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13 results on '"MESH : Mice, Nude"'

1. Fluticasone Propionate Inhibits Lipopolysaccharide-Induced Proinflammatory Response in Human Cystic Fibrosis Airway Grafts

Author

Jacky Jacquot, Claire Danel, Caroline Majer-Teboul, Edith Puchelle, Sandie Escotte, Jean-Michel Triglia, Daniel Dusser, Dominique Gaillard, Sylvie Benoit, Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologique (SACP), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire d'histologie, cytologie, biologie cellulaire et moléculaire Pol Bouin, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Biomolécules : interactions moléculaires, cellulaires et cellules-matrice extracellulaire (BIMCCME), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ORL et Chirurgie cervico-faciale pédiatrique - [Hôpitaux Timone et Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital Nord [CHU - APHM], Département de Pharmacologie Clinique (DPC), Laboratoire GlaxoSmithKline, Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM), Birembaut, Philippe, Université de Reims Champagne-Ardenne ( URCA ) -IFR53-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Anatomie et de Cytologie Pathologique ( SACP ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ), Biomolécules : interactions moléculaires, cellulaires et cellules-matrice extracellulaire ( BIMCCME ), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) - Hôpital Nord [CHU - APHM], and Département de Pharmacologie Clinique ( DPC )

Subjects
Lipopolysaccharides, Male, MESH: Inflammation, Cystic Fibrosis, Lipopolysaccharide, MESH : Cytokines, Anti-Inflammatory Agents, MESH : Body Fluids, MESH : Lipopolysaccharides, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cystic fibrosis, Immunoenzyme Techniques, MESH: Body Fluids, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH : Child, MESH: Child, MESH : Female, MESH: Animals, Child, Lung, MESH: Cytokines, 0303 health sciences, MESH : Mice, Nude, Interleukin, MESH : Pseudomonas aeruginosa, respiratory system, Body Fluids, 3. Good health, Trachea, Pseudomonas aeruginosa, MESH: Pseudomonas aeruginosa, MESH : Tr, Cytokines, Molecular Medicine, Female, medicine.symptom, MESH : Interleukin-8, MESH: Cystic Fibrosis, MESH : Lung, MESH : Male, MESH : Trachea, Transplantation, Heterologous, Mice, Nude, MESH : Androstadienes, Inflammation, MESH : Anti-Inflammatory Agents, Proinflammatory cytokine, 03 medical and health sciences, MESH : Immunoenzyme Techniques, MESH : Cystic Fibrosis, MESH : Mice, MESH: Mice, Nude, MESH: Tr, medicine, Animals, Humans, MESH: Lung, Interleukin 8, MESH: Immunoenzyme Techniques, MESH: Mice, 030304 developmental biology, Pharmacology, MESH : Inflammation, MESH: Humans, business.industry, Interleukin-8, MESH : Humans, medicine.disease, MESH: Male, MESH: Interleukin-8, Androstadienes, 030228 respiratory system, chemistry, MESH: Androstadienes, MESH: Anti-Inflammatory Agents, Immunology, Fluticasone, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Respiratory epithelium, MESH : Animals, MESH: Lipopolysaccharides, business, Airway, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Trachea
Abstract

Airway inflammation, one of the major factors leading to lung damage in cystic fibrosis (CF) patients, is associated with an abnormal increase in proinflammatory cytokines. In this work, we demonstrate the increased release of the proinflammatory cytokines after lipopolysaccharide (LPS) stimulation: human interleukin (hIL)-8 in CF and non-CF airway xenografts, and hIL-6 and human growth-related oncogene-alpha (hGRO-alpha), which could be only analyzed in non-CF xenografts. Under basal conditions, we observed that hIL-8 was higher in CF xenografts compared with non-CF. We also report the anti-inflammatory effect of a glucocorticoid, fluticasone propionate (FP), on CF airway epithelium using a humanized model of airway inflammation developed in nude mice. In CF and non-CF tracheal xenografts, airway inflammation was induced by inoculating Pseudomonas aeruginosa LPS (4 h; 1 microg/ml) in the lumen of the xenografts. FP pretreatment (2 h; 10(-8) M) followed by P. aeruginosa LPS stimulation induced a significant reduction of LPS-induced hIL-8 release in airway liquid collected from CF and non-CF tracheal xenografts (85 and 80%, respectively). In non-CF tracheal xenografts, FP treatment before LPS stimulation induced a significant decrease in hIL-6 and hGRO-alpha. From these data, we suggest that FP exerts anti-inflammatory properties that may be appropriate to CF therapy, at an early stage of the disease. In addition, these results demonstrate that the humanized airway model of inflammation provides a relevant tool for analyzing the effects of anti-inflammatory drugs in different diseases in which airway inflammation is implicated.

Published
2002

2. Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth

Author

Grégoire Mignot, Alice Hervieu, Cédric Rébé, Lionel Apetoh, Frédérique Végran, Fanny Chalmin, François Ghiringhelli, Mélanie Bruchard, Pierre Vabres, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), CHU Dijon, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Mignot, Grégoire, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire Electronique, Informatique et Image ( Le2i ), and Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement

Subjects
Skin Neoplasms, Melanoma, Experimental, CD8-Positive T-Lymphocytes, Pharmacology, MESH: Antineoplastic Agents, Alkylating, Ligands, Biochemistry, Mice, Interleukin 21, 0302 clinical medicine, MESH: Up-Regulation, MESH: Ligands, Cytotoxic T cell, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH : Up-Regulation, MESH : Ligands, MESH : Melanoma, Experimental, Melanoma, MESH : Mice, Nude, MESH : CD8-Positive T-Lymphocytes, MESH: CD8-Positive T-Lymphocytes, Up-Regulation, 3. Good health, Dacarbazine, Killer Cells, Natural, MESH: Melanoma, Experimental, NK Cell Lectin-Like Receptor Subfamily K, 030220 oncology & carcinogenesis, MESH: NK Cell Lectin-Like Receptor Subfamily K, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Killer Cells, Natural, medicine.drug, MESH: Killer Cells, Natural, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Interferon-gamma, MESH : Antineoplastic Agents, Alkylating, Mice, Nude, MESH : Mice, Inbred C57BL, Dermatology, Biology, Major histocompatibility complex, MESH: Dacarbazine, Interferon-gamma, 03 medical and health sciences, Immune system, Downregulation and upregulation, MESH: Mice, Inbred C57BL, Cell Line, Tumor, MESH : Mice, medicine, MESH : NK Cell Lectin-Like Receptor Subfamily K, MESH: Mice, Nude, Animals, Humans, MESH : Dacarbazine, Antineoplastic Agents, Alkylating, Molecular Biology, MESH: Mice, MESH : Interferon-gamma, MESH: Humans, MESH : Cell Line, Tumor, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH : Humans, Cell Biology, medicine.disease, MESH : Disease Models, Animal, Mice, Inbred C57BL, Disease Models, Animal, biology.protein, MESH : Animals, MESH: Disease Models, Animal, CD8, 030215 immunology
Abstract

International audience; Dacarbazine (DTIC) is a cytotoxic drug widely used for melanoma treatment. However, the putative contribution of anticancer immune responses in the efficacy of DTIC has not been evaluated. By testing how DTIC affects host immune responses to cancer in a mouse model of melanoma, we unexpectedly found that both natural killer (NK) and CD8(+) T cells were indispensable for DTIC therapeutic effect. Although DTIC did not directly affect immune cells, it triggered the upregulation of NKG2D ligands on tumor cells, leading to NK cell activation and IFNγ secretion in mice and humans. NK cell-derived IFNγ subsequently favored upregulation of major histocompatibility complex class I molecules on tumor cells, rendering them sensitive to cytotoxic CD8(+) T cells. Accordingly, DTIC markedly enhanced cytotoxic T lymphocyte antigen 4 inhibition efficacy in vivo in an NK-dependent manner. These results underscore the immunogenic properties of DTIC and provide a rationale to combine DTIC with immunotherapeutic agents that relieve immunosuppression in vivo.

Published
2013

3. A novel antiangiogenic and vascular normalization therapy targeted against human CD160 receptor

Author

Stéphanie Brayer, Philippe Le Bouteiller, Nabila Jabrane-Ferrat, Fabienne Meggetto, Armand Bensussan, Salem Chouaib, Julie Tabiasco, Jean Kadouche, Olivier Chose, Maryse Aguerre-Girr, Muhammad Zaeem Noman, Sylvie Giuriato, Muriel Golzio, Sophie Chabot, Karine Bigot, Stéphane Galiacy, François Malecaze, Jérôme Giustiniani, Alexandra C. Provost, Jean-Philippe Jais, Elisabeth Bellard, Marc Abitbol, Justin Teissié, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'étude et de recherche thérapeutiques en ophtalmologie, Université Paris Descartes - Paris 5 (UPD5), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées, Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie [Hopital Purpan - Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Department of Cell Biology (DUMC), Duke University Medical Center, MAT Biopharma, MAT Ltd., Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Sciences et Technologies du Medicament de Toulouse Toulouse, France. (UMR2587, CNRS-PIERRE FABRE), PIERRE FABRE-Centre National de la Recherche Scientifique (CNRS), Fonctions Cellulaires et Moleculaires de l'Appareil Respiratoire et des Vaisseaux, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de recherche biomédicale (IMRB), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Physiopathologie de Toulouse Purpan ( CPTP ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut de pharmacologie et de biologie structurale ( IPBS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Cytokines et Immunologie des Tumeurs Humaines ( U753 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Cell Biology ( DUMC ), Oncodermatologie, immunologie et cellules souches cutanées ( DIO U976 ), and Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, Pathology, MESH : Retinal Diseases, MESH : Antineoplastic Combined Chemotherapy Protocols, Angiogenesis, MESH: Rabbits, Fibroblast growth factor, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Neovascularization, Antibodies, Monoclonal, Murine-Derived, Mice, MESH : Fibroblast Growth Factor 2, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH : Receptors, Immunologic, Immunology and Allergy, MESH : Female, MESH: Animals, Receptors, Immunologic, Melanoma, MESH: Antigens, CD, MESH : Cyclophosphamide, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, 0303 health sciences, Neovascularization, Pathologic, MESH : Mice, Nude, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH : Colonic Neoplasms, MESH : Corneal Neovascularization, 030220 oncology & carcinogenesis, Colonic Neoplasms, Female, Fibroblast Growth Factor 2, Rabbits, MESH : GPI-Linked Proteins, medicine.symptom, Intravital microscopy, Retinopathy, medicine.medical_specialty, MESH: Melanoma, MESH : Male, Immunology, MESH : Melanoma, MESH: Mice, Inbred BALB C, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, GPI-Linked Proteins, Article, 03 medical and health sciences, Retinal Diseases, Antigens, CD, Cell surface receptor, MESH : Mice, MESH : Antigens, CD, medicine, MESH: Mice, Nude, Animals, Humans, Corneal Neovascularization, MESH : Rabbits, Cyclophosphamide, MESH: Mice, MESH: Receptors, Immunologic, MESH : Mice, Inbred BALB C, MESH: Retinal Diseases, 030304 developmental biology, MESH: Colonic Neoplasms, MESH: Humans, MESH: Corneal Neovascularization, MESH: Fibroblast Growth Factor 2, MESH : Humans, MESH : Neovascularization, Pathologic, MESH: Cyclophosphamide, medicine.disease, eye diseases, MESH: Male, MESH : Antibodies, Monoclonal, Murine-Derived, MESH: Antibodies, Monoclonal, Murine-Derived, Corneal neovascularization, MESH : Animals, MESH: GPI-Linked Proteins, MESH: Neovascularization, Pathologic, MESH: Female
Abstract

A monoclonal anti-CD160 antibody inhibits the growth of new vessels in pathological ocular and tumor neoangiogenesis but not in healthy tissues., Angiogenesis plays an essential role in several diseases of the eye and in the growth of solid tumors, but existing antiangiogenic therapies have limited benefits in several cases. We report the antiangiogenic effects of a monoclonal antibody, CL1-R2, in several animal models of neovascularization. CL1-R2 recognizes human CD160, a membrane receptor which is conserved in various mammal species. We show that CD160 is expressed on the endothelial cells of newly formed blood vessels in human colon carcinoma and mouse B16 melanoma but not in vessels of healthy tissues. CL1-R2 reduced fibroblast growth factor 2–induced neovascularization in the rabbit cornea, in a mouse model of oxygen-induced retinopathy, and in a mouse Matrigel plug assay. Treatment of B16 melanoma-bearing mice with CL1-R2 combined with cyclophosphamide chemotherapy caused regression of the tumor vasculature and normalization of the remaining vessels as shown by Doppler ultrasonography, intravital microscopy, and histology. These studies validate CD160 as a potential new target in cases of human pathological ocular and tumor neoangiogenesis that do not respond or become resistant to existing antiangiogenic drugs.

Published
2011

4. A non-covalent peptide-based strategy for ex vivo and in vivo oligonucleotide delivery

Author

Crombez , Laurence, Morris , May C, Heitz , Frederic, Divita , Gilles, Centre de recherches de biochimie macromoléculaire ( CRBM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR122-Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche en Biologie Cellulaire (CRBM), and Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)

Subjects
Male, Peptide Nucleic Acids, MESH : Cell Line, MESH : Molecular Sequence Data, MESH : RNA, Messenger, Oligonucleotides, Cell-Penetrating Peptides, MESH: Amino Acid Sequence, MESH : RNA, Small Interfering, Polyethylene Glycols, Mice, Drug Delivery Systems, MESH: Oligonucleotides, MESH : Cell-Penetrating Peptides, MESH: RNA, Small Interfering, MESH: Animals, MESH : Female, RNA, Small Interfering, MESH: Cell-Penetrating Peptides, MESH: Peptides, MESH : Peptides, MESH : Amino Acid Sequence, MESH : Peptide Nucleic Acids, MESH : Polyethylene Glycols, RNA-Binding Proteins, MESH : Mice, Nude, MESH : Protein Binding, MESH: Oligopeptides, MESH : Drug Delivery Systems, Female, MESH : Transfection, Oligopeptides, MESH : Prostatic Neoplasms, Protein Binding, MESH : Oligopeptides, MESH: Cyclin B1, MESH : Male, Molecular Sequence Data, MESH: Drug Delivery Systems, MESH : RNA-Binding Proteins, Mice, Nude, MESH : Oligonucleotides, Transfection, Cell Line, MESH: Cell Adhesion, MESH: Peptide Nucleic Acids, MESH : Mice, Cell Adhesion, MESH: Mice, Nude, Animals, Humans, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, RNA, Messenger, Cyclin B1, MESH: Mice, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: RNA, Messenger, MESH: Humans, MESH: Molecular Sequence Data, MESH: Transfection, MESH : Humans, Prostatic Neoplasms, MESH : Disease Models, Animal, MESH: Male, MESH: Cell Line, MESH : Cyclin B1, Disease Models, Animal, MESH : Cell Adhesion, MESH: RNA-Binding Proteins, MESH: Polyethylene Glycols, MESH : Nanoparticles, MESH: Prostatic Neoplasms, Nanoparticles, MESH : Animals, MESH: Disease Models, Animal, Peptides, MESH: Female, MESH: Nanoparticles
Abstract

International audience; The dramatic acceleration in identification of new nucleic acid-based therapeutic molecules such as short interfering RNA (siRNA) and peptide-nucleic acid (PNA) analogues has provided new perspectives for therapeutic targeting of specific genes responsible for pathological disorders. However, the poor cellular uptake of nucleic acids together with the low permeability of the cell membrane to negatively charged molecules remain major obstacles to their clinical development. Several non-viral strategies have been proposed to improve the delivery of synthetic short oligonucleotides both in cultured cells and in vivo. Cell-penetrating peptides constitute very promising tools for non-invasive cellular import of oligonucleotides and analogs. We recently described a non-covalent strategy based on short amphiphatic peptides (MPG8/PEP3) that have been successfully applied ex vivo and in vivo for the delivery of therapeutic siRNA and PNA molecules. PEP3 and MPG8 form stable nanoparticles with PNA analogues and siRNA, respectively, and promote their efficient cellular uptake, independently of the endosomal pathway, into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. This chapter describes easy-to-handle protocols for the use of MPG-8 or PEP-3-nanoparticle technologies for PNA and siRNA delivery into adherent and suspension cell lines as well as in vivo into cancer mouse models.

Published
2011

5. CD133, CD15/SSEA-1, CD34 or side populations do not resume tumor-initiating properties of long-term cultured cancer stem cells from human malignant glio-neuronal tumors

Author

Ivan Bièche, Vivaldo Moura-Neto, Jacques Haiech, Francois Renault-Mihara, Maria Mihalescu-Maingot, Cristina Patru, Pascale Varlet, Josette Cadusseau, Luciana Romão, Hervé Chneiweiss, Cécile Thirant, Alain Berhneim, Nadine Leonard, Eric Raponi, Catherine Daumas-Duport, Laure Coulombel, Marie-Pierre Junier, BMC, Ed., Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Anatomy, Universidade Federal do Rio de Janeiro (UFRJ), Service de neuropathologie, Centre Hospitalier Saint-Anne (GHU Paris), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Génomes et cancer (GC (FRE2939)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Centre National de la Recherche Scientifique (CNRS), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Inserm and the following grants: ARC 3952 (HC), Ligue National contre le Cancer (La Ligue 2007, HC), Cancéropole (INCa/Région Ile de France) (CT), Cancer Stem Cell Network Ile de France (HC, MPJ)., Centre Hospitalier Saint-Anne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Psychiatrie et Neurosciences (CPN - U894), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), UFRJ, Université Joseph Fourier - Grenoble 1 (UJF) - CHU Grenoble - Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM) - IFR10 - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Sud - Paris 11 (UP11) - Institut Gustave Roussy (IGR) - Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre de Psychiatrie et Neurosciences (U894)

Subjects
Proteomics, Pathology, Cancer Research, CD34, MESH: Neurons, Antigens, CD34, MESH : Proteomics, MESH: Glioma, Mice, 0302 clinical medicine, Nude mouse, Medicine, MESH: Animals, AC133 Antigen, MESH: Antigens, CD, Neurons, 0303 health sciences, biology, Brain Neoplasms, MESH : Peptides, MESH: Peptides, MESH: Proteomics, MESH: Antigens, CD15, MESH : Mice, Nude, Glioma, MESH: Gene Expression Regulation, Neoplastic, Cell sorting, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Gene Expression Regulation, Neoplastic, Oncology, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Neoplastic Stem Cells, MESH : Antigens, CD34, Stem cell, Research Article, medicine.medical_specialty, MESH: Cell Line, Tumor, MESH : Gene Expression Regulation, Neoplastic, MESH: Glycoproteins, Lewis X Antigen, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, CD15, lcsh:RC254-282, MESH : Neurons, 03 medical and health sciences, MESH : Neoplastic Stem Cells, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer stem cell, Antigens, CD, Cell Line, Tumor, MESH : Mice, Genetics, MESH : Antigens, CD, MESH: Mice, Nude, Animals, Humans, MESH : Neoplasm Transplantation, MESH : Brain Neoplasms, MESH: Mice, 030304 developmental biology, Glycoproteins, Medulloblastoma, MESH: Humans, business.industry, MESH : Cell Line, Tumor, MESH : Humans, MESH: Antigens, CD34, medicine.disease, biology.organism_classification, MESH : Glycoproteins, MESH: Neoplastic Stem Cells, MESH : Antigens, CD15, MESH : Glioma, MESH : Animals, business, Peptides, Neoplasm Transplantation, MESH: Neoplasm Transplantation
Abstract

Background Tumor initiating cells (TICs) provide a new paradigm for developing original therapeutic strategies. Methods We screened for TICs in 47 human adult brain malignant tumors. Cells forming floating spheres in culture, and endowed with all of the features expected from tumor cells with stem-like properties were obtained from glioblastomas, medulloblastoma but not oligodendrogliomas. Results A long-term self-renewal capacity was particularly observed for cells of malignant glio-neuronal tumors (MGNTs). Cell sorting, karyotyping and proteomic analysis demonstrated cell stability throughout prolonged passages. Xenografts of fewer than 500 cells in Nude mouse brains induced a progressively growing tumor. CD133, CD15/LeX/Ssea-1, CD34 expressions, or exclusion of Hoechst dye occurred in subsets of cells forming spheres, but was not predictive of their capacity to form secondary spheres or tumors, or to resist high doses of temozolomide. Conclusions Our results further highlight the specificity of a subset of high-grade gliomas, MGNT. TICs derived from these tumors represent a new tool to screen for innovative therapies.

Published
2010

6. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells

Author

Alain Rouleau, Jean-Paul Remy-Martin, David Lanneau, Benoit Simon, Lionel Apetoh, Christophe Borg, Gabriele Multhoff, Grégoire Mignot, Cédric Rébé, Bruno Chauffert, François Ghiringhelli, François Martin, Fanny Chalmin, Eric Solary, Sylvain Ladoire, Mélanie Bruchard, Carmen Garrido, Arlette Hamman, Bernhard Ryffel, Wilfrid Boireau, Julie Vincent, Aurélie de Thonel, Laurence Zitvogel, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies ( FEMTO-ST ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Department of Radiation Oncology [Munich], Ludwig-Maximilians-Universität München, Role des Cellules Dendritiques Dans la Regulation des Effecteurs de l'Immunite Antitumorale, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Center for Neurologic Diseases, Harvard Medical School [Boston] ( HMS ), This work was supported by special grants from the Fondation de France, the Association pour la Recherche sur le Cancer, the Institut National de la Santé et de la Recherche Médicale, and the Ligue Nationale Contre le Cancer (Region Bourgogne). F. Chalmin was supported by the Conseil Régional Bourgogne/INSERM, J. Vincent by the Institut National contre le Cancer. G. Mignot was funded by the Association pour la Recherche sur le Cancer. C. Garrido and E. Solary lead teams supported by the 'Ligue Nationale Contre le Cancer.' L. Apetoh is supported by EMBO., Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Ludwig-Maximilians-Universität München (LMU), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Mignot, Grégoire, and Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)

Subjects
MAPK/ERK pathway, MESH : Cell Line, [SDV]Life Sciences [q-bio], T-Lymphocytes, HSP72 Heat-Shock Proteins, Exosomes, T-Lymphocytes, Regulatory, MESH: Amiloride, Amiloride, MESH : T-Lymphocytes, Regulatory, Mice, 0302 clinical medicine, Neoplasms, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Neoplasms, ComputingMilieux_MISCELLANEOUS, MESH : Cyclophosphamide, 0303 health sciences, education.field_of_study, MESH: Immunosuppression, MESH : Mice, Nude, General Medicine, 3. Good health, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : HSP72 Heat-Shock Proteins, Research Article, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Population, Mice, Nude, Biology, Exosome, MESH: HSP72 Heat-Shock Proteins, Cell Line, 03 medical and health sciences, MESH : Amiloride, Cell Line, Tumor, MESH : Mice, medicine, MESH: Mice, Nude, Animals, Humans, MESH: Exosomes, education, Autocrine signalling, MESH: Mice, Cyclophosphamide, 030304 developmental biology, MESH : T-Lymphocytes, Immunosuppression Therapy, MESH: Humans, MESH : Cell Line, Tumor, MESH: T-Lymphocytes, Regulatory, MESH : Humans, MESH: Cyclophosphamide, MESH : Exosomes, MESH : Neoplasms, Microvesicles, MESH: Cell Line, TLR2, MESH: T-Lymphocytes, MESH : Immunosuppression, Myeloid-derived Suppressor Cell, MESH : Animals
Abstract

International audience; Myeloid-derived suppressor cells (MDSCs) have been identified in humans and mice as a population of immature myeloid cells with the ability to suppress T cell activation. They accumulate in tumor-bearing mice and humans and have been shown to contribute to cancer development. Here, we have isolated tumor-derived exosomes (TDEs) from mouse cell lines and shown that an interaction between TDE-associated Hsp72 and MDSCs determines the suppressive activity of the MDSCs via activation of Stat3. In addition, tumor-derived soluble factors triggered MDSC expansion via activation of Erk. TDE-associated Hsp72 triggered Stat3 activation in MDSCs in a TLR2/MyD88-dependent manner through autocrine production of IL-6. Importantly, decreasing exosome production using dimethyl amiloride enhanced the in vivo antitumor efficacy of the chemotherapeutic drug cyclophosphamide in 3 different mouse tumor models. We also demonstrated that this mechanism is relevant in cancer patients, as TDEs from a human tumor cell line activated human MDSCs and triggered their suppressive function in an Hsp72/TLR2-dependent manner. Further, MDSCs from cancer patients treated with amiloride, a drug used to treat high blood pressure that also inhibits exosome formation, exhibited reduced suppressor functions. Collectively, our findings show in both mice and humans that Hsp72 expressed at the surface of TDEs restrains tumor immune surveillance by promoting MDSC suppressive functions.

Published
2009

7. Drug development in oncology assisted by noninvasive optical imaging

Author

Didier Boturyn, Philippe Rizo, Stéphane Roux, Anne-Charlotte Faure, Jérôme Boutet, Sandrine Dufort, Lucie Sancey, Anne Koenig, Véronique Josserand, Pascal Dumy, Michelle Keramidas, Claire Rome, Stéphanie Foillard, Jean-Luc Coll, Christian Righini, Olivier Tillement, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), UF Cancérologie Biologique et Biothérapie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, INSERM U823, équipe 5 (cibles diagnostiques ou thérapeutiques et vectorisation de drogues dans le cancer du poumon), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Physico-Chimie des Matériaux Luminescents (LPCML), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Département de Chimie Moléculaire (DCM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), INSERM, INCA, ARC, ANR, EMIL and N2L NoE of the 6th FWP, ANR-06-BLAN-0071,PEPVEC4THER,Peptide based nanostructure for the delivery of therapeutics: from mechanism to application(2006), 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 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Physico-Chimie des Matériaux Luminescents ( LPCML ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Département de Chimie Moléculaire ( DCM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Laboratoire d'Electronique et des Technologies de l'Information ( CEA-LETI ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes [Saint Martin d'Hères], ANR-06-BLAN-0071,PEPVEC4THER,Peptide based nanostructure for the delivery of therapeutics: from mechanism to application ( 2006 ), Hurbin, Amandine, Programme 'blanc' - Peptide based nanostructure for the delivery of therapeutics: from mechanism to application - - PEPVEC4THER2006 - ANR-06-BLAN-0071 - BLANC - VALID, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : Cell Line, Oncology, MESH : Microscopy, Fluorescence, MESH : Diagnostic Imaging, Pharmaceutical Science, MESH: Microscopy, Fluorescence, MESH : Radiation Oncology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Metastasis, Mice, Drug Delivery Systems, 0302 clinical medicine, Neoplasms, Drug Discovery, MESH : Female, MESH: Animals, MESH: Neoplasms, MESH : Drug Discovery, 0303 health sciences, Optical Devices, MESH : Mice, Nude, Primary tumor, MESH: Radiation Oncology, 3. Good health, MESH : Optical Devices, MESH : Antineoplastic Agents, Drug development, 030220 oncology & carcinogenesis, Drug delivery, MESH : Drug Delivery Systems, Female, Diagnostic Imaging, medicine.medical_specialty, MESH: Cell Line, Tumor, MESH: Drug Delivery Systems, Cancer therapy, Mice, Nude, Antineoplastic Agents, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Line, 03 medical and health sciences, optical imaging, Optical imaging, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: Drug Discovery, Cell Line, Tumor, Internal medicine, MESH : Mice, medicine, MESH: Mice, Nude, Animals, Humans, MESH: Mice, 030304 developmental biology, MESH: Optical Devices, MESH: Humans, MESH : Cell Line, Tumor, business.industry, tumor targeting, MESH: Diagnostic Imaging, MESH : Humans, Cancer, medicine.disease, MESH : Neoplasms, MESH: Cell Line, Microscopy, Fluorescence, Radiation Oncology, MESH: Antineoplastic Agents, MESH : Animals, business, MESH: Female
Abstract

International audience; Early and accurate detection of tumors, like the development of targeted treatments, is a major field of research in oncology. The generation of specific vectors, capable of transporting a drug or a contrast agent to the primary tumor site as well as to the remote (micro-) metastasis would be an asset for early diagnosis and cancer therapy. Our goal was to develop new treatments based on the use of tumor-targeted delivery of large biomolecules (DNA, siRNA, peptides, or nanoparticles), able to induce apoptosis while dodging the specific mechanisms developed by tumor cells to resist this programmed cell death. Nonetheless, the insufficient effectiveness of the vectorization systems is still a crucial issue. In this context, we generated new targeting vectors for drug and biomolecules delivery and developed several optical imaging systems for the follow-up and evaluation of these vectorization systems in live mice. Based on our recent work, we present a brief overview of how noninvasive optical imaging in small animals can accelerate the development of targeted therapeutics in oncology.

Published
2009

8. CD4+CD25+ Tregs control the TRAIL-dependent cytotoxicity of tumor-infiltrating DCs in rodent models of colon cancer

Author

Bruno Chauffert, Grégoire Lauvau, Eric Solary, Hideo Yagita, Laurence Zitvogel, François Martin, Stephan Roux, Fanny Chalmin, Pierre Emmanuel Puig, Grégoire Mignot, Sylvain Ladoire, François Ghiringhelli, Lionel Apetoh, Role des Cellules Dendritiques Dans la Regulation des Effecteurs de l'Immunite Antitumorale, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Immunologie des Maladies Infectieuses Allergiques et Autoimmunes, Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Immunology, Juntendo University School of Medicine, We received grant support from Fondation pour la Recherche Médicale (to S. Roux and L. Apetoh), Association pour la Recherche contre le Cancer (to G. Mignot), and Institut National de la Santé et de la Recherche Médicale (to F. Ghiringhelli). This work was supported by special grants from the Ligue contre le Cancer de Bourgogne and the Association pour la Recherche contre le Cancer., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Université Nice Sophia Antipolis (... - 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), Mignot, Grégoire, and Université Nice Sophia Antipolis (1965 - 2019) (UNS)

Subjects
CD4-Positive T-Lymphocytes, Male, MESH : Rats, Inbred Strains, T-Lymphocytes, Regulatory, MESH : TNF-Related Apoptosis-Inducing Ligand, TNF-Related Apoptosis-Inducing Ligand, MESH : T-Lymphocytes, Regulatory, Mice, 0302 clinical medicine, Neoplasms, Cytotoxic T cell, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, MESH: Neoplasms, IL-2 receptor, Cytotoxicity, Cells, Cultured, 0303 health sciences, Mice, Inbred BALB C, MESH: Dendritic Cells, MESH : Rats, MESH: CD4-Positive T-Lymphocytes, MESH : Mice, Nude, hemic and immune systems, General Medicine, MESH: Rats, Inbred Strains, 3. Good health, MESH : Colonic Neoplasms, MESH : CD4-Positive T-Lymphocytes, Colonic Neoplasms, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: TNF-Related Apoptosis-Inducing Ligand, MESH: Cells, Cultured, Research Article, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Rats, MESH : Male, MESH: Mice, Inbred BALB C, Mice, Nude, chemical and pharmacologic phenomena, Biology, 03 medical and health sciences, Immune system, Cell Line, Tumor, MESH : Cells, Cultured, MESH : Mice, MESH: Mice, Nude, Animals, MESH: Mice, MESH : Mice, Inbred BALB C, 030304 developmental biology, MESH: Colonic Neoplasms, Innate immune system, MESH : Cell Line, Tumor, MESH: T-Lymphocytes, Regulatory, TLR9, Rats, Inbred Strains, Dendritic Cells, MESH : Neoplasms, MESH : Disease Models, Animal, MESH: Male, Rats, TLR2, Disease Models, Animal, MESH : Dendritic Cells, Immunology, TLR4, MESH : Animals, MESH: Disease Models, Animal, 030215 immunology
Abstract

International audience; Tumors that progress do so via their ability to escape the antitumor immune response through several mechanisms, including developing ways to induce the differentiation and/or recruitment of CD4(+)CD25(+) Tregs. The Tregs, in turn, inhibit the cytotoxic function of T cells and NK cells, but whether they have an effect on the cytotoxic function of tumor-infiltrating DCs (TIDCs) has not been determined. Here we have shown, in 2 rodent models of colon cancer, that CD4(+)CD25(+) Tregs inhibit the ability of CD11b(+) TIDCs to mediate TNF-related apoptosis-inducing ligand-induced (TRAIL-induced) tumor cell death. In both models of cancer, combination treatment with Mycobacterium bovis Bacillus Calmette-Guérin (BCG), which activates the innate immune system via TLR2, TLR4, and TLR9, and cyclophosphamide (CTX), which depletes Tregs, eradicated the tumors. Further analysis revealed that the treatment led to a marked increase in the number of CD11b(+) TIDCs that killed the tumor cells via a TRAIL-dependent mechanism. Furthermore, acquisition of TRAIL expression by the CD11b(+) TIDCs was induced by BCG and dependent on signaling through TLR2, TLR4, and TLR9. In vivo transfer of Tregs abrogated the ability of BCG to induce CD11b(+) TIDCs to express TRAIL and thereby nullified the efficacy of the CTX-BCG treatment. Our data have therefore delineated what we believe to be a novel mechanism by which Tregs inhibit the antitumor immune response.

Published
2008

9. Multimodal imaging for the detection and characterization of liver lesions in a mouse model of neuroendocrine tumor

Author

Jean-Baptiste Langlois, Jean-Yves Scoazec, Laurent Milot, Frank Pilleul, Olivier Beuf, Loredana Baboi, Carole Lartizien, Colette Roche, Centre de Recherche et d'Application en Traitement de l'Image et du Signal ( CREATIS ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Exploration et de Recherche Médicales par Émission de Positons ( CERMEP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon ( HCL ) -CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Tumeurs endocrines digestives : mécanismes de la tumorigenèse et de la progression tumorale, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etude et de Recherche Multimodal Et Pluridisciplinaire en imagerie du vivant (CERMEP - imagerie du vivant), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH : Autoradiography, Pathology, Time Factors, MESH : Liver Neoplasms, Biopsy, MESH : Diagnostic Imaging, Neuroendocrine tumors, 030218 nuclear medicine & medical imaging, MESH: Magnetic Resonance Imaging, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, MESH: Biopsy, 0302 clinical medicine, MESH: Autoradiography, MESH: Liver Neoplasms, MESH: Fluorodeoxyglucose F18, MESH: Animals, medicine.diagnostic_test, Liver Neoplasms, Gastroenterology, MESH : Mice, Nude, MESH : Neuroendocrine Tumors, General Medicine, Magnetic Resonance Imaging, 3. Good health, MESH : Chromogranin A, Neuroendocrine Tumors, 030220 oncology & carcinogenesis, medicine.symptom, MESH: Radiopharmaceuticals, medicine.drug, MESH : Time Factors, Diagnostic Imaging, medicine.medical_specialty, MESH: Cell Line, Tumor, MESH: Neuroendocrine Tumors, Ratón, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Injections, Lesion, 03 medical and health sciences, In vivo, Fluorodeoxyglucose F18, Cell Line, Tumor, MESH : Magnetic Resonance Imaging, MESH : Mice, medicine, MESH: Mice, Nude, Animals, Humans, MESH: Injections, MESH: Mice, Fluorodeoxyglucose, MESH: Humans, business.industry, MESH: Diagnostic Imaging, MESH : Cell Line, Tumor, MESH: Time Factors, MESH : Humans, Magnetic resonance imaging, MESH : Fluorodeoxyglucose F18, medicine.disease, MESH : Disease Models, Animal, MESH : Injections, Disease Models, Animal, MESH : Radiopharmaceuticals, MESH : Biopsy, Autoradiography, Chromogranin A, MESH: Chromogranin A, MESH : Animals, Radiopharmaceuticals, MESH: Disease Models, Animal, Nuclear medicine, business, Ex vivo
Abstract

International audience; BACKGROUND: The aim of this study was to compare in vivo magnetic resonance imaging (MRI) and ex vivo autoradiography with histopathological results for the detection and characterization of liver lesions in an experimental model of human neuroendocrine tumors. MATERIAL AND METHODS: Intestinal STC-1 endocrine tumor cells were injected into 30 nude mice to achieve hepatic dissemination. Seven to 30 days after injection, T2-weighted in vivo images covering the entire liver were acquired with a 7-T system. Autoradiographs were also obtained in 28 mice after injection of fluorodeoxyglucose (18F-FDG). The autoradiographic liver samples were then stained with an antichromogranin antibody before histological analysis. Tumor size and the hepatic tumor fraction were measured using the three imaging modalities. RESULTS: Metastatic tumors visualized on the histological liver sections ranged in size from 50 microm (day 7) to 3 mm (day 30). The hepatic tumor fraction increased with time, reaching 30% of the hepatic surface area on day 30. Visual analysis revealed variable tumor distribution and type (solid and/or cystic). On MRI, lesions were identified from day 12 (about 100 icrom in diameter) and the hepatic tumor fraction was up to 48% at day 30. The smallest lesions (350 microm in diameter) were also detected at day 12 on the autoradiographs. There was good correlation between tumor fractions determined from autoradiographic and histological data. CONCLUSION: In vivo, MRI appears to be well suited to the follow-up of liver lesions in a mouse model of neuroendocrine tumor. Preliminary results using 18F-FDG in this animal model are promising, showing differences in FDG uptake.

Published
2008

10. Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging

Author

Stéphane Roux, Jean-Luc Bridot, Jean-Luc Coll, Bassem Hiba, Marc Janier, Claire Billotey, Sophie Laurent, Luce Vander Elst, Olivier Tillement, Pascal Perriat, Robert N. Muller, Véronique Josserand, Anne-Charlotte Faure, Charlotte Rivière, Laboratoire de Physico-Chimie des Matériaux Luminescents (LPCML), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de RMN, Université de Mons-Hainaut, NanoH-sas, Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), INSERM U823, équipe 5 (cibles diagnostiques ou thérapeutiques et vectorisation de drogues dans le cancer du poumon), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physico-Chimie des Matériaux Luminescents ( LPCML ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche et d'Application en Traitement de l'Image et du Signal ( CREATIS ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Matériaux, ingénierie et science [Villeurbanne] ( MATEIS ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Hurbin, Amandine, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Fluorescence-lifetime imaging microscopy, MESH : Siloxanes, Nanoparticle, Contrast Media, Gadolinium, 02 engineering and technology, [SPI.MAT] Engineering Sciences [physics]/Materials, MESH : Gadolinium, 01 natural sciences, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Polyethylene Glycols, MESH: Magnetic Resonance Imaging, [SPI.MAT]Engineering Sciences [physics]/Materials, Paramagnetism, Mice, Colloid and Surface Chemistry, Nuclear magnetic resonance, Heterocyclic Compounds, MESH: Animals, Lung, medicine.diagnostic_test, Chemistry, MESH : Rats, MESH : Polyethylene Glycols, MESH : Mice, Nude, 021001 nanoscience & nanotechnology, Magnetic Resonance Imaging, Liver, Covalent bond, MESH : Organometallic Compounds, 0210 nano-technology, Preclinical imaging, MESH : Fluorescence, Siloxanes, MESH: Rats, MESH: Heterocyclic Compounds, MESH : Lung, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, 010402 general chemistry, Catalysis, Fluorescence, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Magnetic Resonance Imaging, MESH: Contrast Media, PEG ratio, MESH : Mice, medicine, Organometallic Compounds, MESH: Mice, Nude, Animals, MESH: Lung, MESH: Siloxanes, MESH: Mice, MESH : Contrast Media, MESH: Fluorescence, MESH : Liver, Magnetic resonance imaging, MESH: Organometallic Compounds, General Chemistry, 0104 chemical sciences, Rats, MESH : Heterocyclic Compounds, MESH: Polyethylene Glycols, MESH : Nanoparticles, Nanoparticles, MESH : Animals, Luminescence, MESH: Gadolinium, MESH: Nanoparticles, MESH: Liver
Abstract

International audience; Luminescent hybrid nanoparticles with a paramagnetic Gd2O 3 core were applied as contrast agents for both in vivo fluorescence and magnetic resonance imaging. These hybrid particles were obtained by encapsulating Gd2O3 cores within a polysiloxane shell which carries organic fluorophores and carboxylated PEG covalently tethered to the inorganic network. Longitudinal proton relaxivities of these particles are higher than the positive contrast agents like Gd-DOTA which are commonly used for clinical magnetic resonance imaging. Moreover these particles can be followed up by fluorescence imaging. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in lungs and liver.

Published
2007

11. A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127

Author

Benedita Rocha, Ana Cumano, Sophie Ezine, Erwan Corcuff, Lars Rogge, Marcos E. García-Ojeda, Odile Richard-Le Goff, Christian A. J. Vosshenrich, Sandrine I. Samson-Villeger, Delphine Guy-Grand, James P. Di Santo, Valérie Pasqualetto, Laurence Enault, Cytokines et Développement Lymphoïde, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Differenciation Thymique et Physiologie des Lymphocytes T (U591), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Développement des Lymphocytes, Immunorégulation, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Differenciation Thymique et Physiologie des Lymphocytes T ( U591 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS )

Subjects
Cytotoxicity, Immunologic, MESH: Signal Transduction, MESH : GATA3 Transcription Factor, MESH : Cytokines, MESH : Cytotoxicity, Immunologic, MESH : Interleukin-7 Receptor alpha Subunit, Interleukin 21, Mice, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, MESH: Animals, 0303 health sciences, MESH: Cytokines, MESH : Lymphocyte Subsets, MESH : Mice, Nude, Interleukin, virus diseases, Cell Differentiation, hemic and immune systems, Natural killer T cell, MESH : Mice, Transgenic, Cell biology, Killer Cells, Natural, MESH : Immunophenotyping, Interleukin 12, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Killer Cells, Natural, MESH : Cell Differentiation, Signal Transduction, MESH : Interleukin-7, MESH: Cell Differentiation, MESH: Killer Cells, Natural, MESH: Immunophenotyping, MESH: Mice, Transgenic, Immunology, MESH: Lymphocyte Subsets, Mice, Nude, Mice, Transgenic, chemical and pharmacologic phenomena, MESH : Mice, Inbred C57BL, GATA3 Transcription Factor, Thymus Gland, Biology, CD16, Immunophenotyping, Interleukin-7 Receptor alpha Subunit, 03 medical and health sciences, MESH: Mice, Inbred C57BL, MESH : Mice, MESH: GATA3 Transcription Factor, MESH: Mice, Nude, Animals, Humans, MESH : Thymus Gland, MESH: Cytotoxicity, Immunologic, MESH: Mice, 030304 developmental biology, MESH : Signal Transduction, Lymphokine-activated killer cell, MESH: Humans, Cell growth, Interleukin-7, MESH : Humans, MESH: Interleukin-7 Receptor alpha Subunit, MESH: Thymus Gland, Lymphocyte Subsets, MESH: Interleukin-7, Mice, Inbred C57BL, Myeloid-derived Suppressor Cell, MESH : Animals, 030215 immunology
Abstract

International audience; Natural killer (NK) cell development is thought to occur in the bone marrow. Here we identify the transcription factor GATA-3 and CD127 (IL-7R alpha) as molecular markers of a pathway of mouse NK cell development that originates in the thymus. Thymus-derived CD127+ NK cells repopulated peripheral lymphoid organs, and their homeostasis was strictly dependent on GATA-3 and interleukin 7. The CD127+ NK cells had a distinct phenotype (CD11b(lo) CD16- CD69(hi) Ly49(lo)) and unusual functional attributes, including reduced cytotoxicity but considerable cytokine production. Those characteristics are reminiscent of human CD56(hi) CD16- NK cells, which we found expressed CD127 and had more GATA-3 expression than human CD56+ CD16+ NK cells. We propose that bone marrow and thymic NK cell pathways generate distinct mouse NK cells with properties similar to those of the two human CD56 NK cell subsets.

Published
2006

12. Differentiation of mouse embryonic stem cells into endothelial cells: genetic selection and potential use in vivo

Author

Gimond , Clotilde, Marchetti , Sandrine, Pagès , Gilles, Institut de signalisation, biologie du développement et cancer (ISBDC), 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), Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Nice Sophia Antipolis ( UNS ), and Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
MESH: Cell Differentiation, MESH : Cell Culture Techniques, Cell Transplantation, Green Fluorescent Proteins, Cell Culture Techniques, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Stem Cells, MESH: Extracellular Matrix, MESH : Green Fluorescent Proteins, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Mice, MESH: Green Fluorescent Proteins, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Mice, MESH : Cells, Cultured, MESH: Mice, Nude, MESH : Embryo, Mammalian, Animals, Humans, MESH: Animals, MESH: Endothelial Cells, MESH: Mice, Cells, Cultured, MESH: Cell Culture Techniques, MESH: Humans, MESH : Endothelial Cells, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, MESH : Humans, MESH : Reverse Transcriptase Polymerase Chain Reaction, MESH : Extracellular Matrix, MESH: Embryo, Mammalian, MESH : Mice, Nude, Endothelial Cells, MESH: Antigens, CD31, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Differentiation, Embryo, Mammalian, MESH : Cell Transplantation, Extracellular Matrix, Platelet Endothelial Cell Adhesion Molecule-1, MESH: Cell Transplantation, MESH : Antigens, CD31, MESH : Stem Cells, MESH : Animals, MESH : Cell Differentiation, MESH: Cells, Cultured
Abstract

International audience; Embryonic stem (ES) cells are pluripotent cells derived from blastocyst-stage embryos. They are characterized by their infinite self-renewal capacity and their ability to differentiate into many cell types in vitro as well as in vivo. The present protocol describes culture conditions that allow efficient differentiation of mouse ES cells toward the endothelial lineage, both in two-dimensional cultures and in three-dimensional, multicellular embryoid bodies. We also provide a protocol for establishing recombinant ES cell clones, giving the example of cells expressing green fluorescent protein and an antibiotic resistance gene under the control of an endothelial-specific promoter. These transgenes allow the visualization and the genetic selection of endothelial cells from a heterogeneous population of differentiating ES cells. Potential applications for these differentiation models are given, including the study of the endothelial cell lineage and its derivatives, the testing of molecules involved in angiogenesis, and the potential use of selected endothelial cells in vivo.

Published
2006

13. Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells

Author

Gerard Eberl, Lees R, St, Smiley, Taniguchi M, Mj, Grusby, Hr, Macdonald, Ludwig Institute for Cancer Research, Harvard School of Public Health, Centre de Recherche en Économie et Statistique (CREST), Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] (ENSAI)-École polytechnique (X)-École Nationale de la Statistique et de l'Administration Économique (ENSAE Paris)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Économie et Statistique ( CREST ), and Ecole Nationale de la Statistique et de l'Analyse de l'Information [Bruz] ( ENSAI ) -École polytechnique ( X ) -École Nationale de la Statistique et de l'Administration Économique ( ENSAE ParisTech )

Subjects
Antigens, Differentiation, T-Lymphocyte, MESH : Protein Biosynthesis, MESH: Antigens, CD1, Receptors, Antigen, T-Cell, alpha-beta, MESH : Antigens, MESH: Antigens, CD4, MESH: Antigens, Differentiation, B-Lymphocyte, MESH: T-Lymphocyte Subsets, MESH : Antigens, Ly, Lymphocyte Activation, MESH : Proteins, Antigens, CD1, Mice, MESH: Genes, T-Cell Receptor alpha, T-Lymphocyte Subsets, MESH : Lectins, C-Type, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Antigens, Ly, MESH : Female, MESH: Animals, MESH: Proteins, MESH : Biomarkers, MESH: Organ Specificity, Mice, Inbred BALB C, MESH: Receptors, Antigen, T-Cell, alpha-beta, MESH : Mice, Nude, hemic and immune systems, MESH: Antigens, Ly, MESH : NK Cell Lectin-Like Receptor Subfamily B, Killer Cells, Natural, MESH : Genes, T-Cell Receptor alpha, MESH : Antigens, Differentiation, T-Lymphocyte, MESH: NK Cell Lectin-Like Receptor Subfamily B, MESH : Histocompatibility Antigens Class II, MESH : Receptors, Antigen, T-Cell, alpha-beta, Organ Specificity, MESH: Protein Biosynthesis, Antigens, Surface, CD4 Antigens, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Antigens, Female, MESH : Killer Cells, Natural, MESH : Antigens, Surface, Genes, T-Cell Receptor alpha, NK Cell Lectin-Like Receptor Subfamily B, MESH: Killer Cells, Natural, MESH : Antigens, CD1d, MESH: Antigens, Surface, CD8 Antigens, MESH: Mice, Inbred BALB C, Mice, Nude, chemical and pharmacologic phenomena, MESH : Mice, Inbred C57BL, Thymus Gland, MESH : Organ Specificity, MESH: Mice, Inbred C57BL, MESH : Mice, MESH: Mice, Nude, Animals, MESH : Thymus Gland, Lectins, C-Type, Antigens, MESH: Lymphocyte Activation, MESH: Mice, MESH : Lymphocyte Activation, MESH : Mice, Inbred BALB C, MESH : Antigens, Differentiation, B-Lymphocyte, Histocompatibility Antigens Class II, Proteins, MESH: Thymus Gland, MESH : T-Lymphocyte Subsets, Antigens, Differentiation, B-Lymphocyte, Mice, Inbred C57BL, MESH: Antigens, Differentiation, T-Lymphocyte, MESH : Antigens, CD1, MESH: Antigens, CD1d, Protein Biosynthesis, MESH: Biomarkers, MESH: Histocompatibility Antigens Class II, MESH : Antigens, CD4, MESH : Animals, MESH: Antigens, CD8, Antigens, CD1d, MESH : Antigens, CD8, MESH: Female, MESH: Lectins, C-Type, Biomarkers
Abstract

International audience; NKT cells, defined as T cells expressing the NK cell marker NK1.1, are involved in tumor rejection and regulation of autoimmunity via the production of cytokines. We show in this study that two types of NKT cells can be defined on the basis of their reactivity to the monomorphic MHC class I-like molecule CD1d. One type of NKT cell is positively selected by CD1d and expresses a biased TCR repertoire together with a phenotype found on activated T cells. A second type of NKT cell, in contrast, develops in the absence of CD1d, and expresses a diverse TCR repertoire and a phenotype found on naive T cells and NK cells. Importantly, the two types of NKT cells segregate in distinct tissues. Whereas thymus and liver contain primarily CD1d-dependent NKT cells, spleen and bone marrow are enriched in CD1d-independent NKT cells. Collectively, our data suggest that recognition of tissue-specific ligands by the TCR controls localization and activation of NKT cells.

Published
1999

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