine, one of the major phospholipid species of cell membranes and low-density lipoprotein (LDL). Our study examined the presence of hGX sPLA2 in human atherosclerotic lesions and investigated the ability of hGX modified LDL to alter human endothelial cell (HUVEC) function. Our results show that hGX sPLA2 is present in human atherosclerotic lesions and that the hydrolysis of LDL by hGX sPLA2 results in a modified particle that induces lipid accumulation in human monocyte-derived macrophages. Acting on endothelial cells, hGX-modified LDL activates the MAP kinase pathway, which leads to increased arachidonic acid release, increased expression of adhesion molecules on the surface of HUVEC, and increased adhesion of monocytes to HUVEC monolayers. Together, our data suggest that LDL modified by hGX, rather than hGX itself may have strong proinflammatory and proatherogenic properties, which could play an important role in the propagation of atherosclerosis.

Published
2006

23. Lepidic predominant adenocarcinoma and invasive mucinous adenocarcinoma of the lung exhibit specific mucin expression in relation with oncogenic drivers

Author

Nathalie Rabbe, Martine Antoine, Michael Duruisseaux, Jacques Cadranel, Isabelle Van Seuningen, Virginie Poulot, Belinda Duchêne, Anne Mc Leer-Florin, Roger Lacave, Anita Rodenas, Marie Wislez, Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, We would like to thank the « Tumorothèque HUEP (AP-HP − GH-HUEP) », representing by Pr. Isabelle Brochériou (the East Paris University Hospitals Tumor Bio-bank), AP-HP, Hôpital Tenon, Service d'Anatomie Pathologique, F-75970, Paris, for providing us with the samples., HAL-UPMC, Gestionnaire, Service d'Anatomie et cytologie pathologiques [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, Lung Neoplasms, Carcinogenesis, medicine.disease_cause, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Epithelium, 0302 clinical medicine, Lepidic predominant adenocarcinoma, skin and connective tissue diseases, MUC1, respiratory system, Adenocarcinoma, Mucinous, Up-Regulation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Hepatocyte Nuclear Factor 4, 030220 oncology & carcinogenesis, Immunohistochemistry, Adenocarcinoma, Female, KRAS, Pulmonary and Respiratory Medicine, medicine.medical_specialty, EGFR, [SDV.CAN]Life Sciences [q-bio]/Cancer, digestive system, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, ROS1, medicine, Adenocarcinoma of the lung, Biomarkers, Tumor, Invasive mucinous adenocarcinoma, Humans, neoplasms, Aged, Lung, business.industry, Gene Expression Profiling, Mucin, Mucins, Genes, erbB-1, Oncogenes, medicine.disease, digestive system diseases, Pulmonary Alveoli, 030104 developmental biology, Cancer research, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Transcription Factors
Abstract

Objectives To evaluate MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression in invasive lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA) of the lung, and the impact of oncogenic drivers. Materials and methods MUC1, MUC2, MUC5B, MUC5AC, MUC6, TTF1 and Hnf4α immunohistochemistry was performed on surgical samples from 52 patients with IMA (n = 25) or LPA (n = 27). We searched for EGFR , KRAS , BRAF , and HER2 mutations and ALK , ROS1 , and NRG1 rearrangements. Results MUC1, MUC2, MUC5B, MUC5AC, and MUC6 expression was detected in tumor cells in 77%, 2%, 63%, 36%, and 21% of cases, respectively. MUC1 was significantly more overexpressed in LPA. MUC5B, MUC5AC, and MUC6 were typically detected in goblet cells and overexpressed in IMA. Hnf4α-positive IMA (n = 11) were TTF1-negative and typically did not expressed MUC1 and expressed MUC5AC and MUC6. Hnf4α-negative IMA (n = 14) showed a reverse profile of mucins expression, with MUC1 expression and a lack of MUC5AC and MUC6 expression. EGFR -positive status was significantly associated with LPA, MUC1 expression, and no MUC5B, MUC5AC, or MUC6 expression. KRAS -positive status was significantly associated with IMA and MUC5B and MUC5AC expression. Conclusions LPA and IMA exhibit specific mucin expression profiles, with MUC1 being associated with LPA, while MUC5B, MUC5AC, and MUC6 were associated with IMA. Hnf4α expression and EGFR and KRAS mutations may play a role in mucin expression profiles of these lung adenocarcinoma subtypes.

Published
2017

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