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1. Intra-individual Dose Escalation of Abiraterone According to Its Plasma Exposure in Patients with Progressive Metastatic Castration-Resistant Prostate Cancer: Results of the OPTIMABI Trial

Author

Alexandre, Jérôme, Oudard, Stephane, Golmard, Lisa, Campedel, Luca, Mseddi, Mourad, Ladoire, Sylvain, Khalil, Ahmed, Maillet, Denis, Tournigand, Christophe, Pasquiers, Blaise, Goirand, Françoise, Berthier, Joseph, Guitton, Jérôme, Dariane, Charles, Joly, Florence, Xylinas, Evanguelos, Golmard, Jean Louis, Abdoul, Hendy, Puszkiel, Alicja, Decleves, Xavier, Carton, Edith, Thomas, Audrey, Vidal, Michel, Huillard, Olivier, and Blanchet, Benoit

Published
2024
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5. Intra-individual dose escalation of abiraterone (ABI) according to its plasma exposure in patients (pts) with progressive metastatic castration-resistant prostate cancer (mRCPC): Results of the OPTIMABI trial.

Author

Alexandre, Jerome, primary, Oudard, Stephane, additional, Campedel, Luca, additional, Golmard, Lisa, additional, Ladoire, Sylvain, additional, Khalil, Ahmed, additional, Maillet, Denis, additional, Tournigand, Christophe, additional, Goirand, Françoise, additional, Guitton, Jerome, additional, Dariane, Charles, additional, Joly, Florence, additional, Xylinas, Evanguelos, additional, Golmard, Jean Louis, additional, Abdoul, Hendy, additional, Khoudour, Nihel, additional, Puskiel, Alicja, additional, Carton, Edith, additional, Huillard, Olivier, additional, and Blanchet, Benoit, additional

Published
2023
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19. Role of Extracellular HSP27 in pulmonary fibrosis

Author

Pommerolle, Lenny, primary, Burgy, Olivier, additional, Dondaine, Lucile, additional, Boutanquoi, Pierre-Marie, additional, Beltramo, Guillaume, additional, Tanguy, Julie, additional, Loriod, Sabrina, additional, Garrido, Carmen, additional, Bonniaud, Philippe, additional, and Goirand, Françoise, additional

Published
2020
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21. TRIM33 prevents pulmonary fibrosis by impairing TGF-β1 signalling

Author

Boutanquoi, Pierre-Marie, primary, Burgy, Olivier, additional, Beltramo, Guillaume, additional, Bellaye, Pierre-Simon, additional, Dondaine, Lucile, additional, Marcion, Guillaume, additional, Pommerolle, Lenny, additional, Vadel, Aurélie, additional, Spanjaard, Maximilien, additional, Demidov, Oleg, additional, Mailleux, Arnaud, additional, Crestani, Bruno, additional, Kolb, Martin, additional, Garrido, Carmen, additional, Goirand, Françoise, additional, and Bonniaud, Philippe, additional

Published
2020
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23. [18F]FMISO PET/CT imaging of hypoxia as a non-invasive biomarker of disease progression and therapy efficacy in a preclinical model of pulmonary fibrosis: comparison with the [18F]FDG PET/CT approach.

Author

Tanguy, Julie, Goirand, Françoise, Bouchard, Alexanne, Frenay, Jame, Moreau, Mathieu, Mothes, Céline, Oudot, Alexandra, Helbling, Alex, Guillemin, Mélanie, Bonniaud, Philippe, Cochet, Alexandre, Collin, Bertrand, and Bellaye, Pierre-Simon

Subjects
*COMPUTED tomography, *PULMONARY fibrosis, *IDIOPATHIC pulmonary fibrosis, *DISEASE progression, *BIOMARKERS, *POSITRON emission tomography computed tomography
Abstract

Purpose: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor outcome and limited therapeutic options. Imaging of IPF is limited to high-resolution computed tomography (HRCT) which is often not sufficient for a definite diagnosis and has a limited impact on therapeutic decision and patient management. Hypoxia of the lung is a significant feature of IPF but its role on disease progression remains elusive. Thus, the aim of our study was to evaluate hypoxia imaging with [18F]FMISO as a predictive biomarker of disease progression and therapy efficacy in preclinical models of lung fibrosis in comparison with [18F]FDG. Methods: Eight-week-old C57/BL6 mice received an intratracheal administration of bleomycin (BLM) at day (D) 0 to initiate lung fibrosis. Mice received pirfenidone (300 mg/kg) or nintedanib (60 mg/kg) by daily gavage from D9 to D23. Mice underwent successive PET/CT imaging at several stages of the disease (baseline, D8/D9, D15/D16, D22/D23) with [18F]FDG and [18F]FMISO. Histological determination of the lung expression of HIF-1α and GLUT-1 was performed at D23. Results: We demonstrate that mean lung density on CT as well as [18F]FDG and [18F]FMISO uptakes are upregulated in established lung fibrosis (1.4-, 2.6- and 3.2-fold increase respectively). At early stages, lung areas with [18F]FMISO uptake are still appearing normal on CT scans and correspond to areas which will deteriorate towards fibrotic lesions at later timepoints. Nintedanib and pirfenidone dramatically and rapidly decreased mean lung density on CT as well as [18F]FDG and [18F]FMISO lung uptakes (pirfenidone: 1.2-, 2.9- and 2.6-fold decrease; nintedanib: 1.2-, 2.3- and 2.5-fold decrease respectively). Early [18F]FMISO lung uptake was correlated with aggressive disease progression and better nintedanib efficacy. Conclusion: [18F]FMISO PET imaging is a promising tool to early detect and monitor lung fibrosis progression and therapy efficacy. [ABSTRACT FROM AUTHOR]

Published
2021
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28. 5-fluorouracil therapeutic drug monitoring Update and recommendations of the STP-PT group of the SFPT and the GPCO-Unicancer

Author

Lemaitre, Florian, Goirand, Françoise, Launay, Manon, Chatelut, Etienne, Boyer, Jean-Christophe, Evrard, Alexandre, Paludetto, Marie-Noelle, Guilhaumou, Romain, Ciccolini, Joseph, Schmitt, Antonin, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut Claudius-Regaud [IUCT-O, Toulouse], Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Marseille, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Antimetabolites, Antineoplastic, Polymorphism, Genetic, Recommandation, Dihydropyrimidine Dehydrogenase Deficiency, Dose-Response Relationship, Drug, Toxicity, Pharmacocinétique, 5-fluorouracile, [SDV.CAN]Life Sciences [q-bio]/Cancer, Therapeutic drug monitoring, Suivi thérapeutique pharmacologique, Toxicité, Neoplasms, Practice Guidelines as Topic, Humans, Pharmacokinetics, Fluorouracil, Drug Monitoring, Dihydrouracil Dehydrogenase (NADP), Societies, Medical, Fluoropyrimidine, Follow-Up Studies
Abstract

International audience; Despite being 60-years old now, 5-FU remains the backbone of numerous regimen to treat a variety of solid tumors such as breast, head-and-neck and digestive cancers either in neo-adjuvant, adjuvant or metastatic settings. Standard 5-FU usually claims 15-40% of severe toxicities and up to 1% of toxic-death. Numerous studies show a stiff relationship between 5-FU exposure and toxicity or efficacy. In addition, 5-FU pharmacokinetics is highly variable between patients. Indeed, 80% of the 5-FU dose is catabolized in the liver by dihydropyrimidine dehydrogenase (DPD) into inactive compounds. It is now well established that DPD deficiency could lead to severe toxicities and, thus, require dose reduction in deficient patients. However, despite dosage adaptation based on DPD status, some patients may still experience under- or over-exposure, leading to inefficacy or major toxicity. The "Suivi thérapeutique pharmacologique et personnalisation des traitements" (STP-PT) group of the "Société française de pharmacologie et de thérapeutique" (SFPT) and the "Groupe de pharmacologie clinique oncologique" (GPCO)-Unicancer, based on the latest and most up-to-date literature data, recommend the implementation of 5-FU Therapeutic Drug Monitoring in order to ensure an adequate 5-FU exposure.

Published
2018

32. TIF1? has a protective role in pulmonary fibrosis

Author

Boutanquoi, Pierre-Marie, primary, Beltramo, Guillaume, additional, Burgy, Olivier, additional, Bellaye, Pierre-Simon, additional, Dondaine, Lucile, additional, Mailleux, Arnaud, additional, Crestani, Bruno, additional, Garrido, Carmen, additional, Goirand, Françoise, additional, and Bonniaud, Philippe, additional

Published
2018
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33. Suivi thérapeutique pharmacologique du 5-fluorouracile : mise au point et recommandations du groupe STP-PT de la SFPT et du GPCO-Unicancer

Author

Lemaitre, Florian, primary, Goirand, Françoise, additional, Launay, Manon, additional, Chatelut, Etienne, additional, Boyer, Jean-Christophe, additional, Evrard, Alexandre, additional, Paludetto, Marie-Noelle, additional, Guilhaumou, Romain, additional, Ciccolini, Joseph, additional, and Schmitt, Antonin, additional

Published
2018
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35. P105 Deglycosylated bleomycin has the antitumor activity of bleomycin without pulmonary toxicity

Author

Burgy , Olivier, Wettstein , Guillaume, Bellaye , Pierre-Simon, Decologne , Nathalie, Racoeur , Cindy, Goirand , Françoise, Beltramo , Guillaume, Hernandez , Jean-Francois, Kenani , Abderraouf, Camus , Philippe, Bettaieb , Ali, Garrido , Carmen, Bonniaud , Philippe, 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 ), Laboratoire d'Immunologie et Immunothérapie des Cancers ( LIIC ), École pratique des hautes études ( EPHE ) -Université de Bourgogne ( UB ), Université de Montpellier ( UM ), Faculté de Médecine de Monastir [Tunisie], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de Pneumologie Soins Intensifs, Appareillage Respiratoire [CHU de Dijon], 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), Laboratoire d'Immunologie et Immunothérapie des Cancers (LIIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Bourgogne (UB), Université de Montpellier (UM), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)

Subjects
carbohydrates (lipids), bleomycin, respiratory system, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, pulmonary toxicity, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, respiratory tract diseases
Abstract

IF 2.824; International audience; Bleomycin is an anti-cancer drug used to treat different malignancies, mainly lymphomas, germ cell tumors. Unfortunately, bleomycin has major, pulmonary toxicity that affects 20% of treated individuals with pulmonary fibrosis being the most devastating form. Deglyco-bleomycin is a molecule derived from bleomycin in which the sugar residue D-mannosyl-L-glucose disaccharide has been deleted. The objective of this study is to assess the anti-cancerous activity and the lung toxicity of deglyco-bleomycin.We compared in vivo the antitumor activity in three rodent models after intraperitoneal administrated deglyco-bleomycin and bleomycin. Pulmonary toxicity was in depth examined after intratracheal administration of both chemotherapeutic agents.We demonstrate in vivo in rodent cancer models, including a human Hodgkin lymphoma xenograft and a syngeneic melanoma model, that intra-peritoneal deglyco-bleomycin is as effective as bleomycin...

Published
2016

37. Liste des auteurs

Author

Goirand, Françoise, Bardou, Marc, Ayme-Diétrich, Estelle, Barau, Caroline, Ghezala, Inès Ben, Bénévent, Justine, Berdai, Driss, Blacher, Jacques, Bouquié, Régis, Bourneau-Martin, Delphine, Briet, Marie, Carton, Louise, Cheriet, Sarah, Cracowski, Jean-Luc, Davani, Siamak, Despas, Fabien, Devos, David, Djerada, Zoubir, Fedrizzi, Sophie, Feliu, Catherine, Gautier, Sophie, Ghaleh, Bijan, Grenet, Guillaume, Konecki, Céline, Labriffe, Marc, Lafaurie, Margaux, Lafay-Chebassier, Claire, Renosi, Jennifer Lagoutte, Le Tilly, Olivier, Luu, Maxime, Pressiat, Claire, Sommet, Agnès, Verdier, Marie-Clémence, and Wils, Julien

Published
2023
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41. Lack of everolimus diffusion in pleural fluid during pleural progression of breast cancer: A case report.

Author

Vaury, Célia, Macaire, Pauline, Goirand, Françoise, Coudert, Bruno, Guérard, Pascal, and Schmitt, Antonin

Subjects
BREAST tumors, PLEURAL effusions, PROTEIN-tyrosine kinase inhibitors, DISEASE progression, EXEMESTANE, EVEROLIMUS
Abstract

Background: We report here a case where no everolimus pleural diffusion was evidenced at the same time of pleural progression of a metastatic breast cancer treated with everolimus and exemestane. Case description: A 69-year-old woman was diagnosed in October 2006 with stage III invasive ductal breast adenocarcinoma. After nine months of everolimus and exemestane treatment, she presented with a pleural progression. Everolimus concentration was measured in blood and in pleural fluid. Residual blood concentration was at 9.1 ng/mL, while no everolimus was observed in the pleural fluid. Management and outcome: Due to inefficacy of everolimus in this patient, she was switched to palbociclib and fulvestrant. Conclusion: Everolimus seems to have a poor diffusion in the pleural fluid. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Deglycosylated bleomycin has the antitumor activity of bleomycin without pulmonary toxicity

Author

Burgy, Olivier, primary, Wettstein, Guillaume, additional, Bellaye, Pierre S., additional, Decologne, Nathalie, additional, Racoeur, Cindy, additional, Goirand, Françoise, additional, Beltramo, Guillaume, additional, Hernandez, Jean-François, additional, Kenani, Abderraouf, additional, Camus, Philippe, additional, Bettaieb, Ali, additional, Garrido, Carmen, additional, and Bonniaud, Philippe, additional

Published
2016
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43. Pharmacologie et thérapeutiques : Unité d'enseignement 2.11

Author

Goirand, Françoise, Collège National de Pharmacologie Médicale (CNPM), Goirand, Françoise, and Collège National de Pharmacologie Médicale (CNPM)

Subjects
Pharmacology, Therapeutics
Abstract

L'objectif des Cahiers des Sciences Infirmières est d'offrir aux étudiants en IFSI des ouvrages complets et détaillés couvrant l'ensemble des savoirs définis dans les Unités d'Enseignement (UE) du nouveau référentiel. Ce cahier, consacré à l'UE 2.11 Pharmacologie et thérapeutiques, correspond étroitement au nouveau programme (semestres 1, 3 et 5). Il explicite les modalités, les risques et les dangers de l'administration médicamenteuse à travers : - les principes de chimie pertinents ; - la définition, la classification et le développement du médicament ; - les notions de pharmacodynamie et de pharmacocinétique ; - les voies d'administration et les formes pharmaceutiques ; - la préparation et l'administration des médicaments. L'UE est aussi centrée sur la connaissance des familles thérapeutiques : les antibiotiques, la chimiothérapie anticancéreuse, les psychotropes, les anticoagulants et antiagrégants plaquettaires, les anti-inflammatoires stéroïdiens et non stéroïdiens, les antalgiques et les anesthésiques. Cet ouvrage aborde enfin la responsabilité infirmière à travers : - les effets iatrogènes et la pharmacodépendance ; - les particularités de l'administration médicamenteuse chez les enfants et les personnes âgées ; - la prescription médicale et son application par l'infirmière ; - la réglementation concernant les médicaments listés et les stupéfiants ; - le circuit du médicament. Toutes ces thématiques sont illustrées par de nombreux schémas et photographies en couleurs. De nombreuses fiches de prescription « Pharmacologie » décrivent le rôle infirmier : administration, surveillance, contre-indications, éducation-conseils aux patients. Tout au long de l'ouvrage, de nombreuses fiches « Acte et/ou surveillance infirmiers » décrivent les différents soins et des fiches « Situation intégrative » mettent en évidence la conduite à tenir de l'infirmière auprès du patient. Certains chapitres se terminent par une rubrique « Situation clinique » exposant et analysant, de manière détaillée, un cas concret en rapport avec la thématique proposée dans le chapitre. Et en fin d'ouvrage, un Cahier d'entraînement permet à l'étudiant de tester ses connaissances et de s'entraîner à l'analyse de situations intégratives.

Published
2011

44. [Level of evidence for therapeutic drug monitoring of everolimus]

Author

Goirand, Françoise, Royer, Bernard, Hulin, Anne, Saint-Marcoux, Franck, Marquet, Pierre, Laboratoire de Pharmacologie-Toxicologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de pharmacologie clinique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Pharmacologie, toxicologie et pharmacovigilance [CHU Limoges], CHU Limoges, groupe Suivi Thérapeutique Pharmacologique de la Société Française de Pharmacologie et de Thérapeutique, and Laboratoire de Pharmacologie et Toxicologie

Subjects
Graft Rejection, Sirolimus, MESH: Humans, Evidence-Based Medicine, Dose-Response Relationship, Drug, MESH: Heart Transplantation, MESH: Graft Rejection, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Kidney Transplantation, MESH: Dose-Response Relationship, Drug, MESH: Kidney Transplantation, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Drug Monitoring, Heart Transplantation, Humans, MESH: Immunosuppressive Agents, MESH: Sirolimus, Everolimus, Drug Monitoring, MESH: Evidence-Based Medicine, Immunosuppressive Agents
Abstract

International audience; Everolimus has proven efficacy for prevention of rejection in adult de novo renal and cardiac transplant recipient in combination with ciclosporine and corticosteroids. Therapeutic drug monitoring (TDM) with target trough concentration (C0) value from 3 to 8 µg/L has been proposed. Through a systematic review of the literature, this work explored a level of recommendation for this TDM. Everolimus exhibits both wide interindividual pharmacokinetic variability and poor relationship between dose and exposure. A good relationship has been reported between C0 values and global exposure to the drug (i.e. AUC). Although C0 > 3 µg/L has been associated with a decreased incidence of rejection, the upper limit of 8 µg/L has never been formally validated. No clinical trial testing other exposure indices or comparing efficacy and/or toxicity of everolimus therapy with and without TDM has been published so far. Consequently the level of recommendation for everolimus monitoring is "recommended".

Published
2010

45. Changes in Maternal Blood Inflammatory Markers As a Predictor Of Chorioamnionitis: A Prospective Multicenter Study

Author

Le Ray, Isabelle, primary, Mace, Guillaume, additional, Sediki, Mourad, additional, Lirussi, Frédéric, additional, Riethmuller, Didier, additional, Lentz, Nathalie, additional, Ramanah, Rajeev, additional, Hoyek, Toufic, additional, Spagnolo, Gilles, additional, Laurent, Nicole, additional, Goirand, Françoise, additional, Sagot, Paul, additional, and Bardou, Marc, additional

Published
2014
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46. ADRB3 adrenergic receptor is a key regulator of human myometrial apoptosis and inflammation during chorioamnionitis

Author

Lirussi, Fréderic, Rakotoniaina, Zo, Madani, Siham, Goirand, Françoise, Breuiller-Fouché, Michelle, Leroy, Marie-Josèphe, Sagot, Paul, Morrison, John, Dumas, Monique, Bardou, Marc, Laboratoire de Pharmacologie et Toxicologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), 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), Departments of Gynaecology and Obstetrics, Clinical Science Institute-National University of Ireland [Galway] (NUI Galway), Hôpital du Bocage, Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), 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 ), Clinical Science Institute-National University of Ireland [Galway] ( NUI Galway ), Unité de Pharmacologie Clinique, Laboratoire de Physiopathologie et de Pharmacologie Cardiovasculaire Expérimentale (LPPCE), Université de Bourgogne (UB), 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), Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], and Breuiller-Fouche, Michelle

Subjects
Lipopolysaccharides, MESH : Benzoates, MESH: Inflammation, Pregnancy Trimester, Third, MESH : Cytokines, MESH : Receptors, Adrenergic, beta-3, MESH: Sulfonamides, Adrenergic beta-3 Receptor Agonists, Apoptosis, MESH : Pregnancy Trimester, Third, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH : Lipopolysaccharides, Benzoates, MESH : Chorioamnionitis, MESH: Pregnancy, Pregnancy, Humans, MESH : Female, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH : Sulfonamides, Inflammation, Sulfonamides, MESH: Cytokines, MESH : Inflammation, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Myometrium, MESH: Apoptosis, MESH: Chorioamnionitis, MESH : Humans, MESH: Benzoates, MESH : Pregnancy, Chorioamnionitis, Receptors, Adrenergic, beta-3, Myometrium, MESH: Pregnancy Trimester, Third, Cytokines, MESH: Myometrium, Female, MESH: Lipopolysaccharides, MESH: Receptors, Adrenergic, beta-3, MESH: Female, MESH : Apoptosis
Abstract

International audience; The pathophysiology underlying preterm labor triggered by inflammatory conditions such as chorioamnionitis remains largely unclear. It has already been suggested that beta-3 adrenergic (ADRB3) agonists might be of interest in the pharmacological management of preterm labor. Although there is evidence implicating ADRB receptors in the control of inflammation, there are minimal data relating specifically to ADRB3. To explore the cellular consequences of chorioamnionitis and detect apoptosis, we first performed immunostaining and Western blot experiments on human myometrial samples obtained from women with confirmed chorioamnionitis. We then developed an in vitro model of chorioamnionitis by incubating the myometrial samples obtained from uncomplicated pregnancies with Escherichia coli lipopolysaccharide (LPS). We observed that chorioamnionitis was associated with a significant increase in cleaved CASP3 protein expression, as well as chromatin condensation, which were reproduced experimentally by LPS stimulation (10 microg/ml, 48 h). Lipopolysaccharide stimulation of normal human myometrium also induced CASP3 transcripts, increased the proapoptotic marker BAX, and decreased the antiapoptotic marker BCL2. Lipopolysaccharide-induced apoptosis was antagonized by neutralization of secreted tumor necrosis factor by a specific antibody. Furthermore, LPS stimulation increased medium culture levels of proinflammatory cytokines interleukin 6 (IL6) and IL8. Lipopolysaccharide-induced apoptosis and cytokine production were prevented by the new and potent ADRB3 agonist SAR150640 in a concentration-dependent manner. SAR150640 by itself did not exhibit any effect on apoptosis or cytokine production in control tissues. This study shows that chorioamnionitis is associated with apoptosis of human myometrial cells. It emphasizes the potential therapeutic interest of ADRB3 agonists in the field of preterm labor and other inflammatory conditions.

Published
2008

47. Activation of AMP kinase alpha1 subunit induces aortic vasorelaxation in mice

Author

Goirand, Françoise, Solar, Myriam, Athea, Yoni, Viollet, Benoit, Mateo, Philippe, Fortin, Dominique, Leclerc, Jocelyne, Hoerter, Jacqueline, Ventura-Clapier, Renée, Nutrition Lipidique et Régulation Fonctionnelle du Cœur et des Vaisseaux (UMR INRA 1154), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11), Signalisation et physiopathologie cardiaque, Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Association Française contre les Myopathies, Fondation de France and the European Union Contracts n°LSHM-CT-2005-018833/EUGeneHeart and LSHM-CT-2004-005272/exgenesis., 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 Recherche Agronomique (INRA) - Université Paris-Sud - Paris 11 (UP11), Université Paris-Sud - Paris 11 (UP11) - IFR141 - Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)

Subjects
AMPK, MESH: Enzyme Activation, MESH: Aorta, Thoracic, AICAR, Enzyme Activators, Aorta, Thoracic, AMP-Activated Protein Kinases, In Vitro Techniques, Protein Serine-Threonine Kinases, Cardiovascular, MESH: Aminoimidazole Carboxamide, MESH: Multienzyme Complexes, MESH: Mice, Knockout, Muscle, Smooth, Vascular, MESH: Protein-Serine-Threonine Kinases, MESH: Dose-Response Relationship, Drug, smooth muscle, MESH: Vasodilation, Mice, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Multienzyme Complexes, MESH: Mice, Inbred C57BL, Animals, MESH: Animals, MESH: Enzyme Activators, Phosphorylation, MESH: Mice, Mice, Knockout, Dose-Response Relationship, Drug, MESH: Phosphorylation, MESH: Muscle, Smooth, Vascular, Ribonucleotides, Aminoimidazole Carboxamide, vasodilatation, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Enzyme Activation, Isoenzymes, Mice, Inbred C57BL, Vasodilation, transgenic mouse, MESH: Ribonucleotides, cardiovascular system, MESH: Isoenzymes
Abstract

International audience; Vasodilatation is a vital mechanism of systemic blood flow regulation that occurs during periods of increased energy demand. The AMP-dependent protein kinase (AMPK) is a serine/threonine kinase that is activated by conditions that increase the AMP-to-ATP ratio, such as exercise and metabolic stress. We hypothesized that AMPK could trigger vasodilatation and participate in blood flow regulation. Rings of thoracic aorta were isolated from C57Bl6 mice and mice deficient in the AMPK catalytic alpha1 (AMPKalpha1-/-) or alpha2 (AMPKalpha2-/-) subunit and their littermate controls, and mounted in an organ bath. Aortas were preconstricted with phenylephrine (1 microM) and activation of AMPK was induced by addition of increasing concentrations of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). AICAR (0.1-3 mM) dose-dependently induced relaxation of precontracted C57BL6, AMPKalpha1+/+ and alpha2+/+ aorta (P

Published
2007

48. Stimulation of the ADRB3 adrenergic receptor induces relaxation of human placental arteries: influence of preeclampsia

Author

Rouget, Céline, Barthez, O., Goirand, Françoise, Leroy, Marie-Josèphe, Breuiller-Fouché, Michelle, Rakotoniaina, Zo, Guérard, P., Morcillo, Esteban, Advenier, C., Sagot, Paul, Cabrol, Dominique, Dumas, Monique, Bardou, Marc, Laboratoire de Physiopathologie et de Pharmacologie Cardiovasculaire Expérimentale ( LPPCE ), Université de Bourgogne ( UB ), Pharmacologie, Université Paris Descartes - Paris 5 ( UPD5 ) -EA220, Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), 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 ), Department of Pharmacology, Universitat de València ( UV ), Maternité, Obstétrique et Gynécologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Maternité Port-Royal [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Supported, in part, by the Fondation pour la Recherche Médicale and, in part, by the grant SAF2003–07206-C02 (Spain)., Breuiller-Fouche, Michelle, Laboratoire de Physiopathologie et de Pharmacologie Cardiovasculaire Expérimentale (LPPCE), Université de Bourgogne (UB), Université Paris Descartes - Paris 5 (UPD5)-EA220, 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), Universitat de València (UV), Service de Gynécologie Obstétrique, Médecine Foetale et Stérilité Conjugale - Chirurgie Gynécologie et Oncologique [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
MESH: Pre-Eclampsia, Placenta, MESH : Receptors, Adrenergic, beta-3, MESH : Adrenergic beta-Agonists, MESH : Receptors, Adrenergic, beta-2, MESH : Isoproterenol, MESH: Adrenergic beta-Agonists, MESH: Isoproterenol, MESH : Vasodilation, MESH: Pregnancy, Pre-Eclampsia, Pregnancy, MESH : Female, MESH : Albuterol, MESH : Pre-Eclampsia, Arteries, Adrenergic beta-Agonists, MESH: Placenta, MESH: Tetrahydronaphthalenes, Vasodilation, MESH: Nucleotides, Cyclic, MESH : Placenta, Ethanolamines, MESH : Tetrahydronaphthalenes, Female, Nucleotides, Cyclic, Tetrahydronaphthalenes, Adrenergic beta-3 Receptor Agonists, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, MESH: Ethanolamines, MESH: Vasodilation, MESH : Ethanolamines, Humans, Albuterol, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Arteries, Adrenergic beta-2 Receptor Agonists, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Albuterol, MESH : Humans, Isoproterenol, MESH : Arteries, MESH : Nucleotides, Cyclic, MESH : Pregnancy, Receptors, Adrenergic, beta-3, Receptors, Adrenergic, beta-2, MESH: Receptors, Adrenergic, beta-3, MESH: Receptors, Adrenergic, beta-2, MESH: Female
Abstract

International audience; Preeclampsia, which complicates 3-8% of pregnancies, is one of the leading causes of neonatal morbidity and mortality. Its pathophysiology remains unclear. The aim of the present study was to investigate the presence and the role of beta2- and beta2-adrenergic receptors (ADRB2 and ADRB3, respectively) in human placental arteries and to assess the influence of preeclampsia on ADRB responsiveness. SR 59119A, salbutamol, and isoproterenol (ADRB3, ADRB2, and nonselective ADRB agonists, respectively) induced a concentration-dependent relaxation of placental artery rings obtained from women with uncomplicated or preeclamptic pregnancies. SR 59119A-induced relaxation was unaffected by the blockade of ADRB1 and ADRB2 by 0.1 microM propranolol but was significantly decreased by the blockade of ADRB1, ADRB2, and ADRB3 by 10 microM propranolol. Both SR 59119A and salbutamol were associated with a significant increase in cAMP production that was significantly inhibited by pretreatment with 0.1 microM propranolol only for salbutamol. SR 59119A-induced relaxation (E(max) = 28% +/- 5% vs. 45% +/- 4%, respectively) and cAMP production (2.7 +/- 0.5 vs. 4.9 +/- 0.4 pmol/mg of protein, respectively; P < 0.01) were decreased in arteries obtained from preeclamptic compared to normotensive women. Both ADRB2 and ADRB3 transcripts were expressed at the same level between arteries from normotensive and preeclamptic women. Western blot analysis, however, revealed a decreased expression of the ADRB3 immunoreactive protein in arteries from preeclamptic compared to normotensive women. We suggest the presence of functional ADRB2 and ADRB3 in human placental arteries. Even if preeclampsia is associated with an impairment of the ADRB3 responsiveness, ADRB3 agonists may have future pharmaceutical implications in the management of pregnancy-related disorders.

Published
2005

50. Role of potassium channels and nitric oxide in the relaxant effects elicited by β-adrenoceptor agonists on hypoxic vasoconstriction in the isolated perfused lung of the rat

Author

Dumas, Jean-Paul, Goirand, Françoise, Bardou, Marc, Dumas, Monique, Rochette, Luc, Advenier, Charles, and Giudicelli, Jean-François

Subjects
Male, Pulmonary Circulation, Potassium Channels, Muscle Relaxation, Adrenergic beta-Agonists, In Vitro Techniques, Nitric Oxide, Muscle, Smooth, Vascular, Rats, NG-Nitroarginine Methyl Ester, Vasoconstriction, Papers, Glyburide, Potassium Channel Blockers, Respiratory Mechanics, Animals, Cyclooxygenase Inhibitors, Enzyme Inhibitors, Nitric Oxide Synthase, Rats, Wistar, Hypoxia, Lung
Abstract

1. The aims of this study were to compare, in the rat isolated perfused lung preparation, the antagonist effects of a nonselective beta-adrenoceptor agonist (isoprenaline), a selective beta2-adrenoceptor agonist (salbutamol) and a selective beta3-adrenoceptor agonist (SR 59104A) on the hypoxic pulmonary pressure response, and to investigate the role of K+ channels, endothelium derived relaxing factor and prostaglandins in these effects. K+ channels were inhibited by glibenclamide, charybdotoxin or apamin, NO synthase and cyclo-oxygenase were inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin, respectively. 2. Hypoxic ventilation produced a significant increase in perfusion pressure (+65%, P0.001) and L-NAME significantly increased this response further (+123%, P0.01). After apamin, L-NAME, indomethacin, post-hypoxic basal pressure did not return to baseline values (P0.001). 3. Glibenclamide partially inhibited the relaxant effects of isoprenaline (P0.05) and salbutamol (P0.001) but not that of SR 59104A. In contrast, charybdotoxin and apamin partially inhibited the relaxant effects of SR 59104A (P=0.053 and0.01, respectively) but did not modify the effects of isoprenaline and salbutamol. L-NAME partially inhibited the dilator response of salbutamol (P0.01) and SR 59104A (P0.05) but not that of isoprenaline. 4. We conclude that (a) EDRF exerts a significant inhibition of the hypoxic pulmonary response, (b) SK(Ca) channel activation, EDRF and prostaglandins contribute to the reversal of the hypoxic pressure response, (c) the vasodilation induced by isoprenaline is mediated in part by activation of K(ATP) channels, that of salbutamol by activation of K(ATP) channels and EDRF. In contrast, SR 59104A partly operates through BK(Ca), SK(Ca), channels and EDRF activation, differing in this from the beta1 and beta2-adrenoceptor agonists.

Published
1999

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