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7 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. 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

5. 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

6. 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

7. 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

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